Loss of renal graft due to recurrent IgA nephropathy with rapidly progressive course: an unusual clinical evolution

Recurrence of IgA nephropathy following renal transplantation has been described in 40-50% of patients, and it usually has a good outcome. We present the case of a 54-year-old man with IgA nephropathy who developed terminal renal failure in 1985, 3 years after the onset of the disease. In March 1986 he received a cadaveric renal allograft following treatment with ciclosporin and steroids. Eight months later he developed microhaematuria and proteinuria and 10 months later he developed acute nephritic syndrome and rapidly progressive renal failure. Renal biopsy disclosed an IgA nephropathy with epithelial crescents in 60% of glomeruli. Treatment with plasma exchange and cyclophosphamide was unsuccessful and the patient lost his graft and returned to regular haemodialysis 15 months after renal transplantation.     

肾移植术后IgA肾病复发危险因素分析

目的探讨肾移植术后IgA肾病复发的危险因素。方法选取2008年1月—2019年12月在郑州人民医院器官移植中心接受肾移植的149例原发病为IgA肾病的肾衰竭患者为研究对象。根据程序性肾活检结果,将肾移植后是否有IgAN复发分为复发组(40例)和未复发组(109例)。分别记录两组患者的性别、年龄、供体类型、透析时间、进展至终末期肾病(end-stage renal disease,ESRD)时间,移植病史、高血压以及糖尿病病史、术后感染病史、免疫抑制方案、人类白细胞抗原(human leucocyte antigen,HLA)错配数,统计分析术后复发的危险因素。结果复发组与未复发组患者相比,两组性别、肾移植次数、有无糖尿病、有无高血压、免疫抑制方案、术后有无感染病史、透析时间,差异无统计学意义(P>0.05)。将单因素分析中有统计学意义的因素进行Logistic分析,结果显示:供体来源、受体年龄、HLA错配数是肾移植术后IgAN复发的危险因素,差异有统计学意义(均P<0.05)。结论肾移植术后IgA肾病复发与供体来源、受体年龄、HLA错配数有关,针对以上因素采取干预措施,为临床控制IgAN的复发提供思路。     

Higher Incidence of Renal Allograft Glomerulonephritis in Living-Related Donor Kidney Transplantation

Glomerulonephritis recurrence has emerged as one of the leading causes of allograft loss. We aimed to investigate the effect of living-related and deceased donation on the incidence of renal allograft glomerulonephritis and its effect on renal allograft survival.

Plasma exchange in patients with rapidly progressive idiopathic IgA nephropathy: a report of two cases and review of literature

Primary IgA nephropathy is generally considered an indolent disease, but progression to chronic renal failure is not uncommon, and a rapidly progressive course is observed in some cases, especially when extensive fibrocellular crescents are present. The therapeutic benefit of immunosuppression and plasma exchange remains controversial. We described two patients with primary IgA nephropathy and rapidly progressive renal failure. Both patients showed extensive glomerulosclerosis and crescent formation in their renal biopsies. Corticosteroid and immunosuppressive therapy failed to control the progression of the disease, and plasma exchanges were performed. In both cases, the serum creatinine and creatinine clearance initially improved with plasma exchange and the rapid progression of renal failure was apparently halted. In one patient, the serum creatinine rose when treatment was discontinued and fell again when plasma exchange was recommenced. Nevertheless, the long-term benefit of plasma exchange in crescentic IgA nephropathy was unsatisfactory as the renal function continued to deteriorate in the following 12 months despite an initial stabilization.     

Recurrent IgA nephropathy in living-related donor transplantation: recurrence or transmission of familial disease?

