Options for Patients with End-Stage Renal Disease

Gabriel M. Danovitch

Before 1970, therapeutic options for patients with end-stage renal disease (ESRD) were quite limited. Only a small number of patients received regular dialysis because few dialysis facilities had been established. Patients underwent extensive medical screening to determine their eligibility for ongoing therapy, and treatment was offered only to patients who had renal failure as the predominant clinical management issue. Kidney transplantation was in the early stages of development as a viable therapeutic option. Transplant immunology and immunosuppressive therapy were in their infancy, and for most patients, a diagnosis of chronic renal failure was a death sentence.

In the decades that followed, the availability of care for patients with kidney failure grew rapidly throughout the developed world. In the United States, the passage of Medicare entitlement legislation, in 1972, to pay for renal replacement therapy (RRT—maintenance dialysis and renal transplantation), provided the major stimulus for this expansion. In the so-called developed world, RRT services are now available, in principle if not always in practice, for all those in need. In the developing world, such services are still sporadic. It has been estimated that in South Asia, more than 90% of patients with ESRD die within months of diagnosis, and in most parts of Africa, the reality is even starker.

Despite numerous medical and technical advances, patients with kidney failure who are treated with dialysis often remain unwell. Constitutional symptoms of fatigue and malaise persist despite better management of anemia with erythropoietin. Progressive cardiovascular disease (CVD), peripheral and autonomic neuropathy, bone disease, and sexual dysfunction are common, even in patients who are judged to be treated adequately with dialysis. Patients may become dependent on family members or others for physical, emotional, and financial assistance. Rehabilitation, particularly vocational rehabilitation, remains poor. Such findings are not unexpected, however, because the most efficient hemodialysis regimens provide less than 15% of the small-solute removal of two normally functioning kidneys. Removal of higher-molecular-weight solutes is even less efficient.

For most patients with kidney failure, kidney transplantation has the greatest potential for restoring a healthy, productive life. Renal transplantation does not, however, occur in a clinical vacuum. Virtually all transplant recipients have been exposed to the adverse consequences of chronic kidney disease (CKD). Practitioners of kidney transplantation must consider the clinical impact of CKD on the overall health of renal transplantation candidates when this therapeutic option is first considered. They must also remain cognizant of the potential long-term consequences of previous and current CKD (see Chapter 7) during what may be decades of clinical follow-up after successful renal transplantation (see Chapter 10). For updated reviews of the medical literature relating to ESRD and dialysis and transplantation, readers are referred to the American Society of Nephrology Self-Assessment Program (NephSAP) (see “Selected Readings”).

STAGES OF CHRONIC KIDNEY DISEASE

Table 1.1 summarizes the stages of CKD as defined by the National Kidney Foundation Disease Outcome Quality Initiative (K/DOQI). The purpose of this classification is to permit more accurate assessments of the frequency and severity of CKD in the general population, enabling more effective targeting of treatment recommendations. Note that the classification is based on estimated values for glomerular filtration rate (GFR) and that the terms kidney failure and ESRD are used for patients with values less than 15 mL per minute. It has been estimated that close to 20 million adults in the United States have CKD that can be categorized as stage 1, 2, 3, or 4, whereas nearly half a million have overt kidney failure, or stage 5 CKD. The classification may overestimate the incidence of CKD in elderly people because of the impact of normal aging on renal function. The known population of patients with ESRD thus represents only the “tip of the iceberg” of progressive CKD. It is also evident from Table 1.1 that most, if not all, kidney transplant recipients can be regarded as having some degree of CKD because their kidney function is rarely normal.

A discussion of the management of CKD in the general population is beyond the scope of this text. Strict blood pressure control and the use of angiotensin-converting enzyme inhibitors and receptor blockers, both in diabetic patients and those with proteinuria from other glomerular diseases, are standard practice. There is less certainty, however, about the benefits of these agents in patients without significant proteinuria. Low-protein diets may delay the onset of kidney failure or death in patients with established CKD, but there is insufficient evidence to recommend restricting dietary protein intake to less than 0.8 g/kg per day on a routine basis, and malnutrition is a real concern (see Chapter 19). Lipid-lowering agents and lifestyle changes, particularly smoking cessation, may slow disease progression. Many of the concerns and treatment recommendations pertaining to the long-term management of kidney transplant recipients, which are discussed in Chapter 10, also apply to patients with CKD.

Estimation of Glomerular Filtration Rate

Measurements of GFR provide an overall assessment of kidney function in both the transplantation and nontransplantation settings. The GFR is measured best by the clearance of an ideal filtration marker such as inulin or with radiolabeled filtration markers (see Chapter 13). In clinical practice, GFR is usually estimated from measurements of creatinine clearance or serum creatinine levels to circumvent the need for timed urine specimen collections. Several equations have been developed to estimate GFR after accounting for variations in age, sex, body weight, and race. The most popular and easiest to use among Stages of Chronic Kidney Disease
these are the Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) equations. The Cockcroft-Gault equation is as follows:

TABLE 1.1 Stages of Chronic Kidney Disease

Stage	Description	GFR (mL/min/1.73m²)
1	Kidney damage with normal or increased GFR	>90
2	Kidney damage with mild decrease in GFR	60-90
3	Moderate decrease in GFR	30-59
4	Severe decrease in GFR	15-29
5	Kidney failure	<15 or dialysis
GFR, glomerular filtration rate.

