Comparisons of isonitrogenous supplements (1.2 g N) of essential amino acids and five keto acid analogues with four essential amino acids were made in seven patients with stable chronic renal failure (creatinine clearance, 4.6 to 16 ml/min) on moderately protein-restricted diets (4.60 to 7.8 g N per day). Full nitrogen balance data on the four patients who have already completed studies lasting 24 weeks are presented. No benefits of keto acid over amino acid supplements were observed. Two transient episodes of hypercalcemia occurred during keto acid treatment. There was no improvement of renal function with keto acids. Also, no carry-over effects were seen after keto acid treatment. It is concluded that any beneficial effects of keto acids in patients with chronic renal failure are only likely to occur in those taking a diet of less than 30 g protein daily.

Methylprednisolone hemisuccinate (MPS) and methylprednisolone (MP) concentrations in plasma and urine were monitored in renal transplant and glomerulonephritis patients who were given i.v. infusions of 0.5 g or 1 g of MPS. A marked individual variation of peak plasma levels of both MPS and MP was observed after the same dose and MPS disappeared from plasma more rapidly than MP. Their clearances from the circulation, however, did not appear to be significantly influenced by the peak plasma levels of the drug, creatinine clearance, administration of previous pulses of MPS or the urinary excretion of unconjugated MPS and MP. Even in patients with profoundly reduced renal function, no accumulation of the drug was apparent when repeated doses of MPS were administered at 48-h intervals.

The effects of the acetate content of hemodialysis fluids on the relation between L-carnitine (free carnitine, cr FC) and acetyl-L-carnitine (AC) have not previously been examined in detail. The net fluxes of FC, AC, and acetate between intra- and extracellular pools during hemodialysis were calculated using a kinetic model with dialysates containing three concentrations of FC (0, 40, and 80 mumol/L) and either 40 or 3 mmol acetate/L. Radioenzymatic assays of FC and AC were optimized for use with samples taken during hemodialysis. Acetate stimulated a tissue uptake of FC (P < 0.05) that could exceed the rate of FC delivery and was related to the dialysate FC composition (P < 0.02). There were associated changes in tissue AC output. With dialysate containing 40 mmol acetate/L, AC tissue output was directly related to the dialysate FC composition (P < 0.05). The AC tissue output was less with dialysate containing 3 mmol acetate/L (P < 0.05) but the significant increase with the provision of FC in the dialysate was retained (P < 0.05). Hemodialysis may therefore represent an acute period of relative carnitine deficiency when regeneration of free coenzyme A from acetyl coenzyme A consequent to metabolism of acetate is limited.

No abstract

In an open crossover trial, 15 patients with evidence of renal impairment, defined by proteinuria, raised serum creatinine or impaired creatinine clearance, were randomly allocated to treatment with either 40 mg frusemide or 40 mg xipamide daily for 7 days. After a 3-day mid-point wash-out period, patients were changed the alternative drug for a further 7 days. Assessment measures involved a wide range of clinical and biochemical parameters. Whilst both drugs significantly reduced oedema, xipamide was more effective than frusemide, and this was associated with a significantly greater effect on sodium excretion with xipamide. With the exception of standing systolic blood pressure where the reduction was significantly more pronounced with xipamide, no significant changes in resting systolic, resting diastolic or standing diastolic pressure were observed to be associated with change of treatment. Three patients noticed minor side-effects during xipamide therapy. There were no adverse reactions inpatients taking frusemide.