Treatment of Membranous Nephropathy in Chinese Patients: Comparison of Rituximab and Intravenous Cyclophosphamide with Steroids.

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on primary membranous nephropathy (PMN). However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥4 g/24 h, serum albumin <30 g/L, and eGFR ≥30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/day and intravenous CTX 500 mg/m2 per month until the total dose reached 6-8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint (p = 0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, p = 0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, p = 0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, p = 0.03) among patients with massive proteinuria (urine protein ≥8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, p = 0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.

Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy.

INTRODUCTION: This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy. METHODS: Patients with primary membranous nephropathy who had urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 despite six months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) based on age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan Meier curves, and absolute risk differences were employed to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab. RESULTS: Sixty-three patients with primary membranous nephropathy were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab vs. rituximab: 95% vs. 67%; odds ratio (OR): 10.00, 95% confidence intervals (CI):1.21-82.35, P=0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab vs. rituximab: 38% vs. 14%; OR: 3.69, 95% CI:1.08-12.68, P=0.04). In PLA2R-associated primary membranous nephropathy subgroup analyses, patients in obinutuzumab group sustained lower CD19 B cell counts (CD19 B cell counts: median (IQR) 0 (0-6) cells/ul vs. 20 (3-58) cells/ul, P=0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at six months [obinutuzumab vs. rituximab: 92% (12 out of 13) vs. 64% (16 out of 25), P=0.06] than rituximab. Both treatment regimens were well tolerated. CONCLUSIONS: Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared to rituximab at 12 months which may be due to higher immunological remission at six months with a similar safety profile in patients with primary membranous nephropathy.

Combined Serologic and Genetic Risk Score and Prognostication of Phospholipase A2 receptor-Associated Membranous Nephropathy.

INTRODUCTION: The aim of this study was to test whether a combined risk score on the basis of genetic risk and serology can improve the prediction of kidney failure in phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy. METHODS: We performed a retrospective analysis of 519 biopsy-proven PLA2R-associated primary membranous nephropathy patients with baseline eGFR ≥25 ml/min per 1.73 m 2 . The combined risk score was calculated by combining the genetic risk score with PLA2R ELISA antibody titers. The primary end point was kidney disease progression defined as a 50% reduction in eGFR or kidney failure. Cox proportional hazard regression analysis and C-statistics were applied to compare the performance of PLA2R antibody, genetic risk score, and combined risk score, as compared with clinical factors alone, in predicting primary outcomes. RESULTS: The median age was 56 years (range, 15-82 years); the male-to-female ratio was 1:0.6, the median eGFR at biopsy was 99 ml/min per 1.73 m 2 (range: 26-167 ml/min per 1.73 m 2 ), and the median proteinuria was 5.3 g/24 hours (range: 1.5-25.8 g/24 hours). During a median follow-up of 67 (5-200) months, 66 (13%) had kidney disease progression. In Cox proportional hazard regression models, PLA2R antibody titers, genetic risk score, and combined risk score were all individually associated with kidney disease progression with and without adjustments for age, sex, proteinuria, eGFR, and tubulointerstitial lesions. The best-performing clinical model to predict kidney disease progression included age, eGFR, proteinuria, serum albumin, diabetes, and tubulointerstitial lesions (C-statistic 0.76 [0.69-0.82], adjusted R 2 0.51). Although the addition of PLA2R antibody titer improved the performance of this model (C-statistic: 0.78 [0.72-0.84], adjusted R 2 0.61), replacing PLA2R antibody with the combined risk score improved the model further (C-statistic: 0.82 [0.77-0.87], adjusted R 2 0.69, difference of C-statistics with clinical model=0.06 [0.03-0.10], P < 0.001; difference of C-statistics with clinical-serologic model=0.04 [0.01-0.06], P < 0.001). CONCLUSIONS: In patients with PLA2R-associated membranous nephropathy, the combined risk score incorporating inherited risk alleles and PLA2R antibody enhanced the prediction of kidney disease progression compared with PLA2R serology and clinical factors alone.

Validity of the SARC-F questionnaire in assessing sarcopenia in patients with chronic kidney disease: a cross-sectional study.

Objective: To examine the validity of the 5-component SARC-F questionnaire for screening sarcopenia among patients with chronic kidney disease (CKD). Methods: Eligible participants were enrolled from the Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2019 to November 2019. Evaluations were performed using the self-administered SARC-F questionnaire. Sarcopenia was diagnosed by grip strength, the chair stand test and appendicular skeletal muscle mass. The severity of sarcopenia was evaluated by gait speed. We calculated the sensitivity and specificity of the SARC-F to evaluate construct validity. Moreover, receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff value for nondialysis-dependent (NDD) CKD patients' and maintenance hemodialysis (MHD) patients' scores. Results: A total of 105 NDD-CKD patients and 125 MHD patients were included, and the prevalence of sarcopenia was 5.7 and 31.2%, respectively. Among them, there were 21 (16.8%) MHD patients with severe sarcopenia but no NDD-CKD patients with severe sarcopenia. The sensitivity and specificity of the SARC-F were 16.7 and 98.0% for NDD-CKD patients, and 48.7 and 89.5% for MHD patients, respectively. For NDD-CKD patients, the area under the receiver operating characteristic curve (AUROC) of the total SARC-F score was 0.978 (95% confidence interval (CI): 0.929-0.997, p < 0.001), and the cutoff value of 1 reached the highest Youden index of 0.950 and max ROC curve area of 0.974. For MHD patients, the AUROC of the total SARC-F score was 0.730 (95% CI: 0.644-0.806, p < 0.001), and the cutoff value of 4 reached the highest Youden index of 0.383 and max ROC curve area of 0.691. Conclusion: CKD patients, especially MHD patients, were at high risk of suffering sarcopenia. The SARC-F had low-to-moderate sensitivity but high specificity for screening sarcopenia among patients with CKD. The best cutoff values of the SARC-F score were different for screening sarcopenia among NDD-CKD and MHD patients.

The Role of Renal PLA2R Staining Combined with Serum PLA2R Antibody in Membranous Nephropathy Risk Stratification.

BACKGROUND: This study aimed to examine the clinicopathological profiles and prognosis of membranous nephropathy in different subtypes classified by serum PLA2R antibody (SAb) and glomerular PLA2R antigen staining (GAg). METHODS: A total of 372 biopsy-proven membranous nephropathy (MN) cases, unrelated to lupus, with urine protein > 2 g/24 h and eGFR > 25 mL/min/1.73 m2 were included and categorized into four groups according to the presence or absence of PLA2R antibody and glomerular PLA2R antigen staining. Clinical profiles were compared among four subtypes. Treatment response and renal outcomes were compared among four groups with primary MN. Cox and logistic regression models were used to examine the association between time-to-renal progression and early remission within 6 months in the four subgroups with primary MN. RESULTS: MN patients who were SAb-/GAg+ presented with a more severe disease onset, whereas those who were SAb-/GAg- had a mild clinical manifestation with a higher prevalence of MN-associated secondary causes. During a median follow-up of 79.2 months (IQR: 48.70-97.40), SAb+/GAg- was identified as an independent risk factor for renal progression [HR: 9.17, 95% CI: 2.26-37.16, p < 0.01] and early remission [OR: 0.06, 95% CI: 0.01-0.56, p = 0.01] in primary MN. Additionally, SAb-/GAg- with primary MN showed an independent association with spontaneous remission after adjusting for age, sex, baseline proteinuria, and eGFR (Before adjustment: OR: 8.33, 95% CI: 1.89-36.76, p = 0.0; after adjustment: OR: 12.25, 95% CI: 2.48-60.53, p < 0.01). CONCLUSION: Our findings indicated that SAb+/GAg-MN patients exhibited a more severe disease onset and had a poorer prognosis, necessitating an aggressive treatment approach. On the other hand, in the SAb-/GAg- group, the elimination of secondary causes should be considered, and a watchful waiting approach may be appropriate.

Hypophosphatemia is an independent risk factor for AKI among hospitalized patients with COVID-19 infection.

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

Fulminant type I cryoglobulinemic glomerulonephritis with unique ultrastructural plugs: a case report.

INTRODUCTION:  Type I cryoglobulinemia is a rare disease which affects the skin, central nervous system and kidneys. It is usually associated with lymphoproliferative disorders such as multiple myeloma, lymphoma and monoclonal gammopathy of renal significance. Proteinuria and membranoproliferative glomerulonephritis are the most common renal manifestations; Case presentation: Here we report the case of a female patient in her late 40 s who had proteinuria accompanied by Raynaud's phenomenon, high blood and plasma viscosity, hearing loss, and cardiac and central nervous system involvement. Monoclonal immunoglobulin G-λ protein was detected and serum was positive for cryoglobulin. Renal biopsy revealed massive cryo-plugs with unique ultrastructural appearance in the glomerular and peritubular capillary lumina. Immunofluorescence showed predominant IgG3/λ deposition in cryo-plugs. As reported, the clinical manifestations of this patient resulted from cryoprecipitate and hyperviscosity syndrome; Conclusion: Cryoglobulinemia should be considered as a possible diagnosis in patients with Raynaud's phenomenon, hyperviscosity syndrome and monoclonal immunoglobulin.

