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BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Background and Purpose: Endothelin‐1 (ET‐1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging. Approach: We utilized a previously developed mathematical model of ET‐1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR). Background and Key Results: An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR. Conclusions and Impact: These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output. [ABSTRACT FROM AUTHOR]

Background Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most estimated GFR (eGFR) equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (cysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR. Methods We assessed the performance of Chronic Kidney Disease Epidemiology Collaboration equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cysC (eGFRCysC-2012) or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation (mGFR) GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex stratified and height indexed). Results Pre-donation eGFRcombined-2012 and eGFRcombined-2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined-2021 was most accurate for estimating both pre-donation (bias 0.01 ± 11.9 ml/min/1.73 m2) and post-donation mGFR (bias 1.3 ± 8.5 ml/min/1.73 m2). In donors with high/low muscle mass, cysC-based equations (with or without creatinine) performed better compared with equations based on only creatinine. Conclusions Combined eGFR equations yielded a better estimate of pre- and post-donation mGFR compared with estimates based on creatinine or cysC only. The added value of cysC seems particularly pronounced in donors with high or low muscle mass. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy, also known as diabetic kidney disease (DKD), remains a challenge in clinical practice as this is the major cause of kidney failure worldwide. Clinical trials do not answer all the questions raised in clinical practice and real‐world evidence provides complementary insights from randomized controlled trials. Real‐life longitudinal data highlight the need for improved screening and management of diabetic nephropathy in primary care. Adherence to the recommended guidelines for comprehensive care appears to be suboptimal in clinical practice in patients with DKD. Barriers to the initiation of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors for patients with DKD persist in clinical practice, in particular for the elderly. Attainment of blood pressure targets often remains an issue. Initiation of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in routine clinical practice is associated with a reduced risk of albuminuria progression and a possible beneficial effect on kidney function. Real‐world evidence confirms a beneficial effect of SGLT2 inhibitors on the decline of glomerular filtration, even in the absence of albuminuria, with a lower risk of acute kidney injury events compared to GLP‐1RA use. In addition, SGLT2 inhibitors confer a lower risk of hyperkalaemia after initiation compared with dipeptidyl peptidase‐4 inhibitors in patients with DKD. Data from a large population indicate that diuretic treatment increases the risk of a significant decline in glomerular filtration rate in the first few weeks of treatment after SGLT2 inhibitor initiation. The perspective for a global approach targeting multifaceted criteria for diabetic individuals with DKD is emerging based on real‐world evidence but there is still a long way to go to achieve this goal. [ABSTRACT FROM AUTHOR]

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin‐creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin‐angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long‐standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non‐steroidal mineralocorticoid receptor antagonists are used in detail. [ABSTRACT FROM AUTHOR]

Purpose The objective of this study was to evaluate the impact of a pharmacist consult service on rates of hypoglycemia in adult inpatients with renal dysfunction receiving antidiabetic medications. Methods This was a single-center, institutional review board–approved, quasi-experimental, 2-phase prospective study. Adult inpatients admitted within 48 to 96 hours of hospitalization with a creatine clearance of less than 30 mL/min or estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 and an active antidiabetic medication order were included. Patients located in a critical care unit or with a previous or planned transplantation were excluded. Each phase was conducted over 4 months. The primary endpoint was the change in the incidence of hypoglycemic episodes (blood glucose [BG] of <70 mg/dL) per 100 patient days when comparing the cohorts. Secondary endpoints included the incidence of recurrent and severe (BG of <40 mg/dL) episodes of hypoglycemia per 100 patient days, occurrence of a BG concentration of higher than 300 mg/dL, and length of stay. Results Overall, 150 patients were included in the retrospective preimplementation phase and 172 were included in the prospective postimplementation phase. In the postimplementation group, there was a significant decrease in the rate of hypoglycemia per 100 patient days when compared to the retrospective group (5.8 vs 9.0; incidence rate ratio, 1.55; 95% confidence interval, 1.2-2.0; P < 0.05). There was no difference in secondary endpoints between the groups. Conclusion The implementation of a pharmacy consult service resulted in lower rates of hypoglycemic events, which supports pharmacist involvement to prevent hypoglycemia in this at-risk population. Additional studies involving pharmacists working under collaborative practice agreements may reinforce the results. [ABSTRACT FROM AUTHOR]

Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors for these adverse outcomes which we have investigated in this study. We compared renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal outcome and to unveil associations between kidney function and blood pressure. This study included 93 former ELBW children and 87 healthy controls with a mean age of 11 years at assessment. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children. ELBW children have significantly higher blood pressure (mean SBP percentile 75thvs. 47th, p <0.001) and lower mean eGFR (94 vs. 107 ml/min/1.73 m2, p = 0.005) compared to the control group. Elevated blood pressure did not correlate with perinatal characteristics and none of them had microalbuminuria. ELBW children with eGFR <90 ml/min/1.73 m2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40% vs. 15.8%, p = 0.056). There was no association between blood pressure and kidney dysfunction. Conclusions: Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney dysfunction. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage but not with blood pressure. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk. What is Known: • Extremely Low Birthweight (ELBW) neonates suffer later in life from adverse renal and cardiovascular outcomes. • Perinatal risk factors that further predict the individual risk for adverse outcomes are not well known. What is New: • Poorer eGFR in adolescence was associated with male sex, longer ventilation and intra-ventricular hemorrhage at birth but not with blood pressure. • Former ELBW infants had higher blood pressures compared to controls, but no microalbuminuria. • This knowledge can lead to potential precision medicine, safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk. [ABSTRACT FROM AUTHOR]

