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Findley first proposed the presence of age-related dysfunction of the hypothalamic-neurohypophyseal-renal axis more than 60 years ago. More sophisticated studies have since corroborated his findings. As a result, it is now clear that multiple abnormalities in water homeostasis occur commonly with aging, and that the elderly are uniquely susceptible to disorders of body volume and osmolality. This article summarizes the distinct points along the hypothalamic-neurohypophyseal-renal axis where these changes have been characterized, as well as the clinical significance of these changes, with special attention to effects on cognition, gait instability, osteoporosis, fractures, and morbidity and mortality.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

ObjectiveInflammation may be present with chronic kidney disease CKD and diet composition high in protein intake and fats may affect inflammation thereby impacting kidney health. We investigated whether acid load estimated from urine measures is associated with kidney function decline and whether the effect of acid load on an inflammatory marker, serum albumin, is a pathway to this association.MethodsWe studied 188 postmenopausal women in a randomized clinical trial of potassium bicarbonate treatment for up to 36months. Twenty-four-hour urine and arterialized blood collections were done at baseline and at subsequent follow-up visits at 3months interval. Acid load was estimated from potential renal acid load calculated using urinary measures of chloride, phosphate, sodium, potassium, calcium, and magnesium (UPRAL). Mixed effects model with random-intercept and slope was used to estimate subjects' annual decline rate in creatinine clearance (CrCl), and the association between (i) UPRAL and serum albumin and (ii) serum albumin and CrCl, adjusting for age, body mass index, systolic BP, and glucose. A Cox proportional regression model was used to study the relative hazard (RH) for rapid progression of kidney function decline (defined as loss of ≥5mL/min CrCl/yr based on the last CrCl in the rolling window) with UPRAL, adjusting for the potential covariates and baseline CrCl.ResultsA 25 mEq/day increase in UPRAL was inversely associated with serum albumin (Adjusted β[95% CI]: -0.02[-0.09;-0.001). During a mean follow-up of 28months, 19 women (10%) had a rapid decline in kidney function. For each 25 mEq/day increase in UPRAL, the risk of a rapid decline in CrCl increased by 17% (95% CI: 1.06-1.28). On adjustment for potential confounders, the risk attenuated to 5% (1.02-1.14). Mediation analysis indicated that of the total effect of the association between UPRAL and CrCl, the proportion mediated by serum albumin increased to 0.346 (i.e. 34.6%).ConclusionHigher UPRAL was associated with lower serum albumin as well as greater kidney function decline in postmenopausal women. Our findings suggest inflammatory response may exert a modulatory effect on the association of UPRAL and kidney function and might be a potential pathway explaining the effects of systemic acid load on progression of kidney failure.

The failure of arteriovenous fistulas (AVF) to mature is a major problem in patients with kidney failure who require haemodialysis (HD). Preoperative planning is an important factor in increasing functional AVF. Upper limb exercise has been recommended to gain AVF maturation. Studies of pre- and post-operative upper limb exercises in patients with kidney failure patients have been reported; however, the optimal program for this population is unknown due to inconsistent results among these programs.We aimed to determine if upper limb exercise would be beneficial for AVF maturation (prior to and post AVF creation) in patients with kidney failure and to improve AVF outcomes. This review also aimed to identify adverse events related to upper limb exercise.We searched the Cochrane Kidney and Transplant Register of Studies up to 15 March 2022 through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov, and other resources (e.g. reference list, contacting relevant individuals, and grey literature).We included randomised controlled trials (RCTs) and quasi-RCTs, comparing upper limb exercise training programs with no intervention or other control programs before or after AVF creation in patients with kidney failure. Outcome measures included time to mature, ultrasound and clinical maturation, venous diameter, blood flow in the inflow artery, dialysis efficacy indicator, vascular access function (functional AVF), vascular access complications, and adverse events.Study selection and data extraction were taken by four independent authors. Bias assessment and quality assessment were undertaken independently by two authors. The effect estimate was analysed using risk ratio (RR) with 95% confidence intervals (CI) for dichotomous data, or mean difference (MD) or standardised mean difference (SMD) for continuous data. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Nine studies (579 participants) were included, and seven studies (519 participants) conducting post-operative exercise training could be meta-analysed. Three comparisons were undertaken: (i) isotonic exercise training versus no intervention; (ii) isometric versus isotonic exercise training; and (iii) isotonic (high volume) versus isotonic exercise training (low volume). Due to insufficient data, we could not analyse pre-operative exercise training. Overall, the risk of bias was low for selection and reporting bias, high for performance and attrition bias, and unclear for detection bias. Compared to no intervention, isotonic exercise training may make little or no difference to ultrasound maturation (2 studies, 263 participants: RR 1.09, 95% CI 0.94 to 1.25; I² = 0%; low certainty evidence), but may improve clinical maturation (2 studies, 263 participants: RR 1.14, 95% CI 1.02 to 1.27; I² = 0%; low certainty evidence). Compared to isotonic exercise training, isometric exercise training may improve both ultrasound maturation (3 studies, 160 participants: RR 1.56, 95% CI 1.21 to 2.00; I² = 22%; low certainty evidence) and clinical maturation (3 studies, 160 participants: RR 1.80, 95% CI 1.18 to 2.76; I² = 53%; low certainty evidence). Venous diameter (3 studies, 160 participants: MD 0.84 mm, 95% CI 0.45 to 1.23; I² = 0%; low certainty evidence) and blood flow in the inflow artery (3 studies, 160 participants: MD 140.62 mL/min, 95% CI 38.72 to 242.52; I² = 0%; low certainty evidence) may be greater with isometric exercise training. It is uncertain whether isometric exercise training reduces vascular access complications (2 studies, 110 participants: RR 2.54, 95% CI 0.38 to 17.08; I² = 47%; very low certainty evidence). It is uncertain whether high volume isotonic exercise training improves venous diameter (2 studies, 93 participants: MD 0.19 mm, 95% CI -0.75 to 1.13; I² = 34%; very low certainty evidence) or blood flow in the inflow artery (1 study, 15 participants: MD -287.70 mL/min, 95% CI -625.99 to 60.59; very low certainty evidence) compared to low volume isotonic exercise training. None of the included studies reported time to mature, dialysis efficacy indicator, vascular access function, or adverse events.Our findings suggest that the current research evidence examining upper limb exercise programs is of low quality, attributable to variability in the type of interventions used and the overall low number of studies and participants.

Background and objective: With the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT), long-term complications have come to the fore. The aim of this study was to determine the prevalence and risk factors of chronic kidney disease (CKD) developing in the long term in patients who underwent allo-HSCT in childhood and also to investigate the superiority of eGFR formulas. Methods: The present study evaluated CKD in patients who underwent allo-HSCT. We analyzed the 94 children who received allo-HSCT at the Ege University in İzmir between August and November, 2019. The patients were evaluated at 2 years after transplantation. CKD was defined as a glomerular filtration rate (GFR) 120 months during transplantation were found to be associated with the development of CKD. Conclusion: We may be delayed in detecting CKD by calculating SCr-based formulas in allo-HSCT cases, which is a patient group where early diagnosis and treatment of CKD is very important. Resumo Antecedentes e objetivo: Com o uso generalizado do transplante alogênico de células-tronco hematopoiéticas (TCTH-alo), as complicações a longo prazo tornaram-se evidentes. O objetivo deste estudo foi determinar a prevalência e os fatores de risco do desenvolvimento de doença renal crônica (DRC) a longo prazo em pacientes submetidos a TCTH-alo na infância, e também investigar a superioridade das fórmulas de TFGe. Métodos: O presente estudo avaliou a DRC em pacientes que foram submetidos ao TCTH-alo. Analisamos as 94 crianças que receberam TCTH-alo na Universidade Ege em İzmir entre Agosto e Novembro de 2019. Os pacientes foram avaliados aos 2 anos após o transplante. A DRC foi definida como uma taxa de filtração glomerular (TFG) 120 meses durante o transplante foram associados ao desenvolvimento de DRC. Conclusão: Pode haver atraso na detecção da DRC quando usamos fórmulas baseadas em CrS em casos de TCTH-alo, que é um grupo de pacientes onde o diagnóstico e tratamento precoces da DRC são muito importantes.

