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Background : Patients with advanced kidney disease have a symptomatic and psychological burden which warrant renal supportive care or palliative care. However, the impact of do-not-resuscitate consent type (signed by patients or surrogates) on end-of-life treatments in these patients remains unclear. Objective : We aim to identify influential factors correlated with different do-not-resuscitate consent types in patients with advanced kidney disease and the impact of do-not-resuscitate consent types on various life-prolonging treatments. Methods : This was a retrospective observational study. We included patients aged 20 years and over, diagnosed with advanced kidney disease and receiving palliative and hospice care consultation services between January 2014 and December 2018 in a tertiary teaching hospital in Taiwan. We reviewed medical records and used logistic regression to identify factors associated with do-not-resuscitate consent types and end-of-life treatments. Results : A total of 275 patients were included, in which 21% signed their do-not-resuscitate consents. A total of 233 patients were followed until death, and 32% of the decedents continued hemodialysis, 75% underwent nasogastric (NG) tube placement, and 70% took antibiotics in their final seven days of life. Do-not-resuscitate consents signed by patients were associated with reduced life-prolonging treatments including feeding tube placement and antibiotic use in the last seven days (odd ratio and 95% confidence interval were 0.16, 0.07-0.34 and 0.33, 0.16-0.69, respectively) compared to do-not-resuscitate consents signed by surrogates. Conclusions: Do-not-resuscitate consent signed by patients and not by surrogates may reflect better patients' autonomy and reduced life-prolonging treatments in the final seven days of patients with advanced kidney disease.

Background and Objectives: The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality., Design, Setting, Participants, & Measurements: The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m 2 ) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011., Results: A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance ( P interaction =0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance ( i.e. , <1.5 ml/min per 1.73 m 2 ), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance ( i.e. , ≥1.5 ml/min per 1.73 m 2 ; P interaction <0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk ( P trend <0.001 for both) irrespective of residual renal urea clearance strata ( P interaction =0.34 and P interaction =0.53, respectively)., Conclusions: Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population., (Copyright © 2017 by the American Society of Nephrology.)

The prevalence of renal disease continues to increase worldwide. When normal kidney is injured, the damaged renal tissue undergoes pathological and physiological events that lead to acute and chronic kidney diseases, which frequently progress to end stage renal failure. Current treatment of these renal pathologies includes dialysis, which is incapable of restoring full renal function. To address this issue, cell-based therapy has become a potential therapeutic option to treat renal pathologies. Recent development in cell therapy has demonstrated promising therapeutic outcomes, in terms of restoration of renal structure and function impaired by renal disease. This review focuses on the cell therapy approaches for the treatment of kidney diseases, including various cell sources used, as well recent advances made in preclinical and clinical studies.

Background/aims: We analyzed chronological changes in hemoglobin according to renal function changes over a 5-year follow-up period., Methods: We enrolled 5,266 adults with a glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m(2) at an initial examination at a routine health check-up; a follow-up examination was conducted 5 years later. We categorized the subjects according to GFR ratio (groups 1, 2, and 3, defined as GFRratio ≥ 1.00, 0.75 to 0.99, and < 0.75, respectively)., Results: The mean hemoglobin level in subjects with a GFR of 60 to 74 was higher than in those with a GFR of 75 to 89 or ≥ 90 mL/min/1.73 m(2) at the initial examination (all p < 0.001). Among females and males, the frequencies of increased hemoglobin were 46.8% and 40.6% in the GFRratio group 1, 52.4% and 46.1% in group 2, and 59.6% and 52.5% in group 3 over the 5-year period, respectively (all p < 0.001). With multiple logistic regression, group 3 showed 1.594-fold (95% confidence interval [CI], 1.127 to 2.225) and 1.353-fold (95% CI, 1.000 to 1.830) higher likelihoods of increased hemoglobin over the 5-year follow-up period in females and males, respectively. The estimated difference in hemoglobin level was highest in group 3 in both genders. These findings were more evident in subgroups without metabolic syndrome, diabetes mellitus, hypertension, or GFR less than 90 mL/min/1.73 m(2)., Conclusions: Among a population with GFR ≥ 60 mL/min/1.73 m(2), a mild decrease in GFR over a 5-year follow-up period was associated with an increase in hemoglobin levels.

Acute kidney injury (AKI) is a complication associated with vancomycin use. There is evidence that this was related to the presence of supratherapeutic vancomycin levels rather than the drug itself. The area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC) dosing for vancomycin has replaced trough‐based dosing, but the impact of this change on AKI rates remains unclear. A retrospective cohort study was conducted in a tertiary care teaching hospital. Patients from the trough cohort were recruited from January 1, 2019, to June 30, 2019, and the AUC/MIC cohort from July 1, 2021, to January 1, 2022. Sociodemographics, clinical characteristics, and concomitant medications were obtained. AKI was defined by The Kidney Disease Improving Global Outcomes. A total of 1056 patients were included, 509 in the trough cohort and 547 in the AUC/MIC cohort. The baseline rates of chronic kidney disease were 15.4% and 9.9%, respectively. The AKI rates were 15.9% and 11.9% for trough and AUC/MIC cohorts, respectively (P‐value .045). The most frequent nephrotoxins were piperacillin/tazobactam (TZP), diuretics, and IV contrast for both groups. The rates of supratherapeutic levels were higher in the trough cohort (20.7%) than in the AUC/MIC cohort (6.6%). The multivariate logistic regression analysis showed that trough dosing was not associated with increased rates of AKI (OR = 0.96 CI 0.64–1.44). Supratherapeutic levels (OR = 4.64), diuretics (OR = 1.62), TZP (OR = 2.01), and ICU admission (OR = 1.72) were associated with AKI. Vancomycin AUC/MIC dosing strategy was associated with decreased rates of supratherapeutic levels of this drug compared to trough dosing, with a trend toward lower rates of AKI. [ABSTRACT FROM AUTHOR]

Summary Persistent albuminuria (PA) is common in sickle cell anaemia (SCA). With the association of chronic kidney disease (CKD) with increased mortality, biomarkers that predict its development or progression are needed. We evaluated the association of select biomarkers with PA in adults with SCA using Kruskal–Wallis rank‐sum test and logistic regression models, with adjustment for multiple testing. Of 280 subjects, 100 (35.7%) had PA. Median plasma levels of soluble vascular cell adhesion molecule‐1 (VCAM‐1) (1176.3 vs. 953.4 ng/mL, false discovery rate [FDR] q‐value <0.003), thrombin–antithrombin complex (5.5 vs. 4.7 ng/mL, FDR q‐value = 0.04), and urinary angiotensinogen (AGT) (12.2 vs. 5.3 ng/mg, FDR q‐value <0.003), urinary nephrin (30.6 vs. 27.2 ng/mg, FDR q‐value = 0.04), and urinary kidney injury molecule‐1 (KIM‐1) (0.8 vs. 0.5 ng/mg, FDR q‐value <0.003), normalized to urine creatinine, were significantly higher in subjects with PA. In multivariable analysis, only urinary AGT (odds ratio = 1.058, FDR q‐value <0.0001) remained a significant predictor of PA. In addition, soluble VCAM‐1 (FDR q‐value <0.0001), D‐dimer (FDR q‐value <0.0001), urinary AGT (FDR q‐value <0.0001), KIM‐1 (FDR q‐value <0.0001), and nephrin (FDR q‐value <0.0001) were significantly associated with urine albumin–creatinine ratio in multivariable analyses. Longitudinal studies to evaluate the predictive capacity of biomarkers for the development and progression of CKD in SCA are warranted. [ABSTRACT FROM AUTHOR]

Light chain deposition disease (LCDD) is a rare, clonal plasma cell proliferative condition. The deposition of nonamyloid monoclonal immunoglobulin light chains predominantly affects the kidneys, which may lead to end-stage renal disease, eventually requiring renal replacement therapy. The present study reported a rare case of LCDD that was confirmed after renal transplantation. A 49-year-old man initially presented with heavy proteinuria, hypoproteinemia, hyperlipidemia and renal insufficiency. The patient was diagnosed with nephrotic syndrome and pathological examination revealed fibrillary glomerulonephritis in 2014. Treatment was started with prednisolone. About 5 years later, the patient began to receive continuous hemodialysis due to worsening serum creatinine levels. Renal allograft transplantation was performed in 2020 and dialysis independence was achieved. Laboratory findings before renal transplantation revealed that serum and urine immunofixation electrophoresis was negative. Allograft kidney biopsy established the pathological diagnosis of LCDD at >1 year after renal transplantation for renal dysfunction. The treatment is challenging due to the lack of generally accepted standard treatment practices. Administration of bortezomib combined with dexamethasone was started. As anemia and renal failure developed progressively, the treatment was switched to anti-CD38 antibody and continuous hemodialysis was restarted. The best response achieved was hematological partial response and relief of anemia. However, the patient's renal function did not improve and he remains to have end-stage kidney disease. LCDD is easily missed in cases in which serum and urine immunofixation electrophoresis is negative. Hence, early recognition of LCCD based on kidney biopsy is important. To the best of our knowledge, the use of anti-CD38 antibody therapy in patients with LCDD is rarely reported. Anti-CD38 antibody is effective in treating LCDD, but it may not reverse the marked deterioration of renal function. [ABSTRACT FROM AUTHOR]

Background Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. Methods We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence and survival. Results The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. Immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidences, of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had 5-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death [adjusted hazard ratio 1.8 (95% confidence interval 1.6–1.9)] compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). Conclusion The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach. [ABSTRACT FROM AUTHOR]

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay. [ABSTRACT FROM AUTHOR]

HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)- activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes, and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the profibrogenic PKR-STAT3-platelet-derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN. [ABSTRACT FROM AUTHOR]

This was a retrospective study. This study investigated the occurrence of a composite endpoints (cardiovascular and cerebrovascular events, end‐stage renal disease, and death) in 153 patients (aged ≥ 18 years) with a diagnosis of in chronic kidney disease (CKD). Based on morning blood pressure surge (MBPS) defined as ≥35 mm Hg, patients were divided into two groups: with MBPS (n = 50) and without MBPS (n = 103). All patients were followed up for at least 1 year. Baseline demographic, laboratory and follow‐up data were collected. The clinical characteristics of the two groups were compared. The relationships between MBPS and endpoint events were analyzed using the Kaplan–Meier method and Cox regression model. In total, 153 patients (mean age 41.8 years; 56.86% males) were included in this study. During the follow‐up period (mean 4.3 years), 34 endpoint events occurred. After adjustment for the covariates, the risk of cardiovascular and cerebrovascular events, end‐stage renal disease and death remained significantly higher in patients with MBPS (hazard ratio [HR] and 95% confidence interval [CI] 3.124 [1.096–9.130]]) Among the other variables, systolic blood pressure, and night‐time and daytime pulse pressures remained significantly associated with outcome in patients of CKD (1.789 [1.205–2.654], 1.710 [1.200–2.437], and 1.318 [1.096–1.586], respectively]. In conclusions, MBPS was identified as an independent prognostic factor for composite endpoint events (cardiovascular and cerebrovascular events, end‐stage renal disease and death) patients with chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Background: DKD, a leading cause of chronic kidney and end-stage renal disease, lacks robust immunological research. Recent GWAS utilizing SNPs and CNVs has shed light on immune mechanisms of kidney diseases. However, DKD's immunological basis remains elusive. Our goal is to unravel cause-effect relationships between immune cells and DKD using Mendelian randomization. Methodology: We analyzed FinnGen data (1032 DKD cases, 451,248 controls) with 731 immunocyte GWAS summaries (MP=32, MFI=389, AC=118, RC=192). We employed forward and reverse Mendelian randomization to explore causal links between immune cell traits and DKD. Sensitivity analysis ensured robustness, heterogeneity checks, and FDR correction minimized false positives. Results: Our study explored the causal link between diabetic nephropathy (DKD) and immunophenotypes using two-sample Mendelian Randomization (MR) with IVW. Nine immunophenotypes were significantly associated with DKD at p<0.05 after FDR correction. Elevated CD24, CD3 in Treg subsets, CD39+ CD4+, and CD33-HLA DR-AC correlated positively with DKD risk, while CD27 in B cells and SSC-A in CD4+ inversely correlated. Notably, while none showed significant protection, further research on immune cells' role in DKD may provide valuable insights. Conclusion: The results of this study show that the immune cells are closely related to DKD, which may be helpful in the future clinical study. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes. Methods: We conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups. Results: The CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD. Conclusions: The dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD. [ABSTRACT FROM AUTHOR]

Excessive activation of the mineralocorticoid receptor (MR) is implicated in cardiovascular and renal disease. Decreasing MR activation with MR antagonists (MRA) is effective to slow chronic kidney disease (CKD) progression and its cardiovascular comorbidities in animal models and patients. The present study evaluates the effects of the MR modulator balcinrenone and the MRA eplerenone on kidney damage in a metabolic CKD mouse model combining nephron reduction and a 60% high-fat diet. Balcinrenone and eplerenone prevented the progression of renal damages, extracellular matrix remodeling and inflammation to a similar extent. We identified a novel mechanism linking MR activation to the renal proteoglycan deposition and inflammation via the TLR4 pathway activation. Balcinrenone and eplerenone similarly blunted this pathway activation. [ABSTRACT FROM AUTHOR]

Personalized medicine, which involves modifying treatment strategies/drug dosages based on massive laboratory/imaging data, faces large statistical and study design problems. The authors believe that the use of continuous multidimensional data, such as those regarding gut microbiota, or binary multidimensional systems properly transformed into a continuous variable, such as the epigenetic clock, offer an advantageous scenario for the design of trials of personalized medicine. We will discuss examples focusing on kidney diseases, specifically on IgA nephropathy. While gut dysbiosis can provide a treatment strategy to restore the standard gut microbiota using probiotics, transforming epigenetic omics data into epigenetic clocks offers a promising tool for personalized acute and chronic kidney disease care. Epigenetic clocks involve a complex transformation of DNA methylome data into estimated biological age. These clocks can identify people at high risk of developing kidney problems even before symptoms appear. Some of the effects of both the epigenetic clock and microbiota on kidney diseases seem to be mediated by endothelial dysfunction. These "big data" (epigenetic clocks and microbiota) can help tailor treatment plans by pinpointing patients likely to experience rapid declines or those who might not need overly aggressive therapies. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusions Patients with end‐stage renal disease (ESRD) on maintenance hemodialysis (MHD) are at high risk for major adverse cardiovascular and cerebrovascular events (MACCE), which are prone to be detrimental to patients' lives. Identifying risk factors for MACCE can help target measures to prevent or reduce the occurrence of MACCE.The aim was to investigate the correlation between miR‐142‐3p and MACCE in ESRD patients on MHD and to provide a new predictor for MACCE occurrence.Blood samples were collected from subjects to detect the expression of miR‐142‐3p using RT‐qPCR. The correlation of miR‐142‐3p with HDL‐C and hs‐CRP was assessed by the Pearson method. The occurrence of MACCE in patients during the 36‐month follow‐up period was recorded. The clinical value of miR‐142‐3p in MACCE occurrence was analyzed by the Kaplan–Meier curve, multivariate logistic regression, and ROC curve.In ESRD patients on MHD, miR‐142‐3p was downregulated, and it showed a positive correlation with HDL‐C but a negative correlation with hs‐CRP. The cumulative incidence of MACCE at 1, 2, and 3 years was 8.9%, 20.0%, and 30.4%, respectively. miR‐142‐3p levels were reduced in patients who developed MACCE and were associated with the cumulative incidence of MACCE. miR‐142‐3p was a risk factor for MACCE and showed a predictive value with specificity and sensitivity of 89.36% and 56.10%, respectively.miR‐142‐3p was a risk factor of MACCE in ESRD patients undergoing MHD. [ABSTRACT FROM AUTHOR]

Background Establishing the optimal timing for creating vascular access in patients with chronic kidney disease (CKD) is a critical and challenging aspect of patient management. The Kidney Disease: Improving Global Outcomes guidelines propose using a 40% 2-year threshold based on the Kidney Failure Risk Equation (KFRE) for this purpose. However, the effectiveness of this threshold compared with traditional methods, such as estimated glomerular filtration rate (eGFR), is not well-established. Methods In this monocentric retrospective cohort study, we analyzed data from patients referred for vascular mapping before arteriovenous fistula (AVF) creation between April 2013 and June 2023. The study aimed to compare the ≥40% 2-year KFRE threshold with a <15 mL/min/1.73 m² eGFR threshold for predicting end-stage kidney disease (ESKD). We assessed the probability of ESKD, considering death before AVF creation as a competing risk. Discrimination between KFRE and eGFR was evaluated using C-statistics. Results The study included 238 patients with a mean age of 65.2 years and a mean eGFR of 13.3 mL/min/1.73 m². Over a median follow-up of 10.7 months, 178 patients developed ESKD, and 21 died before ESKD. Probability of ESKD at 1 year was 77.6% (95% CI 69.9%–85.3%) using a ≥40% 4-variable KFRE threshold versus 65.8% (95% CI 58.3%–73.3%) using a <15 mL/min/1.73 m² eGFR threshold. The C-statistics indicated better predictive ability for the 8-variable KFRE at 6 months [0.82 (95% CI 0.76–0.88)], while both 4- and 8-variable KFRE models were effective for 1-year predictions [0.835 (95% CI 0.78–0.89) and 0.82 (95% CI 0.76–0.875), respectively]. Sensitivity and specificity analyses favored the ≥40% KFRE threshold over the eGFR threshold. Conclusions This study suggests that using a ≥40% 2-year KFRE threshold for planning vascular access in CKD patients is promising and potentially superior to the traditional <15 mL/min/1.73 m² eGFR threshold. This approach may offer a balance between minimizing premature AVF creation and the risk of starting dialysis via a central venous catheter. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from autophagy, apoptosis, and necroptosis. It is primarily characterised by a decrease in glutathione peroxidase 4 (GPX4) activity, or by the accumulation of lipid peroxidation and reactive oxygen species (ROS). Renal fibrosis is a common pathological change in the progression of various primary and secondary renal diseases to end-stage renal disease and poses a serious threat to human health with high morbidity and mortality. Multiple pathways contribute to the development of renal fibrosis, with ferroptosis playing a crucial role in renal fibrosis pathogenesis due to its involvement in the production of ROS. Ferroptosis is related to several signalling pathways, including System Xc-/GPX4, abnormal iron metabolism and lipid peroxidation. A number of studies have indicated that ferroptosis is closely involved in the process of renal fibrosis caused by various kidney diseases such as glomerulonephritis, renal ischaemia-reperfusion injury, diabetic nephropathy and renal calculus. Identifying the underlying molecular mechanisms that determine cell death would open up new insights to address a therapeutic strategy to renal fibrosis. The review aimed to browse and summarise the known mechanisms of ferroptosis that may be associated with biological reactions of renal fibrosis. [ABSTRACT FROM AUTHOR]

