allopurinol and Nephritis--Interstitial

Adenine phosphoribosyltransferase (APRT) deficiency (OMIM #614723) is a rare autosomal recessive defect in the purine salvage pathway that causes excessive production of 2,8-dihydroxyadenine, leading to nephrolithiasis and chronic kidney disease (CKD). This case report describes the natural history of CKD in untreated APRT deficiency. We describe a novel APRT mutation (chr16:88877985 G / C; c.195 C>/G; p.His54Asp) presenting with CKD without nephrolithiasis. The patient initially required dialysis, but kidney function improved with allopurinol. We reviewed APRT deficiency reported in the literature to determine the loss of kidney function in individuals with untreated APRT deficiency and its relationship to nephrolithiasis. We identified 95 individuals in whom kidney function was assessed prior to treatment. There was a bimodal distribution of kidney failure. AKI occurred frequently in childhood due to obstructing nephrolithiasis or crystalline nephropathy and was usually reversible. CKD developed after age 20 in all patients irrespective of nephrolithiasis history, with 36/42 patients > 40 years of age having at least stage 3 CKD, and 24/42 having an eGFR > 10 mL/min/1.73m2 or being on dialysis. There were 13 adults without nephrolithiasis and 50 adults with nephrolithiasis. The mean age of end-stage renal diesease (ESRD) was 50.52 ± 13.9 for those without nephrolithiasis and 43.4 ± 15.8 years for those with nephrolithiasis (p = 0.24). APRT deficiency is associated with slowly progressive CKD that occurs independently of nephrolithiasis. Diagnosis should be considered in all individuals with chronic tubulointerstitial kidney disease, with or without the presence of nephrolithiasis. In our patient, allopurinol 300 mg/day resulted in improvement of kidney function.
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Topics: Adenine Phosphoribosyltransferase; Allopurinol; Antimetabolites; Glomerular Filtration Rate; Humans; Kidney Calculi; Male; Metabolism, Inborn Errors; Middle Aged; Nephritis, Interstitial; Renal Insufficiency, Chronic; Urolithiasis

Topics: Allopurinol; Aminoglycosides; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents; Captopril; Cephalosporins; Cisplatin; Diuretics; Glomerulonephritis; Gold; Humans; Kidney; Kidney Diseases; Kidney Tubular Necrosis, Acute; Lithium; Nephritis, Interstitial; Penicillamine; Penicillins; Rifampin; Semustine; Sulfonamides; Tetracycline; Trimethadione

Topics: Allopurinol; Gout; Humans; Kidney Calculi; Kidney Diseases; Nephritis, Interstitial; Purines; Uric Acid

Topics: Allopurinol; Female; Gout; Humans; Kidney Calculi; Male; Nephritis, Interstitial; Purines; Uric Acid

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal adverse drug reaction with variable renal involvement. We report the case of a man who presented with allopurinol-induced DRESS and acute kidney injury (AKI) requiring hemodialysis. Kidney biopsy revealed eosinophilic tubulointerstitial nephritis and necrotizing vasculitis of the intralobular arteries without systemic markers of vasculitis. After cyclophosphamide and glucocorticoids, his symptoms and AKI resolved. To our knowledge, this is the first case of kidney-limited necrotizing vasculitis, questioning whether a biopsy should be routinely performed in patients with DRESS accompanied by severe AKI. It is possible that kidney-limited necrotizing vasculitis is an under-diagnosed manifestation of DRESS syndrome, and in such a setting, early recognition, stopping the offending agent, and use of aggressive immunosuppressive therapy, including cyclophosphamide, may lead to a favorable outcome.
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Topics: Acute Kidney Injury; Allopurinol; Drug Hypersensitivity Syndrome; Humans; Male; Middle Aged; Necrosis; Nephritis, Interstitial; Vasculitis

