Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism

Heme oxygenase-1 (HO-1) has a microsatellite polymorphism based on the number of guanosine-thymidine nucleotide repeats (GT) repeats that regulates expression levels and could have an impact on organ survival post-injury. We correlated HO-1 polymorphism with renal graft function. The HO-1 gene was sequenced (N = 181), and the allelic repeats were divided into subclasses: short repeats (S) (<27 repeats) and long repeats (L) (>/=27 repeats). A total of 47.5% of the donors carried the S allele. The allograft function was statistically improved six months, two and three yr after transplantation in patients receiving kidneys from donors with an S allele. For the recipients carrying the S allele (50.3%), the allograft function was also better throughout the follow-up, but reached statistical significance only three yr after transplantation (p = 0.04). Considering only those patients who had chronic allograft nephropathy (CAN; 74 of 181), allograft function was also better in donors and in recipients carrying the S allele, two and three yr after transplantation (p = 0.03). Recipients of kidney transplantation from donors carrying the S allele presented better function even in the presence of CAN.     

Acute kidney injury as defined by the RIFLE criteria is a risk factor for kidney transplant graft failure

Acute kidney injury (AKI) is not recognized as a major complication at the maintenance phase after kidney transplantation (KTx). Moreover, it is not clear whether the onset of AKI leads to graft failure. We examined the incidence of AKI that developed three months or later after KTx at our institute. We examined whether the incidence of AKI defined by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage kidney disease criteria associates with graft failure by matched-pair Cox regression analysis. A total of 289 patients were available for the final analysis. The overall incidence of AKI was 20.4%, and the common etiology of AKI was bacterial infectious diseases. The group that developed AKI had significantly lower graft survival than non-AKI group independently of acute rejection. AKI Risk represented a high risk for graft failure and AKI Injury/Failure represented a higher risk for graft failure. The analysis by the AKIN classification yielded the similar results. These results indicate that AKI is a relatively common complication of KTx and represents the major risk for graft failure. We should make every effort in the prevention and early detection to avoid the occurrence of AKI and the subsequent graft failure after KTx.     

灌洗量对移植用犬肾的影响

我们以３０条大为研究对象，肾脏切除后分组用不同量的保存液进行道洗，并设不灌洗一组，保存２４小时后自体移植，观察恢复血而后１小时菊粉清除率（Ｃｉｎ），肾小管相对钠重吸收率（ＦＲｎａ）等早期肾功能及术后血肌酐（Ｃｒ）恢复情况。结果各项指标以不灌洗组及灌洗３ｍｌ／ｇ～４ｍｌ／ｇ组为佳，并从组织学角度进一步证实了灌洗损伤的存在和形成机制。     

Autosomal dominant polycystic kidney disease: risk factor for nonmelanoma skin cancer following kidney transplantation

Nonmelanoma skin cancers (NMSC) are the most common malignant tumors following solid organ transplantation. Risk factors for NMSC mainly include immunosuppression, age, sun exposure and patient phototype. Recent findings have suggested that autosomal dominant polycystic kidney disease (ADPKD) may increase the risk of developing NMSC. We performed a monocenter retrospective study including all kidney recipients between 1985 and 2006 (n = 1019). We studied the incidence of NMSC, solid cancers and post‐transplantation lymphoproliferative disease (PTLD), and analyzed the following parameters: age, gender, phototype, time on dialysis, graft rank, immunosuppressive regimen, history of cancer and kidney disease (ADPKD versus others). Median follow‐up was 5.5 years (range: 0.02–20.6; 79 838 patient‐years). The cumulated incidence of NMSC 10 years after transplantation was 12.7% (9.3% for solid cancers and 3.5% for PTLD). Autosomal dominant polycystic kidney disease and age were risk factors for NMSC (HR 2.63; P < 0.0001 and HR 2.21; P < 0.001, respectively) using univariate analysis. The association between ADPKD and NMSC remained significant after adjustments for age, gender and phototype using multivariate analysis (HR 1.71; P = 0.0145) and for immunosuppressive regimens (P < 0.0001). Autosomal dominant polycystic kidney disease was not a risk factor for the occurrence of solid cancers after transplantation (HR 0.96; P = 0.89). Our findings suggest that ADPKD is an independent risk factor for developing NMSC after kidney transplantation.     

