Takeo Kikuchi

Tissue and blood cell concentration of methylguanidine in rats and patients with chronic renal failure.

Methylguanidine concentration in blood cell of nondialysed patients with chronic renal failure was quantitatively determined by the method of the present authors. We also determined tissue methylguanidine concentrations in the liver, blood cell, kidney, colon, muscle and brain of uremic rat experimentally produced by Platts method. Methylguanidine concentrations in blood cell and tissues except the brain of the uremic rats and in blood cell of the uremic patients were 5--7 times higher than those in their serums. An increased methylguanidine concentration in the liver of the uremic rat receiving 40% protein diet was observed. These results imply that methylguanidine acts as one of the important uremic toxins in the intracellular space except for the brain, and suggest that the liver specifically affects the formation of methylguanidine.

Metabolic Pathway of Guanidino Compounds in Chronic Renal Failure

Guanidino compounds are considered to be one of the metabolic products of protein catabolism. Serum concentrations of some guanidino compounds especially methylguanidine (MG)1 and guanidinosuccinic acid (GSA)2 are increased in the uremic state. Recently, MG and GSA were found to have uremic toxicity in vitro3. Giovanetti4, et al., for example, brought out many uremic symptoms in normal dogs by repeatedly injecting MG until the MG concentration reached the uremic state. Cohen5 proposed the metabolic pathway of MG. He suggested that the metabolic origin of MG is mainly creatine and partially of arginine (Arg). The present authors have also suggested that there might be two metabolic origins of MG6. One is possibly Arg itself (or the metabolites of arginine); the other is creatinine (Cr). The present study aims to clarify the metabolic precursor of guanidino compounds, especially MG (Fig.l).

Quantitative Determination of Guanidino Compounds: The Excellent Preparation of Biological Samples

It is well known that the serum concentrations of some guanidino compounds, for example, methylguanidine and guanidinosuccinic acid, increase in the uremic state. Metabolic abnormality of guanidino compounds might be occurred by the aberrations of urea cycle in uremia. The analysis of guanidino compounds in biological fluids provides us with a great deal of useful information on the pathophysiology and treatment for uremia. Recently, the quantitative determination of various guanidino compounds has been performed with the use of high-pressure liquid chromatography and with the use of fluorometric detection of the 9,10-phenanthrenequinone derivative of guanidino compounds1. A rapid, sensitive and quantitative determination of various guanidino compounds with a small amount of sample became possible by this method, but the evaluation of this method for clinical application has not yet been completed.

Amino Acid Supplementation to Hyperalimentation in Uremic Rats: Effects of Amount and Composition of Amino Acids on Nutrition and Uremia

We evaluated amount and composition of amino acids in supplementation of hyperalimentation from the standpoint of whether it may improve nutrition and/or reduce the indexes of uremia such as BUN. Rats with established uremia, by 5/6 nephrectomy, were treated with various isocaloric solutions containing different amount of essential amino acids and histidine (EAA) or standard amino acids (SAA) which were formulated to provide Cal/N ratios of 300, 600, and 900. The BUN was lower and the nutritional index was better in rats infused with EAA compared with those administrated SAA, while severe distortion of plasma amino acid concentration, hyperammonemia, and fatty liver were observed at the Cal/N 300 condition. Rats infused with SAA gained positive nitrogen balance at the condition of Cal/N 300; however, plasma amino acid distortion was still observed. These results indicate that administration of EAA alone for treatment of renal failure needs high-calorie and low-nitrogen conditions such as Cal/N 600 for avoiding complications. Administration of standard amino acid solution is safe and nutritionally effective in the Cal/N 300 condition, but there are a few problems concerning nitrogen availability and plasma amino acid pattern.

New Peritoneal Dialysis Model in Rats with Bilateral Nephrectomy

Many peritoneal dialysis (PD) patients with chronic renal failure (CRF) suffer from metabolic and nutritional abnormalities. However, these abnormalities have been not sufficiently investigated. At present, the resolution of these issues in this field has been hindered by the lack of suitable PD models. We attempt to develop a rat model of PD under no constraints and under non-anesthetization to evaluate amino acid solution as suitable nutritional therapy for renal failure. In our model, bilateral nephrectomy rats were dialyzed 6 h per day for three days. The dialysate was infused and removed continually via a metering pump. Under fasting, rats were infused with 5% glucose or amino acid solution for renal failure, and they remained alive. This model can be used to examine bilateral nephrectomy in rats for three or more days. We were also able to determine protein and calorie malnutrition, negative nitrogen balance, abnormalities in the plasma amino acid pattern, and calcium and phosphorus metabolism. Thus, this model has the characteristics of renal failure in humans and may be used to easily examine the metabolic changes due to loss of kidney function.

Morphological studies on the central nervous system of rats with portacaval anastomosis which were continuously infused with ammonium acetate

Abstract Morphological changes in the striatum of portacaval anastomosis (PCA) rats which were continuously infused with ammonium acetate for 6 days have been studied. PCA rats with the infusion of ammonium acetate showed no neurological symptoms. However, ammonia concentration in the plasma was significantly higher than that in PCA rats without the infusion of ammonium acetate. Histologically, numerous atrophic neurons have been observed in the striatum. Moreover, glial fibrillary acidic protein (GFAP)-positive astrocytes in the same area became hypertrophied and had enlarged processes in hyperammonemic PCA rats. These results suggest that long-term hyperammonemia, which did not produce any visible neurological symptoms, might induce the morphological changes in the brain of PCA rats. These changes might be related to excessive ammonia metabolism in astrocytes.