Renal interstitial fibrosis is the common pathway in progressive renal diseases, where oxidative stress promotes inflammation and macrophage infiltration. Febuxostat is a novel nonpurine xanthine oxidase (XO)-specific inhibitor for treating hyperuricemia. While some reports suggest a relationship between hyperuricemia and chronic kidney disease (CKD), the renoprotective mechanism of an XO inhibitor in CKD remains unknown. Recent reports have focused on XO as a source of oxidative stress.. Here, we investigate the potential of febuxostat to reduce fibrogenic and inflammatory responses in an established interstitial fibrosis model-unilateral ureteric obstruction (UUO). Male Sprague-Dawley rats were divided into three groups: sham-operated group, vehicle-treated UUO group, and febuxostat-treated UUO group.. Treatment with febuxostat diminished XO activity in obstructed kidneys, and suppressed nitrotyrosine, a marker of oxidative stress. Consequently, febuxostat inhibited early proinflammatory cytokine expression, followed by a reduction of interstitial macrophage infiltration. In addition, febuxostat suppressed transforming growth factor-β messenger RNA expression, thereby ameliorating smooth muscle alpha actin and type I collagen expression.. Our results provide evidence for the renoprotective action of febuxostat against the formation of interstitial fibrosis. A decrease in macrophage infiltration and interstitial fibrosis, along with a decrease of the oxidative stress marker, strongly suggests the existence of a causal relationship between them. Febuxostat may have therapeutic value in slowing or preventing interstitial fibrosis in patients with CKD.

Topics: Animals; Cell Movement; Cytokines; Disease Models, Animal; Febuxostat; Fibrosis; Kidney; Kidney Diseases; Macrophages; Male; Nephritis, Interstitial; Oxidative Stress; Rats; Rats, Sprague-Dawley; Thiazoles; Transforming Growth Factor beta; Ureteral Obstruction; Xanthine Oxidase

Nicorandil exhibits a protective effect in the vascular system, which is thought to be due to vasodilatation from opening ATP-dependent potassium channels and donation of nitric oxide. Recently, nicorandil was shown to be renoprotective in models of acute kidney injury and glomerulonephritis. However, the specific mechanisms of renoprotection are unclear. We evaluated the effect of nicorandil on the rat remnant kidney model of chronic kidney disease. Blood pressure was unchanged by a 10-wk course of nicorandil, while albuminuria was significantly reduced. Glomerular injury and tubulointerstitial injury were also ameliorated by nicorandil. Oxidative stress, as noted by renal nitrotyrosine level and urine 8-hydroxy-2'-deoxyguanosine, were elevated in this model and was significantly reduced by nicorandil treatment. Treatment was associated with maintenance of the mitochondrial antioxidant, manganese SOD, in podocytes and with suppression of xanthine oxidase expression in infiltrating macrophages. Interestingly, these two cell types express sulfonylurea receptor 2 (SUR2), a binding site of nicorandil in the ATP-dependent K channel. Consistently, we found that stimulating SUR2 with nicorandil prevented angiotensin II-mediated upregulation of xanthine oxidase in the cultured macrophage, while xanthine oxidase expression was rather induced by blocking SUR2 with glibenclamide. In conclusion, nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.

Topics: Albuminuria; Animals; ATP-Binding Cassette Transporters; Blotting, Western; Cells, Cultured; Disease Progression; Immunohistochemistry; KATP Channels; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Macrophages; Male; Mice; Nephritis, Interstitial; Nicorandil; Nitric Oxide; Oxidative Stress; Paraffin Embedding; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Receptors, Drug; Sulfonylurea Receptors; Xanthine Oxidase

Tubule-interstitial nephritis (TIN) results in decreased renal function and interstitial inflammation, which ultimately leads to fibrosis. Excessive adenine intake can cause TIN because xanthine dehydrogenase (XDH) can convert this purine into an insoluble compound, which precipitates in the tubuli. Innate immune sensors, such as Toll-like receptors (TLR) and inflammasome complex, play a crucial role in the initiation of inflammation. The aim of this study was to evaluate the roles of TLR-2 and -4, Myd88 and inflammasome complex in an experimental model of TIN. Here, we show that wild-type (WT) mice fed adenine-enriched food exhibited significant renal dysfunction and enhanced cellular infiltration accompanied by collagen deposition. They also presented higher gene and protein expression of pro-inflammatory cytokines. In contrast, TLR-2, -4, MyD88, ASC and Caspase-1 KO mice showed renoprotection associated with expression of inflammatory molecules at levels comparable to controls. Furthermore, treatment of WT animals with allopurinol, an XDH inhibitor, led to reduced levels of uric acid, oxidative stress, collagen deposition and a downregulation of the NF-kB signaling pathway. We concluded that MyD88 signaling and inflammasome participate in the development of TIN. Furthermore, inhibition of XDH seems to be a promising way to therapeutically target the developing inflammatory process.

