IgA肾病520例临床病理分析

目的研究IgA肾病(IgAN)的临床和病理特点及其相互关系。方法对1992年11月～2003年6月温州医学院附属第一医院肾内科病理室肾活检诊断的原发性IgAN520例进行临床与病理分型关系的分析。结果520例IgAN临床表现以无症状性尿检异常最常见,占346例(66.5%),其次是慢性肾炎和肾病综合征,分别占77例(14.8%)和66例(12.7%)。病理类型以局灶节段硬化性肾小球肾炎最常见,占186例(35.8%),其次是系膜增生性肾小球肾炎、轻微病变肾小球肾炎和局灶节段增生性肾小球肾炎,分别为116例(22.3%)、104例(20%)和63例(12.1%)。结论IgAN的临床病理表现多样化并具有一定特点。临床表现最常见为无症状性尿检异常,在病理上最常见的是局灶性肾小球病变类型。     

Pre-transplant course and risk of kidney transplant failure in IgA nephropathy patients

Bjørneklett R, Vikse BE, Smerud HK, Bostad L, Leivestad T, Hartmann A, Iversen BM. Pre‐transplant course and risk of kidney transplant failure in IgA nephropathy patients.
Clin Transplant 2011: 25: E356–E365. © 2011 John Wiley & Sons A/S. Abstract: Background: There is lack of knowledge to what degree clinical/morphological presentation and course of IgA nephropathy (IgAN) prior to end‐stage renal disease are risk factors for graft loss after kidney transplantation. Material and Methods: Patients with IgAN between 1988 and 2006 (registered in the Norwegian Kidney Biopsy Registry) who later received a kidney transplant (registered in the Norwegian Renal Registry) were included. The cohort was followed up regarding death‐censored graft loss throughout 2008. Graft survival with a rapid progressive (RP) vs. a slow progressive (SP) course of pre‐Tx IgAN (annual GFR > or <30 mL/min/1.73 m²) was studied. Results: Among 106 included patients, there were 14 graft losses giving a graft loss rate of 1.9/100 patient years. Follow‐up until the first kidney transplant was 6.9 ± 4.4 (range 0.1–19) yr. Patients with pre‐Tx RP had a higher graft loss rate compared with SP patients (6.3 vs.1.3/100 patient years, p < 0.001). Graft loss rate with living‐related donor (LRD) was similar to unrelated donor (UD) grafts. Most RP patients had received LRD grafts, and in SP patients, graft survival with LRD grafts was better than UD grafts (0.3 vs.2.1/100 patient years, p = 0.055). Conclusions: A rapid pre‐transplant course is a strong risk factor for transplant failure in patients with IgAN.     

ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study

A multicentre, randomized, placebo-controlled study was performedin 39 adult patients with biopsy-proven IgA nephropathy withthe aim of comparing the effects of the ACE inhibitor fosinopriland placebo on proteinuria. All patients had normal blood pressureand normal renal function. Proteinuria ranged from 1.0 to 2.5g/24 h. After a 3-month run-in period, fosinopril and placebowere randomly administered in two 4-month sequences separatedfrom crossover treatment by a 1-month interval. The mean valuesof creatinine clearance did not change during either the placeboor the treatment sequences. The mean values of mean arterialpressure (MAP) were significantly lower during the fosinoprilsequence (90.4 ±9.0 mmHg) than in basal conditions (92.8± 9.1 mmHg) (P=0.034). The mean basal values of proteinuriawere 1.74 ±0.84 g/24 h. They were unchanged during theplacebo sequence (1.79 ±1.20) and fell to 1.37 ±0.98g/24 h after 4 months of fosinopril treatment. Using a multivariatestatistical analysis, the treatment effect by time on proteinuriawas significantly evident only in the fosinopril sequence (Wilkstest, P=O.O33). Changes in protein excretion were not correlatedwith changes in MAP, baseline plasma renin activity, and urinarysodium excretion. This controlled study shows that fosinoprilcan significantly reduce proteinuria even in normotensive patientswith IgA nephropathy. Obviously, the results of treatment withACE inhibitors on long-term renal prognosis remain to be elucidated.     

The benefits of renin-angiotensin blockade in renal transplant recipients with biopsy-proven allograft nephropathy.

BACKGROUND: Allograft nephropathy, regardless of aetiology, leads to progressive renal injury and eventual graft loss. In native kidney disease, treatment of hypertension, in particular with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), has proven beneficial in retarding renal function decline. In the present study, we reviewed the clinical course of a renal transplant recipient cohort that was prescribed either an ACEi or ARB for biopsy-proven allograft nephropathy. METHODS: Patients were followed from the time of post-biopsy initiation of ACEi/ARB and were stratified based on biopsy findings. Outcomes of interest included safety, allograft survival, renal function and change in slope of renal function pre- and post-ACEi/ARB. RESULTS: The 5 year allograft survival after biopsy diagnosis of allograft nephropathy was 83%. Serum creatinine was 191+/-97 (86-377) micromol/l at the time of biopsy and 228+/-102 (102-575) micromol/l at last follow-up. The slopes of reciprocal creatinine vs time were used to calculate the decline in renal function and were compared pre- and post-ACEi/ARB. The mean slope+/-SD was -0.06+/-0.21 l/micromol x 10(-3) per month in the 12 months prior to therapy and -0.03+/-0.09 l/micromol x 10(-3) per month following therapy. The absolute difference in slopes was 0.03 (P =<0.0001). CONCLUSIONS: Treatment with ACEi/ARB may be beneficial in the management of allograft nephropathy.     

IgA serology in recurrent and non-recurrent IgA nephropathy after renal transplantation

BACKGROUND: This study investigated whether abnormal circulation of macromolecularIgA and IgA with altered glycosylation or electrical chargeplays a role in the recurrence of IgA nephropathy (IgAN) aftertransplantation. STUDY DESIGN: A total of 92 renal transplant patients were enrolled; 52 IgANpatients and 40 with other non-IgAN. The IgAN group included10 patients showing IgA mesangial deposits in the grafted kidneys(recurrent group) and 10 who did not (immunohistochemicallyproven non-recurrent group). In addition another 22 IgAN transplantpatients were clinically free of recurrent disease. METHODS: The analyses included macromolecular IgA (IgAIC) detected bythe conglutinin assay (K), heavy IgA precipitated in 2.5% polyethyleneglycol (PEG), IgA-fibronectin aggregates (IgA/F Aggr), mixedIgA/IgGIC, IgA binding to mesangial matrix components (fibronectin,laminin, type IV collagen) or polycations (poly-L-lysine) andIgA with altered glycosylation (Jacalin-binding assay). RESULTS: After transplantation, IgAN patients displayed significantlyhigher mean levels for each variable measured than non-IgAN(ANOVA, P <0.05). By stepwise regression analysis, the bindingof IgA to fibronectin had the highest coefficient. By comparingdata in recurrent and clinically non-recurrent IgAN, we observedthat two groups could be distinguished by the results of thetwo assays for macromolecular IgA (conglutinin IgAIC and IgA-fibronectinaggregates) and IgA with increased affinity for type IV collagen(P <0.05). When the selected group of immunohistochemicallyproven non-recurrent IgAN was compared to the recurrent one,a statistically significant difference was found only for thebinding of IgA to type IV collagen (P<0.05). Data from thistest were significantly related with proteinuria (P<0.05)and microscopic haematuria (P <0.04). CONCLUSION: Even though the IgA serology of renal transplant IgAN patientsshows peculiar features and recurrent and non-recurrent IgANdiffer in many aspects, the prevalence of positive data in thetwo groups had no predictive value. This suggests that the recurrenceof IgAN is modulated by factors affecting the interaction betweencirculating abnormal IgA and mesangial cells and/or matrix.     

Impact of recurrent disease and chronic allograft nephropathy on the long‐term allograft outcome in patients with IgA nephropathy

Although recurrent IgA nephropathy (IgAN) may lead to graft dysfunction after transplantation, donation from living related donor (LRD), with whom the risk of recurrence may be higher, is not a contraindication. Herein, we evaluated the natural history of allograft in recipients with IgAN and the risk factors influencing long‐term allograft outcome. Recurrence rate and graft survival were assessed retrospectively in 221 IgAN patients, including transplants from 139 LRDs (62.9%). Ten‐year cumulative rate for recurrent IgAN was 30.8%. The operation at younger age and donation from LRD were significant for the recurrence by multivariate analysis. Ten‐year graft survival was affected by recurrent IgAN (61.0% in recurrent IgAN group vs. 85.1% in nonrecurrent, P < 0.01). However, transplants from LRDs did not show poor graft survival when compared with those from other types of donors. In transplants from LRDs, the incidence of chronic allograft nephropathy (CAN) was lower than those in grafts from deceased donors (10.8% vs. 19.5%, P < 0.05). When CAN was considered in addition to recurrence, the variance of graft survival was affected significantly by the development of CAN than by the recurrence. These results suggest that the detection and adequate management of CAN could improve graft outcome in transplant recipients with IgAN.     

