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.     

Sjogren's Syndrome Complicated with IgA Nephropathy and Leukocytoclastic Vasculitis

We report a case of primary Sjögren's syndrome (SS) with cutaneous leukocytoclastic vasculitis and IgA nephropathy. The accurate diagnosis of SS was established based on objective signs and symptoms of ocular and oral dryness, a characteristic appearance of a biopsy sample from a minor salivary gland, and the presence of anti-SS-A autoantibody. A second autoimmune disorder was not present, so the diagnosis of primary SS was established. A histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. Renal biopsy was performed for nephrotic range proteinuria. The pathologic finding of renal biopsy was IgA glomerulonephritis with crescent formation. The patient was treated with small doses of glucocorticoids and maintenance hemodialysis. Leukocytoclastic vasculitis is one of the most characteristic extraglandular manifestations of SS. However, IgA nephropathy associated with SS and leukocytoclastic vasculitis is a rare finding. SS patients with glomerulonephritis present a more diverse outcome, even requiring hemodialysis. Therefore, renal biopsy is warranted in SS with glomerulonephritis and systemic vasculitis.     

Effect of Immune Complex on the Biomechanics of Blood Flow in Common Glomerulonephritis Diseases

Glomerulonephritis (GN) is a common nephrological disorder. The correlation between degree of glomerular damage, severity of GN, and development of hypertension is an interesting topic in present research on GN. Although the progression of GN is proved to associate with hypertension, no clear pathogenesis is reported. In this study, the author assesses the effect of various sizes of immune complex in three common GN diseases on the biomechanics of blood flow in the renal vascular. Further discussion on the impact on hypertension is also provided.     

Efficacy of antisense monocyte chemoattractant protein-1 (MCP-1) in a rat model of mesangial proliferative glomerulonephritis

Abstract

Objective: The effects of inhibition of monocyte chemoattractant protein-1 (MCP-1) on a rat model of mesangial proliferative glomerulonephritis (MsPGN) were evaluated. Methods: The anti-Thy-1 MsPGN model was developed by intravenously injecting anti-Thy-1 monoclonal antibodies into rats, followed by an injection of mesangial cells transfected with antisense MCP-1 into the renal artery. Exogenous cells were detected by in situ hybridization. Rats (40 total) were randomly divided into five groups: SO (sham operation), TG (Thy-1 glomerulonephritis model), MC (non-transfected normal rat mesangial cell), BC (pLXSN empty vector or blank control), and AM (antisense MCP-1 transfection) groups. Effects of exogenous MCP-1 on urinary protein excretion rate, biochemical parameters, and pathological changes were evaluated. Expression of MCP-1 and transforming growth factor-β₁ (TGF-β₁) were detected by immunohistochemistry. mRNA expression of MCP-1, TGF-β₁, and CC chemokine receptor 2 (CCR2) were detected by RT-PCR. Results: Exogenous MCP-1 cDNA was successfully transfected into mesangial cells. Exogenous mesangial cells were detected in glomeruli by in situ hybridization. Glomerular mesangial cell proliferation, 24-h urinary protein excretion rate, mRNA expression of MCP-1, TGF-β₁, and CCR2, and protein expression of MCP-1 all decreased in the AM group as compared to the control group (p?<?0.05), but there was no significant difference in the expression level of TGF-β₁ protein. Conclusions: (1) Mesangial cells can be used as a vector to transfect exogenous genes into kidneys; (2) antisense MCP-1 decreases mesangial cell proliferation and pathological injury in MsPGN model rats by decreasing expression of MCP-1 and CCR2; and (3) antisense MCP-1 suppressed mesangial cell proliferation and matrix accumulation in anti-Thy-1 MsPGN model rats, which did not entirely depend on TGF-β_1.     

A Case of Kaposi's Sarcoma Following Treatment of Membranoproliferative Glomerulonephritis and a Review of the Literature

Kaposi's sarcoma (KS) is an unusual tumor principally affecting the skin of the lower extremities. Although the association between KS and renal transplant has been well documented, there are a few KS cases in the literature associated with membranoproliferative glomerulonephritis or other glomerular diseases. This report presents a patient with membranoproliferative glomerulonephritis (MPGN) who developed KS following treatment with long-term medium dose glucocorticoid and short-term additional immunosuppressives. The KS cases associated with glomerulonephritis are also reviewed. KS is a rare complication in glomerular diseases that may (or may not) be related to immunosuppression. Hence, immunosuppression treatment should be carefully planned in glomerulonephritis treatment and avoided if they are not essentially necessary.     

Paraoxonase Activity in Glomerulonephritic Patients

Background. Cardiovascular disease is the most common cause of morbidity and mortality in patients with chronic renal failure. Glomerulonephritic patients have an increased risk for cardiovascular disease, but its etiology is unclear. It is known that an increase in oxidizability of apolipoprotein B-containing lipoproteins has a key role in the initiation of atherosclerosis, and paraoxonase enzyme activity particularly has a preventive role against atherosclerosis. The aim of the present study was to evaluate the oxidizability of apolipoprotein B-containing lipoproteins, serum, and urinary paraoxonase/arylesterase activities in glomerulonephritis patients who had normal lipid parameters and creatinine levels. Methods. Thirty-two patients with glomerulonephritis and 22 healthy controls were included in this study. A total of 32 patients (including nine with membranous GN, eight with immunoglobulin A nephropathy, eight with mesangial proliferative GN, five with focal-segmental glomerulosclerosis, one with diffuse proliferative GN, and one with minimal chance disease having biopsy proven GN) were enrolled into the study. We compared serum and urinary paraoxonase, arylesterase, serum lipids, urea, creatinine, hemoglobin, total protein and albumin values between groups. Results. Serum urea, creatinine, total protein, albumin, uric acid, hemoglobin, and lipid parameters were similar in the glomerulonephritis and control groups (p > 0.05). PON1 activity was significantly lower in GN group than controls, but there was no statistically significant difference on arylesterase activity between groups. Oxidizability of apolipoprotein B-containing lipoproteins was significantly higher in GN group than controls. Conclusion. Our study shows that the findings of normal serum levels of creatinine, lipids, and proteins increased the oxidizability of apolipoprotein B-containing lipoproteins, and any decrease in PON1 activity in patients diagnosed with GN should be considered important. Hence, the immediate commencement of preventive as well as curative treatment in other to avoid the risk of cardiovascular and renal problems would be a correct approach.     

Recent Progress in the Pathophysiology and Treatment of FSGS Recurrence

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end‐stage renal disease, and recurrence after kidney transplantation in ～25% of patients, which negatively impacts long‐term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti‐CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile.