A NEW APPROACH: KETOGENIC DIET FOR POLYCYSTIC KIDNEY DISEASE
Updated: Mar 24
Polycystic kidney disease (PKD) is a genetic disorder in which the growth of numerous cysts in the kidneys is formed. PKD cysts can cause enlargement of kidneys resulting in abnormal structure, thus reducing kidney function and even kidney failure. PKD can also cause cysts in different organs like the liver blood vessels in the heart and in the brain.
There are two major inherited types of PKD found.
1. Autosomal dominant PKD is a common form of inherited disease. Symptoms occur between the ages of 30 & 40, but they can occur in earlier stages also even during childhood. Almost 90 percent of all PKD are autosomal dominant PKD.
2. Autosomal recessive PKD is a rare form of inherited disease. Symptoms of autosomal recessive PKD occur in the earliest months of life, or even in the womb.
Polycystic kidney disease is affecting one in 1,000 people in the whole world. In Germany, this results in approximately 80,000 ADPKD patients. About 50 percent of these patients have renal function impairment with advancing age.
Fig. The polycystic kidney roughly retains the same size as of normal kidney.
Source: U.S. Department of health and human service. National Institute Health NIH Publication No. 08–4008 November 2007.
Mild reduction in food intake was recently shown to slow polycystic kidney disease (PKD) progression in mouse models, but whether the effect was due to solely reduced calories, or some other aspect of the diet has been unclear. The benefit is due to the induction of ketosis. Time-restricted feeding, without caloric reduction, strongly inhibits mTOR signaling, proliferation, and fibrosis in the affected kidneys in a PKD rat model. A ketogenic diet had a similar effect and led to regression of renal cystic burden. Acute fasting in rat, mouse, and feline models of PKD results in a rapid reduction of cyst volume, while oral administration of the ketone b-hydroxybutyrate (BHB) in rats strongly inhibits PKD progression. These results suggest that cystic cells in PKD are metabolically inflexible, which could be exploited by dietary interventions or supplementation with BHB, representing a new therapeutic avenue to treat PKD. 
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease characterized by slowly progressive cyst growth in both kidneys, which leads to deterioration of renal function over the course of several decades, necessitating dialysis or kidney transplantation 
Cysts derived from tubule epithelial cells exhibit changes in proliferation and metabolism and activation of signaling pathways that are normally dormant in healthy adult kidneys, such as mTOR and STAT signaling .
Source: Torres, J. A., Kruger, S. L., Broderick, C., Amarlkhagva, T., Agrawal, S., Dodam, J. R., Mrug, M., Lyons, L. A., &Weimbs, T. (2019). Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease. Cell metabolism, 30(6),1007–1023.e5.
ADPKD results from mutations in either the PKD1 or PKD2 genes, coding for polycystin-1 (PC1) and polycystin-2, respectively, but how these two proteins link to the many cellular changes observed within cyst-lining cells is still poorly understood 
A key signaling molecule activated in ADPKD is the kinase mTOR that regulates many cellular behaviors including proliferation, cell growth, and energy metabolism and is normally regulated by numerous inputs including growth factor signaling, cellular energy status, and nutrient availability.
mTOR inhibitors, such as rapamycin, have proved highly effective in PKD rodent models. but unfortunately failed in clinical trials . Most likely, high enough doses cannot be administered over the long term in humans due to significant extra-renal side effects and toxicities.
The researchers published the first evidence that nutritional ketosis which is induced by the ketogenic diet (KD) or time-restricted diet (TRD), ameliorates the disease progression in polycystic kidney disease (PKD). Due to their frequent use for numerous benefits of the health, some autosomal dominant PKD (ADPKD) patients may have had experience with ketogenic dietary interventions (KDIs). The retrospective case series study is designed by the researchers to obtain the first real-life observations of ADPKD patients about the safety, feasibility, and benefits of KDIs in ADPKD.
The study cohort KDIs included 131 ADPKD patients who tried self-initiated KDIs in the past. KDIs included variations of KDs, TRDs, and CR (Caloric Restriction). Participants who were on dialysis or with kidney transplants and on dietary protocols that were not ‘KDI conformable’ were excluded. A separate analysis of participants executing CR showed no significant differences to the other sub-cohorts. Due to the limited number of participants on CR, this subgroup is not separately displayed in the figure.
