Biomedical subjects

E A Burdmann

Publications and source records attributed to E A Burdmann.

At least 19 recordsLinked to original sources

PubMed2001

Rhabdomyolysis, acute renal failure, and death after monensin ingestion.

We report a case of human monensin intoxication; to our knowledge, this is the first reported case in the medical literature. The patient took a dose of monensin three times higher than a dose considered lethal for cattle and developed a clinical picture similar to that reported in veterinary medicine. There was an early and extremely severe rhabdomyolysis followed by acute renal failure, heart failure, and death. The main changes observed at autopsy were extensive skeletal muscle necrosis, complement deposition at the myocardial level, pulmonary edema, and acute tubular damage.

Acute Kidney Injury↗

PubMed2001

Fatal cerebral hemorrhage and acute renal failure after young Bothrops jararacussu snake bite.

An unusual case of a patient developing severe coagulopathy disorder and a clinical picture of cerebral hemorrhage and acute renal failure after young Bothrops jararacussu snake bite is reported. The mechanisms of snake venom-induced injury are discussed and similar cases in literature are revised and compared. The use of bothropic-Crotalus antivenom in severe B. jararacussu envenomation is discussed.

Acute Kidney Injury↗

PubMed2000

The role of renal sympathetic nerves in experimental chronic cyclosporine nephropathy.

BACKGROUND: Sympathetic nervous system hyperactivity has been postulated to play a major role in the intense intrarenal vasospasm and hypertension provoked by cyclosporine. It has been argued that the denervated renal allograft may be partially protected from the tubulointerstitial fibrosis associated with chronic cyclosporine administration compared with innervated kidneys in extrarenal transplantation. METHODS: Utilizing a model of chronic cyclosporine nephropathy in which striped fibrosis develops in the uninephrectomized salt-depleted rat, the effect of renal denervation on renal structure and function was examined. Sprague-Dawley rats maintained on a low-salt diet underwent uninephrectomy and contralateral renal denervation or sham denervation, followed by cyclosporine 15 mg/kg daily by injection. RESULTS: After 21 days, glomerular filtration was markedly depressed and linear zones of tubular atrophy and interstitial fibrosis had developed compared with vehicle-treated control animals (P<0.001). However, there was no significant difference in either renal function or structure between denervated and sham-operated animals treated with cyclosporine. CONCLUSION: We conclude that renal sympathetic neural hyperactivity is not important in the development of chronic cyclosporine nephropathy.

Animals↗

PubMed2000

Renal function changes after elective cardiac surgery with cardiopulmonary bypass.

Cardiac surgery can either induce acute renal failure or improve GFR by improving the cardiac performance. In order to study renal function changes after elective cardiac surgery (CS) with cardiopulmonary bypass (CPBP), 21 patients undergoing valvular CS (VCS) or coronary artery bypass (CAB) were prospectively evaluated in three time periods: before, 24 hours after surgery and 48 hours after surgery. Patients were divided in 2 groups according to the GFR percent change in comparison to the baseline value found 24 hours after CS (deltaGFR24): Group 1, deltaGFR24 decrease higher than 20% (n = 11) and Group 2, deltaGFR24 decrease < or = 20% or deltaGFR24 increase (n = 10). In Group 1, 73% of the patients underwent VCS (p = 0.05 vs. Group 2) and all of them had previous VCS in sharp contrast with Group 2, where none of the patients had previous CS (p = 0.006). Patients in Group I required more volume replacement than Group 2 during the first 24 hours after CS: 2,699+/-704 mL versus 217+/-603 mL respectively, p = 0.019. Despite similar baseline GFR, Group 1 presented lower GFR 24 hours after CS when compared to Group 2 (39+/-5 versus 75+/-8 mL/(min x 1.73m2), p = 0.001) and a significantly different deltaGFR 48 hours after CS as compared to Group 2 (-21+/-11 versus +88+/-36%, p<0.01). Baseline sodium fractional excretion (FENa) in Group 1 was lower than in Group 2 (0.27+/-0.04 versus 0.70+/-0.12%, p = 0.01). No changes were observed after CS in urinary osmolality (Uosm) and urinary pH (UpH) in both groups. The deltaGFR24 showed positive correlation with baseline FENa (r = 0.44 p = 0.04) and negative correlation with volume balance during the first 24h after CS (r = -0.63, p = 0.007). More patients in Group 1 required nitroprusside than in Group 2 (66% vs. 14%, p = 0.04). Anesthesia time was shorter in Group 1 as compared to Group 2: 323+/-21 vs. 395+/-26 min, p = 0.04. No significant hemolysis occurred during CS in either group. There were no differences in age, gender, CPBP time, need for dopamine and/or dobutamine between the two groups. In conclusion, patients who presented GFR decrease after CS underwent VCS more frequently, had more prevalence of previous CS, presented lower baseline FENa, required more volume infusion and more nitroprusside use. On the other hand, no tubular dysfunction was detected in the early follow-up of CS. These results suggest that the observed renal function changes should be the result of an appropriated renal response to a low effective blood volume. In fact, a low baseline FENa anticipated a GFR decrease in these patients. Consistently, CAB patients that usually improve their cardiac output after surgery showed a clear GFR improvement.

