| IgA nephropathy (IgAN) accounts for 45% of the primary glomerulonephritis in China. Clinical presentations and prognosis of IgAN vary considerably. Five clinical features-proteinuria>1.0g/d, hypoalbuminemia, hypertension, decreased eGFR and hyperuricemia have been identified as independent predictors of an unfavorable renal outcome. Rare cases of IgAN patients exhibit nephrotic syndrome, mild glomerular lesions in pathology, rapid response to corticosteroid and promising prognosis more similar to MCD and inconsistent with typical IgAN. This unusual type of disease is known as IgAN with minimal change disease (MCD-IgAN). However, the clinicopothological characteristics and long-term renal outcome of MCD-IgAN in large cohorts have not yet been well described in previous studies. It remains controversial whether MCD-IgAN is a special type of IgAN or a co-existence of IgAN and MCD. We therefore performed a retrospective review to characterize this unusual entity in terms of clinicopathological features, treatment response and long-term prognosis. We compared the long-term prognosis between MCD-IgAN and Non-MCD-IgAN and further compared the clinicopathological features and response to corticosteroid between MCD-IgAN and MCD to better understand this special type of IgAN.Part 1.Clinical and pathological characteristics of IgA nephropathy patients with minimal change diseaseObjective:To analyze the clinic-pathological characteristics, treatment response of IgA nephropathy with minimal change disease (MCD-IgAN).Methodology:Patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgA nephropathy Registry were systematically reviewed.Results:306 patients were diagnosed as MCD-IgAN, which accounted for 2.57% of IgA nephropathy during the same period.247 cases with complete data were enrolled in this study. Male predominance (67.7%) was observed in patients with MCD-IgAN, with an average age of 27.05±11.03 years at renal biopsy. Initial clinical features included:nephrotic syndrome (81.4%), microhematuria (18.7%), hypertension (19.0%), hyponatremia (27.5%), thrombus (2.4%) and acute kidney injury (8.9%). Pathological data revealed that 34 cases (13.7%) had moderate to severe acute tubulointerstitial lesions and 11 cases (4.5%) had mild chronic tubulointerstitial lesions. After 8 weeks of corticosteroid therapy, a complete remission was attained in 216 patients (87.4%), a partial remission in 21 patients (8.5%) patients, and no remission in 10 patients (4.0%). During 2.6 years of observation (range 1-15.2 years),245 cases (99.2%) achieved CR and 112 patients (45.7%) experienced at least one relapse. Multivariate Cox proportional hazards models revealed that higher level of immunoglobulin G, lower level of urine RBP were significantly associated with early remission (HR=1.10, HR=0.97, P<0.05, respectively). Aging, receiving immunosuppressive therapy were associated with less relapse (HR=0.73, HR=0.34, P<0.01, respectively), while patients with AKI were associated with a higher incidence of relapse (HR=1.88, P<0.01).Conclusion:MCD-IgAN patients have good response to corticosteroid therapy but relapse remains a major challenge.Part 2. Long-term outcome of IgA nephropathy with minimal change disease:A comparison between patients with and without minimal change diseaseObjective:To analyze the long-term prognosis of IgA nephropathy with minimal change disease (MCD-IgAN).Methodology:Patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgA nephropathy Registry were systematically reviewed and compared with compared with those without minimal change disease (Non-MCD-IgAN).Results:247 MCD-IgAN patients and 1121 Non-MCD-IgAN patients were enrolled in this study. Compared with the Non-MCD-IgAN group, patients with MCD-IgAN were younger, with male predominance, had higher levels of baseline urine protein, total cholesterol and eGFR, lower incidence of hypertension and microhematuria, lower level of serum creatinine, had less severe glomerular, tubulointerstitial and vascular lesions in renal pathology. In Non-MCD-IgAN group,157 patients (14.0%) reached the renal end point and 103 patients (9.2%) entered ESRD. The 5-,10-,15- and 20-year cumulative renal survival rates, calculated by Kaplan-Meier method, were 95.0,83.0,72.9 and 65.4%, respectively. In MCD-IgAN group, no patients entered ESRD and only 4 patients (1.6%) reached the renal end point. Patients with MCD-IgAN had significantly better renal outcome than Non-MCD-IgAN patients (P<0.01). Multivariate Cox analysis revealed proteinuria>1.0g/day, hypertension, eGFR<60 mL/min/1.73m2, hypoproteinemia and hyperuricemia were the independent risk factors among patient with Non-MCD-IgAN (HR 3.43, P<0.001; HR 1.65, P<0.05; HR 2.61, P<0.001; HR 2.40, P<0.001; HR 2.27, P<0.001, respectively.), whereas these risk factors failed to predict the renal survival among patient with MCD-IgAN.Conclusion:The long-term outcome of patients with MCD-IgAN is significantly better than patients with Non-MCD-IgAN.Part 3. Comparison between IgA nephropathy patients with minimal change disease and patients with minimal change diseaseObjective:To compare the clinic-pathological characteristics, treatment response and prognosis between patients with IgAN with minimal change disease (MCD-IgAN) and patients with minimal change disease (MCD).Methodology:80 patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgA nephropathy Registry and 77 patients with MCD followed for>3 years were retrospectively reviewed.Results:The clinical presentations were similar between the two groups, both with young male predominance, the majority of these patients presented with nephrotic syndrome, only few cases had varying degrees of macroscopic hematuria. Compared with the MCD group, patients with MCD-IgAN had lower levels of baseline serum albumin (P<0.01) and eGFR (P<0.01), higher level of urinary n-acetyglucosaminidase (P<0.01), more severe acute and chronic tubulointerstitial injury in renal pathology (P<0.01, P<0.05,respectively). After 8 weeks of corticosteroid therapy, no significant differences were observed in the rate of complete remission, partial remission and no remission between MCD-IgAN and MCD (88.8% vs.90.9%,10.0% vs.5.2%,1.3% vs.3.9%, P>0.05). The median time to achieve remission was 4 weeks (range 1-24 weeks) and 4 weeks (range 1-28 weeks) respectively. Side effects such as ALT/AST elevated, Infection, steroid-induced diabetes and osteonecrosis of the femoral head were similar between both groups. During the three-year follow-up period, no patients in the two groups entered ESRD, only 2 patients (2.5%) with MCD-IgAN had greater than 50% reduction of eGFR.Conclusion:There were no significant differences in the clinical manifestations, pathological features, response to corticosteroid therapy and renal outcome between MCD-IgAN and MCD. It is noteworthy that, patients with MCD-IgAN had more significant tubulointerstitial injury. |
