Cyclosporine versus Tacrolimus Treated Liver Transplant Recipients with Chronic Hepatitis C: Outcomes Analysis of the UNOS/OPTN Database

Recurrent hepatitis C virus (HCV) remains a problematic cause of morbidity and mortality for liver transplant patients. Immunosuppression including calcineurin‐inhibitors has been implicated in the acceleration of recurrent HCV. Recent studies suggest that outcomes may be better with cyclosporine (CSA‐ME) compared to tacrolimus (TAC), but the data are inconclusive. We retrospectively analyzed data received from the United Network for Organ Sharing on 8809 chronic HCV liver transplant recipients receiving either cyclosporine microemulsion (CSA‐ME) or tacrolimus (TAC) as maintenance immunosuppression prior to discharge. We analyzed patient death, graft failure, failure due recurrent disease and acute cellular rejection (ACR) for CSA‐ME versus TAC treated patients. Three‐year unadjusted patient and graft survival rates were 76.8% and 71.5%, respectively, in the CSA‐ME group versus 79.9% and 75.0% in the TAC group. Propensity score‐adjusted results suggest CSA‐ME treated patients are at increased risk of patient death and graft failure [Hazards ratio (HR) = 1.17; 95% CI = 1.01–1.36 and HR = 1.19; 95% CI = 1.04–1.35, respectively] and biopsy‐confirmed AR (HR = 2.03; 95% CI = 1.54–2.67) compared to TAC treated patients. These results provide evidence to reconsider the targeted administration of CSA‐ME to HCV‐infected liver transplant recipients.     

Early Ultrastructural Changes in Renal Allografts: Correlation With Antibody‐Mediated Rejection and Transplant Glomerulopathy

Transplant glomerulopathy (TG) is associated with antibody‐mediated renal allograft rejection (AMR) and reduced graft survival. Histologically, TG is typically seen >1 year posttransplantation. However, ultrastructural changes including glomerular endothelial swelling, subendothelial widening and early glomerular basement membrane duplication are associated with development of TG but appear much earlier. We examined the specificity of these changes for AMR, and whether these are inevitably associated with development of TG. Of 98 for cause renal allograft biopsies carried out within 3 months of transplantation with available serologic data, 17 showed C4d‐positive AMR and 16 had histologic changes of AMR and donor‐specific antibodies (DSA), but no C4d. All three ultrastructural changes were seen in 11 of 17 biopsies with C4d‐positive AMR, 8 of 16 with histologic changes of AMR and DSA but no C4d, and 0 of 65 without histologic changes of AMR and/or DSA (p < 0.0001 for both of the former groups vs. the latter). Twenty patients with positive DSA (18 with histologic changes of AMR and 11 C4d‐positive) had ≥1 follow‐up biopsy; eight developed overt TG 3.5–30 months posttransplantation. Among the 18 patients with DSA and histologic changes of AMR, 11 C4d‐positive and 7 C4d‐negative, treatment for AMR after the early biopsy significantly reduced subsequent development of overt TG.     

Chronic Kidney Disease After Liver Transplantation for Acute Liver Failure Is Not Associated With Perioperative Renal Dysfunction

Renal dysfunction of acute liver failure (ALF) may have distinct pathophysiological mechanisms to hepatorenal syndrome of cirrhosis. Yet, the impact of perioperative renal function on posttransplant renal outcomes in ALF patients specifically has not been established. The aims of this study were ( 1 ) to describe the incidence and risk factors for chronic renal dysfunction following liver transplantation for ALF and ( 2 ) to compare renal outcomes with age–sex‐matched patients transplanted for chronic liver disease. This was a single‐center study of 101 patients transplanted for ALF. Fifty‐three‐and‐a‐half percent had pretransplant acute kidney injury and 64.9% required perioperative renal replacement therapy. After transplantation the 5‐year cumulative incidence of chronic kidney disease (eGFR <60 mL/min/1.73 m²) was 41.5%. There was no association between perioperative acute kidney injury (p = 0.288) or renal replacement therapy (p = 0.134) and chronic kidney disease. Instead, the independent predictors of chronic kidney disease were older age (p = 0.019), female gender (p = 0.049), hypertension (p = 0.031), cyclosporine (p = 0.027) and nonacetaminophen‐induced ALF (p = 0.039). Despite marked differences in the perioperative clinical condition and survival of patients transplanted for ALF and chronic liver disease, renal outcomes were the same. In conclusion, in patients transplanted for ALF the severity of perioperative renal injury does not predict posttransplant chronic renal dysfunction.     

KCNQ1 gene variants and risk of new-onset diabetes in tacrolimus-treated renal-transplanted patients

Recent genome-wide association studies identified single-nucleotide polymorphisms (SNPs) in the gene encoding the pore-forming subunit of the voltage-gated K+ channel (KCNQ1) as a risk factor for type 2 diabetes. Tacrolimus (Tac) increased the risk of new-onset diabetes after transplantation (NODAT). The aim of this study was to analyze the association between KCNQ1 variants and the risk for NODAT in kidney-transplanted patients who received Tac as primary immunosuppressor. We genotyped three common KCNQ1 SNPs in 145 Spanish patients who received a cadaveric kidney graft and developed NODAT in the first-year post-transplant (the NODAT group), and 260 patients who remained non-diabetics (non-NODAT). In addition, we searched for DNA variants in the whole KCNQ1 coding exons in these patients. SNP rs2237895 (genotype CC) was associated with an increased risk for NODAT in our population (p = 0.008; OR = 1.83, 95% CI = 1.14-2.93), independently of other risk factors as body mass index, recipient age, or tacrolimus dosage. Other KCNQ1 variants were not associated with NODAT in our patients. Our work supported a role for KCNQ1 gene variants as determinants of the risk of developing NODAT among Tac-treated patients.     

Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation. Post‐transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre‐transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre‐transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy.

OBJECTIVE

To analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation.

PATIENTS AND METHODS

A retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken.

RESULTS

There were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43–65). Twenty patients were in the pre‐transplant nephrectomy group, 12 in the post‐transplant group, and three underwent the sandwich technique. Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety). Seven individuals in the pre‐transplant group and three in the post‐transplant group required critical care admission after nephrectomy. Transient renal graft dysfunction occurred in two post‐transplant bilateral nephrectomy patients. Two patients in the bilateral nephrectomy pre‐transplant group and one in the bilateral nephrectomy post‐transplant group died in the immediate post‐operative period. No complications were noted in the sandwich technique group.

CONCLUSION

Native nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre‐transplant group. Post‐transplant unilateral nephrectomy appears to be the safest approach with fewest complications.     

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.     

五酯片对口服他克莫司肾移植受者的影响

目的：探讨肾移植受者术后联用五酯片的安全性、有效性和经济性。方法：自2007年6月～至2009年6月该中心施行同种异体尸肾移植并采用FK506＋吗替麦考酚酯（MMF）＋醋酸泼尼松（Pred）为免疫抑制方案的患者中,随机选取病例纳入治疗组,术后以FK506联合五酯片口服,另随机选取免疫抑制方案相同患者作为对照。随访期满1年后比较两组间FK506用量、移植肾功能、肝功能（ALT）、急性排斥反应（AR）发生率、肺部感染发生率。结果：两组AR及肺部感染发病率比较差异无统计学意义。两组患者每日FK506用量自服用五酯片1月后开始即差异有统计学意义,治疗组服用FK506剂量比对照组低。但两组术后1月、3月、6月及1年复查FK506血药浓度、移植肾功能、肝功能损害发病率差异均无统计学意义。结论：肾移植术后1年以内,五酯片的应用在FK506用量大幅减少的情况下使治疗组取得了与对照组相同的移植效果,肾移植术后联用五酯片有望成为安全、有效的途径来减少社会和患者的经济负担。     

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients

The aim of this study was to evaluate the utility of donor-specific antibodies (DSA) and flow cytometry crossmatch (FCCM) as tools for predicting antibody-mediated rejection (AMR) in desensitized kidney recipients. Sera from 44 patients with DSA at the time of transplant were reviewed. Strength of DSA was determined by single antigen Luminex bead assay and expressed as mean fluorescence intensity (MFI). T- and B-cell FCCM results were expressed as mean channel shift (MCS). AMR was diagnosed by C4d deposition on biopsy. Incidence of early AMR was 31%. Significant differences in the number of DSAs (p = 0.0002), cumulative median MFI in DSA class I (p = 0.0004), and total (class I + class II) DSA (p < 0.0001) were found in patients with and without AMR. No significant difference was seen in MCS of T and B FCCM (p = 0.095 and p = 0.307, respectively). The three-yr graft survival in desensitized patients with DSA having total MFI < 9500 was 100% compared to 76% with those having total MFI > 9500 (p = 0.022). Desensitized kidney transplant recipients having higher levels of class I and total DSA MFI are at high risk for AMR and poor graft survival. Recipient DSA MFI appears to be a more reliable predictor of AMR than MCS of FCCM.     

Transplantation of solid organs procured from influenza A H1N1 infected donors

Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir.     

Do multiple renal arteries in the remnant kidney have a negative influence on kidney donors after kidney donation?

Aim: To investigate whether the presence of multiple renal arteries in the remnant kidney has implications for lower renal function or increased incidence of hypertension. Methods: We reviewed the intraoperative and follow‐up data of 101 live kidney donors who underwent nephrectomies at our institution. Sixty‐nine donors (68.3%) had single artery in the remnant kidney (Group A), while 32 donors (31.7%) had multiple renal arteries in the remnant kidney (Group B). We compared the demographic and intraoperative data between the two groups. The follow‐up data of donors in each group were divided into three subgroups based on the length of the follow‐up period (12–24 months, 24–48 months and ≥48 months). Subgroups were created based on blood pressure and serum creatinine level. The δblood pressure (follow‐up blood pressure minus preoperative blood pressure) and δserum creatinine (follow‐up serum creatinine minus preoperative serum creatinine) in each subgroup in Group A were compared with the counterparts in Group B. Results: Renal arterial stenosis and calcification of renal arterial wall were not observed in all donors. There were no significant differences in the intraoperative characteristics (e.g. age, body mass index, operative duration and estimated blood loss) between the two groups. In addition, the blood pressure and serum creatinine level among subgroups within each group were similar. Furthermore, significant differences in δblood pressure and δserum creatinine were not observed between subgroups within the same follow‐up period. Recipient survival rate and serum creatinine level were similar and acceptable in both groups. Conclusions: The presence of multiple renal arteries in the remnant kidney does not have additional negative influence on kidney donors after kidney donation.