Purpose: Postoperative acute kidney injury is common and associated with increased length of hospital stay, costs and mortality. The impact from postoperative subclinical changes in plasma concentration of creatinine (p-creatinine) on postoperative mortality has received less attention. In this study, the association between the postoperative change of p-creatinine and all-cause mortality was investigated. Methods: A single-centre register-based, retrospective study was conducted including patients ≥ 60 years undergoing open abdominal surgery from 2000 to 2013. Postoperative p-creatinine change was analysed for association with 30-day mortality following adjustment for age, gender, surgical setting and surgical procedure. Main findings A total of 3,460 patients were included in the study of whom 67.6% underwent emergency surgery. The 30-day mortality rate was 18.3%, and a given 10 μmol/L daily postoperative increase in p-creatinine was associated with an increased mortality risk with an odds ratio (OR) of 2.67 (95% CI; 2.28-3.14, P < 0.001). In patients undergoing emergency surgery, a daily 10 μmol/L increase in p-creatinine increased the risk for a fatal outcome a 2.39 OR (CI 95%; 2.05-2.78), P < 0.001). In patients undergoing elective surgery, a similar increase in p-creatinine increased risk of postoperative death with a 28.85 OR (CI 95%; 10.25-81.19). Conclusion: Even a minor postoperative p-creatinine increase following open abdominal surgery below the criteria for acute kidney injury was associated with increased 30-day mortality in patients aged 60 years or above.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space ("hairy kidney" appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comprising 195 consecutive patients with ECD. Retroperitoneal peri-kidney or peri-ureteral involvement was detected at diagnosis in 147 patients. Of them, 70 had hydronephrosis (bilateral in 47), and 16 with kidney atrophy (unilateral in 14). Kidney vascular peduncle infiltration was found in 60 patients, and kidney artery stenosis in 31. The estimated glomerular filtration rate (eGFR) at diagnosis was significantly lower in patients with than in those without peri-kidney involvement (median 74 vs. 98 mL/min/1.73 m

Significant renal insufficiency is identified as a risk factor for post-transplantation mortality in pediatric heart transplant recipients. This study evaluates simultaneous heart-kidney transplantation listing outcomes compared with heart transplant for pediatric candidates with significant renal insufficiency.The United Network for Organ Sharing registry was searched for patients (January 1987 to March 2020) who were simultaneously listed for a heart-kidney transplantation or for heart transplant with significant renal insufficiency at the time of listing. Significant renal insufficiency was defined as needing dialysis or having a low estimated glomerular filtration rate (lt;40 mL/min). Survival was calculated using Kaplan-Meier analysis.A total of 427 cases were identified; 109 were listed for heart-kidney transplantation, and 318 were listed for heart transplant alone. Median time on the waitlist was 101 days (interquartile range, 28-238) for heart-kidney transplantation listings compared with 39 days (14-86) and 23.5 days (6-51) for heart transplant recipients with a low estimated glomerular filtration rate (P = .002) or on dialysis (P lt; .001), respectively. Of all heart-kidney transplantation listings, 66% (n = 71) received a transplant compared with 54% (n = 173) of heart transplantation with significant renal insufficiency (P = .005) with a mean survival of 14.6 years (12.7-16.4 years) for heart transplant without significant renal insufficiency at transplantation and 7.6 years (5.4-9.9 years) for heart transplant with significant renal insufficiency at transplantation. At 1 year after listing, 69% of heart-kidney transplantation listed recipients were alive, compared with 51% of heart transplant listed recipients (P = .029). Heart-kidney transplantation recipients had better 1-year post-transplantation survival (86%) than heart transplantation with significant renal insufficiency at transplant (66%) (P = .001). There was no significant difference in the 1- and 5-year survivals of those undergoing heart transplantation listed with significant renal insufficiency but no significant renal insufficiency at the time of transplant (89% and 78%) and heart-kidney transplantation recipients (86% and 81%; P = .436).Pediatric candidates with significant renal insufficiency listed for heart-kidney transplantation have superior waitlist and post-transplantation outcomes compared with those listed for heart transplant alone. Patients with significant renal insufficiency should be listed for heart-kidney transplantation, however; if their renal function improves significantly, heart transplant alone appears judicious.

IgA nephropathy (IgAN) is characterized by deposition of galactose-deficient IgA1 (Gd-IgA1) in glomerular mesangium associated with mucosal immune disorders. Since environmental pollution has been associated with the progression of chronic kidney disease in the general population, we specifically investigated the influence of exposure to fine particulate matter less than 2.5 μm in diameter (PM2.5) on IgAN progression. Patients with biopsy-proven primary IgAN were recruited from seven Chinese kidney centers. PM2.5 exposure from 1998 to 2016 was derived from satellite aerosol optical depth data and a total of 1,979 patients with IgAN, including 994 males were enrolled. The PM2.5 exposure levels for patients from different provinces varied but, in general, the PM2.5 exposure levels among patients from the north were higher than those among patients from the south. The severity of PM2.5 exposure in different regions was correlated with regional kidney failure burden. In addition, each 10 μg/m

Our study assessed the relationship between the duration of venovenous extracorporeal membrane oxygenation (V-V ECMO) and patient outcomes. We studied patients undergoing V-V ECMO support for acute respiratory distress syndrome (ARDS) between 2009 and 2017 who were reported to the Extracorporeal Life Support Organization registry. We evaluated survival, major bleeding, renal failure, pulmonary complications, mechanical complications, neurologic complications, infection, and duration of V-V ECMO support. Multivariable regression modeling assessed risk factors for adverse events. Of the 4,636 patients studied, the mean support duration was 12.2 ± 13.7 days. There was a progressive increase in survival after the initiation of V-VECMO, peaking at a survival rate of 73% at 10 days of support. However, a single-day increase in V-V ECMO duration was associated with increased bleeding events (odds ratio [OR] 1.038; 95% confidence interval [CI]: 1.029-1.047; p0.0001), renal failure (OR 1.018; 95% CI: 1.010-1.027; p0.0001), mechanical complications (OR 1.065; 95% CI: 1.053-1.076; p0.0001), pulmonary complications (OR 1.04; 95% CI: 1.03-1.05; p0.0001), and infection (OR 1.04; 95% CI: 1.03-1.05; p0.0001). V-V ECMO progressively increases survival for ARDS over the first 10 days of support. Thereafter, rising complications associated with prolonged durations of support result in a progressive decline in survival.

The clinical manifestations and prognosis of IgA nephropathy (IgAN) are diverse. Some patients may present with kidney dysfunction lasting shorter than 3 months and meet the acute kidney disease (AKD) criteria. This study aimed to investigate the clinicopathological features, causes and prognosis of newly diagnosed cases of IgAN with AKD.1320 IgAN patients diagnosed via kidney biopsy between January 2012 and June 2018 were included in this retrospective study, with a median follow-up period of 35 months. We analyzed the clinicopathological, etiological variables, as well as short-term and long-term prognosis. The main outcome was a composite event of 40% decline in eGFR, kidney failure or death.Incidence of AKD was 8.8% in the newly diagnosed IgAN patients, and was found to be an independent risk factor affecting the short-term (HR, 7.1; 95% CI, 2.3-22.2; P = 0.001) and long-term (HR, 1.8; 95% CI, 1.2-2.6; P = 0.006) prognosis, respectively. The most common cause of AKD was malignant hypertension-related AKD (MHT-AKD; 24.1%), followed by hematuria-related AKD (H-AKD; 12.9%), nephrotoxic-drug-exposure-related AKD (NTDE-AKD; 12.1%) and crescents-related AKD (C-AKD; 11.2%). The patients in AKD group had more severe clinicopathological characteristics and poor short-term and long-term prognosis than non-AKD group. In subgroup analysis, the MHT-AKD had the worst 5 years survival rate, followed by NTDE-AKD and C-AKD, whereas H-AKD had the best survival rate.AKD is not rare among IgAN patients, and is an independent risk factor for short-term and long-term prognosis. IgAN patients with AKD resulting from different causes have different prognosis.

IntroductionThe accumulation of tissue-advanced glycation end products in skin results from complex and consecutive reactions and can be measured by skin autofluorescence (SAF) reader devices. This overview discusses studies evaluating the utilization of SAF in screening renal and cardiac disease.Materials and methodsLiterature search was performed using Google Scholar, PubMed, Springer, Ovid, and ScienceDirect.ResultsSAF was an independent predictor of progression of chronic kidney disease (CKD) and was elevated in subjects on hemodialysis and peritoneal dialysis. Furthermore, SAF was significantly associated with cardiovascular events, cardiovascular mortality, and all-cause mortality in CKD patients. Other studies revealed a correlation between SAF and arterial stiffness, vascular damage, and subclinical atherosclerosis. A vegetarian diet was associated with lower SAF levels, whereas malnutrition was correlated with higher levels and increased mortality.ConclusionsSAF measurement may be useful in managing renal and cardiac disease. Future studies are needed to clarify the specific role of SAF in the management of CKD and its noninvasive office utilization to identify comorbidities in inflammatory diseases, such as psoriasis.

Background: Hyperuricemia may predispose to renal damage, but in end-stage renal disease lower uric acid concentrations have been associated with higher mortality. In experimental studies, uric acid has promoted renal fibrosis and inflammation, but some studies have shown nephroprotective effects probably due to alleviated oxidative stress. We studied the influence of moderate hyperuricemia on kidney morphology in 5/6 nephrectomized rats.Methods: Three weeks after subtotal nephrectomy or sham-operation, rats were put on 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Blood pressure was monitored using tail-cuff. At close of the study, blood, urine, and kidney samples were taken, and renal histology, mast cell count, and oxidative stress markers were determined. Kidney tissue inflammation and fibrosis were evaluated using RT‑PCR and immunohistochemistry.Results: Oxonic acid diet increased plasma uric acid levels by >80 µmol/l without influencing blood pressure. Creatinine clearance was reduced by ~60% in both remnant kidney groups, and by ~30% in hyperuricemic sham-operated rats. In remnant kidney rats with suppressed plasma renin activity, moderate hyperuricemia decreased glomerulosclerosis, tubulointerstitial damage, and kidney mast cell count, but did not influence the fibrosis marker collagen I mRNA content. In both hyperuricemic groups, the mast-cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue COX‑2 levels were decreased.Conclusions: Hyperuricemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately increased plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental chronic renal insufficiency.

