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BACKGROUND: The 24-h urine protein (24-hUP) excretion is the gold standard for evaluating proteinuria. This study aimed to evaluate the diagnostic efficacy of protein/creatinine ratio (PCR) for estimating 24-hUP at various levels of renal function and proteinuria levels. METHODS: A cross-sectional study was conducted between December 2021 and December 2023 in Salvador, Bahia-Brazil, as an extension of previously published data from the TUNARI study. The study included 217 samples from 152 patients with various levels of renal function and proteinuria. PCR in isolated samples and 24-hUP were determined conventionally within a 24-h timeframe. Patients were classified into three groups according to the level of renal function (Group 1 = 10 to  60 mL/min) and level of proteinuria ( 3.5 g/day). The data were analyzed using the Spearman correlation (rs), coefficient of determination (r2), Bland-Altman plots and receiver operating characteristic (ROC) curve. Likelihood ratios, positive (LR +), and negative (LR-) were derived from the sensitivity and specificity of PCR. RESULTS: Mean age was 41.5 ± 15.7 years, 61.8% were women, 36.8% Black and 52% Mixed-race. Glomerulopathies constituted 80.3%; 46.1% with lupus nephritis. Of the total urine samples, we observed a high correlation between PCR in the total sample of 24-hUP sample (rs = 0.86, p  0.3-3.5 g/day, the sensitivity was 64.1%, the specificity was 84.6%, and the AUC was 0.76 (95% CI = 0.67; 0.84), PCR detected all cases > 3.5 g/day. CONCLUSIONS: PCR is a suitable measure to be used as an indicator of 24-hUP at different levels of renal function, but may have limitations at higher levels of proteinuria. Analysis of PCR by proteinuria level found that agreement as well as sensitivity decreases at higher levels, but it maintains good specificity and is able to identify nephrotic range proteinuria.

Background and hypothesisIt remains unclear whether the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD), and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants.MethodsWe included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain magnetic resonance imaging late in life (exam cycles 7-9), cognitive outcome data, and available interim hypertension and BP assessments. We related CKD (estimated glomerular filtration rate

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.

Rationale & objectiveNovel approaches to the assessment of kidney disease risk during hypertension treatment are needed because of the uncertainty of how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline.Study designProspective observational study.Setting & participants8,005 SPRINT (Systolic Blood Pressure Intervention Trial) participants with NT-proBNP measurements at baseline and 1 year.Exposure1-year change in NT-proBNP categorized as a ≥25% decrease, ≥25% increase, or  0.2 for interactions).LimitationsPersons with diabetes and proteinuria >1 g/d were excluded.ConclusionsChanges in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Future studies should assess whether routine NT-proBNP measurements may be useful in monitoring kidney risk during hypertension treatment.Plain-language summaryN-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker in the blood that reflects mechanical stress on the heart. Measuring NT-proBNP may be helpful in assessing the risk of long-term losses of kidney function. In this study, we investigated the association of changes in NT-proBNP with subsequent kidney function among individuals with and without chronic kidney disease. We found that increases in NT-proBNP are associated with a faster rate of decline of kidney function, independent of baseline kidney measures. The associations were more pronounced in individuals with chronic kidney disease. Our results advance the notion of considering NT-proBNP as a dynamic tool for assessing kidney disease risk.

Objectives: To describe the clinical characteristics, comorbidity, and medical treatment in a primary care population with chronic kidney disease (CKD). Additionally, to investigate how primary care physicians (PCPs) diagnose, manage and treat impaired kidney function, including uptake of cardio-renoprotective renin–angiotensin–aldosterone system inhibitors (RAASis) and sodium glucose co-transporter 2 inhibitors (SGLT2is). Design: An observational study of CKD prevalence, treatment patterns and comorbidities in primary care based on patient record data combined with a questionnaire on diagnosis, management and treatment of impaired kidney function in a real-world, primary care setting. Setting: In all 128 primary care clinics in Denmark of 211 randomly invited and a quetionnaire completed by 125/128 participating PCPs. Methods: A computerized selection identified 12 random individuals with CKD per clinic with ≥ 2 measurements of eGFR < 60 mL/min/1.73 m2 or UACR > 30 mg/g within two years (N = 1 497). Pre-specified data collected from individual electronic health records included demographics, clinical variables, comorbidities, and relevant prescribed medications. Results: Of the CKD study population (N = 1 497), 80% had hypertension, 32% diabetes (DM), 13% heart failure (HF), 59% no DM/HF. ACEis/ARBs were prescribed to 65%, statins to 56%, SGTL2is to 14%, and MRAs to 8% of all individuals. Treatment patterns differed between individuals with varying comorbidities, e.g., ACEis/ARBs usage was higher in DM (76%) or HF (74%) vs. no DM/HF (58%), as was statin usage (76% in DM vs. 45% in no DM/HF). SGTL2i usage in no DM/HF was low. Most PCPs identified CKD using eGFR < 60 mL/min/1.73 m2 (62%) or UACR > 30 mg/g (58%) and 62% reported initiating treatment to retard kidney function decline. Conclusions: Despite good PCP awareness and wish to use relevant guidelines, a gap exists in implementation of cardio-renoprotective treatment, especially in individuals without DM/HF. This offers an opportunity for clear recommendations to PCPs to optimize early cardio-renal protection in individuals with CKD. [ABSTRACT FROM AUTHOR]

