百令胶囊联合来氟米特治疗慢性肾小球肾炎的临床研究

目的研究百令胶囊联合来氟米特片治疗慢性肾小球肾炎的临床疗效。方法选取2013年12月—2017年12月河南科技大学第一附属医院接收的100例慢性肾小球肾炎患者作为研究对象,将患者随机分为对照组和治疗组,每组各50例。对照组患者口服来氟米特片,2片/次,1次/d。治疗组患者在对照组基础上口服百令胶囊,4粒/次,3次/d。两组患者均持续治疗12周。观察两组患者的临床疗效,同时比较两组治疗前后的肾功能指标和尿液检查指标水平。结果治疗后,对照组和治疗组的总有效率分别为84.00%、96.00%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者尿素氮(BUN)和血肌酐(Scr)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组肾功能指标水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者24h尿蛋白定量(24 hUpro)、尿β2-微球蛋白(β2-MG)和尿红细胞计数(RBC)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组尿液检查指标水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论百令胶囊联合来氟米特片治疗慢性肾小球肾炎具有较好的临床疗效,能显著改善患者肾功能和尿液检查指标,安全性较高,具有一定的临床推广应用价值。     

以大量蛋白尿、水肿为主要表现的乙型肝炎病毒相关性肾炎临床特征分析

[目的]探讨以大量蛋白尿、水肿为主要表现的乙型肝炎病毒相关性肾炎(HBV-GN)的临床特征,以提高对该病的认识。[方法]对我院近5年来收治的5例以大量蛋白尿、水肿为主要表现的HBV-GN患者的临床资料进行回顾分析,并结合文献进行复习。[结果]全部患者均有明显水肿和蛋白尿,3例有腹水,尿蛋白定量为3.58~7.50g/d,(平均5.42g/d),血浆白蛋白为20.4~28.2g/L(平均24.5g/L);4例表现为肾病综合征,1例为肾炎综合征;病理类型4例为膜性肾病,1例为局灶性节段性肾小球硬化。阿德福韦酯与泼尼松联合治疗取得了很好的近期疗效。[结论]以大量蛋白尿、水肿为主要表现的HBV-GN患者大多以肾病综合征、膜性肾病为主要表现,应早期给予抗病毒与糖皮质激素联合治疗。消化内科医师应不断提高对该病的认识,早诊早治,减少误诊。     

Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBV-GN) patients.METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearance of HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN.RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No significant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27].CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBV-GN patients without altering HBV replication or damaging liver and renal functions.     

呈肾病综合征的乙型肝炎病毒相关性肾炎临床病理特点

目的:探讨呈肾病综合征(NS)的乙型肝炎病毒相关性肾炎(hepatitis B virus-associated glomerulonephritis,HBV-GN)的临床病理特点。方法:回顾性分析呈NS且肾穿组织内小动脉≥5条的HBV-GN患者152例的临床病理资料,光镜下观察其肾内小动脉病变,比较伴与不伴肾内小动脉病变患者的临床病理资料。结果:平均年龄26.3岁,男∶女为3.6∶1;伴高血压者36例(23.7%)、贫血52例(34.2%)、肾衰竭者33例(21.7%)、肝功能异常者20例(13.2%)。乙肝大三阳者87例(57.2%);血清和肾组织内HBV-DNA载量呈正相关(P<0.01)。病理表现以膜性肾性(MN)、系膜增生性肾炎(MsPGN)、膜增生性肾炎(MPGN)为主;未成年组与成年组MN、MPGN所占比例不同(P<0.05)。伴有肾内小动脉病变者84例(55.2%),与无肾内小动脉病变者相比,其高血压发生率较高(P<0.05),24h尿蛋白定量显著较高(P<0.01),贫血、肾间质纤维化的发生率显著较高(P<0.01)。结论:呈NS的HBV-GN患者绝大多数为HBV携带者且伴有病毒复制,病理以MN、MsPGN及MPGN为主,半数以上伴有肾内小动脉病变,伴有肾内小血管病变者高血压、贫血及肾小管间质纤维化发生率较高,蛋白尿更严重,为预后不良的病理学指标。     

Challenges of Genomics and Proteomics in Nephrology

An increasing number of patients suffering from renal diseases and limitations in standard diagnostic and therapeutic approaches has created an intense interest in applying genomics and proteomics in the field of nephrology. Genomics has provided a vast amount of information, linking the gene activity with disease. However, proteomic technologies allow us to understand proteins and their modifications, elucidating properties of cellular behavior that may not be reflected in analysis of gene expression. The application of these innovative approaches has recently yielded the promising new urinary biomarkers for acute kidney injury and chronic kidney disease, thus providing a better insight in renal pathophysiology and establishing the basis for new therapeutic strategies. Despite significant improvements in therapeutics, the mortality and morbidity associated with acute renal failure (ARF) remain high. The lack of early markers for ARF causes an unacceptable delay in initiating therapy. These biomarker panels will probably be useful for assessing the duration and severity of ARF, and for predicting progression and adverse clinical outcomes. Kidney failure leads to the uremic syndrome characterized by accumulation of uremic toxins, which are normally cleared by the kidneys. Proteomics has gained considerable interest in this field, as a new and promising analytical approach to identify new uremic toxins. The urinary proteome as a tool for biomarker discovery is still in its early phase. A major challenge will be the integration of proteomics with genomics data and their functional interpretation in conjunction with clinical results and epidemiology.     

The Relationship between the VEGF Levels and VEGF mRNA Expression and Clinical Course in Different Glomerulonephritis

In this study, serum and urinary VEGF levels and VEGF expression in PBMNC were correlated with daily proteinuria, renal function tests, and renal histopathologic findings in untreated patients with different glomerulonephritis and with the course of renal function and proteinuria for one year. Forty-five untreated patients with different glomerulonephritis and 11 healthy persons comprised the study and control groups, respectively. VEGF mRNA expression was detected by RT- PCR in peripheral blood mononuclear cells (PBMNC), and VEGF levels were measured by ELISA in serum and urine samples simultaneously. Male/female ratio was 24/21 and mean ages were 34.49 ± 14.98. Serum and urinary VEGF levels, VEGF expressions in PBMNC, and the ratios of urine VEGF/urine creatinine were found to be similar in patients and controls. There were important correlations between urinary VEGF levels and baseline serum Cr (p = 0.035) and ESR (p = 0.022). There was also a marginal correlation between urinary VEGF levels and baseline CCr (p = 0.072). There was no correlation between serum and urinary VEGF levels and PBMNC mRNA expression and pathological findings such as with or without glomerular sclerosis, tubulointerstitial fibrosis (TIF), periglomerular fibrosis, and mesangial cell proliferation in renal biopsy. Serum and urinary VEGF levels or VEGF expression in PBMNC in patients with renal amyloidosis or proliferative or nonproliferative glomerulonephritis were similar with that of healthy controls and each other. Serum and urinary VEGF levels and PBMNC VEGF mRNA expression in untreated patients with different glomerulonephritis and controls were similar. We found only one important correlation, that between urinary VEGF levels and baseline serum creatinine levels in patients with different glomerulonephritis. Urinary VEGF can be an important pathogenesis of glomerular disease or a simple proteinuria. Serum and urinary VEGF levels and PBMNC VEGFmRNA did not change by periglomerular sclerosis, periglomerular fibrosis, or tubulointerstitial fibrosis on renal biopsy. PBMNC VEGF mRNA expression decreased in patients undergoing remission. In addition to the important correlation between urinary VEGF and serum creatinine, we also found an important correlation between erythrocyte sedimentation rate and urinary VEGF. This finding was interesting because we could not find a similar conclusion in other studies.     

Pulmonary Renal Syndrome Due to Anti-GBM and IgM C-ANCA Disease Requiring the Use of Novel Therapeutic Agents

There are several known causes for the clinical syndrome of pulmonary hemorrhage and acute renal failure. Here, we report a unique case of a 50-year-old man presenting in this manner. The initial diagnosis was one of antiglomerular basement membrane (anti-GBM) disease that responded well to steroids, cyclophosphamide, and plasma exchange (PE). The pulmonary hemorrhage resolved, but he remained dialysis dependent. However, despite falling anti-GBM titers, the symptoms relapsed and standard therapy was reinitiated with limited success. The anti-GBM antibody titer fell to zero despite clinical deterioration, prompting a search for an alternative diagnosis. He was found to be IgM anti-proteinase-3 antineutrophil cytoplasmic antibody (C-ANCA) positive. The pulmonary hemorrhage responded successfully to the use of intravenous immunoglobulin and the antilymphocyte monoclonal antibody CD52. To our knowledge, this is the first known case of IgM C-ANCA in association with anti-GBM disease. As such, it highlights the predominance of pulmonary hemorrhage in this condition, as well as the need to consider alternative therapies in refractory cases.