The Fibrosis-4 index (FIB-4) is a recommended noninvasive fibrosis test in patients at risk of liver fibrosis. Chronic liver diseases are often associated with kidney diseases. This study aimed to investigate the association between FIB-4 and the development of renal failure among the general population. For this study, we used the Disease Analyzer database, which includes diagnoses and basic medical and demographic data of patients followed in general practices in Germany. Using these data, we extensively matched patients with a FIB-4 index ≥ 1.3 (n = 66,084) to patients with a FIB-4 index 1.3 (n = 66,084). The primary outcome was the incidence of renal failure or chronic renal failure during a 10-year period. Within 10 years of the index date, 9.2% of patients with a FIB-4 1.3 and 10.6% of patients with a FIB-4 ≥ 1.3 were diagnosed with renal failure (p = 0.007). The endpoint chronic renal failure was reached by 7.9% with a FIB-4 1.3 and 9.5% with a FIB-4 ≥ 1.3 (p 0.001). A FIB-4 index ≥ 1.3 was associated with a slight increase in renal failure incidence (hazard ratio [HR]: 1.08, p = 0.009). There was an increasing association between an increase in FIB-4 index and the incidence of renal failure with the strongest association for a FIB-4 index ≥ 2.67 (HR: 1.34, p = 0.001). In sensitivity analyses, a significant association was found for the age group of 51-60 years (HR: 1.38, p 0.001), patients with arterial hypertension (HR: 1.15, p 0.001), obese patients (HR: 1.25, p = 0.005), and patients with lipid metabolism disorders (HR:1.22, p 0.001). Conclusion: A higher FIB-4 index is associated with an increased incidence of renal failure. Therefore, the FIB-4 index may be useful in identifying patients who are at risk not only for liver-related events but also for renal disease.

Objective: To evaluate the knees of individuals with renal failure who are on hemodialysis, using magnetic resonance imaging (MRI), comparing them with those of a group of individuals with normal renal function. Materials and Methods: This was a cross-sectional, observational, controlled study conducted between August 2018 and February 2020. The cases consisted of 15 patients who had been on hemodialysis for ≥ 5 years and did not have a quadriceps tendon rupture. The controls consisted of 15 individuals with normal renal function who were matched (1:1) to the cases for sex, age, and physical activity level. The subjects in both groups underwent MRI of the right knee only. Results: The mean ages of the cases and controls were 50 ± 15 years and 49 ± 14 years, respectively. The median time on hemodialysis was 11 years (range, 10-14 years). Serum levels of parathyroid hormone, ferritin, alkaline phosphatase, phosphorus, and creatinine were higher among the cases than among the controls, whereas serum albumin and hemoglobin were lower (p < 0.05 for all). The MRI study showed a hyperintense signal in the quadriceps tendon in 11 of the cases and in three of the controls (p = 0.009). Knee joint effusion was observed in nine of the cases and in three of the controls (p < 0.05). The thickness, length, and width of the tendon did not differ between the groups. A hyperintense signal in the tendon was not associated with the time on hemodialysis; nor with the levels of intact parathyroid hormone, hemoglobin, or alkaline phosphatase. Conclusion: Patients on chronic hemodialysis, even those without a tendon rupture, show a hyperintense signal in the quadriceps tendon on MRI. Resumo Objetivo: Avaliar joelhos de indivíduos com falência renal em hemodiálise por meio de ressonância magnética, em comparação com um grupo controle sem doença renal crônica. Materiais e Métodos: Estudo transversal, observacional, controlado, realizado entre agosto/2018 e fevereiro/2020. Os 15 casos consistiram de pacientes com cinco anos ou mais em hemodiálise, sem ruptura do tendão do quadríceps. Os 15 controles, sem doença renal crônica, foram pareados (1:1) por sexo, idade e nível de atividade física. Resultados: A média de idade dos casos foi 50 ± 15 anos e a dos controles, 49 ± 14 anos. A mediana do tempo em hemodiálise foi 11 anos (variação: 10-14 anos). Nos casos, os níveis séricos de paratormônio, ferritina, fosfatase alcalina, fósforo e creatinina estavam mais altos e os de albumina e hemoglobina, mais baixos (p < 0,05). Hipersinal no tendão foi demonstrado em 11 casos e três controles (p = 0,009). Derrame articular foi observado em nove casos e três controles (p < 0,05). A espessura, o comprimento e a largura do tendão não diferiram entre os grupos. Hipersinal no tendão do quadríceps não mostrou associação com o tempo em hemodiálise ou com os níveis de paratormônio intacto, hemoglobina e fosfatase alcalina. Conclusão: Pacientes em hemodiálise sem episódios de ruptura já apresentam hipersinal no tendão do quadríceps nas imagens de ressonância magnética.

In healthy adults, higher dietary potassium intake is recommended given that potassium-rich foods are major sources of micronutrients, antioxidants, and fiber. Yet among patients with advanced kidney dysfunction, guidelines recommend dietary potassium restriction given concerns about hyperkalemia leading to malignant arrhythmias and mortality.Given sparse data informing these recommendations, we examined associations of dietary potassium intake with mortality in a nationally representative cohort of adults from the NHANES.We examined associations between daily dietary potassium intake scaled to energy intake (mg/1000 kcal), ascertained by 24-h dietary recall, and all-cause mortality among 37,893 continuous NHANES (1999-2014) participants stratified according to impaired and normal kidney function (estimated glomerular filtration rates60 and ≥60 mL · min-1 · 1.73 m-2, respectively) using multivariable Cox models. We also examined the impact of the interplay between dietary potassium, source of potassium intake (animal- compared with plant-based sources), and coexisting macronutrient and mineral consumption upon mortality.Among participants with impaired and normal kidney function, the lowest tertile of dietary potassium scaled to energy intake was associated with higher mortality (ref: highest tertile) [adjusted HR (aHR): 1.18; 95% CI: 1.02, 1.38 and aHR: 1.17; 95% CI: 1.06, 1.28, respectively]. Compared with high potassium intake from plant-dominant sources, participants with low potassium intake from animal-dominant sources had higher mortality irrespective of kidney function. Among participants with impaired kidney function, pairings of low potassium intake with high protein, low fiber, or high phosphorus consumption were each associated with higher death risk.Lower dietary potassium scaled to energy intake was associated with higher mortality, irrespective of kidney function. There was also a synergistic relation of higher potassium intake, plant-based sources, and macronutrient/mineral consumption with survival. Further studies are needed to elucidate pathways linking potassium intake and coexisting dietary factors with survival in populations with and without chronic kidney disease.

Previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) is a novel yet readily evaluable inflammatory biomarker that may be useful for determining cardiovascular prognosis during acute episodes. The study investigated the role of NLR in predicting cardiovascular (CV) outcomes in patients with acute heart failure (HF). Individual patient data from the BLAST-AHF (phase 2b study of the biased ligand of the angiotensin 2 type 1 receptor, TRV027), Pre-RELAX-AHF (phase 2b study of recombinant human relaxin-2, serelaxin), and RELAX-AHF (phase 3 study of serelaxin) randomized, placebo-controlled studies for patients with acute HF were pooled for analysis. Dyspnea visual analog scale area under the curve through day 5, worsening HF through day 5, 30-day all-cause mortality, 60-day HF/renal failure rehospitalizations or CV death, 180-day all-cause mortality, and 180-day CV death were assessed. There were several differences in the baseline characteristics of the patients divided by NLR tertile, with patients in the higher NLR having worse clinical characteristics. NLR was an independent predictor of 30-day all-cause mortality (adjusted hazard ratio [HR] per log2 NLR increment: 1.66 [1.22 to 2.25], p = 0.001), 60-day HF/renal failure rehospitalizations or CV death: 1.33 [1.12 to 1.57], p = 0.001), 180-day all-cause mortality (adjusted HR 1.27 [1.08 to 1.50], p = 0.003), and 180-day CV death (adjusted HR 1.24 [1.04 to 1.49], p = 0.018). NLR, a readily available inflammatory biomarker, was associated with independent risk for short- and long-term adverse outcomes in acute HF, surpassing traditional markers, such as natriuretic peptides.

Cancer is a significant cause of morbidity in the population with kidney failure; however, cancer mortality in people undergoing dialysis has not been well described. We sought to compare cancer mortality in people on dialysis for kidney failure with cancer mortality in the general population.A retrospective cohort study using linked health-administrative and dialysis registry data.All people receiving dialysis represented in the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013.Dialysis; hemodialysis (HD) and peritoneal dialysis (PD).Death and underlying cause of death ascertained using health administrative data and classified using International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes.Indirect standardization on age at death, sex, year, and country to estimate standardized mortality ratios (SMR).Over 269,598 person years of observation, 34,100 deaths occurred among 59,648 people on dialysis, including 3,677 cancer deaths. The relative risk of all-site cancer death in dialysis was twice (SMR, 2.4 [95% CI, 2.33-2.49]) that of the general population and highest for oral and pharynx cancers (SMR, 24.3 [95% CI, 18.0-31.5]) and multiple myeloma (SMR, 22.5 [95% CI, 20.3-23.9]). Women on dialysis had a significantly higher risk of all-site cancer mortality (SMR, 2.7 [95% CI, 2.59-2.89]) compared with men (SMR, 2.3 [95% CI, 2.17-2.36]) (P 0.001). People on HD (SMR, 2.2 [95% CI, 2.11-2.30]) experienced greater excess deaths from all-site cancer compared with people on PD (SMR, 1.3 [95% CI, 1.23-1.44]). Excess deaths have gradually decreased over time for all-site, multiple myeloma, and kidney cancers (P 0.001) but have not kept up with improvements in the general population. By contrast, among people receiving dialysis, excess deaths increased for colorectal and lung cancers (P 0.001).Confirmation of cancer diagnoses and population incidence data were not available; inability to exclude pre-existing cancers.People on dialysis experience excess all-site and site-specific cancer mortality compared with the general population. Mortality differs by modality type, age, and sex. Understanding the role of kidney failure and other morbidities in the treatment of cancer is important for shared decision-making regarding cancer treatments and identifying potential approaches to improve outcomes.

Components of the renin-angiotensin system, including angiotensinogen (AGT), are critical contributors to chronic kidney disease (CKD) development and progression. However, the specific role of tissue-derived AGTs in CKD has not been fully understood. To define the contribution of liver versus kidney AGT in the CKD development, we performed 5/6 nephrectomy (Nx), an established CKD model, in wild-type (WT), proximal tubule (PT)- or liver-specific AGT knockout (KO) mice. Nx significantly elevated intrarenal AGT expression and elevated blood pressure (BP) in WT mice. The increase of intrarenal AGT protein was completely blocked in liver-specific AGT KO mice with BP reduction, suggesting a crucial role for liver AGT in BP regulation during CKD. Nx-induced glomerular and kidney injury and dysfunction, as well as fibrosis, were all attenuated to a greater extent in liver-specific AGT KO mice compared with PT-specific AGT KO and WT mice. However, the suppression of interstitial fibrosis in PT- and liver-specific AGT KO mouse kidneys was comparable. Our findings demonstrate that liver AGT acts as a critical contributor in driving glomerular and tubular injury, renal dysfunction, and fibrosis progression, whereas the role of PT AGT was limited to interstitial fibrosis progression in chronic renal insufficiency. Our results provide new insights for the development of tissue-targeted renin-angiotensin system intervention in the treatment of CKD.

Provedeno je istraživanje pojavnosti ADAMTS-4 proteina u KBB u cilju utvrđivanja ove molekule kao novog biološkog biljega KBB. Uključeno je 150 ispitanika podijeljenih u 9 skupina: 5 (stupnjevi KBB1-5), 1 hemodijaliza, 1 peritonejska dijaliza, 1 nakon transplantacije bubrega te 1 skupina zdravih ispitanika. Metode su uključivale: (1) tekućinsku kromatografiju sa spektrometrijom masa za proteomsku analizu ekspresije proteina u združenim uzorcima plazme svake pojedine skupine te dodatnom analizom signalnih bioloških puteva obogaćivanjem gena; (2) ELISA analizu pojedinačnih uzoraka krvi i mokraće 79 ispitanika iz navedenih 9 skupina; (3) imunohistokemijsku analizu (IHK) ADAMTS-4 na biopsijskim tkivima 19 nativnih i 34 transplantirana bubrega s KBB te 8 bubrega bez KBB. Parna analiza je uključila 15 postransplantacijskih biopsija i njihovih parnih biopsija učinjenih tijekom postupka transplantacije. Proteomska analiza pokazala je da se značajna promjena trenda ekspresije različitih skupina proteina događa u stupnju KBB2. ADAMTS-4 nije utvrđen proteomskom analizom, ali je njegova prisutnost potvrđena ELISA analizom. Njegova koncentracija nije korelirala s napredovanjem KBB. Najviše prosječne koncentracije u plazmi utvrđene su u stupnjevima KBB2 i KBB3. Frekvencija pojavljivanja IHK ekspresije ADAMTS-4 u području intersticija, peritubularnih i glomerularnih kapilara bila je viša u skupinama s KBB u odnosu na kontrole. Ekspresija proteina ADAMTS-4 u području peritubularnih kapilara bila je značajno češća u bubrezima s razvijenom (KBB3-5) u odnosu na početnu (KBB1-2) fazu bolesti. Viši stupanj intersticijske fibroze bio je povezan s ekspresijom ADAMTS-4 u području bubrežnog intersticija. U analizi parova ADAMTS-4 značajno je češće izražen u skupini s nižom glomerulskom filtracijom i višim stupnjem fibroze u odnosu na skupinu biopsija učinjenih tijekom postupka transplantacije. Zaključno, ADAMTS-4 mogao bi biti novi biološki biljeg KBB, povezan sa stupnjem progresije bolesti i pokazateljima bubrežne fibroze te su potrebna daljnja istraživanja., Aim of the study was to investigate ADAMTS-4 molecule as a novel biomarker of CKD. ADAMTS-4 were determined in plasma and urine of 150 participants from 9 investigational groups: 5 (CKD stages 1-5), 1 haemodialysis, 1 peritoneal dialysis, 1 kidney transplant recipients and 1 healthy control. Methods included high-liquid performance chromatography accompanied by mass spectrometry of pooled group samples and ELISA of 79 individual samples. Gene enrichment analysis for significant biological pathways was performed afterwards. Immunohistochemistry (IHC) analysis included biopsy samples from 19 native and 34 transplanted kidneys with CKD and controls without CKD. Paired analysis included 15 posttransplant and their biopsy pairs, taken at transplantation. Expression of considerable number of proteins changed their trend significantly in stage 2 of CKD. ADAMTS-4 was not detected by proteomic analysis, but confirmed by ELISA. The highest plasma concentrations were detected in stages CKD2 and CKD3 but correlated poorly with CKD progression. Biopsy samples with CKD expressed ADAMTS-4 significantly more frequent than controls. Frequencies of IHC staining were significantly higher in biopsies with higher stages of fibrosis. In paired analysis expression was significantly higher in group with lower eGFR and higher fibrosis score. ADAMTS-4 could be a novel biomarker for chronic kidney disease but further validation is needed.

Aim: To examine the association between body mass index (BMI)-independent allometric body shape indices and kidney function. Materials and methods: We performed a two-sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM. BMI-independent allometric body shape indices were: A Body Shape Index (ABSI), Waist-Hip Index (WHI) and Hip Index (HI). Kidney function outcomes were: urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate and blood urea nitrogen. Furthermore, we investigated type 2 diabetes (T2D) as a potential mediator on the pathway to albuminuria. The main analysis was inverse variance-weighted random-effects MR in participants of European ancestry. We also performed several sensitivity MR analyses. Results: A 1-standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (β = 0.039 [95% confidence interval: 0.016, 0.063] log [UACR], P = 0.001 for ABSI, and β = 0.028 [0.012, 0.044] log [UACR], P = 6 x 10−4 for WHI) in women, but not in men. Meanwhile, a 1-SD increase in genetically predicted HI was associated with lower UACR in women (β = −0.021 [−0.041, 0.000] log [UACR], P = 0.05) and in men (β = −0.026 [−0.058, 0.005] log [UACR], P = 0.10). Corresponding estimates in individuals with diabetes were substantially augmented. Risk of T2D increased for genetically high ABSI and WHI in women (P < 6 x 10−19) only, but decreased for genetically high HI in both sexes (P < 9 x 10−3). No other associations were observed. Conclusions: Genetically high HI was associated with decreased risk of albuminuria, mediated through decreased T2D risk in both sexes. Opposite associations applied to genetically high ABSI and WHI in women only.

While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. In the present study, we report exome sequencing of individuals from 3 generations of a family with a dominant disease combining neutropenia, macrothrombocytopenia, and renal failure. We identified a heterozygous missense gain-of-function variant in the WAS gene (c.881T>C, p.I294T) that segregates with the disease and is already known to cause XLN. There was no pathogenic variant in MYH9, TUBB1, or ACTN1. This is the first report of a WAS gain-of-function variant associated with both the hematological phenotype of XLN (neutropenia, macrothrombocytopenia) and renal disease (proteinuria, renal failure) with glomerular tip lesion hyalinosis and actin condensations in effaced podocytes foot processes.

