Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD Progression

Abstract

Background and objectives: Predicting disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) poses a challenge, especially in early-stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasma urea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression.

Design: The urine-to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolonged water deprivation test. Thereafter, association with kidney outcome was evaluated in 583 patients with ADPKD with a broad range of kidney function. Multivariable mixed-model regression was used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cutoff of -3.0 ml/min per 1.73 m² per year. The urine-to-plasma urea ratio was compared with established predictors, namely, sex, age, baseline eGFR, Mayo Clinic height-adjusted total kidney volume class, and PKD gene mutation.

Results: The maximal urine-concentrating capacity and urine-to-plasma urea ratio correlated strongly (R=0.90; P<0.001). Next, the urine-to-plasma urea ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 (interquartile range, 2.6-5.0) years, both crude and after correction for established predictors (β=0.58; P=0.02). The odds ratio of rapidly progressive disease was 1.35 (95% confidence interval, 1.19 to 1.52; P<0.001) for every 10 units decrease in urine-to-plasma urea ratio, with adjustment for predictors. A combined risk score of the urine-to-plasma urea ratio, Mayo Clinic height-adjusted total kidney volume class, and PKD mutation predicted rapidly progressive disease better than each of the predictors separately.

Conclusions: The urine-to-plasma urea ratio, which is calculated from routine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_01_27_CJN10470620_final.mp3.

Keywords: ADPKD; autosomal dominant polycystic kidney disease; renal function decline; urea; urine-to-plasma urea ratio.