Does angiotensin blockade influence graft outcome in renal transplant recipients with IgA nephropathy?

BACKGROUND: IgA nephropathy (IgAN) is a frequent cause of end-stage renal disease (ESRD) and recurrent disease causes deterioration and graft loss in transplant recipients. No definitive management is known to reduce the risk or severity of recurrent IgAN, and the evidence to support the use of renin-angiotensin system blockade in such patients is limited. METHODS: All 1137 renal transplants performed at the Belfast City Hospital over a 27-year period were reviewed. A total of 75 patients with ESRD due to biopsy-proven IgAN were identified; 39 of them had been prescribed an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-II type I receptor blocker (ARB). RESULTS: The two groups were well-matched in terms of demographic details, immunosuppressive regimens and duration of follow-up (median 65 months, range 18-261 months). The 5- and 10-year graft survivals were higher in those prescribed ACEi/ARB therapy compared with those who were not, although these differences did not reach statistical significance (92.9 vs 86.5%; P = 0.34 and 81.6 vs 72.7%; P = 0.32, respectively). These results were similar when censored for death with a functioning graft. In the group where an ACEi/ARB was not prescribed, all four with biopsy-proven recurrent IgAN progressed to ESRD, compared with three out of nine in the group treated with an ACEi/ARB. CONCLUSIONS: In transplant recipients with ESRD due to biopsy-proven IgAN, a trend towards improved 5-year and 10-year graft survival was seen in those prescribed ACEi/ARBs. All with recurrent IgAN in their grafts who were not treated with ACEi/ARB therapy progressed again to ESRD.     

A clinicopathological study of adult Japanese IgA nephropathy patients: Early stage cases and cases with exacerbation

Summary: Most cases of adult type IgA nephropathy (IgAN) have an insidious onset and asymptomatic course. However, some patients reveal recurrent macroscopic haematuria following episodes of respiratory or urinary tract infections. In order to clarify the correlation between clinical features and histological alterations or prognosis, 42 cases of early stage IgAN and 40 cases with acute exacerbation episodes were investigated and compared with a control group. Early stage cases were defined as having had a renal biopsy within 1 year after the first detection of urinary abnormalities, and had normal urinary findings within the 12 months before the first detection of urinary abnormalities. Acute exacerbation cases were defined as macroscopic haematuria or worsening of urinary abnormalities after acute infectious episodes and undergoing a renal biopsy within 120 days after the onset of these episodes. the early stage cases had better renal function and lower systolic and diastolic blood pressure than that of control group. They also showed milder changes in mesangial cell proliferation, mesangial matrix increase, totally sclerotic glomeruli, and tubulo-interstitial changes. However, it is important to note that glomerular and interstitial sclerotic changes were observed even in early stage cases. Endothelial detachment was noticed more frequently in the early stage cases. Acute exacerbation cases revealed lesions of endocapillary proliferation, mesangiolysis and endothelial detachment more frequently, although these changes were segmental in each glomerulus. There was no statistical difference in disease prognosis between cases with and without acute exacerbation. These data indicated that there are characteristic histological changes in early stage cases and acute exacerbation cases of IgAN.     

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.     

