Dear Editor,
We were very interested by the comment submitted by Dr. Gioacchino Li Cavoli and his collaborators, regarding their similar experience of a membranous glomerulonephritis with crescentic overlap. First of all, we would like to thank them for their input.
They reported a case of membranous glomerulonephritis (MGN) with crescentic transformation in a ANCA-negative vasculitis which revealed no evidence of systemic lupus erythematosus (SLE), anti-glomerular basement membrane (GBM) glomerulonephritis, infection, malignancy and showed no improvement after immunosuppressive treatments. The case they presented was similar to the patient that Kwan JT et al. described previously.1 Although several authors have demonstrated the concomitance of MGN and ANCA-associated glomerulonephritis,2-6 MGN accompanied by ANCA-negative crescentic glomerulonephritis has been rarely encountered.
The light microscopic visualization of renal tissue in their case showed the formation of 11 crescents (3 cellular crescents, 1 fibrocellular crescent and 7 fibrotic crescents) and 11 out of 17 glomeruli were globally sclerotic. These histopathological changes indicate the patient has reached to an advanced stage of crescentic glomerulonephritis and the renal disease has progressed to the sclerotic phase at the time of renal biopsy. Nasr SH et al. reported that the percentage of globally sclerotic glomeruli correlated with nonresponse to immunosuppressive agents.5 This is why the patient showed no improvement after treated with steroid plus cyclophosphamide and started chronic haemodialysis treatment eventually. By contrast, our case showed 2 sclerosed glomeruli out of 19 glomeruli, the formation of 9 crescents including 4 cellular crescents and 5 fibrocellular crescents, as well as the fibrinoid necrosis lesions upon light microscopy. This indicates our patient might be at the relatively early stage of crescentic glomerulonephritis and the renal biopsy findings may interpret the better response to immunosuppressive treatments in our case.
Concerning the prognosis of this group of patients, Nasr SH et al. reported that 50% of patients had reached endpoints of end-stage renal stage (ESRD) or death whether or not treated with immunosuppressive agents and the only independent predictor of progression to ESRD was serum creatinine at biopsy.5 However, the different outcomes of the two cases we and Dr. Gioacchino Li Cavoli exhibited reveal that the histological finding is more reliable to predict the prognosis. As Dr. Gioacchino Li Cavoli mentioned in the comment, the importance of recognizing the patients with membranous nephropathy and crescentic glomerulonephritis at early stage of the disease is that early immunosuppressive treatment may ameliorate the progression of renal damage and may contribute to the useful recovery of renal function.
Watanabe S et al. demonstrated that the patient had MPO-ANCA-associated glomerulonephritis superimposed on idiopathic membranous nephropathy in the coexistence of MGN and ANCA-associated glomerulonephritis.6 It is well recognized that ANCA-positive patient may develop ANCA-related crescentic glomerulonephritis; however, the immunopathogenesis of crescentic transformation in ANCA-negative patients with primary membranous nephropathy seemed to be more difficult to elucidate. Whether there are some other undetected autoantibodies involved in the pathogenesis of MGN accompanied by ANCA-negative crescentic glomerulonephritis remains unclear. Therefore, further research is required to clarify the pathogenesis of this rare concomitance and investigate the optimum treatment regimes for it.
Conflict of interest
The authors declare that there is no conflict of interest associated with this manuscript.
