Induction of creatininase activity in chronic renal failure: timing of creatinine degradation and effect of antibiotics.

Creatinine degradation was prospectively studied in four healthy subjects and 35 patients with varying degrees of chronic renal failure by measuring creatininase activity in stool isolates. Patients were subdivided into those with serum creatinine above and below 6 mg/dL. Creatinine degradation in the former group of patients who had not taken antibiotics in the previous 3 months was significantly greater than the latter (64% v 26%; P < 0.

Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus.

Small bowel bacterial overgrowth (SBBO), well known to occur in end-stage kidney failure, is responsible for producing uremic toxins and contributing to the patient's decreased nutritional well-being. In this study, 8 hemodialysis patients were treated with a course of oral Lactobacillus acidophilus (LBA) in an attempt to alter this SBBO. LBA treatment was effective in lowering 2 compounds generated in vivo.

N-nitrosodimethylamine blood levels in patients with chronic renal failure: modulation of levels by ethanol and ascorbic acid.

We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals.

Analysis of human blood for volatile N-nitrosamines by gas chromatography-chemiluminescence detection.

A method was developed to separate and measure trace levels of volatile N-nitrosamines (NAs) in human blood that either eliminated or accounted for in vitro artifactual formation of N-nitrosodimethylamine (NDMA) through the use of water blanks, added inhibitor (ascorbic acid) and added morpholine. The absolute minimum detectable limit was 8 pg; minimum level of reliable measurement was 0.05 microgram/kg for a 20-g blood specimen.

Determination of body burden of uremic toxins.

The body burden of two uremic toxins, di- and trimethylamines, was determined in eight chronic renal failure patients, who received a renal transplant with immediate good function. The "pools" of these amines were calculated on the basis of serum concentration just prior to vascular anastomosis being established and compared to measured amines excreted over a period of five days following transplantation. The amount of DMA and TMA present intra-cellularly in eight muscle samples obtained from these patients was also studied.

Analysis for and intestinal metabolism of precursor nitroso compounds in normal subjects and in patients with chronic renal failure.

We have demonstrated that patients with chronic renal failure generate increased amounts of both dimethylamine and N-nitrosodimethylamine in the small bowel in association with aerobic and anaerobic bacterial overgrowth. The significance of these findings in relation to the reported increased incidence of cancer in patients with chronic renal failure has not yet been defined.

Evidence for generation of the precarcinogen nitrosodimethylamine in the small intestine in chronic renal failure.

We have previously reported raised concentrations of dimethylamine and also bacterial overgrowth in the small intestine in CRF. Evidence for in vivo NDMA formation in the same site in CRF is now presented. Gastroduodenal intubation was performed in 9 healthy volunteers and 7 patients with advanced chronic renal failure.

Generation of dimethylnitrosamine in water purification systems. Detection in human blood samples during hemodialysis.

Dimethylnitrosamine (DMNA), a carcinogen, was detected at levels up to 32 micrograms/L in dialysate from five of 16 dialysis units surveyed. Blood drawn from patients at one of these units in which DMNA was raised in the dialysate showed a significant increase in the amount of DMNA in the patient's blood when predialysis levels were compared with 15-minute intradialysis levels. The presence of a mixed-bed deionizer without an antecedent carbon filter appeared to be necessary for DMNA production.

Importance of aliphatic amines in uremia.

Five main aspects were addressed: 1)The demonstration that creatinine is an endogenous precursor of dimethylamine (DMA) in chronic renal failure. 2) The size of the body amine pool measured in transplant patients suggests sequestration in some intracellular compartment. This illustrates the possible error in directly relating serum concentrations to neurological toxicity.

Bacterial populations of the small intestine in uremia.

The small intestinal bacterial flora of 15 patients with chronic renal insufficiency was compared with that of subjects with blind loop synDROME. 9 patients were on regular hemodialysis with high protein intake and 6 (serum creatinine 7.5 to 12.

Biochemical profile of uremic breath.

We attempted to define the substances that contribute to the characteristic "uremic breath" of patients with end-stage renal disease. Breath samples from nine patients underwent direct analysis before and after hemodialysis with use of gas chromatography and confirmation by mass spectrometry, and indirectly assessment by an organoleptic panel. Concentrations of secondary and tertiary amines, dimethylamine and trimethylamine were increased, with subsequent reduction after hemodialysis (dimethylamine from 2.

Toxicity of aliphatic amines in uremia.

Fifty-three samples in 26 patients were analyzed for aliphatic amines (DMA and TMA), and the levels correlated with 2 neurophysiological tests, choice reaction time (CRT), and electroencephalogram (EEG). A significant correlation was found between TMA and CRT and EEG (p less than 0.001 and 0.

Amine metabolism and the small bowel in uraemia.

Intestinal intubation was carried out in 21 subjects: 9 with end-stage renal failure, 2 with early renal insufficiency, 7 untreated patients with blind-loop syndrome, and 3 normal volunteers. All 9 patients with uraemia had significantly raised duodenal dimethylamine (D.M.

Malignant lymphoma with "myeloma kidney" acute renal failure.

The first cases of malignant lymphoma with a "myeloma kidney" type of acute renal failure are presented. With appropriate therapy, both patients regained partial renal function; the first after three months of dialysis. It is suggested that the term paraproteinemic nephropathy is preferable to "myeloma kidney.