CKD: Common, Harmful, and Treatable—World Kidney Day 2007

Rationale 

Figure 1 shows a conceptual model for CKD as the basis for a public health approach, emphasizing stages of CKD, as well as antecedents, outcomes, and risk factors for the development and progression of CKD. CKD is defined as either kidney damage, estimated by using such markers as albuminuria, or glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 (<1.00 mL/s/1.73 m2) for 3 months or longer.1, 2, 3 Albuminuria usually is defined as a spot urine protein-creatinine ratio greater than 30 mg/g, and GFR usually is determined by using serum creatinine level, age, sex, and race. In the United States, recent data from the National Health and Nutrition Examination Survey (NHANES) estimates a prevalence of CKD of 9.6% in noninstitutionalized adults, corresponding to approximately 19 million people (Table 1).4, 5 The elderly, racial and ethnic minorities, and those with lower socioeconomic status are affected disproportionately. Prevalence estimates in other countries are difficult to interpret because of differences in serum and urine creatinine levels caused by variability among studies in assays, muscle mass, and diet. Nonetheless, in both developed and developing nations, a consistent picture is emerging of increased risk of CKD in people with CVD risk factors or established CVD.

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Figure 1. Conceptual model of the course of CKD. Shaded ellipses, stages of CKD; unshaded ellipses, potential antecedents or consequences of CKD; thick arrows between ellipses, risk factors associated with the initiation and progression of disease that can be affected or detected by interventions: susceptibility factors (black), initiation factors (dark gray), progression factors (light gray), and end-stage factors (white). Interventions for each stage are given beneath the stage. Persons without CKD should be assessed for CKD risk factors. Persons known to be at increased risk of CKD should be tested for CKD. “Complications” refer to all complications of CKD and its treatment, including complications of decreased GFR (hypertension, anemia, malnutrition, and bone and mineral disease) and CVD. Increasing thickness of arrows connecting later stages to complications represents the increased risk of complications as kidney disease progresses. Modified and reprinted with permission.1, 2, 3

Table 1. Stages of CKD With Prevalence in the United States (National Health and Nutrition Examination Survey 1999 to 2000) and Stage-Specific Recommendations for Detection, Evaluation, and Management (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative)

	CKD Stage	Description	GFR (mL/min/1.73 m2)	Detection, Evaluation, and Management	US Prevalence in 2000⁎
	1	Kidney damage with normal or ↑ GFR	>90	Diagnosis and treatment, treatment of comorbid conditions, slowing progression, CVD risk reduction	5,600(2.8)
	2	Kidney damage with mild ↓ GFR	60-89	Estimation of progression	5,700(2.8)
	3	Moderate ↓ GFR	30-59	Evaluating and treating complications	7,400(3.7)
	4	Severe ↓ GFR	15-29	Referral to nephrologist and consideration for kidney replacement therapy	300(0.1)
	5	Kidney failure	<15	Kidney replacement therapy (if uremia present)	300†(0.2)

Note: Prevalence values expressed as number in thousands (percent). To convert GFR in mL/min/1.73 m2 to mL/s/1.73 m2, multiply by 0.01667.

⁎ Kidney damage defined as persistent albuminuria on 2 occasions.4 † Prevalence of stage 5 is from the US Renal Data System for number of patients on dialysis therapy. This is an underestimate because it does not include the additional unknown number with kidney failure not receiving treatment.17

The most important adverse outcomes of CKD include not only complications of decreased GFR and progression to kidney failure, but also increased risk of CVD. Many studies show that albuminuria and decreased estimated GFR each consistently and in a graded fashion increase the risk of CVD.6 Indeed, recent studies show that patients with CKD are 100 times more likely to die, principally of CVD, than to develop kidney failure.7 There now are convincing data for the efficacy of treatment to prevent complications of decreased GFR, slow the progression of kidney disease, and decrease CVD risk.1, 2, 3 Testing for CKD is feasible in clinical practice, and the same methods can be applied in large-scale screening of people at increased risk. Thus, the tools to improve outcomes for patients with CKD already are available. It now is time to establish policies to translate these advances to public health.

Detection 

CKD detection programs could focus on people with such CVD risk factors as older age, hypertension, diabetes, and hyperlipidemia and those with CVD. The prevalence of CKD is greater in these groups, and many studies have demonstrated that CKD is a “multiplier” for CVD risk.6, 8 As with all CVD risk factors, the increase in absolute risk is greater in people with other risk factors. The “CKD subgroup,” particularly in the elderly, constitutes an especially high-risk group that needs special attention (Table 2). In the CKD subgroup, CVD risk-factor levels are greater and more difficult to control, outcomes are worse, and costs are greater. Many clinical trials of patients with CVD risk reduction or treatment excluded patients with later stages of CKD.9 However, analyses of trials that included patients with earlier stages of CKD generally showed that the beneficial effect of treatment in the CKD subgroup is as large or larger than in the group without CKD.10, 11, 12 Most guidelines for CVD risk-factor conditions and for CVD now recommend testing for CKD and different treatments for people found to have CKD compared with treatments for people without CKD.13, 14, 15

Table 2. Rationale for CKD Detection in People With CVD and CVD Risk Factor Conditions

	CVD is the most common cause of death in developed nations
	CKD is more common in people with CVD and CVD risk factors, including hypertension, diabetes, and dyslipidemia
	CKD multiplies risk of CVD
	Patients with CVD and CVD risk factors and CKD are more ill compared with those without CKD
	Risk-factor levels are higher
	Risk-factor control is more difficult
	CVD outcomes are worse
	Costs of care are higher
	CVD risk-factor management differs in patients with compared with without CKD
	Treatments are available and effective
	To reduce CVD risk
	To manage complications of decreased GFR
	To slow kidney disease progression

Children, adolescents, and young adults with obesity, hypertension, or diabetes also are at increased risk of adverse outcomes related to CKD. It is anticipated that these younger patients have a greater risk of CKD and greater lifetime risk of CVD because of their long exposure to CVD risk factors.16 CVD risk-factor detection programs are beginning for this population and could include testing for CKD.

