Zhengzhao Liu

Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide

The presence of renal noninflammatory necrotizing vasculopathy (NNV) is often associated with a severe form of lupus nephritis (LN), which is unresponsive to standard therapy. We conducted a 6-month randomized, prospective, open-label trial comparing mycophenolate mofetil (MMF) (1.5—2.0 g/day) with monthly i.v. cyclophosphamide (CTX) (0.75—1.0 g/m2) as induction therapy for class IV LN with NNV. The primary and second end points were complete remission (CR) and partial remission (PR), respectively. Of 20 patients recruited, nine were randomly assigned to MMF and 11 to CTX. The baseline characteristics between groups were not significant. CR was achieved in four patients (44.4%) receiving MMF and in none of the patients receiving CTX (P = 0.026). PR was achieved in two patients (22.2%) in the MMF group and three patients (27.2%) in the CTX group. The total remission rate (CR + PR) in the MMF and CTX group was 66.6 and 27.2%, respectively (P = 0.17). MMF was more effective than i.v. CTX in reducing proteinuria and haematuria. Adverse events were significantly less frequent with MMF than with CTX (P = 0.028). MMF was superior to i.v. CTX in inducing CR of LN with NNV and had a more favourable safety profile. Lupus (2007) 16, 707—712.

Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy

We retrospectively analyzed the clinicopathologic characteristics and prognosis of 33 patients with diffuse proliferative lupus nephritis (class IV LN) complicated with thrombotic microangiopathy (TMA). Eighty-one percent of patients had renal dysfunction (mean Scr 3.1 ± 2.0 mg/dl), among whom 42.4% needed acute hemodialysis. Nephrotic proteinuria, gross hematuria and hypertension were presented in 57.6%, 24.2% and 93.9% of the patients. Microangiopathic hemolytic anemia, serum anti-dsDNA and anticardiolipin antibodies were found in 60.6%, 75.8% and 33.3% of the patients. Renal biopsy showed IV-G in 75.8%, class IV with class V in 21.2%, and IV-S in 1.23% of the patients. Glomerular segmental necrosis, microthrombi, crescents and arteriolar thrombosis were found in 51.5%, 69.7%, 60.6% and 60.7% of the patients, respectively. The follow up was 1 to 101 months (median 13 months). Only 50% of patients showed response to treatment. Three patients died, 10 developed end-stage renal failure (ESRF). The 5-year patient and renal survival rate was 69.2% and 46.7%, respectively. Major risks for ESRF included: a need for acute dialysis on admission, no response to the treatment and high renal chronic index. The results showed that class IV lupus nephritis with TMA has high mortality and low renal survival.

Pathological spectrums and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis

AbstractnThe objectives of the study were to investigate the pathological features and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. One hundred and one cases of biopsy-proven severe LN with rapidly progressive glomerulonephritis (RPGN) were analyzed in this retrospective study. Another 200 severe LN patients without RPGN were randomly enrolled as a control group. Their clinicopathological data and long-term outcome were compared. There were 76 females and 25 males with an average age of 31.9xa0±xa014.2xa0years followed for a median period of 4xa0years. Compared with controls, patients with RPGN had shorter LN duration (pxa0=xa00.008), higher level of creatinine (pxa0<xa00.001), severe anemia (pxa0=xa00.037), heavier hematuria (pxa0<xa00.001), severe tubular injury parameters [NAG (pxa0<xa00.001), RBP (pxa0<xa00.001), C3 (pxa0<xa00.001)], higher scores of AI (pxa0=xa00.001) and CI (pxa0=xa00.004), higher proportions of glomerular sclerosis (0.033) and crescents (pxa0<xa00.001), severe tubulointerstitial lesions (pxa0<xa00.001) and interstitial inflammation (pxa0<xa00.001), lower rate of complete remission (33.9 vs 68.2xa0%) and higher rate of treatment failure (46.8 vs 7.9xa0%). The 3-, 5- and 10-year cumulative renal survival rates of RPGN and non-RPGN patients were 65.1 versus 53.9 versus 42.9 and 96.9 versus 94.9 versus 91.7xa0%, respectively. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for end-stage renal disease (ESRD) in severe LN with RPGN (pxa0<xa00.001). In conclusion, RPGN occurred in 3.6xa0% of LN and is associated with severe renal manifestations, serious sclerotic and crescentic glomeruli lesions, severe tubulointerstitial inflammation, atrophy and fibrosis, prominent leukocyte infiltration and worse treatment response. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for ESRD. 57.1xa0% of severe LN patients with RPGN might progress to ESRD within 10xa0years.

