Editing Autosomal dominant polycystic kidney disease (section)

===Dietary and lifestyle interventions===
Research using ADPKD mouse models showed that mild food restriction strongly improved disease progression.<ref>{{cite journal | vauthors = Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T | title = A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease | journal = American Journal of Physiology. Renal Physiology | volume = 310 | issue = 8 | pages = F726–F731 | date = April 2016 | pmid = 26764208 | pmc = 4835927 | doi = 10.1152/ajprenal.00551.2015 }}</ref> The mechanism was shown to involve the metabolic state of [[ketosis]], and beneficial effects could be produced by time-restricted feeding, acute fasting, a ketogenic diet, or by supplementation with the ketone [[beta-hydroxybutyrate]] in mouse, rat and cat models of ADPKD.<ref name="rat model">{{cite journal | vauthors = Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T | display-authors = 6 | title = Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease | journal = Cell Metabolism | volume = 30 | issue = 6 | pages = 1007–1023.e5 | date = December 2019 | pmid = 31631001 | pmc = 6904245 | doi = 10.1016/j.cmet.2019.09.012 }}</ref><ref name="ketosis">{{cite journal | vauthors = Carney EF | title = Ketosis slows the progression of PKD | journal = Nature Reviews. Nephrology | volume = 16 | issue = 1 | pages = 1 | date = January 2020 | pmid = 31654043 | doi = 10.1038/s41581-019-0226-4 | s2cid = 204886698 | doi-access = free }}</ref>  A ketogenic diet regimen not only halted further disease progression but led to partial reversal of renal cystic disease in a rat model.<ref name="ketosis"/> The metabolic state of ketosis may be beneficial in ADPKD because renal cyst cells in ADPKD have a metabolic defect similar to the [[Warburg effect (oncology)|Warburg effect]] in cancer that makes them highly dependent on glucose, and unable to metabolize fatty acids and ketones.<ref name="rat model" /><ref>{{cite journal | vauthors = Nowak KL, Hopp K | title = Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Evidence and Therapeutic Potential | journal = Clinical Journal of the American Society of Nephrology | volume = 15 | issue = 4 | pages = 577–584 | date = April 2020 | pmid = 32086281 | pmc = 7133124 | doi = 10.2215/CJN.13291019 }}</ref><ref>{{cite journal | vauthors = Padovano V, Podrini C, Boletta A, Caplan MJ | title = Metabolism and mitochondria in polycystic kidney disease research and therapy | journal = Nature Reviews. Nephrology | volume = 14 | issue = 11 | pages = 678–687 | date = November 2018 | pmid = 30120380 | doi = 10.1038/s41581-018-0051-1 | s2cid = 52033674 }}</ref> Consistent with this, serum glucose levels positively correlate with faster disease progression in ADPKD patients.<ref>{{cite journal | vauthors = Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T | display-authors = 6 | title = Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease | journal = Cell Metabolism | volume = 30 | issue = 6 | pages = 1007–1023.e5 | date = December 2019 | pmid = 31631001 | pmc = 6904245 | doi = 10.1016/j.cmet.2019.09.012 | ref = glucose levels }}</ref> Also, individuals with ADPKD and type 2 diabetes have significantly larger total kidney volume (TKV) than those with ADPKD alone,<ref>{{cite journal | vauthors = Reed B, Helal I, McFann K, Wang W, Yan XD, Schrier RW | title = The impact of type II diabetes mellitus in patients with autosomal dominant polycystic kidney disease | journal = Nephrology, Dialysis, Transplantation | volume = 27 | issue = 7 | pages = 2862–2865 | date = July 2012 | pmid = 22207329 | pmc = 3398061 | doi = 10.1093/ndt/gfr744 }}</ref> and overweight or obesity associate with faster progression in early-stage ADPKD.<ref>{{cite journal | vauthors = Nowak KL, You Z, Gitomer B, Brosnahan G, Torres VE, Chapman AB, Perrone RD, Steinman TI, Abebe KZ, Rahbari-Oskoui FF, Yu AS, Harris PC, Bae KT, Hogan M, Miskulin D, Chonchol M | display-authors = 6 | title = Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease | journal = Journal of the American Society of Nephrology | volume = 29 | issue = 2 | pages = 571–578 | date = February 2018 | pmid = 29118087 | pmc = 5791072 | doi = 10.1681/ASN.2017070819 }}</ref> A retrospective case series study showed that ADPKD disease symptoms - including pain, hypertension and renal function - improved among 131 patients who implemented ketogenic diets for an average duration of 6 months.<ref name = "Strubl_2021" />

