Risks and Benefits of Different Dietary Patterns in CKD

Food has the potential to cause and exacerbate many lifestyle diseases. Or it can be used to prevent and treat illnesses like primary hypertension, the metabolic syndrome, and insulin resistance. In parallel, there is also a growing body of evidence of the role of diet in the treatment of kidney disease and its ensuing complications. Popular diets for this purpose have included low-carbohydrate diets, including the ketogenic diet, and higher carbohydrate diets like Mediterranean diets and other plant-based dietary patterns. Low-carbohydrate diets have not shown harm in patients with kidney disease and may benefit a select few. Mediterranean diets have an established record of cardioprotective benefits but also may be beneficial for the kidney. Intermittent fasting has benefits for metabolic health, but limited research exists on the risk or benefit for patients with kidney disease. Plant-based diets, especially those that are lower in protein, may slow kidney disease progression, mitigate uremia, and delay dialysis initiation. Although each dietary pattern has its unique pros and cons, most healthful dietary patterns favor the inclusion of whole, unprocessed foods, preferably from plant-based sources. In this perspective, we discuss the risks and benefits of major popular diets to help guide health care professionals in treating patients with kidney disease. Food has the potential to cause and exacerbate many lifestyle diseases. Or it can be used to prevent and treat illnesses like primary hypertension, the metabolic syndrome, and insulin resistance. In parallel, there is also a growing body of evidence of the role of diet in the treatment of kidney disease and its ensuing complications. Popular diets for this purpose have included low-carbohydrate diets, including the ketogenic diet, and higher carbohydrate diets like Mediterranean diets and other plant-based dietary patterns. Low-carbohydrate diets have not shown harm in patients with kidney disease and may benefit a select few. Mediterranean diets have an established record of cardioprotective benefits but also may be beneficial for the kidney. Intermittent fasting has benefits for metabolic health, but limited research exists on the risk or benefit for patients with kidney disease. Plant-based diets, especially those that are lower in protein, may slow kidney disease progression, mitigate uremia, and delay dialysis initiation. Although each dietary pattern has its unique pros and cons, most healthful dietary patterns favor the inclusion of whole, unprocessed foods, preferably from plant-based sources. In this perspective, we discuss the risks and benefits of major popular diets to help guide health care professionals in treating patients with kidney disease. The increasing use of plant-based and ketogenic diets for the treatment of comorbidities, such as obesity, diabetes, and hypertension, has created interest regarding the utility of these diets in patients with chronic kidney disease (CKD). Are these diets safe, and if so is there any additional benefit to using them? Although evidence in some areas is still limited, it has undergone significant growth in recent years. In this article, we review the evidence on consuming a low-carbohydrate diet (including a ketogenic diet) or plant-based diet (including Mediterranean diets) or intermittent fasting by patients with CKD who are not receiving kidney replacement therapy. For patients with a kidney transplant, we refer readers to Cyrino et al1Cyrino L.G. Galpern J. Moore L. Borgi L. Riella L.V. A narrative review of dietary approaches for kidney transplant patients.Kidney Int Rep. 2021; 6: 1764-1774https://doi.org/10.1016/j.ekir.2021.04.009Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar for an excellent review of the topic. The modern Western diet is rich in animal-based foods and processed/ultraprocessed foods, resulting in a high intake of saturated fats, refined carbohydrates, and salt. This diet has been linked to metabolic disorders, including obesity, hypertension, diabetes, cardiovascular