Limeng Chen

Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome

To determine whether Th17/Treg balance was abnormal in adult patients with minimal change nephrotic syndrome (MCNS), we studied 25 patients with new-onset MCNS and 20 normal persons. The results showed that MCNS patients exhibited a significant increase in Th17 number, Th17-related cytokines (IL-17 and IL-23), and transcription factor (RORγt) levels, as well as an obvious decrease in Treg number, Treg-related cytokines (TGF-β1 and IL-10), and transcription factor (Foxp3) levels. The Th17/Treg ratios increased along with increased proteinuria and decreased albumin levels in patients with MCNS. IL-17 protein expression was also detected in the renal biopsy tissue of MCNS patients, particularly in patients with acute renal failure. Further, Th17/Treg balance returned to normal after effective corticosteroids therapy in 16 MCNS patients. These results indicated that Th17/Treg imbalance existed in MCNS patients, suggesting a potential role of Th17/Treg imbalance in the pathogenesis of MCNS.

Variants in Vitamin D Binding Protein Gene Are Associated With Gestational Diabetes Mellitus

AbstractTo investigate whether single nucleotide polymorphisms (SNPs) within 4 representative genes (VDR, GC, CYP2R1, and CYP24A1) encoding the core proteins involved in vitamin D production, degradation, and ligand-dependent signaling pathway are associated with gestational diabetes mellitus (GDM) in a Chinese population.A total of 1494 pregnant Han Chinese women (692 women with GDM and 802 women with normal glucose served as controls) were recruited through a 2-step approach. Participants were further divided into 2 groups according to body mass index before gestation (pre-BMI) (25 kg/m2). Nine SNPs (rs3733359, rs2282679, and rs16847024 in GC, rs2060793 and rs10741657 in CYP2R1, rs2248359 and rs6013897 in CYP24A1, rs11574143 and rs739837 in VDR) were genotyped using TaqMan allelic discrimination assays. The relationships between genotypes/alleles of a single locus as well as haplotypes of each gene and GDM were analyzed.We did not observe a significant difference in genotype frequency of each SNP between cases and controls. However, in the obese subgroup (pre-BMI ≥ 25 kg/m2), the risk allele-A of rs3733359 showed an association with increased risk of GDM (OR = 1.739, 95% CI = 1.066–2.837, P = 0.027). The GG-haplotype frequency of rs3733359 and rs2282679 in GC was modestly lower in the GDM group (OR = 0.848, 95% CI = 0.719–0.999, P = 0.048). Rs2060793 and rs10741657 were associated with insulin area under the curve (P = 0.028, P = 0.042, respectively), while rs739837 and rs6013897 demonstrated a correlation with fasting glucose (P = 0.019, P = 0.049, respectively). Additionally, rs2248359 displayed an association with leukocyte counts (B = 0.063 P = 0.033) and rs16847024 was related to high-sensitivity C-reactive protein levels (B = 0.086, P = 0.005).Our results indicate an association between GC variants and GDM, as well as a relation between a subset of loci in CYP2R1, CYP24A1, and VDR and clinical parameters related to GDM. Our findings may provide information for identifying biomarkers for early risk prediction of GDM and the pathways involved in disease progression.

Effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta‐analysis of randomized controlled trials

The aim of this study was to describe the effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, CENTRAL, EMBASE and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to May 20, 2017. A total of 62 studies, comprising 34 941 patients, were included. Any of the SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total weighted mean difference [WMD] −37.73 μmol/L, 95% CI [−40.51, −34.95]). Treatment with empagliflozin resulted in a superior reduction in SUA (WMD −45.83 μmol/L, 95% CI [−53.03, −38.63]). The effect persisted during long‐term treatment. Dapagliflozin decreased SUA in a dose‐dependent manner (from 5 to 50 mg, P = .014). In subgroup analyses, greater reductions could be observed during the course of early diabetes and the SUA‐lowering effect was abolished in patients with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m2). The effect of SGLT2 inhibitors on SUA reduction suggests that this class of drugs might be beneficial for diabetic patients with hyperuricaemia.

