trimethoprim--sulfamethoxazole-drug-combination and Nephritis--Interstitial

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Deprescriptions; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Nephritis, Interstitial; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Antiinfective drugs may show the same mechanisms of nephrotoxicity as other drugs, and these can be subgrouped into vascular, tubulotoxic, tubulo-obstructive, and immunologic effects. While vascular effects of antiinfective drugs are rare, tubulotoxicity is a well known phenomenon, especially in connection with aminoglycosides and amphotericin B as well as cephalosporins, pentamidine, foscarnet, and cidovir. The tubulo-obstructive effect caused by precipitation of the drug and first observed after treatment with sulfonamides in the 1940s, has become a renascent problem now that high doses of sulfonamides are being given to immunocompromised patients (sulfadiazine, cotrimoxazole). Moreover, this effect has also been associated with newer antiviral drugs like acyclovir and indinavir. We describe a transplant patient who received high doses of cotrimoxazole for pneumocystis carinii pneumonia and lost transplant function mainly due to bioptically proven glomerular and tubular crystallization with tubular degeneration caused by sulfamethoxazole. Acute interstitial nephritis is the main immunologic effect of antiinfective drugs (especially rifampicin but also cephalosporins, quinolones, sulfonamides, and penicillins). Immune stimulation by cytokine treatment (mainly interferon-alpha) involves several kinds of autoimmune renal diseases like acute interstitial nephritis or glomerulonephritis as well as interstitial and vascular rejection of renal transplants.

Topics: Adult; Anti-Infective Agents; Autoimmune Diseases; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Nephritis, Interstitial; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antineoplastic Agents, Alkylating; Brain Neoplasms; Diabetes Insipidus, Nephrogenic; Glioblastoma; Humans; Hydrochlorothiazide; Kidney Function Tests; Male; Middle Aged; Nephritis, Interstitial; Sodium Chloride Symporter Inhibitors; Temozolomide; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Acute interstitial nephritis is an infrequent cause of early allograft dysfunction. Prophylactic trimethoprim sulfamethoxazole (cotrimoxazole) is frequently prescribed early in the course of kidney transplantation. Herein we have reported a case of delayed graft function associated with eosinophilia in which the renal biopsy showed interstitial mononuclear infiltrates with abundant eosinophils. An initial methylprednisolone course failed to lower the serum creatinine, but renal function and eosinophilia persistently improved following cotrimoxazole withdrawal and a second course of steroids. Cotrimoxazole acute interstitial nephritis is an infrequent but treatable cause of kidney allograft dysfunction, which should be included in the differential diagnosis of delayed renal allograft function.

Topics: Adult; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Nephritis, Interstitial; Trimethoprim, Sulfamethoxazole Drug Combination

Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts.. We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.. All cases occurred within 1 month of transplantation and accounted for 2.12% (11/518) of the total number of transplant biopsies performed during the study period. However, this figure increased to 10.1% (11/109) when those biopsies performed for early allograft dysfunction (< 1 month) were taken into account. After discontinuation of TMP- SMX alone, all patients had an immediate improvement in serum creatinine with excellent long term allograft function - mean improvement of serum creatinine from 465 micromol/l to 136 micromol/l at last follow-up (range 15 - 55 months).. AIN secondary to TMP-SMX, although an uncommon cause of allograft dysfunction over the study period, accounted for over 10% of cases of allograft dysfunction within the first month of transplantation. Therefore, a high degree of clinical suspicion for TMP-SMX-induced AIN is warranted when confronted with early acute allograft dysfunction.

Topics: Acute Disease; Adult; Aged; Anti-Infective Agents; Creatinine; Female; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Middle Aged; Nephritis, Interstitial; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a patient who sought treatment for acute renal allograft dysfunction 2 weeks after renal transplantation. Renal allograft biopsy (RAB) showed intimal arteritis, severe interstitial infiltration with a few eosinophils, and severe tubulitis. Pathologic diagnosis was acute rejection (grade 2b- Banff 93); however, another clinical diagnosis, drug-induced acute interstitial nephritis (AIN), was not excluded. Before the RAB, his trimethaprim-sulfamethoxazole (TMP-SMZ) treatment was discontinued. Renal function began to improve on biopsy day without antirejection therapy. Recovery of renal function without antirejection treatment and discontinuation of TMP-SMZ shows that renal pathology might be related to drug-induced dysfunction and drug-induced AIN and vasculitis. After 5 years, the patient and his renal allograft function are both well.

