Objective To explore the correlation between serum 25-hydroxyvitamin D3 [25(OH)D3] level and peritoneal dialysis (PD) associated peritonitis, and provide a new idea for the prevention and treatment of peritonitis. Methods In this single-center retrospective cohort study, patients who were≥18 years old and were treated with regular PD≥3 months in PD center from January 1, 2014 to September 30, 2018 were recruited, except those who had a history of malignant tumors or systemic infectious diseases, transferred from permanent hemodialysis (HD) or failed kidney transplantation. Baseline data including demographic characteristics as well as clinical and biochemical data were collected. All the patients were followed up until death, transfer to HD, kidney transplantation, transfer to other centers or the end of our study (December 31, 2018), and were divided into low tertile [serum 25(OH)D3 ≤12μg/L], middle tertile[12 μg/L<serum 25(OH)D3≤17 μg/L] and high tertile[serum 25(OH)D3 >17 μg/L] according to the baseline serum 25(OH)D3 level. Multivariate adjusted Poisson model was used to evaluate the association between serum 25(OH)D3 level and PD related peritonitis. Results A total of 642 patients were enrolled in our study, of whom 341 were male (53.12%), and the age was (47.58±14.10) years old. The serum 25(OH)D3 level was (13.83±6.41) μg/L. As for the primary disease, 67.19% were chronic glomerulonephritis. During a median 42(19, 59) months follow-up period, 232 peritonitis occurred in 139 patients. After adjusting for confounders, including gender, age, albumin, body mass index(BMI), calcium-phosphorus product, intact parathyroid hormone (iPTH), diabetes, charlson index and drug use, multivariate Poisson regression analysis showed that the risk of peritonitis in the middle tertile and the low tertile was 92% (95% CI 0.62-1.38, P= 0.690) and 1.74 times (95%CI 1.19-2.54, P=0.004) of the high tertile respectively. The difference between the low tertile and the high tertile was statistically significant. Conclusions The level of serum 25(OH)D3 is closely related to the occurrence of PD associated peritonitis. Low level serum 25(OH)D3 is an independent risk factor for peritonitis in PD patients.
Objective To evaluate the volume status of hemodialysis patients with hypertension by bioelectrical impedance vector analysis, and investigate the effect of high volume status on the prognosis of patients with hypertension. Methods The study subjects came from the patients with pre-dialysis systolic blood pressure>160 mmHg (mean systolic blood pressure of 6 times of treatment) in the Affiliated BenQ Hospital of Nanjing Medical University. According to the volume status assessed by bioelectrical impedance vector analysis, patients were divided into two groups: fluid overload group and non-overload group (including normal fluid status and fluid decline). The clinical data, laboratory test results, ratio of intracellular and extracellular water (ICW and ECW), body cell mass, lean body mass and the percentage of total body weight, fat percentage of body weight, resistance/height, reactance/height, phase angle and illmarker were compared between two groups. Kaplan-Meier survival curve was used to compare the difference of survival rate between the two groups. Results A total of 51 hemodialysis patients with hypertension were enrolled in this study, including 19 patients in fluid overload group and 32 patients in non-overload group (27 patients with normal volume status and 5 patients with decreased volume). The levels of albumin, prealbumin, hemoglobin, hematocrit and serum phosphorus in patients with fluid overload decreased significantly compared with non-overload patients (all P<0.05), and the proportion of lymphocytes increased in fluid-overload patients (P<0.05). The ratio of extracellular water and illmarker index in fluid overload group were significantly higher than those in the other group (both P<0.01). However, phase angle, resistance/height, reactance/height were lower than those in patients with non-overload (all P<0.01). After 20 months of clinical observation, the control rate of blood pressure (pre-dialysis systolic blood pressure<160 mmHg) in fluid overload group was lower than that in the non-overload group (26.3% vs 43.8%), but not statistically significant (P=0.218). The all-cause mortality rate of patients in the fluid overload group was higher than non-overload group (26.3% vs 15.6%). Kaplan-Meier survival curve analysis suggested that the difference in survival rate between the two groups was not statistically significant. Conclusions The extracellular fluid of hemodialysis patients with hypertension and fluid overload increases significantly, and the nutritional status evaluation index decreases compared with that of patients without increased volume. Increased proportion of lymphocytes may be related to the micro-inflammatory status. Blood pressure is more difficult to control in hypertensive patients with fluid overload and the clinical prognosis can be worse in patients without increased volume.