We describe a patient who developed terminal renal failure of two HLA-identical renal allografts due to crescentic IgA nephropathy. The first graft contained IgA deposits at the time of donation, suggesting that transmission of IgA deposits may have contributed to the nephritis of the first allograft. The second graft was free of IgA deposits at the time of donation, but the recipient developed a similar, rapidly progressive nephritis. This case points up the malignant potential of IgA nephropathy and the complex nature of transplant planning for patients with end-stage renal disease (ESRD) secondary to IgA nephropathy. Living-related donor (LRD) transplants seem to be associated with a higher rate of recurrence than cadaveric grafts. This higher rate may partly reflect the inadvertent transmission of subclinical IgA deposits from donor to recipient and a genetic susceptibility of certain HLA types (specifically B35 and DR4) to recurrent disease. Cadaveric transplants may be preferable in the setting of high-risk HLA types or familial patterns of IgA nephropathy.     

A case of subclinical IgA nephropathy and cyclosporin associated arteriolopathy diagnosed by non-episode biopsy of graft kidney after renal transplantation]

We report a case of subclinical immunoglobulin A (IgA) nephropathy and cyclosporin associated arteriolopathy following renal transplantation. A 39-year-old male with chronic glomerulonephritis received kidney transplantation from a two- human leukocyte antigen (HLA) mismatched cadaveric donor. The initial immunosuppressive therapy was triple-drug therapy with cyclosporin, prednisolone and mizoribine. Four months after transplantation, he had an acute rejection episode, and the renal function was recovered by steroid pulse and 15-deoxyspergualin therapy. Eight years after transplantation, we conducted a non-episode biopsy of the renal allograft to examine subclinical lesions. The histopathological findings showed cyclosporin associate arteriolopathy (CAA) and IgA nephropathy. There was no sign of acute or chronic rejection. At the present time, the renal function of the allograft is good. In conclusion, the non-episode biopsy of renal allograft is useful for examination of subclinical lesions.     

Persistent subclinical rejection associated with nodular B-cell infiltrates in a renal transplant recipient

Abstract:  Recently, B-cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B-cell infiltrates. A 59-yr-old man with end-stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post-operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow-up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B-cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15-deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B-cell infiltrates. We treated the refractory rejection with B-cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B-cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).     

An unusual cause of ureteral obstruction in a renal allograft.

We describe a 66-year-old patient, on haemodialysis since 2002because of chronic renal failure due to chronic glomerulonephritisof uncertain origin (supposedly IgA nephropathy). In March 2006,he underwent cadaveric donor kidney transplantation. The allografthad one polar artery, with the anastomosis made on the right     

The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys

Several reports in animals, and sporadic case reports in humans, have suggested that kidneys with decreased nephron mass may be more susceptible to the development of focal-segmental glomerosclerosis. This prompted a reexamination of our previously reported group of pediatric donor-adult recipient renal transplant combinations. Data were analyzed from 31 adult recipients who had received renal transplants from cadaver pediatric donors (less than 6 years) with graft function for greater than 6 months and no evidence of chronic rejection. These were compared with a control group transplanted during the same period with adult donor kidneys. Immunosuppression consisted of azathioprine/prednisone or quadruple therapy in 16 and 15 patients respectively. End-stage renal disease (ESRD) was secondary to chronic glomerulonephritis (n = 9), diabetes mellitus (n = 6), polycystic kidney disease (n = 5), and miscellaneous causes (n = 11). Twenty patients had radiographic documentation of renal hypertrophy posttransplant. All patients had serial 24-hr urinalysis for protein and creatinine after transplantation during periods of stable renal function. Ten patients had renal biopsies performed at a mean time from transplant to biopsy of 10.4 +/- 1.6 months. Seven recipients had biopsies that revealed glomerulosclerosis at 13 +/- 6 months posttransplant. Protein excretion and serum creatinine in these patients were significantly higher than in control patients (1.6 +/- 0.37 vs. 0.49 +/- 0.15 g/24 hr and 1.96 +/- 0.11 vs. 1.64 +/- 0.09 mg%; P less than 0.03 and P less than 0.01, respectively). Only 3 of 25 control adult donor recipients developed proteinuria greater than 0.8 g/24 hr within 2 years of transplantation vs. 15/31 pediatric donor recipients. No correlations with the etiology of ESRD, age (greater than or less than 40 years), weight, sex, diabetes, hypertension, or the number of acute rejection episodes could be found. Our data suggest that adult recipients of pediatric donor renal transplants may be at greater risk for the development of glomerulosclerosis than those recipients receiving adult donor kidneys.     

