|Year : 2016 | Volume
| Issue : 4 | Page : 109-113
Kidney Transplantation in the Elderly with End-stage Renal Disease
Fei Han, Jianghua Chen
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
|Date of Web Publication||7-Nov-2016|
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province
Source of Support: None, Conflict of Interest: None
The incidence of end-stage renal disease (ESRD) increases in the elderly population. Patients received kidney transplantation have better long-term survival and quality of life than those received maintaining dialysis. However, only a smaller proportion of the elderly patients receive kidney transplantation because of the concerns about high posttransplant complications such as infections and diabetes. In this review, we make a discussion on treatment strategies including prophylaxis of risk factors, donor selection, and postoperative monitoring to raise awareness and improve long-term prognosis in the elderly patients with ESRD.
Keywords: Elderly, end-stage renal disease, kidney transplantation
|How to cite this article:|
Han F, Chen J. Kidney Transplantation in the Elderly with End-stage Renal Disease. J Integr Nephrol Androl 2016;3:109-13
| Introduction|| |
The incidence of end-stage renal disease (ESRD) increases rapidly in the elderly. According to the report of the United States Renal Data System, the morbidity of ESRD has increased from 864.4/1000,000 in 1990 to 1306.8/1000,000 in 2011 in the elderly aged 65-74 years old. Although its growth rate has declined in the recent years, the morbidity is still much higher than the overall population (357.1/1000,000 in 2011). Kidney transplantation is the best treatment method for ESRD. However, for a long time, the elderly patients are inclined to choose maintaining dialysis regard of safety and convenience. From the data of Organ Procurement and Transplantation Network, among patients aged 18-39 years old, 21% of them are included in the waiting list of kidney transplantation. However, the proportion is down to 3.4% in the elderly over 70 years old.  In the total 3691 kidney transplantation cases in our kidney disease center, there are 148 patients over 60 years old, only taking up 4%, which is far below its morbidity.
Although most researches show the long-term survival rate for patients over 65 years old received kidney transplantation is less than young patients, elderly ESRD patients receiving kidney transplantation can enjoy 41-68% mortality decreased compared with those dialysis patients waiting kidney transplantation. Moreover, there is no statistical significance in the aspects of perioperative mortality, incidence of delayed renal allograft and repeated hospitalization rate compared with the young. , Therefore, a number of kidney transplantation guidelines have not list elderly ESRD patients as contraindication for kidney transplantation or defined upper age limit. However, in view of the pathological and physiological and immunological characteristics, elderly ESRD patients may have a high incidence of some complications such as cardiovascular events, infections, and tumor. Moreover, the kidney transplantation with successful death caused by complications can account for about 50%.  Before the operation, taking a comprehensive assessment of patient's condition, organ function, and potential risk as well as adequate preventive measures can make elderly ESRD kidney transplantation recipients pass the perioperative period smoothly. Of course, strengthening monitoring after the operation can get long-term prognosis.
| Prognostic factors of elderly kidney transplantation|| |
The high incidence of cardiovascular diseases, long-term chronic kidney disease, and dialysis treatment among the elderly may cause cardiovascular complications for ESRD patients, which keeps higher incidence rate than their peers. There is a survey for western people indicates the incidence rate of preoperative coronary artery disease can reach to 59.1% for the recipients over 60 years old. Moreover, 18.2% of them need interventional or surgical treatment. However, for young patients, the rates are 15.9% and 4.5%, respectively. Within 1 year after the operation, cardiovascular events rate of the former is 20.5%, whereas the latter is 6.9%.  Successful death caused by acute coronary event is the most common cause for elderly recipients receiving kidney transplantation.  On the one hand, preoperative assessment should be strengthened. To elderly recipients over 60 years old, in addition to cardiac ultrasound, coronary computed tomography (CT) angiography can better assess patients' coronary status. Patients with severe stenosis over 70% need receiving coronary intervention or coronary artery bypass first. On the other hand, kidney disease: Improving Global Outcomes guideline suggests strengthening the monitoring and control of high-risk factors for cardiovascular disease. For example, assess blood pressure (maintain 130/80 mmHg [1 mmHg = 0.133 kPa]) and obesity in each follow-up. Monitor blood pressure every 2-3 months and control smoking. Furthermore, aspirin prevention and treatment are recommended to patients combined with atherosclerotic cardiovascular disease.  To ESRD patients, in addition to traditional high-risk factors, disorder of calcium and phosphorus metabolism may also lead to vascular calcification. Some patients are accompanied by persistent hyperparathyroidism combined with hypercalcemia after they receive kidney transplantation. CT angiography is very important for them before the operation, for the possibility of intimal injury in arterial anastomosis site, anastomotic stenosis, hemorrhage, tarombokinesis, etc., Besides, elderly kidney transplantation recipients keep increased ratio of secondary diabetes. From the data in our center, the incidence rate of diabetes after operation takes up 10.8% in the recipients over 60 years old, which is significantly higher than the matched young recipients. Hence, it is necessary to strengthen the monitoring and management of blood glucose. Meanwhile, stopping or reducing hormone may also improve the condition.
