Effect of Low Protein Diet and Surplus of Essential Amino Acids on the Serum Concentration and the Urinary Excretion of Methylguanidine and Guanidinosuccinic Acid in Chronic Renal Failure

Abstract

20 patients with moderate renal failure (serum creatinine 4.5–12.0 mg/dl) and some uremic symptoms on a diet ad libitum were treated with a high caloric diet containing 0.5–0.7 g/kg/day protein, supplemented with eight essential amino acids and histidine in the form of solution and/or granules. During the treatment uremic symptoms subsided or diminished without the signs of malnutrition, SUN and the ratio SUN/S-creatinine fell and the nitrogen balance and the ratio N-balance/intake N improved. The serum concentration and the urinary excretion of MG and GSA of the 12 patients were determined by Stein’s method using the modified Sakaguchi reaction. In all patients, the serum, concentration and the urinary excretion of MG and GSA diminished remarkably during the treatment with a low protein diet alone and furthermore with a low protein diet and essential amino acid supply. We concluded that conservative treatment – low nitrogen diet supplemented with sufficient calories and essential amino acids – improved the nutritional state of uremic subjects, and decreased the metabolic production of MG and GSA. The results show that the supplementation of essential amino acids to uremic patients may be a useful treatment.

Effects of Methylguanidine on Sodium and Organic Ion Transport

“…In fact, when present in the serosal medium, M G stimulates Na absorption at a higher concentration. These results do not seem to support the notion that M G is a potential uremic toxin, suggested by previous investigators [3,7,8,9,11,12], However, since the studies described here were performed on an acute basis, long-term effects of M G on the kidney were not assessed.…”

“…For example, a low molecular weight fraction o f uremic serum was found to inhibit trans Accepted : June 24,1991 epithelial Na transport by frog skin and PAH uptake by rabbit cortical slices [1,2] and when administered to intact rats increased Na excretion without changing glomerular filtration rate (GFR ) and renal plasma flow (RPF) [2], It has been suggested that methylguanidine (M G ) may play a role in the genesis of the 'uremic syndrome'. This substance is present in the serum o f uremic patients [3][4][5][6][7][8] and dogs [9] at much higher concentrations than in normal subjects. In chronic renal failure, M G levels appear to be related to the severity o f renal insufficiency [9] and the severity o f uremic symptoms [3,7], M G is known to be acutely toxic [10], and its chronic subcutaneous administra tion to normal dogs in amounts sufficient to produce M G concentrations similar to those reported in humans with severe renal failure induces a uremic-like syndrome, includ ing a hypercatabolic state, impaired erythrocyte production and hemolysis, increased serum triglycerides and neurolog ical and gastrointerstinal disturbances [7] as well as high plasma fibrinogen levels and reduced fibrinolytic activity [11].…”

“…This substance is present in the serum o f uremic patients [3][4][5][6][7][8] and dogs [9] at much higher concentrations than in normal subjects. In chronic renal failure, M G levels appear to be related to the severity o f renal insufficiency [9] and the severity o f uremic symptoms [3,7], M G is known to be acutely toxic [10], and its chronic subcutaneous administra tion to normal dogs in amounts sufficient to produce M G concentrations similar to those reported in humans with severe renal failure induces a uremic-like syndrome, includ ing a hypercatabolic state, impaired erythrocyte production and hemolysis, increased serum triglycerides and neurolog ical and gastrointerstinal disturbances [7] as well as high plasma fibrinogen levels and reduced fibrinolytic activity [11]. Marked natriuresis and diuresis was also noted in rats injected with M G [12].…”

Comparison of Toxic Effects of Methylguanidine, Guanidinosuccinic Acid and Creatinine in Rats with Adenine-Induced Chronic Renal Failure

“…Nevertheless, it is considered that MG adminis tration causes destruction of the regulatory mechanism in the body, as observed in in vitro experiments [18][19][20][21], along with the cessation of renal function, subsequently leading to death. On the other hand, many researchers have reported that production of MG is facilitated in a state of renal failure [3,4,II,22,23], and Stein et al [3] have demonstrated that urinary excretion of MG is also increased by active tubular excretion through residual renal function. In addition, since MG accumulates in body organs, it is considered that MG is difficult to remove by hemodialysis, showing a dialytic pattern typi cal of a high or middle molecular weight substance.…”

Nutrition and Control Theory

“…These abnormalities cannot be corrected by low-protein diet therapy alone. To restrict the accumulation of metabolite wastes and to recover nutritional balance, an essential amino acid therapy was developed (14).…”