Aim: To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout‐related outcomes. Materials and Methods: Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3–5.1 mg/dL [>255.8–303.4 µmol/L], >5.1–5.8 mg/dL [>303.4–345.0 µmol/L], >5.8–6.9 mg/dL [>345.0–410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti‐gout medication was assessed. Results: The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively. Ertugliflozin reduced UA over Weeks 6–260 compared with placebo, with least squares mean (LSM) changes (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (−0.02, 0.15) and −0.19 mg/dL (−0.25, −0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo‐adjusted LSM change (95% CI) from baseline in UA was −0.26 mg/dL (−0.36, −0.16) with ertugliflozin. Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo. The incidence of the composite of gout‐related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI 0.580, 1.002]). Conclusions: Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout‐related outcome events. [ABSTRACT FROM AUTHOR]

Aim: Efficient primary prevention of diabetic kidney disease (DKD) is currently lacking. The identification of people at high DKD risk and timely intervention are key to preventing DKD. Therefore, a model to classify people according to their risk for developing DKD was developed previously and used in the current analysis to assess the effect of semaglutide versus placebo on primary DKD prevention. Methods: Participants with type 2 diabetes from the randomized, double‐blind, placebo‐controlled SUSTAIN 6 trial without DKD at baseline who received 0.5/1.0 mg semaglutide or placebo were grouped by baseline DKD risk, calculated using a validated model. The main post hoc outcome was the effect of semaglutide versus placebo on the proportion of participants who developed DKD [urinary albumin/creatinine ratio (UACR) ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m2]. Additional post hoc outcomes included changes in DKD risk score, UACR and estimated glomerular filtration rate over time. Results: Of the total 1139 participants included in the analysis, 28.7% developed DKD; more participants with a high DKD risk (952/1139) developed DKD. Semaglutide significantly reduced the risk of developing DKD in both the total [odds ratio 0.56 (95% confidence interval: 0.42; 0.74; p < 0.0001)], and high DKD risk population [odds ratio 0.51 (95% confidence interval: 0.38; 0.69; p < 0.0001)] and significantly delayed DKD development versus placebo. The beneficial effects of semaglutide were largely driven by UACR changes. The number needed to treat for semaglutide in the high DKD risk population was 7. Conclusions: This post hoc study indicates that semaglutide may have beneficial effects on primary DKD prevention in people with T2D. [ABSTRACT FROM AUTHOR]

Fanconi-Bickel syndrome (FBS) is a rare genetic disorder of carbohydrate metabolism due to pathogenic variants in SLC2A2, a gene encoding glucose transporter 2 (GLUT2), which leads to accumulation of glycogen in the kidney and liver. While consequential complex proximal tubular dysfunction is well acknowledged in the literature, long-term trajectories of kidney function in patients with FBS have not been well characterized, and kidney biopsy is performed infrequently. Here, we report on a patient with FBS followed from infancy through young adulthood who presented early on with hypercalciuria, phosphaturia, and hypophosphatemia, complicated by chronic kidney disease development during childhood. Kidney biopsy, in addition to a widespread glycogen accumulation in proximal tubular epithelial cells, demonstrated medullary nephrocalcinosis. Screening for nephrocalcinosis may be warranted in pediatric patients with FBS, along with close surveillance of their kidney function. [ABSTRACT FROM AUTHOR]

Stereotactic ablative body radiotherapy (SABR) is a novel option to treat primary renal cell carcinoma. However, a high radiation dose may be received by the treated kidney, which may affect its function posttreatment. This study investigates the dose-effect relationship of kidney SABR with posttreatment renal function. This was a prespecified secondary endpoint of the multicenter FASTRACK II (Focal Ablative STereotactic RAdiotherapy for Cancers of the Kidney phase II) clinical trial (National Clinical Trial 02613819). Patients received either 26 Gy in a single fraction (SF) for tumors with a maximal diameter of 4 cm or less or 42 Gy in 3 fractions (multifraction [MF]) for larger tumors. To determine renal function change, 99mTc-dimercaptosuccinic acid (DMSA) single-photon emission computed tomography/computed tomography (SPECT/CT) scans were acquired, and the glomerular filtration rate was estimated at baseline, 12, and 24 months posttreatment. Imaging data sets were rigidly registered to the planning CT where kidneys were segmented to calculate dose-response curves. From 71 enrolled patients, 36 (51%) and 26 (37%) patients were included in this study based on availability of posttreatment data at 12 and 24 months, respectively. The ipsilateral kidney glomerular filtration rate decreased from baseline by 42% and 39% in the SF cohort and by 45% and 62% in the MF cohort, at 12 and 24 months, respectively (P <.03). The loss in renal function was 3.6%/Gy ± 0.8%/Gy and 4.5%/Gy ± 1.0%/Gy in the SF cohort and 1.7%/Gy ± 0.1%/Gy and 1.7%/Gy ± 0.2%/Gy in the MF cohort at 12 and 24 months, respectively. The major loss in renal function occurred in high-dose regions, where dose-response curves converged to a plateau. For the first time in a multicenter study, the dose-effect relationship at 12 and 24 months post-SABR treatment for primary renal cell carcinoma was quantified. Kidney function reduces linearly with dose up to 100 Gy BED 3. [ABSTRACT FROM AUTHOR]

Purpose To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) > 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (>38 °C) within 48 hours of drug administration. Results Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 °C P <.001) but remained below 38 °C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P =.009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P =.8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P =.004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab. [ABSTRACT FROM AUTHOR]

