Three cases of obinutuzumab treatment for rituximab-resistant phospholipase A 2 receptor- associated membranous nephropathy / 中华肾脏病杂志

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

Blood Oxygen Level Dependent MRI of Normal Kidney and Its Correlation with Physiological Indexes / 天津医药

Objective To explore the characteristics of blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) in healthy native kidneys. To investigate the relationship between BOLD-MRI and common physiological in-dexes. Methods GE 3.0T MRI scanner and Torsopa phased-array coil were employed to acquire renal coronal T1WI and BOLD image. Ninety patients who were ruled out chronic kidney diseases underwent BOLD-MRI with T2*-spoiled gradient recalled echo (T2*SPGR) sequence. BOLD images were analyzed on R2*map software. Cortical and medullary R2*values were analyzed in bilateral kidneys and in different gender. Different regional R2*values in cortex and medulla were also ana-lyzed. Physiological indices including age, body height and weight, body mass index (BMI), body surface area (BSA), estimat-ed glomerular filtration rate (eGFR) were recorded. Correlation between R2*value and physiological indices were analyzed. Results Bilateral renal cortical R2*values [left (16.56±1.40) Hz and right (16.66±1.28)Hz, respectively] were less than val-ues in medulla [left (28.82±3.71)Hz and right (28.36±3.72)Hz, respectively]. Female and male cortical R2*values [female (16.55±1.30Hz) and male (16.66±1.38)Hz, respectively] were also less than corresponding values in medulla [female (28.46± 3.64) Hz and male (28.70±3.78) Hz, respectively]. In bilateral renal medullary region, R2*values in low pole (27.29±3.05) Hz was less than values in middle (29.32±3.47) Hz and upper pole (29.16±4.21)Hz (F=15.184, P<0.001). Age was positive-ly correlated with R2* values in medulla (r =0.284, P =0.002). However, eGFR was negatively correlated with medullary R2*value (r=-0.232, P=0.007). Conclusion R2*values reflected the levels of renal partial pressure of oxygen and as-sessed the degree of renal ischemia. BOLD MRI could offer a simple, convenient and noninvasive method for to evaluate renal oxygen metabolism in cortex and medulla.

Association of radial arterial calcification damage with bone mineral density and bone metabolism biomarkers in uremia patients / 中华肾脏病杂志

Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.

A systematic review and meta-analysis of candesartan and losartan in the management of essential hypertension.

BACKGROUND: Candesartan is a relatively novel antihypertensive agent of the angiotensin receptor blocker (ARB). Several clinical trials have compared candesartan with losartan in the management of essential hypertension. However, systematic assessment of efficacy and safety between candesartan and losartan is still lacking. METHODS: We reviewed randomised controlled trials (RCTs) comparing candesartan with losartan for net reduction in blood pressure from baseline, response and control rates, and incidences of common and serious adverse events.Weighted mean differences (WMD), and relative risk (RR) with 95% confidence intervals (CI) were calculated for continuous and dichotomous data, respectively. RESULTS: A total of 12 RCTs with 3644 patients were included in this meta-analysis. When comparing the efficacy of candesartan and losartan in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of the follow-up period, results with candesartan were superior to losartan in the reduction SBP and DBP (WMD, -2.97; 95% CI, -4.18 - -1.77; p < 0.001; WMD, -1.76; 95% CI, -2.57 - -0.96; p < 0.001; respectively). Candesartan had better response and control rates than losartan. (RR, 1.12; 95% CI, 1.06-1.18; p < 0.01; RR, 1.26; 95% CI, 1.06-1.50; p = 0.008). Reported common adverse events for the two agents were not significantly different (RR, 0.98; 95% CI, 0.86-1.12; p = 0.78). The incidence of serious adverse events for candesartan was lower than for losartan (RR, 0.48; 95% CI, 0.25-0.92; p = 0.03). The net reduction of DBP showed negative correlation with baseline DBP in both candesartan and losartan groups (regression coefficient -1.81, p = 0.03 and regression coefficient -1.56, p = 0.02, respectively). CONCLUSIONS: Candesartan is superior to losartan in reducing blood pressure. Candesartan also causes fewer serious adverse events than losartan.