This meta-analysis investigated the long-term efficacy of dietary modifications on renal outcomes in individuals with diabetes. We systematically reviewed six studies, focusing on the impact of specific dietary components, including protein and salt intake and the use of nutraceuticals such as ketoacids, across global settings, including Poland, Nigeria, Taiwan, Italy, Austria, and Japan. The studies varied in design, ranging from observational to randomized controlled trials. The sample sizes and study durations ranged from 28 to 6,213 participants and 28 days to 5 years. Our analysis revealed that dietary protein restriction generally stabilized and improved renal function. However, the response to protein restriction varied, suggesting the need for personalized dietary management strategies. Furthermore, reducing salt intake was consistently beneficial, aligning with its known effects on lowering blood pressure and reducing proteinuria. Nutraceuticals, especially ketoacids, showed their potential as supplements for renal diet management. These findings supported the integration of nutraceuticals into dietary plans to enhance renal outcomes without compromising nutritional status. Thus, our meta-analysis demonstrated the importance of tailored dietary interventions in managing renal outcomes in individuals with diabetes and suggested that personalized nutrition, which considers individual dietary needs and kidney disease stage, should be a fundamental component of comprehensive CKD management. [ABSTRACT FROM AUTHOR]

Cellular senescence contributes to inflammatory kidney disease via the secretion of inflammatory and profibrotic factors. Protease‐activating receptor 2 (PAR2) is a key regulator of inflammation in kidney diseases. However, the relationship between PAR2 and cellular senescence in kidney disease has not yet been described. In this study, we found that PAR2‐mediated metabolic changes in renal tubular epithelial cells induced cellular senescence and increased inflammatory responses. Using an aging and renal injury model, PAR2 expression was shown to be associated with cellular senescence. Under in vitro conditions in NRK52E cells, PAR2 activation induces tubular epithelial cell senescence and senescent cells showed defective fatty acid oxidation (FAO). Cpt1α inhibition showed similar senescent phenotype in the cells, implicating the important role of defective FAO in senescence. Finally, we subjected mice lacking PAR2 to aging and renal injury. PAR2‐deficient kidneys are protected from adenine‐ and cisplatin‐induced renal fibrosis and injury, respectively, by reducing senescence and inflammation. Moreover, kidneys lacking PAR2 exhibited reduced numbers of senescent cells and inflammation during aging. These findings offer fresh insights into the mechanisms underlying renal senescence and indicate that targeting PAR2 or FAO may be a promising therapeutic approach for managing kidney injury. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) impacts over 10% of the global population. Adults with CKD face significant morbidity and mortality. As kidney disease progresses, the risk of adverse outcomes increases. Here, we present an overview of strategies to care for adults with advanced CKD (stage 4–5 CKD, not receiving kidney replacement therapy). We aim to guide clinicians through several aspects of CKD care, ranging from recommended laboratory assessments to interdisciplinary support for patients as they plan for kidney replacement therapy (dialysis, transplantation, or conservative management). We incorporate considerations of health equity and person-centered care, empowering clinicians to deliver high-quality care to people with CKD. [ABSTRACT FROM AUTHOR]

What is this summary about? This is a summary of an article that was published in the medical journal Kidney360 describing results from the NORMALIZE study. The NORMALIZE study looked at how well tenapanor tablets reduced higher-than-normal levels of phosphate in the blood of persons with kidney disease who are on maintenance dialysis. These persons are unable to keep their blood phosphate levels in a normal range, and high levels of phosphate can contribute to several serious health consequences. Tenapanor is approved as an add-on treatment for high levels of phosphate in the blood of adults with chronic kidney disease who are on maintenance dialysis and whose disease does not respond adequately to treatment with phosphate binders or who are not able to take phosphate binders. In earlier clinical studies, tenapanor was studied alone or studied together with phosphate binders. In a 1-year clinical study called PHREEDOM, researchers learned that when tenapanor was used alone, it lowered blood phosphate levels, and treated patients experienced acceptable safety and tolerability as determined by the doctors running the study. In the NORMALIZE study, adult patients took a 30-mg tenapanor tablet twice a day, either alone or with sevelamer, for up to 18 months after they completed the PHREEDOM study. What were the main conclusions reported by the researchers? The researchers found that one-third of patients taking tenapanor, either alone or with sevelamer, achieved normal blood phosphate levels. This is an improvement from the current standard of care with sevelamer alone to reduce blood phosphate levels. As seen in the earlier studies of tenapanor, the most common adverse event experienced by patients was softer or loose stools. No new safety concerns were reported in the NORMALIZE study. What are the key takeaways? The researchers concluded that tenapanor, used alone or combined with sevelamer, can be used long-term by adult patients receiving maintenance dialysis to reduce the phosphate levels in their blood to within the normal range. Patients who take tenapanor may experience softer or loose stools. This summary was developed by the authors to help adult patients with chronic kidney disease receiving dialysis, and their family members and/or caregivers, better understand the effects of taking tenapanor. This is an abstract of the Plain Language Summary of Publication article. of this article to read the full-text Link to original article [ABSTRACT FROM AUTHOR]

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single-nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR), or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after the loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin–angiotensin system blockers to mineralocorticoid receptor blockers to sodium–glucose co-transporter 2 inhibitors to tolvaptan, induce an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predate current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single-nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions. [ABSTRACT FROM AUTHOR]

Background Autosomal dominant Alport Syndrome (ADAS), also known as thin basement membrane disease (TBMD), is caused by pathogenic variants in the COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies have been performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with chronic kidney disease (CKD). Methods This was a retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4 ± 9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease. Results MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7 ± 5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR <45 mL/min/1.73 m2 (63% vs 7%, P  = .006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: –1.8 vs 0.06 mL/min/1.73 m2/year (P  = .009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (P  = .002) and MKD (P  = .02). Conclusion MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3 / COL4A4. [ABSTRACT FROM AUTHOR]

Simple Summary: In cats with chronic kidney disease (CKD), harmful toxins can build up in their blood, causing health problems. Some of these toxins originate from molecules that are generated in the gut by the action of certain microbes on digested food. Renaltec is a supplement that binds to these molecules in the gut before they enter the bloodstream and are transformed into toxins by the liver. In a study with 13 cats with experimentally induced CKD, researchers tested how well Renaltec worked at reducing two specific toxins, indoxyl sulfate and p-cresol sulfate, in the blood. The cats were given Renaltec either once or twice daily for 56 days, and their toxin levels were measured at different times. The study found that Renaltec significantly lowered the levels of these toxins, with the twice-daily dosing showing better results. This suggests that Renaltec is effective at reducing harmful toxins in cats with CKD. Serum uremic toxins markedly increase in cats with chronic kidney disease (CKD) and have deleterious consequences. Renaltec is an oral adsorbent that binds uremic toxin precursors in the gut. In this prospective cohort study utilizing 13 purpose-bred cats with remnant kidney model-induced CKD (12 IRIS Stage 2, 1 IRIS Stage 3) eating a standardized renal diet, we aimed to assess the effect of Renaltec administration on serum indoxyl sulfate (IDS) and p-cresol sulfate (pCS) concentrations. Cats were sequentially treated with standard of care for 56 days, 500 mg Renaltec orally once daily for 56 days, and then three months later, 500 mg Renaltec orally twice daily for 56 days. Serum IDS and pCS concentrations were measured 28 and 56 days after the administration of Renaltec. Blood pressure and kidney function were measured before and 56 days after the administration of Renaltec. Significant decreases in serum IDS and pCS concentrations were observed for both once- and twice-daily dosing, particularly during the first 28 days of administration. More cats with BID dosing had clinically significant reductions in serum IDS and pCS concentrations than with SID dosing. Renaltec can reduce the serum concentrations of deleterious gut-derived uremic toxins in cats with CKD. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease (CKD), a complex and multifaceted health issue, significantly contributes to global mortality rates. Accompanying chronic conditions, depression notably exacerbates health outcomes, increasing both mortality risk and the burden on affected individuals. This study employs bibliometric and visual analytics to evaluate the evolution, current trends, and future research directions in the field of CKD and depression. Methods: We conducted a thorough investigation using the Web of Science Core Collection, focusing on literature published from 2006 to 2022 that examines the interplay between CKD and depression. The analysis was enriched with bibliometric and visualization tools such as bibliometrix, CiteSpace, and VOSviewer to distill the essence of the research corpus. Results: Our analysis incorporated 2,409 CKD-related publications, with significant contributions from the United States, China, and England. BMC Nephrology emerged as the leading publication outlet, while the American Journal of Kidney Diseases featured the most cited articles. Key terms such as "depression," "quality-of-life," "mortality," "prevalence," and "hemodialysis" dominated the keyword landscape, indicating the research focus areas. Conclusion: This bibliometric analysis offers an in-depth view of the research trajectory in CKD and depression. It provides valuable insights for researchers seeking relevant literature, potential collaborators, and an understanding of the field's current hotspots and emerging frontiers. The findings of this study are instrumental in guiding and enriching future research endeavors in this domain. [ABSTRACT FROM AUTHOR]

Background: Hypertensive nephropathy (HN) is one of the main causes of end-stage renal disease (ESRD), leading to serious morbidity and mortality in hypertensive patients. However, existing treatment for hypertensive nephropathy are still very limited. It has been demonstrated that aerobic exercise has beneficial effects on the treatment of hypertension. However, the underlying mechanisms of exercise in HN remain unclear. Methods: The spontaneously hypertensive rats (SHR) were trained for 8 weeks on a treadmill with different exercise prescriptions. We detected the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on inflammatory response, renal function, and renal fibrosis in SHR. We further investigated the relationship between TLR4 and the NLRC4 inflammasome in vitro HN model. Results: MICT improved renal fibrosis and renal injury, attenuating the inflammatory response by inhibiting TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. However, these changes were not observed in the HIIT group. Additionally, repression of TLR4/NF-κB pathway by TAK-242 inhibited activation of NLRC4 inflammasome and alleviated the fibrosis in Ang II-induced HK-2 cells. Conclusion: MICT ameliorated renal damage, inflammatory response, and renal fibrosis via repressing TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. This study might provide new references for exercise prescriptions of hypertension. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure. Objectives: To elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress. Methods: A cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self- Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. Results: Alpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, antiinflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients. Conclusions: DKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD. [ABSTRACT FROM AUTHOR]

Cryopyrin-associated periodic syndromes (CAPS) are orphan hereditary auto-inflammatory diseases with various phenotypes, including chronic kidney disease (CKD). Current therapies inhibit interleukin-1 (IL-1) to achieve clinical and serological remission; however, the effect on kidney involvement remains unclear. The objective of this study was to investigate the long-term efficacy of anti-IL-1 treatment with special emphasis on renal outcome. We retrospectively analysed clinical, genetic and laboratory data of patients with CAPS under anti-IL-1 therapy from a single-centre university outpatient clinic. Patients with CAPS (n = 28) were followed for a median of 11 (IQR 8.5–13) years. Four patients at various ages (19%), bearing the most common CAPS mutation R260W, had significant CKD at presentation. All affected patients were related; however, other family members with the same genetic variant did not develop CKD. While anti-IL-1 therapy was effective in lowering symptom burden and inflammatory parameters in all CAPS patients, two of the four individuals with significant CKD had persistent proteinuria and worsening kidney function. None of the patients without renal affection at therapy initiation developed relevant CKD in the follow-up period. We showed that in patients with CAPS: (1) CKD is a common complication; (2) renal involvement shows familial predisposition beyond the mutational status and is independent of age; (3) anti-IL-1 therapy results in sustained improvement of inflammatory parameters and symptom load and (4) may prevent development of CAPS-associated CKD but not affect kidney involvement when already present. Overall, early therapy initiation might sufficiently prevent renal disease manifestation and attenuate progression. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and is characterized by the accumulation of lipid peroxides to lethal levels. Ferroptosis involves multiple pathways including redox balance, iron regulation, mitochondrial function, and amino acid, lipid, and glycometabolism. Furthermore, various disease-related signaling pathways also play a role in regulating the process of iron oxidation. In recent years, with the emergence of the concept of ferroptosis and the in-depth study of its mechanisms, ferroptosis is closely associated with various biological conditions related to kidney diseases, including kidney organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanisms of ferroptosis (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, and MBOAT1/2 pathways), and the latest research progress on its involvement in kidney diseases. It summarizes research on ferroptosis in kidney diseases within the frameworks of metabolism, reactive oxygen biology, and iron biology. The article introduces key regulatory factors and mechanisms of ferroptosis in kidney diseases, as well as important concepts and major open questions in ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs can be made in understanding the regulation mechanism of ferroptosis and utilizing ferroptosis to promote treatments for kidney diseases, such as acute kidney injury(AKI), chronic kidney disease (CKD), diabetic nephropathy(DN), and renal cell carcinoma. This paves the way for a new approach to research, prevent, and treat clinical kidney diseases. [ABSTRACT FROM AUTHOR]

Background: End-stage and acquired cystic renal disease (ESRD/ACRD) kidneys are characterized by inflammatory remodelling and multiplex renal cell carcinomas (RCC). Eosinophilic vacuolated tumour (EVT) occurs exclusively in ACRD. The aim of this study was to identify the involvement of thioredoxin-interacting protein (TXNIP) and thioredoxin (TXN) in ESRD/ACRD pathology. Methods: Expression of TXNIP and TXN was examined in histological slides of 6 ESRD and 6 ACRD kidneys, precursor lesions and associated tumours as well as of RCCs from the general population by immunohistochemistry. Results: Strong TXNIP expression was seen in epithelial cells, myo-fibroblasts and endothelial cells and weak TXN expression in ESRD/ACRD kidneys and tumours. In ACRD specific EVT and its precursors TXN were translocated into nuclei. Conclusion: The impaired TXNIP/TXN redox homeostasis might be associated with development of multiplex cancer especially of EVT in ESRD/ACRD kidney. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. Methods: We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-β1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. Results: The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-β1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. Conclusion: Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Uromodulin has been known for many years as a normal protein component of urine. However, in recent years, serum as well as urinary uromodulin have been investigated in relation to kidney diseases. Chronic kidney disease (CKD) is a common diagnosis, especially in old dogs, and suitable markers for the early stages of the disease are constantly being investigated. We focused on the effect of age and gender on uromodulin in serum and urine in a healthy population of dogs of the same breed, German shepherd. We compared the results with two groups of other breeds of healthy dogs. Compared with groups of patients in the early stages of CKD, we concluded that urinary uromodulin corrected to creatinine in urine seems to be the most prospective marker. Serum and urinary uromodulin are evaluated as potential biomarkers of kidney disease. The aim of our research was to select a more appropriate form of uromodulin for the diagnosis of early stages of chronic kidney disease (CKD). We also focused on the influence of age and gender in one breed on uromodulin and on the possible interbreed differences. Serum uromodulin had the lowest values in dogs younger than 2 years but no effect of gender, breed, or CKD was observed. Urinary uromodulin indexed to urinary creatinine was significantly reduced in dogs in stage 2 of CKD (p = 0.003) in contrast to uromodulin converted to urine specific gravity. Urinary uromodulin with both corrections was significantly lower in Belgian shepherds compared to German shepherds (p < 0.0001, p = 0.0054) but was not influenced by gender or age. In stage 1 of CKD, urinary uromodulin correlated with kidney disease markers SDMA (p = 0.0424, p = 0.0214) and UPC (p = 0.0050, p = 0.0024). Urinary uromodulin appears to be more associated with CKD than serum uromodulin. Further studies with a larger number of patients are needed for the suitability of urinary uromodulin as a marker of early-stage disease. [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship of thyroid hormones with the development of chronic kidney disease (CKD) has important clinical implications for managing patients with both thyroid and kidney dysfunction. In this review, our purpose was to provide a thorough comprehension of the interplay between thyroid hormones, thyroid dysfunctions, and CKD. Summary: While there is evidence linking thyroid hormone levels to renal diseases, the association between thyroid hormones, specifically within the normal range, and the risk of CKD incidence is still a subject of debate. The Google Scholar, PubMed, Scopus, and Web of Science, were searched using the medical subject heading (MeSH) terms for the relevant keywords up to December 2023. Conclusion: Based on the review, the development of CKD is more consistently associated with higher serum TSH and thereafter lower serum free T3 levels; however, its association with free T4 is more controversial. Furthermore, subclinical and overt hypothyroidisms were considerably associated with incident CKD. Hyperthyroidism and Hashimoto thyroiditis might increase the risk of CKD. [ABSTRACT FROM AUTHOR]

Introduction: Women born with anorectal malformation (ARM) or Hirschsprung disease (HD) may have impaired urologic function resulting in sequelae in adulthood. This study assessed and compared self-reported urinary outcomes in adult females born with ARM or HD to a reference population. Methods: This was an IRB approved, cross-sectional study of female-born patients with ARM or HD, who completed surveys between November 2021 and August 2022. Female patients between the ages of 18 and 80 years were included. Lower Urinary Tract Symptom Questionnaires were administered through REDCap and the responses were compared to a reference population using Chi-squared or Fisher's exact tests. Results: Sixty-six born female patients answered the questionnaires, two of them identified as non-binary. The response rate was 76%. Median age was 31.6 years. The majority were born with cloaca (56.3%), followed by other type of ARMs (28.1%), complex malformation (9.4%), and HD (6.3%). A history of bladder reconstruction was present for 26.6%. Catheterization through a channel or native urethra was present in 18.8%. Two had ureterostomies and were excluded from the analysis. Seven had chronic kidney disease or end-stage renal disease, three with a history of kidney transplantation. Patients with cloaca had significantly higher rates of urinary incontinence, urinary tract infection, and social problems due to impaired urological functioning, when compared to an age-matched reference population (Table 3). Conclusion: This study emphasizes the need for a multi-disciplinary team that includes urology and nephrology following patients with ARM long term, especially within the subgroup of cloaca. Level of Evidence: III. [ABSTRACT FROM AUTHOR]

Introduction: Multiple factors predict the recoverability of renal function post percutaneous nephrostomy (PCN) in obstructive uropathy. The aim is to ascertain parameters with significant predictive value to aid in the stratification of patients requiring urgent PCN. Materials and methods: A retrospective study over a period of 5 years between January 2016 till January 2021 was conducted in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) involving a total of 217 patients who underwent image guided PCN that met the inclusion criteria. The pre-intervention renal imaging, biochemical parameters and the post-intervention serum creatinine were obtained and respective estimated glomerular filtration rate (eGFR) calculated. Patients with post-intervention serum creatinine of less than 130 umol/L and eGFR of more than 60 were categorized as patients with good renal recovery. Subsequently, the significance of each parameter with good renal recovery was analysed. Results: There is significant correlation between the absence of chronic kidney disease and renal parenchymal disease, level of obstruction, age, renal size, hemoglobin, pre-intervention serum creatinine and eGFR with good renal recovery on bivariate analysis. However, only the absence of renal parenchymal disease, renal size of more than 11.2cm (S.D: 7.2 - 23.8) and pre-intervention eGFR of more than 23.0 (S.D: 2.2 - 168.0) remained statistically significant on multivariate analysis. Conclusion: Previous healthy kidneys with good size and function proves to be statistically significant in achieving the best recoverability which are applicable in stratification of PCN requests. A prospective study of a wider population will yield a farther accurate and generally pertinent result. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of chronic kidney disease (CKD) among children of school-going age. Study Design: Cross-sectional study. Setting: Department of Pediatric Medicine, National Institute of Child Health, Karachi, Pakistan. Period: July 2023 to December 2023. Methods: A total of 130 children of both genders, aged between 5-15 years, visiting outpatient department of pediatric medicine were analyzed. Demographic and clinical information were noted. Laboratory investigations like urinalysis and serum creatinine were performed. CKD was diagnosed on the basis of "Kidney Disease Outcomes Quality Initiative (KDOQI)" guidelines. Results: In a total of 130 children, 67 (51.5%) children were male. Overall, the mean age was 8.43±2.45 years. Hypertension was diagnosed in 10 (7.7%) children. Anemia was present in 103 (79.2%) patients. The mean hemoglobin, serum creatinine, and blood urea nitrogen were 9.41±1.98 g/dl, 0.48±0.37 mg/dl, and 34.20±33.18 mg/dl, respectively. CKD was diagnosed in 10 (7.7%) children. Among these 10 children diagnosed with CKD, 7 were having CKD stage-1 whereas CKD stage-2 was noted in 3 children. Presence of hypertension (p=0.006), and albuminuria (p<0.001) were associated with CKD. Conclusion: The prevalence of CKD in school going age children was 7.7%. Presence of hypertension, and albuminuria were linked with CKD. [ABSTRACT FROM AUTHOR]

Introduction: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end‐stage renal disease. We sought to determine the pre‐ and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima‐media thickness (IMT) in KP recipients. Methods: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre‐ and posttransplant IMT measurements. Results: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non‐PAD cohorts. At a median follow‐up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18–24) months posttransplant, showed no evidence of disease progression. Conclusion: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) affects 9.1% of the population worldwide. CKD may lead to structural and functional gastrointestinal alterations, including impairment in the intestinal barrier, digestion and absorption of nutrients, motility, and changes to the gut microbiome. These changes can lead to increased gastrointestinal symptoms in people with CKD, even in early grades of kidney dysfunction. Gastrointestinal symptoms have been associated with lower quality of life and reduced nutritional status. Therefore, there has been considerable interest in improving gastrointestinal health in this clinical population. Gastrointestinal health can be influenced by lifestyle and medications, particularly in advanced grades of kidney dysfunction. Therapies focused on gastrointestinal health have been studied, including the use of probiotics, prebiotics, and synbiotics, yielding limited and conflicting results. This review summarizes the alterations in the gastrointestinal tract structure and function and provides an overview of potential nutritional interventions that kidney disease professionals can provide to improve gastrointestinal health in individuals with CKD. [ABSTRACT FROM AUTHOR]

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected. PBPK modeling software, PK-Sim®, was then used to build and assess the IV, oral, and drug-specific models. Next, the average fold error, visual predictive checks, and predicted/observed ratios were used for the assessment of the robustness of the model for all the essential PK parameters. This evaluation demonstrated that all PK parameters were within an acceptable limit of error, i.e., 2 fold. Also to display the influence of CKD on the total and unbound AUC (the area under the plasma concentration–time curve) and to make modifications in dose, the analysis results of the model on this aspect were further examined. This PBPK model has successfully depicted the variations of PK of vildagliptin in healthy subjects and patients with CKD, which can be useful for medical practitioners in dosage optimization in renal disease patients. [ABSTRACT FROM AUTHOR]

The aim of this consensus statement is to summarize and appraise scientific evidence and combine this with the clinical experience of a panel of experts to optimize recommendations on how to recognize and manage kidney disease in horses. [ABSTRACT FROM AUTHOR]

Background: Membranous nephropathy (MN) is an autoimmune disease in which circulating autoantibodies bind to a podocyte antigen, causing nephrotic syndrome. Despite several treatment options, their long-term benefits are still not established. The aim of this study is to investigate the long-term efficacy of cyclosporine and methylprednisolone in MN treatment. Methods: In this retrospective study, we included adults with biopsy-proven idiopathic MN. At diagnosis, all patients received conservative treatment, and those who did not show remission after 6 months received immunosuppression with cyclosporine and methylprednisolone. Those that despite no remission chose not to receive immunosuppression served as controls. Results: Sixty patients were included in the study with a follow-up of 94.8 ± 55.5 months. Forty-nine patients had nephrotic syndrome, and 47 received immunosuppression, while 13 received no treatment. Out of those who received immunosuppression, 63.8% showed complete, 14.9% partial, and 19.1% no remission of nephrotic syndrome. End-stage kidney disease (ESKD) or doubling of serum creatinine was reached by 12. Out of those who received no immunosuppression, 23.1% showed complete, 30.8% partial, and 23.1% had no remission. Doubling of serum creatinine or ESKD was reached by 1. Kidney survival was not altered by immunosuppression and was not different among those who received immunosuppression and had no or up to 3 relapses. Either complete or partial remission was accompanied by better kidney survival. Conclusion: Treatment of idiopathic MN with cyclosporine and methylprednisolone offers a reliable option for proteinuria remission. Nevertheless, this option does not alter long-term disease progression. [ABSTRACT FROM AUTHOR]

Total parenteral nutrition (TPN) may lead to concerning kidney outcomes with long-term administration. This can be delayed and improved by daily monitoring of the serum concentrations of clinical markers that correlate with kidney function but only in conjunction with changing the parenteral nutrition formula to account for these concentration changes. The current evidence suggests that hyperglycemia, hypertriglyceridemia, and deranged fluid/electrolyte balance remain significant areas of concern with TPN in patients with acute kidney injury, chronic kidney disease, and patients undergoing kidney replacement therapy. Tight monitoring of calorie intake, protein intake, and micronutrients is required in patients with end-stage kidney disease due to the high occurrence of protein-energy wasting or those undergoing kidney replacement therapy due to loss of nutrients during dialysis. Given the complications, TPN should only be used when enteral feeding is completely contraindicated or cannot sufficiently address nutrient intake goals due to secondary issues such as anorexia. These findings are discussed with the clinical practice guidelines recommended by The American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. Mechanisms of TPNinduced kidney diseases are also discussed. [ABSTRACT FROM AUTHOR]