Prevalence of and risk factors for high-altitude hyperuricaemia in Bai individuals: a cross-sectional study.

OBJECTIVE: Hyperuricaemia is common in Bai individuals; however, its prevalence remains unclear. This work aimed to investigate high-altitude hyperuricaemia prevalence and risk factors in Bai individuals. METHODS: All eligible participants of Bai ethnicity (aged ≥18 years and undergoing routine medical examination at the People's Hospital of Jianchuan County between January and December 2019) were consecutively enrolled. Demographic and laboratory data were collected to investigate hyperuricaemia prevalence and associated risk factors. RESULTS: A total of 1393 participants were assessed, comprising 345 (24.8%) with hyperuricaemia showing a male predominance (287/865 [33.2%] males versus 58/528 [11.0%] females). Hyperuricaemia prevalence was significantly higher in participants aged ≥50 years (100/332 [30.1%]) versus those aged 30-40 years (59/308 [19.2%]), and in overweight/obese individuals compared with those showing an underweight or normal body mass index (BMI; 267/885 [30.2%] versus 78/508 [15.4%]). Finally, haemoglobin concentrations and serum uric acid levels were positively correlated. CONCLUSION: Besides traditional risk factors, including age, sex and BMI, polycythaemia due to prolonged exposure to high altitude may also cause hyperuricaemia in Bai individuals residing in Yunnan Province.

A validation study of UCSD-Mayo risk score in predicting hospital-acquired acute kidney injury in COVID-19 patients.

INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. METHODS: Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. RESULTS: Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84-0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. CONCLUSIONS: We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.

Anti-glomerular basement membrane nephritis with bronchial carcinoma: a case report.

Renal insufficiency is common among patients with various types of malignant tumors. However, the occurrence of anti-glomerular basement membrane (GBM) nephritis in a patient with a malignant tumor is relatively rare. Here, we describe a patient with bronchial carcinoma who exhibited acute kidney injury, hematuria, and non-nephrotic-range proteinuria. The patient had positive serum anti-GBM antibody findings and biopsy-proven anti-GBM nephritis. This is a rare instance of anti-GBM nephritis in a patient with a malignant solid tumor. Neoplasia was presumed to contribute to the development of anti-GBM nephritis through secretion of tumor-related antigens or unusual exposure to GBM.

Successful Treatment of Idiopathic Eosinophilic Peritonitis by Oral Corticosteroid Therapy in a Continuous Ambulatory Peritoneal Dialysis Patient.

Eosinophilic peritonitis is a well-described complication of peritoneal dialysis and is often associated with either a reaction to the dialysis system constituent (tubing, sterilant or solution) or an underlying bacterial or fungal reaction. We report a case of eosinophilic peritonitis, which is treated by oral prednisone acetate therapy. A 43-year-old female patient developed end-stage renal disease and underwent continuous ambulatory peritoneal dialysis for 2.5 years. The patient received 2,000 ml of 1.5% dialysis solution (PD2) with three exchanges daily and 2,000 ml of 2.5% PDF overnight (PD2). She went to the consultation because of a constant turbid peritoneal dialysis effluent for 3 months without abdominal pain. Repeated peritoneal effluent samples showed an elevated white blood cell count of 500 cells/mm(3), with 87% eosinophils. The peripheral blood test revealed a white blood cell count of 3.8 × 10(9)/l, with 32.2% eosinophils. Etiology like bacterial and fungal infection was excluded by peritoneal fluid culture. Turbidness persisted in spite of diagnostic antibiotic treatment. Given the fact that we found a significant elevation of eosinophils in the peripheral blood and an absolute increase in the eosinophil count of >30/mm(3) in dialysis fluid (up to 400/mm(3) in our patient), obvious dialysate effluent turbidness, negative results of repeated peritoneal fluid cultures, inefficacy of antibiotic therapy, and negativity of serum tumor and immunological markers, we drew the conclusion that the patient had idiopathic eosinophilic peritonitis. Oral corticosteroid was administered at once (20 mg prednisone acetate daily), which was gradually weaned off and stopped over an 8-week period. Afterwards, the dialysis effluent became clear, and the cytological analysis showed that the white blood cell count decreased to 1 × 10(6)/l, with no eosinophils. This case reminds us that the diagnosis of eosinophilic peritonitis should be considered when repeated cultures are always negative and the turbidness of peritoneal dialysis effluent persists in spite of an antibiotic therapy.