Quantitative estimation of dietary energy deficiency and effects of its supplementation on protein nutritional status of nondiabetic uremic patients undergoing protein restricted dietary regimens.

In chronic renal failure (CRF) patients with a reduced protein intake, if the patients' energy intake could be estimated on the basis of biochemical data together with protein intake, it would be easier to provide them with adequate dietary treatment. Thus, from the relationship among the normalized protein catabolic rate (nPCR) and the intrinsic creatinine generation rate (%GCr) both calculated on the basis of 24-hr urine creatinine, as well as the daily dietary energy intake evaluated by a skilled nutritionist, we devised the following equation to estimate the amount of dietary energy deficiency (delta E) whose supplementation increases the %GCr of patients on protein-restricted dietary regimens to the target level (i.e., the dietary energy deficient amount). This was done by taking the %GCr of average nondiabetic hemodialysis patients of the same age and sex as a temporal target level: delta E = [31.22 - 1.97 (%GCr)0.6]/(nPCR)0.15. In order to examine the clinical usefulness of this equation, the daily dietary energy deficient amount calculated by the equation was supplemented with protein-free jelly. As a result, the %GCr increased from approximately three-fourths of the target level to the target level within 4 months.

New method to calculate creatinine generation rate using pre- and postdialysis creatinine concentrations.

The creatinine (Cr) generation rate reflects the muscle mass, a possible indicator of protein nutritional status. Thus, in this study, we developed equations for calculating the Cr generation rate. Depner and Daugirdas recently developed a method for determining the protein catabolic rate (PCR) from the pre- and postdialysis blood urea nitrogen concentrations. We modified their method to develop equations for calculating the total Cr generation rate from the measured predialysis Cr concentration and estimated postrebound concentration. The total Cr generation rate is defined as the sum of the intrinsic Cr generation rate and the extrinsic Cr generation rate (i.e., the generation rate of Cr derived from food). In the present study, the postrebound Cr concentration was estimated on the basis of postdialysis Cr concentration and the K/V for Cr. The intrinsic Cr generation rate was obtained by subtracting the extrinsic Cr generation rate, which was estimated on the basis of the PCR, from the total Cr generation rate calculated. The intrinsic Cr generation rate determined with this method was virtually the same as that obtained using the postrebound Cr concentration, the concentration immediately before the next hemodialysis (HD) session, and the PCR. The intrinsic Cr generation rate determined with the present method did not vary with changes in the HD prescription (i.e., with an increase in blood flow rate, a prolongation of the HD duration time, or a change in dialyzer membrane area). The present study also indicated that the intrinsic Cr generation rate decreased with age in both males and females.

First evidence for accumulation of protein-bound and protein-free pyrraline in human uremic plasma by mass spectrometry.

Glucose-derived advanced glycation end products (AGEs) cross-link proteins and cause various biological tissue damage. One of them, pyrraline [epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl) -L-norleucine], has been demonstrated by utilizing antibody to accumulate in plasma and sclerosed matrix of diabetic individuals, suggesting responsibility for diabetic complications. To elucidate the involvement of pyrraline in uremia, we examined the pyrraline levels in patients with chronic renal failure by a mass spectrometric approach. Here we show that protein-free pyrraline as well as pyrraline with binding protein are significantly increased in non-diabetic uremic plasma compared to healthy subjects. Our results suggest that circulating pyrraline could be a substance contributing to complications in uremia.

[Protective effect by piperacillin against renal impairment caused by amikacin].

This study is aimed to demonstrate that renal impairment caused by administration of amikacin (AMK) alone can be lessened by co-administration of piperacillin (PIPC). The patients in the present study were divided into three groups. In "group P" and "group A", PIPC alone and AMK alone were administered, respectively. In "group P+A", PIPC and AMK were co-administered. Dosage of AMK was individualized based upon the therapeutic drug monitoring method, and that of PIPC was adjusted depending upon the creatinine clearance of a patient. In group A, urinary concentrations of beta 2-microglobulin and lysozyme, and urinary excretion of beta 2-microglobulin, lysozyme and gamma-GTP per day were significantly higher (p less than 0.05) than those in group P. These differences were not observed, however, between group P and group P+A. The trough value of AMK, 11 days after AMK administration, was significantly higher in group A (p less than 0.05) than that in group P+A. Incidence of renal impairment, as judged from urinary excretion of beta 2-microglobulin per day and urinary lysozyme concentration, was significantly higher in group A (p less than 0.05) than that in group P+A. These findings indicate that co-administration of PIPC with AMK can lessen the renal impairment caused by administration of AMK alone.