Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Rhein alleviates renal interstitial fibrosis by inhibiting tubular cell apoptosis in rats.

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.

Association Analysis of the MHC in Lupus Nephritis.

Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRß1 amino acid 11 (Pomnibus<0.001), HLA-DQß1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA-DPß1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

[The clinical efficacy and safety of modified Ponticelli regimen for treatment of idiopathic membranous nephropathy].

OBJECTIVE: To explore the clinical efficacy and safety of modified Ponticelli regimen in treating patients with idiopathic membranous nephropathy(IMN). METHODS: A retrospective analysis was performed in 90 patients with IMN (type Ⅰ/Ⅱ, 79/11 respectively) diagnosed by clinical data and renal biopsy. The patients were divided into modified Ponticelli group (n=23), steroid plus cyclophosphamide(CTX) (CTX group, n=39) and steroid plus cyclosporine A(CsA) (CsA group, n=28) according to the treatment. Liver function, renal function, serum lipid, proteinuria were recorded before and after treatment. Efficacy and adverse reactions were evaluated in three groups. RESULTS: (1)In all three groups, the quantity of proteinuria after treatment for 3 months [(3.33 ± 1.53) g/d, (4.70 ± 2.97) g/d, (3.92 ± 2.57) g/d], 6 months [(1.60 ± 1.10) g/d, (2.34 ± 1.61) g/d, (2.25 ± 1.78) g/d] was significantly decreased compared with baseline level[(7.26 ± 2.06) g/d, (7.50 ± 2.55) g/d, (7.54 ± 2.70) g/d; P<0.05]. Serum albumin levels at 3 months[(31.42 ± 3.86) g/d, (30.59 ± 5.79) g/d, (30.90 ± 7.87) g/d], 6 months [(36.25 ± 4.20) g/d, (34.70 ± 6.70) g/d, (35.36 ± 8.29) g/d] were significantly increased compared with baseline levels [(24.13 ± 2.61) g/d, (23.98 ± 3.79) g/d, (22.94 ± 4.57) g/d; P<0.05], whereas serum creatinine at 3 and 6 months had no significant changes (P>0.05). (2)After treatment for 3 months, partial remission rates in modified Ponticelli group, CTX group and CsA group were 39.1%, 35.9%, 35.7% respectively and complete remission rates were 8.7%, 5.1%, 10.7%, which were not statistically significant in all three groups (P>0.05). At 6 months, partial remission rates in three groups were 56.5%, 41.0%, 42.9% respectively and complete remission rates were 21.7%, 20.5%, 28.6%, which did not suggested significant difference in all three groups either (P>0.05). (3)In modified Ponticelli group, steroid diabetes, impaired liver dysfunction, infections and gastrointestinal adverse events occurred in 1, 1, 2 and 2 patients, respectively. In CTX group, steroid diabetes, infections and gastrointestinal adverse events occurred in 5, 8 and 2 patients, respectively. In CsA group, steroid diabetes and infections occurred in 1 and 3 patients, respectively. CONCLUSION: Modified Ponticelli regimen to treat patients with IMN has a trend of better outcome than classic CTX regimen. The efficacy is not inferior to CsA regimen with fewer side effects.

PTEN Inhibits High Glucose-Induced Phenotypic Transition in Podocytes.

Accumulating evidence has suggested that podocytes undergo epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN). However, the underlying mechanisms of EMT in podocyte are not well understood. PI3K/Akt pathway is involved in the progression of DN. In the present study, we demonstrated that PI3K/Akt pathway was activated in podocytes exposed to high glucose conditions, accompanied by down-regulation of the podocalyxin (PCX) and nephrin expression and up-regulation of the desmin and α-smooth muscle actin (α-SMA) expression. Inhibition of PI3K/Akt pathway by chemical LY294002 or Phosphase and tensin homology deleted on chromosome ten (PTEN) prevented the phenotypic transition. These findings indicate that PTEN/PI3K/Akt pathway mediates high glucose-induced phenotypic transition in podocytes.

A Novel Wick-Like Paper-Based Microfluidic Device for 3D Cell Culture and Anti-Cancer Drugs Screening.