Depression is common in patients with chronic kidney disease (CKD). Experimental studies suggest the role of urea toxicity in depression. We assessed both the incidence of antidepressant prescriptions and depressive symptoms (measured by CESD (Center for Epidemiologic Depression) scale) in 2505 patients with CKD (Stage 3–4) followed up over 5 years in the Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) cohort. We used a joint model to assess the association between the serum urea level and incident antidepressant prescriptions, and mixed models for the association between the baseline serum urea level and CESD score over the 5-year follow-up. Among the 2505 patients, 2331 were not taking antidepressants at baseline. Of the latter, 87 started taking one during a median follow-up of 4.6 years. After adjustment for confounding factors, the hazard ratio for incident antidepressant prescription associated with the serum urea level (1.28 [95%CI, 0.94,1.73] per 5 mmol/L increment) was not significant. After adjustment, the serum urea level was associated with the mean change in the CESD score (β = 0.26, [95%CI, 0.11,0.41] per 5 mmol/L increment). Depressive symptoms burden was associated with serum urea level unlike depression events. Further studies are needed to draw firm conclusions and better understand the mechanisms of depression in CKD. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic Nephropathy (DN) is a major cause of increased morbidity and mortality in patients with Diabetes Mellitus (DM). The development of novel biomarkers for kidney disease, especially DN, is becoming a focus of medical research. Serum creatinine and urine albumin measurements had been the gold standards for the diagnosis of DN until the advent of newer markers like Cystatin C, Kidney Injury Molecule-1, etc. Currently, there is no non invasive investigation for the prediction of DN. Nevertheless, the field of proteomics is advancing at a rapid pace, such that urinary proteomic biomarkers have found a spot in the diagnosis of DN. The role of the urinary proteomic Chronic Kidney Disease 273 (CKD273) classifier, in particular, has been demonstrated in early prediction. Aim: To highlight the performance of the CKD273 classifier in the early prediction of DN. Materials and Methods: Pubmed and Scopus databases were extensively searched using the keywords diabetes, DM, renal disease or kidney disease, proteomics or peptide, urinary markers or biomarkers. Full-text original articles conducted on humans and written in English, published between 2014 and 2022, specifically prospective and retrospective observational studies, cross-sectional studies, Randomised Controlled Trials (RCT), and case-control studies investigating the efficacy of the urinary biomarker CKD273 in the prediction of DN were included in the review. The literature search, strictly based on Preferred Reporting Items for Systematic Reviews and Metaanalysis (PRISMA) guidelines, led to the identification of eight relevant studies, which were included in the present review. The quality and Risk of Bias (RoB) of the selected articles were assessed using the Newcastle Ottowa scale (NOS) and Risk of Bias 2 (ROB2) tool. Results: The selected studies proved the efficacy of the urinary proteomic classifier CKD273 as a cost-effective biomarker in predicting the decline in renal function in both normoalbuminuric diabetics and DN patients. Conclusion: Based on the articles included in the present systematic review, it has been found that CKD273 plays a vital role in the early prediction of renal dysfunction in normoalbuminuric diabetics as well as in the detection of progressing renal disease in DN patients. It has also been found to be cost-effective compared to established markers such as estimated Glomerular Filtration Rate (eGFR), Urine Albumin Excretion Rate (UAER), etc. [ABSTRACT FROM AUTHOR]

The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes. However, epithelial injury is currently neither monitored clinically nor addressed therapeutically after kidney transplantation. Several factors can contribute to allograft epithelial injury, including allograft rejection, drug toxicity, recurrent infections and postrenal obstruction. The injury mechanisms that underlie allograft injury overlap partially with those associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in the native kidney. Studies using advanced transcriptomic analyses of single cells from kidney or urine have identified a role for kidney injury-induced epithelial cell states in exacerbating and sustaining damage in AKI and CKD. These epithelial cell states and their associated expression signatures are also observed in transplanted kidney allografts, suggesting that the identification and characterization of transcriptomic epithelial cell states in kidney allografts may have potential clinical implications for diagnosis and therapy. This Review describes parallels in the injury mechanisms that underlie acute kidney injury, chronic kidney disease and allograft injury, and explains how our understanding of the molecular changes that occur in epithelia in the context of kidney disease may contribute to the therapeutic targeting of specific epithelial cell phenotypes for the treatment of transplantation complications. Key points: Transcriptomic studies using single-cell sequencing and spatial transcriptomics have identified epithelial cell populations associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in mouse and human kidneys. These injured epithelial cell populations are especially predominant in the proximal tubules but extend to other cell types, particularly in human AKI and CKD. AKI- and CKD-associated epithelial cell populations show a marked downregulation of marker genes associated with the healthy kidney epithelium and can show a pro-inflammatory and pro-fibrotic gene expression profile. Some injured epithelial cell populations can persist for a period of time after AKI and in CKD, attracting and activating fibroblasts and leukocytes, and thereby potentially promoting further kidney damage. Epithelial injury is an under-appreciated major risk factor of allograft survival after episodes of rejection in kidney transplants. Molecular signatures of injured epithelial cell populations in kidney transplants after post-transplantation complications are highly reminiscent of those seen in AKI and CKD, and offer potential new avenues for monitoring and therapy. [ABSTRACT FROM AUTHOR]

Context The impairment of bone microarchitecture is a key determinant of skeletal fragility in patients with chronic kidney disease (CKD). The trabecular bone score (TBS) has been developed as a reliable noninvasive index of bone quality. However, its utility in this setting is still debated. Objective The aim of this systematic review and meta-analysis was to summarize the available evidence about TBS as a marker of skeletal fragility across the spectrum of CKD. Methods PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until July 2023 for studies reporting data about TBS in patients with CKD. Effect sizes were pooled through a random-effect model. Results Compared to controls, lower TBS values were observed in CKD patients not on dialysis (−0.057, 95%CI:[−0.090, −0.024], P <.01), in dialysis patients (−0.106, 95%CI:[−0.141, −0.070], P <.01), and in kidney transplant recipients (KTRs) (−0.058, 95%CI:[−0.103, −0.012], P =.01). With respect to fracture risk, TBS was able to predict incident fractures in nondialysis patients at unadjusted analyses (hazard ratio [HR] per SD decrease: 1.45, 95%CI:[1.05, 2.00], P =.02), though only a nonsignificant trend was maintained when fully adjusting the model for FRAX® (HR = 1.26, 95%CI:[0.88, 1.80], P =.21). Dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones (−0.070, 95% CI:[−0.111, −0.028], P <.01). Some studies supported a correlation between TBS and fracture risk in KTRs, but results could not be pooled due to the lack of sufficient data. Conclusion CKD patients are characterized by an impairment of bone microarchitecture, as demonstrated by lower TBS values, across the whole spectrum of kidney disease. TBS can also be helpful in the discrimination of fracture risk, with lower values being correlated with a higher risk of prevalent and incident fractures. [ABSTRACT FROM AUTHOR]