Lieske, John C

Key Points Studies on GFR assessment in people with cancer are needed. In this study, the creatinine–cystatin C equations performed better than other equations, and this was observed in solid and hematological cancers. Our findings give support to the preferential use of creatinine and cystatin C–based equations in people with cancer. Background GFR assessment is important in clinical practice with implications for diagnosis, prognostication, and drug dosing. People with cancer are at risk of imprecision in GFR estimation. This cross-sectional study evaluated the performance of various creatinine and cystatin C–based equations in comparison with measured GFR (mGFR) in people with cancer. Methods We retrieved data for all adult patients who had mGFR by urinary iothalamate clearance between 2011 and 2023 at Mayo Clinic and use of an electronic health record diagnosis code for cancer within 2 years before mGFR. The CKD Epidemiology Collaboration (CKD-EPI), European Kidney Function Consortium, and Cockcroft–Gault equations were computed, along with performance metrics (bias, precision, and root mean square error [RMSE]. Confidence intervals were generated by bootstrapping, and analysis were stratified by solid and hematological cancers. Results From all adults with cancer and mGFR, 1145 had both creatinine and cystatin C available within 7 days of mGFR. Among all equations, the creatinine–cystatin C CKD-EPI equation provided the best performance, with small bias (median, 3.0; 95% confidence interval, 2.3 to 3.8) and higher precision (RMSE, 14.5) compared with creatinine-only or cystatin C–only equations (RMSE varying from 16.6 to 20), and this was also true in solid and hematological cancers. The creatinine–cystatin European Kidney Function Consortium equation had a similar performance to CKD-EPI, Cockcroft–Gault showed worst precision (30% of people with errors above 30%), and cystatin C CKD-EPI equation was the most biased, prone to underestimation of mGFR. Conclusions In our cohort of patients with mGFR and cancer, the CKD-EPI creatinine–cystatin C equation performed best for GFR assessment, and this was true for both solid and hematological cancers. Our findings give support for the preferential use of creatinine and cystatin C–based equations instead of creatinine-only or cystatin C–only equations in people with cancer. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2025_03_25_CJASNMar20.3.3252025.mp3

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Key Points Common kidney stones are unlikely to be an independent and direct cause of CKD in the general population. CKD may protect against kidney stones because of changes in key urinary factors critical for stone formation. Background Kidney stones and CKD are common disorders with a substantial interaction. Although observational studies have suggested a potential for enhanced CKD risk after prior kidney stones, the exact relationship remains ambiguous. Methods Shared comorbidities between two diseases were identified using unbiased screening. Genome-wide association study summary statistics were obtained from the UK Biobank (UKBB), FinnGen, and CKDGen, followed by genetic association analyses across various traits. Bidirectional Mendelian randomization (MR) analyses were performed to define causal links, complemented by multivariable MR that included the shared comorbidities including hypertension, diabetes, and obesity. Observational analyses were undertaken using cohorts from the Mayo Clinic and a UKBB subset. Results Despite identifying a total of 123 conditions as shared comorbidities, there was no significant genetic correlation between kidney stones and CKD. Unadjusted MR analysis revealed no significant association between kidney stones and CKD risk (UKBB [exposure]/FinnGen [outcome]: odds ratio [OR]=0.97, 95% confidence interval [CI], 0.88 to 1.06; FinnGen/UKBB: OR=1.17, 95% CI, 0.98 to 1.39). Kidney stones did significantly associate with a higher urinary albumin-creatinine ratio ( β =0.014, 95% CI, 0.002 to –0.025), but this association disappeared in the multivariable MR model ( β =0.009, 95% CI, −0.003 to 0.020). Furthermore, in a cross-sectional analysis limited to the UKBB cohort, a robust regression model did not detect an independent association between kidney stones and urinary albumin-creatinine ratio ( β =0.16, 95% CI, −0.04 to 0.35) or eGFR ( β =0.10, 95% CI, −0.07 to 0.28). Conversely, CKD associated with a diminished risk of kidney stones in multivariable MR models (UKBB/FinnGen: OR=0.77, 95% CI, 0.69 to 0.87; FinnGen/UKBB: OR=0.73, 95% CI, 0.66 to 0.81). Furthermore, in the Mayo Clinic cohort with available urinary biochemistries, lower eGFR was associated with lower urinary calcium excretion and urinary calcium oxalate/phosphate supersaturation. Conclusions In this study, kidney stones were not independently associated with CKD. Conversely, CKD was associated with a lower risk of calcium kidney stones likely via changes in key urinary traits, including lower calcium excretion.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration–approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.

