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Background: ADPKD is the most common monogenetic kidney disease and results in kidney failure in over 75% of affected individuals. As a systemic disorder, ADPKD is associated with a variety of extrarenal manifestations affecting the majority of patients including cardiac manifestations. We characterized the cardiac involvement in ADPKD patients from the German AD(H)PKD registry and compared them to kidney donor candidates as controls. Methods: In this single-center cohort study, we evaluated 141 ADPKD (44.17 ± 11.23 years) patients from the German AD(H)PKD registry and 60 kidney donor candidates (55.08 ± 10.21 years). All patients underwent clinical examination, abdominal MRI, and transthoracic echocardiography. Results: 65% of ADPKD patients showed hypertrophy of the left ventricle (as defined by an end-diastolic left ventricular septal wall thickness (IVSd) greater than 10mm) compared to 55% in control patients. Mitral regurgitation was the most common finding among 53.57 % of ADPKD patients who exhibited valvular dysfunction, albeit mild in the majority of patients. Interestingly, left ventricular ejection fraction (LV-EF) differed significantly between both groups with higher values in ADPKD patients (63.53±6.38% vs. 60.21±5.72%), while other parameters including IVSd, left ventricular end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE) and pressure gradients across the aortic and tricuspid valve were similar between groups. Correlations of echocardiographic parameters with markers of disease progression revealed statistically significant associations for aortic root diameter (p = 0.014), the pressure gradient across the aortic valve (AV dPmax) (p = 0.0003) and left ventricular septal wall thickness (IVSd) (p = 0.0001), indicating that rapid kidney disease progression may also be associated with cardiac findings. Conclusion: Cardiovascular abnormalities are prevalent in ADPKD patients. Considering the importance of cardiovascular disease for outcome in CKD, early management and possibly prevention are important goals of any treatment scheme. Consequently, echocardiography should be offered to all ADPKD patients in routine management.

Background Ketogenic dietary interventions (KDI) have been shown to be effective in animal models of polycystic kidney disease, but data from clinical trials are lacking. Methods Ten ADPKD patients with rapid disease progression were enrolled at visit V1 and initially maintained a carbohydrate (CHO)-rich diet. At V2, patients entered one of the two KDI arms: a 3-day water fast (WF) or a 14-day ketogenic diet (KD). At V3, they resumed their normal diet for 3 to 6 weeks until V4. At each visit, MRI kidney and liver volumetry was performed. Ketone bodies were evaluated to assess metabolic efficacy and questionnaires were used to determine feasibility. Results All participants (KD n = 5, WF n = 5; age 39.8 ± 11.6 years; eGFR 82 ± 23.5 ml/min; total kidney volume (TKV) 2224 ± 1156 ml) were classified as Mayo Class 1C to 1E. Acetone levels in breath and BHB blood levels increased in both study arms (V1 to V2 average acetone: 2.7±1.2 ppm, V2 to V3: 22.8±11.9 ppm, p = 0.0006; V1 to V2 average BHB: 0.22±0.08 mmol/l, V2 to V3: 1.88±0.93 mmol/l, p = 0.0008). 9/10 patients reached a ketogenic state and 9/10 evaluated KDIs as feasible. TKV did not change during this trial. However, we found a significant impact on total liver volume (ΔTLV V2 to V3: -7.7%, p = 0.01), mediated by changes in its non-cystic fraction. Conclusions RESET-PKD demonstrates that short-term KDIs potently induce ketogenesis and are feasible for ADPKD patients in daily life. While TLV quickly changed upon the onset of ketogenesis, changes in TKV may require longer-term interventions.