The ABCD‐GENE score was developed to predict poor response to clopidogrel and includes Age, Body mass index, Chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2), Diabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). Estimation of GFR without a race variable via the CKD‐EPI Scr 2021 equation is now recommended. We examined the impact of using the CKD‐EPI Scr 2021 vs. 2009 equation on the ABCD‐GENE score for post‐PCI patients. A total of 4335 adult patients (n = 925 Black) who underwent PCI and CYP2C19 genotyping were included, with GFR estimated for each patient via the CKD‐EPI Scr 2021 and CKD‐EPI 2009 equations. The ABCD‐GENE score, calculated based on each GFR estimation, was compared. With the CKD‐EPI Scr 2021 vs. 2009 equation, median (IQR) eGFR was lower (74 [55–94] vs. 81 [60–103] mL/min/1.73 m2, P < 0.001), and CKD prevalence was higher (31% vs. 25%, P < 0.001) among Black patients, whereas eGFR was higher (85 [65–99] vs. 80 [61–94] mL/min/1.73m2, P < 0.001), and CKD prevalence was lower (20% vs. 24%, P < 0.001) in non‐Black patients. This led to 12 (1%) Black patients being reclassified from low to high risk of poor clopidogrel response and 30 (1%) non‐Black patients being recategorized from high to low risk (P < 0.001 for both comparisons). Removal of the race variable from GFR estimation significantly impacted the prediction of clopidogrel effectiveness via the ABCD‐GENE score. [ABSTRACT FROM AUTHOR]

Determination of serum creatinine concentrations and subsequent calculation of estimated glomerular filtration rates (eGFR) is a cornerstone of clinical medicine. Crucial clinical decisions such as drug treatment discontinuations are based on eGFR calculated from serum creatinine measurements. However, creatinine is not only filtered in the kidneys, but also actively secreted into urine. Creatinine transporters such as OCT2, OCT3, MATE1, MATE2‐K, and OAT2 expressed in proximal tubular cells are responsible for active renal secretion of creatinine. Multiple drugs (e.g., oral antitumor drugs) inhibit these transporters thereby causing a pseudo‐worsening of kidney function with an increase in serum creatinine concentrations and a decrease in eGFR while other methods for eGFR determination (e.g., by cystatin C) reveal normal kidney function. Since US Prescribing Information (PI) and European Summaries of Product Characteristics (SmPCs) are the most relevant source of information for physicians, we investigated the quality of information in US PI/German SmPCs of drugs with clear evidence for pseudo‐worsening of kidney function. 514 drugs putatively interacting with creatinine transporters were identified. For 149 of those drugs, an increase in serum creatinine concentrations has been described. Available data confirmed the existence of pseudo‐worsening of kidney function for 30 of those drugs, for the remaining 119 drugs existing data are insufficient. Only 23.5% (12/51) of the 30 drugs' PI/SmPCs contained unambiguous statements on this proven pseudo‐worsening of kidney function and gave clear recommendations for clinical management. Taken together, inadequate information provided in PI or SmPCs on the pseudo‐worsening of kidney function poses patients at unnecessary risks. [ABSTRACT FROM AUTHOR]