A case of allograft dysfunction with antibody-mediated rejection developing 13 yr after kidney transplantation

Abstract:  Antibody-mediated rejection is an important cause of chronic allograft dysfunction. We report a case of chronic antibody-mediated rejection 13 yr after transplantation. This patient is a 19-yr-old man who had renal insufficiency since infancy because of bilateral polycystic kidneys. Peritoneal dialysis was started when he was four yr old and he received a renal allograft from his mother at the age of six yr. Donor and recipient were ABO compatible and immunosuppressive treatment was started with cyclosporine, mizoribine, and methylprednisolone. No acute rejection was experienced and histological acute rejection was not proven on any subsequent protocol biopsies. Ten yr after transplantation, a protocol biopsy revealed moderate chronic allograft nephropathy and severe cyclosporine-associated arteriolopathy. His allograft function was preserved at this time and the cyclosporine dose was tapered to 125 mg/d. His renal function gradually deteriorated starting 12 yr after transplantation. Although mizoribine was changed to mycophenolate mofetil, he required dialysis one yr later. A diagnosis of antibody-mediated rejection was made based upon the renal biopsy findings (including C4d staining) and circulating anti-human leukocyte antigen (HLA) antibody levels (12 yr after transplantation). We conclude that it is necessary to pay attention to antibody-mediated rejection, even in allograft cases with good function for over 10 yr and no risk factors for the development of de novo anti-HLA antibodies.     

大鼠慢性移植肾肾病动物模型的制作经验总结

目的 总结制作稳定的大鼠慢性移植肾肾病(CAN)动物模型的经验.方法 以F344近交系大鼠为供者,取供者左肾作为供肾,原位低温灌注;以Lewis近交系大鼠为受者,行左侧原位肾移植,供肾动脉与受者腹主动脉端侧吻合,供肾静脉与受者肾静脉端端吻合,输尿管带膀胱瓣与受者膀胱吻合.术后用环孢素A灌胃10 d,剂量为10 mg·kg-1·d-1.每月采集受者血液和尿液,测定血肌酐及24 h尿蛋白,分别于术后2、4个月获取移植肾进行病理检查.结果 45只进行移植,手术成功率为85%,单次手术时间为(120±20)min.移植后1个月,大鼠即出现血肌酐、尿素氮及血胱抑素升高,24 h尿蛋白增加,与术前相比,各项指标均升高(P<0.05);术后2个月及4个月,除尿蛋白继续增加外,其余观察指标上升不明显.移植术后2个月,移植肾有轻度至中度的间质纤维化,淋巴细胞和浆细胞的浸润;4个月时,移植肾可见广泛的间质纤维增生,间质细胞大量浸润,肾小球基底膜增厚、硬化、闭塞,肾小管萎缩退化,符合CAN的病理改变.结论 通过充分的手术强化训练及改进,规范大鼠取、肾、移植术中、术后管理的每个细节,大鼠CAN模型的成功率及稳定性高.

Abstract：

Objective To summarize the experience of establishing the stable rat model of chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients.After the left kidney of the donor perfused in situ under hypothermic condition, the left renal vein,abdominal aorta and bladder flap of the donor was anastomosed with the left renal vein, renal artery and bladder of the recipient, respectively. The recipients were given cyclosporin oral solution 10 mg/kg every day by gavage for 10 days after transplantation. The blood and urine samples were collected 1 month, 2 months and 4 months after transplantation and renal function and total urine protein were examined. The pathological changes of the renal allograft were observed 2 and 4 months after transplantation. Results Forty-five rats received operation and achievement ratio was 85%. The renal transplantations were finished in 120 ± 20 min. The Scr, BUN, Cycs and total urine protein demonstrated a significant increase one month after transplantation. On the second and fourth month,with the exception of urine protein continued to increase, the other indicators did not change significantly. Two months after transplantation renal pathology demonstrated light to moderate interstitial fibrosis, infiltration of lymphocytes and plasma cells. At 4th month the renal allografts showed extensive interstitial fibrosis, a large number of infiltrating interstitial cells, thickening,hardening, occlusion of glomerular basement membrane, and renal tubular atrophy that were consistent with pathological changes of chronic allograft nephropathy. Conclusion Through adequate surgical training and improvement, and specification for rat nephrectomy, transplantation surgery,and postoperative management in every detail, the model with high success rate and stability can be achieved.     

Dual Kidney Transplantation Involving Organs From Expanded Criteria Donors: A Review of Our Series and an Update on Current Indications

BackgroundOur purpose was to review our kidney transplantation program based on the use of expanded criteria donors, and to determine current indications for dual kidney transplantation (DKT). In 1996, a program was initiated to transplant kidneys from donors of over 60 years performing single or dual transplantation.MethodsIn 1996, a program was initiated to transplant kidneys from donors of over 60 years performing single or dual transplantation. DKT were performed with donors >75 and donors between 60 and 74 years of age and glomerulosclerosis of >15%. The kidneys of donors between 60 and 74 years of age and with glomerulosclerosis of <15% were used for single kidney transplantation (SKT). In 2005, we started to perform SKT despite glomerulosclerosis being >15%, taking into account donor and recipient characteristics.ResultsFrom 1996 to 2004, 222 SKTs and 88 DKTs were performed. Graft survival after 1 and 4 years was, respectively, 91% and 78% for SKT and 95% and 79% for DKT. In 2005, we started to perform SKT despite glomerulosclerosis being >15%, taking into account donor and recipient characteristics. From 2005 to 2011, 328 SKT and 32 DKT were performed. During this period most kidneys used for DKT were from female donors >75 years old, weighing <65 kg, with a creatinine of >1 mg/dL and glomerulosclerosis of >15%. The recipients for DKT were mostly male, <70 years old and whose weight was >75 kg.ConclusionDKT from expanded criteria donors shows good outcomes. However, in many cases SKT may fulfill the need of the recipient. The archetype for DKT is an older female weighing <65 kg and the most common recipient is an overweight male who is <70 years old.     

BK virus nephropathy in a patient with ABO-incompatible renal transplantation

Abstract:  A 43-year-old woman with end-stage renal disease originating from IgA nephropathy entered chronic haemodialysis therapy. She then received an ABO-incompatible living related renal transplantation. Initial immunosuppression consisted of azathioprine, methylprednisolone and tacrolimus. At 155 days after transplantation, the azathioprine was changed to mycophenolate mofetil for continuous graft dysfunction. Furthermore, a total of three courses of anti-rejection therapy was given. At 665 days after transplantation, diagnosis of BK-virus nephropathy was made by immunohistochemical analysis and viral DNA assay. Therefore the immunosuppression therapy was reduced for graft dysfunction. All five renal biopsy specimens were examined retrospectively in order to determine when the BK virus nephropathy had developed. The expressions of SV40 large T antigens were detected from the third (117 days) to the fifth (665 days) biopsies, with increasing numbers of SV40 large T antigen positive cells. In addition, many cells contained inclusion bodies which were already present in the urinary sediment for 3 months post-transplantation. Although it is difficult to make a diagnosis of early stage of BKVN, we have to consider with caution if urinary cells with inclusion body are seen. Awareness of BKVN at the earliest opportunity is important in order to avoid over-immunosuppression.     

Recipient age and weight affect chronic renal allograft rejection in rats.

