Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease

Abstract

Background and objectives: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by increased total kidney volume (TKV) and renal failure. This study aimed to determine if height-adjusted TKV (htTKV) predicts the onset of renal insufficiency.

Design, setting, participants, & measurements: This prospective, observational, longitudinal, multicenter study included 241 adults with ADPKD and preserved renal function. Magnetic resonance imaging and iothalamate clearance were used to measure htTKV and GFR, respectively. The association between baseline htTKV and the attainment of stage 3 CKD (GFR <60 ml/min per 1.73 m(2)) during follow-up was determined.

Results: After a mean follow-up of 7.9 years, stage 3 CKD was attained in 30.7% of the enrollees. Using baseline htTKV, negative correlations with GFR increased from -0.22 at baseline to -0.65 at year 8. In multivariable analysis, a baseline htTKV increase of 100 cc/m significantly predicted the development of CKD within 8 years with an odds ratio of 1.48 (95% confidence interval: 1.29, 1.70). In receiver operator characteristic curve analysis, baseline htTKV of 600 cc/m most accurately defined the risk of developing stage 3 CKD within 8 years with an area under the curve of 0.84 (95% confidence interval: 0.79, 0.90). htTKV was a better predictor than baseline age, serum creatinine, BUN, urinary albumin, or monocyte chemotactic protein-1 excretion (P<0.05).

Conclusions: Baseline htTKV ≥600 cc/m predicted the risk of developing renal insufficiency in ADPKD patients at high risk for renal disease progression within 8 years of follow-up, qualifying htTKV as a prognostic biomarker in ADPKD.

Figure 1.

Age-related development of renal insufficiency. Cumulative number of participants reaching specified renal insufficiency end points >20% or >40% decline in iothalamate GFR from baseline or a GFR <60 (stage 3 CKD) or <30 ml/min per 1.73 m² (stage 4 CKD).

Figure 2.

Average standardized change in htTKV and iothalamate GFR. htTKV determined at baseline and iothalamate GFR at baseline and five subsequent visits until year 8 (n=93 with complete data). P<0.01 based on paired t test comparing each year to baseline for htTKV (*) and GFR (#). htTKV, height-adjusted total kidney volume.

Figure 3.

Correlations between baseline htTKV and GFR during follow-up. Pearson correlation coefficients determined for baseline htTKV and iothalamate GFR at baseline and five subsequent visits (n=114 with complete data) to year 8. The degree of correlation at each time point is shown. htTKV, height-adjusted total kidney volume.

Figure 4.

Receiver operating characteristic curve defining baseline height-adjusted total kidney volume prediction of stage 3 CKD end point. Area under the curve is 0.84, with 74% sensitivity, 75% specificity, and a cut point of 600 cc/m. Ten participants who had reached stage 3 CKD at baseline were excluded. AUROC, area under the receiver operating characteristic curve; 95% CI, 95% confidence interval.