Purpose: To develop a multivariate liniear model for predicting long-term (> 3 months) post-adrenalectomy renal function decline in patients with primary aldosteronism (PA). The model aims to help identify patients who may experience a significant decline in renal function after surgery. Methods: We retrospectively analyzed the clinical data of 357 patients who were diagnosed with PA and underwent adrenalectomy between September 2012 and February 2023. LASSO and multivariate linear regression analyses were used to identify significant risk factors for model construction. The models were further internally validated using bootstrap method. Results: Age (P < 0.001), plasma aldosterone concentration (PAC) measured in the upright-position (PACU, P = 0.066), PAC measured after saline infusion (PACafterNS, P = 0.010), preoperative blood adrenocorticotropic-hormone level (ACTH, P = 0.048), preoperative estimated glomerular filtration rate (eGFR, P < 0.001) and immediate postoperative eGFR (P < 0.001) were finally included in a multivariate model predictive of post-adrenalectomy renal function decline and the coefficients were adjusted by internal validation. The final model is: predicted postoperative long-term (> 3 months) eGFR decline =-70.010 + 0.416*age + 6.343*lg PACU+4.802*lg ACTH + 7.424*lg PACafterNS+0.637*preoperative eGFR-0.438*immediate postoperative eGFR. The predicted values are highly related to the observed values (adjusted R = 0.63). Conclusion: The linear model incorporating perioperative clinical variables can accurately predict long-term (> 3 months) post-adrenalectomy renal function decline. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the differences in perioperative outcomes between transperitoneal and retroperitoneal techniques in cutaneous ureterostomy (CUS). Methods: Between 2018 and 2023, 55 patients underwent CUS following robot-assisted radical cystectomy. Among the 55 patients, we compared 33 patients who underwent transperitoneal CUS (t-CUS) and 22 who underwent retroperitoneal CUS (r-CUS). Results: Compared with the r-CUS group, the t-CUS group had significantly shorter operative times (p < 0.001); significantly less estimated blood loss (p < 0.001); and significantly lower incidence of complications (Clavien–Dindo classification grade ≤ 2) within 30 days (p = 0.005). Unexpectedly, the incidence of ileus within 30 days was lower, though the difference was not statistically significant (p = 0.064). During the median follow-up period of 24.3 months, no ileus was observed in either group after 30 days postoperatively. There was no significant difference in the stent-free rate between the groups (p = 0.449). There were also no significant differences in the rates of change in estimated glomerular filtration rate from preoperatively at 3, 6, 12, and 24 months postoperatively between the groups (p = 0.590, p = 0.627, p = 0.741, and p = 0.778, respectively). Conclusions: Compared with r-CUS, t-CUS was associated with a shorter operative time and lower incidence of perioperative complications, including gastrointestinal complications. We believe that t-CUS can be performed safely and effectively. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) was one of the most prevalent comorbidities among patients with coronavirus disease 2019 (COVID-19). Interactions between different metabolic parameters contribute to the susceptibility to the virus; thereby, this study aimed to rank the importance of clinical and laboratory variables as risk factors for COVID-19 or as protective factors against it by applying machine learning methods. Method: This study is a retrospective cohort conducted at a single center, focusing on a population with T2DM. The patients attended the Yazd Diabetes Research Center in Yazd, Iran, from February 20, 2020, to October 21, 2020. Clinical and laboratory data were collected within three months before the onset of the COVID-19 pandemic in Iran. 59 patients were infected with COVID-19, while 59 were not. The dataset was split into 70% training and 30% test sets. Principal Component Analysis (PCA) was applied to the data. The most important components were selected using a 'sequential feature selector' and scored by a Linear Discriminant Analysis model. PCA loadings were then multiplied by the PCs' scores to determine the importance of the original variables in contracting COVID-19. Results: HDL-C, followed by eGFR, showed a strong negative correlation with the risk of contracting the virus. Higher levels of HDL-C and eGFR offer protection against COVID-19 in the T2DM population. But, the ratio of BUN to creatinine did not show any correlation. Conversely, the AIP, TyG index and TG showed the most positive correlation with susceptibility to COVID-19 in such a way that higher levels of these factors increase the risk of contracting the virus. The positive correlation of diastolic BP, TyG-BMI index, MAP, BMI, weight, TC, FPG, HbA1C, Cr, systolic BP, BUN, and LDL-C with the risk of COVID-19 decreased, respectively. Conclusion: The atherogenic index of plasma, triglyceride glucose index, and triglyceride levels are the most significant risk factors for COVID-19 contracting in individuals with T2DM. Meanwhile, high-density lipoprotein cholesterol is the most protective factor. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Editorial Comment Estimating equations for the assessment of glomerular filtration rate (GFR) have been poorly investigated in the critical care setting. We evaluated the agreement between the GFR measured with 51CrEDTA/iohexol (mGFR) and four estimating equations based on serum concentrations of creatine and/or cystatin C (eGFR) in two cohorts: critically ill patients and outpatients with normal‐to‐moderately reduced GFR.Forty‐three patients in the critical care group and 48 patients in the outpatient group were included. GFR was measured (mGFR) by plasma infusion clearance of 51Cr‐EDTA/iohexol (critical care group) and the single injection, one‐sample plasma 51Cr‐EDTA clearance technique (outpatients). The following estimating equations (eGFR) were used: the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation for creatinine (CKD‐EPICr), cystatin C (CKD‐EPICys C), creatinine+cystatin C (CKD‐EPICr + Cys C) and the Lund‐Malmö creatinine+cystatin C equation (LMCr + Cys C). Agreement between mGFR and eGFR was assessed by the Bland–Altman method and accuracy by calculating P30 and P10.In the critically ill group, the bias between the estimating equations and mGFR was −3.6 to 2.8 mL/min/1.73 m2, while the error was 121%–127% and the accuracy (P30) 33%–40%. In the outpatients, the bias between the estimating equations and mGFR was −13.0 to 7.6 mL/min/1.73 m2, while the error was 31%–41% and the accuracy (P30), 67%–96%.All four equations performed poorly in assessing GFR in the critically ill cohort with an unacceptably high error and low accuracy in contrast to the outpatient group. To accurately assess GFR in critically ill patients, GFR must be measured not estimated.For the assessment of glomerular filtration rate (GFR), it can be measured directly, but is frequently estimated using a point measure of serum creatinine concentration. In this study, ICU case GFR estimations, by different adjusted equations, done also for a cohort of outpatients, showed that these serum creatinine‐based estimations for ICU cases are not highly precise or reliable. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium–glucose cotransporter‐2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome.We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135–145 mmol/L) and follow‐up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021.After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non‐steroidal anti‐inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow‐up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83–3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16–2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73–2.96) and all‐cause death (HR: 2.98; 95% CI: 2.17–4.11) after adjusting for clinically relevant factors. Non‐linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events.While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion We have previously reported the mid‐term efficacy and safety of tacrolimus (Tac)‐based immunosuppressive therapy in such patients, and herein, we aimed to determine their long‐term outcomes (over 10 years).We retrospectively evaluate the data of 13 consecutive patients with biopsy‐proven long‐standing LN who underwent a long‐term Tac‐based treatment regimen. Tac was administered once daily at a dose of 3 mg as reinduction or maintenance treatment. Treatment outcomes were defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein/creatinine ratio (Up/cr), serum creatinine, estimated glomerular filtration rate (eGFR) and serological lupus markers (complement C3, complement hemolytic activity [CH 50], and anti‐dsDNA antibody titre), and the concomitantly administered prednisolone (PDN) dose. Data on clinical parameters and serological lupus activity were collected annually from each patient throughout the study period.The patients' baseline characteristics at the treatment initiation were as follows: mean age, 18 years; Up/cr, 0.63 ± 0.69; serum C3 level, 57.2 ± 22.4 mg/dL (normal range, 79–152 mg/dL); CH50, 27.9 ± 15.7 U/mL (normal range, 23.0–46.0 U/mL); serum anti‐dsDNA antibody titre, 111.7 ± 123.4 IU/mL (normal range, <12.0 IU/mL); serum creatinine, 0.60 ± 0.19 mg/dL; eGFR, 115.6 ± 21.3 mL/min and SLEDAI, 13 ± 8.1. Despite the gradual tapering of the concomitantly administered PDN dose from 18.7 ± 13.5 mg/day at baseline to 3.5 ± 2.8 mg/day at 10 years (p = .002), a marked improvement in the outcomes, compared with the baseline values, was observed within a year. Additionally, these favourable changes persisted throughout study period in most patients. Compared with the baseline values, the following measures confirmed sustained outcome improvements after a 10‐year treatment: SLEDAI, 1.7 ± 2.0; serum C3 level, 83.8 ± 16.1 mg/dL; CH50, 45.6 ± 10.9 U/mL (all p < .01) and Up/cr, 0.16 ± 0.18 and serum anti‐dsDNA antibody titre, 25.8 ± 28.8 IU/mL (both p < .05). Serum creatinine level and eGFR remained within the normal range in all study participants except for one patient who experienced several flare‐ups. No serious adverse effects were observed.Our results suggest that long‐term Tac‐based immunosuppressive treatment as maintenance therapy is beneficial and has low cytotoxicity. Therefore, it represents an attractive option for the treatment of selected patients with paediatric‐onset LN in a real‐world setting. [ABSTRACT FROM AUTHOR]

Introduction: The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals. Methods: This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure. Results: The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors. Discussion: Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics. [ABSTRACT FROM AUTHOR]

Background: Uric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels. Methods: A total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985–1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women. Results: Over a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30–59 ml/min/1.73 m2) had a higher risk of AF compared to those with normal eGFR (60–89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29–2.30; HR = 1.10, 95% CI: 1.03–1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72–1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64–4.07). Conclusion: Uric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed is combined with cisplatin to treat cancer. Whether pemetrexed-cisplatin combination chemotherapy exacerbates cisplatin nephrotoxicity is unclear. Here, we investigated kidney injury in mice administered a non-lethal low-dose regimen of pemetrexed or cisplatin alone and compared it with a pemetrexed-cisplatin combination. Methods: Mice were randomly divided into four groups and administered intraperitoneally the experimental drugs solubilized in captisol (sulfobutylether β-cyclodextrin). Group 1 received captisol, Group 2 pemetrexed (10 mg/kg), Group 3 cisplatin (1 mg/kg), and Group 4 pemetrexed (10 mg/kg) plus cisplatin (1 mg/kg). The mice were treated every other day for two weeks, three times per week. Glomerular filtration rate (GFR) was determined on the third day after the last treatment, followed by a necropsy. Results: Whereas the relative kidney weight was comparable in the control vs. pemetrexed or cisplatin alone group, it was significantly increased in the combination group. Mice treated with cisplatin and pemetrexed-cisplatin combination exhibited reduced GFR. The pemetrexed-cisplatin combination caused significant increases in the plasma or urinary levels of kidney injury biomarkers, renal lipid peroxidation, and nitrosative stress compared with pemetrexed or cisplatin alone. Histopathology revealed that pemetrexed or cisplatin alone had minimal effects on the kidneys. By contrast, the pemetrexed-cisplatin combination caused tubular degeneration, dilatation, and granular casts. Live-cell imaging showed that the pemetrexed-cisplatin combination caused more severe apoptosis of primary renal epithelial cells than individual concentrations. Conclusions: These findings suggest that combining pemetrexed and cisplatin causes oxidative kidney damage at individual doses that do not cause significant nephrotoxicity. Hence, the renal function of patients undergoing treatment with the pemetrexed-cisplatin combination needs extensive monitoring. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram's area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD. [ABSTRACT FROM AUTHOR]

AbstractA low eGFRcystatin C/eGFRcreatinine-ratio is characteristic of a group of serious kidney disorders called ‘Selective Glomerular Hypofiltration Syndromes’. This study examines if such a low ratio can also be used to evaluate the risk for women with hypertensive disorders in pregnancy to develop severe maternal morbidity. All women discharged from the perinatal ward at the Skåne University Hospital in Lund during the period of 1-9-2016 to 31-8-2017 under one of the diagnoses within hypertensive disorders in pregnancy were considered for inclusion in the study. After delivery and discharge from the hospital, records from included patients were reviewed and all registered measures of renal function were analysed. An eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 in a sample drawn not earlier than three days before delivery was considered as defining a high risk for severe maternal morbidity. A strong association (p-value: 0.035) between severe maternal morbidity and an eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 was found in a subgroup of 32 women diagnosed with ‘preeclampsia with severe features’. A total of 69 women were included in the study. Fifty were defined as high-risk and seventeen of them (34%) developed severe maternal morbidity. Among the nineteen women defined as low-risk only two (10.5%) developed severe maternal morbidity (p-value: 0.051). A low eGFRcystatin C/eGFRcreatinine-ratio seems promising as a predictive marker for maternal morbidity in hypertension in pregnancy. Its performance as a tool in the monitoring of progressing disease should be evaluated further in larger cohorts. Delivery before the eGFRcystatin C/eGFRcreatinine-ratio decreases to, or below, 0.60 might help avoid maternal complications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To compare cardiorenal outcomes of dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) in a national diabetic kidney disease (DKD) population.A cohort study was conducted using Taiwan's National Health Insurance Research Database and Laboratory Databases. Propensity score‐matched prevalent new users of SGLT‐2is (n = 1524) and DPP‐4is (n = 6005) during 2017‐2018 were selected from adults with DKD and an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2. Composite renal outcomes included sustained eGFR decrease, renal failure and renal mortality. Composite cardiovascular (CV) outcomes included acute myocardial infarction, stroke, hospitalization for heart failure and CV death. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).Compared with DPP‐4i users, SGLT‐2i users had a reduced risk of composite renal endpoint (HR: 0.16; CI: 0.12‐0.24), consistently for a prolonged time to 50% or higher eGFR decrease (HR 0.17; CI: 0.11‐0.27), renal failure (HR: 0.14; CI: 0.08‐0.23) and decreased renal death (HR: 0.10; CI: 0.01‐0.70). SGLT‐2i users had a better composite CV outcome than DPP‐4i users (HR: 0.74; CI: 0.64‐0.85), and lower risks of stroke (HR: 0.76; CI: 0.62‐0.92) and hospitalization for heart failure (HR: 0.68; CI: 0.55‐0.84). Findings were consistent in analyses stratified by concomitant antidiabetic agents or intervals between DKD diagnosis and study drug initiation.This study shows the superior cardiorenal benefits of SGLT‐2is compared with DPP‐4is in the DKD population, regardless of concomitant antidiabetic agents or time from DKD onset to study drug initiation. SGLT‐2is should be prioritized in adult patients with DKD. [ABSTRACT FROM AUTHOR]

Background: The present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China. Methods: A total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60–90 ml·min–1·(1.73 m2)–1. The relationship between changes in SUA levels and the eGFR was assessed. Results: (1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P < 0.05). When classified into five groups by the degree of eGFR change (ΔeGFR), analysis of variance revealed no statistically significant differences between baseline SUA and follow-up SUA (P > 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P < 0.01). (3) Multifactorial logistic regression, in which the endpoint event was an eGFR decreasing to 60 to 90 ml·min–1·(1.73 m2)–1, revealed that the ΔSUA was a risk factor that independently predicted a reduced eGFR (OR = 1.347, P < 0.001). Conclusion: In people with a normal eGFR in Urumqi, a high SUA level is associated with a mild reduction in the eGFR. [ABSTRACT FROM AUTHOR]

Background: Altitude influences bicarbonate levels, it is a variable that is hardly considered in diagnosing Renal Tubular Acidosis (RTA), so it should be a factor to consider when diagnosing this pathology, especially at 2250 mts over the sea level as it is the case of Mexico City. RTA is most often misdiagnosed. Regarding of this, the present study established reference limits for bicarbonate levels in healthy children without pathologies associated with alterations in the acid-base balance in Mexico City and it´s metropolitan area. Methods: A total of 267 healthy pediatric patients were included, within normal estimated glomerular filtration rate (eGFR), and without any associated pathology of any alteration in the acid-base balance. Results: Compared to older children, children younger than two years of age showed statistically higher levels of calcemia and cystatin C. On the other hand, this same group showed lower values of creatininemia, pCO2, and HCO3-. Percentile 50 of bicarbonate in children under two years of age were 19.9 mEq/L and 21.9 mEq/L in those over that age. A correlation was identified between HCO3- levels and pCO2 (r = 0.68; p < 0.001). Conclusions: In the study population, an effect of altitude on blood levels of pCO2 and HCO3- was observed. [ABSTRACT FROM AUTHOR]

Background: Perioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias. Objective: We aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant. Methods: This single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes. Results: Twenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05). Conclusion and Relevance: Both AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications. [ABSTRACT FROM AUTHOR]

Introduction: Treating extensive burn injury requires an individually tailored resuscitation protocol that includes hourly-titrated intravenous fluid infusion to avert both hypovolemic shock and edema. Due to the complexity of burn pathophysiology and significant variability in treatment protocols, there is an ongoing effort to optimize burn resuscitation. The goal of this work is to contribute to this effort by developing a mathematical model of burn pathophysiology and resuscitation for in silico testing of burn resuscitation protocols and decision-support systems. Methods: In our previous work, we developed and validated a mathematical model consisting of volume kinetics, burn-induced perturbations, and kidney function. In this work, we expanded our previous mathematical model to incorporate novel mathematical models of cardiovascular system and hormonal system (renin-angiotensin-aldosterone (RAAS) system and antidiuretic hormone) which affect blood volume and pressure regulation. We also developed a detailed mathematical model of kidney function to regulate blood volume, pressure, and sodium levels, including components for glomerular filtration rate, reabsorption rates in nephron tubules, Tubuglomerular feedback, and myogenic mechanisms. We trained and validated the expanded mathematical model using experimental data from 15 pigs and 9 sheep with extensive burns to quantitatively evaluate its prediction accuracy for hematocrit, cardiac output, mean arterial pressure, central venous pressure, serum sodium levels, and urinary output. We then trained and tested the mathematical model using a clinical dataset of 233 human burn patients with demographic data and urinary output measurements. Results: The mathematical model could predict all tested variables very well, while internal variables and estimated parameters were consistent with the literature. Discussion: To the best of our knowledge, this is the first mathematical model of burn injury and resuscitation which is extensively validated to replicate actual burn patients. Hence, this in silico platform may complement large animal preclinical testing of burn resuscitation protocols. Beyond its primary purpose, the mathematical model can be used as a training tool for healthcare providers delivering insight into the pathophysiology of burn shock, and offering novel mathematical models of human physiology which can be independently used for other purposes and contexts. [ABSTRACT FROM AUTHOR]

Background: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods: In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results: The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac (p < 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. −3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions: Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios. [ABSTRACT FROM AUTHOR]

Background/Objectives: Renal function influences bone metabolism, as kidney failure can increase the risk of fractures. Denosumab is an approved osteoporosis treatment, but its efficacy in relation to renal function has not yet been studied in real-life scenarios. This study aimed to investigate the denosumab-induced change in bone mineral density (BMD) according to kidney function. Methods: A retrospective analysis was conducted at the outpatient clinic in postmenopausal women receiving denosumab (60 mg subcutaneously administered every 6 months). The glomerular filtration rate (eGFR) was measured by the 2021 CKD-EPI equation and patients were stratified for eGFR categories. BMD was measured by dual-energy X-ray absorptiometry. Results: 128 women (mean age 70.3 ± 9.4 years) were recruited. The mean denosumab treatment duration was 3.9 ± 1.4 years and all the participants had improved BMD values. In stepwise multiple regression analysis—after controlling for age, BMI, and treatment duration—the eGFR value (ß = −0.11, SE 0.04, p = 0.01) was independently associated with the lumbar spine BMD change. The same association remained when the eGFR categories were considered (ß = 3.564, SE 1.29, p = 0.007). In addition, after controlling for BMI and the duration of denosumab treatment, age (ß = −0.7915, SE 0.37, p = 0.03) and eGFR (ß = −0.3257, SE 0.1567, p = 0.04) were found to be associated with femoral neck BMD change. The association remained when considering eGFR categories (ß = 8.7339, SE 4.29, p = 0.04). Conclusions: This retrospective study suggests that eGFR is associated with denosumab efficacy in postmenopausal women treated for osteoporosis. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To assess the preoperative disease characteristics and indications for living donor liver transplantation (LDLT), complications, patient survival, and prognosis after LDLT for fibropolycystic liver disease (FLD) in children.We undertook a cross‐sectional survey of patients who underwent LDLT for FLD between January 2002 and December 2020.A total of 35 patients (22 male and 13 female individuals) with FLD were included in this study, of whom 19 (54.3%) had isolated congenital hepatic fibrosis and 16 (45.6%) had Caroli syndrome. Refractory gastrointestinal bleeding was the most frequent symptom related to the indication for LDLT, being found in 48.6% of our patients, followed by uncontrollable cholangitis and ascites. The median age at the time of LDLT was 8.1 years old. Of the 27 patients presenting with renal involvement, 13 patients required kidney transplantation (KT). Overall, the renal function after LDLT decreased regardless of renal involvement; however, patients with renal involvement had a significantly lower estimated glomerular filtration rate than those without renal involvement throughout the course of this study (p < 0.01). The 5‐year overall patient survival rate was 97.1%. Two patients died with a median follow‐up of 8.9 years after LDLT; one died due to sepsis 2 weeks after simultaneous liver–kidney transplantation and the other committed suicide 10 years after LDLT.The prognosis of the pediatric patients who underwent LDLT for FLD was excellent. However, an individualized treatment approach based on the status of the renal function and liver disease is important, as a certain proportion of patients require KT. [ABSTRACT FROM AUTHOR]

