Joy L. Logan

Coccidioidomycosis in Solid Organ Transplantation

Coccidioidomycosis is an endemic fungal infection of the southwestern United States. Normally a self-limited infection in healthy hosts, coccidioidomycosis can become a serious complication in patients who have had solid organ transplantation. Among patients whose solid organ transplantation was complicated by coccidioidomycosis, the infection has a variety of clinical presentations. Disseminated disease is common and has substantial morbidity. Patients at risk for coccidioidal infection should be identified so that antifungal prophylactic therapy can be initiated. Treatment options include amphotericin B or azoles. Secondary prophylaxis is recommended because relapse is frequent.

Immunosuppressive Therapy and Plasmapheresis in Rapidly Progressive Glomerulonephritis Associated With Bacterial Endocarditis

A 25-year-old male presented with new cardiac murmurs and acute renal insufficiency. Blood cultures grew Streptococcus viridans and appropriate antibiotic therapy was initiated. A renal biopsy revealed diffuse proliferative glomerulonephritis with crescents involving more than 50% of the glomeruli. Treatment with antibiotics, plasmapheresis, and steroids resulted in renal recovery that paralleled reductions in circulating immune complexes. The rationale for this therapeutic approach is discussed, as well as a review of two similar case reports. These experiences suggest a possible role for plasmapheresis and immunosuppressive drugs in patients who develop rapidly progressive glomerulonephritis as a complication of bacterial endocarditis.

Exertional Heat Stroke and Acute Renal Failure in a Young Woman

Strenuous exercise leading to heat stroke is known to cause rhabdomyolysis and acute renal failure in men, but there are no reports of this environmental illness in otherwise healthy women. We report the first case of heat and exercise induced acute renal failure in a young nonacclimated adult female following intense exertion in the Grand Canyon. This individual displayed the typical clinical features of exertional heat stroke including hyperpyrexia, CNS disturbance, rhabdomyolysis, oligoanuric acute renal failure, and disseminated intravascular coagulopathy. The pathophysiology is discussed as well as sexual differences in response to heat and exercise. The specific factors that may have predisposed this young woman to heat stroke from exertion are identified.

Inhibition of compensatory renal growth by indomethacin

Renal prostaglandins may be important in the modulation of compensatory renal growth. Reductions in renal mass are associated with increased synthesis of these substances by the remaining kidney, and inhibition of prostaglandin synthesis diminishes renal function in partially nephrectomized animals and in patients with reduced functioning renal mass. We examined the effects of uninephrectomy and treatment with indomethacin on renal prostaglandin E2 and 6-keto prostaglandin F1 alpha concentrations in adult male Sprague Dawley rats. The renal content of these prostaglandins was significantly increased in the remaining kidney two days following uninephrectomy (p less than 0.01). Treatment with 5 mg/kg/day of indomethacin over this period abolished the compensatory increase in renal prostaglandin synthesis and significantly attenuated compensatory increases in renal mass, protein and RNA concentrations (p less than 0.05). No alterations in kidney weight, protein or RNA concentrations were found in intact animals treated with the same dose of indomethacin. These findings suggest renal prostaglandins may participate in the biological events leading to compensatory renal growth.

Dietary fish oil interferes with renal arachidonic acid metabolism in rats: Correlations with renal physiology

Dietary fish oil has been reported to have both beneficial and deleterious effects in animal models of renal disease, which may be related to alterations in renal eicosanoid metabolism. The influence of dietary fish oil on glomerular and renal tubular responses that are linked to arachidonic acid metabolism was examined. Dietary fish oil had antidiuretic and antinatriuretic effects, which correlated with reduced renal cortical endogenous prostaglandin E2 (PGE2). Fish oil altered the renal balance of dienoic prostacyclin (PGI2) to thromboxane (TXA2) in favor of vasodilation, which may explain the observed exaggerated compensatory increases in glomerular function in response to uninephrectomy. Intact rats fed fish oil for 6 months developed proteinuria and impaired glomerular filtration rates (GFR). These deleterious effects were associated with evidence of increased renal lipid peroxidation. These results suggest that dietary fish oil modifies glomerular and renal tubular function in rats, and worsens age-associated proteinuria and declines in GFR. These effects may reflect the impact of dietary fish oil on renal fatty acid composition and arachidonic acid metabolism.