diseases (CVD), and other associated conditions, including cognitive impairment and emotional disorders.2Cordain L. Eaton S.B. Sebastian A. et al.Origins and evolution of the Western diet: health implications for the 21st century.Am J Clin Nutr. 2005; 81: 341-354https://doi.org/10.1093/ajcn.81.2.341Abstract Full Text Full Text PDF PubMed Scopus (1676) Google Scholar We will discuss recent the evidence on selected downsides of this diet, but for a fuller examination we refer readers to Hariharan et al3Hariharan D. Vellanki K. Kramer H. The Western diet and chronic kidney disease.Curr Hypertens Rep. 2015; 17: 1-9https://doi.org/10.1007/s11906-014-0529-6Crossref Scopus (67) Google Scholar for a review on the potential harms of Western diets on CKD. A high consumption of meat and animal protein has been associated with the risk of incident CKD and kidney failure.4Joshi S. McMacken M. Kalantar-Zadeh K. Plant-based diets for kidney disease: a guide for clinicians.Am J Kidney Dis. 2021; 77: 287-296https://doi.org/10.1053/j.ajkd.2020.10.003Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar Underlying mechanisms may relate to the effect of protein intake on hyperfiltration.5Kalantar-Zadeh K. Fouque D. Nutritional management of chronic kidney disease.N Engl J Med. 2017; 377: 1765-1776https://doi.org/10.1056/NEJMra1700312Crossref PubMed Scopus (327) Google Scholar Some studies have suggested that animal protein may cause more hyperfiltration than nonanimal protein.6Kontessis P. Jones S. Dodds R. et al.Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins.Kidney Int. 1990; 38: 136-144https://doi.org/10.1038/ki.1990.178Abstract Full Text PDF PubMed Scopus (216) Google Scholar In addition, fermentation of protein in the gut by proteolytic bacteria results in the production of uremic toxins, which may lead to oxidative stress, inflammation, and progressive loss of kidney function.7Fujii H. Goto S. Fukagawa M. Role of uremic toxins for kidney, cardiovascular, and bone dysfunction.Toxins. 2018; 10: 202https://doi.org/10.3390/toxins10050202Crossref PubMed Scopus (74) Google Scholar A recent study in mice with CKD suggested that limiting the intake of aromatic amino acids (tyrosine, tryptophan, and phenylalanine, which are primarily present in animal protein) could be as effective as limiting overall protein intake in mitigating kidney damage through decreased production of uremic toxins. The study compared 3 different diets for 6 weeks and observed that both a low-protein diet and a diet low in aromatic amino acids reduced proteinuria, kidney fibrosis, and inflammation compared with a normal protein diet. However, the greatest reduction in uremic toxin production was achieved by the diet low in aromatic amino acids.8Barba C. Benoit B. Bres E. et al.A low aromatic amino-acid diet improves renal function and prevent kidney fibrosis in mice with chronic kidney disease.Sci Rep. 2021; 11: 1-13https://doi.org/10.1038/s41598-021-98718-xCrossref PubMed Scopus (11) Google Scholar Western diets are typically high in added sugars and sweeteners. The consumption of added sugar, soft drinks, and sodas has been associated with the risk of albuminuria, incident CKD, and loss of estimated glomerular filtration rate (eGFR).9Kramer H. Shoham D. The millennial physician and the obesity epidemic: a tale of sugar-sweetened beverages.Clin J Am Soc Nephrol. 2019; 14: 4-6https://doi.org/10.2215/CJN.13851118Crossref PubMed Scopus (4) Google Scholar The underlying mechanisms have not been well described but may involve the promotion of obesity, diabetes, or hypertension and the increase in uric acid levels, all of which are risk factors for CKD. Limiting fructose intake lowers blood pressure and inflammation. In a crossover trial, 28 patients with CKD stages 2-3 were switched from a regular (60 g/24 h) to a low (12 g/24 h) fructose diet for 6 weeks, then resumed their regular diet for another 6 weeks. The main intervention to reduce fructose intake was limiting the consumption of soft drinks. The low-fructose diet resulted in significant reductions in blood pressure, insulin, and inflammatory molecules. No changes were seen in uric acid levels.10Brymora A. Flisiński M. Johnson R.J. Goszka G. Stefańska A. Manitius J. Low-fructose diet lowers blood pressure and inflammation in patients with chronic kidney disease.Nephrol Dial Transplant. 