Renal Hemodynamic and Functional Changes in Patients with ADPKD

Key Points:

1. The mechanism of decreased renal function in autosomal dominant polycystic kidney disease has not been elucidated yet.

2. The presented data highlight specific renal hemodynamic changes that occur in patients with autosomal dominant polycystic kidney disease.

Background: Although the mechanisms underlying cyst enlargement in autosomal dominant polycystic kidney disease (ADPKD) are becoming clearer, those of renal dysfunction are not fully understood. In particular, total kidney volume and renal function do not always correspond. To elucidate this discrepancy, we studied in detail glomerular hemodynamic changes during ADPKD progression.

Methods: Sixty-one patients with ADPKD with baseline height-adjusted total kidney volume (Ht-TKV) of 933±537 ml/m and serum creatinine of 1.16±0.62 mg/dl were followed for 2 years. GFR and renal plasma flow (RPF) slopes were calculated from inulin clearance (C_in) and para-aminohippuric acid clearance (C_PAH), respectively, while glomerular hydrostatic pressure (P_glo), afferent resistance (R_A), and efferent resistance (R_E) were estimated using the Gomez formulas. Each parameter was compared with baseline Ht-TKV. Patients were also subclassified into 1A–1B and 1C–1E groups according to the baseline Mayo imaging classification and then compared with respect to GFR, RPF, filtration fraction, and glomerular hemodynamics.

Results: After 2 years, Ht-TKV increased (933±537 to 1000±648 ml/m, P < 0.01), GFR decreased (66.7±30 to 57.3±30.1 ml/min per 1.73 m², P < 0.001), and RPF decreased (390±215 to 339±190 ml/min per 1.73 m², P < 0.05). Furthermore, P_glo was decreased and R_A was increased. Baseline Ht-TKV was inversely correlated with GFR (r=−0.29, P < 0.05), but there was no association between baseline Ht-TKV and RPF, P_glo, R_A, or R_E annual changes. However, despite an increase in R_E in the 1A–1B group, R_E was decreased in the 1C–1E group. As a result, R_E slope was significantly lower in the 1C–1E group than the 1A–1B group over time (−83 [−309 to 102] to 164 [−34 to 343] dyne·s·cm⁻⁵, P < 0.01).

Conclusions: This is the first report examining yearly changes of GFR (inulin), RPF (para-aminohippuric), and renal microcirculation parameters in patients with ADPKD. Our results demonstrate that GFR reduction was caused by R_A increase, which was faster because of R_E decrease in patients with faster Ht-TKV increase.