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Can Ketoanalogues Help with Kidney Disease? - Albutrix, Ketosteril, Ketorena

What are Ketoanalogues

Ketoanalogues are amino acids that contain no nitrogen. Essentially it provides protein to the body without adding any nitrogen into the diet. This is of great interest because many of the main toxins that buildup in the body in those with kidney disease are primarily due to the accumulation of excess nitrogen. This nitrogen is harmful because it leads to the production of major nitrogen-based toxins, such as urea, uric acid, and ammonia. When these rise to high enough levels this is called uremia, a common complication of kidney disease. This can cause damage to the lungs, heart, brain, skin and other organs. Furthermore, research suggests patients with kidney disease who maintain lower levels of nitrogen-based toxins in the body tend to have slower rates of kidney disease progression.[1]

Why Are Ketoanalogues Used?

Ketoanalogues are used as a nitrogen-free protein alternative for the body. The idea is that it allows a person to consume the same amount of protein (amino acids) without causing a buildup of urea, ammonia and other wastes in the body. Consuming enough protein is very important in kidney disease because protein is used by every cell and organ in the body. The challenge is protein is normally restricted because the kidney cannot handle as much protein in kidney disease. The hope is that ketoanalogues offer a way to provide protein without harming the kidneys.

What Does Research Suggest?

There is a mix of research, some positive, negative or inconclusive. Undoubtedly, there is some concern, as there are a number of negative studies that suggest there may be potential harm. That being said, the largest studies have shown some promising results and are better built to detect risks and benefits. These studies have shown that benefits generally outweigh the risks. Although, there are other factors that appear to affect study results as well, such as dosing and total protein intake.

Negative Research Studies

A 2009 study compared a low protein diet to a very low protein diet with ketoanalogue supplementation in those with kidney disease.[2] There was a small trend towards slowed progression of kidney disease in the ketoanalogue group, however this group had nearly double the rate of mortality. So even though it may have benefits to the kidney, when used in combination with a very low protein diet it appears overall health and nutrition may be impacted, leading to lower overall longevity. That being said, due to the size of the study (255 patients), the results just slightly passed the level of statistical significance (a measure of whether a result is due to random chance). In addition, it used extremely low protein intake in the ketoanalogue group - which can adversely affect longevity.

There was a 2020 study that found those using ketoanalogues had a 41% increased risk of mortality and 41% increased risk of requiring dialysis in comparison to those not using ketoanalogues. This study used higher protein intake and the risk of mortality was lower compared to the previous study above. In addition, the mortality statistic no longer reached statistical significance (SS).[3] Again, this study was small (330 patients), and hence results are difficult to interpret.

A 2022 study found 17% increased risk of mortality, 12% increased risk of progression to end stage renal disease (again the study was not quite large enough to reach SS - 223 patients).[4]

Positive Research Studies

A large 2019 study combined the results of several studies and found:[5]

3.14 point improvement in GFR (kidney function)

.86 point improvement in protein loss

4.96 point improvement in blood pressure (systolic)

A trend towards reduced muscle mass (a little concerning, but this was minimal and not SS)

This study was a reasonable size - with 1,459 patients.

A 2017 study studied 1483 patients over an average of 1.57 years and found that:[6]

Risk of requiring dialysis decreased in half (48% reduction)

Risk of mortality or requiring dialysis decreased by more than half (57% reduction)

These effects existed regardless of whether diabetes, hypertension or nephrotic syndrome was present

A 2021 study followed 15,782 non–dialysis patients with stage 5 CKD and diabetes for 5 years and found:[7]

34.7% (ketoanalogue users) versus 42.7% (non-users) 5-year mortality rate

27% reduced risk of mortality (after adjusting for confounders)

Those with either long duration of use (>8 months) or higher dose of KA had double the rate of survival compared to those who did not use ketoanalogues

This is the largest study and the results were statistically significant. These results outweigh most of the other studies above due to the sheer size.

Ketoanalogues Available

There are several companies that sell ketoanalogues. Some examples of ketoanalogue products on the market include: Albutrix, Ketosteril, and Ketorena. Some of these may not be as well regulated as certain brands and they can be difficult to source. Furthermore, not all of these products have been tested in clinical research trials. Lastly, depending on a number of blood work readings, some of these products have added ingredients that may be harmful to certain individuals.

Concluding Remarks

Nutrition is very complex in kidney disease and there are many factors that can affect long term success. It is important to speak with a health professional before deciding on any therapies. Dr. Baker (ND) can discuss options in more detail during a Naturopathic consultation and considers all therapies after a comprehensive intake and assessment of your case and blood work.

[1] Gonçalves DLN, Moreira TR, da Silva LS. A systematic review and meta-analysis of the association between uric acid levels and chronic kidney disease. Sci Rep. 2022 Apr 15;12(1):6251. doi: 10.1038/s41598-022-10118-x. PMID: 35428828; PMCID: PMC9012819. [2] Menon V, Kopple JD, Wang X, Beck GJ, Collins AJ, Kusek JW, Greene T, Levey AS, Sarnak MJ. Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis. 2009 Feb;53(2):208-17. doi: 10.1053/j.ajkd.2008.08.009. Epub 2008 Oct 31. PMID: 18950911. [3] Wang YC, Juan SH, Chou CL, Hsieh TC, Wu JL, Fang TC. Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet. Nutrients. 2020 Sep 4;12(9):2708. doi: 10.3390/nu12092708. PMID: 32899821; PMCID: PMC7551296. [4] Bellizzi V, Signoriello S, Minutolo R, Di Iorio B, Nazzaro P, Garofalo C, Calella P, Chiodini P, De Nicola L; ERIKA Study Group Investigators of the Italian Society of Nephrology-Conservative Therapy of CKD Work Group. No additional benefit of prescribing a very low-protein diet in patients with advanced chronic kidney disease under regular nephrology care: a pragmatic, randomized, controlled trial. Am J Clin Nutr. 2022 May 1;115(5):1404-1417. doi: 10.1093/ajcn/nqab417. PMID: 34967847. [5] Chewcharat A, Takkavatakarn K, Wongrattanagorn S, Panrong K, Kittiskulnam P, Eiam-Ong S, Susantitaphong P. The Effects of Restricted Protein Diet Supplemented With Ketoanalogue on Renal Function, Blood Pressure, Nutritional Status, and Chronic Kidney Disease-Mineral and Bone Disorder in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis. J Ren Nutr. 2020 May;30(3):189-199. doi: 10.1053/j.jrn.2019.07.005. Epub 2019 Oct 10. PMID: 31607548. [6] Wu CH, Yang YW, Hung SC, Kuo KL, Wu KD, Wu VC, Hsieh TC; National Taiwan University Study Group on Acute Renal Failure (NSARF). Ketoanalogues supplementation decreases dialysis and mortality risk in patients with anemic advanced chronic kidney disease. PLoS One. 2017 May 5;12(5):e0176847. doi: 10.1371/journal.pone.0176847. PMID: 28475591; PMCID: PMC5419544. [7] Chen HY, Sun CY, Lee CC, Wu IW, Chen YC, Lin YH, Fang WC, Pan HC. Ketoanalogue supplements reduce mortality in patients with pre-dialysis advanced diabetic kidney disease: A nationwide population-based study. Clin Nutr. 2021 Jun;40(6):4149-4160. doi: 10.1016/j.clnu.2021.01.045. Epub 2021 Feb 6. PMID: 33597108.


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