2012; 27: 608-612https://doi.org/10.1093/ndt/gfr223Crossref PubMed Scopus (71) Google Scholar The consumption of ultraprocessed foods has increased globally in recent decades, especially in Western diets. These foods are usually energy dense: high in saturated fat, sugar, salt, and additives, and low in dietary fiber and vitamins. The primary motivation of ultraprocessing is to create products that are ready-to-consume and hyperpalatable with a longer shelf-life.11Monteiro C.A. Cannon G. Levy R.B. et al.Ultra-processed foods: what they are and how to identify them.Public Health Nutr. 2019; 22: 936-941https://doi.org/10.1017/S1368980018003762Crossref PubMed Scopus (784) Google Scholar Studies have consistently found associations between these foods and the risk of cardiometabolic diseases, cancer, and premature death.12Lane M.M. Davis J.A. Beattie S. et al.Ultraprocessed food and chronic noncommunicable diseases: a systematic review and meta-analysis of 43 observational studies.Obes Rev. 2021; 22e13146https://doi.org/10.1111/obr.13146Crossref PubMed Scopus (209) Google Scholar Two studies have evaluated the associations between diets rich in ultraprocessed foods and the risk of kidney outcomes. In a prospective Dutch cohort of over 78,000 individuals with normal kidney function, 38% of the total food intake came, on average, from ultraprocessed foods. During a follow-up of 3.6 years, the participants in the highest quartile of ultraprocessed food consumption experienced a higher risk of a composite kidney outcome of incident CKD or a relative eGFR decline of more than 30%. This was observed regardless of their macro- or micronutrient intake or diet quality.13Cai Q. Duan M.-J. Dekker L.H. et al.Ultraprocessed food consumption and kidney function decline in a population-based cohort in the Netherlands.Am J Clin Nutr. 2022; 116: 263-273https://doi.org/10.1093/ajcn/nqac073Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar In another study from the ARIC cohort, there was a linear relationship between ultraprocessed food intake and the risk of developing CKD. The authors estimated that substituting 1 serving per day of ultraprocessed foods with minimally processed foods was associated with a 6% lower risk of CKD (hazard ratio, 0.94 [95% CI, 0.93-0.96], P < 0.001).14Du S. Kim H. Crews D.C. White K. Rebholz C.M. Association between ultraprocessed food consumption and risk of incident CKD: a prospective cohort study.Am J Kidney Dis. 2022; 80: 589-598.e1https://doi.org/10.1053/j.ajkd.2022.03.016Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar There has been recent interest in advising a carbohydrate intake less than the recommended range for CKD patients to preserve kidney function by addressing underlying conditions such as obesity and diabetes. The ketogenic diet, a type of low-carbohydrate diet, is of interest because it metabolizes fat as the body’s main energy source instead of glucose, thereby reducing blood glucose concentrations. Clinical trials assessing low-carbohydrate diets in CKD are limited. Therefore, this guidance is inferred from studies in the general population. Table 1 defines carbohydrate intake patterns based on the percentage of daily carbohydrate consumption derived from various studies.15Oh R. Gilani B. Uppaluri K.R. Low carbohydrate diet.StatPearls. July 11, 2022; https://www.ncbi.nlm.nih.gov/books/NBK537084/Google Scholar It is unclear whether these diets benefit body weight control and cardiovascular risk. A Cochrane review meta-analyzed 61 trials that randomized 6,925 participants, who were either overweight or living with obesity, to either low-carbohydrate (<45% of total energy) or balanced-carbohydrate weight-reducing diets (>45% of total energy).16Naude C.E. Schoonees A. Nguyen K.A. et al.Low carbohydrate versus balanced carbohydrate diets