Predictors of Incident ESRD among Patients with Primary Hyperoxaluria Presenting Prior to Kidney Failure

Abstract

Background and objectives: Overproduction of oxalate in patients with primary hyperoxaluria (PH) leads to calcium oxalate deposition in the kidney and ESRD in a substantial number of cases. However, the key determinants for renal outcome remain unclear. Thus, we performed a retrospective analysis to identify predictors for renal outcome among patients with PH participating in the Rare Kidney Stone Consortium (RKSC) PH Registry.

Design, setting, participants, & measurements: We characterized clinical and laboratory features of patients enrolled in the RKSC PH Registry. We assessed correlation between urinary measures and eGFR at diagnosis by Spearman rank correlation and estimated renal survival using the Kaplan-Meier method. We determined factors associated with renal survival by Cox proportional hazard models.

Results: Of 409 patients enrolled in the RKSC Registry as of March 2014, we excluded 112 patients who had ESRD at PH diagnosis from analysis. Among the remaining 297 patients, 65% had PH type 1, 12% had type 2, 13% had type 3, and 11% had unclassified PH. Median (25th, 75th percentile) age at PH diagnosis was 8.1 (4.0, 18.2) years with an eGFR of 73.0 (56.4, 97.5) ml/min per 1.73 m(2) and urinary oxalate excretion rate of 1.64 (1.11, 2.44) mmol/1.73 m(2) per 24 hours. During a median follow-up of 3.9 (1.0, 12.8) years, 59 (20%) patients developed ESRD. Urinary oxalate excretion at diagnosis stratified by quartile was strongly associated with incident ESRD (hazard ratio [HR], 3.4; 95% confidence interval [95% CI], 1.4 to 7.9). During follow-up there was a significant association between urinary oxalate quartile (Q) and incident ESRD (Q4 versus Q1: HR, 3.3; 95% CI, 1.2 to 9.3). This association remained even when adjusted for sex, age, and baseline eGFR (HR, 4.2; 95% CI, 1.6 to 10.8).

Conclusions: Among patients with PH, higher urinary oxalate excretion is predictive of poor renal outcome.

Keywords: calcium oxalate; follow-up studies; genetic renal disease; humans; hyperoxaluria, primary; kidney failure, chronic; kidney stones; mineral metabolism; oxalates; registries.

Figure 1.

Urinary oxalate (U_[ox]) excretion by primary hyperoxaluria (PH) type in patients without ESRD at diagnosis. Urinary oxalate was greatest in primary hyperoxaluria type 1 (PH1) and lowest in primary hyperoxaluria type 3 (PH3) (P<0.001 for trend). Boxes represent the interquartile range (25th, 75th percentiles) while the line inside each box indicates the median value; upper bars indicate the maximum values while the lower bars indicate the minimum values. Diamond symbols indicate the mean values; circles indicate outliners. PH2, primary hyperoxaluria type 2.

Figure 2.

Kaplan–Meier plots of renal survival. (A) Among all patients with primary hyperoxaluria (PH) who did not have ESRD at diagnosis, renal survival estimates at 10, 20, and 30 years after diagnosis were 84%, 61%, and 43%, respectively. (B) Among patients with PH who did not have ESRD at diagnosis, renal survival estimates at 10, 20, and 30 years after diagnosis were lowest for primary hyperoxaluria type 1 (PH1) (hazard ratio [HR], 13.2 for PH1 versus others; 95% confidence interval [95% CI], 3.2 to 54.4). (C) Renal survival was examined by quartile of urine oxalate (U_[ox]) excretion (mmol/1.73 m²/24 hours) at diagnosis. Among patients with PH who did not have ESRD at diagnosis, renal survival estimates at 10, 20, and 30 years were lowest for those with a U_[ox] excretion ≥2.4 mmol/1.73 m² per 24 hours (HR, 3.4 for quartile Q4 versus quartiles Q1–Q3; 95% CI, 1.4 to 7.9). PH2, primary hyperoxaluria type 2; PH3, primary hyperoxaluria type 3.

Figure 3.

ESRD rate by urinary oxalate (U_[ox]) quartile during follow-up (f/u). ESRD rates were similar for the lower three quartiles (Q) but increased for a urinary oxalate level >1.87 mmol/1.73 m² per 24 hours (hazard ratio, 3.30; 95% confidence interval, 1.17 to 9.33; P=0.02).