Purpose of review Advanced glycation endproducts (AGE) have an important role in the development of chronic complications in diabetes mellitus and in renal failure. Skin autofluorescence (SAF) is a simple noninvasive optical technique to estimate AGE levels in the dermis. SAF increases with age, but rises more rapidly in diabetes and renal failure, and is also associated with, and a predictor of their complications. Recent findings In recent large population studies, SAF is a strong predictor of development of type 2 diabetes (T2D), and in persons with known diabetes of its complications. SAF also predicts new cardiovascular disease (CVD) and mortality not only in individuals with known type 2 diabetes but also in the general population. SAF is a simple, powerful and independent predictor for development of type 2 diabetes (T2D), and also for cardiovascular disease and mortality in both persons with diabetes, and in the general population.

BACKGROUND: Heart failure and kidney disease share common pathophysiological pathways which can lead to mutual dysfunction, known as cardiorenal syndrome. The formation of cardiorenal syndrome in patients with chronic heart failure (CHF) is a natural manifestation of a functionally interconnected process at the organ level. Renal dysfunction is a common and independent factor in the progression of the disease, a high incidence of cardiovascular events, and death in the population. AIM: The aim of the study of the relationship between kidney dysfunction and the clinical course of the disease, quality of life, and indicators of the left ventricular systolic function in patients with CHF. MATERIALS AND METHODS: The study involved 150 patients with CHF I–III functional class according to the New York Heart Association. Exercise tolerance (6 min walk test) was assessed, the clinical condition was assessed using the clinical assessment scale, and the quality of life of patients with CHF (QoL) was assessed according to the Minnesota QOL questionnaire. An assessment of the functional state of the kidneys was carried out: The level of serum creatinine was determined; glomerular filtration rate (GFR) was calculated using the calculation formulas CKD-EPI. The assessment of renal blood flow was carried out using the ultrasound apparatus “SONOACEX6” (Korea). The structural and functional state of the myocardium and the process of left ventricle (LV) remodeling were assessed using the “MEDISON ACCUVIX V20” echocardiograph (Korea), using a 3.25 MHz transducer in standard echocardiographic positions, by the transthoracic method in accordance with the recommendations of the American Association of Echocardiography. RESULTS: The results of the study of physical performance according to 6 min walk test in patients of Group I with CHF GFR >60 ml/min/1.73 m2 were 363.59 ± 7.6 m, respectively. The decrease in the distance traveled according to the 6 min walk test data in Group II of patients with eGFR ≤60 ml/min/1.73 m2, exercise tolerance was more pronounced than in patients of Group I and this figure was 248.7 ± 11.0 m, which was 46.2% lower than the results of Group I of the study (p < 0.001). Analysis of the parameters of clinical manifestations according to the data of the clinical assessment scale showed that in patients of Group I, the total score was 5.5 ± 0.13 points. In CHF patients with renal dysfunction, changes were also noted at the level of the lobar and segmental renal arteries, characterized by a significant increase in pulsatility index and resistance index, there was a decrease in speed indicators during diastole, systole, and the average blood flow velocity. Further analysis of the parameters of LV systolic function ejection fraction (EF), as well as fractional shortening of the LV in systole (Fs%), showed that in Group II, these indicators had significant differences with Group I. There was a significant difference in EF by 10.5% and 25.4% and Fs% by 11.2% (p < 0.001). CONCLUSION: In CHF patients with impaired renal function, changes in renal blood flow were characterized by a significant increase in pulsatile and resistive indices, a decrease in the rate of renal blood flow at the level of the lobar and segmental renal arteries.

Objectives Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients. Methods A population pharmacokinetic model was developed using pharmacokinetic data from 18 patients with measured creatinine clearance (CLCR) ranging between 83 and 309 mL/min. Monte Carlo simulations were conducted to determine the PTA and the cumulative fraction of response (CFR) against Streptococcus pneumoniae and MRSA for five dosing regimens. Study registered at ClinicalTrials.gov (NCT03025841). Results Ceftaroline clearance increased non-linearly with CLCR, with lower concentrations and lower probability of reaching pharmacokinetic/pharmacodynamic targets when CLCR increases. For the currently recommended dosing regimen, the probability of having unbound ceftaroline concentrations above the MIC over the entire dose range is greater than 90% for MICs below 0.125 mg/L. Considering the distribution of MICs, this regimen would not be effective against MRSA infections (CFR between 21% and 67% depending on CLCR), but would be effective against S. pneumoniae infections (CFR >86%). Conclusions The recommended dosing regimen of ceftaroline seems sufficient for covering S. pneumoniae in ICU patients with ARC, but not for MRSA. Among the dosing regimens tested it appears that a constant infusion (50 mg/h) after a loading dose of 600 mg could be more appropriate for MRSA infections.

OBJECTIVE To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or RESULTS There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

Background: Adenine phosphoribosyl transferase (APRT) deficiency has great implications on graft survival in kidney transplant patients. This systematic review investigated the diagnostic pattern, treatment approach, and kidney transplant outcomes among kidney transplant patients with adenine phosphoribosyl transferase deficiency. Material and methods: Articles reporting the APRT enzyme deficiency and kidney allograft dysfunction were retrieved from PubMed/Medline, ScienceDirect, Cochrane library and Google scholar databases. Descriptive analysis was used to draw inferences. Results: The results from 20 selected studies covering 30 patients receiving 39 grafts had an average age of 46.37 years are presented. Graft survival time of more than 6 months was reported in 23 (76.7%) patients, while other 7 (23.3%) patients had graft survival time of less than 6 months. Only 4 (13.3%) patients had APRT deficiency before transplantation. After follow-up, one-third of the patients 10 (33.3%) had stable graft function, 1 patient had allograft loss, 8 (26.6%) patients had delayed graft function while the remaining 11 (36.6%) patients had chronic kidney graft dysfunction. Conclusions: APRT deficiency is an under-recognized, treatable condition that causes reversible crystalline nephropathy, leading to loss of allograft or allograft dysfunction. The study results showed that inclusion of genetic determination of APRT deficiency in the differential diagnosis of crystalline nephropathy, even in the absence of a history of nephrolithiasis, can improve renal outcomes and may improve allograft survival. Resumo Antecedentes: A deficiência de adenina fosforibosiltransferase (APRT) tem grandes implicações na sobrevida do enxerto em pacientes transplantados renais. Esta revisão sistemática investigou o padrão diagnóstico, a abordagem de tratamento e os desfechos do transplante renal entre pacientes transplantados renais com deficiência de adenina fosforibosiltransferase. Material e métodos: Os artigos que relatam sobre a enzima APRT e a disfunção do aloenxerto renal foram recuperados do PubMed/Medline, ScienceDirect, Biblioteca Cochrane e bancos de dados do Google Acadêmico. Utilizou-se a análise descritiva para extrair inferências. Resultados: Foram incluídos participantes que receberam 39 enxertos, a maioria dos quais provenientes de doadores vivos seguidos por doadores falecidos e doadores cadáveres. Foi relatado tempo de sobrevida do enxerto superior a 6 meses em 23 (76,7%) pacientes, enquanto outros 7 (23,3%) pacientes tiveram tempo de sobrevida do enxerto inferior a 6 meses. Apenas 4 (13,3%) pacientes apresentaram deficiência de APRT antes do transplante. Após acompanhamento, um terço dos pacientes, 10 (33,3%) apresentaram função do enxerto estável, 1 paciente teve perda do aloenxerto, 8 (26,6%) pacientes apresentaram função retardada do enxerto, enquanto os 11 (36,6%) pacientes restantes tiveram disfunção crônica do enxerto renal. Conclusões: A deficiência de APRT é uma causa subestimada e reversível de nefropatia cristalina que leva à disfunção do aloenxerto renal ou à perda total do aloenxerto. Os resultados deste estudo pedem a inclusão desta condição no diagnóstico diferencial de nefropatia cristalina, mesmo na ausência de um histórico de nefrolitíase.

Bradycardia, renal failure, atrioventricular (AV) nodal blockade, shock, and hyperkalemia (BRASH) syndrome is a recently-established entity precipitated by medication-induced AV nodal blockade. Despite its serious consequences, including death, clinical presentations, risk factors, and outcomes of the syndrome have not been well defined. We aim to summarize the existing evidence of BRASH syndrome.According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including"BRASH syndrome" and "bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia," from the inception of these databases to March 4, 2022.34 articles, including one observational study, 15 conference abstracts, and 18 case reports and case series, were included. While most patients were on beta blockers (83.3%) or calcium channel blockers (45.2%), other medications such as amiodarone were identified as precipitating agents. Atropine or glucagon were ineffective in reversing patients' symptoms, and 59.5% required inotropes or chronotropes. 7.1% expired due to BRASH syndrome.This systematic review summarizes the clinical characteristics of BRASH syndrome. Further studies to identify risks associated with the onset of BRASH syndrome and awareness of the critical syndrome are warranted.

