Biomedical subjects
Publications and source records attributed to W M Bennett.
In our experience, primary cadaver kidney transplantation is a reasonable alternative to dialysis in the older patient with ESRD. The probability for a transplant success is no different from that of other age groups receiving their first grafts from cadaver donors and the quality of life after transplantation is equal to or exceeds that obtained with chronic dialysis.
Fischer 344 rats were treated with tobramycin or gentamicin, 40 mg/kg/day, for up to 10 days or with tobramycin, 120 mg/kg/day, for up to 14 days. Serum creatinine and BUN at the time of sacrifice were determined, and kidney tissues were examined by light and electron microscopy. Rats receiving gentamicin demonstrated progressive renal proximal tubular necrosis which was nearly universal at the end of 10 days. Their BUN and creatinine levels rose progressively over the same period. Even at the higher dosage, tobramycin therapy resulted in only rare foci of proximal tubular necrosis and minimal elevation of BUN and creatinine. Although they occurred later and were substantially less severe, the ultrastructural changes induced by tobramycin were the same as those seen following gentamicin administration. These results indicate that the mechanism of tobramycin-induced renal injury is probably similar to that of gentamicin and that tobramycin is significantly less nephrotoxic in this experimental model.
Ultrastructural changes in renal proximal tubule lysosomes, including the formation of myeloid bodies, occur reliably with gentamicin administration in experimental animals. The present study reviewed the electron microscopic tubular morphology of renal biopsies and nephrectomies performed in our institution over a 2-year period. The frequency of myeloid bodies and their relation to drug therapy and selected clinical features were determined. Myeloid bodies were found in the proximal tubules of 19 of 109 cases that were judged adequate for study. On review of the drug histories of these 19 patients, 15 had received gentamicin within 6 weeks of biopsy or nephrectomy. None of the 90 patients without myeloid bodies had received the drug within 6 weeks of tissue examination. Of 4 patients with myeloid bodies who had not received gentamicin, 1 had received chloroquin and 3 had received drugs with no known or suspected capacity to induce myeloid bodies. The presence of myeloid bodies in proximal tubules did not appear to be related to the total dose of gentamicin, duration of therapy, or serum drug concentration. Clinical evidence of gentamicin nephrotoxicity was present in only 1 case.
A case of partial lipodystrophy with C3 nephritic factor was found to be associated with mesangiocapillary glomerulonephritis although all clinical parameters of renal function were normal. Diagnosis of mesangiocapillary glomerulonephritis required renal biopsy. Nephriti factor obtained from this patient was immunochemically related to nephritic factor isolated from the serum of patients with typical mesangiocapillary glomerulonephritis without partial lipodystrophy.
20 patients with active SLE without clinical evidence of renal involvement underwent percutaneous renal biopsy. 12 had varying proliferative changes on light microscopy. Of 19 ultrastructural examinations performed only 3 had no electron-dense deposits. Serum C3 and C4 levels were 63 +/- 8 and 8 +/- 2 mg% in patients with subendothelial deposits, compared to 142 +/- 27 and 27 +/- 6 mg%, respectively, in patients without deposits (p less than 0.01). All patients with diffuse proliferative changes had subendothelial deposits; however, one with normal light microscopy and another with focal proliferation also had them. It is concluded that no variant of lupus nephropathy can be excluded on clinical grounds alone.
Five tables are presented that provide guidelines for drug usage in patients with renal insufficiency. The data are derived from the current medical literature. If specific information about a drug is unavailable, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity of adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.
The major clinical presentations of disease to a nephrologist can be grouped into six general areas: acute renal failure, chronic renal failure, nephrotic syndrome, fluid-electrolyte disorders, acid-base disturbances, and the uremic symptom-complex. Each of these major clinical syndromes can be caused by, or related to, drugs or environmental toxins. Prototype drugs can be used to highlight the features of each drug-related syndrome. Although it is preventable, drug-related disease may present opportunities to learn about general pathophysiologic mechanisms in clinical nephrology.