Source: Sebastian et al, Ketogenic dietary interventions in autosomal dominant polycystic kidney disease—a retrospective case series study: first insights into the feasibility, safety, and effects, Clinical Kidney Journal, 2021; sfab162, https://doi.org/10.1093/ckj/sfab162
FIGURE: The study cohort KDIs. (A) Flow diagram of the case series study cohort KDIs. PKD patients were recruited by the Weimbs Laboratory and the University Hospital of Cologne to participate in questionnaire-based interviews about the experience of PKD patients with KDIs. (B) Description of the study cohort: distribution of age, sex, and type of KDIs. (C) Average time on KDIs. Time on the diet is displayed as the median average. (D) Controlling measures of participants on a KD. Participants were asked how they control to reach ketosis. (E) Self-reported ketone body levels of participants who measured KB in the blood or urine. KB levels are displayed as the median average. N for KB in blood ¼ 24. N for KB in urine ¼ 10. (F) Fasting cycles used by participants executing a TRD. Participants were asked to specify their fasting cycle when practicing a TRD. n ¼ 48. (G) Reason for experimenting with KDIs. Participants were asked why they started a KDI. (H) Resources used for starting a KDI. Participants were asked how they found out about KDIs in PKD. 
Results: A total of 131 ADPKD patients took part in this study. About 74 executed a KD and 52 a TRD for 6 months on average. A total of 86% of participants reported that KDIs had improved their overall health, 67% described improvements in ADPKD associated health issues, 90% observed significant weight loss, 64% of participants with hypertension reported improvements in blood pressure, 66% noticed adverse effects that are frequently observed with KDIs, 22 participants reported safety concerns like hyperlipidemia, 45 participants reported slight improvements in estimated glomerular filtration rate and 92% experienced KDIs as feasible while 53% reported breaks during their diet. 
Polycystic disease is a hereditary and relatively common disease and researchers have long thought polycystic kidney disease (PKD) was irreversible and progressive, condemning people with the condition to a slow, long, and usually painful as fluid-filled cysts formed in the kidneys, grow and eventually damage the organs of their function.
Once kidneys fail, PKD patients usually require dialysis several times a week or must have a kidney transplant. Furthermore, a host of other PKD-related conditions add to the patients’ burden on health, including vascular problems, high blood pressure problems, and cysts inside the liver. And this doesn’t take into account the costs of medical and the reduced life quality.
Progress toward finding a cure has been slow, with only one drug which is proven to be slow but will not stop the progression of PKD. But researchers suggest that diet has emerged as a possible solution.
Ketogenic diet to FIGHT POLYCYSTIC KIDNEY DISEASE
The studies done by researchers show that reducing food intake in mouse models slowed the progression of polycystic kidneys by a specific metabolic process that is responsible for slowing the progress of the disease.
Ketosis is a natural response to fasting. When we fast, our carbohydrate reserves are very quickly used up. In order to not die, our bodies switch over to a different energy source and that comes from our fat reserves.
The body continues to break down the fat reserves into fatty acids and ketones which are then taken by the body to provide energy to the body. The researchers found that having ketones in the blood particular inhibits the growth of the kidney cysts and with the steady supply of ketones, they actually acted to reverse the condition in their animal studies.
The problem with typical Western diets is that we almost never go into ketosis: we eat high-carb, high-sugar foods almost continuously throughout the day, securing for ourselves a continuous supply of glucose. In the ketogenic diet, the body’s typical “go-to” source of energy glucose is taken away as ketogenic dieters focus on low-carbohydrate foods, eventually forcing their bodies to mimic the fasting response. Time-restricted feeders, meanwhile, reach that state by limiting the window of time they eat to a small part of the day, leaving the remaining 16-20 hours of their day for the body to use up the carbs and sugars and switch over into ketosis.
Are you ready for your personalized pH Balanced Ketogenic Diet therapy?
1 U.S department of health and human services National Institutes of Health NIH Publication No. 08–4008 November 2007.
3 Jacob A. Torres, Samantha L. Kruger, Caroline Broderick, ..., Michal Mrug, Leslie A. Lyons, Thomas Weimbs
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