Objective To investigate the risk factor of renal anemia in maintenance hemodialysis patients (MHD) and the association of N-terminal pro-brain natriuretic (NT-proBNP) level with renal anemia. Methods Patients who received MHD for more than 3 months at Huashan Hospital affiliated to Fudan University from August 2018 to November 2018 were selected as the subjects. The patients were divided into anemia group and non-anemia group according to the hemoglobin level. The patients' general data, the laboratory examination and dialysis related data during the observation period were collected. Pearson correlation analysis was used to analyze the correlation between anemia indicators, dialysis-related indicators and blood NT-proBNP levels. Stepwise multiple linear regression analysis was used to analyze the risk factors for anemia in MHD patients. Results A total of 160 patients with MHD were included in this study, aged (63.11± 11.35) years. There were 79 males (49.4%) and 81 females (50.6%). The dialysis age was (118.01± 82.32) months, hemoglobin was (110.09±13.48) g/L, and the median NT-proBNP was 3 985 ng/L. There were 73 cases (45.6%) in anemia group and 87 cases (54.4%) in non-anemic group, and NT-proBNP levels were significantly higher in anemia group than that in the non-anemia group (t=-3.714, P<0.001). Hemoglobin levels were positively correlated with weekly dialysis time (r=0.228) and albumin (r=0.349), and negatively correlated with NT-proBNP levels (r=-0.318). Hematocrit was positively correlated with weekly dialysis time (r=0.283), serum calcium (r=0.317), phosphorus (r=0.264) and albumin (r=0.513) with significance (all P<0.05). Univariate regression analysis showed that the level of ln (NT-proBNP) was negatively correlated with hemoglobin (P<0.001). Stepwise multiple linear regression results showed that low albumin level and high NT-proBNP level were independent risk factors for renal anemia in MHD patients. Conclusions The increase level of NT-proBNP in MHD patients is independently associated with the decrease level of hemoglobin. Low albumin level and high NT-proBNP level are risk factors for renal anemia, suggesting that the treatment of renal anemia needs to consider improving the factors such as malnutrition and high volume.
Objective To investigate the incidence of acute kidney injury (AKI) following cardiac surgery and related risk factors in 4 878 patients. Methods The information from patients who underwent cardiac surgery through March 2015 to October 2015 was collected retrospectively from the electronic database of Beijing Anzhen Hospital. A total of 4 878 patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac surgery. The incidence of AKI was calculated, and the AKI incidence in different types of cardiac surgeries were compared. Clinical data such as baseline clinical information, operation information, comorbidity, hospital stay time, life ability score in discharge from the hospital, and so on, were compared between AKI group and the non-AKI group using univariate analysis. Risk factors for AKI following cardiac surgery were analyzed using the binary multivariate logistic regression. Results A total of 933 patients suffered from AKI (19.1%) following cardiac surgery. The time of stay in the hospital was longer in AKI group than that in the non-AKI group [(14.4±8.9) vs (13.7±7.7) d, P<0.05)]. The incidence of AKI in different types of cardiac surgeries varied significantly (P<0.001). The logistic regression analysis showed that male, diabetes, hypertension, the elevated basic serum creatinine, cardiac dysfunction (NYHA grade≥Ⅲ), cardiopulmonary bypass, a combination of operations≥3, the rethoracotomy exploration and hemostasia, and using an invasive ventilator for over 96 hours were the independent risk factors for the AKI following cardiac surgery (all P<0.05), and the odds ratio (95% confidence interval) were 1.81(1.46-2.24), 1.29(1.03-1.62), 5.85(4.73-7.22), 1.81(1.36-2.40), 4.49(3.60-5.60), 1.84(1.49-2.27), 23.24(18.25-29.59), 2.34(1.45-3.77) and 1.94(1.09-3.43) respectively. Conclusions The incidence of AKI after cardiac surgery in Beijing Anzhen Hospital is 19.1%. AKI following cardiac surgery prolongs the time of stay in the hospital. Independent risk factors for AKI following cardiac surgery are multiple, and one of the most critical factors is a combination of operations≥3.