for reducing weight and cardiovascular risk.Cochrane Database Syst Rev. 2022; 1: CD013334https://doi.org/10.1002/14651858.CD013334.pub2Crossref PubMed Scopus (5) Google Scholar They reported little to no difference in weight loss (mean difference, −0.93 [95% CI, −1.81 to 0.04] kg; I2 = 40%) between these diets over the span of 1 to 2 years. The presence of type 2 diabetes mellitus (T2DM) did not modify this conclusion, nor was glycemic control affected. Although some highly adherent individuals had a remarkable response to the diet, in published trials the benefits mostly waned after 12 months.17Joshi S. Ostfeld R.J. McMacken M. The ketogenic diet for obesity and diabetes—enthusiasm outpaces evidence.JAMA Internal Med. 2019; 179: 1163-1164https://doi.org/10.1001/jamainternmed.2019.2633Crossref PubMed Scopus (75) Google Scholar, 18Clifton P. Condo D. Keogh J. Long term weight maintenance after advice to consume low carbohydrate, higher protein diets—a systematic review and meta analysis.Nutr Metab Cardiovasc Dis. 2014; 24: 224-235https://doi.org/10.1016/j.numecd.2013.11.006Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 19Bueno N.B. de Melo I.S.V. de Oliveira S.L. da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.Br J Nutr. 2013; 110: 1178-1187https://doi.org/10.1017/S0007114513000548Crossref PubMed Scopus (458) Google ScholarTable 1Dietary Classification of Carbohydrate ConsumptionCarbohydrate Diet ClassificationPercent of Daily Energy Intake From CarbohydratesVery-low-carbohydrate diet<10% carbohydratesLow-carbohydrate diet10%-25% carbohydratesModerate-carbohydrate diet26%-44% carbohydratesHigh-carbohydrate diet≥45% carbohydratesBased on information in Oh et al15Oh R. Gilani B. Uppaluri K.R. Low carbohydrate diet.StatPearls. July 11, 2022; https://www.ncbi.nlm.nih.gov/books/NBK537084/Google Scholar; percentages based on total calories. Open table in a new tab Based on information in Oh et al15Oh R. Gilani B. Uppaluri K.R. Low carbohydrate diet.StatPearls. July 11, 2022; https://www.ncbi.nlm.nih.gov/books/NBK537084/Google Scholar; percentages based on total calories. The 2020 KDOQI nutrition guideline recommends a low protein intake (0.55-0.60 g/kg/d without diabetes, 0.6-0.8 g/kg/d with diabetes) for patients with CKD stages 3-5 to retard the progression to kidney failure and prevent uremic symptoms.20Ikizler T.A. Burrowes J.D. Byham-Gray L.D. et al.KDOQI clinical practice guideline for nutrition in CKD: 2020 update.Am J Kidney Dis. 2020; 76 (3)(suppl 1):S1-S107https://doi.org/10.1053/j.ajkd.2020.05.006Abstract Full Text Full Text PDF Scopus (581) Google Scholar Low-carbohydrate/high-protein diets may conflict with this recommendation because excess protein intake can promote kidney injury21Ko G.-J. Rhee C.M. Kalantar-Zadeh K. Joshi S. The effects of high-protein diets on kidney health and longevity.J Am Soc Nephrol. 2020; 31: 1667-1679https://doi.org/10.1681/ASN.2020010028Crossref PubMed Scopus (79) Google Scholar due to hyperfiltration and increased intraglomerular pressure.5Kalantar-Zadeh K. Fouque D. Nutritional management of chronic kidney disease.N Engl J Med. 2017; 377: 1765-1776https://doi.org/10.1056/NEJMra1700312Crossref PubMed Scopus (327) Google Scholar Clinically, this may be observed as a rise in estimated or measured GFR. In a randomized, crossover feeding trial of 163 participants without CKD, those consuming a low–glycemic index diet, a low-carbohydrate diet, or both had an increase in eGFR based on cystatin C of 1.9 to 4.5 mL/min/1.73 m2 compared with those eating a reference diet that was high in carbohydrates and glycemic index.22Juraschek S.P. Chang A.R. Appel L.J. et al.Effect of glycemic index and carbohydrate intake on kidney function in healthy adults.BMC Nephrol. 