Paper is increasingly recognized as a portable substrate for cell culture, due to its low-cost, flexible, and special porous property, which provides a native cellular 3D microenvironment. Therefore, paper-based microfluidics has been developed for cell culture and biomedical analysis. However, the inability of continuous medium supply limits the wide application of paper devices for cell culture. Herein, a paper-based microfluidic device is developed with novel folded paper strips as wick-like structure, which is used for medium self-driven perfusion. The paper with patterns of hydrophilic channel, culture areas, and hydrophobic barrier could be easily fabricated through wax-printing. After printing, the hydrophilic paper strip at the periphery of the lower layer is then folded at 90° and extended into the medium container for continuous automatic supply of medium to the cell culture area. Tumor cells cultured in the paper device are tested for anti-cancer drug screening. Visualized cell viability and chemical sensitivity testing can be achieved by colorimetry combined with simple smartphone imaging, effectively reducing precision instrument dependence. The wick paper-based microfluidic device for cell culture endows the method the advantages of lower cost, ease-of-operation, miniaturization, and shows a great potential for large-scale cell culture, antibody drug production, and efficient screening.

Hypertension Control in Adults With CKD in China: Baseline Results From the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

BACKGROUND: Hypertension contributes to increased morbidity and mortality in the chronic kidney disease (CKD) population. Studies on blood pressure control in CKD patients in China are limited. In this study, we aimed to describe the status of blood pressure control in Chinese CKD patients based on the first national prospective CKD cohort data. METHODS: A subgroup of Chinese Cohort Study of Chronic Kidney Disease participants with hypertension at baseline was included in the present study. Uncontrolled blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg. Defined daily doses (DDDs) are used as a standard measurement of drug utilization in this population. Factors associated with uncontrolled blood pressure were analyzed using multivariable logistic regression. RESULTS: There were 2,251 hypertensive CKD subjects among 2,873 predialysis CKD participants. The awareness, treatment, and control rates of hypertension were 80.7%, 95.6%, and 57.1%, respectively. Factors independently associated with uncontrolled blood pressure were overweight, obesity, albuminuria, decreased estimated glomerular filtration rate (eGFR), and diabetes. Over 50% of study subjects were prescribed 2 or more antihypertensive medications and only 7% were prescribed diuretics. Uncontrolled hypertensive patients were prescribed less antihypertensive medication than controlled hypertensives (DDD 1.3 [1.0-2.3] vs. 2.0 [1.0-3.1], P < 0.001). CONCLUSIONS: Hypertension control was suboptimal among hypertensive CKD patients in China, especially among those overweight or with obesity, albuminuria, lower eGFR, and diabetes. Patients with uncontrolled hypertension should undergo treatment regimen evaluation to select the appropriate dosage and type of antihypertensive medications.

Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients: A Multicenter Study in China.

BACKGROUND: Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death. METHODS: Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality. RESULTS: In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis. CONCLUSIONS: Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Rhein alleviates renal interstitial fibrosis by inhibiting tubular cell apoptosis in rats

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.

[Clinical and histo-pathological characteristics of 2874 cases with chronic kidney diseases in Southern parts of Hebei province].

OBJECTIVE: The aim of this study was to analyze the characteristics of patients with chronic kidney disease (CKD) in Southern parts of Hebei province. METHODS: Records of 2874 CKD patients during January, 2008 to May, 2011 were retrospectively reviewed. Demographic, clinical and histo-pathological data were analyzed and compared to ones from the past five years. RESULTS: The age distribution of the groups was between 16 and 84 years old, with 62.39% of them between 20 and 50. All patients underwent renal biopsy that with primary glomerulonephritis occurring in 1966 cases (68.41%), secondary glomerulonephritis in 826 cases (28.74%). The frequently seen pathological patterns were IgA nephropathy (IgAN), membranous nephropathy (MN) and minimal change disease (MCD) in proper order in the former group while Henoch-Schonlein purpura nephritis (HSPN) and lupus nephritis (LN) were seen in the latter group. Comparing to data of the past five years, the incidence rates of MN, MCD and HBV-GN increased to 16.84%, 15.73% and 4.41% respectively, but all IgAN, HSPN and LN had respectively decreased to 24.70%, 5.50% and 6.65%. MN, IgAN, MCD were commonly appeared in histo-pathological patterns among patients over 50 years of age. CONCLUSION: IgAN was still the most commonly seen renal disease. Compared to data of the past five years, the incidence rates of MN, MCD and HBV-GN showed an increase at different levels. Epidemiological and pathological pattern of patients with CKD in Southern Hebei province had only mild changes over the last 3 years.