Pulmonary hypertension is not a risk factor for grade 3 primary graft dysfunction after lung transplantation

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single‐center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1) <25 mm Hg, (2) 25‐34 mm Hg and (3) ≥35 mm Hg. Forty‐seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%‐CI 8‐23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion >1000 mL during surgery (OR: 5.25, P = .005), the need for intra‐operative cardio‐pulmonary bypass (CPB) or extra‐corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein‐cholesterol (HDL‐C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL‐C (OR 0.10, P = .016) was associated with PGD3 based on our single‐center cohort data analysis.     

Elevated calcium phosphate product after renal transplantation is a risk factor for graft failure

BACKGROUND: Abnormal mineral metabolism is not uncommon after renal transplant (TXP). In dialysis patients, elevated serum phosphorous (P), calcium (Ca), CaP product, and parathyroid hormone (PTH) are associated with increased morbidity and mortality. The effect of these abnormalities on recipient and graft survival after renal transplantation is unknown. METHODS: We retrospectively analyzed 422 kidney-only transplants performed between June 1996 and June 2003. Cases with graft or recipient survival less than three months, pre-TXP parathyroidectomy (PTX), cinacalcet therapy and incomplete records were excluded, leaving 303 cases for analysis using Cox models that included post-TXP PTX, levels of albumin-adjusted Ca(Ca(adj)), P, Ca(adj)P product and PTH. RESULTS: There was an 11-25% prevalence of abnormal serum Ca(adj), P or Ca(adj)P product within the first year post-TXP. At least 24% of recipients not undergoing PTX with an equation estimated GFR of 40-60 mL/min had PTH levels >130 pg/mL at one yr post-TXP. This is above levels recommended by the U.S National Kidney Foundation kidney disease quality initiative for patients with stages I-IV chronic kidney disease. Adjusted Ca > 10.5 mg/dL at three months post-TXP was an independent risk for recipient death (OR 3.0; 95% CI: 1.2-7.4). A Ca(adj)P product >35 mg(2)/dL(2) at six months (OR 4.0; 95% CI: 1.2-13.1), and Ca >10.5 mg/dL at 12 months post-TXP (OR 4.0; 95% CI: 1.2-14) were independent risks for death-censored graft loss. Twenty-two recipients underwent PTX for severe hyperparathyroidism. CONCLUSION: Abnormalities of mineral metabolism are common early after renal TXP. An elevated serum Ca(adj) at three months post-TXP increases the risk for recipient death, while an elevated Ca(adj)P and Ca(adj) later in the first post-TXP year increases the risk of long-term death-censored graft loss.     

Former smoking is a risk factor for chronic kidney disease after lung transplantation

Chronic kidney disease (CKD) is a common complication after lung transplantation (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking cessation for >6 months is required for LTx enlistment. However, the impact of smoking history on CKD development after LTx remains unclear. We investigated the effect of former smoking on CKD and mortality after LTx. CKD was based on glomerular filtration rate (GFR) ((125) I-iothalamate measurements). GFR was measured before and repeatedly after LTx. One hundred thirty-four patients never smoked and 192 patients previously smoked for a median of 17.5 pack years. At 5 years after LTx, overall cumulative incidences of CKD-III, CKD-IV and death were 68.5%, 16.3% and 34.6%, respectively. Compared to never smokers, former smokers had a higher risk for CKD-III (hazard ratio [HR] 95% confidence interval [95%CI]= 1.69 [1.27-2.24]) and IV (HR = 1.90 [1.11-3.27]), but not for mortality (HR = 0.99 [0.71-1.38]). Adjustment for potential confounders did not change results. Thus, despite cessation, smoking history remained a risk factor for CKD in LTx recipients. Considering the increasing acceptance for LTx of older recipients with lower baseline renal function and an extensive smoking history, our data suggest that the problem of post-LTx CKD may increase in the future.     

The significance of bile secretion after the transplantation of long-preserved livers in the rat

Although one of the simplest indicators for predicting liver viability is bile secretion, it has never been proven whether it could be a good index for the viability of grafts in liver transplantation after cold ischemia. The present study, conducted on male Wistar rats, was undertaken to determine whether bile secretion reflects the viability of livers which have been preserved long-term. Livers were stored for up to 24 h in Euro-Collins (EC) or University of Wisconsin (UW) solution at 4°C, and transplanted orthotopically. The correlation between 1-week survival, bile flow, and the tissue adenosine triphosphate (ATP) level 4 h after transplantation was then investigated for each subgroup. The survival rates of the animals in the UW subgroups were much higher than those in the EC subgroups. In the rats transplanted with livers preserved for 6h in EC solution (EC-6), in which 100% survival was observed, both bile flow and ATP recovered sufficiently. Conversely, in the EC-12 group, in which only 10% survival was seen, restoration of bile flow, in ml/h per kg body weight, and ATP resynthesis, in pmol/g wet weight, were severely suppressed, with levels of 1.35 ± 1.05 and 0.77 ± 0.34, respectively. Moreover, in the EC-18 group, with 0% survival, neither bile flow nor ATP recovered. In the rats transplanted with livers preserved for 18h in UW solution (UW-18), bile flow and ATP, being 1.03 ± 0.56 and 1.12 ± 0.59, respectively, were much higher than those in the EC-18 group. A good correlation was found between bile flow and ATP (r = 0.84). The results of this study thus led us to conclude that bile secretion is a reliable index for predicting the viability of orthotopically transplanted grafts damaged by cold ischemia.     

Ten-year graft survival of deceased-donor kidney transplantation: a single-center experience

Background: Kidney transplantation is the treatment of choice for end-stage renal disease that restores the patients' quality of life and reduces the morbidity and mortality rates induced by renal failure and its complications. However, after transplantation the organ and patient survival rates are important issues of interest in many centers worldwide. Subjects and methods: This is a historical cohort study planned to determine the organ survival rate after kidney transplantation from deceased donor during a period of 10 years (March 1999–March 2009) in Shiraz Transplant Center, Namazi Hospital, Shiraz, Iran. We tried to clarify the probable contributory risk factors implicating in graft loss. Kaplan–Meier method was used to determine the survival rate. Log-rank test was used to compare survival curves, and Cox regression model to define the hazard ratio and for modeling of factors implicating in survival rate. Results: Mean follow-up period was 37.54 ± 28.6 months. Allograft survival rates at 1, 3, 5, and 9 years after kidney transplantation from deceased donor (calculated by Kaplan–Meier method) was found to be 93.7, 89.1, 82.1, and 80.1%, respectively. Duration of dialysis before operation and creatinine level at discharge were showed to be the most important factors influencing survival rate of renal allograft. Conclusion: Overall long-term graft survival in our cohort is satisfactory and comparable with reports from large centers in the world. Duration of dialysis before operation and creatinine level at discharge are the only independent factors that could correlate with long-term graft survival in our cohort.     

Predictive risk factors for primary graft failure requiring temporary extra-corporeal membrane oxygenation support after cardiac transplantation in adults

Objective: Primary graft failure (PGF) is a major risk factor for death after heart transplantation. We investigated the predictive risk factors for severe PGF that require extra-corporeal membrane oxygenation (ECMO) circulatory support after cardiac transplantation. Methods: Between January 2003 and December 2008, 402 adult patients underwent isolated cardiac transplantation at our institution. PGF was defined as the need for ECMO support in the immediate postoperative period. Thirty-three recipient and 37 donor variables were analyzed for the risk of PGF occurrence. Results: PGF occurred in 91 (23%) patients. Predictive risk factors for PGF occurrence were, in the recipient, being aged >60 years (odds ratio (OR) 2.11, p = 0.01) and preoperative mechanical circulatory support (MCS) (OR 2.65, p = 0.01); in the donor, they were mean norepinephrine dose (OR 2.02, p < 0.01), trauma as the cause of death (OR 2.45, p < 0.01), left-ventricle ejection fraction (LVEF) <55% (OR 2.72, p = 0.02), and the ischemic time (OR 1.01, p < 0.01). Weaning and discharge rates after ECMO support for PGF were, respectively, 60% (55/91 patients) and 46% (42/91 patients). The absence of PGF was correlated with improved long-term survival: 78% at 1 year and 71% at 5 years without PGF versus 39% at 1 year and 34% at 5 years with PGF (p < 0.01). Surviving patients treated with ECMO for PGF have similar conditional 1-year survival rates as non-PGF patients: 93% at 3 years and 91% at 5 years without PGF versus 93% at 3 years and 84% at 5 years with PGF (p = 0.46, NS). Conclusions: Occurrence of PGF is a multifactorial event that depends on both donor and recipient profiles. ECMO support is a reliable treatment for severe PGF; furthermore, surviving patients treated with ECMO have the same 1-year conditional survival rates as patients not having suffered a PGF.     

肾移植术后移植肾功能延迟恢复的处理(附14例报告)

目的探讨肾移植术后移植肾功能延迟恢复（DGF）的原因及处理措施。方法通过对发生DGF的14例患者临床表现、血肌酐、环孢素A（CsA）血浓度、彩色多普勒超声、移植肾细针穿刺吸抽细胞学检查（FNAB）等分析，诊断移植肾静脉栓塞1例，CsA中毒性肾损害2例，急性肾小管坏死（ATN）6例，急性排斥反应（AR）5例。分别予血液透析、手术探查、调整免疫抑制剂种类或剂量等处理。结果1例移植肾静脉栓塞患者行移植肾切除术；13例患者9—27d尿量增多，术后1个月复查肾功能良好。结论DGF原因包括技术性并发症、CsA中毒性肾损害、ATN、排斥反应等，应结合临床表现及辅助检查，早期诊断，及早采取血液透析、手术探查、调整免疫抑制剂种类或剂量等措施，可取得良好效果。     

Metabolic outcomes and renal function after simultaneous kidney/pancreas transplantation compared with kidney transplantation alone for type 2 diabetes mellitus patients

In this study, we aimed to compare the metabolic outcomes, renal function, and survival outcomes of simultaneous pancreas and kidney transplantation (SPK) and kidney transplantation alone (KTA) among end-stage kidney disease (ESKD) patients with type II diabetes mellitus (T2DM). Patients with ESKD and T2DM who underwent KTA (n = 85) or SPK (n = 71) in a transplant center were retrospectively reviewed. Metabolic profiles, renal function, and survival outcomes were assessed repeatedly at different follow-up time points. Propensity score procedures were applied to enhance between-group comparability. The levels of renal and metabolic outcomes between SPK and KTA over time were examined and analyzed using mixed-model repeated-measures approaches. The median follow-up period was 1.8 years. Compared with KTA, SPK resulted in superior metabolic outcomes and renal function, with lower levels of glycated hemoglobin (HbA1c; P = 0.0055), fasting blood glucose (P < 0.001), triglyceride (P = 0.015), cholesterol (P = 0.0134), low-density lipoprotein (P = 0.0161), and higher estimated glomerular filtration rate (eGFR; P < 0.001). SPK provided better metabolic outcomes and renal function. The survival outcomes of the recipients and grafts were comparable between the two groups.     

Impact of the ratio of graft kidney volume to recipient body surface area on graft function after live donor kidney transplantation

Functioning nephron mass is a determinant of the graft function of kidney transplant recipients. The graft kidney volume and its weight have been reported to be surrogates of the nephron mass. To investigate the impact of the ratios of the surrogates to recipient body surface area (BSA) and body weight on the graft function within six months post-transplantation, we measured the graft kidney volume, using computed tomography with 3-dimensional reconstruction before transplantation, and measured the graft kidney weight during surgery. Ninety-four cases of live donor kidney transplants were included in this study. The graft kidney volume/recipient BSA ratio was correlated with the glomerular filtration rate (GFR) of recipients at one and six months post-transplantation (r = 0.416, p < 0.001 and r = 0.381, p < 0.001, respectively). We found a difference in the graft function between recipients with a graft kidney volume/recipient BSA ratio of ≥90.9 mL/m(2) and those with a ratio of <90.9 mL/m(2) (p < 0.001). Multivariate analysis demonstrated that the graft kidney volume/recipient BSA ratio and donor age are independent predictors of recipient GFR at one and six months post-transplantation (p < 0.05). During living donor and recipient matching, both the potential volume of the donated kidney and the body size of recipient should be considered.     

Surgical prevention and management of vascular complications of kidney transplantation

The main surgical changes in kidney procurement, preparation, and transplantation procedures occurred 20 years ago and were undertaken despite the inability to design randomized studies. The objective was to assess the evolution of vascular complications after kidney transplantation in a setting of surgical preventive measures in a historical series. A monocentric series of 3129 consecutive kidney transplantations performed over 3 decades was reviewed. The occurrence of arterial or venous thromboses, stenoses, and aneurysms was analyzed in relation with kidney procurement, preparation, and transplantation techniques. Vascular complications occurred in 13.5% of the recipients with a mean 3‐year decrease in kidney graft function. The transplantation of a right kidney without renal vein extension, multiple renal arteries, ex vivo vascular repairs, and end‐to‐end arterial anastomoses were the unfavorable surgical vascular factors. It was possible to manage Transplant Renal Artery Stenosis (TRAS) nonsurgically in 80% of the cases. The prevention of vascular complications begins from the time of organ procurement by skilled surgeons. The aims of organ preparation are to evaluate the vascular risk, select the organs, and to simplify the anatomical constraints of vascular implantations. The three surgical steps of kidney transplantation are determinant in postoperative vascular complications and the duration of graft function.