Acute interstitial nephritis (AIN) represents a frequent cause of acute kidney injury, accounting for 15-27% of renal biopsies performed because of this condition. By and large, drug-induced AIN is currently the commonest etiology of AIN, with antimicrobials and nonsteroidal anti-inflammatory drugs being the most frequent offending agents. Pathogenesis is based on an immunologic reaction against endogenous nephritogenic antigens or exogenous antigens processed by tubular cells, with cell-mediated immunity having a major pathogenic role. The characteristic interstitial infiltrates, mostly composed of lymphocytes, macrophages, eosinophils, and plasma cells, experience a rapid transformation into areas of interstitial fibrosis. A significant proportion of AIN has nowadays an oligosymptomatic presentation, although the presence of specific extrarenal symptoms such as fever, skin rash, arthralgias, and peripheral eosinophilia has an important role to orientate clinical diagnosis. Identification and removal of the offending drug are the mainstay of the treatment, but recent studies strongly suggest that early steroid administration (within 7 days after diagnosis) improves the recovery of renal function, decreasing the risk of chronic renal impairment. Delayed steroid treatment, when interstitial fibrosis has taken place, would have a less pronounced or nule therapeutic benefit.

The role of steroid treatment in drug-induced acute interstitial nephritis (DI-AIN) is controversial. We performed a multicenter retrospective study to determine the influence of steroids in 61 patients with biopsy-proven DI-AIN, 52 of whom were treated with steroids. The responsible drugs were antibiotics (56%), non-steroidal anti-inflammatory drugs (37%) or other drugs. The final serum creatinine was significantly lower in treated patients while almost half of untreated patients remained on chronic dialysis. Among treated patients, over half showed a complete recovery of baseline renal function, whereas the rest remained in renal failure. There were no significant initial differences between these two subgroups in terms of duration or dosage of steroids. After withdrawal of the presumed causative drug, we found that when steroid treatment was delayed (by an average of 34 days) renal function did not return to baseline levels compared to those who received steroid treatment within the first 2 weeks after withdrawal of the offending agent. We found a significant correlation between the delay in steroid treatment and the final serum creatinine. Renal biopsies, including three patients who underwent a second biopsy, showed a progression of interstitial fibrosis related to the delay in steroid treatment. Our study shows that steroids should be started promptly after diagnosis of DI-AIN to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function.

Abstract. Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria Ն 0.5 g/d, and serum creatinine (SCr) Յ 1.5 mg/dl were randomly assigned either to receive enalapril (n ϭ 23) or to a control group (n ϭ 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr Ͼ 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapriltreated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 Ϯ 37 mo in the enalapril group and 74 Ϯ 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P Ͻ 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P Ͻ 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr Ͼ 1.5 mg/dl at the last visit (P Ͻ 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P Ͻ 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.A considerable proportion (40 to 60% according to different series) of IgA nephropathy (IgAN) patients develop progressive renal insufficiency (1-4). Impairment in renal function, high BP, and proteinuria Ͼ 1 g/d are considered as the more important clinical predictors of an unfavorable evolution (1-6). With the exception of those patients who develop glomerular crescents or malignant hypertension, the rate of progression in IgAN patients with an unfavorable evolution is remarkably slow; end-stage renal failure develops in 20% of the cases after 10 yr and in 30% after 20 yr (1).Notwithstanding to be the most common type of glomerular disease in the world, surprisingly few prospective and controlled studies focused on the therapy of IgAN have been performed. Corticosteroids have shown a beneficial effect on the progression of IgAN in some randomized clinical trials (7,8), but concerns about its possible side effects in a disease with such a lengthy clinical course have been raised. Fish oil induced a decline in the rate of progression in a controlled study (9), but other studies failed to confirm this beneficial influence (10).Several multicenter and prospective studies have demonstrated that ACE inhibitors induce a significant renoprotective effect on the progression rate of both diabetic and nondiabetic chronic proteinuric nephropathies (11,12,13). This beneficial influence is closely related...

Acute interstitial nephritis (AIN) is an important cause of acute kidney injury that has experienced significant epidemiological and clinical changes in the last years. The classical presentation, mostly induced by antibiotics and accompanied by evident hypersensitivity manifestations (skin rash, eosinophilia, fever) has been largely replaced by oligosymptomatic presentations that require a higher index of suspicion and are increasingly recognized in the elderly, having non-steroidal anti-inflammatory agents and proton pump inhibitors as frequent offending drugs. Drug-induced AIN continues to be the commonest type, but it requires a careful differential diagnosis with other entities (tubulointerstitial nephritis with uveitis syndrome, IgG4-related disease, drug reaction with eosinophilia and systemic symptom syndrome, sarcoidosis and other systemic diseases) that can also induce AIN. Cortico-dependant, relapsing AIN is a recently recognized entity that poses an important therapeutic challenge. Although corticosteroids are widely used in drug-induced AIN to speed kidney function recovery and avoid chronic kidney disease, their efficacy has not been tested by randomized controlled trials. New diagnostic tests and biomarkers, as well as prospective therapeutic studies are needed to improve AIN diagnosis and management.

Background and objectives: Isolated case reports have shown a beneficial effect of rituximab on pediatric patients with primary FSGS, but there is no information about rituximab treatment of FSGS in adults.Design, setting, participants, & measurements: All patients who had biopsy-proven FSGS and were treated with rituximab in Spain were identified, independent of their positive or negative response, among the nephrology departments that belong to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Their characteristics and outcome after rituximab treatment were studied.Results: Eight patients were identified. Rituximab failed to improve nephrotic syndrome in five of eight patients, who continued to show massive proteinuria and exhibited a rapidly deteriorating renal function in two cases. Among the remaining three patients, two of them showed an improvement of renal function and a remarkable proteinuria reduction and one experienced a beneficial but transitory effect after rituximab. There were no differences in clinical or laboratory characteristics or in the CD20 B lymphocyte count after rituximab between these three patients and the five who had a negative response. The only difference was in the regimen of rituximab administration: Whereas the five patients with a negative response received only four weekly consecutive infusions of 375 mg/m 2 , the three remaining patients received additional doses of rituximab.Conclusions: Only a minority (three of eight) of patients in our series of adult patients with FSGS showed a positive influence of rituximab. More studies are necessary to characterize further the optimal dosages and the mechanisms of action of rituximab in FSGS.