Shuwen Liu

Aging Promotes Progression of IgA Nephropathy: A Systematic Review and Meta-Analysis

Background: There has been considerable interest in whether old age is associated with IgA nephropathy (IgAN) progression, which is still controversial. Methods: We searched multiple databases for studies published from 1980 to 2012. The inclusion criteria were case-control, cohort studies published in any language. The included studies needed to have an older group. IgAN was proven by biopsy. Results: We included 9 studies with a total of 6,543 patients. The meta-analyses of other risk factors between the older group (>50 years old) and the non-older group (15-50 years old) found significant differences in the presence of hypertension, proteinuria, serum cholesterol levels and baseline renal function. In the overall analysis, compared to the non-older group, older age significantly increased the incidence of developing end-stage renal disease [ESRD; relative risk (RR) random model 1.95; 95% CI: 1.27-3.01]. In the subgroup analyses, we found the age limit and traditional risk factors of IgAN may be the sources of heterogeneity between studies. Moreover, the RR (2.56) of the Asian countries was much higher than the RR (1.11) of the European countries. Conclusions: This comprehensive review revealed that old age is a real risk factor for IgAN progression to ESRD. The incidence of ESRD in the older IgAN patients was 1.95 times higher than that in the non-older IgAN patients. Moreover, the risk of IgAN progression to ESRD of the older patients in Asia was higher than that of the older patients in Europe.

Clinical evaluation of serum cystatin C and creatinine in patients with chronic kidney disease: A meta-analysis

Objective Glomerular filtration rate (GFR) is an important indicator of renal function. This meta-analysis aimed to evaluate the diagnostic value of serum cystatin C (CysC) and serum creatinine (SCr) for estimating GFR in patients with chronic kidney disease. Methods Google Scholar, PubMed®, Cochrane Library and China National Knowledge Infrastructure databases were searched, to identify randomized controlled trials that determined the diagnostic value of CysC and SCr, for estimating GFR in patients with chronic kidney disease. Results The inclusion criteria were met by 17 studies (total number of patients with chronic kidney disease, 2521). Meta-analysis showed that when the diagnostic cut-off value of GFR was 80–90 ml/min/1.73 m2, the heterogeneity was modest for CysC (I2 = 48%, summary sensitivity [SEN] = 0.803, summary specificity [SPE] = 0.821), but there was no heterogeneity for SCr (I2 = 0.0%, SEN = 0.697, SPE = 0.787). Meta-analysis of the studies demonstrated a significant difference between patients with chronic kidney disease and controls, for CysC and SCr. Conclusions This meta-analysis demonstrated significant correlations between CysC, SCr and GFR. CysC was more sensitive, but less specific, than SCr for the estimation of GFR.

Validation of a differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases and the establishment of a new diagnostic model 糖尿病肾病和非糖尿病性肾脏疾病的鉴别诊断模型的验证及新模型的建立

The aims of the present study were to validate the differential diagnostic model of diabetic nephropathy (DN) and non‐diabetic renal diseases (NDRD) established in 2003 and to establish a new diagnostic model suitable for the current clinical characteristics of DN.

Kruppel-like factor-15 inhibits the proliferation of mesangial cells.

