Weixin Hu

Successful Treatment of Class V+IV Lupus Nephritis with Multitarget Therapy

Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis. In this prospective study, 40 patients with class V+IV lupus nephritis were randomly assigned to induction therapy with mycophenolate mofetil, tacrolimus, and steroids (multitarget therapy) or intravenous cyclophosphamide (IVCY). Patients were treated for 6 mo unless complete remission was not achieved, in which case treatment was extended to 9 mo. An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo (50 and 65%, respectively) than with IVCY (5 and 15%, respectively). At 6 mo, eight (40%) patients in each group experienced partial remission, and at 9 mo, six (30%) patients receiving multitarget therapy and eight (40%) patients receiving IVCY experienced partial remission. There were no deaths during this study. Most adverse events were less frequent in the multitarget therapy group. Calcineurin inhibitor nephrotoxicity was not observed, but three patients developed new-onset hypertension with multitarget therapy. In conclusion, multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated.

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.

Effects of mycophenolate mofetil for patients with crescentic lupus nephritis.

Objective:  To compare the effects, relapse ratio and outcomes between mycophenolate mofetil (MMF) and pulse intravenous cyclophosphamide (CTX) for the induction therapy in patients with crescentic lupus nephritis.

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.

Clinical–Morphological Features and Outcomes of Lupus Podocytopathy

BACKGROUND AND OBJECTIVES Lupus podocytopathy, which is characterized by diffuse foot process effacement without peripheral capillary wall immune deposits and glomerular proliferation, has been described in SLE patients with nephrotic syndrome in case reports and small series. This study aimed to better characterize the incidence, clinical-morphologic features, and outcomes of such patients from a large Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Lupus podocytopathy was identified from 3750 biopsies of SLE patients obtained from 2000 to 2013 that showed mild glomerular histology in patients with a clinical sign of nephrotic syndrome. The biopsy results were divided into three groups: glomerular minimal change, mesangial proliferation, and FSGS. RESULTS Fifty (1.33%) cases were identified as lupus podocytopathy and included minimal change in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases. Extensive foot process effacement appeared in all the biopsies and mesangial electron-dense deposits were present in 47 biopsies. All patients demonstrated nephrotic syndrome, and the median proteinuria was 5.72 g/24 h (interquartile range [IQR], 3.82, 6.92). Seventeen (34%) cases presented with AKI. Forty-seven (94%) patients achieved remission after immunosuppressive therapy for a median time of 4 weeks (IQR, 2, 8). Compared with the patients with minimal change and mesangial proliferation, patients with FSGS showed significantly higher incidence of AKI and severe tubule-interstitial injury and a much lower complete remission rate. During follow-up of a median of 62 (IQR, 36, 84) months, renal relapses occurred in 28 (59.6%) patients. No patient died or developed ESRD. CONCLUSIONS The findings from this cohort study suggest that lupus podocytopathy may represent a special entity of lupus nephritis with distinct clinical-morphologic features. The differences in AKI incidence, tubular injury severity, and response to treatment between the patients with minimal change/mesangial proliferation and those with FSGS patterns indicate two different subtypes of lupus podocytopathy.

Long-term renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis.

In the present study, we observed the renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis (LN) and evaluated the risk factors associated with poor renal prognosis. The 5 -, 10 -, 15 - and 20-year renal survival rates were 93.1%, 87.9%, 81.0% and 68.3%, respectively. Gender, LN duration, mean arterial pressure (MAP), proteinuria, serum creatinine, haemoglobin and pathological classification at the time of biopsy were independent risk factors for end-stage renal disease (ESRD). The long-term renal outcomes of patients with class II LN were unfavorable as opposed to those with class V. Additionally, the time-average proteinuria (TA-Pro) and the time-average mean arterial pressure (TA-MAP) during the follow-up were important risk factors for ESRD, with better predictive values than the baseline proteinuria and MAP. The results underscore the need for proteinuria and blood pressure control during follow-up in patients with LN; proteinuria levels should be controlled at least to < 1.0 g/24 h, and optimally to < 0.5 g/24 h; MAP should not exceed 96.5 mmHg. More attention should be paid to class II LN and emphasis should be placed on recurrence prevention of class II LN.

Significance of histological crescent formation in patients with diffuse proliferative lupus nephritis.

Background: Although crescentic nephritis is not rare in diffuse proliferative lupus nephritis (DPLN), little is known about the clinicopathological features in DPLN with crescents worldwide. This study was undertaken to investigate the clinicopathological features and outcome of Chinese DPLN patients with different degrees of crescents. Methods: 520 DPLN patients with more than 10% histological crescents (cDPLN) were enrolled in this retrospective study. They were divided into three groups: group 1 (10%≤ crescents <25%, n = 240), group 2 (25%≤ crescents <50%, n = 160), and group 3 (crescents ≥50%, n = 120). Another 100 patients without histological crescents were enrolled as a control group. Clinicopathological features, treatment responses, and outcomes were compared among the four groups. Results: There were 450 (86.6%) females and 70 (13.4%) males with an average age of 31.7 ± 11.4 years. Compared with the control group, cDPLN patients had shorter lupus nephritis duration (20.7 ± 34.1 vs. 30.4 ± 48.9 months), higher prevalence of rapidly progressive glomerulonephritis syndrome (21.8%), and gross hematuria (26.7%). Laboratory findings indicated more severe hypoproteinemia, hyperlipidemia, and renal insufficiency; heavier proteinuria and microscopic hematuria; higher tubular injury parameters, and lower serological activity in crescentic groups. Histologically, cDPLN patients have severe glomerular and tubulointerstitial lesions as well as extensive leukocyte infiltration together with a lesser degree of immune complex deposition. The proportion of death, end-stage renal disease, and treatment failure correlates positively with the degree of histological crescents. Conclusions: cDPLN patients with acute onset and short disease duration mostly show severe renal manifestations, less extrarenal organ involvement, lower serological activity, serious capillary necrosis, severe tubulointerstitial inflammation, atrophy and fibrosis, prominent leukocyte infiltration, less glomerular immune complex deposition, poor treatment response, and worse renal outcome.

Clindamycin-induced acute kidney injury: large biopsy case series.

Background: While clindamycin-induced acute kidney injury (AKI) is uncommon, it has occurred more frequently in recent years. Summary: We investigated 24 patients diagnosed with clindamycin-induced AKI retrospectively. The dosage of clindamycin was 1.0-1.5 g/day. Fifteen patients had episodes of gross hematuria, but fever, skin rash and eosinophilia were rare. Urine analysis revealed mild proteinuria and severe tubular dysfunction. Twenty-three patients were diagnosed with AKI stage 3 upon admission. The clindamycin lymphocyte transformation assay was positive for 63.2% of the patients. Acute interstitial nephritis (AIN) and acute tubular necrosis (ATN) were proven by renal biopsy, and renal insufficiency appeared to result from tubular toxicity and drug crystals. In the majority (87.5%) of the patients, AKI was severe and required renal replacement therapy, but all of their renal function recovered significantly 2 months after discharge. Clindamycin-induced AKI is largely reversible and has episodes of gross hematuria. Renal biopsies confirmed AIN or ATN in these patients.

Etiology and Outcome of Crescentic Glomerulonephritis From a Single Center in China: A 10-Year Review

BACKGROUND The disease spectrum of crescentic glomerulonephritis (GN) has been described in only a few previous studies, and detailed epidemiologic data from China are unavailable to date. STUDY DESIGN Case series. SETTING & PARTICIPANTS 528 patients with biopsy-proven crescentic GN in 2003 to 2013 from a single center. PREDICTOR Crescentic GN was classified into 3 types according to immunofluorescence findings: type I was defined as linear deposition of immunoglobulins along the glomerular basement membrane; type II, as glomerular deposition of immune complex; and type III, as pauci-immune deposition. OUTCOMES Demographic, clinical, and serologic characteristics. RESULTS Of 528 cases identified, 208 (39.4%) were men, with a mean age of 37.6±16.4 (SD) years at kidney biopsy. 61 (11.6%) patients had type I crescentic GN, 331 (62.7%) had type II (lupus nephritis, 34.3%; immunoglobulin A [IgA] nephropathy, 17.4%), and 136 (25.8%) had type III. Proportions of patients with acute kidney injury (AKI), acute kidney diseases and disorders without AKI, and chronic kidney disease were 86.9%, 0%, and 13.1% for type I; 42.0%, 19.6%, and 38.4% for type II; and 84.6%, 2.9%, and 12.5% for type III crescentic GN, respectively. Serum antineutrophil cytoplasmic antibodies were detected in 11 (18.0%) patients with type I, 15 (4.5%) with type II, and 117 (86.0%) with type III. Anti-glomerular basement membrane antibodies were found in 60 (98.4%) patients with type I, 3 (0.9%) with type II, and 5 (3.7%) with type III. 5-year cumulative renal survival rates for patients with types I, II, and III were 17.6%, 70.1%, and 44.3%, respectively. LIMITATIONS Retrospective study, single-center experience. CONCLUSIONS Lupus nephritis may be the most common type of crescentic GN in China, followed by pauci-immune crescentic GN and IgA nephropathy. Almost half the patients presented with AKI, whereas 28.8% of cases showed chronic kidney disease. Clinical manifestations and outcomes varied according to crescentic GN type. The distinction between subtypes based on immunofluorescence and serologic findings has important implications for therapy and outcome.

Prediction of Renal Outcomes in Patients With Crescentic Lupus Nephritis

Background:Few studies are currently available about the renal survival and risk factors of crescentic lupus nephritis (cLN). We retrospectively analyzed data from Chinese patients with cLN in our center to identify the prognostic factors. Methods:One hundred twenty-four cases of biopsy-proven LN with ≥50% crescents (cLN) were included in this study. Another 100 patients with LN without crescents were randomly enrolled as a control group. Their clinicopathological data and long-term outcome were compared. Results:There were 101 females and 23 males with an average age of 32.0 ± 13.5 years followed for a median period of 4 years. At biopsy, the mean SCr level was 2.4 ± 2.0 mg/dL, and the mean percentage of crescents was 64.4 ± 13.3%. The renal survival rates at years 1, 3 and 5 after biopsy of cLN group and the control group were 82.3% versus 97.8%, 78.4% versus 92.6% and 70.2% versus 84.9%, respectively. Multivariate Cox regression revealed initial SCr concentration as the only independent risk factor for end-stage renal disease (hazard ratio: 1.433, P < 0.001). Logistic regression showed that the risk of end-stage renal disease at 5 years after biopsy increased rapidly at SCr >1.4 mg/dL and reached 90% at SCr >5.5 mg/dL. Conclusions:Crescentic LN had worse treatment response and lower probability of renal survival than those without crescents. Initial SCr concentration may predict kidney failure in patients with crescentic disease.