MDRD uses a formula based on serum creatinine, age, gender, and race. These equations were validated in studies of white patients with nondiabetic CKD. Their validity in other populations, including renal transplant recipients and their living donors, may be inconsistent.

DEMOGRAPHICS OF THE END-STAGE RENAL DISEASE POPULATION

United States

Each year, the United States Renal Data System (USRDS) provides updated demographic information about patients with kidney disease who are treated either with dialysis or renal transplantation in the United States. Excerpts of this massive report, presented in an easily accessible fashion, are published annually in the January issue of the American Journal of Kidney Diseases (see “Selected Readings”). According to the 2008 report, as of December 2006, about 400,000 patients were receiving maintenance dialysis in the United States (Table 1.2 and Fig. 1.1) and about 150,000 had a functioning transplant. The increase in number of dialysis patients has slowed somewhat, and this number now increases at an annual rate of about 4%. By the year 2010, the number of dialysis patients is expected to approach 500,000. About 7% of the Medicare population suffers from CKD.

About 40% of patients receiving regular dialysis are older than 65 years, and the mean age of those beginning treatment is greater than 60 years; these numbers are projected to increase in the next decade. This phenomenon has been described as the “gerontologizing” of nephrology, and accounts for the frequency of aged of patients being evaluated for, awaiting, and undergoing renal transplantation (see Chapters 7 and 10). In the ESRD population, men slightly outnumber women, and more than 30% are African American. The prevalence of African Americans in the ESRD population thus exceeds by threefold their percentage in the general population of the United States. Much evidence also links poverty to CKD, either as a direct impact of poverty on CKD or indirectly through the increased health care burden linked to poverty-associated diabetes and hypertension. The poor and socially deprived have a greater prevalence of ESRD. Access to renal care, dialysis, and transplantation may also be affected by social deprivation. Poverty and social deprivation are emerging as major risk markers for CKD in both developing and developed countries.

Despite improvements in the clinical management of both diabetes mellitus and hypertension, these two diagnostic categories remain by far the most common causes of ESRD. In Hispanic and Native American patients, the burden of diabetes is particularly heavy. Older patients and those with diabetes are more likely to be accepted for dialysis in the United States than in other countries. Moreover, patients now beginning dialysis in the United States have more comorbid medical conditions than those accepted for treatment in the 1980s. Congestive heart failure is present in 35% of the incident dialysis population, whereas coronary artery disease can be found in up to 40% of the incident dialysis population in some published reports.

There has been a steady increase the number of deceased donor kidney transplants performed each year: about 8500 in 2002 and 10,500 in 2008. This increase largely reflects the efforts of the Organ Donation and Transplantation Breakthrough Collaborative (see Chapter 4). The annual number of living donor
transplants has fallen somewhat to about 6000 in 2008 despite an increase in the number of transplants from living donors who are not biologically related to the recipient (see Chapter 6). The number of patients who are awaiting deceased donor renal transplantation is progressively rising (Fig. 1.1), reaching more than 80,000 by early 2009. About one third of these patients have been designated “inactive,” and the “active” transplant waiting list has remained stable (see Chapter 4). There are likely many ESRD patients who are potential transplant candidates but have not been referred to transplant programs, so there remains a massive gap between the supply of and the demand for deceased donor kidneys. Consequently, the average waiting time for a deceased donor transplant has increased substantially, and it is now measured in years for most patients (see Chapters 4 and 7). The increasing incidence of CKD and ESRD, in a background of a national “epidemic” of obesity, diabetes, and inadequately treated hypertension, makes it unlikely that waiting time for a transplant will be eradicated in the absence of more effective CKD prevention. Demographics of the Dialysis Population in the United States*

TABLE 1.2 Demographics of the Dialysis Population in the United States^*

Demographic Age (yr)	Percentage
<20	0.7
20-44	15
45-64	41
65-74	22
>75	21
Sex
Male	54
Female	46
Race
African American	37
White	55
Asian	4
Native American	2
Primary ESRD Diagnosis
Diabetic nephropathy	43
Hypertension	28
Glomerulonephritis	11
Cystic kidney disease	3
Urologic disease	2
Other^†	13
^*Point prevalence as of December 31, 2006. ^†Nearly 10% of patients with end-stage renal disease (ESRD) have a failed transplant.
From Collins AJ, Foley RN, Herzog C, et al: Excerpts from the United States Renal Data System 2008 Annual Data Report. Am J Kidney Dis 2009;53(Suppl 1):S1—S374, with permission.

Worldwide

The worldwide dialysis population is estimated to be greater than 1 million persons. The highest prevalence and incidence rates for ESRD are reported from Taiwan, Japan, and the United States. The high rate in the United States (Fig. 1.2) reflects, in part, the high incidence of ESRD in African Americans.
Other factors, particularly limitations on the availability of dialysis, also play a role. Age is an important factor for patient selection in some countries, whereas in the United States, there is no age restriction for providing dialysis, and this largely explains the steady rise in the average age of the U.S. dialysis population. Modalities for the management of ESRD vary among countries. For example, in the United Kingdom, Australia, and Canada, home dialysis is used extensively, whereas this therapeutic approach is uncommon in Japan and the United States. Renal transplantation rates from both deceased and living donors vary considerably among developed countries (Fig. 1.3

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