Positive and negative hepatitis B virus in renal biopsies of IgA nephropathy: an 85-case clinicopathological analysis

SUMMARY: The aetiological role of hepatitis B virus (HBV) antigens in IgA nephropathy remains uncertain. In a clinicopathological study, we examined 85 patients with primary IgA nephropathy divided into two groups depending on whether renal biopsy specimens were positive or negative for HBV antigens (HBsAg, HBcAg and HBeAg) using immunohistochemical methods. Compared with patients in the negative group ( n = 59), those in the positive group ( n = 26) had more obvious gross haematuria, proteinuria, hypertension and renal impairment. Their haemoglobin level, serum IgA concentration and creatinine clearance were also significantly abnormal. Immunofluorescence microscopy indicated that immunoglobulins deposited were mainly found in the combination of IgA + IgG + IgM. Consistent with the clinical manifestations, the pathological lesions revealed more glomerular sclerosis, tubular epithelial degeneration and necrosis and interstitial inflammation and fibrosis ( P < 0.05). Thus, we concluded that the presence or absence of HBV in renal tissue from patients with IgA nephropathy results in significant differences in the clinical features, types and severity of pathological lesions and, consequently, prognosis. Tissue deposition of HBV might play an aetiological role in the pathogenesis of IgA nephropathy and may be an exacerbating factor in renal progressive deterioration. Antiviral therapy could be an important intervention in HBV antigen-positive patients.     

肾移植术后一年体质量指数对慢性移植物肾病的影响

目的 研究肾移植患者术后1年体质量指数(BMI)对慢性移植物肾病(CAN)的影响.方法 肾移植术受者564例,依据BMI分3组:①I组:18.5≤BMI≤25(正常);②Ⅱ组:25＜BMI≤30(超重);③Ⅲ组,BMI＞30(肥胖).比较各组术后高血压、糖尿病、CAN等发生情况.结果 各组术后1年的BMI均较术前增加,其中Ⅱ、Ⅲ组与术前比较差异有统计学意义(P值分别＜0.05和0.01).3组CAN发生率分别为34.9%(128/367)、38.4%(48/125)、43.1%(31/72),术后1年随着BMI的升高而增加,Ⅲ组与Ⅰ组比较差异有统计学意义(P＜0.05);高血压、糖尿病和高脂血症的发病率随着BMI升高而增加,Ⅲ组与Ⅰ组高血压、糖尿病和高脂血症的发生率分别为30.6%(22/72)和21.0%(77/367)、26.4%(19/72)和15.8%(58/367)、29.2%(21/72)和18.1%(66/367),2组比较差异有统计学意义(P＜0.05);急性排斥反应发生率:Ⅰ组26.4%(97/367),Ⅱ组25.6%(32/125),Ⅲ组22.2%(16/72),3组之间急性排斥反应发生率比较差异无统计学意义(P＞0.05).结论 肾移植患者术后1年BMI和CAN的发生密切相关,通过饮食控制、适当体育锻炼、免疫抑制剂减量等措施可以控制移植后BMI,进而最大限度降低CAN的发生.     

Serological and genetic factors in early recurrence of IgA nephropathy after renal transplantation

BACKGROUND: The relative role of IgA anomalies and genetic factors in IgA nephropathy (IgAN) recurrence after transplantation has never been investigated in a single cohort. METHODS: Sixty-one transplanted patients who had IgAN as an original disease (30 with biopsy-proved early recurrence, median 2.9 yr post-transplant), and 120 controls, were investigated for aberrantly glycosylated IgA1, IgA binding to mesangial matrix, macromolecular IgA (IgA/fibronectin and uteroglobulin/IgA/fibronectin complexes), and polymorphisms of cytokines [tumor necrosis factor alpha (TNFalpha), interleukin 10 (IL-10), IL-6, interferon gamma and transforming growth factor beta 1] and renin-angiotensin system (angiotensinogen converting enzyme, angiotensin II receptor 1, and angiotensinogen) genes. RESULTS: At multivariate logistic regression analysis, recurrence showed a border-line association with aberrantly glycosylated IgA1 [odds ratio (OR) 8.172, p = 0.077], and was significantly less frequent in carriers of -308 AG/AA TNF-alpha"high producer" genotype (OR 0.125, p = 0.036) and -1082, -819, -592 ACC/ATA IL-10 "low producer" (OR 0.038, p = 0.009) genotypes. CONCLUSION: High levels of aberrantly glycosylated IgA1 do not appear to play a strong crucial role in recurrence of IgAN. Polymorphisms of TNFalpha and IL-10 known to condition Th1 prevalence were associated with protection from early recurrence of IgAN.     