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To ascertain whether diuretics have an antihypertensive effect independent of natriuresis, 12 stable patients on maintenance hemodialysis underwent a crossover evaluation with hydrochlorothiazide, 50 mg daily, metolazone, 5 mg daily, or placebo in 4-wk treatment periods for 6 mo. Compliance was assured by pill counts and serum drug concentrations. All patients had daily urine less than 100 ml. Pre- and postdialysis blood pressure, body weight, plasma volume, and plasma renin activity were monitored. Over the 6-mo study period there were no statistically significant changes in any parameter related to diuretic therapy. It is concluded that a functioning kidney with the ability to respond to diuretics with a natriuresis is necessary for the antihypertensive action of diuretics. Direct vascular effects of diuretics to lower peripheral resistance could not be demonstrated in this unique patient population.
Using NPT monitoring, we have evaluated the complaints of impotency in 11 patients with chronic renal insufficiency. Eight of these 11 demonstrated objective evidence of sexual dysfunction. These findings support a predominant role for organic factors in the etiology of sexual dysfunction in this group of patients.
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Twelve patients with severe renal failure and intercurrent urinary tract infections were treated with either ampicillin trihydrate, 500 mg four times a day, or trimethoprim-sulfamethoxazole, two tablets (80 mg trimethoprim, 400 mg sulfamethoxazole) twice a day. All patients achieved bacteriologic cure, including six with proved upper tract infection. Serum levels of all drugs were increased to values above those seen in normal subjects without adverse effects. Urine concentrations of trimethoprim, 28.6 mug/ml, and ampicillin, 88.6 mug/ml, were well above the minimum inhibitory concentrations of urinary pathogens. Urine sulfamethoxazole concentrations were less than 10 mug/ml in four of the six patients treated; however, this did not hamper bacteriologic success. It is concluded that both drugs can be used to treat urinary tract infections in patients with renal functional impairment.
The posttransplant courses of 27 chronic dialysis patients with 29 grafts who had undergone pretransplant bilateral nephrectomy were compared to those of 49 patients with 55 transplant who had no pretransplant surgery during the same time period. The latter had better survival and fewer rejection episodes (P less than .05). The six patients who died of bacterial sepsis after transplantation all had pretransplant surgery. The frequency of post transplant hypertension was similar in both groups. Apparently, pretransplant bilateral nephrectomy offers no advantage to the patient awaiting an allograft.
A case of arteriovenous fistula of the major transplant vessels contributing to posttransplant hypertension hypertension and severe microangiopathic hemolytic anemia is reported. Improvement in blood pressure and correction of anemia followed ligation of the fistula. This case reinforces the need for diagnostic evaluation of all patients with sustained post-transplant hypertension.
The effects of p-aminohippurate (PAH) on electrolyte clearances were measured in 8 human volunteers. At plasma PAH levels used to measure renal plasm flow, the only significant increase was in sodium clearance, while with PAH levels used to measure maximum tubular secretion, the clearances of sodium, potassium and phosphorus were all significantly increased. The antriuresis combined with a depression of free water clearance and the absence of a chloruresis led to the conclusion that PAH- changed the anion composition of the filtrate delivered to the ascending limb, thus interfering with coupled Na+ reabsorption. This finding must be taken into account when electrolyte excretion is being measured during PAH infusion. A similar mechanism may operate in patients with chronic uremia whose endogenous hippurate level is increased.
Gentamicin nephrotoxicity was examined in rats on normal, high, and low sodium diets. Low sodium diet markedly potentiated nephrotoxic effects of the drug as evidenced by animal mortality, renal failure, pathological changes, and increased renal cortical concentration of the drug. High sodium intake reduced the cortical concentration of gentamicin but renal function and ultrastructure were similar to normally fed rats given in the same dose.
A patient with severe nephrotic syndrome who was too debilitated to undergo surgical nephrectomies, underwent therapeutic bilateral renal artery occlusion by the selective injection of isobutyl 2-cyanoacrylate into the renal arteries. The therapy resulted in dramatic cessation of urine flow and elimination of proteinuria.
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