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Biomedical subjects

W M Bennett

Publications and source records attributed to W M Bennett.

At least 271 records · Page 15Linked to original sources
PubMed1982

Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity.

Acquired insensitivity to the nephrotoxic effects of gentamicin develops in Fischer 344 rats after 10 to 14 days' treatment after development of histologic acute tubular necrosis in a setting of extensive histologic regeneration. To determine the relative importance of aminoglycoside exposure, necrosis, and regeneration in the induction of insensitivity, we examined the effect on gentamicin toxicity of prior non-aminoglycoside-mediated tubular necrosis, antecedent nonnecrotizing aminoglycoside exposure, and unilateral Nx-induced renal tubular hyperplasia. Pretreatment with potassium dichromate, which causes tubular necrosis in the same part of the renal cortex as gentamicin, reduced gentamicin-mediated elevation of Scr but had little effect on gentamicin-related tubular dysfunction or structural damage. Pretreatment with netilmicin, which does not cause tubular necrosis, increased the sensitivity of the kidney to gentamicin; toxicity occurred earlier and was more severe. Antecedent unilateral Nx had no demonstrable effect on susceptibility to gentamicin-associated dysfunction, but histologic renal tubular epithelial regeneration and recovery from dysfunction occurred earlier, These results suggest that necrosis and/or regeneration is the major prerequisite for development of gentamicin insensitivity and that the onset of insensitivity is temporally related to the appearance of necrosis and regeneration. However, non-aminoglycoside-mediated necrosis and regeneration fail to fully-re-create insensitivity, suggesting that exposure to gentamicin is also necessary.

Acute Kidney Injury↗
PubMed1982

Renal cortical interstitial volume in mesangial IgA nephropathy. Dissociation from creatinine clearance in serially biopsied patients.

It has recently been proposed that renal cortical interstitial fibrosis is causally related to progressive decreases in glomerular filtration rate in a variety of renal diseases including glomerulonephritis. One hundred and eighty-eight renal biopsies in 81 patients with mesangial IgA nephropathy were analyzed for the percentage of relative interstitial volume by a point-counting technique. These data were correlated with serum creatinine, endogenous creatinine, endogenous creatinine clearance, and from age-matched donors were used as controls for the interstitial volume measurement. There was a negative nonlinear correlation between percentage of interstitial volume measurement. There was a negative nonlinear correlation between percentage of interstitial volume and creatinine clearance (r = 0.601, p less than 0.001). These correlations were not explained by age. However, serial biopsies in 39 patients clearly demonstrated that the percentage of interstitial volume could be dissociated from creatinine clearance. The prognosis in individual patients for progression to chronic renal failure could not be predicted from the relative interstitial volume at initial biopsy. Patients with mesangial IgA nephropathy demonstrated higher interstitial volumes than age-matched cadaver donors (p less than 0.001). Although interstitial volume and creatinine clearance are inversely related, the ability to dissociate these two variables in serial biopsies draws into question the hypothesis that interstitial fibrosis is causally related to changes in creatinine clearance. Studies to validate this hypothesis should involve patients followed with serial biopsies and renal function studies. In mesangial IgA nephropathy, interstitial changes are most likely secondary to the activity of the glomerular process.

Adult↗
PubMed1981

Cyst fluid antibiotic concentrations in polycystic kidney disease: differences between proximal and distal cysts.

The concentrations of several antibiotics were measured in the cyst fluid of six adult patients with polycystic kidney disease. Seventy-nine cysts were aspirated at surgery or autopsy. Sixty-one cysts could be categorized as arising from the proximal nephron and 16 from the distal nephron by cyst fluid to serum sodium ratios. Serum, urine, and cyst fluid were simultaneously analyzed for sodium, creatinine, and various antibiotics. Gentamicin, tobramycin, cephapirin, and ticarcillin were either undetectable or present in low concentrations in renal cysts. Cyst fluid antibiotic concentrations did not correlate with cyst volume or creatinine clearance. Cysts of proximal nephron origin had higher antibiotic concentrations than distal cysts. In one patient with normal renal function, inulin was undetectable in renal cysts after a continuous 36-hour i.v. infusion. Para-aminohippurate, however, was detected in the renal cysts of this patient. These data help explain the poor clinical response of infected renal cysts to antibiotic therapy. They also suggest that antibiotics and other solutes may enter cyst fluid across tubular cells in addition to entry by glomerular filtration.