Background/Aims: The Kruppel-like factor-15 (KLF15), a DNA-binding transcription factor, is highly expressed in endothelial and mesangial cells of the kidney. However, its effects on mesangial cell proliferation have not previously been investigated. In this study, we investigated the effect of KLF15 on mesangial cell proliferation. Methods: We established a classic rat anti-Thy1 mesangial proliferative nephritis model. Affymetrix rat U230 2.0 chip was used to detect the gene expression profiles at different time point in the model. The different expression of KLF15 was shown during mesangial cell proliferation period and proliferation declined period of anti-Thy1 nephritis model by microarray analysis, Real-time PCR and Western blotting. Then we determined the effects of KLF15 and its downstream target, cell cycle regulation factor E2F1 on the proliferation of mesangial cells and the expression of the positive-acting cell cycle regulatory proteins, cyclinD1 and CDK2, by means of positive and negative interference experiments in cultured rat mesangial cells. We detected also protein expression of E2F1, cyclinD1 and CDK2 in vivo. Results: By real-time PCR, Western blotting, and microarray analysis, KLF15 expression was shown to be lower during mesangial cell proliferation period and higher during proliferation declined period and under normal conditions. The mesangial cell proliferation was reduced and the expression of E2F1, cyclin D1 and CDK2 was downregulated in mesangial cells overexpressing KLF15. When KLF15 expression was inhibited by siRNA, the expression of E2F1, cyclin D1 and CDK2 and mesangial cell proliferation were increased. When E2F1 was inhibited by siRNA, protein level of CDK2 and cyclin D1 were lower than control. When siE2F1 was co-transfected with siKLF15 into mesangial cells, the increase of cell proliferation induced by siKLF15 was eliminated partly by siE2F1. Moreover, E2F1, cyclin D1 and CDK2 were higher expression during mesangial cell proliferation period, and were downregulated during proliferation declined period in vivo. Conclusions: These results suggest that KLF15 inhibits mesangial cell proliferation, possibly by regulating the expression of cell cycle regulation proteins through E2F1. Thus, KLF15 may be a useful target for therapeutic intervention in mesangial proliferative glomerulonephritis.

Reversible Acute Kidney Injury Caused by Paroxysmal Nocturnal Hemoglobinuria

The authors report a 57-year-old male patient who presented with diarrhea, darkened urine, jaundice and increased blood urea nitrogen and creatinine. Initially, his symptoms, which included hemolytic anemia, acute renal failure and low platelet count, seemed to be caused by renal injuries associated with thrombotic microangiopathy, hemolytic-uremic syndrome in particular. However, a renal biopsy indicated acute tubular necrosis and hemosiderin deposition. A CD55 and CD59 assay, Ham test and sugar-water hemolysis test confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria. After fluid infusion, diuresis and urine alkalization, the patient gradually regained nearly normal renal function. This case illustrates that paroxysmal nocturnal hemoglobinuria may present with acute kidney injury when hemolysis, diarrhea and hemosiderin deposits in the renal tubular epithelial cells and renal tubules are present. Early diagnosis and treatment is crucial to prevent disease progression and irreversible chronic renal failure.

Applicability of Chronic Kidney Disease Epidemiology Collaboration equations in a Chinese population

BACKGROUND Accurate estimated glomerular filtration rates (eGFR) is an important step in the diagnosis of chronic kidney disease (CKD). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, based on creatinine alone (eGFRcr), was developed to improve on the Modification of Diet in Renal Disease equation, in particular by addressing the systematic underestimation of high GFR. Whether the CKD-EPI equation, based on cystatin C alone (eGFRcys), or the combined creatinine-cystatin C CKD-EPI equation (eGFRcr-cys C), actually perform better than the CKD-EPI equation based on creatinine (eGFRcr) remains unknown, especially in Asians including Chinese populations, where eGFR equations may overestimate true GFR. METHODS A standard dual plasma sampling method (DPSM) of estimating (99m)Tc-diethylene triamine penta-acetic acid clearance was used to determine the reference or measured GFR (mGFR). Linear regression analysis, Bland-Altman analysis, bias, absolute bias and accuracy (P30) were used to compare the performance of the combined creatinine-cystatin C equation (eGFRcr-cys) and equations based on each marker alone (eGFRcr and eGFRcys) in Chinese subjects, including both patients with CKD and healthy individuals. RESULTS We enrolled 617 Chinese participants (49.11% female, 47.11 ± 17.25 years old), with a mean mGFR of 73.80 ± 37.55 mL/min/1.73 m(2). The predictive abilities (r), the accuracy (P15, P30, P50), bias and absolute bias of the eGFRcr-cys equation were superior to eGFRcr equation and the eGFRcys equation in overall samples. Bland-Altman analysis also demonstrated a consistent result. When compared in subgroups, the accuracy (P30) of all three equations exceeded 90% at mGFR ≥90 mL/min/1.73m(2); the eGFRcr-cys equation had the highest accuracy (P30: 95.56%). At mGFR 60-89 mL/min/1.73 m(2), the accuracies (P30) of the eGFRcr-cys and eGFRcr equations exceeded the acceptable level (≥70%), and there was no significant difference between them (P = 0.58). At mGFR <60 mL/min/1.73 m(2), the accuracy (P30) of all three equations was below 70%, but the eGFRcr-cys equation had the greatest precision. CONCLUSIONS The performances of the eGFRcr-cys and eGFRcr equations were similar to superior to that of the eGFRcys equation at higher GFR levels in an Asian population, especially in normal and mild to moderate kidney disease. Further improvement is needed for these equations at GFR <60 mL/min per 1.73 m(2).

Effectiveness of supine/standing urinalysis for differential diagnosis of left renal vein entrapment syndrome combined with or without glomerulopathy

To assess the effectiveness of supine/standing urinalysis for differential diagnosis of left renal vein entrapment syndrome (LRVES) combined with or without glomerulopathy.

The Evolution of Academic Performance in Nine Subspecialties of Internal Medicine: An Analysis of Journal Citation Reports from 1998 to 2010

Background Internal medicine includes several subspecialties. This study aimed to describe change trend of impact factors in different subspecialties of internal medicine during the past 12 years, as well as the developmental differences among each subspecialty, and the possible influencing factors behind these changes and differences. Methods Nine subspecialties of internal medicine were chosen for comparison. All data were collected from the Science Citation Index Expanded and Journal Citation Reports database. Results (1) Journal numbers in nine subspecialties increased significantly from 1998 to 2010, with an average increment of 80.23%, in which cardiac and cardiovascular system diseases increased 131.2% rank the first; hematology increased 45% rank the least. (2) Impact Factor in subspecialties of infectious disease, cardiac and cardiovascular system diseases, gastroenterology and hepatology, hematology, endocrinology and metabolism increased significantly (p<0.05), in which gastroenterology and hepatology had the largest increase of 65.4%. (3) Journal impact factor of 0–2 had the largest proportion in all subspecialties. Among the journals with high impact factor (IF>6), hematology had the maximum proportion of 10%, nephrology and respiratory system disease had the minimum of 4%. Among the journal with low impact factor (IF<2), journal in nephrology and allergy had the most (60%), while endocrinology and metabolism had the least (40%). There were differences in median number of IF among the different subspecialties (p<0.05), in which endocrinology and metabolism had the highest, nephrology had the lowest. (4) The highest IF had a correlation with journal numbers and total paper numbers in each field. Conclusion The IF of internal medicine journals showed an increasingly positive trend, in which gastroenterology and hepatology increase the most. Hematology had more high IF journals. Endocrinology and metabolism had higher average IF. Nephrology remained the lowest position. Numbers of journals and total papers were associated with the highest IF.

Development and validation of a prognostic nomogram for IgA nephropathy

IgA nephropathy (IgAN) shows strong heterogeneity between individuals. IgAN prognosis is associated with pathological lesions and clinical indicators. However, simple tools for evaluating the clinical prognosis remain inadequate. Our objective was to develop an intuitive estimation tool for predicting the IgAN prognosis. 349 patients with IgAN at The Chinese People’s Liberation Army General Hospital were retrospectively analyzed from data between 2000 and 2006. A nomogram was developed using COX regression coefficients to predict decline of estimate Glomerular filtration rate (eGFR) ≥ 50% and end-stage renal disease (ESRD). The discriminative ability and predictive accuracy of the nomogram was determined via concordance index (C-index) and calibration curve. The results were verified in an independent validation cohort. In the derivation cohort, the nomogram was developed using mesangial hypercellularity, tubular atrophy/interstitial fibrosis, average proteinuria (A-P), and average mean arterial pressure (A-MAP) during hospitalization. The C-index of the nomogram was 0.88 (95% CI, 0.80 to 0.96). The calibration curve showed good agreement between prediction and actual observation. Furthermore, the nomogram demonstrated good discrimination (C-index = 0.87, 95% CI 0.78 to 0.95) and calibration in the validation cohort. The nomogram could predict the prognosis of IgAN effectively and intuitively.

Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial

Background:The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods:It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results:The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18–0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44–96.49] &mgr;mol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54–12.44] &mgr;mol/L, P < 0.001), and in estimated glomerular filtration rate (−6.72 [95% CI −9.46 to −3.98] ml[BULLET OPERATOR]min−1[BULLET OPERATOR]1.73 m−2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions:Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients. Trial Registration:chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.