Topics: Adenine; Allopurinol; Animals; Diet; Disease Progression; Inflammasomes; Inflammation; Kidney Tubules; Mice; Mice, Knockout; Myeloid Differentiation Factor 88; Nephritis, Interstitial; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4; Xanthine Dehydrogenase

Hyperlipidemia can induce or aggravate renal tubulointerstitial injury. Experiments in a complex rat model with chronic glomerulonephritis and long-standing, coexisting hyperlipidemia suggested that induction of xanthine oxidase (XO), with increased oxygen radical generation, is involved in aggravation of tubulointerstitial injury. To separate the role of XO in the initial events of lipid-mediated tubulointerstitial injury, short-term experiments with diet-induced hyperlipidemia over 21 and 35 days were performed in otherwise healthy rats. XO expression in relation to the antioxidant enzymes was examined in the cortical tubulointerstitium (TIS) and proximal tubules (PT). Subsequent experiments with XO inhibition were performed, examining tubulointerstitial infiltration with ED1-positive cells and expression of adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) as indicators of early injurious events. Hyperlipidemia increased XO activity in TIS by 40 and 86%, and in PT by 28 and 90% at days 21 and 35, compared with controls on regular diet. This increased activity was associated with increased reactive oxygen species. Among the antioxidant enzymes, glutathione peroxidase activity increased in TIS by 40% and in PT by 90%. Histological evaluation showed a three-fold increase in ED1-positive cells and increased MCP-1 and vascular cell adhesion molecule-1 (VCAM-1) expression at day 35 in the TIS. Inhibition of XO prevented tubulointerstitial ED1 cell infiltration, together with a decreased expression of MCP-1 and VCAM-1. These results point to an important role for XO in the early stage of hyperlipidemia-associated renal injury, mediating macrophage infiltration by a putatively redox-dependent upregulation of MCP-1 and VCAM-1.

Topics: Animals; Antioxidants; Cell Adhesion Molecules; Chemokine CCL2; Ectodysplasins; Glomerulonephritis; Hyperlipidemias; Immunohistochemistry; Kidney Tubules; Macrophages; Male; Membrane Proteins; Nephritis, Interstitial; Rats; Rats, Wistar; Reactive Oxygen Species; Tumor Necrosis Factors; Up-Regulation; Vascular Cell Adhesion Molecule-1; Xanthine Oxidase

A 12-year-old girl, who had been diagnosed as having Cockayne syndrome (CS), was admitted for emaciation and dehydration. On admission the patient had mild chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and hyperuricemia. After rehydration, allopurinol was commenced for her hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with enhancement of proximal tubular dysfunction and hypertension. A renal biopsy showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per day), following which the renal tubular function improved. However, the proteinuria intensified to become nephrotic syndrome. After 1 month the patient developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and renal proximal tubular dysfunction re-occurred. The renal pathology was evaluated by referring to the previous reports of renal pathology in CS. It is suggested that rapid deterioration of the renal function in CS patients might be the result of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by ATIN, as in other reports.

