Dietary Care for ADPKD Patients: Current Status and Future Directions

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic nephropathy, and tolvaptan is the only therapy available. However, tolvaptan slows but does not stop disease progression, is marred by polyuria, and most patients worldwide lack access. This and recent preclinical research findings on the glucose-dependency of cyst-lining cells have renewed interest in the dietary management of ADPKD. We now review the current dietary recommendations for ADPKD patients according to clinical guidelines, the evidence base for those, and the potential impact of preclinical studies addressing the impact of diet on ADPKD progression. The clinical efficacy of tolvaptan has put the focus on water intake and solute ingestion as modifiable factors that may impact tolvaptan tolerance and ADPKD progression. By contrast, dietary modifications suggested to ADPKD patients, such as avoiding caffeine, are not well supported and their impact is unknown. Recent studies have identified a chronic shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis (Warburg effect) as a contributor to cyst growth, rendering cyst cells exquisitely sensitive to glucose availability. Therefore, low calorie or ketogenic diets have delayed preclinical ADPKD progression. Additional preclinical data warn of potential negative impact of excess dietary phosphate or oxalate in ADPKD progression.

Food as medicine: targeting the uraemic phenotype in chronic kidney disease

“…For example, ketogenic diets, with limitation of carbohydrates and liberal intake of fats, may reduce serum hemoglobin A1c in type-2 diabetes, but may also cause a substantial rise in low density lipoprotein cholesterol levels 4 . In adult polycystic kidney disease (ADPKD), ketogenic diets result in a chronic shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis ( the Warburg effect), delaying cyst growth, thus rendering cyst cells exquisitely sensitive to glucose availability, and therefore delaying progression of the disease 5 . Intriguing new data suggest that even mild reduction in food intake promoting ketosis slows the progression of ADPKD in a mouse model 6 .…”

The effect of energy restriction on development and progression of chronic kidney disease: review of the current evidence

“…Indeed, the lower relative kidney weight of newborns of diet-restricted mothers raises the issue of potential lower kidney reserve capacity and a potential negative impact on kidney ageing, which was not addressed. ER was also beneficial to experimental PKD (15) . Mild to moderate (10-40 %) food restriction decreased cyst growth, interstitial fibrosis and inflammation in association with suppression of the mammalian target of rapamycin (mTOR) pathway and activation of the liver kinase B1/adenosine monophosphate-activated protein kinase (AMPK) pathway (16) .…”

Undiagnosed cardiovascular risk factors in overweight and obese individuals: a low income country experience

“…In this regard, the local climate may favor continuous water losses through skin. High ADH levels have been associated with CKD progression, most notably in so-called Mesoamerican nephropathy and in polycystic kidney disease, that is now treated with an ADH receptor V2 blocker, tolvaptan ( Carriazo et al, 2019 ; Perez-Gomez et al, 2018 ).…”