The effect of angiotensin converting enzyme gene polymorphism on chronic allograft dysfunction in living donor renal transplant recipients

BACKGROUND: Chronic allograft dysfunction (CAD), the major cause of the failure of kidney allografts, may be caused by immunological and non-immunological haemodynamic factors. Renin-angiotensin system has been implicated in the development of intraglomerular hypertension and has a central role on progression in chronic renal disease. Polymorphism in 16th intron of the ACE gene has been reported to predict the circulating angiotensin II levels. The aim of this study was to investigate the effect of the both recipient and donor angiotensin converting enzyme (ACE) genotype on the development of CAD in renal allograft recipients. PATIENTS AND METHODS: A total of 143 renal transplant recipients (95 male, 48 female, mean age 32 +/- 10 yr) were included. In order to exclude the effect of cold ischaemia, only patients transplanted from living donors were selected. Factors analysed in the development of CAD were donor and recipient age, past history of acute rejection, presence of hypertension and hypercholesterolaemia, serum uric acid level and ACE gene polymorphism. RESULTS: Forty of the patients (28%) had CAD. Homozygous deletion type ACE gene polymorphism was detected in 59 renal transplant recipients (42%) and in 31 donors of the patients (37%). On comparing patients with and without CAD, donor age, rate of acute rejection and hypertension and serum uric acid levels were significantly higher in CAD (+) groups. Neither recipient nor donor ACE genotype was associated with time to CAD. Cox regression analysis revealed donor age (p < 0.001), presence of hypertension (p=0.002) and serum uric acid levels (p=0.009), but neither donor nor recipient ACE genotype as independent factors for predicting development of CAD. CONCLUSION: Donor age, presence of hypertension and serum uric acid levels was independent factors. Donor and recipient ACE genotype seemed to have no influence on the development of CAD in living donor transplanted patients.     

Recurrence of IgA nephropathy in renal transplants

SUMMARY: The present article provides an update from the literature on the clinical significance of recurrent IgA disease in renal transplant patients, and it identifies possible reasons for the differences between the data that have been published. the clinical features of recurrent IgA nephropathy are described here, along with suggestions for the management of these patients.     

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3±5.8 (range 3.1–82.6) months after transplantation. Patients were followed up for a mean of 13.2±2.9 (range 1.2–51.1) months. The mean initial MMF dose was 660±56 mg/m² per day, increased to 1,042±73 mg/m² per day a year later. Cyclosporin was reduced from 138±10 mg/m² per day at MMF introduction, to 116±15 mg/m² per day at 6 months and 107±24 mg/m² per day at 1 year. Six months prior to MMF introduction GFR deteriorated by –32.7±7.3 ml/min per 1.73m² per year. Six months after the introduction of MMF, GFR improved by +26.2±7.1 ml/min per 1.73m² per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.Preliminary results of this study were presented at the 7th Annual Congress of the British Transplantation Society, 2004, Birmingham, UK, and at the 13th Congress of the Internal Pediatric Nephrology Association, 2004, Adelaide, Australia     

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients

OBJECTIVE: BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15-deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living-related renal transplantation between January 1999 and April 2003. METHODS: A total of 114 biopsy specimens from 88 living-related kidney transplantation recipients (performed between January 1999 to April 2003) were retrospectively analyzed. Patients received immunosuppression therapy based on calcineurin inhibitors and corticosteroid [tacrolimus (TAC) 33 and cyclosporin (CyA) 55]. Additionally, mycophenolate mofeteil (MMF) was used in 21 patients; DSG was used in seven patients; and anti-CD3 monoclonal antibody was used in 16 patients. We analyzed the degree of donor/recipient human leucocyte antigen (HLA) compatibility assessed by the number of HLA-A, -B, and -DR-mismatched antigens in 88 patients. The diagnosis of BKVN was made by the light microscopic examination and a positive immunohistochemical staining of anti-40 antibody in biopsy specimens. Patients were divided into two groups of group A (mild histological change) and group B (moderate or severe histological change) to determine the risk factors in different histological staging. The clinical course of two typical patients in different histological stage is described briefly to outline the risk factors of BKVN. RESULTS: We identified seven cases of BKVN (8.0%) from 88 transplanted patients. Significantly higher incidence of combination regimen consisting of TAC and MMF in BKVN group was noticed compared with non-BKVN group (57.1% vs. 9.9%; p = 0.003). BKVN was associated with a significantly higher incidence of DSG administration compared with non-BKVN group (57.1% vs. 3.7%; p 相似文献