Topics: Acute Disease; Acute Kidney Injury; Allopurinol; Child; Cockayne Syndrome; Fatal Outcome; Female; Humans; Kidney Glomerulus; Microscopy, Electron, Transmission; Nephritis, Interstitial; Nephrotic Syndrome; Prednisolone; Recurrence

Although drug induced interstitial nephritis is a relatively common cause of renal failure,granulomatous forms remain a rare condition. The development of a chronic granulomatous interstitial nephritis due to allopurinol is exceptional, only three cases have been described previously. We report on a patient who presented a granulomatous interstitial nephritis after 10 years of allopurinol administration (300 mg/day). At diagnosis, he had end stage renal disease and dialysis treatment was needed. Two months after drug withdrawal and on corticoid treatment a slow recovery of renal function was observed, allowing the interruption of dialysis. Two years after, the creatinine clearance is 23 ml/min,being dialysis free. We discuss the differential diagnosis of granulomatous interstitial nephritis and its rare association with allopurinol treatment.

Topics: Adrenal Cortex Hormones; Aged; Allopurinol; Chronic Disease; Creatinine; Diagnosis, Differential; Granuloma; Humans; Hyperuricemia; Kidney Failure, Chronic; Male; Nephritis, Interstitial; Renal Dialysis; Sarcoidosis

Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase deficiency on renal tubulointerstitial injury induced by unilateral ureteral obstruction (UUO) has been studied in homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) compared with wild-type mice (C3H/AnLCs(a)Cs(a)). Complete UUO caused interstitial cell infiltration, tubular dilation and atrophy, and interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys (OBK) of both mouse groups. However, the degree of injury showed a significant increase in OBK of acatalasemic mice compared with that of wild-type mice until day 7. The deposition of lipid peroxidation products including 4-hydroxy-2-hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of mitochondrial pathway-derived apoptosis, increased in dilated tubules of acatalasemic mice. The level of catalase activity remained low in acatalasemic OBK until day 7 without compensatory upregulation of glutathione peroxidase activity. The data indicate that acatalasemia exacerbated oxidation of renal tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This study demonstrates that catalase deficiency enhanced tubulointerstitial injury and fibrosis in a murine model of UUO and thus supports the protective role of catalase in this model.

Topics: Acatalasia; Animals; Apoptosis; Body Weight; Catalase; Epithelial Cells; Fibrosis; Glutathione Peroxidase; Immunohistochemistry; In Situ Nick-End Labeling; Kidney Tubules; Male; Malondialdehyde; Mice; Mice, Inbred C3H; Mice, Knockout; Microscopy, Electron; Nephritis, Interstitial; Organ Size; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Ureteral Obstruction; Xanthine Oxidase

Adenine phosphoribosyltransferase (APRT) deficiency is a rarely diagnosed cause of renal allograft dysfunction. We report the case of a 42-year-old man who presented in 1996 with idiopathic renal failure. Native kidney biopsy showed extensive microcrystalline interstitial nephritis. The patient subsequently underwent a living-related kidney transplant with excellent early graft function. During the next year, however, he had worsening allograft function, and allograft biopsy showed recurrent interstitial nephritis. Further chemical and spectroscopic analysis showed this lesion to be an annular microcrystalline nephritis consistent with APRT deficiency. This diagnosis was confirmed on erythrocyte assay. Treatment with allopurinol and a low-purine diet led to improvement and stabilization of renal function. APRT is a rare cause of renal allograft dysfunction requiring a high index of suspicion for early diagnosis and treatment. Increased physician awareness in the United States may hasten diagnosis and limit the morbidity associated with this disease.

Topics: Adenine Phosphoribosyltransferase; Adult; Allopurinol; Antimetabolites; Humans; Kidney; Kidney Transplantation; Male; Metabolism, Inborn Errors; Nephritis, Interstitial; Recurrence

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, the 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 +/- 6.39 mg/24 h; NCG = 59.8 +/- 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 +/- 17.5 mg/24 h; TNG-I = 49.1 +/- 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 +/- 22.23 mg/24 h and 72.66 +/- 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48%) and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Topics: Allopurinol; Animals; Antineoplastic Agents; Biopsy; Disease Models, Animal; Disease Progression; Doxorubicin; Follow-Up Studies; Free Radical Scavengers; Glomerulosclerosis, Focal Segmental; Kidney Glomerulus; Kidney Tubules; Male; Nephritis, Interstitial; Proteinuria; Random Allocation; Rats; Rats, Wistar; Ultrasonography

Topics: Allopurinol; Chemical and Drug Induced Liver Injury; Drug Eruptions; Female; Gout Suppressants; Humans; Middle Aged; Nephritis, Interstitial; Syndrome

Topics: Acute Disease; Acute Kidney Injury; Aged; Allopurinol; Antimetabolites, Antineoplastic; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Nephritis, Interstitial

Topics: Allopurinol; Female; Granuloma; Humans; Kidney; Middle Aged; Nephritis, Interstitial; Uric Acid

Topics: Adult; Alkaline Phosphatase; Child; Circadian Rhythm; Creatine Kinase; Humans; L-Lactate Dehydrogenase; Nephritis, Interstitial; Uric Acid; Xanthine Oxidase

Preservation of rat kidneys by simple ice-storage has been demonstrated after 48 hr using the University of Wisconsin (UW) solution; hypothermic preservation of the rat kidney was dramatically improved. A modified UW solution without hydroxyethyl starch (HES) also gave uniform survival after 48 hr of storage, and even better function and morphology. Substitution of HES from another source also improved renal function when compared with UW (Dupont) and it is suggested that prolonged storage of UW solution prior to use may reduce its effectiveness. Reversing the Na:K ratio of the solution still allowed successful preservation, but significantly worsened morphology of the surviving kidney.

Topics: Adenosine; Allopurinol; Animals; Creatinine; Electrolytes; Glutathione; Hydroxyethyl Starch Derivatives; Insulin; Kidney Transplantation; Nephritis, Interstitial; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Strains; Solutions; Starch; Urea

Topics: Aged; Allopurinol; Female; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Nephritis, Interstitial; Uric Acid

Allopurinol is widely used in the treatment of hyperuricemia. Unusual (78 cases published up to 1984) but severe toxicity includes renal, skin and hepatic involvement. We report a new case of serious toxic manifestations with acute interstitial nephritis. We stress the need to adapt the daily dosage of the drug to the glomerular filtration rate and to interrupt drug administration rapidly if allergic manifestations develop.

Topics: Acute Disease; Aged; Allopurinol; Humans; Male; Nephritis, Interstitial

Topics: Allopurinol; Granuloma; Humans; Male; Middle Aged; Nephritis, Interstitial

Between January 1979 and June 1985, 10 patients with acute allergic interstitial nephritis were seen in a clinical nephrology service at a large regional hospital. The onset of renal failure was temporally related to the use of a drug: a nonsteroidal anti-inflammatory agent (NSAID) (in four patients), cimetidine (in three), antibiotics (in two) or allopurinol (in one). The onset of renal failure was acute in three patients and insidious in seven. Two patients also exhibited marked proteinuria. Clinical features such as fever, rash, hematuria, pyuria with or without eosinophiluria, and mild to marked proteinuria had led to suspicion of the disease. The diagnosis was confirmed by renal biopsy findings of inflammatory cells, predominantly lymphocytes, plasma cells and eosinophils. Three patients required hemodialysis; two of them received steroids as well. Steroid therapy was also used in two patients with NSAID-induced proteinuria. Renal function improved in nine patients by 35 days, but one patient continued to have slow but progressive deterioration of renal function. Acute interstitial nephritis can be distinguished from other forms of acute renal failure by heavy renal uptake of gallium 67, maximal 48 hours or more after injection. The improvement in renal function after discontinuation of the implicated drug, the characteristic histopathological findings of allergic interstitial nephritis, and the presence of eosinophils and sometimes IgE in the blood suggest a hypersensitivity reaction.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cephaloridine; Cimetidine; Female; Fenoprofen; Humans; Indomethacin; Kidney; Male; Middle Aged; Nephritis, Interstitial; Penicillins

Acute granulomatous interstitial nephritis and acute granulomatous hepatitis were simultaneously observed in the same patient. Clinical and anamnestic arguments suggest that allopurinol could be responsible for this double localization, but a possible part played by furosemide cannot be excluded. The patient spontaneously recovered without corticosteroid therapy. Such an acute drug induced association did not have been proved so far.