Adult↗

PubMed1999

Cyclosporine-induced interstitial fibrosis and arteriolar TGF-beta expression with preserved renal blood flow.

BACKGROUND: Cyclosporine A (CsA)-induced chronic nephrotoxicity is characterized by interstitial fibrosis and afferent arteriole hyalinosis. CsA lesion has been linked to maintained renal vasoconstriction and narrowing of the afferent arteriole lumen diameter, leading to preglomerular ischemia. We investigated the role of renal hemodynamics in CsA-induced transforming growth factor (TGF-beta) expression and interstitial fibrosis. METHODS: Groups of rats fed a low salt diet were given CsA 5 mg/kg/day (CsA) or the vehicle (olive oil, [VH]) s.c. and had the renal blood flow (RBF), glomerular filtration rate (GFR), mean arterial pressure, renal vascular resistance, renal histologic changes, and immunohistochemical features for macrophages and TGF-beta evaluated after 1, 2, and 8 weeks of treatment. RESULTS: At week 1, despite normal renal hemodynamics and MAP, there was a significant macrophage interstitial influx in CsA-treated rats (70+/-16 vs. 29+/-4 cells+/0.5 mm2, in CsA vs. VH, P=0.02) that was progressive with treatment (80+/-13 vs. 32+/-8 cells+/0.5 mm2, P=0.016 and 197+/-36 vs. 23+/-3 cells+/0.5 mm2, P=0.0002, CsA vs. VH at 2 and 8 weeks, respectively). After 2 weeks of treatment, CsA animals developed a significant interstitial fibrosis, with preserved RBF, even when it was assessed 2 hr after CsA injection. There was a significant increase in the immunostaining for TGF-beta in the juxtaglomerular arterioles in CsA-treated rats (48.6+/-3.8 vs. 35.1+/-1.1%, CsA vs. VH at 2 weeks, P<0.05 and 59.0+/-3.2 vs. 37.0+/-2.1%, CsA vs. VH at 8 weeks, P=0.0001). A significant and progressive GFR decrease followed the renal structural injury of CsA treatment. Arteriolar and glomerular anatomic injury were not found throughout the study. CONCLUSIONS: Low CsA doses might generate interstitial fibrosis without any decrease in RBF or structural arteriolar lesion evidence, possibly through early macrophage influx and increased TGF-beta expression. It clearly seems that CsA-induced ischemia and tubulointerstitial injury may occur independently, suggesting that chronic CsA nephrotoxicity may be very hard to prevent or even not be preventable at all.

Animals↗

PubMed1998

Acute bilateral renal artery occlusion due to granulomatous and necrotizing vasculitis.