Dietary intake of sodium is associated with worse renal function decline in ADPKD,<ref>{{cite journal | vauthors = Kramers BJ, Koorevaar IW, Drenth JP, de Fijter JW, Neto AG, Peters DJ, Vart P, Wetzels JF, Zietse R, Gansevoort RT, Meijer E | display-authors = 6 | title = Salt, but not protein intake, is associated with accelerated disease progression in autosomal dominant polycystic kidney disease | journal = Kidney International | volume = 98 | issue = 4 | pages = 989–998 | date = October 2020 | pmid = 32534051 | doi = 10.1016/j.kint.2020.04.053 | s2cid = 219637514 | doi-access = free | hdl = 2066/225147 | hdl-access = free }}</ref> and limiting sodium intake is generally recommended to patients. Dietary protein intake was not found to correlate with ADPKD progression.<ref>{{cite journal | vauthors = Kramers BJ, Koorevaar IW, Drenth JP, de Fijter JW, Neto AG, Peters DJ, Vart P, Wetzels JF, Zietse R, Gansevoort RT, Meijer E | display-authors = 6 | title = Salt, but not protein intake, is associated with accelerated disease progression in autosomal dominant polycystic kidney disease | journal = Kidney International | volume = 98 | issue = 4 | pages = 989–998 | date = October 2020 | pmid = 32534051 | doi = 10.1016/j.kint.2020.04.053 | s2cid = 219637514 | first8 = Priya | first6 = A.G. | first7 = D.J.M. | doi-access = free | hdl = 2066/225147 | hdl-access = free }}</ref>

Increased water intake is thought to be beneficial in ADPKD and is generally recommended.<ref name = "Torres_2019">{{cite journal | vauthors = Torres JA, Rezaei M, Broderick C, Lin L, Wang X, Hoppe B, Cowley BD, Savica V, Torres VE, Khan S, Holmes RP, Mrug M, Weimbs T | display-authors = 6 | title = Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease | journal = The Journal of Clinical Investigation | volume = 129 | issue = 10 | pages = 4506–4522 | date = July 2019 | pmid = 31361604 | pmc = 6763267 | doi = 10.1172/JCI128503 }}</ref><ref>{{cite journal | vauthors = Amro OW, Paulus JK, Noubary F, Perrone RD | title = Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial | journal = American Journal of Kidney Diseases | volume = 68 | issue = 6 | pages = 882–891 | date = December 2016 | pmid = 27663039 | pmc = 5123924 | doi = 10.1053/j.ajkd.2016.07.023 }}</ref> The underlying beneficial mechanism of increased water intake may be related to effects on the vasopressin V2 receptor or may be due to the suppression of harmful micro-crystal formation in renal tubules by dilution of solutes such as calcium oxalate, calcium phosphate and uric acid.<ref name = "Torres_2019" /><ref>{{cite journal | vauthors = Allison SJ | title = Crystal deposition aids cystogenesis | journal = Nature Reviews. Nephrology | volume = 15 | issue = 12 | pages = 730 | date = December 2019 | pmid = 31551591 | doi = 10.1038/s41581-019-0215-7 | s2cid = 202733384 | doi-access = free }}</ref>

Dietary intake of oxalate or inorganic phosphate has been shown to accelerate PKD disease progression in several rodent models.<ref name = "Torres_2019" /> Low levels or urinary citrate – a natural antagonist of the formation of harmful crystals in kidney tubules – have been shown to associate with worse disease progression in ADPKD patients.<ref name = "Torres_2019" />