Efficacy of tonsillectomy for patients with recurrence of IgA nephropathy after kidney transplantation

Abstract:  From January 2007, we started to perform the tonsillectomy for every patient with recurrent IgA nephropathy (IgAN) after kidney transplantation. Up to September 2008, four recipients with primary IgAN had biopsy-proven recurrent IgAN. They had also progressive hematuria or proteinuria from on the average 14.3 months after transplantation. Then their specimens diagnosed as recurrent IgAN were collected and they underwent tonsillectomies on the average 52.3 months after transplantation. Abnormal urinary findings of all patients favorably improved after tonsillectomy. All cases but one had mild renal injury, where the severity of glomerular lesions, glomerular hypercellularity, segmental lesions, and sclerosis was mild, and no deteriorated serum creatinine (SCr) before their tonsillectomies. Even the case with exacerbated SCr and severe renal injury, where the severity of glomerular lesions was severe, had her urinary findings ameliorated promptly after tonsillectomy likely as others. At present, they have almost no symptoms after tonsillectomy and no remarkable change of SCr level compared with before and after tonsillectomy and maintain ameliorated urinary findings continuously. Tonsillectomy had possibility to be a favorable treatment of hematuria or proteinuria in recurrent IgAN recipients.     

Beneficial Effects of Tonsillectomy for Mesangial Immunoglobulin A (IgA) Deposition and Clinical Outcome in Five Kidney Transplant Patients With Recurrent IgA Nephropathy: Case Report

Introduction

Tonsillectomy has been applied for recurrent immunoglobulin (Ig)A nephropathy (IgAN) in kidney transplantation recipients, but allograft histologic changes after this treatment remain unclear.

Methods

Five patients with recurrent IgAN underwent tonsillectomy for persistent proteinuria (average, 397.2 mg/d; >6 months). Six repeated biopsies were taken 33.8 ± 17.1 months after treatment. Glomerular IgA deposition was detected by immunofluorescence staining on frozen tissue. Histologic and clinical data have been collected.

Results

An average of 11.2 months (range, 6–20) after tonsillectomy, proteinuria decreased to 60.8 ± 49.3 mg/d. Serum creatinine (SCr) slightly decreased (1.33 ± 0.31 before vs 1.24 ± 0.29 after treatment; P > .05). In 5 of the 6 repeated biopsy samples month after tonsillectomy, there was decreased mesangial IgA deposition. Glomerular crescent and endothelial proliferation were no longer found, although there was increased focal sclerosis and adhesion. After tonsillectomy, there were increased interstitial fibrosis and tubular atrophy, with no significant differences in Banff scores.

Conclusions

Tonsillectomy can reverse not only persistent proteinuria, but also mesangial IgA deposition in patients with recurrent IgAN. Tonsillectomy may have both favorable clinical and histologic effects in recurrent IgAN after kidney transplantation.     

Treatment of Immunoglobulin A Nephropathy Recurrence Post–Renal Transplant

Immunoglobulin A nephropathy (IgAN) is the most commonly occurring glomerulonephritis. Recurrence of disease in the transplanted kidney can significantly reduce allograft survival rates. Currently, there is no definitive management plan for IgAN recurrence in a transplant that reduces the rate of decline of allograft function and prolongs time to dialysis or re-transplantation. Herein we present a 48-year-old man who had received a renal transplantation in 2006 following his diagnosis of IgAN. In 2015, the patient was noted to have an elevated blood pressure and proteinuria (urinary protein:creatinine ratio [uPCR] 170 mg/mmol). A transplant biopsy confirmed recurrent IgAN. A year later, he presented with dipstick hematuria, nephrotic-range proteinuria (uPCR 820 mg/mmol), and a serum creatinine of 90 to 140 μmol/L. A second biopsy revealed mesangioproliferative glomerulopathy consistent with crescentic IgAN. An optimal management plan is currently unknown for recurrent crescentic IgAN in the transplanted kidney. We decided to treat this patient with oral cyclophosphamide daily and high-dose prednisolone. The treatment has so far yielded a positive response and managed to preserve allograft function without significant adverse effects for our patient. Our case illustrates the importance of timely biopsies to identify recurrence of disease and highlights an effective therapeutic option for recurrent IgAN with crescent formation in a transplant.     

The fate of glomerular mesangial IgA deposition in the donated kidney after allograft transplantation

OBJECTIVE: To investigate the fate of the mesangial IgA deposits in the donor kidney after allograft transplantation. METHODOLOGY: Routine pre-transplant cadaveric donor kidney biopsy and repeated renal biopsies were performed at months 1, 3, and 6 after renal transplantation. The patients, 342 in number, were divided into IgA positive deposition kidney group (group A, n = 83) and non-IgA deposition kidney group (group B, n = 259). There were no significant differences between the two groups' sex, age, time of hemodialysis, warm ischemia time, cold ischemia time, complement-dependent cytotoxicity, level of panel-reactive assay, and the distribution of original disease. RESULTS: Recipients in group A received donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition. All of them showed edema, nephrotic range protienuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. Borderline change was higher in group A than in group B, 37.3 and 16.2% (p < 0.001), respectively. Acute allograft rejection was higher in group A than in group B, 31.3 and 19.3% (p < 0.001), respectively. The glomerular mesangial IgA deposits gradually disappeared from the mesangial regions in grafts of acute rejection. Graft survival in both groups was not significant, being 93.8 and 95.6% in 1 yr, and 86.7 and 88.3% in 3 yr. CONCLUSION: Clinical features of the recipients which received from donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition: edema, proteinuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. The presence of IgA deposits on donated kidney, by a possible increase of the immunogenicity of these kidneys, might be a cause of increased rejection. There were no significant differences between the two groups on long-term allograft survival.     

Acute poststreptococcal glomerulonephritis superimposed on IgA nephropathy

Superimposition of poststreptococcal glomerulonephritis (PSGN) on the course of IgA nephropathy (IgAN) is uncommon. A case of PSGN during IgA nephropathy is presented. A 30-year-old man who had alternating gross and microscopic hematuria for 7 months underwent a renal biopsy. The first renal biopsy revealed IgAN with mesangial deposits of IgA and C3. Two months later, the patient suffered generalized edema, proteinuria, hematuria, an increased ASO titer and a decreased C3 level. A second renal biopsy revealed diffuse endocapillary proliferative glomerulonephritis with epimembranous hump-like electron-dense deposits of C3, but the original mesangial IgA deposits had disappeared. A diagnosis of acute PSGN was indicated. Two months after the onset of acute nephritic syndrome, the patient remained asymptomatic, except for microscopic hematuria and proteinuria. Some cases with persistent proteinuria or hematuria after PSGN are probably related to preexisting IgAN.     

MCNS, which secondary developed into incidental IgA nephropathy--a case report]

There have been a number of case reports on nephrotic syndrome with histological findings of minimal change on light microscopy and mesangial IgA deposition on fluorescent microscopy. The pathogenesis of these cases is, however, yet to be clarified. Here, we report a case of minimal change nephrotic syndrome (MCNS) associated with IgA nephropathy, which developed later in the course of MCNS. The patient was 18 years old male with steroid-responsive nephrotic syndrome. First episode of proteinuria occurred when he was 4 years old. On the fourth episode of proteinuria, renal biopsy revealed minimal change on light microscopy and no evidence of deposition of immunoglobulins or complements on immunofluorescent and electron microscopy. On the fifth relapse of MCNS, microhematuria developed concomitantly with massive proteinuria. Renal biopsy, then, showed light microscopic findings of mild focal segmental glomurulonephritis. Significant mesangial IgA deposition was observed on immunofluorescence study. Electron microscopy revealed electron dense deposit in the mesangial and paramesangial area. The patient was well-responsive to steroid although microhematuria persisted after disappearance of proteinuria. We concluded that IgA nephropathy may have developed subsequently in the course of MCNS in our case.     

Glomerular pathology of allograft kidneys in Hong Kong

AIMS: Our goal was to define the spectrum of glomerular diseases in allograft kidneys and to correlate them with clinical parameters. METHODS: Eight hundred ninety-one renal graft biopsies and 43 graft nephrectomies from 1980 to 2004 were obtained from 442 allografts transplanted to 425 patients. RESULTS: Glomerular diseases were diagnosed in 33% of kidney grafts. Indications for biopsy were baseline assessment (23 biopsies, 2.5%); renal dysfunction (790 biopsies, 88.7%); proteinuria (154 biopsies, 17.3%); hematuria (11 biopsies, 1.2%); and study protocol (four biopsies, 0.4%). The median time to take a biopsy was less than 8 months posttransplant. The mean time posttransplant when the biopsy diagnosis was made was 70 months for IgA nephropathy (IgAN); 66 months for transplant glomerulopathy (TG); 65 months for focal segmental glomerulosclerosis (FSG); 55 months for mesangiocapillary glomerulonephritis (MCGN); 45 months for membranous glomerulonephritis (GN); 49 months for mesangial proliferative GN; and 101 months for diabetic nephropathy. Recurrent glomerular disease was documented in 31 (7.0%) grafts. Specific glomerular diseases were diagnosed by biopsies in 106 (89.1%) of 119 proteinuric allografts. CONCLUSIONS: Glomerulopathy was common in allografted kidneys. IgAN, TG, FSG, mesangial proliferative GN, and membranous GN were the majority. A higher proportion of grafts from donors related to the recipients than from unrelated donors showed IgAN (P < .05), suggesting that genetic factors might play a role in the pathogenesis of IgAN. Recurrence of glomerulopathy underlying ESRD was frequent for IgAN, FSG, and MCGN, but this was rarely seen in membranous GN.     

Risk factors for graft loss in patients with recurrent IGA nephropathy after renal transplantation

BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys has been reported to be >50%. Although recurrent IgAN has a benign clinical course, recent data suggest that it leads to graft loss in a substantial number of patients. METHODS: We performed a retrospective single-center analysis of 34 renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients, of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN. Recurrent transplant IgAN was more often detected in men and at later timepoints after post-transplantation. Four patients with recurrent transplant IgAN progressed to graft failure. Progression to graft failure was associated with worsened renal function, higher systolic blood pressure, and the lack of presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA typing, and immunosuppression did not show a relation to recurrence or graft loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft survival and risk factors for graft loss due to recurrent IgAN were similar to those among IgAN in native kidneys.     

De novo fibrillary glomerulopathy in the renal allograft of a patient with systemic lupus erythematosus

Lupus glomerulonephritis is a complication of systemic lupus erythematosus, with 10% of the patients developing end-stage renal disease. It is accepted that lupus patients are good candidates for kidney transplantation and that the disease activity is subdued after transplantation due to rigorous immunosuppression, with a low rate of graft loss due to recurrent glomerulonephritis. While recurrent fibrillary glomerulopathy has been reported in renal allografts, de novo disease has not. We report a patient with systemic lupus who underwent a renal transplantation and subsequently lost her allograft due to de novo fibrillary glomerulopathy. Four years after her first kidney transplant, the patient presented with acute deterioration of her renal function. A renal biopsy was performed, and it revealed a focal mesangioproliferative pattern with positive amorphous mesangial immunofluorescence staining for IgG and C3. Congo red staining was negative. Electron microscopy demonstrated the presence of randomly oriented nonamyloid fibrils in the mesangiun. The diagnosis of de novo fibrillary glomerulopathy was made. The patient lost her allograft and received a second cadaveric renal transplant 1 year later. She has had a stable renal function since then.     

Successful Treatment of Recurrent Henoch–Schönlein Purpura in a Renal Allograft with Plasmapheresis

Acute and severe cases of Henoch–Schönlein purpura (HSP) nephritis have been treated with plasmapheresis (PA) in both adults and children. It has been used either alone or with steroids, antiplatelets or cytoxic drugs. Generally, renal function has been shown to improve when PA is utilized. The role of PA in recurrent HSP after renal transplantation is unclear and has not been well described in the literature. We report a 29-year-old female with HSP who developed end-stage renal disease and subsequently underwent a renal transplantation with eventual loss of the allograft 5 years later due to recurrent HSP nephritis. Retransplantion was performed and the patient developed active HSP nephritis in her second allograft within a week after transplantation. In an effort to preserve her allograft, four cycles of PA were performed. Her proteinuria resolved and renal biopsies afterwards demonstrated marked reduction in mesangial IgA deposition. We conclude that PA may be useful in recurrent HSP nephritis, especially when used early. The risk of additional immunosuppression caused by PA needs to be considered. More studies need to be done to evaluate the efficacy of PA in this setting as well as to define the optimal treatment regimen.     

Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.     

Recurrent nephrotic syndrome after living-related renal transplantation resistant to plasma exchange: report of two cases

Abstract:  We encountered two patients of recurrent nephrotic syndrome (NS) after renal transplantation that was resistant to plasma exchange (PEX). Case 1 was a 34-year-old man with a living-related renal transplant for type-I membranoproliferative glomerulonephritis (MPGN) related end-stage renal disease (ESRD). He developed overt proteinuria 7 months post-transplant and presented with NS 5 months later. Biopsy of the transplant kidney revealed recurrent type I MPGN, but no features of acute rejection (AR) or chronic allograft nephropathy (CAN). He was treated with cyclophosphamide (CP), oral prednisolone (40 mg/d), an anti-platelet agent, heparin sulfate, and PEX, but the nephrotic state persisted and renal function was deteriorated. He recommenced hemodialysis 3 yr and 9 months after renal transplant. Case 2 was a 47-year-old male who underwent living-related renal transplant for ESRD due to focal segmental glomerulosclerosis (FSGS). He presented with proteinuria shortly after renal transplantation. He also had frequent episodes of AR. Graft biopsy revealed recurrent FSGS. Treatment of pulse methylprednisolone and PEX was transiently effective, but NS relapsed shortly after PEX. Graft biopsy at our hospital showed features of CAN with moderate interstitial fibrosis and tubular atrophy, presence of intraglomerular foam cells but no segmental sclerosis. Treatment with 12 courses of low-density lipoprotein apheresis (LDL-A) reduced proteinuria from 9.6 to 2.0 g/d, and incomplete remission has been maintained for more than 1 yr after LDL-A with slowly progressive renal dysfunction. Despite recent therapeutic advances, including the use of immunosuppressants and PEX, treatment of recurrent disease remains difficult. The LDL-A might be useful in cases with recurrent FSGS resistant to PEX.     

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.     

Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis

Relapse of focal segmental glomerulosclerosis (FSGS) after renal transplantation is 20-40%. Recurrence after a first relapse is 80%. The only current treatment is plasmapheresis and/or cyclophosphamide. We report successful treatment of a second relapse in a 48-year-old patient. At age 33, FSGS was diagnosed. The patient began hemodialysis 1 year later. In her first renal transplant, she developed recurrent FSGS and reached terminal transplant failure 3 years later. Eight years later, a second transplant was performed. Immunosuppressive regimen: steroids, mycophenolate mofetil (MMF), tacrolimus (TAC), and rabbit anti-thymocyte globulin. Proteinuria of 2-6 g/day was detected and a biopsy showed recurrent FSGS. Plasmapheresis was started without success. Another biopsy still showed FSGS. The patient received two doses of rituximab (375 mg/m2 each) i.v. Three weeks later, proteinuria was 350 mg/day (serum-creatinine 1.6 mg/dl). Twelve months later, proteinuria was at 90 mg/day. Rituximab might be an option for recurrent FSGS after renal transplantation.     

Clinicopathological features of paediatric renal biopsies in Shanghai over a 31 year period

Aim: To identify the variations in paediatric renal biopsy pathology and clinicopathological features during the past 31 years. Methods: A retrospective analysis of paediatric renal biopsies performed at a single institution in Shanghai from January 1979 to December 2009 was conducted. Results: The major pathologies included minor glomerular abnormalities (MGA, 26.1%), IgA nephropathy (IgAN, 17%) and mesangial proliferative glomerulonephritis (MsPGN) without IgA deposition (11.3%). The major clinical presentations included nephrotic syndrome (NS, 39.4%), haematuria with proteinuria (24.4%) and persistent microscopic haematuria (15.1%). MGA accounted for 46.9% of the cases in NS. IgAN and HSN accounted for 24% and 28.9% of patients with concomitant haematuria and proteinuria, and thin basement membrane nephropathy accounted for 51.2% of cases with persistent microscopic haematuria. The frequency of IgAN (78.6%) was much higher than that of TBMN (29.0%) in patients with persistent microscopic haematuria with abnormal urinary albumin. Conclusion: Minor glomerular abnormalities and IgAN were the major renal diseases in our study population, and the focus of our paediatric nephrologists. The high proportion of TBMN suggested that there should be limited use of renal biopsy for patients with persistent microscopic haematuria and renal biopsy should be performed in the presence of proteinuria or abnormal levels of urinary albumin.     

Clinical and pathological features of IgA nephropathy with macrohematuria in history

Objective To investigate the clinical and pathological characteristics of IgA nephropathy (IgAN) with macrohematuria (MH). Method 1512 consecutive patients with biopsy-proven IgAN diagnosed from January 2006 to December 2011 were enrolled, and divided into MH group and control group respectively, according to whether there existed episodes of MH before renal biopsy. The clinical and pathological characteristics were compared between two groups. Patients in MH group were then divided into three groups according to the interval from the last episode of MH to renal biopsy to clarify the concomitant clinicopathological changes associated with occurrence of MH. Results The rate of MH in history was 22.1%. MH group patients had significantly lower serum creatinine, slighter proteinuria, lower prevalence of hypertension and heavier microhematuria than control group (all P＜0.001). The prebiopsy durations were similar in two groups (P=0.627). In MH group, chronic pathological indicators, including global/segmental sclerosis, tubule atrophy/interstitial fibrosis were all slighter (all P＜0.001), whereas activity indicators, including necrosis lesions, crescents and mesangial proliferation were all more severe compared with control group (all P＜0.05). Those who underwent renal biopsy within 30 days of the last episode of MH had more severe proteinuria and microhematuria, higher prevalence of necrosis lesions, more severe crescents formation, and endothelial proliferation (all P＜0.05). Conclusions IgAN patients with MH in history have relatively milder clinical and chronic pathological manifestations, however more active pathological changes especially in those who suffer episode of MH recently.     

Posttransplant proteinuria due to Apolipoprotein E2 deposition in a kidney allograft

Lipoprotein deposition disorders limited to the kidney and causing proteinuria are rare. We present a case of nephrotic range proteinuria presenting within 4 months after deceased donor renal transplantation in a patient with end-stage kidney disease presumed secondary to hypertension. Two transplant kidney biopsies were performed sixteen weeks after transplantation, and one year after the first biopsy, both showing lipoprotein deposits in the glomeruli, progressive focal segmental glomerulosclerosis, and effacement of visceral foot processes. The patient had a normal lipid profile. Based on previous case reports of Apolipoprotein E variants causing proteinuria in native kidneys, Apolipoprotein E genotyping was performed. Genotyping showed Apolipoprotein E2 homozygosity. This Apolipoprotein E variant has been associated with lipoprotein deposition, proteinuria, and progressive kidney disease in the native kidneys. However, this is the first case of Apolipoprotein E2 homozygosity-related kidney disease in a transplant recipient. The patient was treated with fenofibrate, angiotensin enzyme inhibition, and angiotensin receptor blockade with reduction in proteinuria, and he kept good stable kidney function.     

A case of de novo glomerulonephritis with electron-dense deposits following renal transplantation

Abstract:  We present here a case of de novo glomerulonephritis (GN) two yr after kidney transplantation. The patient was a 13-yr-old girl who had renal insufficiency because of bilateral hypoplastic kidneys. She received a renal allograft from her father at the age of 11 yr. Immunosuppressive treatment was started with tacrolimus, mizoribine (MZB), basiliximab, and methylprednisolone (mPSL). There were no findings of GN at the one-h biopsy (first biopsy). Two yr after transplantation, she showed proteinuria, hematuria and increased serum creatinine level with no apparent trigger. The biopsy specimen (fourth) showed mesangial proliferative GN with electron-dense deposits in a variety of regions and borderline changes indicating acute rejection. She was treated with mPSL pulse therapy, deoxyspergualin, replacement of MZB with mycophenolate mofetil, an increase of the mPSL dose, and candesartan. Her serum creatinine and urinary protein excretion levels improved after the treatment. One month later, she developed deterioration in her renal function again. Renal biopsy findings (fifth) were almost the same as the lesions observed in the fourth allograft biopsy. After she recovered from these episodes, she appeared to improve in clinical findings of GN. Protocol biopsies at three yr and five months after transplantation (sixth) showed no evidence of acute rejection, but we still observed the features of de novo GN. We could not resolve the underlying causes by reference to the clinical history and serological findings. We speculate that some kind of immunological reactions might be associated with the pathophysiology.     

移植肾IgA肾病三例报告及文献复习

目的 探讨移植肾IgA肾病的病理特征、临床表现及预后。方法 回顾分析移植肾穿刺活检病理及临床资料。结果 3例IgA肾病,1例为复发性膜增殖型,2例为复发／发性系膜增殖型,临床表现主要是镜下血尿、轻度蛋白尿、或／和高血压、高脂血症;病理改变与普通人群的IgA肾病相同,此外存在多灶性肾小管萎缩及间质纤维化;其对治疗的反应与病理改变密切相关,以双嘧达莫、小剂量华法林及雷公藤多甙治疗2年,2例系膜增殖型者肾功能稳定,膜增殖型的1例治疗2年半后血肌酐上升。结论 移植肾IgA肾病复发迅速,其进展速度及治疗效果与病理分型和病变程度密切相关,无特效治疗方法。     

Recurrent nephrotic syndrome in renal allografts

We describe the clinicopathologic course of two patients with recurrent focal segmental glomerular sclerosis (FSGS). In both patients, FSGS was initially demonstrated during the evaluation of proteinuria. After progressing to end-stage renal disease, each patient received a living-related renal transplant. Shortly after transplantation, proteinuria recurred in both patients, progressing to the nephrotic syndrome. Serial renal biopsies were obtained from each patient. These initially demonstrated focal segmental epithelial proliferation (the "cellular lesion"), but focal segmental scars were observed in subsequent biopsies. None of the biopsies demonstrated immunoglobulin, complement deposition, or diffuse epithelial cell foot process fusion. These findings suggest that the scarring lesion in recurrent FSGS may be the result of a primary process involving damage to a limited number of visceral epithelial cells.