肾病-肾炎型鸡传染性支气管炎的病理学研究

对43只14日龄的SPF鸡人工感染从上海市分离获得的1株肾致病型鸡传染性支气管炎病毒（上海株IBV），分别于接种后第2、7、14、24、28和36d扑杀，对肾、肺等组织器官进行了动态病理学观察。结果显示，感染鸡主要表现呼吸系统和泌尿系统的病理变化。在感染后的第2d，支气管和气囊呈急性炎症变化；第5d肾实质变性坏死，炎性细胞浸润，肺充血；第8～13d，肾和肺的病变最为严重；第14d后，支气管和输尿管转变为慢性炎症，肾出现弥漫性或局灶性间质性肾炎病理变化。将M41标准毒株与上海株IBV的致病力进行比较，发现2个毒株引起的呼吸器官病变基本相同，但M41，毒株对肾的致病力较轻，未见间质性肾炎和输尿管炎病理变化。证实，上海株IBV主要侵害肺和肾，并造成肾实质变性坏死和间质性肾炎变化。

鸡传染性支气管炎肾炎的病原分离和鉴定

从具有传染性支气管炎肾炎临床特征的病鸡体内,分离到一株病毒,该分离株通过鸡胚传代(6～8代),能引起半数以上的鸡胚卷缩,发育阻滞和死胚;鸡胚适应毒能在鸡胚肾细胞(CEK)培养中生长繁殖;产生细胞病变(CPE)的病毒在 CEK 培养中传5代以后,能形成融合细胞,具有较高的感染滴度。病毒粒子具有典型的冠状结构,核酸型为 RNA,有囊膜,对氯仿和乙醚敏感,经反复冻融后,毒力下降,而 pH 3和 pH 11,在56℃经30min即被灭活,无血凝发生。本分离株与 IB-M_41株有明显的抗原差别,但用它攻击经 H_52疫苗免疫的鸡,可获得部分保护。综合本分离株的特性,初步鉴定为肾病变型 IBV。

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 (HBVGN) 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, clearanceof 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 signif icant 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 HBVGN patients without altering HBV replication or damaging liver and renal functions.

Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy

AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg)detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization.Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50),and 42% (21/50) in glomeruli, respectively; and was 94%(47/50), 56% (28/50) and 78% (39/50) in tubular epithelia,respectively. Positive HBV DNA was detected in 72% (36/50)and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in Situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form.CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex,renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN.

Complement activation in progressive renal disease

Chronic kidney disease(CKD) is common and the cause of significant morbidity and mortality. The replacement of functioning nephrons by fibrosis is characteristic of progressive disease. The pathways that lead to fibrosis are not fully understood, although chronic non-resolving inflammation in the kidney is likely to drive the fibrotic response that occurs. In patients with progressive CKD there is histological evidence of inflammation in the interstitium and strategies that reduce inflammation reduce renal injury in pre-clinical models of CKD. The complement system is an integral part of the innate immune system but also augments adaptive immune responses. Complement activation is known to occur in many diverse renal diseases, including glomeruloneph-ritis, thrombotic microangiopathies and transplant rejection. In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease.

