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 (31±6 years of age, 65% women, BMI: 26.8 [22.7, 30.4] kg/m2 , eGFR (2021 CKD-EPI Creatinine): 103±18 ml/min/1.73m2 , height-adjusted total kidney volume [HtTKV]: 731±370 ml/m, Mayo Classifications: 1B [5%], 1C [42%], 1D [21%], 1E [32%]) and 11 controls in normal weight category (NWC; 25±3 years of age, 45% women, BMI: 22.5 [21.7, 24.2] kg/m2 , eGFR: 113±15 ml/min/1.73m2 , HtTKV: 159±31 ml/m) at the University of Colorado Anschutz Medical Campus.

PREDICTORS: ADPKD status (yes/no) and severity (Mayo Classifications).

OUTCOMES: HtTKV and cyst burden by MRI, kidney oxidative metabolism and perfusion by 11 C-acetate PET/CT, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]).

ANALYTICAL APPROACH: Chi-square/Fisher's exact tests used for categorical variables and t-tests/ Mann-Whitney U tests for continuous variables. Pearson correlation used to estimate the relationships between variables.

RESULTS: Compared to NWC, participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs. 0.424±0.171 (mg/kg lean/min) / (μIU/mL), p=0.04), lower median [p25, p75] cortical perfusion (1.93 [1.80, 2.09 vs. 0.68 [0.47, 1.04] mL/min/g, p<0.001) and lower median [p25, p75] total kidney oxidative metabolism (0.17 [0.16,0.19] vs. 0.14 [0.12, 0.15] min-1 , p=0.001) in voxel-wise models excluding cysts. HtTKV 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.

CONCLUSION: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements.