Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study

Rationale & Objective: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden. Study Design: Cross-sectional study. Setting & Participants: Twenty adults with ADPKD (age, 31 +/- 6 years; 65% women; body mass index [BMI], 26.8 [22.7-30.4] kg/m(2); estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103 +/- 18mL/min/1.73m(2); height-adjusted total kidney volume [HTKV], 731 +/- 370mL/m; Mayo classifications 1B [5%], 1C [42%], 1D [21%], and 1E [32%]) and 11 controls in normal weight category (NWC) (age, 25 +/- 3 years; 45% women; BMI, 22.5 [21.7-24.2] kg/m2; eGFR, 113 +/- 15mL/min/1.73m(2); HTKV, 159 +/- 31mL/m) at the University of Colorado Anschutz Medical Campus. Predictors: ADPKD status (yes/no) and severity (Mayo classifications). Outcome: HTKV and cyst burden by magnetic resonance imaging, kidney oxidative metabolism, and perfusion by C-11-acetate positron emission tomography/computed tomography, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]). Analytical Approach: For categorical variables, chi(2)/Fisher's exact tests, and for continuous variables t tests/Mann-Whitney U tests. Pearson correlation was used to estimate the relationships between variables. Results: Compared with NWC individuals, the participants with ADPKD exhibited lower mean +/- SD M/I ratio (0.586 +/- 0.205 vs 0.424 +/- 0.171 [mg/kg lean/min]/(mu IU/mL), P=0.04), lower median cortical perfusion (1.93 [IQR, 1.80-2.09] vs 0.68 [IQR, 0.47-1.04] mL/min/g, P<0.001) and lower median total kidney oxidative metabolism (0.17 [IQR, 0.16-0.19] vs. 0.14 [IQR, 0.12-0.15] min(-1), P=0.001) in voxel-wise models excluding cysts. HTKV correlated inversely with cortical perfusion (r: -0.83, P < 0.001), total kidney oxidative metabolism (r: -0.61, P<0.001) and M/I (r: -0.41, P = 0.03). Limitations: Small sample size and cross-sectional design. Conclusions: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements.