Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis

This study updates assessment of post‐transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score‐based matching techniques were used to estimate hazard ratios (HRs) for death‐censored allograft survival (DCGS) and patient survival in IgAN compared to non‐IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non‐IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non‐IgAN. IgAN had higher patient survival compared to non‐IgAN (HR 0.54, 95% CI 0.47–0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33–0.54, p < 0.0001 for living donors). Propensity score‐matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non‐IgAN group (HR 0.54, 95% CI 0.47, 0.63; p‐value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non‐IgAN recipients. Results can be used in prognostication and informed decision‐making about kidney transplantation in patients with IgAN.     

Recurrent IgA nephropathy after renal transplantation and steroid withdrawal

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13%‐50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single‐center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51 of 123 transplants, at least one post‐transplantation biopsy for clinical indication was performed; in 28 of 51 transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28) was compared with a group without IgANr (G2; N = 23). In our study, clinically evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy time were associated with IgANr. However, IgANr was significantly higher in patients who experienced steroid withdrawal at any post‐transplantation time (OR 7.7 P = .03). The median time to recurrence after steroid withdrawal was 59 months (min 4.18, max 113.2).     

肾移植术后IgA肾病复发

IgA肾病（IgAN）是常见的原发性肾小球肾炎之一,也是导致终末期肾病的重要危险因素。肾移植是IgAN导致的终末期肾病患者的首选治疗方式,但肾移植术后仍存在IgAN复发风险。目前有关肾移植术后IgAN复发的相关研究进展缓慢。IgAN复发的发病机制尚未明确,其病理表现不具备特异性,确诊仍依赖于肾活组织检查,且尚未见有效的复发性IgAN防治方案。本文主要从肾移植术后IgAN复发的发病机制、诊断、危险因素及治疗手段等方面介绍肾移植术后IgAN复发的最新进展,以期为临床肾移植术后IgAN复发的防治提供参考,改善肾移植受者的预后。     

Re‐transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database

Outcomes of kidney re‐transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre‐emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death‐censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.     

The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

Recurrent glomerulonephritis is an important cause of kidney allograft failure. The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear. We analyzed the impact of steroids and other immunosuppression on the risk of recurrent IgAN post‐kidney transplantation. Between June 1989 and November 2008, 3311 kidney transplants were performed at our center. IgAN was the primary disease in 124 patients; of these, 75 (60.5%) patients received steroid‐based immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were maintained on steroid‐free immunosuppression. Recurrent IgAN was diagnosed in 27 of 124 (22%) patients in clinically indicated kidney allograft biopsies over a median follow‐up of 6.86 ± 5.4 yr. On cox proportional hazards model multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly higher in patients managed with steroid‐free (HR 8.59: 3.03, 24.38, p < 0.001) and sirolimus‐based (HR = 3.00:1.16, 7.75, p = 0.024) immunosuppression without antilymphocyte globulin induction (HR = 4.5: 1.77, 11.73, p = 0.002). Mycophenolate use was associated with a lower risk (HR = 0.42: 0.19, 0.95, p = 0.036), whereas cyclosporine did not have a significant impact on the risk of IgAN recurrence (p = 0.61). These results warrant future prospective studies regarding the role of steroids and other immunosuppression drugs in reducing recurrence of IgAN and other glomerulonephritis post‐transplant.     

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.     

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.     

Outcomes of Simultaneous Heart–Kidney Transplant in the US: A Retrospective Analysis Using OPTN/UNOS Data

Simultaneous heart–kidney transplantation (SHK) remains uncommon in the US. We examined outcomes of SHK compared to heart transplant alone (HTA) and deceased donor kidney transplant (DDKT).
Data from OPTN/UNOS heart and kidney data bases were used to identify 16 710 HTA, 263 SHK transplants and 68 833 DDK transplants between 1998 and 2007. Outcomes included patient survival (PS), acute cardiac and renal rejection and renal graft survival (rGS).
The adjusted risk of death was 44% lower with SHK compared to HTA. Over half of SHK were performed in cases where pretransplant dialysis was not initiated. In these cases, there was no significant difference in the risk of death between SHK and HTA (HR 1.01; 95% CI 0.67–1.50).
Recipients of SHK had worse 1-year rGS and PS and had a higher relative risk of overall renal graft loss compared to DDKT recipients. One-year rates of cardiac (14.5%) and renal (6.5%) rejection were lower in SHK compared to HTA and DDKT, respectively.
Recipients of SHK had a lower adjusted risk of death compared to HTA recipients, particularly in patients who required pretransplant dialysis. These data suggest that SHK should be considered in heart transplant candidates with renal failure requiring dialysis, whereas the utility of SHK in cases of renal failure not requiring dialysis warrants further study.     

Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database.

Assignment of liver allocation priority for hepatocellular carcinoma is predicated on accurate imaging staging. We analyzed radiographically defined stage (radiologic stage [RS]) at listing and most recent extension and pathologic stage (PS) data from 789 liver transplant recipients for whom no pretransplant ablative treatment was given. There were no predetermined imaging or pathological protocols in this retrospective analysis of wait list data. Seventy-two (9.1%), 690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively. Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used with no difference in time to transplant for listing or most recent scan among the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different if original listing RS or most recent RS was used for comparison with PS. No one type of imaging technique had superior accuracy (P = 0.13); however, CT scan used alone or in combination compared to not being used at all, had higher odds of being accurate (odds ratio [OR] 1.38 [1.03-1.84], P = 0.031). In addition, imaging done less than 90 days before transplant had higher odds of being accurate (OR 1.49 [1.06-2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70-11.11], P < 0.0001). We observed considerable variation in RS accuracy among the United Network for Organ Sharing and Organ Procurement and Transplantation Network regions that is unexplained. In conclusion, current imaging requirements for RS prior to liver transplantation are unacceptably inaccurate. Future policy should require more accurate modalities or combinations of techniques.     

