Michael L. Simenhoff

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 12.5 mg/dl) were maintained on low protein diet. The chronic renal patients harbored a greatly increased microbial flora of both anaerobes and aerobes in the duodenum and jejunum, quantitatively comparable to those in blind loop subjects. The composition did not differ significantly in the two groups. Some organisms may have the potential to metabolize substrates which reach the intestinal lumen from the diet and bile, and perhaps to generate toxic metabolites that could contribute to uremic toxicity or malabsorption.

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 < 0.001), which was similar to healthy controls. This degradation was abolished when antibiotics were added directly to the patients stool during incubation (P < 0.002). In a subset of five patients, duodenal intubation demonstrated small bowel bacterial overgrowth associated with high concentrations of toxic methylamines generated there from and increased stool creatinine consumption. We conclude that retained creatinine in advanced chronic renal failure induces bacterial creatininase activity throughout the bowel, causing creatinine degradation and subsequent potential loss of creatinine to the creatinine pool. The modifying effects of antibiotics on creatinine degradation has important clinical implications for the interpretation of serum creatinine measurements in renal failure.

N-nitrosodimethylamine in human blood

Abstract Whole blood from 38 healthy persons (19 males and 19 females) was analysed for volatile nitrosamines. N-Nitrosodimethylamine was detected in blood samples from 97% of the individuals tested at a mean value (±1 SD) of 0·6 ± 0·4 ng/ml.

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. Recovery of NDMA from blood was 93 +/- 5%. Coefficient of variation was 25%. Bloods from 242 people were analyzed for volatile NAs. NDMA was the only NA found. Positive specimens were presumptively confirmed by their non-detection after ultraviolet photolysis and/or mass spectrometry. This paper presents additional evidence that in vivo NA formation occurs.

Altered gut Flora in uremia

The objective of this review is to show the influence of altered gut flora in patients with chronic renal failure (CRF). This flora produces toxic metabolites that can be reduced by a biological intervention that acts through modification of bacterial overgrowth in the small intestine. The toxic metabolites are responsible for two major problems: they cause general CRF symptoms as well as target organ dysfunction especially in the brain, leading to neurological abnormalities, and they may interfere with the absorption of digested nutrients from the small intestines that promote normal nutrition. One group of toxic compounds [the methylamines (MA)] has been used as a biochemical marker to monitor the course of CRF. The origin of these MAs is choline and lecithin, important constituents of the normal diet and bile. Based on the results with nonabsorbable antibiotics and a pilot study using freeze-dried Lactobacillus acidophilus (LBA), amines (especially dimethylamine [DMA] and the carcinogen, nitrosodimethylamine [NDMA]), and nutritional parameters (appetite, caloric intake, weight, anthropometrics, and serum albumin) were measured in an extended study in dialysis patients using LBA for at least 1 month. Results indicate a uniform biochemical response with significant decreases in DMA and NDMA. This type of intervention produces the only reported reversal of objective neurological dysfunction (electroencephalographic change, asterixis) other than dialysis and transplantation. Longer-term LBA administration also improved nutritional parameters with caloric intake and weight assuming statistical significance. Usage is particularly attractive because LBA is safe, easy to administer, abundantly available, and inexpensive. o 1996 by the National Kidney Foundation, Inc.