IgA Nephropathy

Idiopathic immunoglobulin A nephropathy is characterized by an extreme variability in clinical course and sometimes by the unpredictability of the ultimate outcome. Among the numerous studies published in the last 15 years that have calculated the actuarial renal survival and tried to individuate the prognostic role of the clinical and histological features present at the onset of the disease or the time of biopsy, we chose to analyze critically the results of the most valid (30 studies). Actuarial renal survival at 10 years in adults was between 80% and 85% in most of the European and Asian studies, but it was less in studies from the United States and exceeded 90% in the few studies of children. Concordance existed in this selected literature that impairment of renal function, severe proteinuria, and arterial hypertension are the strongest and more reliable clinical predictors of an unfavorable outcome. However, analysis of the prognostic value of morphological lesions was more difficult because they have been characterized in some studies using an overall score or histological classes of progressively more severe involvement and, in others, using a semiquantitative grading of individual glomerular, tubular, interstitial, and vascular changes. In adult patients, a high score of glomerular and tubulointerstitial lesions, corresponding to classes IV and V of the Lee or Haas classifications, predicted a more rapid progression. When single lesions were analyzed separately, glomerulosclerosis and interstitial fibrosis appeared to be the strongest, most reliable predictors of unfavorable prognosis. More controversial was the role of crescents and capsular adhesions. None of the immunohistological features was found to be a risk factor for progression in the more accurate statistical analyses. The same histological features predicted outcome in children, although the severity of lesions at the time of biopsy was usually less than that in adults. However, in the single patient, even the evaluation of these prognostic markers sometimes fails to correctly predict outcome, probably because of the heterogeneity of the disease and the discontinuous activity of some injuring mechanisms during its course.

Present angiotensin-converting-enzyme inhibitor treatment fails to prevent progression of non-diabetic renal disease. We aimed to assess the efficacy and safety of combined treatment of angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker, and monotherapy of each drug at its maximum dose, in patients with non-diabetic renal disease. 336 patients with non-diabetic renal disease were enrolled from one renal outpatient department in Japan. After screening and an 18-week run-in period, 263 patients were randomly assigned angiotensin-II receptor blocker (losartan, 100 mg daily), angiotensin-converting-enzyme inhibitor (trandolapril, 3 mg daily), or a combination of both drugs at equivalent doses. Survival analysis was done to compare the effects of each regimen on the combined primary endpoint of time to doubling of serum creatinine concentration or end-stage renal disease. Analysis was by intention to treat. Seven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients on combination treatment reached the combined primary endpoint compared with 20 (23%) of 85 on trandolapril alone (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.018) and 20 (23%) of 86 on losartan alone (0.40, 0.17-0.69, p=0.016). Covariates affecting renal survival were combination treatment (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.011), age (1.30, 1.03-2.29, p=0.009), baseline renal function (1.80, 1.02-2.99, p=0.021), change in daily urinary protein excretion rate (0.58, 0.24-0.88, p=0.022), use of diuretics (0.80, 0.30-0.94, p=0.043), and antiproteinuric response to trandolapril (0.81, 0.21-0.91, p=0.039). Frequency of side-effects with combination treatment was the same as with trandolapril alone. Combination treatment safely retards progression of non-diabetic renal disease compared with monotherapy. However, since some patients reached the combined primary endpoint on combined treatment, further strategies for complete management of progressive non-diabetic renal disease need to be researched.