OBJECTIVE: This study assessed the risk of developing chronic kidney disease (CKD) and decline in estimated glomerular filtration rate (eGFR) over a period of up to 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) compared with a historical control cohort of patients not treated with rhPTH(1-84).DESIGN: Retrospective cohort study of patients with chronic hypoparathyroidism treated with rhPTH(1-84) derived from the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309) and HEXT (NCT01199614, and its continuation study NCT02910466) clinical trials and a historical control cohort who did not receive PTH selected from an electronic medical record database.PATIENTS: One hundred and eighteen patients treated with rhPTH(1-84) and 497 patient controls.MEASUREMENTS: Incident CKD was defined as ≥2 eGFR measurements RESULTS: Over the 5-year period, Kaplan-Meier analyses showed that rhPTH(1-84)-treated patients had a significantly lower risk of developing CKD (log-rank p = .002) and a lower risk for a sustained eGFR decline ≥30% from baseline (log-rank p CONCLUSIONS: Patients with chronic hypoparathyroidism treated with rhPTH(1-84) in long-term clinical trials had a significantly lower risk of developing CKD compared with patients in a historical control cohort not treated with rhPTH(1-84).

BACKGROUND: The availability of dialysis facilities and distance traveled to receive care can impact health outcomes for patients with newly onset kidney failure. We examined recent changes in county-level number of dialysis facilities between 2012 and 2019 and assessed the association between county-level dialysis facility supply and the distance incident kidney failure patients travel to receive care. METHODS: We conducted a cross-sectional study of 828,427 adult patients initiating in-center hemodialysis for incident kidney failure between January 1, 2012, and December 31, 2019. We calculated the annual county-level number of dialysis facilities, and counties were categorized as having zero, one, two, or three or more dialysis facilities at the time of treatment initiation. We then measured the distance traveled between a patient’s home address and dialysis facility at treatment initiation (in miles) and evaluated the association between county-level number of dialysis facilities and distance traveled to initiate treatment. RESULTS: The average annual county-level number of facilities increased from 1.8 to 2.3 between 2012 and 2019. In our study period, 5% of incident adult kidney failure patients resided in a county that had zero dialysis facilities between 2012 and 2019. Compared with counties with three or more dialysis facilities, patients living in counties with no facilities in our study period traveled 14.3 miles (95% CI, 13.4 to 15.2) further for treatment. CONCLUSIONS: Kidney failure patients in counties that had no dialysis facilities traveled further, limiting their access to dialysis. Counties with no dialysis facilities at the end of the study period were more rural and had higher poverty than other counties.

Background: In a post hoc analysis, the frequency of occurrence of an early decline (dip) in estimated glomerular filtration rate (eGFR) after initiation of dapagliflozin and its association with outcomes were evaluated in patients with heart failure and reduced ejection fraction randomized in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial. Methods: Patients with heart failure with reduced ejection fraction with or without type 2 diabetes and an eGFR ≥30 mL·min −1 ·1.73 m −2 were randomized to placebo or dapagliflozin 10 mg daily. The primary outcome was the composite of worsening heart failure or cardiovascular death. The extent of the dip in eGFR between baseline and 2 weeks, patient characteristics associated with a >10% decline, and cardiovascular outcomes and eGFR slopes in participants experiencing this decline were investigated. Time-to-event outcomes were assessed in Cox regression from 14 days; eGFR slopes were assessed with repeated-measures mixed-effect models. Results: The mean change in eGFR between day 0 and 14 was −1.1 mL·min −1 ·1.73 m −2 (95% CI, −1.5 to −0.7) with placebo and −4.2 mL·min −1 ·1.73 m −2 (95% CI, −4.6 to −3.9) with dapagliflozin, giving a between-treatment difference of 3.1 mL·min −1 ·1.73 m −2 (95% CI, 2.6–3.7). The proportions of patients randomized to dapagliflozin experiencing a >10%, >20%, and >30% decline in eGFR were 38.2%, 12.6%, and 3.4%, respectively; for placebo, they were 21.0%, 6.4%, and 1.3%, respectively. The odds ratio for a >10% early decline in eGFR with dapagliflozin compared with placebo was 2.36 (95% CI, 2.07–2.69; P 10% decline in eGFR on dapagliflozin were older age, lower eGFR, higher ejection fraction, and type 2 diabetes. The hazard ratio for the primary outcome in patients in the placebo group experiencing a >10% decline in eGFR compared with ≤10% decline in eGFR was 1.45 (95% CI, 1.19–1.78). The corresponding hazard ratio in the dapagliflozin group was 0.73 (95% CI, 0.59–0.91; P interaction 10% initial decline in eGFR was not associated with greater long-term decline in eGFR or more adverse events. Conclusions: The average dip in eGFR after dapagliflozin was started was small and associated with better clinical outcomes compared with a similar decline on placebo in patients with heart failure with reduced ejection fraction. Large declines in eGFR were uncommon with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

Renal impairment (RI) confers a poor prognosis in multiple myeloma. Reversibility of renal function is associated with improved survival in such patients. Patients in developing countries often present at an advanced stage and renal impairment is present in up to 40% of patients at diagnosis. We studied the renal outcome and survival of these patients with bortezomib-based induction therapy.It was a single-center prospective study in a tertiary care multi-specialty institute in patients of newly diagnosed multiple myeloma (NDMM) who presented with RI from July 2018 to December 2019. The diagnosis of multiple myeloma was made based on IMWG14 criteria. All patients received bortezomib and or immunomodulatory drug-based triplet or quadruplet induction therapy. Hematological and renal outcomes were assessed as per IMWG 2016 criteria.Among 216 consecutive patients of NDMM, RI was seen in 91 (42.2%) patients. The median age of 91 patients was 60 years. (range- 32-80 years). Light chain myeloma was seen in 26% (n = 24) of patients. The median estimated glomerular filtration rate (eGFR) was 15.36 mL/min (3.1-38 mL/min) and a majority of patients were in the advanced ISS stage. (ISS III = 85.7%). Thirty-six (39.5%) patients received hemodialysis at presentation. Renal response was seen in 67 (73%) patients and 20 (out of 36; 55%) became dialysis independent over a median time of 38 days (Range 15-160 days). At a median follow-up of 14.7 months, 30 (33%) patients had died, of which, 14 (15.4%) patients had early mortality (within 2 months of diagnosis). Presence of light chain myeloma and cast nephropathy (definite or probable) were identified as independent predictors of poor renal recovery on multivariate analysis. (HR = 2.841; 95% CI [1.471-5.486], P = .002 for light chain myeloma; HR = 1.859; 95% CI (1.087-3.180); P = .024 for cast nephropathy) Patients with low eGFR at presentation (12.5 mL/min) were more likely to have persistent renal insufficiency. (HR-3.521; 95% CI (1.856-6.679), P = .000). Patients who attained sustained renal recovery had improved survival as compared to patients in whom renal function failed to improve. (median OS- not reached vs. 8.3 months, P = .000) Achievement of hematological response and independence from hemodialysis was associated with improved survival on multivariate analysis.Renal impairment was reversible in almost three-fourths of NDMM patients. achievement of hematological response and hemodialysis independence were independent predictors of improved overall survival in NDMM patients with RI.

To determine predisposing factors that may lead to the development of compartment syndrome (CS) in patients with acute lower limb ischemia (ALLI) managed with intra-arterial catheter-directed thrombolysis (CDT).This is a retrospective study of patients admitted between 01/2002 and 12/2015 to three university hospitals in Tampere, Turku, and Oulu, Finland, with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb). Patients managed with CDT and aspiration thrombectomies (AT) as an adjunct to CDT were included in the study. Multivariable binary logistic regression models were used to detect possible risk factors for the development of CS and its impact on the limb salvage and survival. Amputation-free survival (AFS) rates of CS and non-CS patients were compared using Kaplan-Meier survival analysis. The length of hospitalization was calculated and compared between the CS and non-CS groups.A total of 292 CDTs with or without ATs were performed on patients with a mean age of 71 years (standard deviation 13 years), 151 (51.7%) being male. Altogether, 12/292 (4.1%) treatment-related CS cases were registered. Renal insufficiency (odds ratio [OR] 4.27, P = 0.07) was associated with an increased risk of CS. All CS cases were managed with fasciotomies. Treatment with fasciotomy was associated with a prolonged hospitalization of a median of 7 days versus the 4 days for non-CS patients, P0.001. During the median follow-up of 51 months (interquartile range 72 months), 152/292 (52.1%) patients died and 51/292 (17.5%) underwent major amputations. CS was not associated with an increased risk of mortality, but it was associated with a higher risk of major amputation (OR 3.87, P = 0.027). The AFS rates of patients with or without CS did not significantly differ from each other in the long term.CS after CDT for the treatment of ALLI is uncommon. Renal insufficiency is associated with an increased risk of CS. Fasciotomy prolongs the hospitalization. Patients with CS are exposed to an increased risk of major amputation.

Gefapixant, a P2X3 receptor antagonist, has demonstrated efficacy in patients with refractory or unexplained chronic cough. We investigated the effect of renal impairment (RI) on the pharmacokinetics (PK) of gefapixant 50 mg in an open-label, single-dose study enrolling participants with moderate (n = 6) or severe (n = 6) RI, end-stage renal disease (ESRD; n = 6) under hemodialysis (HD) and non-HD conditions, and healthy matched controls (n = 6). Serial plasma and urine samples for gefapixant concentrations were collected at selected time points over 72 and 48 hours after dosing, respectively. Linear regression analysis predicted a 1.87-, 2.79-, and 3.76-fold higher exposure (area under the plasma concentration-time curve) for participants with mild, moderate, and severe RI, respectively, than that for healthy matched control participants. Categorical analysis exhibited a 2.98-, 4.43-, and 4.74-fold higher exposure for participants with moderate RI, severe RI, and ESRD, respectively, than that for healthy matched control participants. Apparent oral clearance and renal clearance was lower in participants with various degrees of RI, by 66% to 90%, compared with healthy matched control participants, explaining the increased gefapixant exposure with increasing degrees of renal impairment. Gefapixant area under the plasma concentration-time curve and maximum plasma concentration decreased by ≈25% under HD conditions compared to non-HD conditions. Single-dose administration of gefapixant was generally well tolerated in this study. The data from this trial informed the enrollment of phase 3 clinical trials that evaluated the efficacy and safety of gefapixant in2000 participants with refractory or unexplained chronic cough. Those efficacy and safety data, combined with analysis of population pharmacokinetics from across the entire development program, will be used to evaluate the magnitude of the renal impairment effect in the refractory or unexplained chronic cough population and to determine any dose adjustment recommendations.

Renal failure (RF) is a risk factor for mortality among hospitalized patients. However, its role in COVID-19-related morbidity and mortality is inconclusive. The aim of the study was to determine whether RF is a significant predictor of clinical outcomes in COVID-19 hospitalized patients based on a retrospective, nationwide, cohort study.The study sample consisted of patients hospitalized in Israel for COVID-19 in two periods. A random sample of these admissions was selected, and experienced nurses extracted the data from the electronic files. The group with RF on admission was compared to the group of patients without RF. The association of RF with 30-day mortality was investigated using a logistic regression model.During the two periods, 19,308 and 2994 patients were admitted, from which a random sample of 4688 patients was extracted. The 30-day mortality rate for patients with RF was 30% (95% confidence interval (CI): 27-33%) compared to 8% (95% CI: 7-9%) among patients without RF. The estimated OR for 30-day mortality among RF versus other patients was 4.3 (95% CI: 3.7-5.1) and after adjustment for confounders was 2.2 (95% CI: 1.8-2.6). Furthermore, RF patients received treatment by vasopressors and invasive mechanical ventilation (IMV) more frequently than those without RF (vasopressors: 17% versus 6%, OR = 2.8, p0.0001; IMV: 17% versus 7%, OR = 2.6, p0.0001).RF is an independent risk factor for mortality, IMV, and the need for vasopressors among patients hospitalized for COVID-19 infection. Therefore, this condition requires special attention when considering preventive tools, monitoring, and treatment.

Diabetic kidney disease is the most frequent cause of kidney failure, accounting for half of all cases worldwide. Moreover, deaths from diabetic kidney disease increased 106% between 1990 and 2013, with most attributed to cardiovascular disease. Recommended screening and monitoring for diabetic kidney disease are conducted in less than half of patients with diabetes. Standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker is correspondingly low. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid antagonist are highly effective therapies to reduce kidney and cardiovascular risks in diabetic kidney disease. However

Background and objectives: C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years. Design, setting, participants, & measurements: To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome. Results: Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitialfibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores. Conclusions: Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

RATIONALE AND OBJECTIVE: Non-Hispanic Black and Hispanic patients present with kidney failure at younger ages than white patients. Younger patients are also more likely to receive transplants and home dialysis than in-center hemodialysis (ICHD), but it is unknown whether racial/ethnic disparities in treatment differ by age. We compared use of kidney replacement therapies between racial/ethnic groups among patients with incident kidney failure, overall, and by age. STUDY DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 830,402 U.S. adult (>21 years) patients initiating kidney failure treatment during 2011–2018. EXPOSURES: Patient race/ethnicity (non-Hispanic Black, non-Hispanic white, Hispanic, or other) and age group (22–44, 45–64, 65–74, or 75–99). OUTCOME: Treatment modality (transplantation, peritoneal dialysis [PD], home hemodialysis [HHD], or ICHD) as of day 90 of treatment. ANALYTICAL APPROACH: Differences in treatment modalities were quantified for patient subgroups defined by race/ethnicity and age. Log-binomial regression models were fit to estimate adjusted risk ratios (ARRs). RESULTS: Eighty-one percent of patients were treated with ICHD, 3.0% underwent transplantation (85% pre-emptive, 57% living donor), 10.5% were treated with PD, and 0.7% were treated with HHD. Absolute disparities in treatment were most pronounced among patients aged 22–44. Compared to non-Hispanic White patients whose percentages of treatment with transplantation, PD, and HHD were 10.9%, 19.0%, and 1.2%, non-Hispanic Black patients were less commonly treated with each modality (unadjusted percentages: 1.8%, 13.8%, and 0.6%, respectively) as were Hispanic patients (4.4%, 16.9%, and 0.5%, respectively; all differences p

RATIONALE & OBJECTIVE: Heavy metals are known to induce kidney damage and recent studies have linked minor exposures to cadmium and arsenic with increased risk of kidney allograft failure, yet the potential association of lead (Pb) with late graft failure in kidney transplant recipients (KTR) remains unknown.STUDY DESIGN: Prospective cohort study in the Netherlands.SETTING & PARTICIPANTS: We studied outpatient KTR (n=670) with a functioning graft for ≥1 year recruited at a university setting (2008-2011, NCT02811835) and followed, on average, for 4.9 (IQR, 3.4‒5.5) years. Additionally, end-stage kidney disease patients (n=46) enrolled in the ongoing TransplantLines Cohort and Biobank Study (2016-2017, NCT03272841) were studied at admission for transplantation and at 3, 6, 12, and 24 months after transplantation.EXPOSURE: Plasma Pb was log2 transformed to estimate the association with outcomes per doubling of plasma Pb concentration and also considered categorically as tertiles of the Pb distribution.OUTCOME: Kidney graft failure (restart of dialysis or re-transplantation) with the competing event of death with a functioning graft.ANALYTICAL APPROACH: Multivariable-adjusted cause-specific hazards models where follow-up of KTR who died with a functioning graft was censored.RESULTS: Median baseline plasma Pb was 0.31 (IQR, 0.22─0.45) μg/L among all KTRs. During follow-up, 78 (12%) KTR developed graft failure. Higher plasma Pb was associated with increased risk of graft failure (HR 1.59, 95% CI 1.14‒2.21 per doubling; P=0.006) independent of age, sex, transplant characteristics, eGFR, proteinuria, smoking status, alcohol intake, and plasma concentrations of cadmium and arsenic. These findings remained materially unchanged after additional adjustment for dietary intake and were consistent with those of analyses examining Pb categorically. In serial measurements, plasma Pb was significantly higher at admission for transplantation than at 3-months post-transplant (P=0.001), after which it remained stable over 2 years of follow-up (P=0.2).LIMITATIONS: Observational study design.CONCLUSIONS: Pretransplant plasma Pb concentrations, which fall after transplantation, are associated with increased risk of late kidney allograft failure. These findings warrant further studies to evaluate whether preventive or therapeutic interventions to decrease plasma Pb may represent novel risk-management strategies to decrease the rate of kidney allograft failure.

BACKGROUND: Kidney Failure (KF) is associated with impaired physical function, reduced health-related quality of life (HRQoL), increased healthcare costs, and high rates of cardiovascular complications and mortality. Among individuals with KF, well-being and related constructs, such as positive affect, optimism, self-efficacy, and resilience, may have both mental and physical health benefits, independent of the effects of negative emotions and affective syndromes. However, there has been minimal review of these characteristics in people with KF. METHODS: We conducted a scoping review, using a semi-systematic approach, to summarize the relationships between well-being characteristics and renal health, the potential mechanisms mediating these relationships, and the effects of interventions that promote positive constructs on adherence and health outcomes. We conducted database searches using PubMed and PsycInfo until November 2020. Articles were included if they examined (1) relationships between a wellbeing construct and health outcome in patients with KF, (2) potential biological or behavioral mediators, or (3) interventions that target positive psychological constructs as outcomes or mediators in KF, and (4) were written in English or Spanish. RESULTS: Among patients with KF, well-being constructs are associated with increased health-related quality of life (HRQoL), reduced morbidity and complications, and increased survival. Potential mechanisms mediating these associations include reduced inflammation, improved autonomic and endothelial function, and improved health behavior adherence. Psychological and psychosocial interventions promoting well-being have primarily focused on improving selfefficacy to promote behavior change, with limited study of interventions to promote positive psychological constructs in this population. CONCLUSIONS: Further research is needed to better understand the relationship between well-being constructs and health, specific to KF populations. This could inform the development of needed interventions that harness the promotion of other positive characteristics to improve well-being and health.

Chronic kidney disease (CKD) after solid organ transplant is a common clinical presentation, affecting 10% to 20% of liver, heart, and lung transplant recipients and accounting for approximately 5% of the kidney transplant waiting list. The causes of CKD are different for different types of transplants and are not all, or even predominantly, due to calcineurin inhibitor toxicity, with significant heterogeneity particularly in liver transplant recipients. Many solid organ transplant recipients with advanced CKD benefit from kidney transplantation but have a higher rate of death while waitlisted and higher mortality after transplant than the general kidney failure population. Recent organ allocation policies and proposals have attempted to address the appropriate identification and prioritization of candidates in need of a kidney transplant, either simultaneous with or after nonkidney transplant. Future research should focus on predictive factors for individuals identified as being at high risk for progression to kidney failure and death and on strategies to preserve kidney function and minimize the CKD burden in this unique patient population.

Objective Proteinuria is the clinical expression of lupus nephritis and despite recent advances in the therapeutic armamentarium for lupus nephritis, morbidity and mortality rates remain high. Therefore, the identification of factors that predict lupus nephritis is paramount in preventing damage accrual and disease progression. Lipoprotein (a) (Lp[a]) is a primarily genetically inherited plasma lipoprotein with pro-thrombotic and pro-atherosclerotic effects. Elevated Lp(a) has been observed at early stages of renal impairment in the general population and is associated with the development of chronic kidney disease. However, little is known about renal implications of Lp(a) in SLE. Thus, we evaluated Lp(a) and atherosclerotic events, thrombotic events, renal disease, and disease activity in patients with SLE. Methods SLE patients fulfilling the revised American College of Rheumatology (ACR) or SLICC classification criteria with a measurement of Lp(a) were included in the analysis. A cutoff of 125 nmol/L was chosen based on expert opinion. Chi-square test was used to compare the differences between patient characteristics and Lp(a) levels. Logistic regression or linear regression were used, where appropriate, to assess the association between Lp(a) values and the measured outcomes. Results Lp(a) levels from 562 patients were analyzed. There was an association between elevated Lp(a) and a history of proteinuria (OR 1.58, p-value = 0.02). This association remained significant following adjustment for age, sex, race, low C3, and elevated anti-dsDNA (OR = 1.55, p-value = 0.04). There was also an association with eGFR < 60 ( p = 0.02). Patients with elevated Lp(a) had higher physician global activity ( p = 0.01) and erythrocyte sediment rate ( p = 0.03). Conclusion Elevated Lp(a) was associated with proteinuria, independent of known factors associated with lupus proteinuria, as well as reduced eGFR and physician global activity. Our findings highlight the potential role of Lp(a) as a noninvasive biomarker for early renal disease in SLE.

BACKGROUND: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization.OBJECTIVES: The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk.METHODS: Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations.RESULTS: Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78).CONCLUSIONS: In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532).

Chronic kidney disease (CKD) is a major global epidemic associated with increased morbidity and mortality. Despite the effectiveness of kidney protection strategies of hypertension, diabetes, and lipid control and use of newer hypoglycemic agents and anti-angiotensin II drugs, the nephropathy in CKD continues unabated toward irreversible kidney failure. Thus, interventions targeting modifiable risk factors in CKD such as metabolic acidosis (MA) are needed. Acid reduction with sodium-based alkali has been shown to be an effective kidney-protection strategy for patients with CKD and reduced glomerular filtration rate (GFR). Small-scale studies reveal diets emphasizing ingestion of plant-sourced over animal-sourced protein reduce dietary acid, improve MA, and slow further nephropathy progression in patients with CKD and reduced GFR. Additionally, veverimer, an investigational, nonabsorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as a novel treatment for MA. As further studies define how to best use these interventions for kidney protection, clinicians must become aware of their potential utility in the management of patients with CKD. The aim of the present review is to explore the various intervention strategies that increase or normalize serum [HCO

Renal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4α (HNF4α), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4α expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4α resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4α1 and Hnf4α2, we showed that HNF4α2 is the main osseous Hnf4α isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4α2 prevented bone loss in mice with CKD. Our results showed that HNF4α2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.

BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of biomarkers in murine models of repair and atrophy after ischemic reperfusion injury (IRI).RESULTSAfter 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney atrophy in mice after IRI.CONCLUSIONSustained tissue injury and inflammation, and slower restoration of tubular health, are associated with higher risk of kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.FUNDINGNIH and NIDDK (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, K01DK120783, and R01DK093771).

Objetivo: Identificar, nas evidências científicas, os cuidados dos enfermeiros da unidade de terapia intensiva para o manejo dos pacientes submetidos à hemodiálise.Metodologia:Trata-se de um estudo de revisão bibliográfica, na qual objetivou estudar as vivências de pacientes em tratamento de hemodiálise. Á vista disso, foi encontrado um total de 25 artigos, sendo 10 que não mencionavam diretamente do assunto tratado, restando 15 artigos, porém alguns eram muito antigos ou abordavam o assunto muito amplamente, assim, foram escolhidos 10 artigos para ser a base do estudo, atendendo todos os critérios de inclusão relatados na metodologia.Resultado e discussão:A doença e o tratamento hemodialítico podem afetar a autopercepção, o comportamento e as relações sociais, diversos projetos existenciais tendem a ser anulados ou modificados pela situação vivida. O cuidado a essas pessoas deve ser realizado de maneira coerente, responsável, humanizado e direcionado para sua singularidade.Conclusão:O presente estudo evidenciou que a prática baseada em evidências e tomada de decisão do profissional enfermeiro atuante na unidade de terapia intensiva frente ao procedimento de hemodiálise, garantindo uma assistência segura e com vistas à integralidade, no que tange aos cuidados para o manejo nos períodos pré, trans e pós hemodiálise.

Background and Objectives: Chronic Kidney Disease of uncertain or non-traditional etiology (CKDnT) is a form of chronic kidney disease of undetermined etiology (CKDu) and is not associated with traditional risk factors. The aim of this study was to investigate the association of polymorphisms rs2070744, 4b/a and rs1799983 of the NOS3 gene with CKDnT in Mexican patients. Materials and Methods: We included 105 patients with CKDnT and 90 controls. Genotyping was performed by PCR-RFLP’s, genotypic and allelic frequencies were determined and compared between the two groups using χ2 analysis, and differences were expressed as odd ratios with 95% confidence intervals (CI). Values of p < 0.05 were considered statistically significant. Results: Overall, 80% of patients were male. The rs1799983 polymorphism in NOS3 was found to be associated with CKDnT in the Mexican population (p = 0.006) (OR = 0.397; 95% CI, 0.192–0.817) under a dominant model. The genotype frequency was significantly different between the CKDnT and control groups (χ2 = 8.298, p = 0.016). Conclusions: The results of this study indicate that there is an association between the rs2070744 polymorphism and CKDnT in the Mexican population. This polymorphism can play an important role in the pathophysiology of CKDnT whenever there is previous endothelial dysfunction.

Introduction: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). Methods: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1–4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried’s frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. Results: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. Conclusion: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients. RESUMO Introdução: Fragilidade e sua associação com DRC foram estabelecidas anteriormente. O presente estudo aprofundou esta associação, estudando distribuição da fragilidade entre grupos definidos por diferentes estágios da doença. Também identificou déficits de saúde associados e explorou sua associação com taxa de filtração glomerular estimada (TFGe) e relação albumina/creatinina urinária (RAC). Métodos: Realizou-se uma pesquisa transversal em 90 pacientes com DRC Estágios 1–4 não dependentes de diálise, recrutados em três grupos estratificados de 30 participantes cada, conforme estágio da doença. Avaliou-se fragilidade usando os critérios de fragilidade de Fried e registraram-se os déficits de saúde associados usando uma lista pré-determinada. A depressão foi verificada utilizando a escala de depressão de 4 pontos. Resultados: 21,1% dos participantes eram frágeis e 43,3% eram pré-frágeis. A proporção de fragilidade nos grupos de DRC A (Estágios 1 e 2), B (Estágio 3a), e C (Estágios 3b e 4) foi de 10%, 13,3%, 40% respectivamente. A associação de déficits de saúde, incluindo comorbidades, parâmetros físicos, estado mental, atividades diárias etc. com RAC, TFGe e estágios da DRC não foi estatisticamente significativa. Cerca de um em cada dois participantes frágeis estava depressivo comparados com 14% entre não frágeis. Conclusão: A distribuição enviesada de 21% dos indivíduos frágeis identificados em nosso estudo indica associação entre fragilidade e doença renal progressiva. Indivíduos frágeis apresentaram menor TFGe, maior RAC, eram mais propensos a depressão, tinham maior índice de déficits de saúde e desempenho inferior no Índice de Atividades da Vida Diária de Barthel e WHOQOL. A identificação precoce da depressão melhoraria o atendimento desses pacientes.