Kristian Heldal

Benefit of kidney transplantation beyond 70 years of age

Background. Kidney transplantation generally improves long-term survival in patients with end-stage renal disease. However, in patients older than 70 years of age, only limited data are available that directly compare the potential survival benefit of transplantation versus dialysis. Methods. All patients aged above 70 years who started dialysis between 1990 and 2005 and were waitlisted for kidney transplantation were included in the study. They were categorized according to time periods of inclusion (1990–99 vs 2000–05). Survival rates of altogether 286 dialysis patients were analyzed with a Kaplan–Meier model, as well as with a time-dependent Cox model. Comparisons were made between those who received a transplant and those who did not, and further between the two time periods. Results. Median age at inclusion was 73.6 years (interquartile range 72.3–75.6). Two hundred and thirty-three patients (81%) received a kidney transplant during follow-up. Transplant recipients experienced an increased mortality in the first year after transplantation when compared to waitlisted patients. Patients starting dialysis between 1990 and 1999 had no significant long-term benefit of transplantation; HR for death 1.01 (0.58–1.75). In contrast, there was a substantial long-term benefit of transplantation among those starting dialysis after 2000; HR for death 0.40 (0.19–0.83), P = 0.014. Conclusions. Survival after kidney transplantation in patients over 70 years has improved during the last decade and offers a survival advantage over dialysis treatment. Our experience supports the use of kidney transplantation in this age group if an increased early post-operative risk is accepted. This transplant policy may be challenged for priority reasons.

Clinical outcomes in elderly kidney transplant recipients are related to acute rejection episodes rather than pretransplant comorbidity.

Background. Deciding whether an elderly patient with end-stage renal disease is a candidate for kidney transplantation can be difficult. We aimed to evaluate pre- and early posttransplant risk factors that could predict outcome in elderly kidney recipients. Methods. Data from all elderly (≥70 years, n=354), senior (60–69 years, n=577), and control (45–54 years, n=563) patients receiving their first kidney transplant at our center from 1990 to 2005 were retrieved. Patient and graft survival were analyzed in a Cox model addressing the common risk factors including Charlson comorbidity index (CCI), pretransplant dialysis time, and early acute rejection episodes. Results. Acute rejection in the first 90 days, Hazard ratio (HR) 1.74 (1.34–2.25); time on dialysis, HR 1.02 (1.01–1.03) per month; and donor age more than 60 years, HR 1.52 (1.14–2.01) predicted mortality in the elderly. CCI score did not predict mortality in the elderly, HR 1.05 (0.98–1.12); but did so both in senior, HR 1.17 (1.08–1.27) and control recipients, HR 1.33 (1.19–1.48). Delayed graft function, HR 3.69 (2.01–6.79); donor age more than 60 years, HR 2.42 (1.30–4.49); and presence of human leukocyte antigen antibodies, HR 3.96 (1.38–11.37) were independent predictors for death-censored graft loss in the elderly. Conclusion. Adequate immunosuppresion with low frequency of rejection episodes improves the outcome for elderly kidney recipients as does a reduction of time on dialysis. CCI score at transplantation does not seem helpful in the selection of elderly patients for kidney transplantation but plays a significant role in patients under 70 years of age.

Kidneys From Deceased Donors More Than 75 Years Perform Acceptably After Transplantation

Background. Organ shortage has resulted in an increased use of expanded criteria donors for transplantation, in particular kidneys from older donors. There is limited data on the impact of donor age more than 75 years on kidney transplant outcome. Methods. A retrospective single-center analysis on deceased donors more than 75 years and kidney transplant outcome in an old for old setting was performed. Histologic findings (global kidney score) in graft biopsies and deceased-donor scores were evaluated to observe if this information could be helpful in predicting outcome. Results. Evaluation of data from 54 single kidney transplantations from 29 donors more than 75 years (median 77.5, range 75.2–86.1) were assessed. Ninety-three percent of the donors died of intracranial bleeding, and 69% had a history of hypertension or cardiovascular event(s). Median recipient age was 70.1 (range 50.6–82.4). Fifty-two grafts (96%) had posttransplant function. Death censored graft survival at 1, 3, and 5 years were 87%, 83%, and 83%, respectively. Patient survival was 81%, 75%, and 59% at the same time points. At follow-up at median 23 months (range 6–144 months), thirty-five recipients were alive with a median serum creatinine of 163 &mgr;mol/ L (range 103–348). Global kidney score and deceased donor score did not predict graft outcome. Conclusion. Kidney transplants from deceased donors more than 75 years perform acceptable as single transplants and should be considered for use in older recipients.

