Industrialized nations are today confronted by a pandemic of diabetes which, in turn, is fueling a mounting increase in end stage renal disease (ESRD). In the United States, with annual reports derived from reliable data bases of ESRD incidence and prevalence, maintained by superb dual key resources, [the United States Renal Data System (USRDS) and the United Network for Organ Sharing (UNOS)], the unfolding story is explicitly documented. Dialysis units in Japan, Western Europe, and the United States report that diabetes is listed as the cause of ESRD in from 35% to 60% of newly treated uremic patients.

As indicated in Table 1, the mean age of incident ESRD patients now lies in the sixth decade of life, transforming uremia therapy into a geriatric endocrinology practice.

Table 1. Incident Diabetic ESRD Patients Now = Geriatric Nephrology.

For the primary care physician, internist, endocrinologist, nephrologist, geriatrician, and transplant surgeon, concerned with the management of geriatric diabetic ESRD patients, the role of kidney transplantation is largely undefined. In this Cyberounds^®, we (a transplant surgeon and a nephrologist) look at the challenging task of coping with renal failure in the midst of myriad enervating comorbidities.

Physiologic Versus Chronologic Age

Continuous evolution of the overall quality of medical care available to patients in the developed world has facilitated the successful application of nearly every therapy and intervention to increasingly aged patients. If octogenarians are successfully managed through colon and cardiac bypass surgeries,(1),(2) why shouldn't they be offered a chance at kidney transplantation? Should once absolute age barriers be replaced by individualized consideration of the patient's likely ability to tolerate transplantation?

UNOS data show that patients aged 65 years and over have one-year patient survival rates of 90.3% for deceased donor and 95.5% for live donor kidney transplants.(3) These outcomes, though less than the comparable rates of 96.1% and 98.3% for all patients, are still excellent. Nevertheless, it is apparent that long-term survival expectations for the majority of elderly ESRD patients will still be far lower than for younger patients, principally because of causes unrelated to the transplant itself.

The question of whether elderly patients should (must?) have equal access to the limited supply of organs thus becomes a complex societal issue of the appropriate utilization of limited healthcare resources. From a purely financial perspective, transplantation becomes more cost effective than other renal replacement therapies by the second and third years, because yearly costs are principally due to maintenance medications, not expensive interventions such as vascular access surgery.(4) If outright expense favors transplantation even for the elderly, why does this therapy still seem intuitively questionable?

It seems apparent that, in light of the severe organ shortage, use of a deceased donor kidney for an elderly patient will deprive another patient, likely substantially younger, of the opportunity. Or, if a live donor comes forward, kidney procurement will subject an entirely healthy person to real, though low, risks including a .03% chance of death,(5) in order to benefit the elderly recipient.

Until a comprehensive approach to resource utilization for the elderly is broadly adopted, exclusion of these individuals from transplantation would be inconsistent with the rest of modern health care. It is logical to understand both why transplant centers are receiving increasing referrals of geriatric ESRD transplant candidates and why more kidney transplants are being performed in this same group. (Tables 2 and 3)

Table 2. U.S. Renal Transplants: Recipient Age.

Table 3. Percentage of Geriatrics Patients (> 65 Years) on the UNOS Kidney Waiting List.

Case 1

A patient's spouse requests kidney transplantation to resolve newly diagnosed ESRD. The patient, a 76-year-old former judge, had been under treatment for type 2 diabetes for 35 years, was admitted for amputation of his left leg because of unhealing gangrenous ulcers. Past medical and personal history were provided by the patient's wife, as the patient was disoriented to time and place and was only minimally responsive. His right leg was amputated six years previously. Bilateral blindness followed unsuccessful vitrectomies and panretinal laser photocoagulation four years earlier. During the preceding two years, a series of three strokes induced left hemiparesis, bowel and bladder incontinence, and slurred speech.

Glucose regulation was attempted with twice daily doses of regular and intermediate insulin modulated by finger-stick glucose testing performed twice weekly with values ranging from 155 to 280 mg/dl. Vital signs included a subnormal weight for age, blood pressure 116/62 mmHg, and a pulse that was regularly irregular at 91.

Cardiac evaluation, prompted by persistent edema and atrial fibrillation, disclosed electrocardiographic evidence of past anteroseptal myocardial infarction. The left ventricular ejection fraction was 34%. Progressive decline in renal function was evident in the change in serum creatinine from 2.1 mg/dl one year earlier at the patient's nursing home to 6.7 mg/dl at the current admission. The hematocrit was 28%, the serum albumin concentration was 2.2 g/dl, while the 24-hour urine protein excretion was 7.1g. The hemoglobin A1c was 9.4%. Liver function was normal and there were no increases in cardiac enzymes. The specific question posed on the consultation request was: "Please start dialysis and arrange early kidney transplantation at the family's request."

The issue of whether maintenance hemodialysis or peritoneal dialysis should be initiated is a difficult discussion that compels religious and ethical examinations of the practice of medicine. For this man, who had been highly functional in the past, subsistence as a non-interactive, immobile person, dependent entirely on others for his care, seems unlikely to provide meaningful life quality. Further, the combined medical issues pose excessive threat to his survival through any renal replacement modality even if the highest level of care is delivered. The presence of numerous end organ complications of diabetes contribute significantly to the likelihood of infections, cardiovascular decompensation and poor nutrition. All of these factors substantially increase the mortality and morbidity rates to be expected from renal transplantation.

The decision to perform any invasive procedure must be based on an assessment that it is more likely to benefit than hurt the patient. In addition to the major infectious and cardiovascular risks, a new transplant, producing a continuous high volume stream of urine, will almost certainly require permanent urinary catheterization or surgical intervention that will further limit both the patient's survival and his dignity. Given the extensive risk factors in a patient unable to participate in his care, there is no rational basis for undertaking a renal transplant that will not provide rehabilitation. In the authors' view, extension of life in a noncomprehending patient serves no identifiable purpose.

Case 2

A 71-year-old retired policeman with type 1 diabetes for 42 years has been on maintenance hemodialysis for 11 years and is advised that he is fast approaching exhaustion of available vascular access sites. Extensive abdominal adhesions, resulting from peritonitis after sigmoid diverticulitis with perforation, preclude peritoneal dialysis. Despite his renal failure, the patient has been generally well, able to work part-time as a watchman. Diabetic retinopathy has been stable for 14 years after laser surgery with visual acuity of 20/40 in both eyes.

Vital signs included normal weight for age, blood pressure 130/78 mmHg, and a pulse that was regular at 66. Cardiac evaluation found the patient with no past or active heart disease and a left ventricular ejection fraction of 69%. Metabolic control has been effected by twice daily finger-stick blood tests and three or more doses of intermediate and regular insulin. The hematocrit is 38% (patient treated with erythropoietin), the serum albumin is 4.1 g/dl, liver function is normal, and the hemoglobin A1c is 6.9%.

Pancreas transplantation is performed to prevent both the progression of end organ complications of diabetes and the recurrence of diabetic nephropathy in a transplanted kidney through sustained maintenance of euglycemia. The risks of this procedure are substantially higher than those associated with renal allografting, including a 32% chance of returning to the operating room.(6) The pancreas is fragile, generally intolerant of injuries such as the ischemia that is an obligate part of the organ procurement and transplantation process. For the geriatric patient who is likely to have difficulty overcoming the potential complications, and whose expected survival is not long enough to benefit from years of optimal glucose control, the risk/benefit ratio for pancreas transplantation is inordinately high. The oldest recipient of a pancreas transplant was 62 years at the time of engraftment.(7)

Kidney transplantation, however, should be seriously considered for this patient who will soon have no other means of renal replacement therapy. Thorough evaluation of the medical condition of the diabetic ESRD kidney transplant candidate includes comprehensive assessment of the medical/surgical history and current problems. General contraindications include any condition that is likely to preclude survival beyond 1 or 2 years (at a minimum), including a malignancy (other than non-melanoma skin cancers) and active infections. With diabetic patients commonly unable to perceive angina because of autonomic neuropathy, evaluation of both the heart's pump function and coronary perfusion is essential.

Today, acceptance of the patient's candidacy by the transplant team does not provide assurance that transplantation will take place. If the patient declines to accept an offer from a live donor, or none is available, the chance of his receiving a conventional deceased donor kidney before he runs out of access sites, or his condition deteriorates to an untransplantable state, is small. To serve the rapidly growing cohort of candidates like this one, whose expected survival is shorter than the anticipated wait time, two options are now available.