The immune system function degradation of the elderly kidney transplantation recipients includes involution of thymus, T-cell migration decreased, peripheral effector T-cell decreased, and decreased expression of costimulatory signal. These will cause T-cell dysfunction and eventually lead to infection.  From the data in our center, generally, the elderly kidney transplantation recipients have equivalent overall survival and failure rates compared with young recipients. They have relatively low acute rejection incidence, whereas keep higher incidence rate of pulmonary infection after the operation. Under immunosuppression state, especially 1 year after the operation, some specific infections, such as cytomegalovirus, pneumocystosis, and fungus, often take place with severe condition, rapid spread, and high mortality. Although the usage of ganciclovir and compound sulfamethoxazole (at least 3 months) after the operation has reached consensus, pneumocystosis (about 1 year after the operation) often occurs after drug withdrawal of compound sulfamethoxazole. Hence, to high-risk and elderly recipients, it is necessary to prolong the preventive treatment of compound sulfamethoxazole and use it again after antirejection therapy (at least 6 weeks).  Currently, with increased awareness and the popularity of monitoring, the incidence of BK virus infection is also increasing but without effective treatment method. High failure rate of kidney transplantation and excessive immunosuppression may be the high-risk factors of the infection. Hence, every 1-3 months, monitoring plasma nucleic acid quantification of BK virus and taking down the regulation of immune inhibitor when necessary may be helpful to prevent the infection.  Maintaining reasonable immunosuppression intensity is also the important means to prevent infection. However, the commonly used immunosuppression plans are always not made according to old people's pharmacokinetic and immunological characteristics. Moreover, people over 65 years old are always excluded from a clinical trial of immune inhibitor. Therefore, it is very important to strengthen the monitoring of pathogenic microorganisms and immune status and explore individual immunosuppression plan.
The elderly always keep the high incidence of tumor, and their immunosuppression state after kidney transplantation is easy to cause internal control ability decreased and the occurrence of tumor. According to the statistics of western people, the incidence rate of tumor in the elderly recipients over 65 years old is more than one time higher than those of the same age,  and the common tumors are skin tumor, urinary system tumor, lymphadenoma, etc. Preoperative screening and postoperative monitoring, such as imaging and fluid tumor markers screening, are very important to patients. To new hematuria patients, these examinations should not be ignored for the existence of kidney transplantation. It is essential to take in situ renal imaging examination and exfoliative cell examination of urine. There are some researches put forward the plan of routine switching rapamycin resistance routine switching can reduce the incidence rate of tumor effectively.  However, to the immunosuppression plan based on rapamycin, for the relatively high incidence of acute rejection and proteinuria exacerbation to existed proteinuria patients, it is essential to choose suitable patients, switch time (usually 3 months after the transplantation with stable renal function), and strengthen monitoring in the process of switching.
Primary kidney disease
Diabetic nephropathy has become the main cause among elderly ESRD patients. Besides, amyloidosis nephropathy and antineutrophil cytoplasmic antibody (ANCA) associated vasculitis are also very common, which can affect multiple organ systems of the whole body. To these patients, the comprehensive assessment involving various organs is more important. The transplantation effect always depends on the involvement of other organs in the body, especially for cardiovascular system. To ANCA-associated vasculitis patients, they should receive kidney transplantation 12 months later after the complete remission of renal external activity.