Studies on Renal Growth Regulation by Urea and Ammonia in Normal Rat Kidney Cells

The hypothesis that protein metabolites regulate renal growth has been considered for decades, and the overall objective of this work was to test this hypothesis in vitro using an established line of renal tubular epithelial cells, NRK-52E. The addition of urea to the medium of confluent cultures stimulated DNA synthesis which was dependent on the concentration of urea, but independent of the presence of serum. Urea enhanced proliferation of subconfluent cultures of NRK cells in the presence of dilute serum to a similar degree as epidermal growth factor (EGF). Either deletion of serum from the medium or allowing the cultures to achieve confluence prevented the proliferative response to urea, but not EGF. Ammonium chloride stimulated the uptake of 3H-thymidine but did not increase cell number. Ammonium chloride increased the uptake of 3H-leucine and total cellular protein/DNA, while urea had no effect on these markers of growth. The rate of hydrolysis of urea to ammonia in vitro was not altered by the presence of NRK cells. These results suggest that urea and ammonia may regulate renal mass, and that their actions are separate and different.

Studies on Serum Renotropic Activity after Uninephrectomy in Rabbits

The present study was undertaken to critically examine the hypothesis that circulating renotropin is the primary stimulus for compensatory renal growth. Blood was collected before and after either left nephrectomy or sham operation from a total of 34 rabbits and the serum renotropic activity assessed by the uptake of 3H-thymidine in primary cultures of rabbit kidney cells. Sera obtained after uninephrectomy had significantly more renotropic activity than sera collected before surgery. In some cases, sera obtained after sham operation had more renotropic activity than those collected before, but the mean response was not increased after sham operation. The difference between sera collected before and after uninephrectomy was not transferrable to primary cultures of rabbit liver cells. These data confirm a modest but significant influence of uninephrectomy on the renotropic activity of blood in rabbits.

CARDIOVASCULAR COLLAPSE FOLLOWING ORTHOCLONE OKT3 ADMINISTRATION : A CASE REPORT

Orthoclone OKT3 has been described to have significant adverse effects on the cardiovascular system, including pulmonary edema, angina, dysrhythmias, hypertension, and hypotension, usually following the first or second doses of the drug. We describe a case of cardiopulmonary arrest in a patient 1 minute after the initial injection of OKT3. Two subsequent doses were successfully administered with the guidance of hemodynamic monitoring, which showed profound, immediate effects of OKT3 on the cardiovascular system. Potential mechanisms of these effects are discussed.

Studies on the impact of dietary fat composition on proteinuria in diabetic rats

Rats with streptozotocin diabetes were pair-fed diets containing 20% beef tallow (BT), fish oil (FO), or safflower oil (SO) for up to six months. After one month, differences in glucose control were not observed but rats fed FO had more renal hypertrophy. FO reduced glomerular prostaglandin E2 and 6-keto F1 alpha, and BT increased thromboxane B2 production, but there were no differences in glomerular filtration rate (GFR) or renal plasma flow (RPF). Animals fed BT needed more insulin after two months than rats fed FO followed by SO. After six months, diabetic rats fed FO had larger relative kidney weights than SO or BT, but a similar pattern was present in non-diabetic controls fed the same diets. Diabetic rats fed BT had more proteinuria than diabetic rats fed SO but not FO. However, FO-fed controls had more proteinuria than controls fed SO and similar levels of proteinuria as diabetic rats fed FO. The composition of dietary fat alters glucose tolerance in diabetic rats after two months. BT increases glomerular thromboxane production and hastens proteinuria compared to SO. FO enhances renal growth and proteinuria, but this effect is independent of the diabetic condition.

Dietary fish oil enhances renal hypertrophy in experimental diabetes.

Renal hypertrophy occurs early in the natural history of human and experimental diabetes and may be a manifestation of the same pathophysiological process which ultimately results in diabetic nephropathy. The precise biological events which stimulate and regulate this growth process remain incompletely understood. We postulated that renal eicosanoids contribute to the development of renal hypertrophy in diabetes. We elected to test the effects of suppression of dienoic eicosanoid metabolism (arachidonic acid metabolism) on renal hypertrophy in diabetic rats by feeding fish oil. Diabetic rats fed fish oil had markedly reduced insulin requirements compared to control rats pair-fed a beef tallow-rich diet. The concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were depressed in the renal cortex of diabetic rats fed fish oil. This alteration in eicosanoid metabolism was associated with a substantial enhancement of diabetic renal hypertrophy. These results indicate that dietary fish oil has profound effects on renal eicosanoid metabolism in experimental diabetes and that these autocoids may participate in the biological events which regulate diabetic renal hypertrophy.