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Glucose metabolism in muscle of sedentary and exercised rats with azotemia.

Insulin resistance has been demonstrated in chronic renal failure patients and may be improved by exercise training, but the mechanisms have not been identified. In this study, the response of glucose uptake, glycogen synthesis, and glucose utilization via glycolysis (glycolytic utilization) to stimulation by insulin and/or acute exercise were determined in isolated muscles from rats with moderate renal insufficiency that were exercise trained or remained sedentary. Moderate renal insufficiency had no effect on the basal rate, insulin sensitivity, or insulin responsiveness of glucose uptake, glycogen synthesis, or glycolytic utilization in muscle. The enhanced insulin responsiveness of both glycogen synthesis and glucose uptake following acute exercise, noted in control animals, was less in rats with moderate renal insufficiency, but the enhanced basal rate and insulin sensitivity after exercise were unaffected by moderate renal insufficiency. Exercise training increased the insulin sensitivity and responsiveness of muscle glucose uptake and glycolytic utilization in rats with moderate renal insufficiency and in controls. The effects of acute exercise and exercise training on insulin responsiveness of glucose uptake were additive in controls but not in animals with moderate renal insufficiency. These findings are compatible with the concept that moderate renal insufficiency is associated with a postreceptor defect in insulin's action in muscle, detectable only following maximal stimulation of glucose transport by insulin and exercise, and partially correctable by exercise training.

Animals↗

Effect of 1 alpha-hydroxyvitamin D3 and dietary calcium and phosphate on the aortic mineral content in rabbits with mild azotemia.

The effect of treatment with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) and different diets on uremic arterial disease was studied. Three groups of rabbits with chronic renal failure (CRF) were kept on three diets with a low, medium or high content of calcium and phosphate. Half the rabbits in each group were treated for 18 weeks with 1 alpha-OH-D3, 0.02 micrograms/kg/day, without any significant changes in the serum concentrations of calcium or phosphate compared to placebo treatment. In the thoracic aorta, the content of calcium and phosphate was significantly increased in placebo-treated CRF rabbits on medium and high calcium and phosphate intakes compared to rabbits with normal renal function (p less than 0.05). The cholesterol content was unchanged. Treatment with 1 alpha-OH-D3 caused a further increase in the aortic content of calcium and phosphate in the CRF rabbits on medium and low calcium and phosphate intakes (p less than 0.05). No increase in the aortic cholesterol content was observed. The histological changes in the abdominal aorta consisted of medial proliferations with calcifications and intimal proliferations. The severity of these changes paralleled the mineral content of the thoracic aorta. Aggravation of uremic arterial disease may be a hitherto unrecognized side-effect of treatment with 1 alpha-OH-D3 in CRF.

Animals↗

Urolithiasis with blind-ending ureteral duplication and azotemia treated with shock wave therapy.

A case of bilateral urolithiasis and renal insufficiency with a blind-ending branch of the right bifid ureter is presented. The diagnosis was made by retrograde ureterogram which revealed a blind-ending branch originating in the middle third of the right ureter. Stones were treated with phased extracorporeal shock wave lithotripsy after preliminary bilateral JJ stenting. The renal parameters reverted to normal and the patient was stone-free.

Humans↗

Effect of experimental azotemia on intestinal transport of butyric acid.

Earlier studies have revealed an impairment of jejunal absorption of long chain fatty acids in experimental uremia. We investigated the intestinal absorption of butyric acid which is a short chain fatty acid in experimental renal failure (RF). Sprague-Dawley rats were randomized into the RF group which had subtotal nephrectomy, a sham-operated control group, and a pair-fed group. In vivo recirculating perfusion (n = 5) and in vitro everted sac incubation (n = 8) were employed. The in vitro experiments were repeated substituting the serosal buffer by either predialysis or postdialysis sera from uremic individuals, or normal serum (n = 10). The rate of in vivo butyric acid absorption was significantly lower while the in vitro absorption was significantly higher in the RF group than those observed in the sham-operated and pair-fed groups which showed comparable values. The normality of butyric acid absorption in the pair-fed animals despite comparable weight loss with the RF group tends to exclude anorexia and weight loss as a cause of altered butyric acid transport in RF animals. The disparity between the in vivo and in vitro data is suggestive of an inhibitory influence of uremic environment which is present in vivo and absent in vitro. This viewpoint was corroborated by the observed fall in butyric acid absorption by sacs containing predialysis uremic serum as compared with those containing normal or postdialysis sera. The latter further suggests that the inhibitory factor(s) is dialyzable.

Animals↗

Minimally dilated obstructive nephropathy initially suspected as pre-renal azotemia in a kidney donor with volume depletion.

Although ultrasonography is regarded as the gold standard in the diagnosis of obstructive nephropathy, dilatation is sometimes not observed by ultrasonography. We report upon a case of minimally dilated obstructive nephropathy due to an ureter stone in a kidney donor with volume depletion. A 54-year-old man was admitted due to anuria and abdominal pain of 2 days duration. Ten years previously, his right kidney was donated for transplantation, and one month before admission, he abstained from all food except water and salt, for 30 days for religious reasons. He had lost 8 kg of body weight. On admission, he had clinical signs of volume depletion, i.e., a dehydrated tongue and decreased skin turgor. Laboratory data confirmed severe renal failure, his blood urea nitrogen level was 107.3 mg/dL, and his serum creatinine 16.5 mg/dL. The plain X-ray was unremarkable and ultrasonography showed only minimal dilatation of the renal collecting system. On follow-up ultrasonography, performed on the 5th hospital day, the dilatation of the collecting system had slightly progressed and a small stone was found at ureter orifice by cystoscopy. Removal of stone initiated dramatic diuresis with a rapid return of renal function to normal by the third day.

Anuria↗

The possible role of postoperative azotemia in enhanced survival of patients with metastatic renal cancer after cytoreductive nephrectomy.

Cytoreductive nephrectomy prior to systemic therapy significantly increases survival in patients with metastatic renal cancer. This result is generally ascribed to the benefits of resection of the primary tumor including reduction of tumor burden, removal of a source for growth factors and metastases, and enhanced immune response. On the basis of mathematical models of tumor invasion, we propose that the observed effects of cytoreductive nephrectomy may be caused by resection of the kidney rather than the cancer. The models predict that the graded metabolic acidosis associated with mild renal failure after unilateral nephrectomy may alter the dynamics of the tumor-host interface sufficiently to reduce and even reverse the rate of invasion. A review of patient data from the surgical arm of the Southwest Oncology Group (SWOG) 8949(2) trial demonstrates significantly improved survival in patients who experienced postoperative increase in blood urea nitrogen (BUN) and creatinine compared with those who did not (17-month survival versus 4-month survival; P = 0.0007). This is generally consistent with the predictions of the mathematical models. If confirmed, these results suggest novel and broadly applicable tumor therapies.

Acidosis↗