Anti-Bacterial Agents↗
PubMed1981

Nephrotoxic acute renal failure due to common drugs.

Antibiotics are the most common drugs implicated in clinical reports of drug-induced nephrotoxicity. The experimental basis for proposed mechanisms of acute renal failure in association with three groups of antibiotics--aminoglycoside, cephalosporin, and amphotericin B--are reviewed in detail. Proposed mechanisms of antibiotic-induced acute renal tubular necrosis involve either altering plasma membrane permeability or interference with cellular energy derived from mitochondria, For either aminoglycoside or cephalosporin antibiotics, cellular accumulation followed by interruption of mitochondrial respiration is the concept that has greatest support, although the possibility of an induced phospholipidosis involving intracellular lysosomes cannot be excluded. Altered renal tubular cell permeability due to the incorporation of amphotericin B into the pore structure of the plasma membrane is consistent with in vivo observation in either clinical or experimental examples of nephrotoxicity with this agent. The metal cis-platinum, used in treatment of neoplastic disease, has a clearly defined incidence of clinical nephrotoxicity with little insight as to cellular mechanisms. A possible mediation involving cis-platinum reducing the protein-bound sulfhydryl group of renal tissue has been proposed. With the ever increasing potency of modern pharmacologic agents come a rising risk of serious toxic side effects.

Acute Kidney Injury↗
PubMed1981

Urinary calcium excretion at extremes of sodium intake in normal man.

To elucidate the relationship between the renal regulation of sodium and calcium excretion at extremes of sodium intake, we studied 6 normal men ingesting a fixed, 400 mg/day calcium intake and four levels of sodium intake from 10 to 1,500 mEq/day. Serum ionized calcium was not influenced by sodium intake. Blood pressure and cardiac index increased modestly. Urinary calcium excretion increased to 262 +/- 53 mg/day (mean +/- SE). Plasma norepinephrine concentration, serum PTH levels, hematocrit, total serum protein concentrations and CO2 content decreased with increasing sodium intake. Urinary cAMP increased as sodium intake was raised from 10 to 300 mEq/day, but subsequently decreased to basal values. Urinary calcium and sodium excretion were related (p less than 0.001) in a nonlinear fashion as were the fractional excretions of these cations (p less than 0.001). The filtered calcium load and the fractional calcium excretion were directly and linearly related (p less than 0.001). We conclude that the effect of sodium intake on urinary calcium excretion principally reflects changes in the filtered calcium load rather than changes in renal sodium handling. Calcium homeostasis at extremes of sodium intake does not appear to be critically dependent upon PTH-mediated mechanisms. The data suggest that the proximal tubule has a remarkable capacity to dissociate calcium resorption from that of sodium.

Adolescent↗
PubMed1981

Lack of nephrotoxicity of intravenous dimethylsulfoxide.

Intravenous dimethylsulfoxide (DMSO) was used to treat seven patients with stable spinal cord injuries. Because of drug-associated hemoglobinemia and hemoglobinuria, the patients were studied for subtle evidence of renal tubular dysfunction by serial measurements of urinary beta-2-microglobulin excretion. No increases in tubular protein excretion or decreases in glomerular filtration rate were observed following short-term infusions of 10-40% DMSO. It is concluded that there is no significant short-term nephrotoxicity from intravenous DMSO.

Adolescent↗
PubMed1981

Aspirin-induced depression of glomerular filtration rate in normal humans: role of sodium balance.

The renal clearance of endogenous creatinine, inulin and para-aminohippurate was measured in 10 healthy human volunteers taking aspirin during severe dietary sodium restriction (10 meq/d) to clarify the clinical significance and pathophysiology of aspirin-induced changes in renal function. Sodium restriction alone had no effect on renal clearances but did increase plasma renin activity and urinary prostaglandin E excretion. The addition of aspirin decreased the urinary clearance of prostaglandin E but not plasma renin activity, and caused a significant fall in both endogenous creatinine (from 92.3 +/- 4.1 SE ml/min . 1.73 m2 body surface area to 80.8 +/- 4.4 mL/min . 1.73 m2, p = 0.02) and inulin (from 95.3 +/- 7.0 mL/min . 1.73 m2 to 80.9 +/- 7.0 mL/min . 1.73 m2, p less than 0.001). The fall in inulin clearance was directly related to the salicylate level. The clearance of para-aminohippurate showed only a slight, statistically insignificant decline with aspirin. The results of this study suggest that aspirin-induced depression of glomerular filtration rate may be independent of total renal plasma flow. Aspirin should be used cautiously, with careful attention to dosage, in sodium-restricted patients whose glomerular filtration rate may, in part, be under the homeostatic control of renal prostaglandins.

Adult↗
PubMed1981

Renal manifestations of sarcoidosis.

Sarcoidosis may involve the kidneys in several ways. Most commonly, aberrations of calcium metabolism, including hypercalcemia, hypercalciuria, and nephrocalcinosis, are responsible for the renal manifestations of sarcoidosis. Granulomatous infiltration of the renal interstitium may also produce severe derangements of renal function. Glomerulonephritis can occur with sarcoidosis, although the pathogenesis remains unclear. Besides renal insufficiency and frank renal failure, nephrotic syndrome, nephrolithiasis, hypertension, and a variety of tubular defects may complicate sarcoidosis. The sensitivity of "sarcoid nephropathy" to corticosteroids usually warrants therapeutic trial.

Glomerulonephritis↗
PubMed1981

Comparative nephrotoxicity of dibekacin and gentamicin in rats.

To evaluate the nephrotoxicity of the new aminoglycoside, dibekacin, relative to gentamicin, we administered both drugs in doses of 40 and 120 mg/kg per day to male and female Fischer 344 rats. At sacrifice, we determined serum creatinine, in vitro renal cortical uptake of 14C N-methyl nicotinamide and para-aminohippurate, renal cortical antibiotic concentrations, and real histology. Dibekacin and gentamicin were similar in overall toxicity. Dibekacin differed from gentamicin and other aminoglycosides (1) in failing to cause early transient stimulation of para-aminohippurate uptake in male rats and (2) in the location of histologic damage at the 120 mg/kg dose. We conclude that: 1) in this model, dibekacin is comparable to gentamicin in nephrotoxic potential, and 2) the lack of early stimulation of para-aminohippurate uptake in male rates after dibekacin treatment may be related to greater initial injury to the late proximal tubule than is caused by gentamicin.

Animals↗
PubMed1980

Effects of dimethyl sulfoxide on renal function in man.

To ascertain the clinical significance of dimethyl sulfoxide-induced pigmenturia, we evaluated renal function and indicators of systemic hemolysis in stable quadriplegic patients receiving the drug intravenously (IV) for spinal cord injury. Despite a dose-dependent transient hemolysis with resultant hemoglobinuria, no alteration of renal function could be appreciated. Other than the presence of urinary hemoglobin, there were no changes from baseline in the urinary sediment and all patients remained without severe hematuria. Our results indicate that patients treated with IV dimethyl sulfoxide for severe cerebral edema could serve as donors for renal transplantation.

Adolescent↗
PubMed1980

Pathogenesis of renal failure due to aminoglycosides and contrast media used in roentgenography.

The etiology of acute renal failure has changed in recent years due to the recognition of drug nephrotoxicity as a more common cause. In this communication we emphasize recent information concerning the pathophysiology of nephrotoxic acute renal failure produced by aminoglycoside antibiotics and the contrast media used in roentgenography. The aminoglycosides are excreted primarily by glomerular filtration; however, net tubular reabsorption and renal parenchymal accumulation do occur. The exact mechanism of uptake is not clear, but the luminal membrane seems primarily involved. The pathogenesis of nephrotoxicity, although probably linked to cortical accumulation, is complex since experimental animals recover from gentamicin-induced renal failure despite continued administration of the drug. Knowledge of the precise cellular mechanisms of injury awaits further studies. Histologic damage is usually limited to proximal tubular necrosis and, clinically, the renal failure is nonoliguric. Although reports of the contrast media used in roentgenography producing acute renal failure have increased, the pathogenesis is unclear. Evidence supporting various theories is reviewed.