"Expanded Criteria Donor (ECD)" kidneys are defined as kidneys with a relative risk of graft loss of 1.7 or greater, based on a combination of donor variables. Known to be associated with lower graft survival rates than standard kidneys, these organs should infrequently be considered by younger, more robust candidates. With a small percentage of waiting list patients choosing to accept these organs, the waiting time for those who will is shortened substantially, thus affording an opportunity to achieve transplantation, albeit with a "lesser quality" organ. Faced with the reality of the organ shortage, this approach has rapidly been embraced by elderly patients, with one-fifth of these kidneys now being used for patients 65 years and older.(8)

Some centers, will consider using two DCD ("donation after cardiac death") organs (that have already been declined for individual) for one recipient, hypothesizing that more nephrons will provide more function. Though this practice is much less common than the first, the results are also reasonable.

Case 3

An 81-year-old retired nurse, now a nursing home resident with renal failure attributed to hypertension, is generally well, yet unable to care for herself because of a poorly healed hip fracture. Though she had been hospitalized for community acquired pneumonia one year earlier, past medical history is remarkably benign with intact vision, hearing, and cardiac function including a left ventricular ejection of 56%. The course of renal insufficiency had been progressive deterioration with serum creatinine levels rising to 9.1 mg/dl from 4.3, and 6.0 mg/dl two and one year previously, respectively.

Vital signs included normal weight for age, blood pressure 151/75 mmHg, and a pulse that was regular at 81. The serum albumin was 3.7 g/dl and the hematocrit was 31%. A urinalysis showed trace proteinuria but was otherwise unremarkable. Over the past four months, however, blood glucose levels between 135 and 163 mg/dl were noted in her routine monthly blood tests and the diagnosis of diabetic nephropathy was made by the nursing home physician. Because of a hemoglobin A1c value of 6.7% (normal for the laboratory: 4.0 to 5.9%), treatment for diabetes was started with an oral hypoglycemic agent.

In response to the patient's intact mentation, strong family support, and general good health, the patient'sprimary care physician requested the Transplantation Service to consider a kidney transplant for the patient.

Old age does not preclude highly satisfactory kidney transplantation. Diabetes, of late onset, is probably inconsequential in this patient, though attention to blood pressure and blood glucose regulation should be an important component of overall transplant management. An important element of her pre-transplant education should include discussion of management of the patient's diabetes after transplantation. Most immunosuppressive agents are independently diabetogenic.(9) A large percentage of diabetic transplant recipients who were managed with oral hypoglycemic(s) before the procedure will require insulin therapy to attain adequate glycemic control, even if steroids are eliminated from the regimen.

Advanced knowledge of this issue may dissuade some individuals who focus predominantly on the potential for improved quality of life after transplantation. For example, those who are unable to self-inject because of physical limitations that are common among the elderly may find the level of independence they hope to achieve less than acceptable.

As charted by UNOS, death censored graft and patient survival in kidney transplant recipients over the age of 65 years is equal or superior to that of younger aged recipients. If they survive the short-term risks of transplantation, the elderly patient is actually at an advantage vis a vis younger patients because of their aging immune system. Elderly patients will require lesser amounts of pharmacologic immunosuppression and, as a consequence, acute rejection episodes are uncommon.(10) With respect to prescribed medication compliance, it is suspected that elderly patients, who have a more tangible awareness of their own mortality, behave more consistently as instructed than those of younger ages.

Selection bias is so strong that survival of dialysis patients who are placed on a wait list for a kidney transplant (but have not received a kidney graft) is remarkably superior when compared with those remaining on dialysis -- those fit enough to be considered for a transplant are "different" from those not as fit and thus after-the-fact comparisons are flawed.

These excellent results should be seen not as indication for pursuing transplantation for all elderly ESRD patients, but rather as corroboration of the stringent medical and psychosocial selection criteria that are applied to them (and to candidates of all ages). Selection of relatively few but hardy candidates is most consistent with society's expectation that the scarce societal resource of transplantable organs will be used wisely.

Conclusion

Kidney transplantation may be a reasonable option for the elderly diabetic ESRD patient with realistic expectations and the absence of a medical or psychosocial contraindication. Geriatric patients represent an increasing percentage of the waiting list (Table 4).

Table 4. New Kidney Transplant Candidates 2003, Yale - New Haven Transplant Center.