Renal Hemodynamic and Functional Changes in ADPKD Patients

Kidney360. 2024 Mar 21. doi: 10.34067/KID.0000000000000412. Online ahead of print.

Abstract

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 (TKV) and renal function do not always correspond. To elucidate this discrepancy, we studied in detail glomerular hemodynamic changes during ADPKD progression.

Methods: Sixty-one ADPKD patients with baseline height-adjusted TKV (Ht-TKV) of 933±537 ml/m and serum creatinine of 1.16±0.62 mg/dl were followed for 2 years. Glomerular filtration rate (GFR) and renal plasma flow (RPF) slopes were calculated from inulin clearance (Cin) and para-aminohippuric acid (PAH) clearance (CPAH), respectively, while glomerular hydrostatic pressure (Pglo), afferent resistance (RA), and efferent resistance (RE) were estimated using the Gomez formulae. 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 (MIC), and then compared with respect to GFR, RPF, FF 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/1.73m2, P<0.001), and RPF decreased (390±215 to 339±190 ml/min/1.73m2, P<0.05). Further, Pglo was decreased and RA 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, Pglo, RA, or RE annual changes. However, despite an increase in RE in 1A-1B group, RE was decreased in 1C-1E group. As a result, RE slope was significantly lower in 1C-1E group than 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 (PAH), and renal microcirculation parameters in ADPKD patients. Our results demonstrate that GFR reduction was caused by RA increase, which was faster due to RE decrease in subjects with faster Ht-TKV increase.