Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence
Abstract
:1. Introduction
2. Brief Overview of Glucose Metabolism, Warburg Effect, and Ketosis
3. Ketosis in ADPKD Animal Models
Intervention and Study Design | Model (Orthologous: ✓/✕) | Control Group | Kidney Outcomes | Notes | |
---|---|---|---|---|---|
Fasting | 48 h WF [47] | ✕ Han:SPRD-Cy/+ rats aged 8 wk | 48 h WF WT | KHW ↓ * (male). CI ↓ *. Cysts apoptosis. | NK achieved. ↓ BW (both groups). |
24 h WF [47] | ✓ Pkd1cond/cond:NesCre mice aged 8 wk | 24 h WF WT | No TKV changes. Cysts apoptosis. | NK achieved. | |
72 h WF [47] | ✓ Pkd1 Persian cat aged 34.2–64.9 mo | N/A | TKV ↓ (~15%) | No NK evaluation. ↓ BW. | |
DCR | 6 mo DCR (−40%) [45] | ✓ Pkd1RC/RC miceaged 6 wk | AL model AL WT | KHW, CI, IF, cystogenesis ↓ *. | No NK evaluation. ↓ * BW. |
3 mo DCR (−40%) [45] | ✓ Pkd1RC/RC miceaged 5.5 mo | AL model AL WT | KHW ↓ *. Improvement in BUN and CysC. | No NK evaluation. | |
2 mo DCR (−10%, −20%, −40%) [45] | ✓ Pkd1RC/RC miceaged 5.5 mo | AL model | KHW ↓ *. CI ↓ (↓ * 20%, 40%). | No NK evaluation. ↓ BW. | |
2 mo DCR (−40%) [45] | ✓ Pkd2WS25/- mice aged 8 wk | AL model | KHW, CI ↓ * | No NK evaluation. | |
12 wk DCR (−23%) [46] | ✓ Pkd1cond/cond:NesCre mice aged 35 days | AL model DCR WT | KBW ↓ *. IF ↓ | No NK evaluation. | |
TRF | 5 wk TRF (8 h window) [47] | ✕ Han:SPRD-Cy/+ rats aged 3–8 wk | AL NC model TRF WT AL NC WT | KBW, CI, cystogenesis ↓ *. IF, SC ↓. | NK achieved. |
DCR IMF TRF | 3 mo DCR (−40%), IMF (−80% 3 days/wk), TRF (8 h window) [53] | ✓ Pkd1RC/RC miceaged 3 mo | AL model | KBW, CI ↓ * (DCR). | ↓ * BW (DCR). |
KD | 5 wk AL cKD [47] | ✕ Han:SPRD-Cy/+ rats aged 3–8 wk | AL NC model AL KD WT AL NC WT | KBW, KHW, CI, cystogenesis, SC ↓ *. IF ↓. | NK achieved. ↓ * BW gain. |
4 wk AL cKD [47] | ✕ Han:SPRD-Cy/+ rats aged 8–12 wk | AL NC model AL KD WT AL NC WT | TKV, KBW, CI ↓. IF ↓ (male). | NK achieved. ↓ BW gain. | |
Exogenous ketosis | 5 wk Na and K BHB salt in water [47] | ✕ Han:SPRD-Cy/+ rats aged 3–8 wk | Water model Water + Na/KCl model | KBW, CI, IF ↓ *. IF ↓ *. SC, cystogenesis ↓. | No BW changes. |
5 wk Na and K BHB salt and/or citrate [52] | ✕ Han:SPRD-Cy/+ rats aged 3–8 wk | Water model Analogous titrations WT | KBW, SC ↓ * (BHB, BHB/citrate). CI ↓ * (80, 160 Mm BHB; 40/60, 80/60 Mm BB/citrate). | ||
5 wk Na and K BHB salt and citrate [52] | ✕ Han:SPRD-Cy/+ rats aged 8–12 wk | Water + Na/KCl model | KBW, CI ↓. SC ↓ *. |
4. Ketosis in ADPKD Patients
5. Focus on RCTs in ADPKD Patients
6. Kidney Disease, Ketosis, and Microbiota
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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KDI | Overview | Evidence | Comments |
---|---|---|---|
DCR [23,24,25,26] |
|
| Challenging long-term. Unclear evidence on achieving NK. |
IMF [27,28,29] |
|
| Different fasting schedules: reduced or normocaloric intake, and fasting period varying from hours (e.g., 16/8) to days (e.g., 5:2). |
TRF [27,29,30] |
|
| Different eating window duration. |
cKD [31,32] |
|
| Requires the use of specifically calculated recipes measured in grams to meet the patient’s needs. |
MCT [31,32,33] |
|
| Requires the use of specifically calculated recipes measured in grams. Greater food variety compared to cKD. |
MAD [31,32,33,34,35] |
|
| Food can be measured using standard household measurements. |
LGIT [31,32,33] |
|
| Food can be measured using standard household measurements |
VLCKD [36,37] |
|
| Rapid weight loss effects but requires monitoring to avoid nutritional deficiencies. |
KDI | Study Design | Length and Sample | BMI | Weight Loss Outcomes | Kidney Outcomes | Status Completed: ✓, Recruiting: ● |
---|---|---|---|---|---|---|
DCR vs. IMF (both with ~34% weekly energy deficit) | 2 EAs, masked (Inv, OA) | 12 mo (n = 29) | 25–45 | ↓ BW, SAT, VAT, TAT (MRI) (independent of KDI) | ↓ htTKV correlated with BW VAT and TAT loss independent of KDI. No changes in eGFR. | ✓ [53] |
TRF (8 h window) vs. HE | 1 EA, 1 CA, masked (Inv, OA) | 12 mo (n = 29) | 25–45 | ↓ BW (independent of KDI) | ↓ htTKV correlated with BW and VAT loss independent of KDI. | ✓ [57] |
KD (carbohydrate < 30 g/day, 0.8 g/kg BW protein intake) and 3-days WF vs. AL diet | 2 EAs, 1 CA, no masking | 3 mo (n = 63) | 18.6–34.9 | ↓ BW and significant ↓ WC (KD and WF), significant ↓ fat mass (KD), ↓ lean mass (KD and WF) | Significant creatinine-based and CysC-based eGFR ↑ with KD. Significant htTKV ↓ in a subset of KD patients reaching NK at 2/3 study visits. | ✓ [58,75] |
DCR (30%) and increased physical activity vs. SNC | 1 EA, 1 CA, masked (Inv, OA) | 24 mo (n = 126) | 25–45 | N/A | N/A | ● [60] |
MAD (<20 g/day of carbohydrates) vs. BND | 1 EA, 1 CA, masked (Inv, OA) | 24 mo (n = 92) | 20–30 | N/A | N/A | ● [53] |
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Pezzuoli, C.; Biagini, G.; Magistroni, R. Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence. Nutrients 2024, 16, 2676. https://doi.org/10.3390/nu16162676
Pezzuoli C, Biagini G, Magistroni R. Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence. Nutrients. 2024; 16(16):2676. https://doi.org/10.3390/nu16162676
Chicago/Turabian StylePezzuoli, Carla, Giuseppe Biagini, and Riccardo Magistroni. 2024. "Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence" Nutrients 16, no. 16: 2676. https://doi.org/10.3390/nu16162676
APA StylePezzuoli, C., Biagini, G., & Magistroni, R. (2024). Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence. Nutrients, 16(16), 2676. https://doi.org/10.3390/nu16162676