The most common symptoms present before initiation of maintenance dialysis in older patients tend to be anorexia, weight loss, fatigue, nausea, and vomiting. The recognition of uremia in the elderly patient, however, may prove more difficult than in the younger patient. Behavioral changes, unexplained dementia, “adult failure to thrive,” unexplained worsening of congestive heart failure, or a change in sense of well-being may represent uremia in the geriatric patient.
The trend has been for earlier initiation of dialysis in older patients, perhaps because of the increased burden of comorbid disease (Figure 87-5). The Center for Medicare and Medicaid Services (CMS) bases reimbursement for chronic hemodialysis upon a creatinine clearance below 10 mL/min for patients not having diabetes and less than 15 mL/min for patients with diabetes. Creatinine clearance can be calculated by using one of the formulas illustrated in Chapter 44 or with a 24-hour urine collection.
Timely initiation of RRT (Table 87-4) not only avoids the need for urgent dialysis, but also is associated with decreased mortality. A strong correlation between “baseline” serum albumin just prior to initiation of dialysis and patient survival has been demonstrated. Although hypoalbuminemia itself does not necessarily indicate protein-energy malnutrition, it is believed to be a major contributing factor. Analysis of the Modification of Diet in Renal Disease (MDRD) study showed that patients tend to adapt to their declining GFR and associated uremic symptoms by reducing their protein intake. Nevertheless, approximately 60% of American ESRD patients experience nausea and vomiting at the time dialysis is initiated. NKF-K/DOQI guidelines (Table 87-5) recommend evaluating renal function by monitoring weekly urea clearance (Krt/Vurea). Once the Krt/Vurea falls below 2.0 (equivalent to a creatinine clearance of 9 to14 mL/min/1.73 m2), there is increased risk for development of uremic anorexia leading to malnutrition, and RRT should be considered.
Contraindications to Renal Replacement Therapy
There are few absolute medical contraindications to RRT. Some authors propose that advanced dementia, metastatic cancer, and advanced liver disease are reasons for withholding RRT. However, progressive dementia can be confused with uremia-induced delirium in a patient with advanced kidney dysfunction, and a “trial” of dialysis is often justified. It may take as long as 3 to 4 weeks to clear uremic symptoms with dialysis. The patient's family should be aware that if the patient's mental status fails to improve, RRT may be inappropriate. Similarly, providing dialysis for a patient with metastatic cancer or end-stage liver disease may allow the patient to get their affairs in order and spend some quality time with friends and family. Cognitive and behavioral contraindications may play an even larger role in the elderly than medical contraindications. Dialysis units are communities where a patient with inappropriate, unsafe, or violent behavior adversely impacts care provided to others at that unit. For example, most nephrologists would discourage the use of dialysis in a patient who is severely cognitively impaired and unable to understand the requirements for safe dialysis treatment.
Health-Related Quality of Life
Maintaining health-related quality of life (HRQOL) may be the most important role of health care in elderly patients with chronic illness. Studies of older patients undergoing dialysis have shown markedly lower functional status compared to older community-dwelling adults. However, hemodialysis has improved since these early studies and there have been advances in technology, treatment of comorbidities such as anemia and hyperparathyroidism, and quality improvement initiatives that have improved the HRQOL of patients on dialysis. While HRQOL was impaired in the hemodialysis population, the HRQOL scores at baseline reflect a preserved multidimensional quality of life among respondents in the HEMO Study >70 years compared to younger hemodialysis patients. A large study in the Netherlands demonstrated decline in scores on physical domains over time in the age groups >55 years. Stability of mental domains is consistent with a previous study of incident patients remaining on hemodialysis over 18 months. These authors also suggest that comorbid disease burden rather than age was associated with a composite outcome of hospitalization, decline in albumin, and a quality of life score of 2 standard deviations below the general population mean score. These longitudinal HRQOL data are also consistent with the North-of-Thames Study findings showing rather moderate use of resources and cross-sectional differences in quality of life among hemodialysis patients older than 65 years. In cross-sectional studies of HRQOL in the ESRD population, there have been larger differences in HRQOL for younger patients on hemodialysis compared to younger norms than for older patients on hemodialysis compared to older norms. While these findings may be informative to older patients and health care providers, they also underline the need to improve HRQOL among all patients undergoing dialysis. Interventions aimed at preserving residual renal function, monitoring HRQOL, treatment of anemia, engaging the patient in physical therapy and rehabilitation, applying palliative care principles, and perhaps more frequent and longer hemodialysis treatments may preserve HRQOL among elderly patients undergoing hemodialysis.
