What does the research show about ketoanalogues?

Ketoanalogues

Several meta-analyses of trials in chronic kidney disease report slower eGFR decline and lower phosphate when ketoanalogues are added to a low-protein diet, compared with the diet alone. Effects on reaching dialysis are smaller and less consistent. Death rates did not differ. Blood calcium rose, and nutrition markers held steady.

Add to Bio HackChecked 2026-11-09

Status: Not approved by the FDA for any use, and not listed in the FDA's Drugs@FDA or National Drug Code databases as of 2026-11-04. Sold as a medicine under the name Ketosteril outside the US.
Also called: keto acid analogues, ketoacid analogues, keto-analogues of essential amino acids, alpha-keto acids, KA, Ketosteril, calcium ketoleucinate, ketoanalogue-supplemented low-protein diet
Taken for: kidney health, chronic kidney disease, slowing kidney decline, delaying dialysis, low-protein diet

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

StrongShown to slow kidney function decline in adults with chronic kidney disease when added to a protein-restricted diet. Diet and supplement effects overlap.
StrongShown to lower blood phosphate, urea and parathyroid hormone in adults with chronic kidney disease on a protein-restricted diet.

Reported risks1

ModerateShown to raise blood calcium in adults with chronic kidney disease, mainly when paired with a low-protein diet.How often is not known

What people take it for, and what was found

Shown to help2

Strong

Kidney function decline in chronic kidney disease

Shown to slow kidney function decline in adults with chronic kidney disease when added to a protein-restricted diet. Diet and supplement effects overlap.

The numbers and sources

Effect: In 16 RCTs (1,344 people with stage 3 to 5 CKD, median 13 months), ketoanalogues added to a protein-restricted diet gave a higher GFR than a low-protein diet alone, and a marginally lower risk of kidney failure in people without diabetes [1]. In 17 RCTs (1,459 participants), protein-restricted diets with ketoanalogues preserved eGFR and reduced proteinuria and blood pressure, with a larger eGFR effect on very low-protein diets [2]. In 10 RCTs and 2 non-randomized studies (951 patients), the combination delayed CKD progression (p 0.008), particularly with eGFR above 18 mL/min/1.73 m² [3]. In diabetic kidney disease, a review of 11 studies reported pooled GFR and urinary protein results in favor of ketoanalogues [4]. In non-diabetic adults with eGFR below 30, a ketoanalogue-supplemented vegetarian very low-protein diet for 15 months reduced the composite of starting dialysis or losing half of eGFR (number needed to treat 4.4) against a conventional low-protein diet [5].
Population: Adults with CKD stages 3 to 5 not on dialysis [1][2][3][5]. Adults with diabetic kidney disease not on dialysis [4].
Sources: [1], [2], [3], [4], [5]
Caveats: Many trials paired ketoanalogues with a stricter diet than the control arm, so the effects of diet and supplement overlap [2][5]. Only 14% of screened patients were randomized in [5]. The authors of [1] call for larger, longer trials, especially in diabetes. A Cochrane review of very low-protein diets, with or without ketoanalogues, found 165 fewer people per 1,000 reached kidney failure than on a low-protein diet (RR 0.65, 95% CI 0.49 to 0.85, moderate certainty) [6].

Strong

Phosphate and parathyroid hormone

Shown to lower blood phosphate, urea and parathyroid hormone in adults with chronic kidney disease on a protein-restricted diet.

The numbers and sources

Effect: Ketoanalogues added to a protein-restricted diet lowered blood urea nitrogen and phosphorus and raised calcium against a low-protein diet alone [1]. In 17 RCTs, they lowered serum phosphate and parathyroid hormone [2].
Population: Adults with CKD not on dialysis [1][2].
Sources: [1], [2]
Caveats: These are blood markers, not fractures or heart events.

Risks

Reported risks1

ModerateHow often is not known

Blood calcium

Shown to raise blood calcium in adults with chronic kidney disease, mainly when paired with a low-protein diet.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Blood calcium rose with ketoanalogues against a low-protein diet alone [1]. In a second meta-analysis, calcium rose significantly only when ketoanalogues were paired with a low-protein diet, not a very low-protein diet [2].
Population: Adults with CKD [1][2].
Sources: [1], [2]
Caveats: The abstracts do not report how many people developed high calcium.

Checked, no increase found1

Moderate

Nutritional status

Nutritional measures such as albumin and lean mass did not differ from a low-protein diet alone in adults with chronic kidney disease.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: Albumin, mid-arm muscle circumference, lean body mass and subjective global assessment did not differ from a low-protein diet alone [1]. Albumin and cholesterol did not fall against placebo [3]. In the 15-month trial, nutritional measures did not change and no adverse reactions occurred [5]. Across protein restriction trials, 12 studies reported no protein energy wasting and 3 reported small numbers in each group [6].
Population: Adults with CKD [1][3][5][6].
Sources: [1], [3], [5], [6]
Caveats: The 15-month trial enrolled well-nourished patients who had followed the diet in a run-in phase [5]. Few studies reported weight [6].

Claims tested and not found

That ketoanalogues with a low-protein diet lower death rates in CKD. All-cause mortality did not differ against a low-protein diet alone in 16 RCTs [1].

Sources

Chen CH, Tsai PH, Tsai WC, et al. Efficacy and safety of ketoanalogue supplementation combined with protein-restricted diets in advanced chronic kidney disease: a systematic review and meta-analysis. Journal of Nephrology. 2024. https://doi.org/10.1007/s40620-024-02065-9
Chewcharat A, Takkavatakarn K, Wongrattanagorn S, et al. 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. Journal of Renal Nutrition. 2020. https://doi.org/10.1053/j.jrn.2019.07.005
Li A, Lee HY, Lin YC. The Effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-Analysis. Nutrients. 2019. https://doi.org/10.3390/nu11050957
Bellizzi V, Garofalo C, Ferrara C, et al. Ketoanalogue Supplementation in Patients with Non-Dialysis Diabetic Kidney Disease: A Systematic Review and Meta-Analysis. Nutrients. 2022. https://doi.org/10.3390/nu14030441
Garneata L, Stancu A, Dragomir D, et al. Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression. Journal of the American Society of Nephrology. 2016. https://doi.org/10.1681/ASN.2015040369
Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD001892.pub4

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