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DOI: 10.1016/j.nefroe.2020.05.008
Open Access
Available online 5 September 2021
Ketoacid analogues in patients with chronic kidney disease
Análogos de cetoácidos en pacientes con enfermedad renal crónica
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Sandra Martínez-Pizarro
Hospital Comarcal de Huércal Overa, Huércal-Overa, Almería, Spain
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Dear Editor,

Nutrition is a key component of the care of chronic kidney disease (CKD) patients. Management of dietary protein intake is the basis of nutritional treatment of these patients aiming to reduce the uraemic toxin and reduce uraemic toxicity and delay the need for dialysis. To reduce the risk of nutritional disorders in low-protein diets (LPD) and very low-protein diets (VLPD), studies in recent years have proposed supplementation with nitrogen-free ketoacids (KA) in patients with CKD.1

The review by Koppe et al.2 conducted in France and Brazil in 2019 analysed the effects of KA supplementation on renal function. It included 23 randomised clinical trials and 12 experimental studies. The results shows that LPD/VLPD + KA appears to be nutritionally safe. VLPD + KA appears to lower the production of uraemic toxins, but the impact on the intestinal microbiota has not yet been explored. All studies observed a reduction in acidosis, phosphorous and possible sodium intake, while providing an adequate calcium intake. The impact of this diet on carbohydrate and bone parameters is preliminary and needs to be confirmed with further studies. The most recent meta-analyses and clinical trials suggest that these diets may reduce the rate of glomerular filtration loss over and above the beneficial effects of renin inhibitors on the angiotensin–aldosterone system. Current evidence suggests that LPDs supplemented with KA should be included as part of the clinical recommendations for both nutritional prevention and metabolic management of CKD.

The study by Wang et al.3 conducted in China in 2019 explored alternative mechanisms by which KA supplements influence kidney injury and the effects of KA administration on CKD progression in Chinese patients with different stages of CKD. The results revealed that KA has a protective effect on kidney injury and fibrosis by attenuating inflammatory infiltration and apoptosis through the inhibition of the nuclear factor kappa B and mitogen-activated protein kinase pathways. Stage 4 and 5 patients in the KA group presented a much slower and more delayed incidence of glomerular filtration rate (GFR) reduction compared with those in the group without KA, demonstrating a protective effect of KA on CKD progression. KA improved chronic kidney damage and fibrosis, and appears to be a prospective protective factor in end-stage renal disease.

The study by Zemchenkov et al.4 conducted in Russia in 2016 assessed the effect of essential amino acids (EAA) and KA on CKD progression. The effect of LPD supplemented by EAA/KA on changes in GFR slope between the first and second treatment periods (five sequential visits per period) in 96 patients with stage 3B-5 CKD was compared with changes in GFR slope in the control group of 96 patients, selected at random from a paired cohort of 320 patients. The results revealed that LPD combined with EAA/KA supplementation leads to a reduction in CKD progression in both well-designed clinical studies and real nephrology practice in very varied diseases and settings. The therapy’s effect was strongest in older patients with higher proteinuria, lower phosphate levels, patients with glomerular and interstitial disease and in women.

After analysing the above scientific studies conducted in recent years, it can be seen that KA has potential as a supplement to LPD for patients with CKD. This treatment has the capacity to improve patients’ clinical and metabolic status, thereby improving their quality of life and delaying dialysis.

However, although the evidence reviewed appears to indicate that positive results can be expected from KA supplementation, the limited body of research in humans and the low sample numbers in the studies are insufficient for making general recommendations. Hence, there is a need for more studies in this field. This will make it possible to examine the efficacy and possible short- and long-term complications of this treatment, explore its possible synergistic effect with other therapies, and analyse the most appropriate dose and economic viability. This would in turn allow healthcare professionals to offer their patients the best care based on the latest scientific evidence.

Funding

The authors declare that they received no funding to conduct this study.

References
[1]
A. Cupisti, P. Bolasco.
Keto-analogues and essential aminoacids and other supplements in the conservative management of chronic kidney disease.
Panminerva Med, 59 (2017), pp. 149-156
[2]
L. Koppe, M. Cassani de Oliveira, D. Fouque.
Ketoacid analogues supplementation in chronic kidney disease and future perspectives.
[3]
M. Wang, H. Xu, O.L. Chong Lee Shin, L. Li, H. Gao, Z. Zhao, et al.
Compound α-keto acid tablet supplementation alleviates chronic kidney disease progression via inhibition of the NF-kB and MAPK pathways.
J Transl Med, 17 (2019), pp. 122
[4]
A. Zemchenkov, I.N. Konakova.
Efficacy of the essential amino acids and keto-analogues on the CKD progression rate in real practice in Russia - city nephrology registry data for outpatient clinic.
BMC Nephrol, 17 (2016), pp. 62

Please cite this article as: Martínez-Pizarro S. Análogos de cetoácidos en pacientes con enfermedad renal crónica. Nefrologia. 2020. https://doi.org/10.1016/j.nefro.2020.05.011

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