Tubular secretion of creatinine in autosomal dominant polycystic kidney disease: consequences for cross-sectional and longitudinal performance of kidney function estimating equations

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal tubular cell proliferation and dedifferentiation, which may influence tubular secretion of creatinine (CCr[TS]).

Study design: Diagnostic test study.

Setting & participants: We therefore investigated CCr(TS) in patients with ADPKD and controls and studied consequences for the performance of glomerular filtration rate (GFR) estimating equations.

Index & reference tests: In patients with ADPKD and healthy controls, we measured GFR as (125)I-iothalamate clearance while simultaneously determining creatinine clearance.

Other measurements: 24-hour urinary albumin excretion.

Results: In 121 patients with ADPKD (56% men; mean age, 40 ± 11 [SD] years) and 215 controls (48% men; mean age, 53 ± 10 years), measured GFR (mGFR) was 78 ± 30 and 98 ± 17 mL/min/1.73 m(2), respectively, and CCr(TS) was 15.9 ± 10.8 and 10.9 ± 10.6 mL/min/1.73 m(2), respectively (P < 0.001). The higher CCr(TS) in patients with ADPKD remained significant after adjustment for covariates and appeared to be dependent on mGFR. Correlation and accuracy between mGFR and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated GFR (eGFR) were 0.95 and 99%, respectively; between mGFR and MDRD (Modification of Diet in Renal Disease) Study eGFR, they were 0.93 and 97%, respectively. Values for bias, precision, and accuracy were similar or slightly better than in controls. In addition, change in mGFR during 3 years of follow-up in 45 patients with ADPKD correlated well with change in eGFR.

Limitations: Cross-sectional, single center.

Conclusions: CCr(TS) in patients with ADPKD is higher than that in controls, but this effect is limited and observed at only high-normal mGFR. Consequently, the CKD-EPI and MDRD Study equations perform relatively well in estimating GFR and change in GFR in patients with ADPKD.

Keywords: Autosomal dominant polycystic kidney disease (ADPKD); creatinine; estimated glomerular filtration rate (eGFR); measured GFR; tubular secretion of creatinine.