For some benign diseases, such as benign prostatic hyperplasia, often take place among elderly females, which takes up 27% in female recipients over 60 years old.  Moreover, it is often ignored for the sake of oliguresis or anuria in the process of dialysis. This becomes the main cause of urinary obstruction and infection after kidney transplantation. Hence, elderly female recipients should receive routine imaging to assess the conditions of bladder and urinary passage.
| Donor selection for elderly kidney transplantation|| |
According to the retrospective analysis of large samples, to kidney transplantation recipients over 60 years old, the 4-year graft survival rate has no statistical difference from the living donor kidney aged more than 55 years old or less. The rates are, respectively, 78% and 81%, significantly better than standard cadaver donor (70%).  To elderly ESRD patients, they keep high death risk in the waiting period and do not want to accept their children's kidney. Hence, living donor kidney from their spouse or sibling is preferred. Besides, although the long-term survival rate of expanded standard donor kidney is not as good as standard cadaver donor (such as donor kidney, over 60 years old, combined with hypertension and serum creatinine >132.6 μmol/L), it can still reduce mortality compared with maintaining dialysis, especially for the elderly ESRD patients >60 years old.  Therefore, expanding standard donor kidney is the suitable choice to shorten the waiting period for elderly ESRD patients. While for the high delayed recovery rate after kidney transplantation, it is very important to strengthen preoperative comprehensive organ function assessment (especially for cardiopulmonary function), postoperative monitoring and alternative treatment transition when necessary.
| Prevention and postoperative monitoring of elderly kidney transplantation|| |
Adequate preoperative treatment adjustment
This includes adequate blood purification therapy, supportive therapy to correct anemia, electrolyte disorder, and cardiopulmonary anomaly. The aim is to adjust the body organ function to its best (especially for cardiopulmonary function) to adapt to the wounds and side effects of transplantation operation and immunosuppressive therapy. Meanwhile, invest and treat latent infection and the high-risk status of tumor. By ultrasound and angiography to fully identify vascular conditions of the surgical site, estimate possible surgical problems in transplantation and avoid postoperative delayed recovery caused by the operation.
Intensity monitoring of immunosuppression
Due to the decreased immune response and low-incidence rate of acute rejection,  elderly recipients can appropriately reduce the maintenance intensity of required immune inhibitor. For the increased risk of the possible acute rejection, inductive treatment may be helpful to the reduction of immune inhibitor. Although the guideline has not recommended the use of inductive treatment, it has increased significantly in elderly recipients over 60 years old, according to statistics: In 2001, 40% patients did not receive inductive treatment, but in 2008, these proportion was decreased to 18%.  To low risk and elderly recipients, inductive treatment should take anti-interleukin 2 receptor monoclonal antibody and other mild treatments. For the monitoring of immunosuppression intensity, programmed renal biopsy can accurately reflect the risk of renal allograft rejection but with traumatic. Through monitoring the content of ATP released by peripheral blood CD4 + T lymphocytes, cell mediated immune response state can be judged, which is also significant to monitor recipient's cellular immune function. Currently, many researches indicate it may predict recipients' infection risk.  Moreover, there are reports of using recipients' blood and urine biomarkers and high throughput group study to monitor immunosuppression state and immune level. However, due to the complicated process of immune reaction and the involvement of many factors, the practice of using one marker to get the high sensitivity and specificity at the same time is difficult. Hence, diagnostic model with combined biomarkers may have better clinical value.
Individualized immunosuppressive therapy
To elderly recipients, the pharmacokinetics of immune inhibitor is different from those of young recipients. Under the same dose of calcium-regulated protein inhibitor, elderly recipients over 65 years old keep high minimum concentration.  The data in our center also show recipients over 60 years old need a small dose of cyclosporine or tacrolimus (1 month later) compared with young recipients. However, it has no statistical difference. Hence, individualized therapy should be made according to recipients' immune state and pharmacokinetic characteristics. Moreover, the clinical dose of immune inhibitor should be adjusted by area under the drug curve, blood concentration monitoring, kidney transplantation function of the recipient and high-risk factors, etc. Currently, pharmaceutical genomics research has already gotten multiple genetic polymorphisms which can affect pharmacokinetics of related immune inhibitors. Moreover, it may be used to guide clinical use of immune inhibitors in the future to get appropriate and stable drug concentration and reduce side effects.  Even so, the adjustment should be made combined with recipients' immune state. This depends on the accurate monitoring means or markers reflecting recipients' immune state and level.