Topics: Adult; Biopsy; Diagnosis, Differential; Graft Rejection; Humans; Kidney; Kidney Transplantation; Male; Nephritis, Interstitial; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Drug-induced acute interstitial nephritis is a common cause of dysfunction in native kidneys, but is rarely reported in renal allografts. This report describes six renal transplant recipients with acute renal allograft dysfunction or delayed allograft function in whom a renal transplant biopsy showed histopathologic features of drug-induced interstitial nephritis with no diagnostic evidence of acute rejection, cyclosporine or tacrolimus nephrotoxicity, or other lesion that could account for the graft dysfunction. In five of the six patients, interstitial nephritis occurred within 4 weeks of transplantation. All the patients were receiving trimethaprim-sulfamethoxazole and/or other drugs associated with interstitial nephritis. After discontinuation of these drugs and short-term corticosteroid treatment, all patients showed improvement in renal function, although the time course of this improvement varied considerably, with three patients showing a return to baseline serum creatinine level within 2 weeks and two patients showing a gradual improvement over 8 weeks. Four of the five patients followed up for more than 1 year (range, 14 to 33 months) after the episode of interstitial nephritis had good allograft function (serum creatinine level

Topics: Acute Disease; Adult; Biopsy; Diagnosis, Differential; Drug Therapy, Combination; Female; Graft Rejection; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Nephritis, Interstitial; Postoperative Complications; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

A 51-year-old man with diabetes mellitus and mild hypertension developed acute interstitial nephritis 4 days after starting a course of co-trimoxazole for bronchopneumonia. Following initial symptoms of overt hypersensitivity, he developed azotemia and renal tubular dysfunction with malaise and anorexia requiring hospitalization. Renal pathology demonstrated an acute granulomatous interstitial nephritis superimposed on chronic diabetic renal disease.

Topics: Anti-Infective Agents; Bronchopneumonia; Diabetic Nephropathies; Drug Combinations; Humans; Kidney; Male; Middle Aged; Nephritis, Interstitial; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole may cause life-threatening reactions and even death, but such reactions are rare and do not detract from its usefulness. As with any therapy, however, caution should be observed in its use in children, and especially in the elderly.

Topics: Anti-Infective Agents; Child; Dermatitis, Exfoliative; Drug Combinations; Humans; Male; Nephritis, Interstitial; Pulmonary Fibrosis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Nine episodes of drug associated acute interstitial nephritis, in seven patients, were treated between 1972 and 1980. The drugs implicated were cotrimoxazole (three times), ampicillin, Magnapen (ampicillin and flucloxacillin), penicillin, gentamicin, paracetamol and bendrofluazide. The time from exposure to the onset of symptoms ranged from one to 30 days. Presentation was with acute renal failure, which was non-oliguric in five cases, accompanied by rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristic interstitial infiltrate comprising substantial numbers of lymphocytes and plasma cells, with a variable number of neutrophils, eosinophils and histiocytes. Immunofluorescence was negative in all four cases studied in the acute phase, and showed scattered deposits of IgG, IgM, IgA and C3 on the tubular basement membrane in one patient during recovery. Significant proteinuria and an abnormal urine deposit were present in all cases, and seven of nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisolone and in all there was a response with a diuresis or spontaneous fall in serum creatinine within 72 hrs, and recovery of virtually normal renal function. Of two cases who did not initially receive steroids, one improved more slowly and one developed chronic renal impairment.

Topics: Acetaminophen; Acute Disease; Adult; Ampicillin; Anti-Infective Agents, Urinary; Bendroflumethiazide; Drug Combinations; Female; Floxacillin; Gentamicins; Humans; Kidney; Male; Methylprednisolone; Middle Aged; Nephritis, Interstitial; Penicillins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Arteritis; Drug Combinations; Exanthema; Female; Humans; Liver Function Tests; Middle Aged; Nephritis, Interstitial; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination