Xuewang Li

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.

Conventional versus ultrapure dialysate for lowering serum lipoprotein(a) levels in patients on long-term hemodialysis: A randomized trial

Purpose In patients on long-term hemodialysis, high lipoprotein(a) [Lp(a)] levels are difficult to lower with medications, although they remain a risk factor for cardiovascular disease. We investigated whether ultrapure dialysate (UPD) could lower Lp(a). Methods: We randomly assigned patients stabilized on long-term dialysis to either a low-flux synthetic polysulphone membrane (the UPD group; n=14) or to a conventional dialysate (the CD group; n=13). Blood samples were collected 1 week before dialysis and 1 week, 1 month, 6 months and 12 months after dialysis; Lp(a) was measured by the immunotur-bidimetry method. Hemoglobin, interleukin-6, hypersensitive C-reactive protein, β2 microglobulin and albumin were also measured. The erythropoietin dosage, Kt/V, and normalized protein catabolic rate were recorded monthly. Results At 12 months, mean (SD) serum levels of Lp(a) in the CD patients increased from 143.46 (125.11) to 283.89 (145.81) mg/L (p<0.01), whereas levels in the UPD group remained unchanged: 131.38 (201.45) to 120.90 (122.11) mg/L. Endotoxin levels in the 10 CD patients who completed the study ranged from 0.116 to 0.349 EU/mL and were undetectable in the 11 UPD patients who completed the study. The cultures were less than 200 CFU/mL in CD patients and negative all the time for all UPD patients. Changes in Lp(a) from baseline values were lower in the UPD group than in the CD group (p<0.05). However, changes in other variables did not differ between groups. Conclusions Ultrapure dialysate can prevent the rise of Lp(a), potentially decreasing the risk of cardiovascular disease in hemodialysis patients.

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.

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.

Variability in Predialysis Systolic Blood Pressure and Long-Term Outcomes in Hemodialysis Patients

Background/Aims: While systolic blood pressure variability (SBPV) is an independent risk factor for mortality in the general population, its association with outcomes in hemodialysis patients has been less well-investigated. Methods: In this retrospective study, we enrolled 99 eligible HD patients from 2006 to 2016. Predialysis blood pressure measurements obtained over 1-year period were used to determine each patient’s BPV. The standard deviation (SD), the coefficient of variation (CV) and the variation independent of the mean (VIM) were used as metrics of BPV. Results: During a median follow-up period of 68 months, 52 patients died, and cardiovascular disease (31.3%) was the primary cause of death in these patients. After adjusting for covariates, the hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.80 (95% confidence interval (CI) 1.11-2.92) and 1.71 (95% CI 1.01-2.90), respectively, for a one percent increase in CV. Variability in the volume removed per session and predialysis serum albumin and calcium levels were identified as factors associated with BPV. Conclusion: In this study, we demonstrate that greater variability in predialysis SBP is associated with long-term mortality in hemodialysis patients. Controlling volume variation, avoiding hypoalbuminemia and reducing blood calcium levels might reduce SBP variability and thereby improve prognoses in these patients.

An impaired hepatic clock system effects lipid metabolism in rats with nephropathy

Hyperlipidemia is a key clinical feature in patients with nephrotic syndrome (NS) that is associated with the incidence of cardiovascular events. Recent studies have suggested that the disorders of triglycerides, gluconeogenesis and liver glucose metabolism are associated with the abnormal transcription of clock genes. However, changes to the circadian rhythm of blood lipids in NS require further exploration, and the effects of NS on the hepatic clock system remain to be elucidated. In the present study, the impaired diurnal rhythm of the hepatic core clock genes (BMAL1, CLOCK, CRY1, CRY2, PER1 and PER2) significantly induced circadian rhythm abnormalities in liver-specific clock-controlled genes (LXR, CYP7A1, SREBP-1, ABCA1, DEC1 and DEC2; all P<0.05), which were significantly associated with the abnormal diurnal rhythms of triglyceride, total cholesterol, aspartate aminotransferase and alanine aminotransferase (all P<0.05) in rats with Adriamycin-induced nephropathy. Furthermore, a protein-protein interaction network was identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses based on the human database was conducted to obtain signaling pathway and correlation prediction analyses of overall human clock and clock-controlled gene correlations. Strong correlations of the aforementioned clock genes were detected (avg. local clustering coefficient, 0.849) which suggested significant enrichment in circadian rhythm signaling. The present results indicated that damage to hepatic clock systems may impact blood lipid circadian rhythm disorders in NS, and offer a starting point for understanding the crosstalk between peripheral organs and peripheral clock systems.

Diffusional kurtosis imaging in assessing renal function and pathology of IgA nephropathy: a preliminary clinical study

AIM To evaluate renal fibrosis in immunoglobulin A nephropathy (IgAN) using diffusion kurtosis imaging (DKI). MATERIALS AND METHODS Twenty patients with biopsy-proven IgAN were enrolled. DKI was performed on a clinical 3 T magnetic resonance imaging (MRI) system, and region-of-interest measurements were conducted to determine mean kurtosis (K), mean diffusivity (D), and apparent diffusion coefficient (ADC) of the kidney cortex. Renal biopsy specimens were scored based on the severity of renal fibrosis. The associations between the DKI data and clinicopathological parameters were investigated. RESULTS Both the K and ADC were not only well correlated with the estimated glomerular filtration rate, but also significantly associated with the pathological scores of fibrosis, including the glomerular sclerosis index (K: r=0.759, p<0.001; ADC: r=-0.636, p=0.003) and the percentage of tubular atrophy and interstitial fibrosis (K: r=0.767, p<0.001; ADC: r=-0.702, p=0.001). Further receiver operating characteristic analysis showed that K demonstrated better diagnostic performance in discriminating severe glomerulosclerosis (area under curve [AUC] 0.970, sensitivity 81.8%, specificity 100%), and ADC displayed better capabilities in identifying severe tubular atrophy/interstitial fibrosis (AUC 0.976, sensitivity 100%, specificity 92.9%). CONCLUSION This DKI method can be used to detect renal fibrosis in IgAN in a non-invasive manner and may provide additional information for characterisation and surveillance.

Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis

Objective To investigate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN) with nephrotic syndrome with a systematic review and meta-analysis. Methods PubMed, Embase, Cochrane Library and Clinical Trials (December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission (CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated. Result Seven studies involved 120 patients (73% were men) were included in our systematic review and meta-analysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric (four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44 (36.7%) had immunosuppressive treatment]. In 12- and 24-month, 56% (95%CI, 0.47-0.65) and 68% (95%CI, 0.41-0.87) patients could reach remission, while 15% (95%CI, 0.09-0.23) and 20% (95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions. Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

Renal involvement in primary Sjögren's syndrome: A retrospective study of 103 biopsy-proven cases from a single center in China.

To retrospectively investigate the features of renal involvements in patients with primary Sjögrens syndrome (pSS) with biopsy results.