Membranous nephropathy in the kidney allograft

Membranous nephropathy (MN) may occur in a kidney transplant as recurrence of the original disease (rMN) or as a de novo MN (dnMN). rMN often occurs early, within the first year, and often in a mild or subclinical fashion. Recurrence cannot be predicted by clinical features at the time of transplantation. The natural history is increasing proteinuria over time, with less chance for spontaneous remission compared to primary MN (pMN). Antiphospholipase A2 receptor (PLA2R) antibodies should be evaluated in all patients with pMN at the time of transplantation and serially. If titers persist or rise, biopsy is indicated. Irrespective of PLA2R status, any case with proteinuria reaching 1 g/day should be biopsied. No randomized controlled trials have been published regarding treatment of rMN. Observational data support use of rituximab. Given the progressive nature of rMN and lack of spontaneous remissions, a period of observation does not seem justifiable. dnMN occurs with about equal frequency as rMN and shares features of secondary MN in native kidneys. Causes include viral infections (e.g., hepatitis B or C), which should be treated. In some cases, dnMN may represent an atypical alloimmune response. The role of rituximab in dnMN is undefined.     

Tumor biology and pre‐transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre‐transplant locoregional therapy (LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty‐five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha‐fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five‐yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre‐transplant LRT did not affect post‐transplant outcomes in patients meeting Milan criteria but did result in lower three‐yr HCC recurrence (7% vs. 75%, p < 0.001) and better three‐yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre‐transplant LRT are important factors that determine the post‐transplant outcomes in patients with HCC who meet R4T3 criteria.     

Antibodies to m‐type phospholipase A2 receptor in children with idiopathic membranous nephropathy

Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m‐type phospholipase A2 receptor (PLA2R) are seen in two‐thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti‐PLA2R in paediatric IMN. We evaluated anti‐PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti‐PLA2R titer. The present report suggests that PLA2R has a contributory role in the pathogenesis of paediatric IMN.     

Clinical and virologic outcomes in high‐risk adult Epstein‐Barr virus mismatched organ transplant recipients

Epstein‐Barr virus (EBV) D+/R? organ transplant recipients are a high‐risk group for developing post‐transplant lymphoproliferative disease (PTLD). Little data are available for prevention in the adult EBV mismatched population. We conducted a retrospective study of EBV D+/R? organ transplants performed during 2002‐2014. Of the 153 patients identified, 82.4% patients received antiviral prophylaxis with valganciclovir for a median of 4.5 months (range: 0.8‐22 months) and 36.6% underwent viral load monitoring in the first post‐transplant year. EBV viremia developed in 67.2% monitored patients. In viremic patients, immunosuppression was reduced in 20/37(54.1%) in response to viremia and 17/37 (45.9%) received therapeutic dose valganciclovir. In patients with EBV viremia who received valganciclovir and/or had a reduction in immunosuppression and had sufficient viral load time points (n=31), 28 (90.3%) had a significant decline in viral load at day 14 (median log decline 0.49 (0.24‐0.64), P<.001) and at day 30 (0.87 (0.52‐1.21), P<.001). PTLD developed in 27 (15%) patients (biopsy proven=25, possible=2) at median 8 months (range: 2.4‐130) post‐transplant with the majority (81.5%) within the first year. In multivariate analysis, viral load monitoring and use of mycophenolate were associated with a lower incidence of PTLD. Antiviral prophylaxis was not associated with a lower risk of PTLD, but viral load monitoring and use of mycophenolate mofetil were protective.     

Primary endoluminal stenting of transplant renal artery stenosis from cadaver and non-heart-beating donor kidneys

This study evaluated the efficacy of primary endovascular stenting in cases of transplant renal artery stenosis (TRAS) from cadaver and non-heart-beating donor kidneys. Patients with TRAS (n = 13) from a single-centre transplant population (n = 476) were treated by primary percutaneous angioplasty and endovascular stenting. The short-term efficacy of this intervention is demonstrated in terms of serum creatinine, glomerular filtration rate (GFR) biochemical, anti-hypertensive medications and mean arterial blood pressure control. Stenting for TRAS was performed in male (n = 10) and female (n = 3) recipients. The median age at transplantation was 55 yr (range 10-67 yr). Stenting occurred at a median duration of 410 d post-transplantation (range 84-5799 d). Mean serum creatinine (pre, 247 micromol/L; post, 214 micromol/L; p = 0.002), GFR (pre, 82.6 mL/min; post, 100.9 mL/min; p < 0.001), arterial blood pressure (pre, 104 mmHg; post, 97 mmHg; p = 0.036) and the number of anti-hypertensive medications required (pre, 3.4; post, 3.0; p = 0.002) showed significant improvement after post-endovascular therapy. There were no serious complications encountered. Primary endovascular stenting of TRAS produces a significant improvement in biochemical parameters of renal graft function and in blood pressure stability, with the benefit of low patient morbidity and single arterial puncture. Primary endoluminal stenting of TRAS is a safe and effective procedure for the treatment of TRAS.     

Pre‐transplant angiotensin receptor II type 1 antibodies and risk of post‐transplant focal segmental glomerulosclerosis recurrence

Post‐kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA, we tested pre‐transplant sera of 28 patients with history of idiopathic FSGS for anti‐AT1R levels and serum soluble urokinase‐type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as controls. Twelve patients had biopsy proven post‐transplant FSGS recurrence at 1.5 months. No difference was found in the pre‐transplant suPAR levels of FSGS patients (5993 ± 2292 pg/mL) vs. PKD (7334 ± 4538 pg/mL) (p = 0.23). Serum suPAR levels in patients with FSGS recurrence (5786 ± 1899 pg/mL) vs. no FSGS recurrence (6149 ± 2598 pg/mL) (p = 0.69) were not different. Anti‐AT1R levels in patients with FSGS were 12.66 ± 11.85 U/mL vs. 8.69 ± 6.52 U/mL in PKD (p = 0.32); however, a difference was found in patients with and without FSGS recurrence 20.41 ± 14.36 U/mL 6.84 ± 4.181 U/mL, respectively (p < 0.01). Area under curve for suPAR and anti‐AT1R to predict post‐transplant FSGS recurrence was 0.51 and 0.84, respectively. Pre‐transplant anti‐AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post‐transplant FSGS recurrence.     

Role of BK virus infection in end‐stage renal disease patients waiting for kidney transplantation – viral replication dynamics from pre‐ to post‐transplant

We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre‐ to post‐transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre‐transplantation, 12 h, and three and six months post‐transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication – considered a marker of infection – was 20% in pre‐transplant patients. All pre‐transplant‐positive patients remained positive post‐transplant, whereas the majority of pre‐transplant‐negative patients remained negative. Viremia dynamics classification revealed three clusters of patients: Cluster A++, pre‐transplant‐positive patients (20%) who tested positive at least once post‐transplant; Cluster B?+, pre‐transplant‐negative patients (28%) who tested positive at least once post‐transplant; and Cluster C– –, pre‐transplant‐negative patients (52%) who remained negative throughout. These clusters presented significant differences related to the prevalence of substantially positive patients with high plasma viral load (>10³ copies/mL) in cluster A, but not in donors’ or grafts’ characteristics. We suggest that pre‐transplant viral status should be considered as an additional risk factor for post‐transplant BKV replication. Therefore, pre‐transplant BKV infection screening in kidney transplant patients should be performed for improving planning of personalized immunosuppressant schemes and specific post‐transplant surveillance.     

适合中国人的抗磷脂酶A2受体抗体临界值的界定

目的分析中国原发性膜性肾病(PMN)患者抗磷脂酶A2受体(phospholipase A2 receptor,PLA2R)抗体水平,及其与临床指标的相关性,探讨更适合中国人的诊断临界值。方法入选2018年1月至2018年8月期间北京大学人民医院所有接受肾活组织检查者为研究对象,按照原发病分为原发性膜性肾病(PMN)组(包括特发性膜性肾病及原因未明的不典型膜性肾病患者)和对照组(除PMN以外的其他病理类型,包括继发性膜性肾病患者),回顾性收集和分析患者临床及病理资料。用酶联免疫吸附法(ELISA)检测入选者血抗PLA2R抗体水平,比较两组患者血抗PLA2R抗体水平的差异。采用Spearman相关分析法分析PMN患者血抗PLA2R抗体水平与临床指标的相关性;用Logistic回归模型法分析鉴别患者发生PMN的相关因素;用ROC曲线分析诊断PMN的优化临界值。结果共354例患者入选本研究,其中PMN组114例,对照组240例。PMN组年龄(51.7±14.1)岁,男/女比例为2.2∶1。PMN组患者血抗PLA2R抗体水平显著高于对照组[16.87(1.88,57.26)RU/ml比1.43(1.20,1.62)RU/ml,P<0.001]。PMN患者血抗PLA2R抗体水平与24 h尿蛋白量(r=0.278,P=0.003)、尿红细胞(r=0.190,P=0.043)呈正相关,与血白蛋白(r=-0.149,P=0.114)、血肌酐(r=0.136,P=0.149)无相关。ROC曲线分析结果显示,当设定抗PLA2R抗体的临界值为2.28 RU/ml时,鉴别PMN与其他病理类型的灵敏度为69.3%(95%CI 60.3%~77.0%),特异度92.9%(95%CI 89.0%~95.5%),曲线下面积0.859(95%CI 0.813~0.905,明显优于临界值为20.00 RU/ml(灵敏度46.5%,特异度97.5%)及14.00 RU/ml(灵敏度53.5%,特异度97.1%)。结论下调PMN主要致病抗体抗PLA2R抗体临界值至2.28 RU/ml,可提高鉴别诊断PMN与其他病理类型的灵敏度而不显著降低特异度。     

Massive ascites after living donor liver transplantation with a right lobe graft larger than 0.8% of the recipient’s body weight

Shirouzu Y, Ohya Y, Suda H, Asonuma K, Inomata Y. Massive ascites after living donor liver transplantation with a right lobe graft larger than 0.8% of the recipient’s body weight.
Clin Transplant 2010: 24: 520–527.
© 2009 John Wiley & Sons A/S. Abstract: Background: There are only limited data on post‐transplant ascites unrelated to small‐sized grafts in living donor liver transplantation (LDLT). Methods: The subjects were 59 adult patients who had received right lobe LDLT with a graft weight‐to‐recipient weight ratio (GRWR) > 0.8%. Patients were divided into either Group 1 (n = 14, massive ascites, defined as the production of ascitic fluid > 1000 mL/d that lasted longer than 14 d after LDLT) or Group 2 (n = 45, no development of massive ascites). Patients were followed for a median period of 3.0 yr (range, 0.5–7.5 yr). Results: Group 1 had both higher Model for End‐Stage Liver Disease score and Child‐Pugh score than Group 2. Portal venous flow volume just after reperfusion was significantly greater in Group 1 than Group 2 (307.8 ± 268.8 vs. 176.2 ± 75.0 mL/min/100 g graft weight, respectively; p < 0.05). Post‐transplant infectious complications including ascites infection developed more frequently within the first post‐transplant month in Group 1. Massive ascites was significantly associated with early graft loss (p < 0.05). Conclusion: Post‐transplant massive ascites associated with portal over‐perfusion into the graft liver can develop in patients with a GRWR over 0.8%. Recipients with post‐transplant massive ascites require careful management to prevent infection.     

Long-term outcome in 42 pediatric liver transplant patients with alpha 1-antitrypsin deficiency: a single-center experience

Hughes MG Jr, Khan KM, Gruessner AC, Sharp H, Hill M, Jie T, Kandaswamy R, Humar A, Payne WD, Gruessner RWG. Long‐term outcome in 42 pediatric liver transplant patients with alpha 1‐antitrypsin deficiency: a single‐center experience.
Clin Transplant 2011: 25: 731–736. © 2010 John Wiley & Sons A/S. Abstract: Introduction: We examined the long‐term outcome of transplantation for alpha 1‐antitrypsin deficiency (A1ATD). Method: Data were reviewed on 42 transplants in 35 children with A1ATD over 42 yr and compared with 129 transplants in 116 children with biliary atresia (BA). Results: Over 50% of patients were followed up for >10 yr. A1ATD were older than BA at transplantation, median age, 6.0 vs. 1.0 yr (p < 0.0001), and transplanted earlier in the course of liver failure (total bilirubin, 2.7 mg/dL [1.4–6.9] vs. 9.7 mg/dL [2.9–15.4], p = 0.005). Patient survival was greater in A1ATD than BA: one‐yr post‐transplant, 82.7% vs. 67.9%; five yr, 76.5% vs. 60.2%; and 10 yr, 76.5% vs. 55.9% (p = 0.03). Death‐censored graft survival was similar: one‐yr post‐transplant, 68.4% vs. 66.2%; five yr, 68.4% vs. 55.8%; and 10 yr, 68.4% vs. 52.5% (p = 0.2). Deaths were from infection, hemorrhage, and graft failure <6 months post‐transplant. Patient survival improved at five yr from 33.3% pre‐cyclosporine (CSA) (1969–1984) (n = 6) to 76.5% in the CSA era (1985–1994) (n = 17) and 100% with tacrolimus (1995–2006) (n = 12) (p = 0.007). Conclusions: The age at transplantation and the degree of liver dysfunction were related to the differences in graft and patient survival between A1AT and BA.     

Renal function in type 1 diabetics one year after successful pancreas transplantation

Chatzizacharias NA, Vaidya A, Sinha S, Smith R, Jones G, Sharples E, Friend PJ. Renal function in type 1 diabetics one year after successful pancreas transplantation.
Clin Transplant 2011: 25: E509–E515. © 2011 John Wiley & Sons A/S. Abstract: The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single‐unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty‐nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post‐transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m²) and low (≤45 mL/min/1.73 m²) pre‐transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post‐transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post‐transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre‐existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.     

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.     

Obstetric and long‐term kidney outcomes in renal transplant recipients: a 40‐yr single‐center study

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case?cohort study was performed identifying 83 pairs of pregnant and non‐pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre‐eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre‐pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non‐pregnant controls and a pregnancy was not associated with poorer 10‐yr transplant or 20‐yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long‐term transplant function.     

The significance of pre‐operative coronary interventions on outcome after pancreas transplantation

Pancreas transplant candidates are at very high risk of coronary vascular disease. We hypothesized that the requirement for pre‐operative coronary intervention (PCI) may be associated with an adverse impact on short‐ and long‐term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n = 48) and those who had not (n = 318). In 48% (23/48) of instances, the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6 yr vs. 41.9 yr, respectively, p < 0.0001). Although not statistically significant, there was a higher rate of post‐operative major cardiovascular events (MCVE) in the PCI group (10.4%) compared with those not undergoing PCI (4.7%) (RR [95% CI]: 2.0 [0.90–4.5]; p = 0.17). In the long term, there were no differences in the rate of death with graft function (p = 0.77) or rejection (p = 0.17). There were no statistically significant differences between the groups with respect to patient (p = 0.54), kidney (p = 0.76), or pancreas (p = 0.63) graft survival. PCI is not a risk factor for short‐term perioperative events, and long‐term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself, should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk.     

Risk factors associated with moderate‐to‐severe renal dysfunction among heart transplant patients: results from the CAPRI study

Delgado JF, Crespo‐Leiro MG, Gómez‐Sánchez MA, Paniagua MJ, González‐Vílchez F, Vázquez de Prada JA, Fernández‐Yáñez J, Pascual D, Almenar L, Martínez‐Dolz L, Díaz B, Roig E, Segovia J, Arizón JM, Garrido I, Blasco T, López J, Brossa V, Manito N, Muñiz J. Risk factors associated with moderate‐to‐severe renal dysfunction among heart transplant patients: results from the CAPRI study.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01249.x
© 2010 John Wiley & Sons A/S. Abstract: The longer survival of patients with heart transplantation (HT) favors calcineurin inhibitor–related chronic kidney disease (CKD). It behoves to identify risk factors. At 14 Spanish centers, data on 1062 adult patients with HT (age 59.2 ± 12.3 yr, 82.5% men) were collected at routine follow‐up examinations. Glomerular filtration rate, GFR, was estimated using the four‐variable MDRD equation, and moderate‐or‐severe renal dysfunction (MSRD) was defined as K/DOQI stage 3 CKD or worse. Time since transplant ranged from one month to 22 yr (mean 6.7 yr). At assessment, 26.6% of patients were diabetic and 63.9% hypertensive; 53.9% were taking cyclosporine and 33.1% tacrolimus; and 61.4% had MSRD. Among patients on cyclosporine or tacrolimus at assessment, multivariate logistic regression identified male sex (OR 0.44), pre‐ and post‐HT creatinine (2.73 and 3.13 per mg/dL), age at transplant (1.06 per yr), time since transplant (1.05 per yr), and tacrolimus (0.65) as independent positive or negative predictors of MSRD. It is concluded that female sex, pre‐ and one‐month post‐HT serum creatinine, age at transplant, time since transplant, and immunosuppression with cyclosporine rather than tacrolimus may all be risk factors for development of CKD ≥ stage 3 by patients with HT.     

Thoracic muscle cross‐sectional area is associated with hospital length of stay post lung transplantation: a retrospective cohort study

Low muscle mass is common in lung transplant (LTx) candidates; however, the clinical implications have not been well described. The study aims were to compare skeletal muscle mass in LTx candidates with controls using thoracic muscle cross‐sectional area (CSA) from computed tomography and assess the association with pre‐ and post‐transplant clinical outcomes. This was a retrospective, single‐center cohort study of 527 LTx candidates [median age: 55 IQR (42–62) years; 54% male]. Thoracic muscle CSA was compared to an age‐ and sex‐matched control group. Associations between muscle CSA and pre‐transplant six‐minute walk distance (6MWD), health‐related quality of life (HRQL), delisting/mortality, and post‐transplant hospital outcomes and one‐year mortality were evaluated using multivariable regression analysis. Muscle CSA for LTx candidates was about 10% lower than controls (n = 38). Muscle CSA was associated with pre‐transplant 6MWD, but not HRQL, delisting or pre‐ or post‐transplant mortality. Muscle CSA (per 10 cm² difference) was associated with shorter hospital stay [0.7 median days 95% CI (0.2–1.3)], independent of 6MWD. In conclusion, thoracic muscle CSA is a simple, readily available estimate of skeletal muscle mass predictive of hospital length of stay, but further study is needed to evaluate the relative contribution of muscle mass versus functional deficits in LTx candidates.     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.     

Late conversion of tacrolimus to sirolimus in a prednisone‐free immunosuppression regimen in renal transplant patients

Chhabra D, Grafals M, Cabral B, Leventhal J, Parker M, Gallon L. Late conversion of tacrolimus to sirolimus in a prednisone‐free immunosuppression regimen in renal transplant patients.
Clin Transplant 2009: DOI: 10.1111/j.1399‐0012.2009.01047.x
© 2009 John Wiley & Sons A/S. Abstract: Background: One of the most important causes of graft loss is chronic nephrotoxicity from calcineurin inhibitors. The aim of this study was to evaluate the feasibility and to assess the impact on rejection risk, graft loss and renal allograft function of converting patients from tacrolimus (Tac) to sirolimus (SRL) at one yr post‐transplantation (Tx) using a prednisone‐free immunosuppressive regimen. Methods: Two hundred fifty‐five kidney transplant patients were induced with Alemtuzumab and maintained on a steroid‐free regimen with Tac and mycophenolate mofetil. Thirty‐seven stable patients (14%) were converted from Tac to SRL at one yr post‐Tx. Results: The two groups were demographically similar. Mean post‐tx follow‐up was 2.8 ± 0.2 yr. Patient and graft survival were not statistically different. There was no significant difference in acute rejection episodes between the SRL and Tac groups (21% vs. 15%, p = 0.2). Calculated glomerular filtration rate (GFR), in the SRL group at 2.8 yr post‐tx, was 69 ± 13 mL/min from the one month post‐tx GFR of 53 ± 19 and 59 ± 23 mL/min from the one month post‐tx GFR of 56 ± 21 mL/min in the Tac group. Conclusions: Using a prednisone‐free regimen, the conversion of Tac to SRL at one yr post‐Tx was not associated with an increased risk of acute rejection or graft loss.     

CD30, a marker to detect the high‐risk kidney transplant recipients

Abstract: Background: Sensitization of potential renal transplant recipients may impact the selection of donors and the outcome of transplant. Another element of the potential kidney transplant recipient immune system that provides useful information regarding the transplant outcome is the immunologic CD30 molecule. Methods and results: This study shows a significant correlation between the pre‐transplant high level of soluble CD30 and increased incidence of post‐transplant infection. Only 7/34 (20.6%) of the patients who had a low level of sCD30 (<90 U/mL) developed infection as compared with the 25/58 (43.1%) of the patients who had a high level (>90 U/mL) of sCD30 (p < 0.04). Higher level of sCD30 pre‐transplant was also correlated with the increased level of serum creatinine (p < 0.05) and pre‐transplant malignancy (p < 0.04). A significant higher level of sCD30 was also noted among females (74%), as compared with males (50%) with p < 0.03. In addition, significant effect of 3–6 human leukocyte antigen (HLA) mismatches on rejection was seen. Conclusions: These results show that higher pre‐transplant immunologic reactivity measured by sCD30 level was associated with post‐transplant outcome. The high level of sCD30 among females may indicate an active immunologic status, perhaps because of previous pregnancies.     

Slope of changes in renal function in the first year post‐transplantation and one‐yr estimated glomerular filtration rate together predict long‐term renal allograft survival

Wu J, Li H, Huang H, Wang R, Wang Y, He Q, Chen J. Slope of changes in renal function in the first year post‐transplantation and one‐yr estimated glomerular filtration rate together predict long‐term renal allograft survival.
Clin Transplant 2010: 24: 862–868. © 2010 John Wiley & Sons A/S. Abstract: Background: Few studies have examined the predictive value of the slope of changes in renal function in the first year post‐transplantation when combined with one‐yr estimated glomerular filtration rate (eGFR). Methods: We reviewed 1062 recipients who underwent renal transplantations from deceased donors between January 1992 and June 2003. Recipients were stratified into four groups: (a) one‐yr eGFR <45 mL/min and slope ?2 mL/min/month, (c) one‐yr eGFR >45 mL/min and slope 45 mL/min and slope >?2 mL/min/month. Survival was assessed by Kaplan‐Meier analysis and the significance of variables with the Cox proportional hazard model. Results: Both the slopes of eGFR changes and one‐yr eGFR were significantly associated with survival in univariate analysis. The hazard ratio of graft loss was 2.645 when one‐yr eGFR was <45 mL/min. The risk increased to 7.438 when this was combined with slope ?2 mL/min/month had five‐ and 10‐yr graft survival rates similar to those with one‐yr eGFR >45 mL/min. Conclusions: Long‐term graft survival was related to one‐yr eGFR and the slope of changes in eGFR within the first year. Their combination provides a more discriminatory predictive value.