2016; 17: 1-10https://doi.org/10.1186/s12882-016-0288-5Crossref PubMed Scopus (17) Google Scholar The increase in GFR has been shown by other studies.23Schwingshackl L. Hoffmann G. Comparison of high vs. normal/low protein diets on renal function in subjects without chronic kidney disease: a systematic review and meta-analysis.PloS One. 2014; 9e97656https://doi.org/10.1371/journal.pone.0097656Crossref Scopus (81) Google Scholar The possibility of harm is suggested in a community-based observational study of 1,797 persons who were observed for a mean of 6.1 years and responded to a food frequency questionnaire.24Farhadnejad H. Asghari G. Emamat H. Mirmiran P. Azizi F. Low-carbohydrate high-protein diet is associated with increased risk of incident chronic kidney diseases among Tehranian adults.J Renal Nutr. 2019; 29: 343-349https://doi.org/10.1053/j.jrn.2018.10.007Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar In those adhering to a low-carbohydrate/high-protein diet, there was an association with a higher risk of developing CKD (odds ratio, 1.48 [95% CI, 1.03-2.15]). Trials, however, generally fail to observe signs of kidney injury. In a meta-analysis of randomized controlled trials (RCTs) of up to 2 years’ duration there was nearly no change in eGFR in those consuming low-carbohydrate diets compared with those eating control diets of higher carbohydrate content.25Oyabu C. Hashimoto Y. Fukuda T. et al.Impact of low-carbohydrate diet on renal function: a meta-analysis of over 1000 individuals from nine randomised controlled trials.Br J Nutr. 2016; 116: 632-638https://doi.org/10.1017/S0007114516002178Crossref PubMed Scopus (27) Google Scholar Another meta-analysis of RCTs of patients with diabetes and normal eGFR suggested no difference in any measure of kidney function with this diet intervention.26Suyoto P.S.T. Effect of low-carbohydrate diet on markers of renal function in patients with type 2 diabetes: a meta-analysis.Diabetes Metab Res Rev. 2018; 34e3032https://doi.org/10.1002/dmrr.3032Crossref PubMed Scopus (14) Google Scholar Both meta-analyses noted that the RCTs considered carbohydrate intakes ranging from <4% to 43% at initiation, reported substantial dropout rates, and had nonadherence issues that may have confounded the effects reported. Admittedly, the short duration of the trials (up to 2 years) may have limited their ability to detect long-term kidney damage. All in all, current evidence suggests little benefit to low-carbohydrate diets in managing CKD and its complications. There is a possibility of harm by high protein intake, but the short duration of these trials prevents us from establishing a clear cause and effect. It is possible to consume a low-carbohydrate diet that also limits protein consumption to amounts recommended in the KDOQI guideline by increasing the fat content of the diet. However, when taken to the extreme this type of diet can become a ketogenic diet. The ketogenic diet generally draws at least 70% of calories from fat with no more than 15% of calories from carbohydrates. The remaining calories come from protein, but protein excess is avoided so that gluconeogenic substrates are not created. Table 2 lists the macronutrient breakdowns of several ketogenic diets used in studies as effective treatments for diseases such as epilepsy, cancer, and Alzheimer disease.27Charlie Foundation for Ketogenic TherapiesTherapies: diet variations.https://charliefoundation.org/diet-plans/Date: 2021Date accessed: May 7, 2022Google Scholar Ketogenic diets recently have also become popular for the treatment of obesity and T2DM. Meta-analyses of mostly short-term (<12 months) trials have shown substantial decreases in glycemic markers and weight.28Rafiullah M. Musambil M. David S.K. Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis.Nutri Rev. 2022; 80: 488-502https://doi.org/10.1093/nutrit/nuab040Crossref PubMed Scopus (13) Google Scholar However, it may be difficult to adhere to this dietary pattern for long: trials report high dropout rates and/or increased consumption of carbohydrates that prevent ketosis.17Joshi S. Ostfeld R.J. McMacken M. The ketogenic diet for obesity and diabetes—enthusiasm outpaces evidence.JAMA Internal Med. 2019; 179: 1163-1164https://doi.org/10.1001/jamainternmed.2019.2633Crossref PubMed Scopus (75) Google Scholar A meta-analysis of long-term trials (with a duration of >12 months) randomizing individuals to very-low-carbohydrate ketogenic