JU INSIGHT: Cystatin C Is Sensitive in Kidney Dysfunction Detection in Nonweight-bearing Patients

By: Glenn T. Werneburg, MD, PhD; Daniel Hettel, MD; Stacy Jeong, MD; Gregory Nemunaitis, MD; Jonathan J. Taliercio, DO; Hadley M. Wood, MD | Posted on: 16 Feb 2023

Werneburg GT, Hettel D, Jeong S, Nemunaitis G, Taliercio JJ, Wood HM. Estimated glomerular filtration rate using cystatin C is a more sensitive marker for kidney dysfunction in nonweight-bearing individuals. J Urol. 2023;209(2):391-398.

Study Need and Importance

Serum creatinine is the most used endogenous biomarker for calculating renal function. Creatinine has been primarily validated in the ambulatory (weight-bearing) population. Creatinine levels are altered by muscle mass, and whether creatinine accurately estimates renal function in those with low muscle mass, such as the nonweight-bearing (NWB) population, is unclear. Those who are NWB also are commonly afflicted with neurogenic lower urinary tract dysfunction. These individuals may be at risk of upper tract deterioration, and often require renal function surveillance. We sought to compare renal function by estimated glomerular filtration rate (eGFR) calculated using creatinine vs cystatin C, which is a muscle-independent renal function biomarker.

What We Found

eGFR was significantly lower when calculated using cystatin C relative to creatinine, and the differences were greater in the NWB population than in a matched ambulatory control group. Fifty-eight percent of the NWB group with evidence of renal dysfunction on imaging or urinalysis was reclassified into a lower eGFR category (corresponding to higher chronic kidney disease stage) when using cystatin C relative to creatinine (see Figure).

Figure. Creatinine vs cystatin C equation performance for nonweight-bearing patients (top) and matched controls (bottom) with radiographic or urinalysis evidence of kidney dysfunction. Pie charts indicate proportions of patients in whom estimated glomerular filtration rate (eGFR) stage changed or remained the same based on comparison of indicated equations used for calculation, as indicated on the left of the Figure. “Upstaged” (teal) refers to patients who were reclassified into a category of lower eGFR (poorer estimated renal function), “Downstaged” (red) refers to patients who were reclassified into a category of higher eGFR (improved estimated renal function), and “Same” (blue) refers to individuals in whom the classification did not change. eGFR stages reflected those of chronic kidney disease stages: >90 mL/min/1.73 m², 60-89 mL/min/1.73 m², 30-59 mL/ min/1.73 m², 15-29 mL/min/1.73 m², <15 mL/min/1.73 m².

Limitations

Limitations of the current study are its retrospective nature and the lack of comparison to inulin clearance or other gold standard glomerular filtration rate measure. The use of International Classification of Diseases codes as a proxy for NWB status is also a limitation, as some codes are heterogenous and may be associated with variable weight-bearing status. Other low muscle mass populations, such as those with cachexia or amputations, were not included in this study, and the generalizability to these populations warrants future investigation.

Interpretation for Patient Care

Cystatin C was more sensitive for the detection of kidney dysfunction in NWB individuals. Identifying kidney dysfunction in such individuals earlier may lead to more rapid nephrological referral, expedite urological interventions to avoid further kidney damage, avoid nephrotoxic studies (eg, iodinated contrast) and medications (eg, antibiotics), and help with pharmaceutical dosing.