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Objective:To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN).Methods:The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi).Results:A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min -1·(1.73 m 2) -1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% ( n=76) and 48.48% ( n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% ( n=85) and 52.78% ( n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% ( n=30) and 53.16% ( n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% ( n=31) and 54.44% ( n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions:HCQ is safe and effective for the treatment of IgAN.
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Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.
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Objective:To analyze the weight score and clinical application of 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) systemic lupus erythematosus (SLE) classification criteria in lupus nephritis patients.Methods:Lupus nephritis patients with renal biopsy results who were admitted in the First Affiliated Hospital of Zhejiang University College of Medicine between January 2014 and December 2018 were enrolled retrospectively. According to whether these patients were treated with glucocorticoids and/or immunosuppressants at the time of renal biopsy, they were divided into untreated group and post-treatment group. The weight scores were compared between the two groups, and the relationship between each weight score and remission after treatment was analyzed. Taking no remission as the end event, Cox regression analysis was used to analyze the influence of each weighted integral on the end event.Results:A total of 153 patients were enrolled, including 131 (85.6%) females. These were 70 (45.8%) patients in the untreated group and 83 (54.2%) patients in the post-treatment group. The patients in the untreated group had higher scores of fever (>38.3℃), blood system involvement, low complement and positive specific antibodies than those in post-treated group (all P<0.05). In a median follow-up of 34 (6-50) months, 99 patients (64.7%) achieved complete remission, 38 patients (24.8%) achieved partial remission and 16 patients (10.5%) had no remission. With no remission as the endpoint event, univariate Cox regression analysis showed that proliferative lupus nephritis (renal score of 10 points vs 8 points) and neuropsychiatric involvement were the risk factors (both P<0.05), while multivariate Cox regression analysis showed that neuropsychiatric involvement ( HR=4.758, 95% CI 1.324-17.101, P=0.017) was an independent risk factor. Conclusion:The weight scores of 2019 EULAR/ACR SLE classification diagnostic criteria have certain predictive value for remission of patients with lupus nephritis.
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Objective:To evaluate the efficacy and safety of rituximab in the treatment of adult primary focal segmental glomerulosclerosis (FSGS).Methods:Adult FSGS patients treated with rituximab in the First Affiliated Hospital of Zhejiang University College of Medicine were retrospectively enrolled. One or two doses of rituximab (375 mg/m 2) were used aiming to achieve B cell depletion (defined as<5 B cells per microliter in peripheral blood) and the interval between the two doses was 2 weeks. The evaluated major outcomes were remission and relapse of nephropathy, and the secondary outcome measures were adverse events and renal outcomes. Results:A total of 14 patients (9 males) were enrolled, among whom 7 cases were steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS), 6 cases were steroid-resistant nephrotic syndrome (SRNS) and one patient was new onset FSGS with contraindication to steroid. After treatment with rituximab, 7 patients with SDNS/FRNS achieved complete remission. At 6 months, the daily oral steroid dose reduced significantly compared with the baseline [(33.3±5.2) mg/d vs (6.7±6.6) mg/d, P<0.01]; while one patient still received tacrolimus 1.0 mg/d, the other 6 patients stopped using immunosuppressants; and the total number of relapse/total follow-up months decreased from 0.257 times/month to 0.058 times/month after the use of rituximab. For the other 6 SRNS patients and one patient with contraindication to steroid, three SRNS patients achieved partial remission and one patient with contraindication to steroid achieved complete remission at 34.50(20.25, 95.25) days after use of rituximab, and the other 3 SRNS patients failed to achieve remission, of whom one patient developed end stage renal disease at 23 months. Conclusions:Rituximab may reduce the risk of relapse and help steroid or immunosuppressant-tapering in adult steroid-dependent/frequently relapsing idiopathic FSGS. However, it is not effective in SRNS patients.
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Objective To investigate the effects of serum uric acid (SUA) on all?cause death and cardiovascular death in patients of maintaining peritoneal dialysis (PD). Methods One thousand and sixty?three PD patients in the First Affiliated Hospital of Zhejiang University Medical College were included. The SUA levels at 6 months after PD start were measured. Patients with SUA≥420 μmol/L were grouped in hyperuricemia group (492 cases) and patients with SUA<420 μmol/L were grouped in normal uric acid group (571 cases). The effects on all ? cause mortality and cardiovascular mortality were retrospectively analyzed. Results The median age of the patients was 51(41, 62) years; 557 cases were male (52.40％); the median follow?up time was 33(20, 54) months (6?96 months); 167 cases (15.71％) died during the follow?up period, including 64 cases (6.02％) withcardiovascular causes. The mortality in hyperuricemia group was 19.11％(94/492) and the cardiovascular mortality was 7.93％(39/492), both rates were higher than those in normal uric acid group, and the differences were statistically significant (P=0.005, P=0.015, respectively). Hyperuricemia (SUA≥420μmol/L) at 6 months after PD start (HR=1.572, 95％CI 1.155-2.141, P=0.004), high uric acid level (continuous variable) at 6 months after PD start (HR=1.002, 95％CI 1.001-1.004, P=0.008), and age≥65 years (HR=3.571, 95％CI 2.556-4.990, P<0.001), serum albumin≤30 g/L (HR=1.907, 95％CI 1.278-2.845, P=0.002), high Charlson comorbidity index (HR=1.209, 95％CI 1.032-1.417, P=0.019) at the beginning of PD start were independent risk factors for all ? causes death in PD patients. Hyperuricemia (SUA≥420 μmol/L) at 6 months after PD start (HR=1.734, 95％CI 1.033-2.912, P=0.037) and age≥65 years (HR=1.761, 95％CI 1.024-3.209, P=0.041), with diabetes (HR=2.775, 95％CI 1.358-5.671, P=0.005) at the beginning of PD start were independent risk factors for cardiovascular death in PD patients. Conclusions SUA at 6 months after PD is an independent risk factor for all?cause death and cardiovascular death in PD patients.
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Objective To elucidate the clinical features of nutcracker syndrome complicated with IgA nephropathy (IgAN) and to increase its level of diagnosis and treatment. Methods Clinical data of 14 cases of nutcracker syndrome complicated with IgA nephropathy (patient group) and 36 cases of nutcracker syndrome (control group) were analyzed retrospectively. Nutcracker syndrome was diagnosed by ultrasonography and magnetic resonance angiography (MRA) and IgAN by renal biopsy. Differences of clinical data and images in two groups were analyzed. Results Gender, age and blood pressure of two groups were not significantly different. Higher Scr level [(81.2±21.3) μmol/L vs (61.2±11.8) μmol/L, P<0.01], more severe proteinuria [(1.1 ± 0.6) g/d vs (0.3±0.2) g/d, P<0.01] and hematuria (2.3±0.9 vs 1.5±1.3, P<0.05) in patient group were found. Differences of ultrasonography and MRA in two groups were not significant. Conclusion Renal biopsy should be considered in cases of nutcracker syndrome with persistence of proteinuria, hematuria or abnormal morphology of urinary red blood cell.