Glomerular Disease Associated with Takayasu Arteritis: 6 Cases Analysis and Review of the Literature

OBJECTIVE To evaluate the clinical features, renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis (TA). METHODS Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively. None of them had renal artery stenosis or occlusive changes. RESULTS Six patients with glomerulopathy, accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period, were analyzed. All of them were females with a mean age of 35.5 +/- 10.0 years. Four cases presented with lower extremity edema. Laboratory tests showed that one was nephrotic syndrome, three were nephrotic range proteinuria, and two of them had mild renal dysfunction. The other two patients were asymptomatic microscopic hematuria and proteinuria. Renal pathology revealed mild immunoglobulin A nephropathy in two cases, mild mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, minimal change disease, and fibrillary GN in one case respectively. Five cases received glucocorticoids and cyclophosphamide therapy. Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases. The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment. CONCLUSIONS TA may induce glomerular disease as a part of its histological spectrum. Apart from ischemic glomerular disease, glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria, that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.

Endoplasmic Reticulum Stress Predicts Clinical Response to Cyclosporine Treatment in Primary Membranous Nephropathy

Background: Little is known about the endoplasmic reticulum stress (ERS) marker glucose regulated protein 78 (GRP78) and calcineurin in the kidney in primary membranous nephropathy (PMN) and if they could predict post-cyclosporine treatment outcome. Methods: This is a retrospective study using a dataset of biopsy-confirmed PMN from Peking Union Medical College Hospital from 1996 to 2014. Seventy-six adult patients treated with cyclosporine as primary immunosuppression for at least 6 months were studied. Immunohistochemistry was used to detect GRP78 and calcineurin in the kidney. Serum calcineurin was assayed by ELISA. Patients were grouped into no-remission (NR, n = 17), partial remission (PR, n = 39), or complete remission (CR, n = 20) at the end of 6 months of treatment. Results: There was no difference of initial dose of cyclosporine among NR, PR, and CR groups. Kidney calcineurin expression in PMN was significantly increased compared to that in controls (p < 0.0083). The glomerular GRP78 in NR PMN was higher than that in control, CR and PR patients (p < 0.0083). Kidney calcineurin expression and GRP78 expression was positively correlated. However, there were no differences in either serum calcineurin levels or kidney calcineurin expressions among NR, PR or CR groups. There was a negative correlation between serum calcineurin activity and whole kidney calcineurin expression (p = 0.034) or glomerular calcineurin expression (p = 0.007). Neither kidney calcineurin nor GRP78 expression was correlated with proteinuria. Conclusions: ERS marker GRP78 in the glomeruli but not serum or kidney calcineurin expression could be a useful marker in PMN to negatively predict the response to cyclosporine treatment at the sixth month.

Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06]), but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]). Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

NORMOMAGNESEMIC GITELMAN SYNDROME PATIENTS EXHIBIT A STRONGER REACTION TO THIAZIDE THAN HYPOMAGNESEMIC PATIENTS.

OBJECTIVE In recent decades, the thiazide test has been introduced to aid the diagnosis of Gitelman syndrome (GS), but the effect of thiazide in normomagnesemic GS patients is currently unknown. This study was conducted to compare the thiazide test results of normomagnesemic and hypomagnesemic GS patients. METHODS Seventeen GS patients with SLC12A3 gene mutations were enrolled, five of whom did not have a history of hypomagnesemia. The clinical data were documented, and SLC12A3 gene screening was performed. The thiazide test was performed in all of the patients and 20 healthy controls. A receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the thiazide test in the diagnosis of GS. RESULTS A 7-fold increase in sodium and chloride excretion was observed after thiazide application in healthy controls, and an approximately 2-fold increase was found in the 5 normomagnesemic GS patients; however, there was no change in the 12 hypomagnesemic GS patients. A weaker reaction to thiazide was observed in hypomagnesemic compared with normomagnesemic GS patients. The clearance of chloride in 1 patient was overestimated because of chronic renal function insufficiency (CRI). When a reasonable cutoff value for chloride fractional excretion was selected, the thiazide test was 95% sensitive and 94.1% specific for the diagnosis of GS. CONCLUSION Hypomagnesemic GS patients exhibited greater sodium-chloride cotransporter dysfunction than normomagnesemic GS patients. When CRI occurs, the chloride and sodium clearance rates, rather than the fractional excretion, should be used in the evaluation of the thiazide test results.

