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

Petter Bjornstad; Gabriel Richard; Ye Ji Choi; Kristen L Nowak; Cortney Steele; Michel B Chonchol; Kristen J Nadeau; Timothy Vigers; Laura Pyle; Kalie Tommerdahl; Daniel H van Raalte; Allison Hilkin; Lynette Driscoll; Carissa Birznieks; Katharina Hopp; Wei Wang; Charles Edelstein; Robert G Nelson; Adriana V Gregory; Timothy L Kline; Denis Blondin; Berenice Gitomer

doi:10.1053/j.ajkd.2024.02.016

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

Am J Kidney Dis. 2024 Apr 13:S0272-6386(24)00716-9. doi: 10.1053/j.ajkd.2024.02.016. Online ahead of print.

Authors

Petter Bjornstad¹, Gabriel Richard², Ye Ji Choi³, Kristen L Nowak⁴, Cortney Steele⁴, Michel B Chonchol⁴, Kristen J Nadeau⁵, Timothy Vigers³, Laura Pyle³, Kalie Tommerdahl⁶, Daniel H van Raalte⁷, Allison Hilkin⁵, Lynette Driscoll⁵, Carissa Birznieks⁵, Katharina Hopp⁴, Wei Wang⁴, Charles Edelstein⁴, Robert G Nelson⁸, Adriana V Gregory⁹, Timothy L Kline⁹, Denis Blondin², Berenice Gitomer⁴

Affiliations

¹ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: petter.m.bjornstad@cuanschutz.edu.
² Department of Medicine, Division of Neurology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS), Québec, Canada.
³ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, CO, USA.
⁴ Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA.
⁵ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
⁶ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Barbara Davis Center for Diabetes, Section of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
⁷ Department of Endocrinology and Metabolism and Diabetes Center, Amsterdam University Medical Centers, VUMC, Amsterdam, Netherlands.
⁸ Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
⁹ Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN.

PMID: 38621633
DOI: 10.1053/j.ajkd.2024.02.016

Abstract

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 ¹¹C-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.

Keywords: hyperinsulinemic-euglycemic clamps; kidney MRI; kidney PET; polycystic kidney disease.

Grants and funding

R21 DK129720/DK/NIDDK NIH HHS/United States