Background and objective: The latest consensus recommends using the ratio between the area under the curve over 24 h (AUC0–24) and minimal inhibitory concentration (MIC) as the therapeutic target for vancomycin in clinical practice, with a Bayesian approach and population pharmacokinetic (popPK) model being particularly recommended. While using both post-dose peak concentration (Cpeak) and pre-dose concentration (Ctrough) is more accurate than Ctrough alone, the optimal sampling strategy for estimating AUC0–24 is still unclear. The objective of this study was to determine the best sampling time(s) to estimate AUC0–24 using the Bayesian approach in these specific adult hematologic cancer patients. Methods: A virtual population (n = 7000) was simulated based on the distribution of the significant covariates (ideal body weight and estimated glomerular filtration rate) from the population used to develop the previous pharmacokinetic model. The dosing regimens from the Le Blanc et al. nomogram were used to generate, with NONMEM® (v.7.5), simulated pharmacokinetic (PK) profiles of one loading dose followed by three maintenance doses (steady state). Strategies involving two samples taken during earlier maintenance doses and one sample taken at steady state were tested using the Bayesian approach to predict PK parameters. These strategies were then evaluated for their ability to predict AUC0–24 at steady state (AUC0–24,ss) Results: For single-sample strategies, a sample taken anytime from 4 h post-dose can estimate AUC0–24,ss with precision similar to Ctrough (R2 ≈ 0.75), regardless of renal function (R2 ≈ 0.73–0.77). For two-sample strategies, taking samples at least midway through the dosing interval provides the highest precision for estimating AUC0–24,ss during the first two maintenance doses (R2 ≈ 0.75–0.77). In both strategies, using Cpeak did not yield as precise results as sampling midway through the dosing interval or at Ctrough. Conclusion: This study is the first to test multiple limited sampling strategies using a dosing nomogram stratified by renal function. The results show that vancomycin sampling can extend beyond traditional Cpeak and Ctrough without compromising the accuracy of maximum a posteriori Bayesian estimation of AUC0–24,ss, thereby providing an opportunity to investigate these limited sampling strategies combined with model-informed precision dosing in a clinical setting. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the relationship between 17 urinary metabolites of volatile organic compounds (mVOCs) in adolescents and renal function parameters (estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), urinary albumin, serum uric acid (SUA), and blood urea nitrogen (BUN)). In adjusted generalised linear models (GLM), mVOCs were positively correlated with eGFR, urinary albumin, and BUN, and mVOCs were negatively correlated with ACR and SUA. Weighted Quartile Sum (WQS) index correlated with eGFR [β(95%CI): 0.040 (0.028, 0.052)], urine albumin [β(95%CI): 0.275 (0.203, 0.622)], SUA [β(95%CI): 0.040 (0.025, 0.055)] and BUN [β(95%CI): 0.102 (0.082, 0.122)]. In Bayesian Kernel Machine Regression (BKMR) model, total compound effect was positively correlated with eGFR, positive associations were observed in high concentration of the mixture with urine albumin and ACR. Findings suggest that single and mixed exposures to mVOCs may affect renal parameters in adolescents. [ABSTRACT FROM AUTHOR]

Background: sNfL, a promising biomarker for neuroaxonal damage in Multiple Sclerosis (MS), requires cautious interpretation due to several comorbidity influences. Objectives: To investigate the impact of renal function on sNfL levels in MS patients. Methods: This retrospective study stratified patients by MS clinical phenotype, acute inflammatory activity (AIA) status—defined as relapse or gadolinium-enhancing lesions within 90 days of sample collection—renal function, assessed by estimated glomerular filtration rate (eGFR), and age (< 40 years, 40–60 years, > 60 years). Comparative analysis of sNfL levels across these groups was performed. The sNfL-eGFR relationship was examined using linear and non-linear regression models, with the best fit determined by R2 and the F estimator. Results: Data from 2933 determinations across 800 patients were analyzed. Patients with renal insufficiency (RI) (eGFR < 60 mL/min/1.73 m2) and mild renal impairment (MDRF) (eGFR 60–90 mL/min/1.73 m2) showed significantly higher sNfL levels compared to those with normal renal function, a pattern also observed in age groups 40 years and older. No significant differences were found between MDRF patients and those with AIA. Among RI patients, no differences in sNfL levels were observed between relapsing-remitting and progressive MS phenotypes. A regression S-Curve model was identified as the best fit, illustrating a marked increase in sNfL levels beginning at an eGFR of approximately 75 mL/min/1.73 m2. Discussion: Caution is advised when interpreting sNfL levels for monitoring MS in patients with impaired renal function. [ABSTRACT FROM AUTHOR]

Background and Aims: Sepsis-associated acute kidney injury (SA-AKI) significantly contributes to morbidity and mortality. Current biomarkers have limitations, necessitating the exploration of alternative indicators. This study aims to evaluate various urinary electrolyte parameters to predict SA-AKI. Methods: A prospective observational study included 111 sepsis patients within 24 h of admission. Urinary electrolyte samples were collected, and indices were calculated. Patients were monitored for 7 days to assess for acute kidney injury (AKI) according to Kidney Disease Improving Global Outcomes (KDIGO) definition criteria, mortality rates, and the need for renal replacement therapy. Mann-Whitney U test and Chi-squared test were used to analyse continuous and categorical variables, respectively. Receiver-operating characteristic (ROC) curves were constructed to determine to discriminatory ability of various parameters in predicting AKI. Results: Of 111 patients, 42.3% developed AKI, with a mortality rate of 59.5%. When evaluating urinary parameters, the product of urine sodium and urine creatinine exhibited the maximum full form [area under the receiver operating characteristic (AUROC): 0.66; 95%CI: 0.56, 0.77)], and the parameter of fractional excretion of potassium (FeK) exhibited an AUROC of 0.62 (95%CI: 0.51, 0.72). Furthermore, 2-hour excretion of potassium revealed a statistically significant correlation with 2-hour creatinine clearance (r = 0.62, P < 0.001). Logistic regression models, incorporating Sequential Organ Failure Assessment (SOFA) score, FeK, and urine sodium concentration as variables (P = 0.020, 0.044, and 0.033, respectively), achieved an AUROC of 0.751 in predicting AKI. Conclusion: Urine sodium levels and fractional potassium excretion moderately effectively predict AKI in sepsis patients. Urine potassium excretion correlates with glomerular filtration rate. [ABSTRACT FROM AUTHOR]

The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation (KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should be implemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent. [ABSTRACT FROM AUTHOR]

The study published in Clinical Chemistry & Laboratory Medicine discusses the impact of a gatekeeping intervention on the appropriateness of blood urea nitrogen (BUN) testing in a Belgian academic hospital. The intervention led to a significant reduction in both tests performed and ordered, resulting in substantial cost savings without compromising the quality of care. The study highlights the effectiveness of gatekeeping interventions in reducing inappropriate laboratory tests and changing clinicians' prescribing behavior, suggesting its potential application in other testing contexts. [Extracted from the article]

Optimised use of kidney function information might improve cardiac risk prediction in noncardiac surgery. In 35,815 patients from the VISION cohort study and 9219 patients from the POISE-2 trial who were ≥45 yr old and underwent nonurgent inpatient noncardiac surgery, we examined (by age and sex) the association between continuous nonlinear preoperative estimated glomerular filtration rate (eGFR) and the composite of myocardial injury after noncardiac surgery, nonfatal cardiac arrest, or death owing to a cardiac cause within 30 days after surgery. We estimated contributions of predictive information, C-statistic, and net benefit from eGFR and other common patient and surgical characteristics to large multivariable models. The primary composite occurred in 4725 (13.2%) patients in VISION and 1903 (20.6%) in POISE-2; in both studies cardiac events had a strong, graded association with lower preoperative eGFR that was attenuated by older age (P interaction <0.001 for VISION; P interaction =0.008 for POISE-2). For eGFR of 30 compared with 90 ml min−1 1.73 m−2, relative risk was 1.49 (95% confidence interval 1.26–1.78) at age 80 yr but 4.50 (2.84–7.13) at age 50 yr in female patients in VISION. This differed modestly (but not meaningfully) in men in VISION (P interaction =0.02) but not in POISE-2 (P interaction =0.79). eGFR contributed the most predictive information and mean net benefit of all predictors in both studies, most C-statistic in VISION, and third most C-statistic in POISE-2. Continuous preoperative eGFR is among the best cardiac risk predictors in noncardiac surgery of the large set examined. Along with its interaction with age, preoperative eGFR would improve risk calculators. ClinicalTrials.gov NCT00512109 (VISION) and NCT01082874 (POISE-2). [ABSTRACT FROM AUTHOR]

Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective, randomized, open-label, blinded endpoint study with a treatment period of 24 weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0 mg/dl and < 10.0 mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint was the change in log-transformed plasma B-type natriuretic peptide (BNP) levels from baseline to week 24 (or at discontinuation). The secondary efficacy endpoints were the changes in LV systolic or diastolic function evaluated by echocardiography, New York Heart Association (NYHA) class, hemoglobin, and estimated glomerular filtration rate from baseline to week 24, and the change in log-transformed plasma BNP levels or serum UA levels from baseline to weeks 4, 8, 12, 16 and 20 (BNP) or weeks 4, 8, 12, 16, 20 and 24 (serum UA). The primary safety endpoints were occurrence of all-cause death or major cardiovascular events. The mean age of participants was 70 years; 14% were female. The febuxostat group and the control group did not differ with respect to the primary efficacy endpoint (p = 0.13), although the decrease in log-transformed plasma BNP levels from baseline to each of weeks 4, 8, 12, 16 and 20 was greater in the febuxostat group. There were no significant differences between the two groups in the primary safety endpoints or the secondary efficacy endpoints except reduced serum UA levels in the febuxostat group. Febuxostat did not reduce plasma BNP levels at week 24 in patients with CHF, but it appeared safe with no increase in major cardiovascular events and all-cause or cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing has enabled non-invasive diagnosis of type IV collagen disease in clinical settings other than the typical presentation of Alport syndrome (AS). Methods: We reviewed the clinical and histological records of children diagnosed with Alport syndrome based on next-generation sequencing. Variants on clinical exome sequencing were categorized using ACMG 2015 criteria. Results: During 2015–2023, we found 43 patients (34 boys) with 39 variants in COL4A5 (n = 27), COL4A4 (n = 7), and COL4A3 (n = 5). Thirty, 8, and 5 patients had X-linked, autosomal recessive, and autosomal dominant disease, respectively. The median (IQR) age and eGFR at diagnosis were 10 (7–13) years and 100.1 (59–140) ml/min/1.73 m2, respectively. Fifteen patients were initially diagnosed with steroid-resistant nephrotic syndrome. Alport syndrome was suspected in these patients due to persistent microscopic hematuria, eGFR < 90 ml/min/1.73 m2, characteristic histology, and/or non-response to immunosuppression. Of 26 patients who underwent kidney biopsy, light microscopy revealed focal segmental glomerulosclerosis, minimal change disease, and mesangial proliferative glomerulonephritis in 9, 9, and 8 patients, respectively. Electron microscopy (n = 18) showed characteristic glomerular basement membrane changes and/or foot process effacement in 12 and 16 cases, respectively. Twenty-one patients (48.8%) had high-frequency sensorineural hearing loss, while two had lenticonus. Twelve patients progressed to chronic kidney disease stages 4–5. Median survival (IQR) with eGFR > 30 ml/min/1.73 m2 was 15.6 (13–18) years. Conclusions: The phenotype of Alport syndrome varies from asymptomatic urinary abnormalities to hematuria, proteinuria and/or low eGFR, and steroid-resistant nephrotic syndrome. Adverse outcomes are common, especially in boys with X-linked disease. [ABSTRACT FROM AUTHOR]

Background: Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking. Methods: A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed. Results: Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m2 (range 47–162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6–31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2–4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure. Conclusions: In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile. [ABSTRACT FROM AUTHOR]

Aim: To assess weight loss and cardiorenal outcomes by baseline body mass index (BMI) in VERTIS CV. Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. These post hoc analyses evaluated cardiometabolic and cardiorenal outcomes (a composite of death from CV causes or hospitalization for heart failure [HHF], CV death, HHF and an exploratory composite kidney outcome including ≥40% estimated glomerular filtration rate [eGFR] decrease) by baseline BMI, using conventional clinical categories and Cox proportional hazards models. Results: In total, 8246 adults were randomized (mean age 64.4 years, diabetes duration 13.0 years, BMI 32.0 kg/m2, 61% with BMI >30 kg/m2). Absolute body weight reduction was greater with ertugliflozin versus placebo at 3 and 5 years in the overall population (p < 0.001) and across BMI subgroups. Ertugliflozin increased the proportion of participants achieving ≥5% and ≥10% body weight reduction (ertugliflozin 34.9% and 13.6%, placebo 19.4% and 4.1%; odds ratio [95% confident interval, CI], 2.21 [1.76–2.77] and 3.65 [2.39–5.57], respectively) at 5 years. No significant difference was observed in the effect of ertugliflozin on HHF across BMI subgroups (Pinteraction = 0.61). Similarly, no significant difference was observed in the effect of ertugliflozin on the kidney composite outcome across BMI subgroups (Pinteraction = 0.39). Results were similar for other CV outcomes, and safety was consistent with the known ertugliflozin profile. Conclusion: Weight loss was observed across baseline BMI and was sustained over 5 years of follow‐up. The effects of ertugliflozin on HHF and kidney composite were consistent across baseline BMI. [ABSTRACT FROM AUTHOR]

Aims The diagnosis of transthyretin amyloidosis (ATTR) significantly impacts the management and prognosis of patients initially presenting with heart failure (HF). Despite recent advancements in treatment, prognosticating ATTR remains challenging. In this study, we aim to assess echocardiographic parameters associated with mid-term prognosis in patients with wild-type ATTR using a biomarker staging system as a reference point. Methods and results We studied 182 consecutive patients with wild-type ATTR (91% male and median age 82 years) who were referred to our centre between 2016 and 2022. Using N-terminal pro-B-type natriuretic peptide and estimated glomerular filtration rate cut-offs, we classified patients into the following three stages: Stage I (101 patients, 55.5%), Stage II (53 patients, 29.0%), and Stage III disease (28 patients, 15.5%). We then compared traditional echocardiographic indices and markers of subclinical ventricular dysfunction [left ventricular (LV) global longitudinal strain, right ventricular (RV) free wall strain, and left atrial (LA) strain] among groups. Over a fixed follow-up period of 18 months, which included treatment with tafamidis 61 mg daily, 48 patients (26.4%) experienced the composite outcome of death or HF hospitalization. When compared with Stage I ATTR, the hazard ratio (HR) for death or hospitalization was 1.55 [95% confidence interval (CI) 0.62–3.86] for Stage II ATTR and 4.53 (95% CI 1.66–12.4, P = 0.0116) for Stage III ATTR. Among echocardiographic parameters, reduced RV free wall strrain (FWS) was independently associated with all-cause mortality or HF hospitalization after adjustment for the staging system (HR 2.03, 95% CI 1.07–3.85, P < 0.05). Conclusion RV FWS should be routinely assessed for all patients with ATTR. It is an independent predictor of poor prognosis and provides additional value beyond biomarker staging systems. [ABSTRACT FROM AUTHOR]

BACKGROUND Wide pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to kidney failure. PP naturally widens with age, but it is unclear whether the risks associated with greater PP are the same across all ages. METHODS We used Cox proportional hazards models to investigate the association of PP with (i) atherosclerotic cardiovascular disease (ASCVD) events or death and (ii) a 50% reduction in estimated glomerular filtration rate or kidney failure in the chronic renal insufficiency cohort (CRIC). We evaluated the association of time-updated PP with these outcomes, accounting for time-updated confounders using inverse probability weighting. RESULTS Among 5,621 participants with CKD, every 10-mmHg greater PP was associated with a 6% higher risk of an ASCVD event or death (hazard ratio [HR] = 1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite kidney outcome (HR = 1.17, 95% CI 1.16, 1.18). Greater PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21–61 years), but a higher risk of the composite kidney outcome in the oldest age tertile (71–79 years). While wide PP in participants that experienced the primary outcomes was predominantly driven by elevated SBP, PP remained significantly associated with the composite kidney outcome across all ages and with ASCVD events or death in the first age tertile when SBP was added to the Cox regression model. CONCLUSIONS Our findings suggest that the mechanism by which PP is associated with adverse outcomes may differ by age. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the long-term impact of superselective renal artery embolization (SRAE) on renal function in cases of severe post-percutaneous nephrolithotomy (PCNL) haemorrhage, and to identify the factors associated with the long-term outcome of renal function. Methods: Patients treated with SRAE for post-PCNL hemorrhage between September 2016 and September 2021 were included. Patients' demographic and clinical data were recorded. Multiple linear regression and logistic regression were used to identify the factors related to the percentages of estimated glomerular filtration rate (eGFR) change and the risk factors of worsening renal function (WRF), respectively. Result: A total of 80 patients were included. There was no significant change in eGFR before and after SRAE immediately within 1.45 ± 1.66 days (66.37 ± 28.45 vs. 63.86 ± 29.26 mL/min/1.73 m², p = 0.202). Patient's eGFR increased significantly from 66.37 ± 28.45 to 70.94 ± 30.48 mL/min/1.73 m² (p = 0.044) with a mean follow-up of 30.4 months after SRAE, especially in patients with compromised renal function before SRAE (β = 0.297, p = 0.039). However, BMI > 24 kg/m2 was significantly associated with the decrease of eGFR (β = -0.343, p = 0.016). 12 (15.0%) patients developed WRF, logistic regression analysis showed that BMI > 24.0 kg/m2 (OR = 4.144, p = 0.045) and atrophic renal cortex (OR = 4.180, p = 0.040) were independent risk factors of WRF. Conclusion: SRAE is an effective treatment for post-PCNL severe haemorrhage, and is not deleterious to long term renal function. Notably, BMI > 24.0 kg/m2 and atrophic renal cortex were significant predictors of long-term WRF in SRAE patients. [ABSTRACT FROM AUTHOR]

Estimated glomerular filtration rate (eGFR) decline is associated with negative health outcomes, but the use of decision tree algorithms to predict eGFR decline is underreported. Among patients hospitalized during the first year of the COVID-19 pandemic, it remains unclear which individuals are at the greatest risk of eGFR decline after discharge. We conducted a retrospective cohort study on patients hospitalized at Stony Brook University Hospital in 2020 who were followed for 36 months post discharge. Random Forest (RF) identified the top ten features associated with fast eGFR decline. Logistic regression (LR) and Classification and Regression Trees (CART) were then employed to uncover the relative importance of these top features and identify the highest risk patients. In the cohort of 1,747 hospital survivors, 61.6% experienced fast eGFR decline, which was associated with younger age, higher baseline eGFR, and acute kidney injury (AKI). Multivariate LR analysis showed that older age was associated with lower odds of fast eGFR decline whereas length of hospitalization and vasopressor use with greater odds. CART analysis identified length of hospitalization as the most important factor and that patients with AKI and hospitalization of 27 days or more were at highest risk. After grouping by ICU and COVID-19 status and propensity score matching for demographics, these risk factors of fast eGFR decline remained consistent. CART analysis can help identify patient subgroups with the highest risk of post-discharge eGFR decline. Clinicians should consider the length of hospitalization in post-discharge monitoring of kidney function. [ABSTRACT FROM AUTHOR]

Objective and background: Hyperspectral imaging (HSI) is an innovative, noninvasive technique that assesses tissue and organ perfusion and oxygenation. This study aimed to evaluate HSI as a predictive tool for early postoperative graft function and long-term outcomes in living donor (LD) and deceased donor (DD) kidney transplantation (KT). Patients and methods: HSI of kidney allograft parenchyma from 19 LD and 51 DD kidneys was obtained intraoperatively 15 minutes after reperfusion. Using the dedicated HSI TIVITA Tissue System, indices of tissue oxygenation (StO2), perfusion (near-infrared [NIR]), organ hemoglobin (OHI), and tissue water (TWI) were calculated and then analyzed retrospectively. Results: LD kidneys had superior intraoperative HSI values of StO2 (0.78 ± 0.13 versus 0.63 ± 0.24; P = 0.001) and NIR (0.67 ± 0.10 versus 0.56 ± 0.27; P = 0.016) compared to DD kidneys. Delayed graft function (DGF) was observed in 18 cases (26%), in which intraoperative HSI showed significantly lower values of StO2 (0.78 ± 0.07 versus 0.35 ± 0.21; P < 0.001) and NIR (0.67 ± 0.11 versus 0.34 ± 0.32; P < 0.001). Receiver operating characteristic curve analysis demonstrated an excellent predictive value of HSI for the development of DGF, with an area under the curve of 0.967 for StO2 and 0.801 for NIR. Kidney grafts with low StO2 values (cut-off point 0.6) showed reduced renal function with a low glomerular filtration rate and elevated urea levels in the first two weeks after KT. Three years after KT, graft survival was also inferior in the group with initially low StO2 values. Conclusion: HSI is a useful tool for predicting DGF in living and deceased KT and may assist in estimating short-term allograft function. However, further studies with expanded cohorts are needed to evaluate the association between HSI and long-term graft outcomes. [ABSTRACT FROM AUTHOR]

Loss of kidney function is a substantial personal and public health burden. Kidney function is typically assessed as estimated glomerular filtration rate (eGFR) based on serum creatinine. UK Biobank provides serum creatinine measurements from study center assessments (SC, n = 425,147 baseline, n = 15,314 with follow-up) and emerging electronic Medical Records (eMR, "GP-clinical") present a promising resource to augment this data longitudinally. However, it is unclear whether eMR-based and SC-based creatinine values can be used jointly for research on eGFR decline. When comparing eMR-based with SC-based creatinine by calendar year (n = 70,231), we found a year-specific multiplicative bias for eMR-based creatinine that decreased over time (factor 0.84 for 2007, 0.97 for 2013). Deriving eGFR based on SC- and bias-corrected eMR-creatinine yielded 454,907 individuals with ≥ 1eGFR assessment (2,102,174 assessments). This included 206,063 individuals with ≥ 2 assessments over up to 60.2 years (median 6.00 assessments, median time = 8.7 years), where we also obtained eMR-based information on kidney disease or renal replacement therapy. We found an annual eGFR decline of 0.11 (95%-CI = 0.10–0.12) versus 1.04 mL/min/1.73m2/year (95%-CI = 1.03–1.05) without and with bias-correction, the latter being in line with literature. In summary, our bias-corrected eMR-based creatinine values enabled a 4-fold increased number of eGFR assessments in UK Biobank suitable for kidney function research. [ABSTRACT FROM AUTHOR]

Optimal fluid strategy for laparoscopic donor nephrectomy (LDN) remains unclear. LDN has been a domain for liberal fluid management to ensure graft perfusion, but this can result in adverse outcomes due to fluid overload. We compared postoperative outcome of living kidney donors according to the intraoperative fluid management. Five hundred and five LDNs performed over a six-year period at a tertiary hospital were analyzed. Donors were divided into tertiles according to intraoperative crystalloid infusion rate (ml/kg/hr), and associations between the tertile and outcomes were investigated with inverse probability of treatment weighting with entropy balancing. Primary outcome was maximal rise of serum creatinine (sCr). Secondary outcomes were sCr rise meeting Acute Kidney Injury (AKI) criteria, time to reach minimal sCr, and length of hospital stay. The following covariates were used: age, sex, body weight, height, diabetes mellitus, hypertension, preoperative estimated glomerular filtration rate, operation duration, surgeon, nephrectomy side, and estimated blood loss. Median intraoperative crystalloid infusion rate was 3.5, 4.6, and 6.0 ml/kg/hr in the first, second, and third tertile, respectively (group 1, 2, and 3). Maximal rise of sCr did not differ between groups (P = 0.274). Twofold increase in sCr (equivalent to stage 2 AKI) during the first week and prolonged hospitalization were most frequent in group 1 [7.8 vs. 1.1 vs. 1.5%, P = 0.004; 7.9 vs. 3.1 vs. 0.7%, P = 0.003]. Time to reach minimal sCr was longest in group 1. No differences were found in recipient early renal function. Hypovolemia is associated with poor postoperative outcomes after LDN. Efforts to find the optimal fluid management should be continued. [ABSTRACT FROM AUTHOR]

Background: To explore the prevalence of hyperuricemia and its associated factors in uremic patients undergoing maintenance hemodialysis (MHD). Methods: Two hundred two uremic patients undergoing MHD for ≥ 3 months, in Jinshan Hospital, Fudan University, were enrolled. Pre-dialysis blood samples were tested during March 1st, 2023 to April 30th, 2023. Demographic characteristics were recorded. The prevalence of hyperuricemia, defined as serum uric acid (SUA) ≥ 420 μmol/L, was investigated. Individuals were divided into hyperuricemia (HUA) and non-hyperuricemia (n-HUA) groups. The demographic characteristics, residual kidney function, nutritional status, acid–base metabolism, electrolyte and lipid metabolism were compared between groups. The associated factors for hyperuricemia in MHD patients were identified by logistic regression. Results: The median SUA level of the enrolled patients was 458.50 (392.25, 510.75) μmol/L. 134 (66.34%) candidates met the diagnostic criteria of hyperuricemia. The median SUA level in HUA group was 491.00 (459.50, 543.50) μmol/L. Compared to those in n-HUA group, subjects in HUA group showed lower estimated glomerular filtration rate and blood CO2 level, but higher levels of body mass index, geriatric nutritional risk index, plasma phosphate, potassium, pre-albumin, albumin, serum creatinine (Scr) and urea nitrogen. Logistic regression indicated that Scr (OR 1.002, 95% CI 1.001–1.004, P = 0.003), albumin (OR 1.165, 95%CI 1.011–1.342, P = 0.035), and blood potassium (OR 1.673, 95% CI 1.009–2.773, P = 0.046) were associated factors for hyperuricemia in uremic patients undergoing MHD. Conclusion: Hyperuricemia was highly prevalent among uremic MHD patients. Elevated levels of Scr, albumin and plasma potassium were independent associated factors for hyperuricemia. [ABSTRACT FROM AUTHOR]

Background: Creatinine-based estimated glomerular filtration rate (eGFR) equations are widely used in clinical practice but exhibit inherent limitations. On the other side, measuring GFR is time consuming and not available in routine clinical practice. We developed and validated machine learning models to assess the trustworthiness (i.e. the ability of equations to estimate measured GFR (mGFR) within 10%, 20% or 30%) of the European Kidney Function Consortium (EKFC) equation at the individual level. Methods: This observational study used data from European and US cohorts, comprising 22,343 participants of all ages with available mGFR results. Four machine learning and two traditional logistic regression models were trained on a cohort of 9,202 participants to predict the likelihood of the EKFC creatinine-derived eGFR falling within 30% (p30), 20% (p20) or 10% (p10) of the mGFR value. The algorithms were internally and then externally validated on cohorts of respectively 3,034 and 10,107 participants. The predictors included in the models were creatinine, age, sex, height, weight, and EKFC. Results: The random forest model was the most robust model. In the external validation cohort, the model achieved an area under the curve of 0.675 (95%CI 0.660;0.690) and an accuracy of 0.716 (95%CI 0.707;0.725) for the P30 criterion. Sensitivity was 0.756 (95%CI 0.747;0.765) and specificity was 0.485 (95%CI 0.460; 0.511) at the 80% probability level that EKFC falls within 30% of mGFR. At the population level, the PPV of this machine learning model was 89.5%, higher than the EKFC P30 of 85.2%. A free web-application was developed to allow the physician to assess the trustworthiness of EKFC at the individual level. Conclusions: A strategy using machine learning model marginally improves the trustworthiness of GFR estimation at the population level. An additional value of this approach lies in its ability to provide assessments at the individual level. [ABSTRACT FROM AUTHOR]

