Kidney Disease After Heart and Lung Transplantation

Kidney disease is a commonly recognized complication of heart and lung transplantation and is associated with increased morbidity and mortality. While the spectrum of kidney disease in this population is wide-ranging, studies indicate that between 3% and 10% of these patients will ultimately develop end-stage renal disease (ESRD). This review examines the risk factors for both acute and chronic kidney injury, with a particular emphasis on the role of calcineurin inhibitor-mediated nephrotoxicity in both these settings. Against the background of current National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, we have further considered and recommended appropriate strategies for long-term management of kidney disease-related manifestations in heart and lung transplant recipients. Specific aspects addressed include retarding progressive renal injury and minimizing nephrotoxicity, as well as treatment of hypertension, hyperlipidemia and anemia. Finally, for patients in this population with advanced kidney disease, renal replacement therapy options are discussed. Based on the impact of chronic kidney disease on outcomes in both heart and lung recipients, we advocate early referral to a nephrologist for patients displaying evidence of significant renal dysfunction.     

Association between Primary Graft Dysfunction among Lung,Kidney and Heart Recipients from the Same Multiorgan Donor

Even organs from an ideal donor will occasionally develop primary graft dysfunction (PGD) causing a significant morbidity and mortality after transplantation. It is likely that this situation represents subtle undetectable levels of ongoing donor organ dysfunction. The aim of this study is to investigate the association of PGD between lung, kidney and heart recipients from the one donor. From 202 multiorgan donors, contributed 231 consecutive lung transplants at the Alfred Hospital, 378 kidney and 114 heart transplants were subsequently performed at multiple centers across Australia and New Zealand. Eight hundred seventy‐five organs were used for 723 transplants. The incidence of PGD after lung, kidney and heart transplants was 20% (47/231), 24% (92/378) and 20% (23/114), respectively. In paired single organ recipients, PGD in one of the pair was a significant risk factor for the development of PGD in the other [lung: odds ratio = 5.63 (1.72–18.43), p = 0.004; kidney: odds ratio = 3.19 (1.90–5.35), p < 0.0001]. In multivariate analysis, same donor heart PGD [3.37 (1.19–9.50), p = 0.02] was an independent risk factor for lung PGD and same donor lung PGD was significant risk factor for kidney PGD [1.94 (1.01–3.73), p = 0.04], if the PGD status of the paired kidney was not known. There was a significant association for the development of PGD across different organs transplanted from the same donor.     

Lung Cancer after Heart Transplantation: Results from a Large Multicenter Registry

In this study we analyzed Spanish Post‐Heart‐Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post‐HT follow‐up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post‐HT. Incidence increased with age at HT from 149 per 100 000 person‐years among under‐45s to 542 among over‐64s; was 4.6 times greater among men than women; and was four times greater among pre‐HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age‐at‐diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan–Meier 2?year survival to 70% versus 16% among inoperable patients.     

Predicting Coronary Heart Disease after Kidney Transplantation: Patient Outcomes in Renal Transplantation (PORT) Study

Traditional risk factors do not adequately explain coronary heart disease (CHD) risk after kidney transplantation. We used a large, multicenter database to compare traditional and nontraditional CHD risk factors, and to develop risk‐prediction equations for kidney transplant patients in standard clinical practice. We retrospectively assessed risk factors for CHD (acute myocardial infarction, coronary artery revascularization or sudden death) in 23 575 adult kidney transplant patients from 14 transplant centers worldwide. The CHD cumulative incidence was 3.1%, 5.2% and 7.6%, at 1, 3 and 5 years posttransplant, respectively. In separate Cox proportional hazards analyses of CHD in the first posttransplant year (predicted at time of transplant), and predicted within 3 years after a clinic visit occurring in posttransplant years 1–5, important risk factors included pretransplant diabetes, new onset posttransplant diabetes, prior pre‐ and posttransplant cardiovascular disease events, estimated glomerular filtration rate, delayed graft function, acute rejection, age, sex, race and duration of pretransplant end‐stage kidney disease. The risk‐prediction equations performed well, with the time‐dependent c‐statistic greater than 0.75. Traditional risk factors (e.g. hypertension, dyslipidemia and cigarette smoking) added little additional predictive value. Thus, transplant‐related risk factors, particularly those linked to graft function, explain much of the variation in CHD after kidney transplantation.     

Survival Advantage of Pediatric Recipients of a First Kidney Transplant Among Children Awaiting Kidney Transplantation

The mortality rate in children with ESRD is substantially lower than the rate experienced by adults. However, the risk of death while awaiting kidney transplantation and the impact of transplantation on long‐term survival has not been well characterized in the pediatric population. We performed a longitudinal study of 5961 patients under age 19 who were placed on the kidney transplant waiting list in the United States. Of these, 5270 received their first kidney transplant between 1990 and 2003. Survival was assessed via a time‐varying nonproportional hazards model adjusted for potential confounders. Transplanted children had a lower mortality rate (13.1 deaths/1000 patient‐years) compared to patients on the waiting list (17.6 deaths/1000 patient‐years). Within the first 6 months of transplant, there was no significant excess in mortality compared to patients remaining on the waiting list (adjusted Relative Risk (aRR) = 1.01; p = 0.93). After 6 months, the risk of death was significantly lower: at 6–12 months (aRR = 0.37; p < 0.001) and at 30 months (aRR 0.26; p < 0.001). Compared to children who remain on the kidney transplant waiting list, those who receive a transplant have a long‐term survival advantage. With the potential for unmeasured bias in this observational data, the results of the analysis should be interpreted conservatively.     

Kidney Transplantation in Patients With Chronic Kidney Disease After a Previous Lung Transplantation

Background

The development of chronic kidney disease is a common complication after a lung transplantation, especially since the introduction of immunosuppressive treatments based on calcineurin inhibitors. Many of these patients reach end-stage renal disease and even need renal replacement therapy. Among the different options of renal replacement therapy, we consider kidney transplantation as a feasible option for these patients.

Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non‐Renal Solid Organ Transplant

Children who receive a non‐renal solid organ transplant may develop secondary renal failure requiring kidney transplantation. We investigated outcomes of 165 pediatric kidney transplant recipients who previously received a heart, lung, or liver transplant using data from 1988 to 2012 reported to the United Network for Organ Sharing. Patient and allograft survival were compared with 330 matched primary kidney transplant (PKT) recipients. Kidney transplantation after solid organ transplant (KASOT) recipients experienced similar allograft survival: 5‐ and 10‐year graft survival was 78% and 60% in KASOT recipients, compared to 80% and 61% in PKT recipients (p = 0.69). However, KASOT recipients demonstrated worse 10‐year patient survival (75% KASOT vs. 97% PKT, p < 0.001). Competing risks analysis indicated that KASOT recipients more often experienced graft loss due to patient death (p < 0.001), whereas allograft failure per se was more common in PKT recipients (p = 0.01). To study more recent outcomes, kidney transplants performed from 2006 to 2012 were separately investigated. Since 2006, KASOT and PKT recipients had similar 5‐year graft survival (82% KASOT vs. 83% PKT, p = 0.48), although 5‐year patient survival of KASOT recipients remained inferior (90% KASOT vs. 98% PKT, p < 0.001). We conclude that despite decreased patient survival, kidney allograft outcomes in pediatric KASOT recipients are comparable to those of PKT recipients.     

Predictors of Chronic Kidney Disease in Long-Term Survivors of Lung and Heart-Lung Transplantation

Renal insufficiency is common after non-renal organ transplants. The predictors of long-term renal outcomes are not well established. A total of 219 lung and heart-lung transplant recipients surviving more than 6 months after transplantation were studied to determine predictors of time to doubling of serum creatinine and end-stage kidney disease (ESKD) with death as a competing risk. Median follow-up was 79 months (range 9-222 months). Baseline estimated glomerular filtration rate (GFR) was 96.3+/-34.5 mL/min/1.73 m2. One hundred twenty-two recipients (55%) doubled their serum creatinine, 16 (7.3%) progressed to ESKD and 143 (65%) died. The majority of recipients who survived >6 years had a GFR<60 mL/min at both 1 and 7 years. Most of the loss of renal function occurred in the first year post-transplant. Older age at transplant, lower GFR at 1 month and cyclosporine use in the first 6 months predicted shorter time to doubling of serum creatinine when death was handled as a competing risk. Based on this prevalence data and using GFR decay and death as study endpoints, we offer sample size estimates for a prospective, interventional trial that is aimed at slowing or preventing the progression of kidney disease.     

Lung Transplantation in Japan

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October 1998 after a long period of waiting for the legalization of thoracic organ transplantation. By May 2003, a further 41 lung transplants had been performed; 28 from living donors and 13 from cadaveric donors. The indications for a lung transplant are very specialized in Japan, the most common being primary pulmonary hypertension. Although the number of lung transplants is still small, survival in Japan, at 72% after 4 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited, at less than 5 per year, LDLLT is a realistic option for properly selected candidates.     

Infectious Complications After Heart Transplantation in Chinese Recipients

Several factors appear to influence the incidence and type of infectious complications among different populations of transplant recipients. This study sought to assess the incidence and type of infection after transplantation in Chinese heart allograft recipients. A total of 130 infectious episodes occurred in 192 consecutive heart transplantation patients between June 1993 and May 2004. The median length of follow-up was 46.7+/-38.4 months. The 1-, 5- and 10-year survival rates were 81.8+/-2.8%, 63.0+/-3.8% and 45.7+/-7.7%. Infection was the leading cause of early and late deaths. Of the infectious episodes, 66 (51%) were caused by bacteria, 35 (27%) by viruses, 10 (8%) by fungi, 7 (5%) by Mycobacterium tuberculosis and 12 (9%) by other pathogens. The most common bacterial infectious episodes were caused by methicillin-resistant Staphylococcus aureus (20 of 66). The most common viral infections were varicella zoster virus infection in 12 (34%), cytomegalovirus infection in 9 (26%) and hepatitis B virus infection in 8 (23%). There was only one episode of clinical syndrome compatible to Pneumocystis jiroveci pneumonia. In conclusion, there was low incidence of Pneumocystis jiroveci pneumonia and cytomegalovirus infection, and high incidence of Mycobacterium tuberculosis infection in Chinese heart allograft recipients.     

Comparison of De Novo Cancer Incidence in Australian Liver,Heart and Lung Transplant Recipients

Population‐based evidence on the relative risk of de novo cancer in liver and cardiothoracic transplant recipients is limited. A cohort study was conducted in Australia using population‐based liver (n = 1926) and cardiothoracic (n = 2718) registries (1984–2006). Standardized incidence ratios (SIRs) were computed by cancer type, transplanted organ and recipient age. Cox regression models were used to compare cancer incidence by transplanted organ. During a median 5‐year follow‐up, the risk of any cancer in liver and cardiothoracic recipients was significantly elevated compared to the general population (n = 499; SIR = 2.62, 95%CI 2.40–2.86). An excess risk was observed for 16 cancer types, predominantly cancers with a viral etiology. The pattern of risk by cancer type was broadly similar for heart, lung and liver recipients, except for Merkel cell carcinoma (cardiothoracic only). Seventeen cancers (10 non‐Hodgkin lymphomas), were observed in 415 pediatric recipients (SIR = 23.8, 95%CI 13.8–38.0). The adjusted hazard ratio for any cancer in all recipients was higher in heart compared to liver (1.29, 95%CI 1.03–1.63) and lung compared to liver (1.65, 95%CI 1.26–2.16). Understanding the factors responsible for the higher cancer incidence in cardiothoracic compared to liver recipients has the potential to lead to targeted cancer prevention strategies in this high‐risk population.     

Extracorporeal Membrane Oxygenation Can Save Lives in Children With Heart or Lung Failure After Liver Transplantation

The risk of cardiac or lung failure after liver transplantation (LT) is significant. In rare cases, the usual intensive care techniques fail to maintain organ oxygenation with a risk of multiorgan dysfunction. Although extracorporeal membrane oxygenation (ECMO) is a difficult and risky procedure, it can be proposed as life‐saving. Four children with either acute pulmonary (three) or cardiac (one) failure after LT, and the criteria that decided the use of ECMO (level of ventilation and results, dosage of inotropic drugs, cardiac ultrasound, blood lactate) were retrospectively reported. These patients, 1–11 years old, were treated with either veno‐arterial (three) or veno‐venous (one) ECMO. Two experienced a full recovery, with 3 and 6 years of follow‐up. Two died of systemic inflammatory response syndrome (SIRS) due to ECMO, and relapse of heart failure due to the underlying disease. Although our patients' survival was only 50%, we showed that ECMO can be useful in children after LT. It should be considered before the development of irreversible multiorgan failure.     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

Voriconazole Prophylaxis in Lung Transplant Recipients

Lung transplant recipients have one of the highest rates of invasive aspergillosis (IA) in solid organ transplantation. We used a single center, nonrandomized, retrospective, sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole (n = 65) or targeted prophylaxis (n = 30) with itraconazole ± inhaled amphotericin in patients at high risk (pre- or posttransplant Aspergillus colonization [except Aspergillus niger ]). The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis (1.5% vs. 23%; p = 0.001). Twenty-nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole. A threefold or higher increase in liver enzymes was noted in 37–60% of patients receiving voriconazole prophylaxis as compared to 15–41% of patients in the targeted prophylaxis cohort. Fourteen percent in the voriconazole group as compared to 8% in the targeted prophylaxis group had to discontinue antifungal medications due to side effects. Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients. Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.     

儿童DCD供肾成人单肾移植与标准DCD供肾移植临床疗效比较研究

目的比较儿童DCD供肾成人单肾移植与标准DCD供肾移植(成人供肾成人单肾移植)的临床疗效。方法回顾性分析本院2011年11月至2014年4月完成的97例DCD供肾移植供受者的临床资料。根据供者年龄将其分为儿童DCD供肾成人单肾移植组(SPKT组,3岁年龄18岁,20例)和标准DCD供肾移植组(SCDKT组,年龄≥18岁,73例),比较两组供受者一般情况、受者术后不同时间点血肌酐水平、各种并发症的发生率及移植肾和人的1年存活率。结果 SPKT组供者年龄、体重、移植肾长度显著小于SCDKT组,差异具有统计学意义(P0.01);SPKT组受者术后1年内蛋白尿发生率显著高于SCDKT组(P0.01);两组受者移植肾和人的1年存活率比较无统计学差异(P0.05);供受者其它指标比较均无统计学差异(P0.05)。结论与标准DCD供肾移植相比,尽管蛋白尿发生率较高,但儿童DCD供肾成人单肾移植近期临床效果良好,远期效果有待进一步研究。     

Heart and Lung Transplantation in the United States, 1997–2006

This article highlights trends in heart and lung transplantation between 1997 and 2006, drawing on data from the OPTN and SRTR. The total number of candidates actively awaiting heart transplantation declined by 45% over the last decade, dropping from 2414 patients in 1997 to 1327 patients in 2006. The overall death rates among patients awaiting heart transplantation declined over the same period. The distribution of recipients among the different status groups at the time of heart transplantation changed little between the inception of the new classification system in 1999 and 2005. Deaths in the first year after heart transplantation have steadily decreased. At the end of 2006, 2885 candidates were awaiting a lung transplant, up 10% from the 1997 count. The median time-to-transplant for listed patients decreased by 87% over the decade, dropping from 1053 days in 1997 to 132 days in 2006. Selection for listing and transplantation has shifted toward more urgent patients since the May 2005 implementation of a new lung allocation system based on survival benefit and urgency rather than waiting time. Only 31 heart-lung transplants were performed in 2006, down from a high of 62 in 1997.     

Heart and Lung Transplantation in the United States, 1996–2005

This article examines the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients data on heart and lung transplantation in the United States from 1996 to 2005. The number of heart transplants performed and the size of the heart waiting list continued to drop, reaching 2126 and 1334, respectively, in 2005. Over the decade, post-transplant graft and patient survival improved, as did the chances for survival while on the heart waiting list. The number of deceased donor lung transplants increased by 78% since 1996, reaching 1407 in 2005 (up 22% from 2004). There were 3170 registrants awaiting lung transplantation at the end of 2005, down 18% from 2004. Death rates for both candidates and recipients have been dropping, as has the time spent waiting for a lung transplant. Other lung topics covered are living donation, recent surgical advances and changes in immunosuppression regimens. Heart-lung transplantation has declined to a small (33 procedures in 2005) but important need in the United States.     

Lung and Heart Allocation in the United States

Lung and heart allocation in the United States has evolved over the past 20–30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.