| Adequate education and society-family psychological assessment|| |
The elderly recipients suffer more complications and poor organ tolerance, so the effect of transplantation is more variable. Before the operation, adequate education can make the recipients have enough mental preparation and understanding to potential risks and serious consequences. After the operation, patients need to take drugs for a long time and monitor urine volume, body weight, and blood pressure, etc. Besides, taking regular follow-up to the hospital and getting economic support from society and family are very important. For hypomnesis, decreased vision and the decrease of their peers, elderly recipients are easy to enter a state of poor compliance, depression, loneliness, etc. Hence, preoperative care should be more carefully taken in elderly recipients' self-care ability and social-family economic support.
In general, elderly ESRD patients receiving kidney transplantation can significantly prolong their survival period and improve the quality of life, and the prognosis is basically equivalent to that of young recipients. However, comprehensive and careful assessment before the operation, especially for the function of other organs, is necessary to be taken to correct complications and potential risk factors. After the operation, it is essential to take close monitoring and adjustment treatment, and concern patients' family and psychological factors. Of course, there are still many problems in elderly kidney transplantation, such as how to configure kidney in the case of serious kidney shortage, whether setting upper age limit and absolute contraindication or not, which still remains to be discussed by medicine and ethics.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2010 Annual Data Report [R]. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2011.
Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al.
Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725-30.
Rao PS, Merion RM, Ashby VB, Port FK, Wolfe RA, Kayler LK. Renal transplantation in elderly patients older than 70 years of age: Results from the scientific registry of transplant recipients. Transplantation 2007;83:1069-74.
Jassal SV, Opelz G, Cole E. Transplantation in the elderly: A review. Geriatr Nephrol Urol 1997;7:157-65.
Debska-Sslizien A, Jankowska MM, Wolyniec W, Zietkiewicz M, Gortowska M, Moszkowska G, et al.
A single-center experience of renal transplantation in elderly patients: A paired-kidney analysis. Transplantation 2007;83:1188-92.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9 Suppl 3:S1-155.
McKay D, Jameson J. Kidney transplantation and the ageing immune system. Nat Rev Nephrol 2012;8:700-8.
Webster AC, Craig JC, Simpson JM, Jones MP, Chapman JR. Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: A cohort study of 15,183 recipients. Am J Transplant 2007;7:2140-51.
Schena FP, Pascoe MD, Alberu J, del Carmen Rial M, Oberbauer R, Brennan DC, et al.
Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the convert trial. Transplantation 2009;87:233-42.
Tsaur I, Jones J, Melamed RJ, Blaheta RA, Gossmann J, Bentas W. Postoperative voiding dysfunction in older male renal transplant recipients. Transplant Proc 2009;41:1615-8.
Gill J, Bunnapradist S, Danovitch GM, Gjertson D, Gill JS, Cecka M. Outcomes of kidney transplantation from older living donors to older recipients. Am J Kidney Dis 2008;52:541-52.
Merion RM, Ashby VB, Wolfe RA, Distant DA, Hulbert-Shearon TE, Metzger RA, et al.
Deceased-donor characteristics and the survival benefit of kidney transplantation. JAMA 2005;294:2726-33.
Tullius SG, Milford E. Kidney allocation and the aging immune response. N Engl J Med 2011;364:1369-70.
Gill J, Sampaio M, Gill JS, Dong J, Kuo HT, Danovitch GM, et al.
Induction immunosuppressive therapy in the elderly kidney transplant recipient in the United States. Clin J Am Soc Nephrol 2011;6:1168-78.
López-Hoyos M, Rodrigo E, Arias M. The usefulness of intracellular adenosine-5'- triphosphate measurement in CD4 cells in renal transplant. Nefrologia 2013;33:381-8.
Jacobson PA, Schladt D, Oetting WS, Leduc R, Guan W, Matas AJ, et al.
Lower calcineurin inhibitor doses in older compared to younger kidney transplant recipients yield similar troughs. Am J Transplant 2012;12:3326-36.
Murray B, Hawes E, Lee RA, Watson R, Roederer MW. Genes and beans: Pharmacogenomics of renal transplant. Pharmacogenomics 2013;14:783-98.