An accurate estimate of glomerular filtration rate (eGFR) is essential for proper clinical management, especially in patients with kidney dysfunction. This prospective observational study evaluated the real-world performance of the nuclear magnetic resonance (NMR)-based GFRNMR equation, which combines creatinine, cystatin C, valine, and myo-inositol with age and sex. We compared GFRNMR performance to that of the 2021 CKD-EPI creatinine and creatinine-cystatin C equations (CKD-EPI2021Cr and CKD-EPI2021CrCys), using 115 fresh routine samples of patients scheduled for urinary iothalamate clearance measurement (mGFR). Median bias to mGFR of the three eGFR equations was comparably low, ranging from 0.4 to 2.0 mL/min/1.73 m2. GFRNMR outperformed the 2021 CKD-EPI equations in terms of precision (interquartile range to mGFR of 10.5 vs. 17.9 mL/min/1.73 m2 for GFRNMR vs. CKD-EPI2021CrCys; p = 0.01) and accuracy (P15, P20, and P30 of 66.1% vs. 48.7% [p = 0.007], 80.0% vs. 60.0% [p < 0.001] and 95.7% vs. 86.1% [p = 0.006], respectively, for GFRNMR vs. CKD-EPI2021CrCys). Clinical parameters such as etiology, comorbidities, or medications did not significantly alter the performance of the three eGFR equations. Altogether, this study confirmed the utility of GFRNMR for accurate GFR estimation, and its potential value in routine clinical practice for improved medical care.

Significance Statement Antibiotics modify human microbiomes and may contribute to kidney stone risk. In a population-based case-control study using 1247 chart-validated first-time symptomatic kidney stone formers and 4024 age- and sex-matched controls, the risk of kidney stones was transiently higher during the first year after antibiotic use. However, this risk was no longer evident after adjustment for comorbidities and excluding participants with prior urinary symptoms. Findings were consistent across antibiotic classes and the number of antibiotic courses received. This suggests that antibiotics are not important risk factors of kidney stones. Rather, kidney stones when they initially cause urinary symptoms are under-recognized, resulting in antibiotic use before a formal diagnosis of kidney stones ( i.e. , reverse causality). Background Antibiotics modify gastrointestinal and urinary microbiomes, which may contribute to kidney stone formation. This study examined whether an increased risk of a first-time symptomatic kidney stone episode follows antibiotic use. Methods A population-based case-control study surveyed 1247 chart-validated first-time symptomatic kidney stone formers with a documented obstructing or passed stone (cases) in Olmsted County, Minnesota, from 2008 to 2013 and 4024 age- and sex-matched controls. All prescriptions for outpatient oral antibiotic use within 5 years before the onset of symptomatic stone for the cases and their matched controls were identified. Conditional logistic regression estimated the odds ratio (OR) of a first-time symptomatic kidney stone across time after antibiotic use. Analyses were also performed after excluding cases and controls with prior urinary tract infection or hematuria because urinary symptoms resulting in antibiotic prescription could have been warranted because of undiagnosed kidney stones. Results The risk of a symptomatic kidney stone was only increased during the 1-year period after antibiotic use (unadjusted OR, 1.31; P = 0.001), and this risk was attenuated after adjustment for comorbidities (OR, 1.16; P = 0.08). After excluding cases and controls with prior urinary symptoms, there was no increased risk of a symptomatic kidney stone during the 1-year period after antibiotic use (unadjusted OR, 1.04; P = 0.70). Findings were consistent across antibiotic classes and the number of antibiotic courses received. Conclusions The increased risk of a first-time symptomatic kidney stone with antibiotic use seems largely due to both comorbidities and prescription of antibiotics for urinary symptoms. Under-recognition of kidney stones that initially cause urinary symptoms resulting in antibiotic use may explain much of the perceived stone risk with antibiotics ( i.e. , reverse causality).