Topics: Acute Disease; Allopurinol; Atenolol; Biopsy; Chemical and Drug Induced Liver Injury; Female; Furosemide; Granuloma; Humans; Middle Aged; Nephritis, Interstitial

Topics: Allopurinol; Animals; Chemistry; Coronary Disease; Gout; History, 20th Century; Humans; Hypertension; Leukemia, Myeloid; National Institutes of Health (U.S.); Nephritis, Interstitial; Purines; United States; Uric Acid; Urinary Calculi; Xanthine Oxidase

Altogether 100 patients with associated podagra and renal injury were examined and treated. Before the first admission to the clinic only 5% of the patients had received combined therapy of renal pathology on a regular basis, 33% of the patients had been given pathogenetic but not systematic therapy. 66% of the patients had not responded to the treatment, whereas 38% manifested a decrease in renal function. Sixty patients were followed up for the results of further dispensary observation during 1.5 to 5 years. These patients were distributed into 2 groups. The first one comprised 26 patients who adhered strictly to the physicians' recommendations, the second group consisted of patients who received treatment irregularly. The clinicolaboratory improvement was attained in almost 3/4 of the first group patients and in less than 1/4 of the second group patients. The best effect was attained in the treatment of the urolithiasis pattern of nephropathy, whereas the less marked in chronic interstitial nephritis. The worst results were attained in patients with glomerulonephritis.

Topics: Adult; Aged; Allopurinol; Ambulatory Care; Cyclophosphamide; Drug Therapy, Combination; Female; Glomerulonephritis; Gout; Humans; Kidney Calculi; Male; Middle Aged; Nephritis, Interstitial; Orotic Acid

Topics: Adult; Allopurinol; Autoantibodies; Basement Membrane; Complement C3; Drug Hypersensitivity; Glomerulonephritis; Humans; Immunoglobulin A; Male; Nephritis, Interstitial; Uveitis, Anterior; Vasculitis

Topics: Allopurinol; Biopsy; Gout; Humans; Kidney Cortex; Male; Middle Aged; Nephritis, Interstitial; Prednisone

Acute interstitial nephritis associated with hepatitis, exfoliative dermatitis, fever and eosinophilia is uncommon. The syndrome has been described previously in association with phenindione administration, leptospirosis and heavy metal poisoning. Four cases are described, two of which were due to phenindione sensitivity. The other two patients had been exposed to a number of toxins including allopurinol, frusemide, chlorothiazide and methyldopa so that the exact aetiological agent is unclear. Interstitial nephritis should be considered as a cause of acute renal failure in patients with other features of drug hypersensitivity.

Topics: Acute Disease; Adolescent; Adult; Allopurinol; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Drug Therapy, Combination; Humans; Male; Middle Aged; Nephritis, Interstitial; Phenindione

An acute crystal nephropathy was produced in pigs by feeding a mixture of guanine and allopurinol. The pathogenesis of the lesion produced was studied by serial histology and renal function tests over 12 months. Tubular blockage by the crystals produced erosion of the basement membrane and an accompanying interstitial nephritis. Tubular degeneration around the crystal mass transferred the crystals to the interstitium. Despite rapid subsequent disappearance of these crystals the interstitial nephritis was still evident nine months later. An early return of renal function to near normal was not sustained beyond nine months. It was shown that even brief periods of intratubular crystal deposition caused irreversible changes, resulting eventually in a reduction in kidney size, nephron population and renal function.

Topics: Allopurinol; Animals; Crystallization; Guanine; Kidney Function Tests; Nephritis, Interstitial; Swine

Topics: Adolescent; Adult; Aged; Allopurinol; Anti-Bacterial Agents; Antihypertensive Agents; Female; Gout; Humans; Kidney Calculi; Kidney Diseases; Male; Middle Aged; Nephritis, Interstitial; Nephrosclerosis; Pyelonephritis; Uric Acid; Uricosuric Agents

Topics: Adolescent; Allopurinol; Anemia, Macrocytic; Athetosis; Chorea; Gout; Humans; Intellectual Disability; Male; Nephritis, Interstitial; Neurologic Manifestations; Uric Acid