CKD testing can be implemented within the same infrastructure used for CVD risk-factor testing and should include an assessment for albuminuria and serum creatinine measurement to estimate GFR.1, 3, 5 These measures should detect most cases of CKD in adults caused by hypertension and diabetes. Additional testing for hematuria may be worthwhile in countries with a high prevalence of glomerular diseases. Patients with positive test results for CKD should be evaluated and treated according to established guidelines for CKD.1 In principle, earlier evaluation and treatment would increase the number of patients with CKD who receive treatment and should increase the effectiveness of treatment by beginning at an earlier stage of the disease. In the United States, the incidence of kidney failure caused by diabetes is decreasing in young whites,17 likely because of testing for albuminuria and treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These improved outcomes need to be extended to young blacks and older people.

Surveillance 

CKD surveillance programs could focus initially on patients with severe CKD (stages 4 to 5). These patients are at greatest risk for CVD and death; the occurrence of common and treatable complications of decreased GFR, such as hypertension, anemia, malnutrition, and bone and mineral disease; and progression to kidney failure. Specific treatments are now available for each of these complications and to slow progression; however, many studies demonstrate suboptimal use of effective therapies.18 In the United States, the average age of people with CKD stage 4 is 75 years, and more than 95% have 2 or more complications of decreased GFR.1, 5 In 1 study, 46% died and 18% were treated by dialysis and transplantation during an average follow-up of 3.1 years.7 Current guidelines now recommend referral of all patients with CKD stages 4 to 5 to nephrologists for specialized care and for preparation for dialysis and transplantation when these treatments are offered.1 Many countries have surveillance programs for patients treated using dialysis and transplantation. However, these programs do not include people with severe CKD who die before the onset of kidney failure or who are not treated with dialysis and transplantation despite the onset of kidney failure. In principle, a surveillance program for patients with CKD stages 4 to 5 would enable all countries to monitor the magnitude and care of this high-risk high-cost population and possibly reduce the risk of progression to kidney failure and reduce the cost of dialysis and transplantation.

A surveillance program for patients with CKD stage 3 would reach many more people (Table 1) and might be an effective way to decrease rates of CVD and death, especially in the elderly with CVD risk factors or CVD. However, a larger surveillance program would require more resources. One possible strategy would be to first implement surveillance programs directed at patients with CKD stages 4 to 5, then, using the experience gained, implement a program directed at high-risk subgroups with CKD stage 3.

Prevention 

It is not too ambitious to consider CKD prevention. Hypertension and diabetes are the major causes of CKD in developed nations. In developing nations, chronic viral infections may contribute substantially to the burden of CKD from glomerular diseases. Strong effective public health policies focusing on the prevention, detection, and treatment of these common chronic diseases may reduce the risk of developing CKD. Reduction in the incidence and prevalence of CKD could be a measure of success of public health programs for these other chronic diseases.

Improving and Paying for Patient Care 

Detection, surveillance, and prevention programs will bring more patients with CKD and CKD risk factors into the health care delivery system. As for all chronic diseases, commitment and innovation will be necessary to treat more patients, improve quality, and remain within public and employer group health plan budgets. Partnerships with government and payers are necessary to establish appropriate measures, standardized information technology platforms, appropriate incentives for improving quality, responsible analysis of the cost of care, and novel reimbursement methods.

Research 

Finally, a health care policy for CKD must include investment in basic and clinical research. Research priorities could include studies of causes of CKD and its progression, complications, and relationship to CVD and aging; new markers of kidney damage and better estimating equations for GFR; new treatments to slow progression, ameliorate complications of decreased GFR, and reduce CVD risk; and more effective strategies to implement existing and new treatments across populations.

What Should Nephrologists Do? 

Nephrologists cannot care for all patients with CKD, but we must join the effort to focus worldwide attention on CKD. We can educate our colleagues, government officials, and the public that CKD is common and harmful and, most important, that we have treatment. We can participate with professional, public, and governmental groups to develop public health policy for CKD. We can work collaboratively with primary care physicians and other specialists to establish care models within nephrology and within primary care, including clear recommendations for consultation, comanagement, and communication among treating physicians. We can develop estimates for the nephrology workforce to care for patients with CKD, and we can develop strategies to train and maintain the workforce. We can improve the quality of care for patients with CKD stages 4 to 5. Nephrologists will continue to shoulder the burden of care for these severely ill and challenging patients, and we must strive to do so with diligence, technical skill, and compassion. We must recognize that improving the care and outcomes for patients with CKD is a long process. World Kidney Day 2007 is an opportunity to begin this process. Hereafter, each year on World Kidney Day, we should measure our progress.