Empirical maturation models (e.g., Johnson and Rhodin models) for glomerular filtration rate (GFR) are commonly used as scaling factors for predicting pediatric renal clearance, but their predictive performance for drugs featured with tubular reabsorption is poorly understood. This study investigated the adequacy of GFR‐based scaling models for predicting pediatric renal clearance in drugs with passive tubular reabsorption by comparing with a mechanistic kidney model (Mech‐KiM) that encompasses the physiological processes of glomerular filtration, tubular secretion, and reabsorption. The analysis utilized hypothetical drugs with varying fractions of tubular reabsorption (Freabs), alongside the model drug metronidazole, which has a Freabs of 96%. Our simulations showed that when Freabs is ≤70%, the discrepancies between the GFR‐based scaling methods and the Mech‐KiM model in predicting pediatric renal clearance were generally within a twofold range throughout childhood. However, for drugs with substantial tubular reabsorption (e.g., Freabs > 70%), discrepancies greater than twofold were observed between the GFR‐based scaling methods and the Mech‐KiM model in predicting renal clearance for young children. In neonates, the differences ranged from 5‐ to 10‐fold when the adult Freabs was 95%. Pediatric physiologically based pharmacokinetic (PBPK) modeling of metronidazole revealed that using a GFR‐based scaling method (Johnson model) significantly overestimated drug concentrations in children under 2 months, whereas utilizing the Mech‐KiM model for renal clearance predictions yielded estimates closely aligned with observed concentrations. Our study demonstrates that using GFR‐based scaling models to predict pediatric renal clearance might be inadequate for drugs with extensive passive tubular reabsorption (e.g., Freabs > 70%). [ABSTRACT FROM AUTHOR]

Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Despite the development of transient elastography (TE)‐based Agile scores for diagnosing fibrotic burden in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), their applicability in predicting kidney outcomes remains unclear. We aimed to investigate the association between liver fibrotic burden, as assessed by Agile scores, and the risk of incident chronic kidney disease (CKD) in patients with MASLD. Methods: A total of 3240 participants with MASLD but without pre‐existing CKD who underwent TE between July 2006 and October 2018 were selected. The primary outcome was incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+ on dipstick) on two consecutive measurements. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. Results: During a median follow‐up of 3.6 years, 187 participants (5.8%) developed incident CKD. When stratified into three groups according to Agile 3+ scores, multivariable Cox models revealed that risk of incident CKD was 2.77‐fold (95% confidence interval [CI], 1.89–4.07; p < 0.001) higher in the high‐risk group (Agile 3+ >0.68), compared to the low‐risk group (Agile 3+ <0.45). During a median follow‐up of 3.4 years, the high‐risk group had a 2.41‐fold higher risk (95% CI, 1.86–3.12; p < 0.001) of experiencing the secondary outcome, compared to the low‐risk group. Similar findings were observed for Agile 4 scores. Prediction testing revealed that Agile scores were better predictors of kidney outcomes, compared to liver stiffness measured by TE. Conclusions: In patients with MASLD, but without CKD, advanced liver fibrosis measured by Agile scores was significantly associated with a higher risk of incident CKD. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aimed to examine the association between the triglyceride‐glucose (TyG) index and chronic kidney disease (CKD) in normotensive adults with hypertension and further investigate potential effect modifiers of this association. A total of 7975 normoweight hypertensive participants were enrolled from the Chinese H‐type hypertension registry (CHHRS) cohort. The TyG index was calculated using the formula: ln (fasting triglyceride [mg/dL] × fasting plasma glucose [mg/dL])/2. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 of body surface area. Multivariate logistic regression analysis revealed a 50% increased risk of CKD (OR: 1.50, 95% CI: 1.26–1.79) for each unit increase in the TyG index. A linear dose‐response relationship between the TyG index and CKD risk was observed using restricted cubic spline analysis. Compared to the first quartile of the TyG index, the fourth quartile showed a significantly higher risk of CKD (OR: 1.88; 95% CI: 1.41–2.50). Subgroup analysis identified a stronger association between the TyG index and CKD risk in males and individuals with a history of alcohol consumption (all p values for interaction < 0.05). In conclusions, the TyG index was significantly associated with an increased risk of CKD in normoweight adults with hypertension, particularly in males and those with a history of alcohol consumption. [ABSTRACT FROM AUTHOR]

Background Results and Conclusion Obesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease.Glucagon‐like peptide‐1 agonists and sodium‐glucose cotransporter‐2 inhibitors are two novel classes of glucose‐lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon‐like peptide‐1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well‐established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. Methods: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. Results: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. Conclusions: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions. Methods: Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification. Results: Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy. Conclusion: Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association. [ABSTRACT FROM AUTHOR]

