Asunto(s)

RESUMEN

Coccidioidomycosis is the most common endemic mycosis to cause disease in solid-organ transplant patients in North America. Underlying renal and liver disease, T-lymphocyte suppression from antirejection medication, and activation of immunomodulating viruses, such as cytomegalovirus, all increase the risk for coccidioidomycosis among these patients. About one half of all cases are the result of reactivation of previously acquired coccidioidal infection and occur during the first year after transplantation. Although disseminated infection is common, most cases manifest pulmonary symptoms. Culture of pulmonary secretions from bronchoscopy is frequently diagnostic. Serologic tests are particularly useful for identifying patients who are at high risk for reactivating coccidioidomycosis posttransplantation. Amphotericin B and azoles are the mainstay of therapy. Although there are no established approaches to preventing coccidioidomycosis among these patients, studies are underway examining the use of prophylactic azole antifungals with documented prior coccidioidal infection.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Posttransplant lymphoproliferative disorder (PTLD) is one of the major complications of immunosuppressive therapy. PTLD is strongly associated with the Epstein-Barr virus (EBV). It is believed that EBV-infected B cells proliferate in an unchecked manner due to suppression of cytotoxic T cells and elevation of B cell-promoting cytokines. There is no consensus on the treatment of PTLD other than reduction of immunosuppressive therapy. We report a case of PTLD with monoclonal B cells confined to the lymph nodes. The patient did not initially respond to reduction of immunosuppression, oral acyclovir, and intravenous immunoglobulin injection. She subsequently responded when subcutaneous injections of interferon alfa (5 million U) were given three times a week. The patient received a 3-mo course of interferon and remained in remission 12 mo after treatment. Her graft function was well maintained, and cyclosporin A was restarted 2 mo after achieving remission. The clinical manifestations, risk factors, pathogenesis, and treatment of PTLD, as well as 12 previously reported cases of PTLD treated with interferon, were reviewed. On the basis of the results presented here, it appears that interferon alfa may be useful in treating PTLD and that there is a need for further clinical trials.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Atrial natriuretic peptide (ANP) inhibits the growth of a variety of cell types in vitro including mesangial cells. The effects of ANP on the growth of the kidney in vivo were evaluated. A 2-h infusion of 0.2 microgram/250 g body wt per minute of ANP suppressed the subsequent uptake of [3H]thymidine into the renal DNA of uninephrectomized but not intact rats. This treatment also depressed the ratio of RNA/DNA in kidneys undergoing compensatory growth. Correlative physiologic studies revealed enhanced GFR in rats with two kidneys infused with ANP, but no increase in the GFR of uninephrectomized rats. It was concluded that ANP may oppose the growth factor(s) mediating compensatory renal growth.

Asunto(s)

RESUMEN

Marine oils contain eicosapentaenoic acid, a fatty acid that competes for cyclooxygenase and reduces the synthesis of dienoic prostanoids including prostaglandin E2 (PGE2). Since PGE2 plays an important role in the estrogen-stimulated release of hypothalamic GnRH on proestrus, it was postulated that a diet containing fish oil would delay first ovulation through inhibitory effects on GnRH release. Thirty, 22-day-old female Sprague-Dawley rats were fed a diet containing fish oil ad libitum. Controls were pair-fed an identical diet with the substitution of safflower oil as the dietary fat. All rats were killed on the morning of first metestrus after vaginal opening and the display of an estrous smear(s). Fish oil feeding did not affect growth as indicated by the lack of an observed effect on body weights or femur lengths. On the other hand, pituitary, ovarian, and uterine weights were significantly lower in the rats fed fish oil (p < 0.001). The age at first estrus of the rats fed fish oil was significantly increased compared with the controls (42.9 +/- 1.0 vs. 36.1 +/- 0.3 days; p < 0.001), whereas the number of rats with corpora lutea (CL), as well as the number of CL per ovary (2.3 +/- 0.4 vs 4.8 +/- 0.6 for controls; p < 0.001) was significantly reduced by fish oil feeding. GnRH concentration in the preoptic area/hypothalamus was significantly increased in the fish oil-fed rats (21.4 +/- 4.0 pg/mg vs. 7.6 +/- 2.2 pg/mg for controls; p < 0.01); radioimmunoassable hypothalamic PGE2 was concomitantly reduced (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

We were able to confirm previous studies demonstrating that administration of thyroxine is capable of ameliorating the severity of acute nephrotoxic renal failure in the rat. Nephrotoxic acute renal failure was induced by the subcutaneous injection of potassium dichromate (6.25 mg/kg) into Sprague-Dawley rats. Twenty-four hours after this injection, rats received an intraperitoneal injection of either thyroxine (80 micrograms/kg body wt) or normal saline. Forty-eight hours after the potassium dichromate injection, renal clearance studies were performed. Inulin clearance was significantly higher in the thyroxine-treated than in the saline-treated acute renal failure rats: 1.12 +/- 0.13 (SEM) mL/g versus 0.75 +/- 0.07 mL/min/g kidney wt (P = 0.025). Thyroxine treatment also effected an increase of p-aminohippuric acid extraction from 0.23 +/- 0.03 to 0.33 +/- 0.02 (P = 0.011) and a decrease in the fractional excretion of sodium from 0.38 +/- 0.21 to 0.11 +/- 0.03% (P = 0.037 by Mann-Whitney U test). In order to investigate one potential mechanism of the beneficial effect of thyroxine we studied renal tubular regeneration in this model of acute renal failure. Renal cortical uptake of labeled thymidine into DNA was significantly increased 48 h after the injection of potassium dichromate, and thyroxine administration further enhanced this repair process: 53.9 +/- 3.6 versus 81.4 +/- 5.3 dpm/200 pg of DNA (P = 0.0033).