A case of anuric acute renal failure due to bilateral renal artery obstruction in a 42 year-old man is presented. The obstruction was caused by bilateral thrombosis secondary to arteritis. Autopsy showed granulomatous and necrotizing vasculitis in both main renal arteries. Scarring and also necrotizing vasculitis were found from interlobular to arcuate renal arteries. The present case indicates that vasculitis should be considered when there is renal artery obstruction in young patients.

Acute Kidney Injury↗

PubMed1997

Nephrology, dialysis and transplantation in Brazil.

The European Renal Association welcomes this opportunity and feels that European nephrologists should be informed about the state of nephrology in South America, with which particularly our Latin colleagues maintain close cultural relationships. The following report on Nephrology in Brazil is a welcome addition to a series of reports designed to provide to European nephrologists a global view of nephrology. It is hoped that this is not misconstrued as a violation of nephrological Monroe doctrine.

Acute Kidney Injury↗

PubMed1997

Anuric acute renal failure caused by dextran 40 administration.

Dextran 40 is largely used in clinical medicine as a plasma substitute because of its beneficial effects on the microcirculation and antithrombogenic properties. An unusual adverse reaction of dextran administration is oligoanuric acute renal failure. We report two cases of anuric ARF induced by dextran 40. Diuresis and renal function were quickly resumed after plasma-pheresis treatment. Renal biopsy revealed normal kidneys except for swelling and vacuolation of renal tubules suggestive of osmotic nephrosis.

Acute Kidney Injury↗

PubMed1997

Prospective study of tetanus-induced acute renal dysfunction: role of adrenergic overactivity.

To assess the mechanisms related to tetanus-induced acute renal failure (ARF), 30 patients with tetanus had their renal function prospectively studied and factors possibly related to renal changes were evaluated during four weeks of hospitalization. Fifty percent of these patients had a glomerular filtration rate (GFR) < or = 50 ml/min in the first or second week of hospitalization (Group I) and 50% had a GFR > 50 ml/min throughout the entire hospitalization period (Group II). Age, gender, tetanus incubation time and tetanus onset time, hospitalization time, use of nephrotoxic drugs, need for mechanical ventilation with intermittent positive pressure, and presence of systemic infection were similar in both groups. None of the patients presented with oliguria. Autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, by increased heart rate and elevated urinary metanephrine excretion, was higher in Group I compared with Group II. Plasma renin activity, serum creatinephosphokinase levels, and myoglobinuria were not significantly different between the two groups. These results strongly suggest that tetanus-induced ARF has a high prevalence, is characterized by early onset, and is probably related to ANS overactivity.

Acute Kidney Injury↗

PubMed1997

Nephrotoxicity of immunosuppressive drugs: experimental and clinical observations.

Cyclosporine has improved patient and graft survival rates in solid organ transplantation since its introduction in 1976, and has been increasingly applied with considerable clinical benefit in the treatment of autoimmune diseases. However, the therapeutic benefits of immunosuppressive therapy for transplantation and autoimmune indications have been frequently limited by the occurrence of acute and chronic nephrotoxicity, which is the most obvious common side effect. Cyclosporine nephrotoxicity therefore remains an important clinical challenge. The clinical aspects and pathophysiology of nephrotoxicity induced by current and future immunosuppressive drugs are reviewed in this article, with an emphasis on the studies of chronic cyclosporine nephropathy, which is characterized by a decrease in glomerular filtration rate, afferent arteriolopathy, and striped tubulointerstitial fibrosis. Insights gained from experimental models of chronic nephrotoxicity associated with tubulointerstitial fibrosis and arteriolopathy are presented to elucidate the pathophysiology. Thus, experimental and clinical data regarding tacrolimus (FK506) and sirolimus (rapamycin) are presented.

Animals↗

PubMed1996

Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506.