Objective To observe the clinical features in Gitelman syndrome (GS) patients with different urinary calcium excretion, and investigate the value of urinary calcium excretion in the clinical classification for GS. Methods GS cases from the National Rare Diseases Registry System of China (NRSC) (2016-2018) with SLC12A3 gene screened in Peking Union Medical College Hospital were collected. The features of urinary calcium excretion were analyzed, and the phenotypes of patients with hypocalciuria were compared to those without. Hydrochlorothiazide (HCT) test was performed according to the standard process, and the maximal increment of chloride excretion fraction (ΔFECl) was calculated. Results A total of 83 GS patients were included, among whom 53 (63.86%) patients had hypocalciuria. The ratio of urinary calcium/creatine was significantly lower in patients with hypocalciuria compared to those without [(0.085±0.058) mmol/mmol vs (0.471±0.284) mmol/mmol, t=7.349, P<0.001]. Age, gender, estimated glomerular filtration rate, blood pressure, serum and urinary electrolytes, and alkalosis were all comparable between groups. Fatigue (χ2=4.595, P=0.032) and polyuria (χ2=5.778, P=0.016) were less frequently reported in hypocalciuria patients, while all the other clinical symptoms were comparable. Sixteen patients in each group underwent HCT test, and the median value of ΔFECl was comparable between patients with and without hypocalciuria [0.539%(0.430%, 1.283%) vs 0.829% (0.119%,1.298%), U=130.000, P=0.956], both of which indicated no response to HCT. Conclusions The proportion of low urinary calcium in GS patients is 63.86%. There is no definite relationship between urinary calcium excretion, phenotype and the extent of NCC dysfunction.
Objective To explore the characteristics of Lowe syndrome, as well as OCRL1 gene mutation and its relationship with phenotype. Methods Children diagnosed with Lowe syndrome during their visit to Nanfang Hospital of Southern Medical University (4 cases) and the First Affiliated Hospital of Sun Yat-sen University (3 cases) from January 2009 to January 2019 were included. The clinical data and peripheral blood samples were collected, and the sequence analysis of OCRL1 was performed after genomic DNA extraction. Then the clinical features of the children and the relationship between OCRL1 mutation and clinical phenotype were analyzed. Results Seven patients from 6 families who presented with Lowe syndrome were included. All of them had different degrees of ocular-neural-renal symptoms. Six cases from 5 families had congenital cataract and neonatal hypotonia, one case from another family only had a thin lens without cataract. Four cases had nystagmus and 2 cases had glaucoma. Six cases from 6 families had psychomotor retardation and had proximal tubular impairment, included low-molecular-weight proteinuria (LMWP). Serum aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) were increased in all 6 patients who were tested. Mutations of OCRL1 were detected in all the 6 families, which located in exon 10, 13, 16, 18, 22 and 23 respectively. The mutations of c.891 G>T, c.1682_1683insAA and c.2564_2567del are novel. Conclusions Three OCRL1 novel mutations in 6 Chinese Lowe syndrome families are identified. The clinical manifestations in different mutations of OCRL1 are heterogeneous. The mutations of c.891 G>T in exon 10 without congenital cataract is rare in clinical.
Objective To analyze the antibody level of phospholipase A2 receptor (PLA2R) in Chinese patients with primary membrane nephropathy (PMN) and its correlation with clinical indicators, and to explore more suitable cut-off value for Chinese patients. Methods All hospitalized patients with renal biopsy at Peking University People's Hospital from January to August 2018 were retrospectively reviewed. According to the primary disease, patients were divided into PMN group (including patients with idiopathic membranous nephropathy and atypical membranous nephropathy of unknown cause) and control group (other pathological types, including secondary membranous nephropathy patients). Their clinical and pathological characteristics were analyzed, and the level of serum PLA2R antibodies was detected using the method of enzyme-linked immunosorbent assay (ELISA). Spearman correlation was used to analyze the correlation between PMN patients' blood anti-PLA2R antibody level and clinical indicators. The risk factors of PMN were analyzed by logistic regression model, and the optimal cut-off value of PMN was analyzed by ROC curve. Results A total of 354 patients were included in this study, including 114 patients in PMN group and 240 patients in control group. The age of PMN group was (51.7±14.1) years old and the ratio of male to female was 2.2∶1. The median concentration of PLA2R antibody in PMN group was 16.87 RU/ml [inter-quartile range (IQR) 1.88-57.26], which was significantly higher than that in control group (1.43 RU/ml, IQR 1.20-1.62, P<0.001). In PMN group, the concentration of anti-PLA2R antibody was correlated with the 24-hour urine protein ration (r=0.278, P=0.003) and urine erythrocyte (r=0.190, P=0.043), but not with serum albumin (r=-0.149, P=0.114) and serum creatinine (r=0.136, P=0.149). The ROC curve showed that the sensitivity of distinguishing PMN from other diseases was 69.3% (95%CI 60.3%-77.0%), the specificity was 92.9%(95%CI 89.0%-95.5%), and the area under the curve was 0.859(95%CI 0.813-0.905) when the cut-off value was set as 2.28 RU/ml, which was significantly better than the cut-off value of 20.00 RU/ml (the sensitivity/specificity was 46.5%/97.5%) and 14.00 RU/ml (the sensitivity/specificity was 53.5%/97.1%). Conclusions PLA2R antibody is one of the main pathogenic antibodies of PMN. In China, it is recommended to lower its cut-off value to 2.28 RU/ml, which can improve the sensitivity of distinguishing PMN from other pathological types without reducing specificity.