Choice of Renal Replacement Modality
When faced with kidney failure, the elderly patient has a number of choices to make regarding therapy consistent with their level of care and plans for the future. The most common form of RRT are three times weekly outpatient hemodialysis, peritoneal dialysis, and renal transplantation. There has been a proliferation of home therapies and therapies tailored to the elderly such as nursing home–based dialysis units. The elderly patient may also choose conservative management and thereby avoid dialysis. The patients should have time to develop a relationship with the nephrologist and team in order to have discussions of goals for care and how RRT may be tailored to meet those goals.
Hemodialysis removes excess fluids and solutes from the blood in order to maintain euvolemia and homeostasis. The conventional hemodialysis schedule requires three treatments for 1 per week for approximately 4 hours per treatment. In order to perform hemodialysis, the patient must have an access placed to circulate the blood through the hemodialysis filter. The three options for hemodialysis access include arteriovenous (AV) fistula, AV graft, and temporary hemodialysis catheters. Permanent hemodialysis access requires minor surgery in the arm or leg. The AV fistula, which creates a connection between the native artery and then the AV fistula vein, matures and thickens to handle the higher blood flow rates and permit the use of a needle for access after approximately 3 months. The use of an AV fistula has been associated with better access survival, fewer infections, fewer hospitalizations, and longer patient survival. The AV Graft uses a synthetic bridge between the artery and the vein. The graft has been used in a broader population than the AV fistula but has the major limitations of shorter access survival as well as more infections and hospitalizations. For elderly patients who have been referred late or who have acute kidney failure, hemodialysis is performed using a dialysis catheter. This is a large bore catheter placed in a major vessel such as the superior vena cava. In the outpatient setting, these catheters are usually tunneled under the skin and treated with sterile precautions by the dialysis unit when accessing the catheters for blood. They have been associated with high rates of bacteremia, catheter malfunction, venous stenosis, and increased costs.
By far, in-center hemodialysis is the predominant form of RRT in the United States. Data derived from the USRDS for patients 65 years of age and older show the incident rate of hemodialysis (by first modality) in 1999 was 2336 per 1 million population, representing 50% of that population initiating RRT. Only 10% of patients older than age 65 years were treated with peritoneal dialysis, and 5% with renal transplantation.
Many elderly patients tolerate hemodialysis well. In addition, some studies demonstrate that older dialysis patients seem to enjoy the scheduled social interaction that in-center dialysis provides them. While most patients maintain a certain quality of life on hemodialysis, the drawbacks to in-center hemodialysis therapy include pain, fatigue, depression, loss of freedom, dietary restrictions, and concern about burden to caregivers.
Peritoneal dialysis (PD) permits elderly patients to maintain more control over their schedule and play a larger role in the management of their kidney failure. PD uses the peritoneal membrane as a dialysis membrane by drawing excess fluid and toxins from the blood and into the peritoneal cavity where the fluid will then be drained through a plastic catheter that has been placed into the abdomen. Depending on the dialysis prescription, the peritoneal cavity is filled with fluid and drained a number of times over the course of the day or night. The advantages to using PD include a less-restrictive diet and avoiding the need to travel to a dialysis unit for treatment. However, the disadvantages include back pain, peritonitis, hyperglycemia, obesity, and hernia formation. PD has been successfully used in elderly patients, but its use in patients with poor functional status depends on a caregiver willing to commit to performing the daily therapy. PD can also be performed safely and effectively in a long-term care facility by staff with specialized training. The preferred mode of peritoneal dialysis in this setting is continuous cyclic peritoneal dialysis or nocturnal peritoneal dialysis, which requires less nursing time, allows patients to be more fully integrated into social activities, and allows interruption-free intensive rehabilitation.
Kidney transplantation represents the optimal therapy for those with kidney failure and access to kidney transplant has increased among elderly patients. Elderly patients, in fact, currently make up the fastest growing segment of the kidney transplant population. Kidney transplant recipients demonstrate improved survival over wait-listed patients on dialysis across all age groups, including the elderly, and across many comorbid diseases, including diabetes. In addition to extending life expectancy, patients both young and old report an improved quality of life following kidney transplantation. Not only do individuals benefit from kidney transplantation, but health care systems also face lower costs in patients receiving a kidney transplant compared to those maintained on hemodialysis, including those aged 60 years and older.
Older kidney transplant recipients have a lower rate of acute rejections and may benefit from tailored immunosuppressant therapy, but have a higher risk of infection, cardiovascular events, and malignancy after kidney transplantation compared to younger patients. Furthermore, older patients may experience more drug toxicity and more drug side effects compared to their younger counterparts. Many older kidney transplant recipients face not only immunological risk but also significant nonimmunological risk of baseline medical comorbidity that may increase their vulnerability to morbidity and mortality associated with delayed or suboptimal graft function.
Because the deceased donor kidney remains a scarce resource, the pursuit of an allocation policy that maximizes the life-year benefit of donor organs has generated strategies, which include matching kidneys with lower expected graft survival time to older patients with lower expected longevity. The elderly are more often offered and more likely to accept expanded criteria donor (ECD) kidneys. ECD kidneys are obtained from donors aged 60 years and older or from donors between the age of 50 and 59 years with at least two of the following risk factors: death from cerebrovascular accident, serum creatinine greater than 1.5mg/dL, or history of hypertension, which carry a higher relative risk of graft failure compared to a reference group of donors aged 10 to 39 years without any of these three conditions. However, older patients may be at increased risk of morbidity and mortality following transplantation with ECD kidneys because of increased baseline comorbidity and decreased physical reserve. Recent discussions focusing on the development of kidney allocation systems to maximize the life-year benefit of donor kidneys has involved “old kidney-for-old recipient” strategies. A potential increase in overall graft survival, with significant associated cost savings to society might be realized by allocating younger kidneys to younger recipients. However, it is important to assess the perception of fairness of such a potentially age-ist allocation schema. In the United States, transplant centers rarely discourage elderly patients from seeking kidney transplantation. Some physicians may be reluctant to encourage elderly transplant candidates to accept kidneys presumed to be of lower quality for the objective of maximizing social justice. Others will be willing to accept such kidneys, using the argument of medical efficacy, while providing subtle or even overt encouragement to the elderly to accept ECD kidneys by framing the option as a means to decrease time on the waiting list. This may in part explain why the odds ratio for willingness to accept an ECD kidney increases significantly with age. In an attempt to ensure good outcome of their grafts in elderly recipients, strict rules have been imposed to limit ischemic damage in the donor and immunological risk by the Eurotransplant Senior Program. Preliminary reports from this program have been positive and this may serve as a model for maximizing kidney resources while offering older patients an opportunity for kidney transplantation.
The degree to which comorbidity influences graft and patient outcomes is significantly less in recipients of living donor kidneys compared to recipients of deceased donor kidneys. A living donor kidney may offset some of the risk of increased comorbidity in the elderly recipient and highlights living donor kidney transplantation as an important opportunity for elderly patients with kidney failure to receive optimal treatment. If the allocation of deceased donor kidneys in the future increasingly favors younger patients over older patients in the distribution of this scarce resource, living donor kidney transplantation may become the only realistic chance at successful kidney transplantation for older patients.
Time-Limited Trial of Dialysis
When the patient, family, or physician is unsure about the prognosis or the impact that dialysis will have upon the patient's quality of life, it is reasonable to offer a time-limited trial of dialysis. If a trial of dialysis is to be conducted, it is important to predetermine a time period (usually 4 to 6 weeks) and to inform all the members of the dialysis team. Such measures will ease the appropriate withdrawal from dialysis.
It is difficult to assess the frequency of conservative palliative therapy, but it is likely that the geriatrician plays a primary role in the decision-making process and management of these patients. In a study from the UK, 84% of patients with CKD Stages 3 to 5 were not referred to nephrology. The proportion of referred patients declined dramatically with older age, with a maximum referral rate of 68% for those 40 to 49 years of age, and 4% of those older than 80 years of age. Another study presented 19% with palliative care as a recommended option based on age and comorbid disease burden; 76% of those recommended for palliative care followed through with management of kidney failure without dialysis. While it was somewhat difficult to provide accurate comparisons of survival times, these investigators reported no substantial difference in expected survival time for those undergoing palliative care compared to hemodialysis. Significantly fewer palliative care deaths (27%) took place in the hospital compared to the proportion of deaths among those patients undergoing hemodialysis (67%). In a study of octogenarians in a single-center where older patients were advised not to undergo dialysis, 25% were conservatively managed. In this report, the median survival of those undergoing conservative management was 8.9 months compared to 28.9 months among those undergoing dialysis. In addition, the cause of death of those managed without dialysis was uremia or pulmonary edema in approximately 60%.