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Compensatory growth of the kidney occurs in response to a partial reduction in renal mass. This compensatory renal growth may be regulated by a circulating renotropic factor. Prostaglandin synthesis has been shown to be increased in kidneys undergoing compensatory renal growth in vivo. In the present study we observed that the addition of rabbit sera obtained after uninephrectomy enhanced DNA synthesis in primary cultures of rabbit kidney cells compared to sera obtained prenephrectomy. The stimulated kidney cells produced more prostaglandin E2 than control cells. Furthermore, the addition of prostaglandin E2 to rabbit kidney cells in the presence of control sera also stimulated DNA synthesis. These results provide further evidence that prostaglandins may participate in the biological events which regulate renal growth in response to a circulating renotropic factor.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Chronic treatment with diethylstilbesterol (DES) induces renal cancer in male Syrian hamsters. This tumor may result from direct carcinogenicity of the estrogen, but extrarenal neuroendocrine effects of DES may also be important in modulating tumor growth in the kidney. Since light deprivation is known to profoundly influence neuroendocrine function in the hamster, we elected to examine the effects of short photoperiod or blinding on the development of the DES-induced renal tumor in this species. Animals were maintained either in long (14 hours of light and 10 hours of dark) or short (10 hours of light and 14 hours of dark) photoperiod or blinded. Groups of six to eight animals were sacrificed after three, six or nine months of treatment with either DES or the vehicle. All animals treated with DES for nine months had evidence of renal tumors, but the rate of growth and final size of the tumors were significantly reduced by either maintenance in short photoperiod or blinding. These data provide unique evidence of the importance of neuroendocrine system in the modulation of the DES-induced renal tumor in hamsters.

Asunto(s)

RESUMEN

The basic mechanisms of renal growth remain poorly understood. The work hypertrophy theory holds that after an acute reduction in renal mass, the growth of the kidney occurs as a consequence of increased renal function. Pharmacological inhibition of renal prostaglandin synthesis impairs the acute adaptive increases in both renal function and mass following partial nephrectomy. The present study examines the effects of four weeks of dietary fish oil on renal growth, function and arachidonic acid metabolites in intact and uninephrectomized male Sprague-Dawley rats. Dietary fish oil interferes with dienoic prostaglandin and thromboxane production in favor of synthesis of trienoic analogues. Control animals were pair-fed an identical diet with the exception that the fat was replaced by beef tallow. Renal cortical concentrations of arachidonic acid metabolites were reduced in animals fed fish oil, and urinary excretion of prostaglandin E2 was impaired. Fish oil feeding resulted in increased kidney weight without concomitant increases in renal function in intact animals. Glomerular filtration rate and renal plasma flow were greater in uninephrectomized rats fed fish oil compared to uninephrectomized controls pair-fed beef tallow. Augmentation of the compensatory increases in renal function observed with fish oil feeding was not associated with any additional renal hypertrophy. These data indicate that dietary fish oil has a profound impact on renal growth and function, which may be the consequence of altered renal and/or extrarenal arachidonic acid metabolism. Furthermore, the direction of the alterations in renal mass oppose that of renal function, providing clear and unique evidence against the work hypertrophy theory of renal growth.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Increases in kidney size and function are characteristic features of the early stages of Type I diabetes mellitus, and may contribute to the pathogenesis of diabetic nephropathy. Other studies have shown that the relative circulating concentrations of insulin and glucagon may be regulatory to renal growth and function. In order to elucidate the role of pancreatic glucagon in diabetic renal growth, subtotal pancreatectomy was performed prior to administration of streptozotocin to rats. Glycosuria and kidney weight were significantly reduced by subtotal pancreatectomy, although creatinine clearance and blood glucose levels were not different from diabetic controls. These data suggest that hyperglucagonemia may be an important mediator of renal growth in insulinopenic diabetes mellitus.

Asunto(s)

RESUMEN

Glucagon has been implicated as a growth-promoting hormone in the kidneys of diabetic animals, but its role in the nondiabetic state is unknown. We evaluated the effect of subcutaneous glucagon administration on renal growth in intact rats with two kidneys and after 50% reduction in renal mass. The relative kidney weight was increased in intact rats treated with a glucagon infusion for 7 days (p less than 0.01), but decreased in uninephrectomized rats treated with glucagon (p less than 0.05). Absolute kidney weight gain and rates of renal DNA synthesis were also significantly blunted by glucagon infusion in uninephrectomized rats. These data suggest that 'physiologic' and 'compensatory' renal growth are governed by separate processes. Furthermore, the observation that glucagon promotes renal growth in intact nondiabetic animals supports its possible role as a growth factor in the early stages of diabetes.

Asunto(s)

RESUMEN

The primary stimulus for compensatory renal growth is unknown. This process may be regulated by a circulating renotropic factor or may reflect a growth response to increased work. Prostaglandins appear to participate in compensatory renal growth as indomethacin has been shown to attenuate increases in both renal mass and function after uninephrectomy in rats. The goal of the present study was to test the effects of other cyclooxygenase inhibitors on compensatory renal growth and to evaluate the effects of indomethacin on renal growth in vitro in response to the purported renotropic factor. Both ibuprofen and meclofenamate retarded compensatory renal growth two days after uninephrectomy in rats (p less than 0.05). The addition of indomethacin to the medium of kidney slices incubating with sera from uninephrectomized rats reduced renal DNA synthesis, whereas indomethacin had no effect on renal growth when added to slices incubating with sera from intact animals. These data provide more support for an important role for prostaglandins in compensatory renal growth.

Asunto(s)