Acute cyclosporine (CsA) nephrotoxicity is characterized by a reduction of glomerular filtration rate (GFR), hypomagnesemia and tubular injury. The mechanisms of CsA's immunosuppressive action and presumably its nephrotoxicity are mediated through inhibition of the renal phosphatase, calcineurin. FK506 (FK), which has a different chemical structure and binding immunophilin, also inhibits calcineurin. We compared the renal effects of these drugs to those of rapamycin (RAPA), which although similar in structure and intracellular binding to FK, does not work by changing calcineurin activity. Rats were given CsA (15 mg/kg/s.c.), FK (6 mg/kg/p.o.), RAPA (3 mg/kg/p.o.) or vehicle (V) for two weeks on a low salt diet. CsA and FK strikingly decreased urinary excretion of nitric oxide, renal blood flow and GFR, whereas RAPA did not. In contrast, all these three drugs caused significant hypomagnesemia associated with inappropriately high fractional excretion of magnesium, suggesting renal magnesium wasting. In addition, with all three drugs there were lesions in the rat kidneys consisting of tubular collapse, vacuolization and nephrocalcinosis. We thus showed that only the calcineurin inhibitors produced glomerular dysfunction in an acute experimental model of nephrotoxicity. The mechanism of hypomagnesemia and tubular injury induced by all three immunosuppressive drugs is unclear but may be independent of calcineurin. The mechanism of renal vasoconstriction on the other hand may be related to inhibition of calcineurin.

Animals↗

PubMed1996

Peculiar electrolytic and hormonal abnormalities in acute renal failure due to leptospirosis.

Hypokalemia in leptospirosis acute renal failure (ARF) was studied in nine patients with severe leptospirosis ARF and five patients with moderate leptospirosis ARF and compared with five patients with severe acute tubular necrosis (ATN) and eight healthy individuals. Urinary volumes of both the severe and moderate leptospirosis groups were higher than those of the severe ATN group. Leptospirosis groups had serum potassium levels lower than those found in the healthy and severe ATN groups. Serum sodium levels were lower in the severe leptospirosis group than in the moderate leptospirosis, the severe ATN, and the healthy groups. There was a positive correlation between the fractional excretion of sodium and potassium in the severe leptospirosis group as well as between serum creatinine and potassium levels in the pooled leptospirosis groups. Urinary pH in the severe and moderate leptospirosis groups was lower than in the severe ATN group. Aldosterone levels were higher in the severe leptospirosis group than in the healthy individuals. Cortisol levels were higher in the leptospirosis groups than in the healthy subjects. These results strongly suggest that hypokalemia in leptospirosis ARF is due to renal potassium wasting potentialized by aldosterone and cortisol, requiring that special attention is given to potassium replacement as well as to volume repletion in the treatment of leptospirosis ARF.

Acute Kidney Injury↗

PubMed1996

Severe acute renal failure induced by the venom of Lonomia caterpillars.

A case of a patient developing anuric acute renal failure and a hemorrhagic syndrome resembling disseminated intravascular coagulation after contact with Lonomia caterpillars is reported. Renal histology showed only mild changes consistent with renal ischemia, although the patient never was hypotensive. The mechanisms of renal injury were obscure and might be related to transient glomerular ischemia due to microcirculation fibrin deposition or to direct venom nephrotoxicity.

Acute Kidney Injury↗

PubMed1995

Cyclosporine A induced arteriolopathy in a rat model of chronic cyclosporine nephropathy.

Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone marrow, and renal transplantation, and is characterized in humans by striped interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar arterioles. This last feature is highly specific for cyclosporine injury and has been difficult to reproduce in normotensive animal models. Salt-depletion has been shown to sensitize rodents to the effects of CsA and accelerate the disease process. We conducted sequential studies in chronically salt depleted, pair fed rats treated with CsA (15 mg/kg, s.c.) or an equivalent dose of olive oil vehicle, and found a histologic lesion associated with CsA that consisted of striped cortical interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of many afferent arterioles. The arteriolopathy was first detected at day 10 with progressive hyalinization of arterioles continuing until termination of the study at day 35. The arteriolopathy consisted initially of eosinophilic granular transformation of smooth muscle cells comprising afferent hilar glomerular arterioles, and progressed to foci of smooth muscle cell vacuolization and accumulation of discrete hyaline deposits in vessel walls. Electron microscopy demonstrated marked accumulation of typical renin granules throughout the smooth muscle cell cytoplasm, corresponding to the eosinophilic granular transformation revealed histologically. Immunocytochemistry confirmed the up-regulated production of renin in these vessels. This study documents a rodent model for CsA arteriolopathy and CsA-associated interstitial fibrosis that strikingly reproduces the most characteristic nephropathic effects of cyclosporine found in human patients treated with this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Cellular proliferation and macrophage influx precede interstitial fibrosis in cyclosporine nephrotoxicity.

Chronic cyclosporine (CsA) nephrotoxicity is a major complication of solid organ transplantation, and is characterized histologically by striped tubulointerstitial fibrosis, tubular atrophy, and hyalinization of the afferent arteriole, a highly specific finding in cyclosporine injury. The salt-depleted rat model of chronic cyclosporine nephropathy mimics these lesions in humans. We conducted sequential studies of this model in groups of pair fed rats (N = 6) treated with CsA (15 mg/kg, s.q.) or an equivalent dose of olive oil. Proliferation of tubular and interstitial cells was documented early in the medulla by day 5 (3.2 +/- 2.1 vs. 0.81 +/- 0.4 cells/HPF in CsA vs. control, P < 0.02), and was maximal in areas of interstitial fibrosis by day 35 (7.9 +/- 3.7 vs. 0.52 +/- 0.2 cells/HPF in CsA vs. control, P < 0.005). The interstitial fibrosis was associated with a significant macrophage influx by day 35 (13.9 +/- 3.5 vs. 1.5 +/- 0.32 cells/HPF, CsA vs. control, P < 0.005), which correlated with increased cortical tubular staining for the macrophage adhesion protein, osteopontin. Elevated serum creatinine correlated with interstitial fibrosis at day 35 (0.85 +/- 0.11 vs. 0.40 +/- 0.03 mg/dl Cr, CsA vs. control, P < 0.005) by linear regression (r = 0.9, P < 0.05). Medullary proliferation and interstitial fibrosis correlated with decreased tubular concentrating ability, and higher urinary volume. Cortical interstitial fibrosis was maximal at day 35 and was associated with an increase in type I and type IV collagen deposition, while tubular injury was associated with increased vimentin expression. Tubular interstitial cells also expressed increased vimentin early in the medulla (day 10) and later in the cortex. Both groups remained normotensive despite significantly elevated juxtaglomerular (JG) apparatus renin expression in CsA treated animals, implicating the intrarenal-renal renin-angiotensin system in this disease. We conclude that cyclosporine nephrotoxicity is associated with early tubular and interstitial cell proliferation, and a significant macrophage influx that precedes the development of cortical interstitial fibrosis and afferent arteriolar hyalinosis. These early cellular changes correlate with functional abnormalities including decreased creatinine clearance (CCr) and decreased medullary concentrating ability, which stabilized despite progressive fibrosis. These cellular events may be important in the pathogenesis of chronic CsA nephrotoxicity.

Animals↗

PubMed1995

Functional and structural characteristics of experimental FK 506 nephrotoxicity.

1. FK 506 (Tacrolimus, Prograf) is a novel immunosuppressant which is effective in solid organ transplantation and autoimmune diseases. The lack of a suitable animal model has hindered the study of the nephrotoxicity of the drug which has emerged as a common adverse effect in clinical trials. We report both acute and chronic nephrotoxicity with tacrolimus (FK) in which renal structure and function are worsened by sodium depletion. 2. Pair fed male Sprague-Dawley rats were given FK (3 or 6 mg/kg, p.o.) or vehicle for 7, 21 and 42 days on low salt or normal diet. The FK whole blood trough levels achieved (3-10 ng/mL) were similar to those observed in FK treated transplant patients. 3. In salt depleted animals treated for 7 days, FK (6 mg/kg) decreased renal blood flow and glomerular filtration rate (1.8 +/- 0.1 and 0.2 +/- 0.1 mL/min per 100 g vs 2.9 +/- 0.2 and 1.1 +/- 0.1 mL/min per 100 g in the vehicle group, P < 0.01). 4. After 21 days of treatment of FK on low salt diet but not normal salt, FK induced focal collapse and vacuolization in proximal tubules and discrete or confluent zones of tubulointerstitial oedema and mononuclear cell infiltration. 5. After 42 days in salt depleted rats, there was significant tubulointerstitial scarring that was associated with an increased plasma renin activity (PRA) (64 +/- 10 vs 30 +/- 4 ng AI/mL per h in the vehicle group, P < 0.05). Animals given normal salt diets did not develop significant histological lesions even up to 42 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Prevention of experimental cyclosporin-induced interstitial fibrosis by losartan and enalapril.

The pathogenesis of renal scarring in chronic cyclosporin nephropathy is unknown. In this study, we evaluated the effects of renin-angiotensin system blockade by enalapril and losartan in a salt-dependent model of cyclosporin-associated chronic tubulointerstitial fibrosis (TIF). Rats kept on normal or low-salt diet were given cyclosporin, cyclosporin+enalapril, cyclosporin+losartan, cyclosporin+enalapril#losartan, or vehicle for 14 and 28 days. Cyclosporin reduced glomerular filtration rate (GFR) in rats fed either diet, but only salt-depleted animals developed significant TIF. Cyclosporin also impaired renal concentrating ability and caused tubular enzymuria. Renin-angiotensin system blockade decreased blood pressure (BP) and promoted afferent arteriolar vasodilatation. Losartan reduced plasma renin activity and prevented cyclosporin-induced increment of cortical alpha 1(I) procollagen mRNA. Renin-angiotensin blockade did not improve GFR and tubular function; however, it strikingly prevented TIF development, even in presence of very low BP. Rats treated with cyclosporin, hydralazine, and furosemide achieved BP values similar to losartan or enalapril groups, but there was no protection against interstitial fibrosis development. These results suggest that cyclosporin-related chronic interstitial injury is mediated by angiotensin II and that the mechanisms promoting the interstitial scarring can be dissociated from glomerular and tubular dysfunction in cyclosporin nephropathy.

Animals↗

PubMed1995

Pathogenesis of cyclosporine nephropathy: roles of angiotensin II and osteopontin.

Low-salt-diet, cyclosporine (CsA; 15 mg/kg per day)-treated rats develop striped interstitial fibrosis, arteriolar hyalinosis, and azotemia similar to the chronic nephropathy observed in humans. To examine the role of angiotensin II in this model, rats on a low-salt diet were given CsA, CsA and the angiotensin II receptor Type I antagonist Losartan (10 mg/kg per day), CsA and hydralazine/furosemide, or vehicle. At Day 35, CsA-treated rats had tubular injury, arteriolopathy of the afferent arteriole, increased expression of the monocyte-macrophage adhesive protein osteopontin, interstitial macrophage infiltration, increased interstitial transforming growth factor-beta expression, and interstitial fibrosis. This study provides new insight in both pathogenic and therapeutic aspects of CsA nephropathy. The pathogenesis of CsA nephropathy involves the expression of osteopontin by tubular epithelial cells, the level of which closely correlates with the degree of macrophage infiltration and interstitial fibrosis in all groups (r = 0.79 and 0.74, respectively; P < 0.001). Therapeutic conclusions can be drawn from the observation that both losartan and hydralazine/furosemide reduced osteopontin expression, macrophage infiltration, transforming growth factor-beta expression, and interstitial fibrosis, but did not prevent the decrease in GFR. Treatment with losartan, but not with hydralazine and furosemide, markedly reduced arteriolopathy. It was concluded that angiotensin II contributes to the vasculopathy (hyalinosis) induced by CsA. In contrast, the interstitial fibrosis mediated by CsA can be partially prevented by both an angiotensin II Type I receptor antagonist or by hydralazine and furosemide. This suggests that the interstitial fibrosis can be dissociated from the vascular effects of CsA. The beneficial effects of lowering blood pressure or vasodilation per se may be difficult to distinguish from the specific effects of angiotensin II receptor blockade.

Angiotensin II↗