Risk variables associated with the outcome of kidney recipients >70 years of age in the new millennium

BACKGROUND New and more potent immunosuppressive protocols have markedly reduced the occurrence of rejections following organ transplantation. Accordingly, survival of elderly kidney transplant recipients has been substantially improved in the new millennium. The present study was performed to identify variables associated with the outcome of kidney transplant recipients >70 years of age in the modern era. METHODS A single center retrospective study was performed, evaluating clinical and survival data from all patients >70 years of age receiving their first kidney transplant between 2000 and 2005. Survival data were analyzed using Cox proportional hazard models and the Kaplan-Meier method. RESULTS During the time period, 160 recipients >70 years of age received their first transplant. The following factors were negatively associated with patient survival: age at transplantation; hazard ratio (HR) 1.09 per year, 95% confidence interval (CI) (1.01-1.18), time on dialysis before transplantation; HR 1.29 per year 95% CI (1.06-1.59) and presence of diabetes at transplantation; HR 1.78 95% CI (1.00-3.16). Thirty-five patients (22%) experienced an acute rejection episode during the first 90 days post-transplant. Acute rejection episodes did not influence on patient or graft survival. Patients with post-transplant pathological oral glucose tolerance test (OGTT) at 10 weeks after transplantation had significantly inferior survival compared to patients with normal OGTT. CONCLUSIONS In a population of kidney transplant recipients >70 years of age with relatively low incidence of acute rejection episodes, age, time on dialysis before transplantation, concomitant diabetes mellitus and development of a pathological OGTT 10 weeks after transplantation were associated with inferior patient survival.

Induction with interleukin-2 antagonist for transplantation of kidneys from older deceased donors: an observational study

BackgroundThe most important limiting factor in kidney transplantation is the scarcity of donor organs. Consequently, there is an increased use worldwide of kidneys from older deceased donors. High donor age is a known risk factor for acute cellular rejection and premature graft failure, and the optimal immunosuppressive regimen in these circumstances remains to be established.MethodsWe investigated whether induction treatment with an interleukin 2 (IL-2) receptor antagonist improves graft survival and reduces rejection episodes in recipients of kidneys from deceased donors aged ≥ 60 years. Data were retrieved for all recipients transplanted at our center from 2004 to 2009 with a kidney from a deceased donor aged > 60 years. The outcome was compared between recipients treated with (IL-2 plus) or without (IL-2 minus) an IL-2 receptor antagonist. All recipients received a calcineurin inhibitor, steroids and mycophenolate.ResultsA total of 232 first-transplant recipients were included (IL-2 plus = 149, IL-2 minus = 83). IL-2 minus was associated with increased risk of early acute rejection (OR 2.42; 95% CI 1.25 to 4.68, P = 0.009) and steroid-resistant rejection (OR 8.04; 2.77 to 23.25, P< 0.001). IL-2 plus patients had superior two-year estimated uncensored (87% versus 70%, P = 0.001) and death-censored (95% versus 79%, P< 0.001) graft survival.ConclusionsInduction treatment with IL-2 receptor antagonist was associated with a reduction in acute rejection episodes and improved two-year graft survival in patients transplanted with kidneys from older deceased donors.

Long-term outcomes after cyclosporine or mycophenolate withdrawal in kidney transplantation – results from an aborted trial

Long‐term triple immunosuppressive therapy with cyclosporine (CsA), mycophenolate mofetil (MMF) and prednisolone may be excessively powerful for many transplant recipients. We compared withdrawal of either MMF or CsA in stable kidney transplants on triple immunosuppression. The study was a prospective, randomized, controlled 12‐months trial in stable kidney transplants. The patients who withdrew CsA were given MMF 2 g/d, and CsA troughs were between 75 and 125 ng/mL in MMF withdrawal. Planned inclusion was 298 patients. The study was prematurely aborted after inclusion of 39 patients. Acute rejection rates were 6/20 (30%) in the MMF group compared with 0/19 (0%) in the CsA group (p = 0.02). Time to acute rejections was 4.0–28.7 months after withdrawal. Trough concentrations of mycophenolic acid (MPA) and CsA showed therapeutic levels. The subjects have been observed for eight yr, and of the 28 patients remaining on randomized therapy, the MMF patients preserved graft function better than CsA patients. Death‐censored graft survival was 75% and 95% (p = 0.18) and patient survival was 70% and 68% (p = 0.99) in the MMF and CsA groups, respectively, at the end of long‐term follow‐up. CsA withdrawal was associated with a high rate of acute rejections. Initially, the treatment of acute rejections was successful. However, five of six lost their grafts in the long term.

Managing Transplant Rejection in the Elderly: The Benefits of Less Aggressive Immunosuppressive Regimens

Organ transplantation is increasingly common in the older population, particularly among end-stage renal disease patients. The outcomes of transplantation are often inferior in older people compared with younger recipients, partly because of the side effects of immunosuppressive medication used after organ transplantation. In this paper, we explore treatment considerations for older transplant patients. The current commonly used immunosuppressive protocols have not been validated sufficiently in older organ recipients. The primary objective for the management of transplant recipients of all ages is to prevent rejection without increasing the risk of infection or other long-term complications. To avoid serious side effects related to immunosuppressive treatment, the clinician should consider modifying and tailoring the long-term regimen for individual patients. Modifications for older recipients include reduction in the dosage or avoidance of calcineurin inhibitors, with or without the introduction of a mammalian target of rapamycin inhibitor and discontinuing the use of corticosteroids. Such modifications must consider the individual risks and needs of each recipient. Treatment of an acute rejection episode should follow the same protocol as for younger recipients, but special attention is needed to ensure reduction in the total immunosuppressive load. One way to achieve this is to avoid anti-thymocyte globulin (ATG) induction and to use on-demand ATG treatment of rejection on the basis of the patient’s CD3 T cell count.

Are octogenarians with end stage renal disease candidates for renal transplantation

Background Elderly patients are the fastest-growing group in need of renal transplantation. This study puts focus on renal transplant recipients in their 80th year or longer at time of engraftment. Is there evidence to support an absolute upper age limit for renal transplantation? Methods Recipients in their 80th year or longer, transplanted between 1983 and 2015, were included. Data were retrieved from the Norwegian Renal Registry in the end of October 2015. Graft and patient survivals were compared with recipients aged 70 to 79 years at transplantation. Results Forty-seven patients older than 79 years were transplanted in the defined period. Median age 80.1 years, 81% were men. Median time on dialysis before transplantation was 18.5 months. All patients received an allograft from a deceased donor (median donor age, 61.8 years). In the death-censored graft survival model, there was no statistical difference between the groups. We found improved patient and graft survivals after introduction of mycophenolate mofetil and induction with basiliximab. Patients transplanted before 2000 had increased risk of death compared with those transplanted after 2000 (hazard ratio, 3.2; 95% confidence interval, 1.2-8.7). Median uncensored graft survival for patients transplanted after the year 2000 was 5.0 year (95% confidence interval, 2.4-7.6). Median patient survival was 5.0 years (3.1-6.9) and 5-year patient survival was 55%. Conclusions Age by itself should not be an absolute contraindication against renal transplantation. An estimated 5-year survival rate of 55% post-engraftment for an 80-year-old patient is in our opinion more than acceptable.

Predictors of mortality in high-risk patients with QT prolongation in a community hospital

Aims To determine predictors of mortality in patients with corrected QT interval (QTc) ≥ 500 ms in a community hospital. Methods and results In this retrospective observational study, we searched the electrocardiogram (ECG) database at Telemark Hospital Trust, Norway, from January 2004 to December 2014. Medication, electrolyte abnormalities, and medical conditions known to prolong the QT interval were recorded. From the medical records, we assessed whether the prolonged QTc was noted by the health care providers. We identified 1531 patients (age = 70 ± 15 years, 59% female) with an ECG with QTc ≥ 500 ms. All-cause mortality during 952 (range 0-4161) days of follow-up was 50% (n =  765/1531). Main predictors of mortality were aborted cardiac arrest [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.44-4.01; P = 0.001], cerebral stroke/head trauma (HR 2.28, 95% CI 1.70-3.05; P < 0.001), and heart failure (HR 1.74, 95% CI 1.43-2.12; P< 0.001). Females with prolonged QTc had better survival compared with males (P = 0.006). We constructed a risk-weighted QTc mortality score. QT prolongation was acknowledged in the medical records in 12% of the cases. Conclusions QTc ≥ 500 ms was associated with high all-cause mortality with increased mortality in males compared with females. A new QTc mortality score was constructed to predict mortality. Only a minority of cases with prolonged QTc ≥ 500 ms were acknowledged in the medical records.

Estimated glomerular filtration rate in stable older kidney transplant recipients-are present algorithms valid? A national cross-sectional cohort study

Several equations have been developed for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), but none were developed based on data from elderly kidney transplant recipients (KTR). The primary aim of this study was to evaluate different creatinine‐based equations in stable elderly KTR. A national cross‐sectional study was performed using data from 263 consecutive kidney transplant recipients 60 years or older who performed a routine GFR measurement one year after engraftment. GFR was measured by iohexol clearance calculation based on two samples. eGFR was calculated from a range of different creatinine‐based equations using information obtained at the time of GFR measurement. Bias, precision, and accuracy were evaluated for each equation. All equations apart from Nankivell had accuracy (P30) > 80%. The BIS1, FAS, LMRCR, and Cockcroft & Gault equations in recipients older than 70 years and the FAS, LMRCR, and MDRD in recipients 60–69 years old had nonsignificant bias. The CKD‐EPI had significant bias in both groups. If one should choose a single equation for follow‐up of individual CKD progression in all recipients ≥ 60 years, the FAS or LMRCR equations are probably the best alternatives.