diets (<10% of energy from carbohydrates) or low-fat diets (<30% of energy from fat) showed that those on the ketogenic diet achieved a statistically significant but small reduction in weight of 0.9 kg.19Bueno N.B. de Melo I.S.V. de Oliveira S.L. da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.Br J Nutr. 2013; 110: 1178-1187https://doi.org/10.1017/S0007114513000548Crossref PubMed Scopus (458) Google Scholar No difference was seen in glycemic control at 12 months between both diets.Table 2Macronutrient Contents of Various Ketogenic DietsMacronutrient RatioaMacronutrient ratio is the relationship between the grams of fat to the grams of protein plus carbohydrate (fat:protein + carbohydrates). In a 4:1 ratio there are four times the amount of fat in grams as there is protein and carbohydrate.Percent of Total CaloriesFatProteinCarbohydrateClassic keto (4:1)90%6%4%Modified keto (3:1)87%10%3% (2:1)82%12%6% (1:1)70%15%15%MCT oil (1.9:1)50%/21%b50% MCT/21% LCT, where MCT refers to medium-chain triglycerides and LCT refers to long-chain triglycerides.19%10%Low glycemic index treatment (2:3)60%28%12%Modified Atkins diet (0.8:1)65%29%-32%3%-6%Reproduced in modified form courtesy of Beth Zupec-Kania from Table12 of Zupec-Kania et al72Zupec-Kania B. Vanatta L. Johnson M. Ketogenic Diet Therapies for Neurological Disorders: Pocket Guide.4th ed. Charlie Foundation, 2018Google Scholar; original content ©2018 The Charlie Foundation.a Macronutrient ratio is the relationship between the grams of fat to the grams of protein plus carbohydrate (fat:protein + carbohydrates). In a 4:1 ratio there are four times the amount of fat in grams as there is protein and carbohydrate.b 50% MCT/21% LCT, where MCT refers to medium-chain triglycerides and LCT refers to long-chain triglycerides. Open table in a new tab Reproduced in modified form courtesy of Beth Zupec-Kania from Table12 of Zupec-Kania et al72Zupec-Kania B. Vanatta L. Johnson M. Ketogenic Diet Therapies for Neurological Disorders: Pocket Guide.4th ed. Charlie Foundation, 2018Google Scholar; original content ©2018 The Charlie Foundation. Two short-term trials evaluated these diets in CKD patients. Goday et al29Goday A. Bellido D. Sajoux I. et al.Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.Nutr Diabetes. 2016; 6 (e230-e230)https://doi.org/10.1038/nutd.2016.36Crossref PubMed Scopus (154) Google Scholar conducted a RCT of 89 participants with T2DM over 4 months and showed no difference in kidney function markers between those consuming a ketogenic diet and a control, low-calorie diet (500-1,000 kcal/d). Another nonrandomized, prospective study by Bruci et al30Bruci A. Tuccinardi D. Tozzi R. et al.Very low-calorie ketogenic diet: a safe and effective tool for weight loss in patients with obesity and mild kidney failure.Nutrients. 2020; 12: 333https://doi.org/10.3390/nu12020333Crossref PubMed Scopus (86) Google Scholar of 92 patients, 38 with CKD stage 2 and 54 with normal kidney function, following a very-low-calorie ketogenic diet (450-800 kcal/d) for approximately 3 months also showed no difference in serum creatinine or eGFR. However, in a separate analysis of those with an eGFR of 60-89 mL/min/1.73 m2, the participants had a statistically significant increase in eGFR from 76.32 to 82.21 mL/min/1.73 m2.30Bruci A. Tuccinardi D. Tozzi R. et al.Very low-calorie ketogenic diet: a safe and effective tool for weight loss in patients with obesity and mild kidney failure.Nutrients. 2020; 12: 333https://doi.org/10.3390/nu12020333Crossref PubMed Scopus (86) Google Scholar Although the researchers attributed the amelioration in eGFR to the diet itself, this effect was not seen in the Goday et al29Goday A. Bellido D. Sajoux I. et al.Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.Nutr Diabetes. 