Conservative management should aim to maintain quality of life while keeping in mind the shared decision to avoid dialysis therapy. In addition to continuing to manage fluid status, anemia, electrolytes, and bone metabolism, symptoms should be addressed by the geriatric, nephrology, and palliative care teams. Among both groups of patients undergoing dialysis and receiving palliative care, symptoms should be treated since pain, dry itchy skin, poor sleep, and fatigue impact mood and quality of life. A study has recently shown improvement in pain among ESRD patients managed using the World Health Organization (WHO) three-step analgesic ladder. A nutritional approach to avoiding dialysis therapy was assessed in nondiabetic patients older than 70 years. In this randomized study, patients with kidney failure were assigned a supplemented very low protein diet compared to usual care with dialysis. This study found that those patients assigned the dietary intervention spent an additional 10.7 months off dialysis without substantial differences in survival between groups. These findings suggest that nutrition may play an important role in managing patients who elect to avoid dialysis.
Management of End Stage Renal Disease on Dialysis
Anemia is a common problem with CKD and kidney failure. The fall in hematocrit correlates roughly with the severity of the renal disease, although individual variation is considerable. In general, anemia presents when the GFR is around 35 mL/min. The bone marrow is hypoproliferative while peripheral blood (red cell) indices are normal unless there is superimposed deficiency of iron or folic acid. Thus, the anemia seen with kidney failure is typically a normochromic, normocytic anemia. The lack of erythropoietin production, which occurs with CKD, is the primary cause of anemia with kidney failure. Since erythropoietin production occurs primarily in the kidney, erythropoietin levels are inadequate with CKD, thus depriving the bone marrow of the stimulus necessary for production of red blood cells. The isolation of human erythropoietin and subsequent production of recombinant erythropoietin has been a major advance in the care of those with CKD. Beginning in 1989, synthetic erythropoietin has been available and effectively treats the anemia of CRF. Recently another recombinant form, darbepoeitin, has become available and permitted less frequent dosing regimens. Correction of anemia has improved quality of life, reduced the need for transfusions, improved cognitive performance, and decreased left ventricular hypertrophy. There are adverse effects of using erythropoeitin in the patient with CKD, including iron deficiency (the stimulation of red blood cell production outstrips iron stores), hypertension, and vascular thrombosis.
The optimal hemoglobin target for patients with anemia caused by chronic kidney failure remains somewhat unclear. Recent data in the CKD population suggest untoward cardiovascular outcomes at higher hemoglobin levels. The current conservative target is a hemoglobin count between 11 and 12 mg/dL. In addition to close attention to erythropoietin dosing and hemoglobin levels, adequate anemia management requires routine analysis and treatment of iron deficiency. Iron levels tend to drop in patients on erythropoietin therapy because of increased iron utilization. All patients, however, should receive routine screening of stool for occult blood and periodic screening colonoscopy. Iron-deficient ESRD patients usually receive intravenous replacement iron at the end of their dialysis treatments, either as dextran, gluconate, or sucrate solution. Because they absorb oral iron poorly, ESRD patients have “functional” iron deficiency when their transferrin falls below 100 ng/mL or their iron saturation is less than 20%.
Many more patients have CKD compared to the numbers receiving RRT. The disparity between the number receiving RRT and the number with CKD is explained by the high mortality from cardiovascular disease prior to needing dialysis in the CKD population. Even on dialysis, the risk of death from cardiovascular disease remains 10 to 100 times higher than the risk of a person from the general population. While traditional risk factors account for only a portion of the increased risk associated with kidney disease, the etiology of the increased cardiovascular risk is unclear. There are a number of potential factors that represent classical risk factors shared between atherosclerosis and kidney disease such as age, hypercholesterolemia, hypertension, smoking, and obesity. In addition, there are a number of factors specific to kidney failure such as anemia, hyperhomocysteinemia, hypervolemia, and hyperparathyroidism. These factors can act to promote both cardiomyopathy and ischemic heart disease. The current treatment recommendations focus on optimizing management of known cardiovascular risk factors and on recognizing harbingers of active cardiovascular disease. Those caring for patients with CKD should consider the cardiovascular disease management as an important part of their care.