Glucocorticoid with or without additional immunosuppressant therapy for patients with lupus podocytopathy: a retrospective single-center study.

Lupus podocytopathy is a newly recognized class of lupus nephritis characterized by extensive glomerular foot process effacement without capillary wall immune deposits. The treatment response and relapse of glucocorticoid with or without additional immunosuppressive agents has not been well investigated. In this study, 50 patients with lupus podocytopathy were included and received glucocorticoid alone (glucocorticoid monotherapy) or glucocorticoid plus additional immunosuppressive agents (combination therapy) for their induction or maintenance treatment regimens. The treatment response and relapse rate in the two groups were respectively analyzed. We found that the induction treatment with glucocorticoid monotherapy and combination therapy led to remission in 47 patients (94.0%) at 12 weeks treatment, with complete remission (CR) occurring in 38 patients (76.0%). The CR rate compared between glucocorticoid monotherapy and combination therapy showed no difference (76.7% vs 75.0%, pu2009=u20090.9), the median time to CR was four weeks (range: 2.0–6.0 weeks) in glucocorticoid monotherapy and 8.0 weeks (range: 3.7–12.0 weeks) in combination therapy (pu2009=u20090.076). Twenty-seven of 47 patients (57.4%) relapsed during maintenance, the relapse rate was much higher in the glucocorticoid monotherapy group than in the combination therapy group (89.5% vs 35.7%, pu2009<u20090.001), regardless of the induction regimens being glucocorticoid monotherapy or combination therapy. No patient developed end stage renal disease or died during follow-up for 6–125 months (median 62 months). In conclusion, the remission of lupus podocytopathy could be induced by glucocorticoid monotherapy or glucocorticoid plus other immunosuppressive agents, while the remission should be maintained by the combination regimen.

Double Filtration Plasmapheresis in the Treatment of Antineutrophil Cytoplasmic Autoantibody Associated Vasculitis With Severe Renal Failure: A Preliminary Study of 15 Patients

Our aim was to investigate the clinical efficacy of double filtration plasmapheresis (DFPP) in the treatment of antineutrophil cytoplasmic autoantibody‐(ANCA) associated vasculitis (AAV) with severe renal involvement. Fifteen AAV patients who had severe renal failure (median SCr 5.6(IQR 5.2–9.0) mg/dL) and needed initial renal replacement therapy (RRT) were treated with DFPP and immunosuppressive therapy. Two plasma volumes were processed during each DFPP session. The changes of serum ANCA and renal function were investigated. After the DFPP treatment for three to five sessions, serum MPO‐ANCA level decreased from 250.0u2009±u200986.9 RU/mL to 70.5u2009±u200964.7RU/mL (Pu2009=u20090.00), with a median reduction rate of 67.6%. Eleven patients (73.3%) no longer needed from RRT 3u2009months after DFPP treatment, while another four patients remained on dialysis. During the follow up for median 10 (IQR 6–24) months, SCr level decreased to normal in one patient, one patient progressed into ESRD. The 1u2009year renal survival rate was 62.9%. Five (33.3%) patients were complicated with pulmonary infection. DFPP combined with immunosuppressive therapy could increase the renal recovery rate through rapidly decreasing serum ANCA levels for AAV patients with severe renal failure, but its clinical efficacy and impact on long‐term renal survival require further studies.