2016; 6 (e230-e230)https://doi.org/10.1038/nutd.2016.36Crossref PubMed Scopus (154) Google Scholar study, which also studied patients with a similar eGFR; the change may have been explained by other causes such as an increase in dietary animal protein consumption (baseline protein consumption not reported) or a reduction in dosage of medications that inhibit the renin-angiotensin-aldosterone system (one-third of those on antihypertensive medications had a reduction in dosage or discontinuation of an antihypertensive medication). Ketogenic diets may be of interest in the treatment of polycystic kidney disease (PKD) because they have shown to reduce the growth of cysts in animal models.31Torres J.A. Kruger S.L. Broderick C. et al.Ketosis ameliorates renal cyst growth in polycystic kidney disease.Cell Metab. 2019; 30: 1007-1023. e5https://doi.org/10.1016/j.cmet.2019.09.012Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Human trials in this area are in progress. A feasibility study of a plant-focused ketogenic diet was conducted with 20 participants who had autosomal dominant PKD with an eGFR range of 24-94 mL/min/1.73 m2.32Bruen D.M. Kingaard J.J. Munits M. et al.Ren.Nu, a dietary program for individuals with autosomal-dominant polycystic kidney disease implementing a sustainable, plant-focused, kidney-safe, ketogenic approach with avoidance of renal stressors.Kidney Dial. 2022; 2: 183-203https://doi.org/10.3390/kidneydial2020020Crossref Google Scholar Favorable results were reported, including average decreases in body weight by 5.6% and fasting blood glucose levels by 16.5%, along with an average increase in eGFR of 8.6%. These diets, however, may be associated with health risks. Observational studies have associated the consumption of saturated fat and animal fat, which are prominent features of traditional ketogenic diets, with an increase in albuminuria.33Lin J. Hu F.B. Curhan G.C. Associations of diet with albuminuria and kidney function decline.Clin J Am Soc Nephrol. 2010; 5: 836-843https://doi.org/10.2215/CJN.08001109Crossref PubMed Scopus (157) Google Scholar,34Lin J. Judd S. Le A. et al.Associations of dietary fat with albuminuria and kidney dysfunction.Am J Clin Nutr. 2010; 92: 897-904https://doi.org/10.3945/ajcn.2010.29479Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Specific concerns regarding the use of ketogenic diets include an increased net acid load, with possible worsening of metabolic acidosis, and the risk of nephrolithiasis, which have all been reported in pediatric patients using the ketogenic diet for the treatment of epilepsy.17Joshi S. Ostfeld R.J. McMacken M. The ketogenic diet for obesity and diabetes—enthusiasm outpaces evidence.JAMA Internal Med. 2019; 179: 1163-1164https://doi.org/10.1001/jamainternmed.2019.2633Crossref PubMed Scopus (75) Google Scholar,35Crosby L. Davis B. Joshi S. et al.Ketogenic diets and chronic disease: weighing the benefits against the risks.Front Nutr. 2021; 8702802https://doi.org/10.3389/fnut.2021.702802Crossref PubMed Scopus (56) Google Scholar Other potential risks of this diet include the potential to cause dyslipidemia and hyperlipidemia and an increased risk of mortality in observational studies.36Seidelmann S.B. Claggett B. Cheng S. et al.Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis.Lancet Public Health. 2018; 3: e419-e428https://doi.org/10.1016/S2468-2667(18)30135-XAbstract Full Text Full Text PDF PubMed Scopus (415) Google Scholar,37Kirkpatrick C.F. Bolick J.P. Kris-Etherton P.M. et al.Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: a scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force.J Clin Lipidol. 2019; 13: 689-711.e1https://doi.org/10.1016/j.jacl.2019.08.003Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar The increase in low-density lipoprotein and apolipoprotein B is concerning in patients with CKD, which is a population already at an increased risk for CVD.37Kirkpatrick C.F. Bolick J.P. Kris-Etherton P.M. et al.Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: a scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force.J Clin Lipidol. 2019; 13: 689-711.e1https://doi.org/10.1016/j.jacl.2019.08.003Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar In order to preserve cardiovascular health, it has been recommended that the carbohydrate and fat intake come from unprocessed, fiber-rich, plant sources.38Arnett D.K. Blumenthal R.S. Alber