Nephron doses and immune responses change with age. Therefore, age is a potential risk factor for graft survival after kidney transplantation. The aim of this study was to determine whether age-related differences are of importance for long-term outcomes after renal transplantation. Kidneys from Fisher 344 rats were orthotopically transplanted into nephrectomized Lewis rats. Kidneys were transplanted using donors and recipients of three age levels, i.e., young (8 wk of age), adult (16 wk of age), and old (40 wk of age). Rats were killed 24 wk after transplantation, and functional, morphologic, and molecular evaluations were performed. Recipient age, rather than donor age, determined graft survival rates. No significant correlation was observed between donor kidney weight on the day of transplantation and morphologic results. Advanced recipient age was associated with reduced creatinine clearance, more severe histologic injuries, including extended glomerular sclerosis, interstitial fibrosis, and vascular lesions, more pronounced cellular infiltration, and greater expression of transforming growth factor-beta and platelet-derived growth factor A and B chains. Although no significant correlation between donor age or kidney weight on the day of transplantation and morphologic results was observed, there was a significant correlation between recipient body weight on the day of transplantation and allograft injury. It is concluded that recipient age and weight affect chronic renal rejection. Renal allografts may benefit from young recipient age but may deteriorate in old recipients, suggesting effects of recipient functional demand on long-term outcomes.     

Outcome of living donor renal transplantation in obese recipients

The increasing prevalence of obesity among patients with end-stage renal disease accompanies more common renal transplantation from living donors. Since several studies have shown a negative impact of recipient obesity on renal transplantation outcomes, we investigated the influence of recipient-weight and donor-recipient-weight ratio on the outcome of living related renal transplantations. From October 2000 until December 2004, we performed 81 living donor renal transplantation with 30.8% (n = 25) of recipients with a body mass index >25 donor. In this group 6 patients lost their grafts (1-year survival rate, =76%). Among 56 recipients of normal body weight only 3 patients lost their graft (1-year graft survival rate, 94.6%; P < .001). Upon multivariate analysis body mass index was an independent risk factor for graft loss within the first year. When the body weights of the donor and recipient were analyzed in detail the quotient (body weight recipient(2)/ body weight donor) was also an independent risk factor. This study confirmed the results of larger analyses suggesting that body weight matching could significantly improve the outcomes in living donor renal transplantation. As a result of this study, in our institutional policy has changed; recipients of living donor grafts are only accepted when their body mass index is <25.     

APOL1 Polymorphisms in a Deceased Donor and Early Presentation of Collapsing Glomerulopathy and Focal Segmental Glomerulosclerosis in Two Recipients

Two common polymorphisms in APOL1 (G1 and G2) are conserved in persons of African ancestry, and the presence of two polymorphisms (commonly referred to as risk variants) has been identified as a risk factor for chronic kidney disease and focal seg‐mental glomerulosclerosis. In kidney transplantation, deceased donors with two APOL1 risk variants carry an increased risk of renal allograft failure in the recipient. An emerging question is whether these data should influence deceased donor assessment or be used to refine prediction of allograft survival. We present the first detailed report of two cases of recipient glomerular disease in the first year following transplant from a deceased donor later defined as carrying two APOL1 risk variants. A possible “second hit” predisposing to renal disease in these recipients is discussed, one with active cytomegalovirus infection concurrent with collapsing glomerulopathy and renal failure and the other with chronic, slowly healing wound infection and focal segmental glomeru‐losclerosis but stable renal function. In retrospect, awareness of the donor APOL1 risk alleles would not have influenced donor selection and ultimately did not influence posttransplant management. These case reports inform further discussion of the value of APOL1 testing for deceased donors.     

The transmission of donor-derived malignant melanoma to a renal allograft recipient

The transmission to organ transplant recipients of donor origin malignancy in the allograft has been described. Here we report the transmission of malignant melanoma in a renal allograft transplanted from a multiorgan donor. The lung transplant recipient presented with an allograft lesion that was proven to be melanoma and of donor-origin based on human leukocyte antigen (HLA)-DR typing. One renal allograft recipient was undergoing his second deceased donor renal transplant, having lost his first graft from recurrent IgA nephropathy. He was unsensitized and immunosuppression consisted of tacrolimus, mycophenolate and prednisolone. He achieved stable graft function and there were no episodes of rejection. Four and a half months post-transplant a diagnosis of donor origin melanoma in the lung recipient was made and his immunosuppression was stopped. He presented with clinical rejection two wk later and a transplant nephrectomy was undertaken. Histology demonstrated vascular and cellular rejection and there was a 3-mm melanoma deposit with no evidence of tumour infiltrating lymphocytes. Three years post-transplant he remained clinically well with no evidence of melanoma and received his third deceased donor renal transplant. This was complicated by cellular rejection in the first week treated with methylprednisolone and vascular rejection at day 10 treated with anti-thymocyte globulin. Three months post-transplant he has achieved good allograft function and remains well with no evidence clinically or on imaging of metastatic melanoma. The other renal allograft recipient was receiving his first deceased donor transplant, having end-stage renal failure of uncertain aetiology. His immunosuppression was not stopped until melanoma was proven in the renal allograft pair six months post-transplant and he then presented with clinical rejection six wk later. Transplant nephrectomy was undertaken and histology did not demonstrate melanoma, but severe vascular and cellular rejection was evident. At three-yr post-transplant he remains disease free clinically and on imaging. At present, the cardiac allograft recipient has no evidence of transmitted melanoma. The highest risk of transmission of donor origin melanoma appears to be from donors who are older and have died from an intracerebral haemorrhage. It is likely these donors have metastatic melanoma and their intracerebral haemorrhage is not primary but has occurred in an unrecognized metastatic cerebral deposit. While the occurrence of donor-transmitted malignancy is not common, the outcome is often fatal.     

Recurrence of IgA nephropathy 17 months after renal transplantation in the allograft transmitted thin basement membrane disease (TBMD) from donor

Recurrence of IgA nephropathy (IgAN) following renal transplantation has been described in 40-50% of such patients and it usually has a good outcome. We present the case of a 20-yr-old woman with IgAN who developed end-stage renal failure in 1995. In November 1996, she received a kidney from a living-related donor and was treated with tacrolimus, azathioprine and steroids. Zero- and one-hour biopsies were performed, which revealed minor glomerular abnormalities in light microscopy, thin basement membrane disease (TBMD) in electron microscopy. Eight months later she developed microscopic hematuria and proteinuria; however, the graft function was normal. Renal biopsy revealed an IgAN that is thought to be due to recurrence of the original disease.     

Early acute rejection does not affect chronic allograft nephropathy and death censored graft failure

BACKGROUND: Even with the development of modern immunosuppression, an acute rejection episode is a major complication after renal transplantation. Acute rejection episodes have been used as clinical indicators for chronic allograft nephropathy and graft loss. We investigated the timing and frequency of acute rejection episodes in relation to long-term graft survival and chronic allograft nephropathy. METHODS: The Long Term Efficacy and Safety Surveillance study of transplant patients receiving cyclosporin (Neoral) included 1706 adult renal transplants (1995 to 2003) with a functioning graft for at least 1 year. The impact on death-censored long-term graft survival was evaluated for acute rejection episodes (single or multiple) within 3 months, at 3 to 6 months, at 6 to 12 months, or at over 1 year posttransplant. A stepwise binary logistic regression was employed to identify independent risk factors for the time to occurrence of an acute rejection episode. RESULTS: An acute rejection episode occurring within 3 months posttransplantation had no effect on either death-censored long-term graft failure (P=.2157) or chronic allograft nephropathy (P=.9331). However, an acute rejection episode occurring at 1 year or later posttransplantation was significantly associated with death censored long-term graft failure (P <.0001) and chronic allograft nephropathy (P <.0001). The numbers of HLA-DR mismatches and younger recipient ages were independent risk factors for early acute rejection. CONCLUSION: Among patients whose graft survives at least 12 months, an early acute rejection episode within 3 months posttransplant was not associated with either death-censored long-term graft survival or chronic allograft nephropathy among adults treated with cyclosporin. However, an acute rejection episode occurring at 1 year or later posttransplantation showed a positive association with death-censored long-term graft survival or chronic allograft nephropathy. Lower numbers of HLA-DR mismatches sum to reduce the occurrence of acute rejection and the hospitalization time.     

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.