Treatment of young patients with lupus nephritis using calcineurin inhibitors

Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis

LUPUS NEPHRITIS COMPLICATED WITH MALIGNANT HYPERTENSION:FROM RENAL VASCULAR PATHOLOGY TO CLINICAL RELEVANCE

Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

Clinicopathological Analysis of 155 Patients with Persistent Isolated Hematuria

Objectives To reveal etiologies of persistent isolated hematuria （PIH） through ultrastructural pathological examination, to disclose clinicopathological correlation in cases with PIH, and to summarize appropriate management of patients with PIH. Methods we retrospectively studied 155 P1H patients receiving renal biopsy between January, 2003 and December, 2008 in Peking Union Medical College Hospital. All the clinical data and follow-up result were analyzed. Results All subjects included 38 children and 117 adults, with mean age of 11.38±3.25 years for children and 35.17±8.44 years for adults. Thin basement membrane nephropathy （TBMN） was the most common pathology （55.3% of children and 49.6% of adults）, followed by IgA nephropathy （18.4% of children and 32.5% of adults, mainly grade 2-3） and mesangial proliferative glomerulonephritis （MsPGN） without IgA deposition （13.2% of children and 12.8% of adults）. Besides, A1port syndrome （2.6% of children） and membrane nephropathy （2.6% of children and 0.9% of adults） were demonstrated as other causes of PIH. Elevated mean arteral pressure or protein excretion rate, as well as episodic macrohematuria, indicated higher risk for MsPGN rather than TBMN. On the other hand, severity of microhematuria was irrelevant to pathological types of PIH. Totally, 86 patients were followed up and 37 cases therein stayed on track for long term （mean duration 41.11±28.92 months, range 8-113 months）. Most cases had benign clinical course except 3 cases with TBMN, 5 cases with IgA nephropathy, 1 case with MsPGN （without IgA deposition）, and 1 case with Alport syndrome, who developed hypertension or proteinuria. All of them were administered timely intervention. Conclusions Close follow-up should be required as the primary management for PIH. Equally important is careful monitoring for early identification of undesirable predictors; while renal biopsy and other timely intervention are warranted if there is hypertension, significant proteinuria or renal impairment.

Oxidative stress and damage induced by abnormal free radical reactions and IgA nephropathy

Objective: To estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients' bodies. Methods: Seventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric mothods. Results: Compared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P＜0.0001), while those ofVC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P＜0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those ofVC, VE, β-CAR,SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P＜0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, β-CAR, SOD, CAT and GPX were decreased gradually (P＜0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%-92.5%, and the correct rates for the HAV were 70.0%-91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters' reliability coefficient (alpha) were used to estimate the oxidative damage of the IgAN patients as 0.8145, the standardized item alpha=0.9730, F=53273.5681, P＜0.0001. Conclusions: A series of free radical chain reactions caused serious pathological aggravation in the IgANP' bodies, thus resulting in oxidative damage in their bodies. In treating IgANP, therefore, it is necessary that suitable dose antioxidants should be supplemented to them so as to alleviate the oxidative damage in their bodies.

Fabry disease combined with acute interstitial nephritis:one case and literature review

Objective:To explore the clinical and pathological features of Fabry disease complication of acute interstitial nephritis.Methods:A retrospective analysis of a patient with Fabry disease and acute interstitial nephritis diagnosed and in the Department of Nephrology,Children’s Hospital Affiliated to Capital Institute of Pediatrics in January 2017 was performed.A literature search was performed with“Fabry disease,acute interstitial nephritis”as the keywords in Wanfang database and PubMeds database.Result:The patient was 10-years-old with acute renal dysfunction.Electron microscopy showed stratified myelin-like bodies,zebra bodies and fused foot segment.The patient was finally diagnosed with the combination of Fabry disease and acute interstitial nephritis.By now,such cases have been reported.Conclusion:Whether Fabry's disease and acute interstitial nephritis shared the common pathogenic mechanism is unclear.Early renal biopsy is important for the diagnosis of this disease.

Gene polymorphism in IL-1 receptor antagonist affects its production by monocytes in IgA nephropathy and Henoch-Schonlein nephritis

Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Methods The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1α and IL-1β in the supernatant of GM-CSF (10ng/ml) treated and untreated monocytes were measured by ELISA.Results The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55±3.08 vs 13.85±2.24ng/ml, P<0.001) and HSPN (23.72±6.68 vs 12.67±2.24ng/ml, P<0.01) as well as in normal controls (20.29±1.45 vs 10.51±2.3ng/ml, P<0.001). All showed no significant differences in monocyte secretion of IL-1α and IL-1β by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers. Conclusions These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.