Calcium, Phosphorous, Hyperparathyroidism, and Bone Disorders
Kidney failure is associated with abnormalities of divalent ions (Ca2+, P) and of the hormones that regulate the concentration of these minerals in body fluids. One of the earliest detectable abnormalities in kidney failure is a rise in parathyroid hormone (PTH), which can occur at a GFR of 40 mL/min. Secondary hyperparathyroidism is a major cause of bone disease in patients with kidney failure. Two inhibitors of parathyroid hormone are ionized calcium (the active form of calcium) and 1,25-(OH)2D3, which has an independent inhibitory effect on parathyroid hormone release. No difference has been found in hyperphosphatemia or severity of renal osteodystrophy in elderly dialysis patients as compared with younger dialysis patients, and there is no correlation between plasma 1,25-dihydroxyvitamin D3 levels and age in patients with kidney failure. Elderly female dialysis patients have significantly lower bone mineral content and bone width when compared with younger dialysis patients matched for duration of dialysis. There is a higher incidence of pathologic fracture, vascular or metastatic calcification, and bone pain in elderly patients on dialysis than in younger patients. The overall result of these disturbances is that patients with ESRD may develop a complex form of bone disease (renal osteodystrophy). Furthermore, there has been a strong association of disordered bone and mineral metabolism and risk of cardiovascular disease. This association between calcium and phosphate metabolism has been most striking when images of the heart demonstrating extensive calcification have been related to levels of both calcium and phosphate.
Treatment of renal osteodystrophy and secondary hyperparathyroidism in the geriatric renal patient is similar to the younger patient. However, the optimal management of patients has been controversial. Hyperphosphatemia is treated with a low phosphate diet and with various phosphate binders. Recent recommendations advise that daily calcium in the phosphate binder should be less than 2 g. Hypocalcemia can be treated with oral calcium, oral or intravenous calcitriol, or other Vitamin D analog, or higher dialysate calcium. Refractory hyperparathyroidism can be treated with parathyroidectomy or with a trial of a calcimimetic. While the agents used to regulate calcium and phosphate levels remain controversial, the goals of normalizing calcium and phosphate levels and improving bone health are widely accepted as important in the management of CKD patients.
The acidosis associated with renal disease is not more severe in the elderly patient despite the decreased ability to handle an acid load seen with normal aging. Acidemia caused by metabolic acidosis is associated with increased oxidation of branched chain amino acids, increased protein degradation, and decreased albumin synthesis. Because of the adverse metabolic effects of chronic acidosis, such as accelerated bone loss and muscle wasting, goals of therapy should be directed at achieving predialysis serum bicarbonate levels of at least 22 mmol/L. If predialysis levels routinely fall below 22 mmol/L, acidemia may be treated by increasing the dialysis bicarbonate in those undergoing hemodialysis, or supplementation with oral sodium bicarbonate tablets.
Nutrition plays an important role in the health and well-being of patients with kidney failure. Patients with kidney failure are thought to benefit from intensive monitoring of nutritional status. The recommended assessments include body weight, dietary interviews and diaries, serum albumin, and total nitrogen appearance. A renal dietician may offer alternative foods and recommendations to patients that feel limited by fluid, sodium, potassium, and phosphate restrictions. Weight loss and inability to maintain nutritional status are indications for initiating hemodialysis and adequacy of dialysis therapy should be evaluated to avoid anorexia and nausea. Dietary supplements and vitamin and mineral supplements, such as zinc or oral pyridoxine (50 mg/day), might be helpful. It is unclear whether intradialytic parenteral nutrition offers real benefit. There are no controlled studies available, and are very expensive to conduct. Dietary restrictions in the elderly patient undergoing dialysis should be minimal. Patients with inadequate intake rarely need food restrictions.
Itching in patients with kidney failure can adversely affect sleep and quality of life. The causes of itching in elderly patients with kidney failure would include xerosis, uremic itching, medication sensitivity, and other chronic health conditions such as diabetes. Pruritus is common in the elderly dialysis patient, possibly because of skin changes seen with aging. As a part of an approach to managing uremic itching, it has been recommended to optimize dialysis treatment by increasing dialysis dose, treating anemia and iron deficiency, and maintaining a low serum phosphate. Treatment of itching caused by xerosis or uremia has been largely symptomatic local treatment consisting of keeping the skin moist with emollients, bathing less frequently and with tepid rather than hot water, and increasing ambient humidity with vaporizers or humidifiers. Capsaicin cream may also be effective. A promising new approach has been tested in two randomized trials of nalfurafine, a k-opioid receptor agonist. These studies of patients with severe uremic itching demonstrated improvement in itching intensity and sleep disturbances compared to placebo. Antihistamines such as diphenhydramine or hydroxyzine may be used, but may cause sedation and cognitive impairment in elderly patients.