Low urine citrate excretion as main risk factor for recurrent calcium oxalate nephrolithiasis in males.

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 less than 0.001) and in C (3.42 +/- 1.33 mmol/24 h, p less than 0.001). Hypocitraturia (uCit less than 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.

Protection of renal function and of nutritional status in uremic rats by means of a low-protein, low-phosphorus supplemented diet.

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.

The role of metabolic acidosis in causing uremic hyperphosphatemia.

Metabolic acidosis was corrected within 1 h in 7 chronic anuric uremic patients on maintenance hemodialysis and, in the course of a week, in 11 other patients on conservative therapy. These patients were on a diet supplying constant amounts of phosphate throughout the duration of the study. In the former group the intravenous infusion of sodium bicarbonate was used, and, in the latter, the oral administration of sodium citrate. In both groups serum phosphate was found to decrease significantly. In the patients on conservative therapy, phosphaturia also had significantly decreased while no changes occurred in their daily fecal loss of phosphate that was measured in 3 patients. These findings indicate that metabolic acidosis is one of the causes of hyperphosphatemia in chronic uremic patients.

Serum oxalic acid in uremia: effect of a low-protein diet supplemented with essential amino acids and ketoanalogues.

Serum oxalic acid (sOx) was determined with a new, specific enzymatic method in 73 uremic patients and the values were plotted against serum creatinine. 41 patients received a free mixed diet, and 32 similar patients were given a low-nitrogen diet supplemented with essential amino acids, ketoanalogues, and calcium carbonate (AD). A significant correlation was found between serum creatinine and sOx levels in patients following a free mixed diet, while no correlation appeared in patients on AD: The sOx concentrations were significantly lower and even normal in this group, and a significant reduction of sOx occurred in 10 patients with chronic renal failure, who changed from a free mixed diet to the AD. The lowering of sOx concentration in patients following AD is attributed both to low intake of its metabolic precursors and to the oral calcium carbonate supplementation.

Restricted phosphorus and nitrogen intake to slow the progression of chronic renal failure: a controlled trial.

Twenty chronically azotemic patients (experimental group) with a mean creatinine clearance of 22.5 +/- 9.4 ml/min followed a diet supplying daily, per kilogram of body weight, 7.0 mg of phosphorus and 0.5 g of protein, mostly of high biological value, for 11.3 months. A group of 19 similar patients (control group) followed a diet supplying daily, per kilogram of body weight, 12 mg of phosphorus and 0.8 g of protein for a similar period of time. In the experimental group, the serum inorganic phosphorus, urea, and iPTH (both N-terminal and C-terminal fragments) decreased significantly. The creatinine clearance decreased by -0.59 +/- 0.7 ml/min per month prior to the commencement of the experimental diet and increased by a mean of 0.1 +/- 0.4 ml/min per month during the period of study. In the control group, the serum inorganic phosphorus increased, the serum urea and iPTH remained practically constant, and the mean creatinine clearance continued to decrease at a rate not significantly different from that prior to the onset of the study (-0.50 +/- 0.66 and -0.44 +/- 0.10 ml/min per month, respectively). The mechanisms by which the low-phosphorus, low-nitrogen diet slows the progression of renal failure are discussed, and the practical importance of prescribing the dietetic restriction early in the course of renal disease is stressed.

Three years experience with a very low nitrogen diet supplemented with essential amino acids and keto-analogues in the treatment of chronic uraemia.

A low nitrogen, low phosphorus diet, supplemented with essential amino acids and keto-analogues, was administered to 48 chronic uraemics for a maximum of 36 months. In 10 cases renal function deteriorated and dialysis was started; eight patients changed to the dialytic therapy having difficulties in complying to the diet and three died for reasons not directly related to renal failure. The remaining twenty-seven patients are still on dietetic treatment and their renal function has not changed significantly. Their serum inorganic phosphorus and their circulating iPTH decreased significantly. Their subjective and objective conditions are satisfactory and no manifestation of protein malnutrition or other unwanted effects are detectable.

Urinary excretion of oxalate in renal failure.

The daily urinary excretion of oxalate has been found to be lower than normal in patients with renal failure and the decrease to be directly proportional to the impairment of renal function. It has also been found that the gut flora from uremic patients destroys oxalate 'in vitro' more efficiently than the gut flora from normal people. It is postulated that an adaptation occurs in the gut flora of uremics to 'metabolize' oxalate, and this enteric elimination may account for its decreased urinary excretion.

Factors affecting the metabolic production of methylguanidine.

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".