A systematic review and meta-analysis of aliskiren and angiotension receptor blockers in the management of essential hypertension.

Aliskiren is a novel antihypertensive agent and the first direct renin inhibitor (DRI) in clinical use. Several clinical trials have compared DRI with angiotensin receptor blockers (ARBs) in the management of essential hypertension. However, systematic comparison of efficacy and safety between DRIs and ARBs is still lacking. We reviewed randomized controlled trials (RCTs) comparing aliskiren with ARBs for net reduction of blood pressure from baseline, achieved rate of control, and incidences of common and serious adverse events. Weighted mean differences (WMD) and relative risk (RR) with 95% confidence intervals (CI) were calculated for continuous and dichotomous data, respectively. Seven RCTs with 5488 patients were included in this meta-analysis. We compared the efficacy of aliskiren and ARBs in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP). No differences were found between the two groups. Aliskiren combined with ARBs was superior to aliskiren monotherapy at the maximum recommended dose on SBP and DBP reduction. (WMD -4.80, 95% CI -6.22-- -3.39, p < 0.0001; WMD -2.96, 95% CI -4.63-- -1.28, p = 0.0001; respectively). Similar results were found with aliskiren combined with ARBs versus ARB monotherapy (WMD -4.43, 95% CI -5.91-- -2.96, p < 0.0001; WMD -2.40; 95% CI -3.41-- -1.39, p < 0.0001; respectively). No differences were found in adverse events between the aliskiren and ARB groups. Similar results were found with aliskiren and ARB combination therapy and its respective monotherapy. We conclude that aliskiren's BP-lowering capabilities were comparable to those of ARBs. Aliskiren and ARB combination therapy provided more effective BP reduction than each respective monotherapy without increasing adverse events.

Correlation between serum bone metabolism biomarkers and bone mineral density in chronic kidney disease patients with different stages / 中华肾脏病杂志

Objective To investigate the correlation between serum bone metabolism biomarkers and bone mineral density (BMD) in chronic kidney disease (CKD) patients with different stages. Methods Seventy-eight CKD patients were enrolled in this study and were assigned to different groups according to their ereatinine clearance (Cer). Patients with Cer ≥ 15 ml/min were divided into 4 groups based on clinical CKD 1-4 stage standard, and those with Ccr<15 ml/min were divided into two groups of hemodialysis (HD) and non-HD. Their levels of serum calcium, phosphorus, alkalinity phosphatase (ALP), urea, Ser, osteocalein (gla-protein, OC), calcitonin (CT), intact parathyroid hormone (iPTH), osteoprotegerin (OPG) and BMD were detected respectively. Results (1) The serum levels of OPG, iPTH and phosphorus increased significantly in stage 3, 4, 5, respectively (P<0.01), and serum OPG level was elevated to (5.1±1.34) ng/L after HD, which was significantly higher than (3.35±0.76) ng/L before HD (P<0.05). The levels of serum OC, CT, calcium, ALP were not significantly different among patients with different CKD stages, while the level of OC was elevated in HD patients (P<0.05). The femoral WARDS triangle BMD of CKD stage 4 patients decreased to 0.77±0.09, which was less than the value of CKD stage 1 patients (P<0.01), with litde influence from hemodialysis treatment. (2) The level of serum OPG was positively correlated with the levels of serum phosphorus, iPTH, OC (r = 0.51, 0.39, 0.36,all P<0.01), and it was negatively correlated with the level of Ccr (r =-0.70, P<0.01). The femoral WARDS triangle BMD was negatively correlated with the levels of iPTH, OC, phosphorus and OPG (r =-0.59,-0.51,-0.45,-0.48, all P<0.05). Conclusions Most of serum bone metabolism biomarkers change according to the declined level of Cer. Compared with serum phosphorus, the levels of iPTH, BGP and femoral WARDS triangle BMD, serum OPG may be early diagnosticmarkers of renal osteodystrophy in CKD patients.