Purpose: The identification of patients with chronic hypoparathyroidism who are adequately (AC) or not adequately controlled (NAC) has clinical interest, since poor disease control is related to complications and mortality. We aimed to assess the prevalence of NAC patients in a cohort of subjects with postsurgical hypoparathyroidism. Methods: We performed a multicenter, retrospective, cohort study including patients from 16 Spanish hospitals with chronic hypoparathyroidism lasting =3 years. We analyzed disease control including biochemical profile and clinical wellness. For biochemical assessment we considered three criteria: criterion 1, normal serum calcium, phosphorus and calcium x phosphorus product; criterion 2, the above plus estimated glomerular filtration rate =60 ml/min/1.73 m2; and criterion 3, the above plus normal 24-hour urinary calcium excretion. A patient was considered AC if he or she met the biochemical criteria and was clinically well. Results: We included 337 patients with postsurgical hypoparathyroidism (84.3% women, median age 45[36-56] years, median time of follow-up 8.9[6.0-13.0] years). The proportions of NAC patients with criteria 1, 2 and 3 were, respectively, 45.9%, 49.2% and 63.1%. Patients who had dyslipidemia at the time of diagnosis presented a significantly higher risk of NAC disease (criterion 3; OR 7.05[1.44-34.45]; P=0.016). NAC patients (criterion 2) had a higher proportion of subjects with incident chronic kidney disease and eye disorders, and NAC patients (criterion 3) had a higher proportion of incident chronic kidney disease, nephrolithiasis and dyslipidemia than AC patients. Conclusion: The present study shows a strikingly high prevalence of NAC patients in the clinical practice of Spanish endocrinologists. Results suggest that NAC disease might be associated with some prevalent and incident comorbidities. [ABSTRACT FROM AUTHOR]

This systematic review explores the relationship between the gut microbiota metabolite trimethylamine N-oxide (TMAO) and heart failure (HF), given the significant impact of TMAO on cardiovascular health. A systematic search and meta-analysis of peerreviewed studies published from 2013 to 2024 were conducted, focusing on adult patients with heart failure and healthy controls. The review found that elevated levels of TMAO are associated with atherosclerosis, endothelial dysfunction, and increased cardiovascular disease risk, all of which can exacerbate heart failure. The analysis also highlights that high TMAO levels are linked to reduced left ventricular ejection fraction (LVEF) and glomerular filtration rate (GFR), further supporting TMAO's role as a biomarker in heart failure assessment. The findings suggest that interventions targeting gut microbiota to reduce TMAO could potentially benefit patients with heart failure, although further research is needed to evaluate the effectiveness of such approaches. [ABSTRACT FROM AUTHOR]

Background: There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this. Methods: Individuals aged 18–75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography–mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 ('no or minimal IFTA' i.e. <10%, IFTA), IFTA 1 ('mild IFTA' i.e. 10–25% IFTA) and IFTA ≥ 2 ('moderate or severe IFTA' i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups. Results: 64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols. Conclusions: We report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression. [ABSTRACT FROM AUTHOR]

Backgrounds: Crush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures. Methods: Mice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols. Results: The results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state. Conclusion: We successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI. [ABSTRACT FROM AUTHOR]

Introduction: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study. Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function. Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73 m2). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m2) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m2) (p < 0.05). Individuals working longer hours exhibited lower eGFR (β = -0.772, 95% CI: -1.241, -0.303, for > 40 h/wk compared to working ≤ 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values (β = 1.159, 95% CI: 0.699, 1.619) compared to low PA ( < 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours. Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours. [ABSTRACT FROM AUTHOR]

Background: Existing studies investigating the impact of serum calcium (Ca), phosphate (P), 25 hydroxyvitamin D (25[OH]D), and parathyroid hormone (PTH) levels on kidney function have produced inconsistent results. Further research is needed to establish the direct causal relationship between these factors and kidney function. Methods: The study used genome-wide association study datasets for exposure and outcome, mainly derived from the UK Biobank and CKDGen Consortium, with sample sizes ranging from 3,310 to 480,699 individuals of European ancestry. Heritability and genetic correlations among these phenotypes were assessed using linkage disequilibrium score regression (LDSC) and phenotypes with a heritability z-score <4 were excluded from further analyses. Pleiotropic analyses were performed to identify potential horizontal pleiotropic variants at gene and LD-independent locus levels. Mendelian randomization (MR) analysis, using instrumental variables (IVs) based on two distinct selection criteria, was conducted to investigate the potential causal relationships between serum Ca, P, 25(OH)D, PTH, and kidney function. Results: PTH was excluded from further analysis due to a heritability z-score < 4. Genetic correlations were observed between serum Ca and urine albumin-tocreatinine ratio (UACR) (rg = 0.202, P-value = 5.0E-04), between serum 25(OH)D and estimated glomerular filtration rate using serum creatinine (eGFRcrea) (rg = -0.094; P-value = 1.4E-05), and between serum25(OH)D and blood urea nitrogen (BUN) (rg = 0.127; P-value = 1.7E-06). In univariableMR analysis using IVs based on two different selection criteria, it consistently demonstrated that genetically predicted serum Ca consistently showed an increase in UACR (beta 0.11, P-value 2.0E-03; beta 0.13, P-value 2.0E-04). Similarly, serum P was associated with a decrease in eGFRcrea (beta -0.01, P-value 2.0E-04; beta -0.005, P-value 2.0E -03) and an increase in BUN (beta 0.02, P-value 3.0E-03; beta 0.02, P-value 7.5E -07). The influence of serum P on kidney function was further supported in multivariable MR analysis. However, genetically predicted 25(OH)D did not have a significant impact on kidney function. Conclusions: Elevated serum Ca or P levels could both impair kidney function, whereas 25(OH)D has no impact on renal function. [ABSTRACT FROM AUTHOR]