Objective To investigate the expression level of vitamin D receptor (VDR) in podocytes of diabetic kidney disease (DKD) and its role in podocyte injury and proteinuria. Methods (1) Sixty-five patients who had been diagnosed with type 2 diabetes mellitus (with or without albuminuria) were enrolled in this study and 25 age-and sex-matched healthy control subjects were enrolled. According to the ratio of urinary excretion of albumin/creatinine (ACR), the type 2 diabetes mellitus patients were classified into without proteinuria group (ACR<30 mg/g, n=24), microalbuminuria group (ACR 30-300 mg/g, n=18) and clinical proteinuria group (ACR>300 mg/g, n=23). Another 25 patients with DKD confirmed by renal biopsy were selected as the DKD group. Normal kidney tissue samples were taken from the same period of urinary surgical department for 10 cases of renal tumors in patients with renal resection. The test indicators in each group were compared. The VDR expression in blood, urine samples and kidney tissues of patients was detected by real-time quantitative PCR, ELISA and immunohistochemistry, and then were compared among different groups. The correlation between VDR and ACR was analyzed by Pearson correlation analysis. (2) Male db/db mice with genetic background of C57BLKs/J and db/m mice born in littermates were randomly divided into normal control group (group A), DKD control group (group B), DKD treated with dimethyl sulfoxide group (group C), DKD treated with paricalcitol (VDR agonist) group (group D). The C and D groups were treated by continuous intraperitoneal injection for 8 weeks, and the group A and B were not treated. The mice were started to intervene continuously for 8 weeks at the age of 10 weeks. At 22 weeks of age (12 weeks after starting intervention), the biochemical indexes of the mice's body weight, blood and urine were compared. The changes of β-catenin and VDR were detected by Western blotting. The expressions of podocyte marker protein podocin and podocyte injury protein α-SMA were observed by immunofluorescence. Results (1) Compared with the normal healthy control group, the plasma levels of VDR mRNA and protein in diabetic patients without proteinuria, microalbuminuria and clinical proteinuria were lower (all P<0.05). Compared with the diabetic patients without proteinuria, the plasma levels of VDR mRNA and protein in diabetic patients with microalbuminuria and clinical proteinuria were lower (all P<0.05). (2) Compared with the normal healthy control group, the plasma levels of VDR mRNA and protein in diabetic patients without proteinuria and DKD patients were lower (all P<0.05). Compared with diabetic patients without proteinuria, the plasma levels of VDR mRNA and protein in the DKD group were also lower (both P<0.05). (3) Immunohistochemical results showed that the expression of VDR in kidney tissue of DKD group was significantly lower than that of normal control group. (4) The relative level of VDR mRNA in plasma of patients with DKD was negatively correlated with ACR (r=-0.342, P<0.05). (5) The levels of VDR in urine supernatant of each group showed opposite trends with the plasma levels. (6) Western blotting results showed that the expression of β-catenin protein in groups B and C was higher than that in group D (both P<0.05), and the expression of VDR protein was lower than that in group D (both P<0.05). Immunofluorescence results showed that the expression of podocin in groups B and C was lower than that in group D (both P<0.05), and the expression of α-SMA was higher than that in group D (both P<0.05). Conclusion VDR overexpression relieves podocyte injury and proteinuria in DKD.