Acute Kidney Injury↗
PubMed1980

Percutaneous aspiration biopsy of renal allografts using ultrasound localization.

Percutaneous aspiration of renal allografts was done employing ultrasound localization and the Jamshidi renal biopsy needle-syringe. Adequate tissue for pathologic assessment was obtained in 19 of 20 biopsy attempts. There were no complications. Ultrasound provides a convenient, nonradiologic means of renal localization for allograft biopsy. The aspiration needle-syringe is well suited for percutaneous transplant biopsy.

Biopsy, Needle↗
PubMed1980

Concentration of antibiotics in simple renal cysts.

Patients with infected renal cysts are known to respond poorly to antibiotic therapy. We evaluated the serum, cyst fluid and urine levels of 3 antibiotics in 4 patients with simple renal cysts. Despite excellent urine and serum concentrations gentamicin was detected in the cyst of only 1 of the 3 patients studied. Neither sulfamethoxazole nor trimethoprim was detected in the cyst of 1 patient despite adequate plasma levels. These data help explain the poor medical response of such patients and support the concept of early surgical intervention.

Anti-Bacterial Agents↗
PubMed1980

An analysis of 100 primary cadaver kidney transplants.

A multifactorial analysis of 100 consecutive first cadaver kidney transplants was done to document the current status of this treatment for end stage renal disease and to determine the influence of the following variables on kidney losses owing to rejection: splenectomy, pre-transplant transfusions, transfusion at the transplantation, recipient sex, pre-transplant nephrectomy, donor and recipient A, B or O blood group, human leukocyte A and B antigen mismatches, kidney preservation method, donor treatment with methylprednisolone and cyclophosphamide, recipient treatment with antilymphocyte serum or antilymphoblast globulin and a low dose of steroid treatment for rejection. Pre-transplant splenectomy for leukopenia, 5 or more pre-transplant blood transfusions and pre-transplant transfusions without development of circulating cytotoxic antibodies significantly reduced kidney losses owing to rejection (p less than 0.05)., A low dose of steroid treatment for rejection resulted in a trend towards improved patient survival without sacrificing kidney graft survival. Clinical studies demonstrating decreases in kidney graft rejection should be controlled for pre-transplant blood transfusions and, possibly, for pre-transplant splenectomy for hypersplenism.

Adolescent↗
PubMed1980

Comparison of intracellular flushing and cold storage to machine perfusion for human kidney preservation.

Transplant teams have been reluctant to accept kidneys preserved with intracellular electrolyte flushing followed by simple cold storage, especially when retrieved by non-transplant surgeons or when preservation time exceeds 24 hours. This study from 1 center is a comparison of 40 primary cadaver kidney grafts preserved with Collins' C2 flushing followed by simple cold storage to 37 primary cadaver kidney grafts preserved with cryoprecipitated plasma on the MOX-100 machine. Cold storage time was 10 to 44.5 hours in the C2 group and 3.5 to 39 hours in the machine-perfused group, with a mean of 23 hours in each group. There was no significant difference between the 2 preservation methods no matter who removed the kidney with respect to 1) the incidence of acute tubular necrosis, 2) the 1-month serum creatinine nadir of surviving grafts and 3) the actuarial graft survivals up to 2 years. Among the 40 C2-preserved kidneys 17 were retrieved by community surgeons and 23 were retrieved by transplant surgeons. Human kidneys removed from beating-heart cadaver donors can be preserved satisfactorily with either Collins' 2 flushing followed by simple cold storage or pulsatile machine perfusion, even when preservation times exceed 24 hours.

Adolescent↗