Background: Limited studies have explored the relationship between estimated Glomerular Filtration Rate(eGFR) and in-hospital mortality(IHM) in low-income sub-Saharan African countries. This study aimed to explores this association, offering insights into its impact in resource-limited settings. Methods and results: We retrospectively included 226 patients(age 45.35 ± 18.85yrs, 54.4% women) admitted to Naguru-referral hospital between January 1st and June 30th, 2024. Baseline demographics and clinical variables, including eGFR, were recorded at admission. Patients were followed from date of admission to discharge and primary outcome was IHM. Multivariable Hazard regression analysis assessed the association between eGFR and IHM, respectively. During follow-up, 45(19.9%) of patients died. Per-standard deviation(SD) increase in eGFR(48.60 mL/min/1.73m2) was associated with Hazard Ratio(HR) of 0.46[95%CI: 0.282–0.759, p = 0.002, β = -0.77] for IHM in fully adjusted models. When stratified by eGFR quartiles, using highest quartile(≥ 120 mL/min/1.73m2) as reference, HR was 1.08[95%CI: 0.276–4.226, p = 0.912, β = + 0.08] for 99.0–120 mL/min/1.73m2; 4.08[95%CI: 1.284–12.954, p = 0.017, β = + 1.41] for 66.8–99.0 mL/min/1.73m2, and 4.08[95%CI: 1.284–12.954, p = 0.037, β = + 1.25] for < 66.8 mL/min/1.73m2. Among age stratification-subgroups: age < 40yrs: 0.93[95%CI: 0.89–0.97, p < 0.001, β = -0.07]; 40-60yrs: 0.98[95%CI: 0.966–0.999, p = 0.039, β = -0.02]; ≥ 60yrs, p < 0.005 with p-value-interaction for age = 0.046; and HIV-positive: 0.94[95%CI: 0.905–0.974, p < 0.001, β = -0.06] with p-value-interaction = 0.021. Significant Pearsons-correlation(r) was observed only in: [< 40yrs, HIV(-)] with p = 0.016, r = -0.275; [40-60yrs, HIV(+)] with p = 0.020, r = -0.397; and [≥ 60yrs,HIV(+)] with p = 0.003, r = -0.997. Conclusions: We report that eGFR was associated with in-hospital mortality, with a stronger association observed in HIV-negative patients(< 40yrs) and HIV-positive patients (aged ≥ 60yrs yrs). Further research is warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: The C-reactive protein/Lymphocyte Ratio (CLR) is a novel biomarker whose role in the development of chronic kidney disease (CKD) is not well understood. This study aimed to investigate the correlation between CLR and the prevalence of CKD. Methods: This cross-sectional study included participants from the US National Health and Nutrition Examination Survey conducted between 1999 and 2010. Multivariate regression analyses and subgroup analyses were performed, controlling for socio-demographic variables, lifestyle behaviors, chronic diseases associated with kidney disease, and biochemical markers of bone metabolism. The associations between CLR and CKD prevalence, as well as indicators of renal damage, were explored. Non-linear relationships were analyzed using weighted restricted cubic splines. The predictive ability of CLR for CKD was assessed by the receiver operating characteristic curve and the area under the curve was calculated. Subgroup and sensitivity analyses were conducted to validate the robustness of the model. Results: A total of 13,862 respondents were included, comprising 2,449 CKD patients and 11,413 non-CKD patients. Weighted logistic regression modeling revealed a positive correlation between CLR levels and CKD prevalence (Odds ratio [OR] = 1.54, 95% Confidence interval [CI] = 1.30 to 1.83, P < 0.001). Additionally, CLR levels were negatively correlated with the glomerular filtration rate, a marker of renal injury, and positively correlated with the urinary albumin/creatinine ratio. The receiver operating characteristic curve demonstrated that the area under the curve for CLR in predicting CKD was 0.653 (95% CI, 0.641–0.665). The optimal cutoff value was 0.856, with a sensitivity of 0.703, specificity of 0.526, positive predictive value of 0.874, and negative predictive value of 0.275. The robustness of the model was confirmed through subgroup and sensitivity analyses. Conclusion: Analysis of a large cross-sectional dataset demonstrated a positive correlation between CLR levels and CKD prevalence, suggesting that CLR may serve as a novel marker for the development and treatment of CKD. [ABSTRACT FROM AUTHOR]

Drug-induced hyponatremia is an adverse reaction with accelerated electrolyte disturbance. This study reported a rare case of delayed hyponatremia in a 68year-old female with recurrent upper tract urothelial carcinoma after Gemcitabine plus Cisplatin (GC) and Tislelizumab treatment. She had left ureter surgery, recurrence a year later with mildly abnormal kidney function (glomerular filtration rate (GFR) was 54.9 ml/min). After the first cycle of GC plus Tislelizumab, severe hyponatremia leading to life-threatening conditions occurred eight days later. Hypothesizing Cisplatin as the cause, its usage was modified in the second cycle (40mg/day for three days). No severe hyponatremia followed. CT showed partial remission. From the third cycle, due to grade IV bone marrow suppression, she had Tislelizumab alone. Now, she is on 21-day Tislelizumab maintenance with a stable tumor status. Low-dose continuous Cisplatin may suit patients with borderline or mildly abnormal renal function (GFR: 40-60mL/min) better than single full-dose use. Tislelizumab alone for maintenance may be an option for those intolerant of chemotherapy. But Na+ decrease may be related to Tirelizumab or Gemcitabine, needing more clinical observation and experiments. [ABSTRACT FROM AUTHOR]