The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

Abstract

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.

Keywords: ADPKD; end-stage renal disease; genetic renal disease; progression of renal failure; risk factors.

Figure 1.

Age at hypertension onset, age at first urologic complication and the causative mutation all influence renal survival. (A) Significant difference in renal survival between patients treated for hypertension before 35 years of age (dotted curve, n=357) and patients who did not receive treatment for hypertension before 35 years of age (black curve, n=788). (B) Significant difference in renal survival between patients presenting with their first urologic event (gross hematuria, flank pain, or cyst infection) before 35 years of age (n=294, dotted curve) and patients without any urologic events before that age (n=824, black curve). (C) Significant differences in renal survival between the PKD2 mutation carriers (genetic group 1, n=248, black dotted curve), PKD1 nontruncating mutation carriers (genetic group 2, n=322, black curve), women with truncating PKD1 mutations (genetic group 3, n=380, gray curve), and men with truncating PKD1 mutations (genetic group 4, n=321, gray dotted curve).

Figure 2.

The PROPKD score enables stratification of risk of progression to ESRD in patients with ADPKD. (A) Renal survival based on PROPKD, with scores ranging from 0 to 9 points. (B) Significant differences in renal survival in patients from the three prognostic categories, as follows: low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of early progression to ESRD.

Figure 3.

Annual loss of kidney function is statistically different in the three prognostic groups defined by the PROPKD score. Median rates of eGFR decline (ml/min per 1.73 m² per year) are presented with their 10% confidence interval (whiskers) in patients at inclusion who had at least two eGFR values (minimum, 2 eGFR values; maximum, 13 eGFR values) of 15–90 separated by at least 1 year. Significant differences are apparent between the low-risk group (n=180; median eGFR decline, 2 [IQR, 0.6–3.4] ml/min per 1.73 m² per year), the intermediate-risk group (n=202; median eGFR decline, 3.4 [IQR, 1.9–4.8] ml/min per 1.73 m² per year), and the high-risk group (n=78; median eGFR decline, 4.4 [IQR, 2.1–6.6] ml/min per 1.73 m² per year).

Figure 4.

The genetic scoring offers a good prediction of ESRD but is less accurate than the PROPKD score. A significant difference was seen between the AUC of the genetic scoring (mean AUC [±SEM], 0.79±0.02; dotted line) and of the PROPKD score (AUC, 0.84±0.02; black line) at 65 years of age (P<0.001).

Figure 5.

Decision-support algorithm to assist in the selection of a prognostic model to predict renal outcomes in patients with ADPKD. For patients younger than 35 years of age who have already experienced urologic events, including gross hematuria, flank pain, or cyst infections, and are already receiving treatment for hypertension and for patients older than 35 years of age with clinical data available, the PROPKD score is applicable. For patients with ADPKD under 35 years of age and/or for whom clinical data are lacking, the genetic score, although less accurate, can be used to predict renal survival.