Diagnosis and Treatment of Infective Endocarditis in Chronic Hemodialysis Patient

OBJECTIVE To analyze the clinical features of hemodialysis patients complicated by infective endo carditis. METHODS The clinical features of six such patients admitted to Peking Union Medical College Hospital during the year 1990 to 2009 were analyzed. All of them were diagnosed based on Chinese Children Diagnostic Criteria for Infective Endocarditis. RESULTS The average age of the six patients was 52.3 +/- 19.3 years old. Four were males. Vascular accesses at the onset of infective endocarditis were as follows: permanent catheters in three, temporary catheters in two, and arteriovenous fistula in one. Three were found with mitral valve involvement, two with aortic valve involvement, and one with both. Five vegetations were found by transthoracic echocardiography, and one by transesophageal echocardiography. Four had positive blood culture results. The catheters were all removed. Four of the patients were improved by antibiotics treatment, in which two were still on hemodialysis in the following 14-24 months and the other two were lost to follow-up. One patient received surgery, but died of heart failure after further hemodialysis for three months. One was well on maintenance hemodialysis for three months after surgery. CONCLUSIONS Infective endocarditis should be suspected when hemodialysis patients suffer from long-term fever, for which prompt blood culture and transthoracic echocardiography confirmation could be performed. Transesophageal echocardiography could be considered even when transthoracic echocardiography produces negative findings. With catheters removed, full course of appropriate sensitive antibiotics and surgery if indicated could improve the outcome of chronic hemodialysis patients complicated by infective endocarditis.

Diminished Appetite Predicts Mortality of Chinese Peritoneal Dialysis Patients

Background: Many maintenance dialysis patients experience a common cluster of symptoms, including diminished appetite (anorexia). This symptom has been associated with reduced quality of life and increased mortality in this population. Aim: The aim of this study was to determine whether diminished appetite is a significant predictor of negative clinical outcomes in patients on peritoneal dialysis (PD). Method: A longitudinal prospective study was conducted in 98 patients receiving PD in Beijing, China. Clinical characteristics, nutritional and inflammatory marker levels, and related peritoneal treatment information were collected. The appetite status and serum albumin levels were assessed initially and reevaluated monthly during the first year of follow-up. All patients were followed for nearly 5 years or until death. Data were collected about mortality, hospitalization, and peritonitis. Results: The mean age of participants was 60.3 ± 14.4, and 22.8% reported diminished appetite. At baseline, female sex, cardiovascular disease, and prealbumin level were the significant predictors of appetite. The average length of follow-up was 39 (range: 2–57) months. The Kaplan–Meier survival curve showed the survival rate was lower in patients reporting diminished appetite than for patients reporting normal appetite. Multivariate analysis indicated that diminished appetite, diabetes, ferritin, and serum albumin levels were independent predictors of mortality. Conclusion: Self-reported appetite was a predictor of clinical characteristics and outcome for patients receiving PD. Conducting appetite evaluation periodically is recommended as a nursing strategy to improve care for these patients.

Effectiveness of self-management support in maintenance haemodialysis patients with hypertension: A pilot cluster randomized controlled trial: Self-management Support

Uncontrolled hypertension is an independent risk factor for cardiovascular disease and is the leading cause of mortality in haemodialysis patients. The aim of this study was to examine the effectiveness of self‐management support (SMS) for blood pressure (BP) control and health behaviours.