Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease
Abstract
:1. Introduction
1.1. Metabolic Reprogramming in ADPKD
1.2. Pathophysiologic Rational
2. Preclinical Trials
3. Clinical Trials
4. Side Effects of Ketogenic Diet
4.1. Metabolic Acidosis
4.2. Kidney Stones and Hyperuricemia
4.3. Elevation of Low-Density Lipoprotein Cholesterol (LDL-C)
4.4. “Keto Flu” Symptoms
5. Ketosis-Inducing Therapies: SGLT2 Inhibitors
6. Dietary Counseling in ADPKD
6.1. Protein Intake
6.2. Salt Intake
6.3. Water Intake
6.4. Caffein Intake
7. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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---|---|---|---|---|
Warner et al., 2016 [39] | 10–40% DCR versus ad libitum | Pkd1RC/RC mice; Pkd2. WS25/− mice | From 6 wk to 7.5 mo | Reduced cyst area, kidney fibrosis, inflammation, and injury; Improved kidney function; Increased activation of LKB1-AMPK and reduced activation of mTOR-S6K. |
Kipp et al., 2016 [40] | 23% DCR versus ad libitum | Pkd1cond/cond:Nescre mice | Postnatal wk 5–12 | Reduced cyst growth, proliferation and fibrosis; Maintained renal function; Reduced mTOR activation, not increased activation of LKB1-AMPK. |
Hopp et al., 2021 [42] | 30% DCR versus ad libitum | Pkd1RC/RC mice | From 3 to 6 mo of age | Reduced cyst area, reduced kidney weight and fibrosis; Increased p-AMPK/AMPK, not reduced p-S6/S6. |
Hopp et al., 2021 [42] | IMF (80% food restriction 3 d/wk, ad libitum other days) versus ad libitum every day | Pkd1RC/RC mice | From 3 to 6 mo of age | No reduction in cyst area; No reduction in kidney weight and fibrosis. |
Hopp et al., 2021 [42] | TRF (8 h during the 12 h dark cycle) versus ad libitum | Pkd1RC/RC mice | From 3 to 6 mo of age | No reduction in cyst area; No reduction in kidney weight and fibrosis. |
Torres et al., 2019 [41] | TRF (8 h during the 12 h dark cycle) versus ad libitum | Han:SPRD rat | Postnatal weeks 3—8 | Reduced cystogenesis and cyst growth; Reduced fibrosis; Reduced activation of mTOR-S6K and STAT3. |
Torres et al., 2019 [41] | Ketogenic diet | Han:SPRD rat, juvenile and adult and male versus female | 5 wk (age 3–8 wk); (age 8–12 wk) | Reduced kidney weight and cystic indices; Reduced increase in serum creatinine; Reduced activation of mTOR-S6K and STAT3, increased p-AMPK (in the juvenile model); Reduced kidney weight and cystic indices; renal function not affected (in the adult model). |
Torres et al., 2019 [41] | Acute fasting | Han:SPRD rat; Pkd1cond/cond:Nescre mice, Feline PKD1 models | 48 h fasting with free access to water (Han:SPRD rat); 24 h fasting with free access to water (Pkd1 cond/cond:Nes cre mice); 72 h fasting with free access to water (Feline PKD1 models) | Reduced cystic area and kidney mass (Han:SPRD rat, Feline PKD1 models); No change in kidney mass (Pkd1cond/cond:Nescre mice). |
Torres et al., 2019 [41] | Ad libitum feed + oral BHB | Han:SPRD rat, juvenile and adult and male versus female | 5 wk | Reduced kidney mass and cystic area; Inhibition of proliferation; Reduced fibrosis; Improved kidney function. |
Authors, Year of Publication | Intervention | Study Design | Population (N) | Duration | Findings |
---|---|---|---|---|---|
Hopp et al., 2021 [42] | 34% DCR versus IMF (80% restriction every other day) | Pilot clinical trial | Adult overweight or obese ADPKD patients (28) | 1 year | Higher adherence with fewer side effects in DCR compared to IMF; Higher weight loss in DCR compared to IMF; Annual change in htTKV qualitatively low versus historical control and correlated with weight loss in both DCR and IMF; No annual change in eGFR in both DCR and IMF; Improved lipid profile only in DCR. |
Testa et al., 2019 [47] | Modified Atkins diet | Pilot clinical trial | Adult patients with rapidly progressive ADPKD (3) | 3 mo | High rate of overall satisfaction; Increase in total cholesterol levels. |
Strubl et al., 2022 [48] | Self-initiated KD and/or TRD | Retrospective case series study of self-reported observation and medical data | Adult ADPKD patients (121) | ≥6 mo | Improvement of overall health with both KD or TRD; Amelioration of ADPKD-related symptoms and weight loss more pronounced in KD compared to TRD; Stabilization of eGFR. |
Bruen et al., 2022 [49] | PFKD including KetoCitra® | Real-life experience clinical trial | Adult ADPKD patients (24) | 12 wk | High rate of adherence and satisfaction; 50% of pts refer amelioration of ADPKD-related symptoms; Weight loss; Improved renal function. |
Oehm et al., 2023 [50] | 3-day WF or a 14-day KD | Prospective interventional short-term clinical trial | Adult patients with rapidly progressive ADPKD (10) | 3 days (WF) 14 days (KD) | High rate of satisfaction; No change in TKV; Weight loss; Increased levels of total and LDL cholesterol in KD; Increased uric acid levels. |
Cukoski et al., 2023 [51] | KD versus WF (3 of 14 d) versus ad libitum diet | Exploratory, randomized, open, single-center, three arm dietary intervention study | Adult ADPKD patients (63); randomized to KD (23), WF (21), and ad libitum diet (19) | 12 wk | Increased eGFR in KD group; Significant weight loss only in KD group; Decrease ht-TKV in KD group (p = 0.08); Increased eGFR in KD group (p = 0.00); Increased cholesterol and uric acid levels in KD group. |
Dietary Intervention | Proposed Mechanism | Available Studies | Conclusions | Status of Clinical Trials |
---|---|---|---|---|
Daily caloric restriction | Inhibition of mTOR pathway and activation of AMPK, preventing cell proliferation, fibrosis, and cyst growth. | Preclinical trial [40,41,43] Pilot clinical trial [42] | Difficult long-term adherence or feasibility; Possible recommendation in overweight or obese patients, under medical monitoring. | No published data yet (NCT03342742); Ongoing clinical trial (NCT04907799). |
Intermittent fasting | Inhibition of mTOR pathway and activation of AMPK, preventing cell proliferation, fibrosis, and cyst growth. | Preclinical trial [42] Pilot clinical trial [42] | Not enough evidence to specifically recommend in ADPKD patients. | No published data yet (NCT03342742). |
Time-restricted feeding | Reduction in mTOR and STAT3 signaling, preventing cell proliferation, fibrosis, and cyst growth. | Preclinical trial [41,42] | Not enough evidence to specifically recommend in ADPKD patients. | Ongoing clinical trials (NCT04534985). |
Ketogenic diet | Inhibition of mTOR pathway and activation of AMPK, preventing cell proliferation, fibrosis, and cyst growth. | Preclinical trial [41] Pilot clinical trial [47] Retrospective case series study [48] Real-life clinical trial [49] Prospective interventional short-term clinical trial [50] RCT [51] | Not enough evidence to specifically recommend in ADPKD patients. | No planned clinical trials. |
BHB | Inhibition of mTOR pathway and activation of AMPK, preventing cell proliferation, fibrosis, and cyst growth. Anti-inflammatory effects. Improvement of mitochondrial efficiency. | Preclinical trial [41] | Not enough evidence to specifically recommend in ADPKD patients. | Not recruiting clinical trial yet (NCT06100133). |
Reduced protein intake | Reduction in hyperfiltration and vasopressin levels. | Preclinical trial [91], Prospective clinical trial [92], Observational cohort study [93,94], Post hoc analysis of the DIPAK observational data [95] | No specific evidence in ADPKD patients, but in accordance with the current management of CKD. | No planned clinical trials. |
Reduced salt intake | Decrease in vasopressin secretion, RAAS activation, and blood pressure. | Observational cohort study [93,94], Pilot RCT [104], Qualitative study [105], Post hoc analysis of the HALT-PKD data [107] | No specific evidence in ADPKD patients, but in accordance with the current management of CKD. | No planned clinical trials. |
High water intake | Reduction in V2 receptor activation and cAMP production. | Preclinical trial [115,116,117,118] Pilot study [119,120], Pilot RCT [104], Prospective clinical trial [123] | No specific evidence in ADPKD patients. Recommendation to reduce water intake as eGFR declines, in line with current CKD management. | Ongoing clinical trials (ANZCTR12614001216606; NCT02933268; NCT03102632). |
Low caffeine intake | Activation of phosphodiesterases, enhanced hydrolysis of cAMP. | Preclinical trial [130], Retrospective, post hoc analysis of the CRISP cohort [131], Prospective analysis of the Suisse PKD cohort [132] | No evidence in animal models or ADPKD patients. | No planned clinical trials. |
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Rosati, E.; Condello, G.; Tacente, C.; Mariani, I.; Tommolini, V.; Calvaruso, L.; Fulignati, P.; Grandaliano, G.; Pesce, F. Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease. Nutrients 2024, 16, 2582. https://doi.org/10.3390/nu16162582
Rosati E, Condello G, Tacente C, Mariani I, Tommolini V, Calvaruso L, Fulignati P, Grandaliano G, Pesce F. Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease. Nutrients. 2024; 16(16):2582. https://doi.org/10.3390/nu16162582
Chicago/Turabian StyleRosati, Erica, Giulia Condello, Chiara Tacente, Ilaria Mariani, Valeria Tommolini, Luca Calvaruso, Pierluigi Fulignati, Giuseppe Grandaliano, and Francesco Pesce. 2024. "Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease" Nutrients 16, no. 16: 2582. https://doi.org/10.3390/nu16162582
APA StyleRosati, E., Condello, G., Tacente, C., Mariani, I., Tommolini, V., Calvaruso, L., Fulignati, P., Grandaliano, G., & Pesce, F. (2024). Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease. Nutrients, 16(16), 2582. https://doi.org/10.3390/nu16162582