No abstract

1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested. 2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling. 3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14-C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high. 4. Creatinine, incubated at 38 degrees C for 24 h in Krebs bicarbonate solution (pH 7-38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur "non-enzymatically".

Serum iPTH levels decreased markedly in 16 severe chronic uremic patients who changed from a standard low-protein diet to a very low-nitrogen and very low-phosphorus diet supplemented with essential amino acids and keto-analogues and with calcium. The fall of serum iPTH levels occurred simultaneously with a fall of serum phosphate and an increase of serum calcium.

To better define the relative role of metabolic factors in the recurrence of stone formation, we studied the 24-hour urinary excretion of calcium (uCa), citrate (uCit), oxalic acid (uOx) and uric acid (uUa) in 73 male patients with primary calcium oxalate urolithiasis. According to the episodes of stone formation per year, we identified 51 recurrent stone formers (RSF) and 22 single stone formers (SSF). 20 normal adult males constituted the control group (C). uCa and uOx were higher in RSF than in C, but quite similar in SSF and RSF. The only difference between RSF and SSF was uCit, significantly lower (2.06 ± 1.04 mmol/24 h) in RSF than in SSF (3.22 ± 1.18 mmol/24 h, p < 0.001) and in C (3.42 ± 1.33 mmol/24 h, p < 0.001). Hypocitraturia (uCit < 1.5 mmol/24 h) was found in 16 of 51 RSF (31.4%) and in 1 of 22 SSF (4.5%). These data confirm that high levels of uCa and uOx represent a risk factor for lithogenesis, but also strongly indicate the low uCit excretion as the most important urinary abnormality accounting for the recurrence of calcium oxalate stones.

A low-protein, low-phosphorus diet supplemented with essential amino acids and keto analogues was given to 12 rats, starting from the 90th day after subtotal nephrectomy. The purpose was to assess its effect on the residual renal function and on the nutritional status in rats with already established severe renal failure. Ten control rats in the same conditions, following a standard diet supplying normal amounts of protein and phosphorus were also studied. The supplemented diet exerted a well-evident protection of residual renal function and structure: lower rate of decline of creatinine clearance, lower mortality, significant decrease of proteinuria and almost total absence of histological signs of activity. The nutritional status was also well protected by the dietary therapy: increase of body weight, normal values of total serum protein, and low-constant values of urea appearance. In the control rats body weight decreased, total serum protein was lower than normal and the values of urea appearance were increasing simultaneously with a decreasing food intake and body weight.