|Year : 2019 | Volume
| Issue : 2 | Page : 51-53
Low-protein diet and very low-protein diet in chronic kidney disease and the role of ketoanalogs in disease retardation
Director, Nephrology and Renal Transplant Service, BLK Super Speciality Hospital, New Delhi, India
|Date of Submission||23-Dec-2019|
|Date of Acceptance||24-Dec-2019|
|Date of Web Publication||08-Jan-2020|
Nephrology and Renal Transplant Service, BLK Super Speciality Hospital, Pusa Road, New Delhi
Source of Support: None, Conflict of Interest: None
Overnutrition is associated with impaired renal function. In renal disease, high protein load acutely increases glomerular filtration rate (GFR) in predialysis stage. Excess protein alters hemodynamics and is converted into urea and other nitrogenous wastes which not only accumulate in the body causing uremic syndrome, but also cause a rapid decline of renal function through increased hyperfiltration and intraglomerular hypertension, severity of micro albuminuria and, over the long term, glomerulosclerosis. This article highlights important studies on very low protein diet.
Keywords: Chronic kidney disease, ketoanalogs, low-protein diet, very low-protein diet
|How to cite this article:|
Prakash S. Low-protein diet and very low-protein diet in chronic kidney disease and the role of ketoanalogs in disease retardation. J Renal Nutr Metab 2019;5:51-3
|How to cite this URL:|
Prakash S. Low-protein diet and very low-protein diet in chronic kidney disease and the role of ketoanalogs in disease retardation. J Renal Nutr Metab [serial online] 2019 [cited 2020 Jul 14];5:51-3. Available from: http://www.jrnm.in/text.asp?2019/5/2/51/275410
| Physiology of Proteins|| |
Protein is an essential macronutrient which is mainly build out of twenty amino acids. They are the essential building material of all our body parts. Of these nine amino acids are essential—histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine which must be obtained from food. Overnutrition is associated with impaired renal function. In renal disease, high protein load acutely increases glomerular filtration rate (GFR) in predialysis stage. Excess protein alters hemodynamics and is converted into urea and other nitrogenous wastes which not only accumulate in the body causing uremic syndrome, but also cause a rapid decline of renal function through increased hyperfiltration and intraglomerular hypertension, severity of micro albuminuria and, over the long term, glomerulosclerosis [Figure 1].,
|Figure 1: Oral or parenteral application of amino acids leads to marked hyperfiltration and increased renal plasma flow. Amino acids stimulate the release of glucagon, which increases hepatic production and release of cyclic adenosine monophosphate (cAMP). In the kidney, the combined effect of cAMP and glucagon increases glomerular filtration rate (GFR), possibly by reducing NaCl concentration at the macula densa and depression of the tubuloglomerular feedback. Vasopressin-dependent urea recycling and delivery to the thick ascending limb could similarly reduce NaCl concentration at the macula densa. Beyond that, amino acids may trigger a hepatorenal reflex or directly interfere with renal function. Mechanisms invoked include dopamine from renal nerves, prostaglandins, nitric oxide (NO), and angiotensin II|
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| Rationale of Prescribing Low Dietary Protein Diets|| |
Protein restricted diet has limited sulphate, phosphates, potassium and sodium and causes less formation of free radicals (lower concentration of free radicals). Restricted intake of phosphates has PTH lowering effect, improves mineral metabolism and decreases or prevents metabolic acidosis Protein restricted diet also reduces proteinuria, increases insulin sensitivity and increases quality of life.
Low dietary protein intake (DPI) prevents glomerulosclerosis by reducing intra glomerular pressure and glomerular hypertrophy and reduces TGF-B and PDGF. Increasing DPI conversely increases GFR by increasing levels of glucagon IGF-I and KININS, RAS and TGF-B.,
| Mechanism of Action of Keto Amino Acids (KAA)|| |
Ketoanalogues lack amino nitrogen. On reaching the body they take endogenous nitrogen and get converted into essential aminoacids (EAA) in liver, muscles and intestines by the process of transamination. Keto analogues of essential amino acids (KAA) efficiently utilize dietary nitrogen by recycling nitrogenous metabolic products and improved nitrogen and amino acid intake in serum and induction of protein anabolism along with reduction in blood urea. Hence a CKD patient remains protein neutral in spite of taking lower protein in diet due to efficient endogenous nitrogen utilization in the body. Ketoanalogue supplemented diet prevents malnutrition.
| Does Ketoanalog-Supplemented Diet Slow Chronic Kidney Disease Progression?|| |
Mitch  studied 24 patients with advanced CKD. Fifty nine percent patients had significantly slower rise in serum creatinine. Forty percent had virtual arrest of the disease progression at average follow up of 20 months. There was no evidence of malnutrition in any patient. Although this study did not have a control group, however, this study showed postponement of dialysis by at least 13 patient years.
IHLE et al did a prospective randomized study of 64 patients for 18 months, 27% patients on regular diet developed end-stage-renal-disease (ESRD) where as only 6% patients on 0.4 gm/kg high biological value(HBV) protein (containing essential amino acids) developed ESRD (p<0.05).
MDRD ,, study took two groups of patients. Group A had 585 patients of GFR 25 to 55ml/min. They were randomly assigned to get 1.3 or 0.58 gm/kg protein and to a usual to low MAP (107 to 92 mmHg). Group B had 255 patients of GFR 13 to 24 ml/min assigned to vLPD (0.28 gm/kg) + KAA or LPD (0.58 g/kg) and a usual or low BP group. Both the groups had average follow up of 2.2 years. This biggest prospective randomized study failed to show any benefit of LPD and vLPD with KAA.
Levey et al re analyzed the MDRD data and showed that 0.2 gm/kg reduction in DPI was associated with 30% slower GFR decline in group B of MDRD study and 50% reduction in risk of ESRD or death (p=0.001).
Menon et al analyzed long term follow up of MDRD study patient group. They reported no retardation in disease progression by vLPD. This important long term follow up study negates any benefit to LPD and vLPD+ KAA diets, rather according to investigators, the VLPD+ KAA diet increased the risk of death because protein intake in vLPD group was 0.28g/kg/d. Bellizi et al have reported antihypertensive benefits of vLPD + KAA diet in a prospective trial of CKD 4 and 5 when compared with LPD and normal protein diets. Brunori et al. conducted a multicentric double-blind control trial. Fifty-six patients were initiated on dialysis and 56 patients on vLPD with GFR 5–7 ml/min. The diet group deferred dialysis by a mean of 10.7 months. One year survival was 83.7% in the dialysis group and 87.3% in the VLPD group. VLPD was effective and safe in postponing dialysis in elderly CKD 5 patients.
Many investigators blame restricted DPI for poorer outcomes in the dialytic stage of CKD. They recommend high DPI in predialytic stages to purportedly prevent malnutrition and ensure an early start to dialysis. Bellizi et al. report that vLPD + KAA in CKD, contrary to popular perception, does not increase mortality in the subsequent renal replacement therapy period. Vendrely et al. compared 15 patients on a usual (0.9 g/kg) protein diet with 15 patients on a keto diet in predialytic phase (0.3 g/kg + KAA). They concluded that a keto diet did not lead to any malnutrition. The keto diet patients adapted very quickly to a high-protein diet, once they were initiated on the dialysis. The authors concluded that treatment with a keto diet in predialysis period was nutritionally safe and effective disease modifier.
Enough recent data have emerged which have shown poorer outcomes in patients who made an early start to dialysis as compared to CKD 5 patients who delayed dialysis by careful and conservative management (REF)., Fouque and Laville , did meta-analysis of 1494 patients, of which 753 had reduced DPI and 741 had higher protein intake. Decreased DPI reduced the number of patients entering ESRD by 40% (P = 0.006). Shah BV  has reviewed most of the studies on dietary protein restriction (DPR) in recent years. He concludes that DPR reduces the disease progression. He recommends starting KAA from CKD Stage 3. prospective, randomized, double-blind, and placebo-controlled study was conducted on 34 adult CKD patients divided into two groups. with GFR 25–30 ml/min. Group 1 was given 0.3 g/kg/d protein plus KAA and Group 2 was on 0.6 g protein/kg/day. Patients on keto diet had better preservation of GFR. The authors conclude that for the period of at least 9 months, they did not find any clinical or biochemical evidence of malnutrition in the VLPD + KAA (keto diet group) On the contrary, the keto diet group had better preservation of the nutritional status.
Garneata et al. conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalog-supplemented vegetarian very LPD compared with conventional LPD. Vegetarian VLPD supplemented with ketoanalogs seems nutritionally safe and could defer dialysis initiation in patients with estimated GFR <20 ml/min by ameliorating CKD-associated metabolic disturbances.,,,,,,, Most of the clinicians agree that LPD and VLPD + KAA are useful in alleviating uremic symptoms. However, there is an ongoing perennial debate whether they are effective in slowing disease progression. The jury is not yet out; however, there is reasonable evidence to suggest that LPD + KAA retards disease progression without detrimental effects on nutrition if used with passion, care, and caution.
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