Risk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA–Associated GN

BACKGROUND AND OBJECTIVESnOur study explored the association of histopathologic classification of ANCA-associated GN with renal survival in Chinese patients with myeloperoxidase-ANCA-associated GN.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnTwo hundred fifteen patients with biopsy-proven myeloperoxidase-ANCA-associated GN were included from January of 1996 to December of 2014. The biopsies included focal (n=27), mixed (n=82), crescentic (n=47), and sclerotic (n=59) classes. The long-term renal outcome and risk factors of myeloperoxidase-ANCA-associated GN for different histopathologic classes were retrospectively analyzed.nnnRESULTSnDuring a median follow-up time of 22 (9-51) months, 88 (40.9%) patients reached ESRD. The 5-year renal survival (overall 58.7%) was highest in the focal class (100.0%) and lowest in the sclerotic class (20.7%), with no difference between the mixed (58.9%) and crescentic (67.4%) classes. Patients in the mixed (hazard ratio, 0.34; 95% confidence interval, 0.20 to 0.57; P<0.001) and crescentic (hazard ratio, 0.31; 95% confidence interval, 0.16 to 0.59; P<0.001) classes were at lower risk for ESRD compared with patients in the sclerotic class, as were patients who received glucocorticoids plus mycophenolate mofetil (hazard ratio, 0.32; 95% confidence interval, 0.18 to 0.60; P<0.001) compared with those receiving glucocorticoids alone. In addition, patients with a serum creatinine level ≥4 mg/dl (hazard ratio, 2.93; 95% confidence interval, 1.77 to 4.85; P<0.001) or hypoalbuminemia (hazard ratio, 2.11; 95% confidence interval, 1.32 to 3.34; P=0.002) were at higher risk for ESRD. A serum creatinine level ≥4 mg/dl and a percentage of global sclerotic glomeruli ≥60% were the two independent risk factors for ESRD in the sclerotic class.nnnCONCLUSIONSnThe histopathologic classification of ANCA-associated GN in combination with serum creatinine and serum albumin levels and treatment regimen is associated with renal outcome in myeloperoxidase-ANCA-associated GN. The evaluation of serum creatinine level and percentage of global sclerotic glomeruli provides additional information on the risk of renal survival in the sclerotic class of myeloperoxidase-ANCA-associated GN.

Mesangial proliferative lupus nephritis with podocytopathy: a special entity of lupus nephritis:

Mesangial proliferative lupus nephritis may coexist with podocytopathy, but its clinical-morphological features, treatment response and outcomes have not been compared with mesangial proliferative lupus nephritis without podocytopathy. In this study, 125 biopsies of lupus nephritis patients showing mesangial proliferation with mesangial immune deposits were collected and divided into podocytopathy group (defined as podocyte foot process effacement (FPE) >50% with nephrotic syndrome (NS)) and mesangial group (FPE ≤50%, or FPE >50% without NS). Mesangial proliferation and tubular- interstitial lesions were semi-quantitatively analyzed. We found that the incidence of renal involvement as the onset symptoms (Pu2009<u2009.001), nephrotic syndrome (Pu2009<u2009.001), acute kidney injury (Pu2009<u2009.001), the degree of acute tubular- interstitial lesions (Pu2009<u2009.001), and renal relapse (51.6% vs. 23.7%, Pu2009=u2009.005) were significantly higher in the podocytopathy group than in the mesangial group. In contrast, the incidence of arthritis (Pu2009<u2009.001), fever (Pu2009=u2009.042), low serum C4 (Pu2009=u2009.008) and hematuria (Pu2009=u2009.033) was significantly lower in the podocytopathy group than in the mesangial group. No patients developed end stage renal disease or death during a median follow-up of 64 (interquartile range (IQR) 37–103) months in the podocytopathy group and 53 (IQR 30–83) months in the mesangial group. In conclusion, mesangial proliferative lupus nephritis with and without podocytopathy should be subdivided into two separate classes of lupus nephritis.

The short-term efficacy of bortezomib combined with glucocorticoids for the treatment of refractory lupus nephritis

Objective The treatment of refractory lupus nephritis (LN) remains challenging for clinicians because these patients either do not respond to conventional therapy or relapse during the maintenance treatment period. The aim of this study was to investigate the efficacy and safety of bortezomib combined with glucocorticoids in refractory lupus patients. Methodology Five refractory LN patients aged 21 to 43 years (four females and one male) with biopsy-proven diagnosis (four with type IV and one with type V+IV) were recruited. These patients received bortezomib therapy for four cycles (1.3u2009mg per square meter of body surface area as an intravenous bolus on days 1, 4, 8, and 11 of 21-day cycles) and glucocorticoids (methylprednisolone 0.5u2009g/d intravenously for three days, followed by prednisone 0.6u2009mg/kg/d orally for four weeks, with gradual tapering to 10u2009mg/d). Proteinuria, serum albumin and creatinine, and immunological parameters were assessed, and adverse effects were also evaluated. Results After two to four bortezomib treatment cycles, four patients achieved partial remission with decreases in SLE disease activity index scores from the range of 12–16 to that of 4–8. The patients also exhibited a decline in proteinuria and an elevation of albumin level after treatment. SCr level was decreased in three of five patients with elevated SCr at baseline. The anti-autoantibodies and complements were also improved. Adverse events were of grades 1–2 and included transient thrombocytopenia, gastrointestinal symptoms and acroesthesia. During a 6- to 24-month follow-up period, three patients achieved complete remission, and one had partial remission. However, one patient received renal replacement therapy. Conclusion Bortezomib combined with glucocorticoids reduces proteinuria, improves renal function and decreases anti-autoantibodies, with good tolerance and mild adverse events, thus representing an alternative therapy for refractory LN and warranting further study.

Long-term outcome of mycophenolate mofetil treatment for patients with microscopic polyangiitis: an observational study in Chinese patients

This study aimed to retrospectively analyze the long-term outcome of mycophenolate mofetil (MMF) therapy for microscopic polyangiitis (MPA) with mild to moderate renal involvement in Chinese patients. Thirty-four MPA patients (24 females, 10 males, aged 44.7xa0±xa017xa0years, BVAS score 13.8xa0±xa03.2, SCr 2.2xa0±xa01.1xa0mg/dl) with SCrxa0<xa05xa0mg/dl and who received glucocorticoids plus MMF therapy for inducing and maintaining remission were included in this study. The remission and relapse rates, patient and renal survival rates and adverse events were retrospectively analyzed. We found that 31 (91.2xa0%) of 34 patients achieved remission and were continuously treated with glucocorticoids plus MMF for maintaining remission. The median duration of MMF treatment was 24xa0months (IQR 15–53xa0months) and follow-up time was 86xa0months (IQR 29–124xa0months). During the follow-up, 7 (22.6xa0%) patients relapsed, one patient died, and one patient progressed into end-stage renal disease. The 5-year patient and renal survival rates were 92.8 and 95.2xa0%, respectively. 11 (32.4xa0%) patients suffered 16 adverse events, 13 of which were pulmonary infection. In conclusion, glucocorticoids plus MMF regimen as induction and maintenance therapy could achieve high remission rate and good long-term renal survival in MPA patients with mild to moderate renal involvement. Prospective controlled trials with a large sample size are needed to confirm the efficacy of MMF in this population.

Long-term outcomes in antineutrophil cytoplasmic autoantibody–positive eosinophilic granulomatosis with polyangiitis patients with renal involvement: a retrospective study of 14 Chinese patients

BackgroundThe clinic-pathological features and outcomes of Chinese patients with antineutrophil cytoplasmic autoantibody (ANCA)-positive eosinophilic granulomatosis with polyangiitis (EGPA) and renal involvement have not been studied.MethodsFourteen EGPA patients with renal involvement were included. All patients underwent renal biopsy. Clinic-pathological features and outcomes were retrospectively analyzed.ResultsThe most common initial symptom of EGPA was asthma (57.1xa0%), followed by hemoptysis (21.4xa0%), gross hematuria (14.3xa0%), and arthritis (7.1xa0%). All patients had positive serum ANCA (anti-MPO in 12, anti-PR3 in 2). Elevated eosinophils (median 15xa0%, range 10–45xa0%) were found in all patients. The median serum IgE level was 463xa0g/L (range 200–1000xa0g/L). All patients presented with renal dysfunction, with a median SCr of 5.4xa0mg/dL (range 1.47–11xa0mg/dL), seven patients (50xa0%) required initial renal replacement therapy. Thirteen patients showed hematuria and proteinuria (median 1.1xa0g/24xa0h, range 0.5–7.8xa0g/24xa0h). Renal biopsy showed pauci-immune segmental necrotizing glomerulonephritis with crescents in 13 patients and acute interstitial nephritis in one patient. Twelve patients (85.7xa0%) showed renal interstitial eosinophil infiltration, among whom three had eosinophilic granuloma. Among seven patients (71.4xa0%) who required initial dialysis, 5 discontinued dialysis, one died, one received maintenance dialysis after glucocorticoids plus immunosuppressive for induction treatment. Twelve patients were followed up for a median of 43.5xa0months (range 6–83 months), during follow-up, two patients progressed to end-stage renal disease, nine had chronic kidney disease with eGFRu2009<u200960xa0mL/min, and two patients had normal eGFR.ConclusionsRenal involvement in ANCA-positive EGPA could be severe and showed varied renal histology. Although intensive immunosuppressive therapy effectively improved the renal function, the long-term renal survival was poor. Early diagnosis and treatment are essential to improve long-term renal survival.