GFR Estimation in Potential Living Kidney Donors: Race- and Nonrace-based Equations and Measured GFR.

Rationale & Objective: Recent studies evaluated and proposed new race-neutral, creatinine-based glomerular filtration rate (GFR) estimation equations. The performance of these equations in diverse potential living kidney donors requires study. Study Design: Cross-sectional study. Setting & Participants: 637 potential living kidney donors from one tertiary hospital with serum creatinine concentration measurement and GFR measurement by iohexol plasma clearance between October 2016 and December 2020. Exposure: Creatinine-based estimation of GFR by Chronic Kidney Disease Epidemiology Collaboration (2009, CKDEPI09; 2021, CKDEPI21) and Modification of Diet in Renal Disease equations with and without inclusion of race coefficient, where applicable. Outcomes: Equation bias, precision, accuracy, and accurate classification of GFR as equal to and above or below 80 mL/min/1.73 m2. Analytical Approach: GFR estimation equation performance compared to measured GFR (mGFR) by iohexol clearance. Results: The median bias of the CKDEPI21 equation underestimated mGFR by 2.8 mL/min/1.73 m2. The bias in the Black subgroup underestimated mGFR by 9.0 mL/min/1.73 m2. Compared to CKDEPI09 with and without race adjustment, the accuracy of CKDEPI21 increased across all subgroups. On average, 3.9% of individuals were misclassified by CKDEPI21 as having a GFR greater than, and 8.9% misclassified less than, 80 mL/min/1.73 m2, compared to 3.1% and 13.2% for CKDEPI09 with race adjustment, respectively. Total misclassification (either above or below 80 mL/min/1.73 m2) was 16.3% for CKDEPI21 and 16.0% for CKDEPI09 (with race adjustment). Limitations: Limited sample of individuals identifying as Black. Lack of cystatin C data. Conclusions: In our potential living donor sample, GFR estimation by creatinine-based CKDEPI21 is less biased and more accurate than previous creatinine-based estimated GFR equations. When evaluated by race, this summative improvement remains in individuals identifying as Asian, Hispanic, or White. More external validation is needed to assess whether the new equation is an improvement over the previous CKDEPI equation with a race coefficient.

New insights into muscle function in chronic kidney disease and metabolic acidosis.

PURPOSE OF REVIEW: : Sarcopenia, defined as decreased muscle mass or function, is prevalent in chronic kidney disease (CKD) increasing the risk of mobility impairment and frailty. CKD leads to metabolic acidosis (MA) and retention of uremic toxins contributing to insulin resistance and impaired muscle mitochondrial energetics. Here we focus on the central role of muscle mitochondrial metabolism in muscle function. RECENT FINDINGS: : Mitochondrial dysfunction underlies muscle wasting and poor physical endurance in CKD. Uremic toxins accumulate in muscle disrupting mitochondrial respiration and enzymes. Changes in mitochondrial quantity, quality, and oxidative capacity contribute to mobility impairment in CKD. Major determinants of muscle mitochondrial function are kidney function, inflammation, and oxidative stress. In CKD, MA is the major determinant of muscle mitochondrial function. Metabolomics reveals defects in pathways linked to mitochondrial energy metabolism and acid-base homeostasis underlying insulin resistance in CKD. SUMMARY: : Decreased mitochondrial capacity and quality control can impair muscle function contributing to decreased physical endurance. MA augments insulin resistance perpetuating the catabolic state underlying muscle wasting in CKD. Further studies are needed to investigate if targeting of MA improves muscle mitochondrial function and insulin resistance translating into meaningful improvements in physical endurance.