Obesity does not significantly impact outcomes following simultaneous liver kidney transplantation: review of the UNOS database ‐ a retrospective study

Simultaneous liver kidney transplantation (SLK) is the only curative option for patients with combined end stage liver and kidney disease. With the global obesity epidemic, an increasing number of obese patients are in need of SLK. However, the impact of pre‐transplant obesity on outcomes after SLK is unknown. An analysis of the United States OPTN registry (Oct 1987 – June 2016) identified 7205 SLK transplants. Of these, 1677 patients were overweight/obese (OW, BMI 30–39) and 183 were morbidly obese (MO, BMI ≥40). 29% of patients had NASH in the MO group versus 16.4% and 4.7% in the OW and normal weight (NW) groups, respectively. The 1, 3 and 5 year overall patient survival, kidney and liver graft survivals were comparable between the three groups. Numerically higher rates of acute kidney rejection were reported in the MO group at 1 year [12.73%, 8.59%, and 10.05% for MO, OW and NW, respectively (P = 0.22)]. Multivariate analysis identified diagnosis of hepatitis C, donor age, diabetes mellitus, and delayed kidney transplant function but not BMI as risk factors for poor patient and both liver and kidney graft survival. Based on these findings, obesity should not be a contraindication for SLK even for patients with BMIs ≥ 40.     

肾移植术后IgA肾病复发并非总是良性预后

目的  探讨肾移植后IgA肾病(IgAN)复发的临床病理特征及其预后。方法  选取1996年1月至2009年4月期间在南京军区南京总医院国家肾脏疾病临床医学研究中心接受肾移植的148例IgAN终末期肾衰竭受者为研究对象。根据肾移植后有否IgAN复发分为IgAN复发组(46例)和非IgAN复发组(102例)。比较IgAN复发组和非IgAN复发组受者肾移植术后0、1、2、3、5年尿沉渣红细胞(U-RBC)计数、24 h尿蛋白定量、肾功能[血清肌酐(Scr)、肾小球滤过率(GFR)]; 比较两组受者术后移植肾病理组织学损伤的发生率和移植肾存活率。结果  IgAN复发组肾移植术后U-RBC计数、24 h尿蛋白定量逐渐增加, 肾功能逐渐变差。与非IgAN复发组比较, IgAN复发组术后2、3、5年的U-RBC计数明显增加, 术后5年的肾功能明显较差(均为P < 0.01~0.001)。移植肾病理学结果示, 与非IgAN复发组比较, IgAN复发组的细胞性新月体形成、肾小球粘连、系膜细胞增生、系膜基质增多、球性硬化、肾小球节段硬化、球性废弃和肾间质纤维化等的发生率均明显升高(均为P < 0.001)。IgAN复发组和非IgAN复发组的慢性移植肾损伤指数分别为7.7±2.3和4.6±1.4(P < 0.01)。与非IgAN复发组比较, IgAN复发组的慢性排斥反应发生率、移植肾肾小球病(不包括IgAN)和C4 d沉积阳性发生率均较高(P < 0.01~0.001)。IgAN复发组和非IgAN复发组肾移植术后1年移植肾存活率分别为93.8%和95.6%(P>0.05), 术后3年分别为86.7%和88.3%(P>0.05), 术后5年分别为51.4%和83.8%(P < 0.001)。IgAN复发组中10例(22%)患者和非IgAN复发组中9例(9%)患者发生移植肾丧失。结论  肾移植术后IgA肾病复发以无症状性镜下血尿、蛋白尿和肾功能呈进行性下降为特征, 会降低移植肾长期存活率, 提示预后不良。     

Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/UNOS database

BACKGROUND: The organ shortage has resulted in increased use of kidneys from expanded criteria donors (ECD). For ECD kidneys unsuitable for single use, dual kidney transplants (DKT) may be possible. There are limited data comparing outcomes of DKT to single kidney ECD transplants, making it unclear where DKT fits in the current allocation scheme. Our purpose was to compare outcomes of DKT and ECD transplants in the United States. METHODS: From 2000 to 2005, a total of 625 DKT, 7686 single kidney ECD, and 6,044 SCD transplants from donors aged>or=50 years were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing data. Allograft survival was the primary outcome. RESULTS: DKT comprised 4% of kidney transplants from donors aged>or=50 years. Compared to the ECD donor group, the DKT donor group was older (mean age 64.6+/-7.7 years vs. 59.9+/-6.2 years) and consisted of more African Americans (13.1% vs. 9.9%), and more diabetic donors (16.3% vs. 10.4%; P<0.001). Mean cold ischemic time was longer in DKT (22.2+/-9.7 hr), but rates of delayed graft function were lower (29.3%) compared to ECD transplants (33.6%, P=0.03). Three-year overall graft survival was 79.8% for DKT and 78.3% for ECD transplants. CONCLUSION: DKT were infrequent and had outcomes comparable to ECD transplants, despite the use of organs from higher risk donors. With a more upfront approach to DKT by offering this option to patients at the time of wait-listing as part of an ECD algorithm, we may be able to further optimize outcomes of DKT and minimize discard of potential organs.     

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.