In most developing countries, strategies targeting early detection of kidney disease must draw on governmental resources. In poor countries, however, WHO data indicate that governmental spending on health care is limited to 0.4% to 4% of gross national product, compared with 10% to 16% in the developed nations. Resources are also disproportionately distributed, with urban areas receiving the lion’s share (14%). Precisely this point is made by Sainath in his book titled Everybody Loves a Good Drought, in which he states: “Only 20% of hospital beds are in rural areas where 80% of Indians live. Across the country are thousands of Primary Health Centres (PHCs) and dispensaries that function largely on paper. Many of these have not seen a doctor for months, even years in some cases.”
In developing countries like India, per capita income is so low that individuals often survive on less than $1 per day. Compounding this scarcity of funds and limited access to health care is the endemic nature of corruption. Millions of dollars are spent on projects that the population does not need while important public health mandates go unfunded.
To sharpen the focus on CKD in poor countries, two important steps are critical: the generation of reliable data showing that CKD prevalence is higher than previously estimated, and second, public awareness and education about CKD. Accurately estimating CKD prevalence would put to rest the issue of whether kidney disease is common in poor countries. It would also identify individuals at greatest risk, and if these were people who are impoverished and/or live in rural settings it would provide for an impetus to channel resources towards them.
Making better than an educated guess about the burden of kidney disease will allow for better planning and more intelligent long-term allocation of resources. Developing awareness in the population and educating both the population and physicians about CKD will facilitate earlier detection, a greater motivation to seek and adhere to treatment, and a more forceful approach to expecting society to provide for treatment.
Accurate data lacking
The importance of obtaining accurate epidemiologic information on CKD should be obvious, but acquiring these data presents substantial challenges. Virtually all studies on CKD prevalence in the developing world have relied on serum creatinine as the primary measure of kidney function. This approach has limitations because creatinine is influenced to a significant degree by muscle mass and meat intake. Impoverished people who are well below their ideal body mass and eating a sparse diet dominated by vegetables and grains are likely to have a lower serum creatinine that will overestimate glomerular filtration rate (GFR).
Furthermore, many developing countries lack national agencies charged with standardizing laboratories, so most of the population will have a creatinine measurement that is not standardized. Creatinine measurement and reporting varies from center to center, so the diagnosis of CKD is open to considerable inaccuracy. Ideally, actual GFR measurements would avoid these pitfalls. Measurement of GFR by either insulin clearance or using an isotope tracer, however, is time consuming, expensive, and requires specialized equipment. Methods of estimating GFR based on serum creatinine, age, race, sex and body size, such as the Cockroft-Gault formula and Modified Diet in Renal Disease (MDRD) study equation, are more accurate than serum creatinine or measured creatinine clearance (J Am Soc Nephrol. 2003; 14:2573-2580).
These two methods, however, have not been validated in different racial and ethnic populations. Moreover, lack of standardization of creatinine measurements becomes an issue when a GFR-estimating equation such as the MDRD equation is used. Over the past two years, the federal National Kidney Disease Education Program has spearheaded a process to standardize creatinine measurement and calibration, and this has gained steam as a national effort in the United States (Clin Chem. 2006; 52:5-18). Making this initiative international should provide for uniformity in creatinine measurement and reporting.
Screening, education programs
Several broad-based efforts targeted at screening for CKD, as well as increasing awareness and education regarding kidney disease, are currently underway. The Commission on Global Advancement of Nephrology (COMGAN), an agency of the International Society of Nephrology (ISN), has initiated programs for education on prevention of CKD through early detection and sustained therapeutic intervention (Kidney Int. 2005; 68:1395-1410; Nat Clin Pract Nephrol. 2006;2:1). Screening programs have been carried out in United States, Australia, Japan, the Netherlands, and Singapore using different screening strategies.
The National Kidney Foundation has introduced the Kidney Early Evaluation Program (KEEP) program in the United States using a ‘high risk’ screening model (Am J Kidney Dis. 2003;42:22-35). This has focused on both screening and education of the at-risk population in the United States, such as individuals with a history of diabetes or hypertension or their first-degree relatives with diabetes, hypertension, or CKD. The study found CKD rates greater than 50%, with CKD awareness among screened individuals less than 5%. NKF wants to roll out KEEP to other countries, some of which have expressed interest.
In Europe, the PREVEND (Prevention of Renal and Vascular End stage Disease) study in the Netherlands has completed screening of 40,000 subjects and has provided important insights about the prevalence of albuminuria and associated risk factors (Kidney Int Suppl. 2005; 94:S28-35). A study in Australia led by Wendy Hoy, MD, has focused on the northern Australian aboriginal (Ethn Dis. 2002;Summer; 12:373-378).
The AusDiab study has screened 11,247 subjects and found a prevalence of CKD (eGFR below 60 mL/min/1.73m2) of approximately 11% and a proteinuria rate of 3%. In Singapore, NKF conducted population screening, workplace screening of taxi drivers, screening of family members of patients with ESRD, and school screening. The researchers observed rates of urinary abnormalities of isolated proteinuria and isolated hematuria of 2.2%-9.1% and 0.8%-5.3%, respectively, and combined proteinuria and hematuria rates of 0.3%-2.9% in the various groups (Kidney Int Suppl. 2003;:S61-S65).
Surprising find in India
In India, M. Krishna Mani, MD, and co-workers in Chennai found a prevalence of kidney disease of approximately 1% (Kidney Int Suppl. 2003;:S86-S89; Kidney Int Suppl. 2005;:S75-S78). In contrast, in Pakistan, Tazeen H. Jafar, MD, and her colleagues observed a CKD prevalence of ap-proximately 15%-20% among people older than 40 years in a population-based screening (J Am Soc Nephrol. 2005;16:1413-1419). Physicians in Boston (the authors) have launched a CKD screening program in the developing world called the Screening and Early Evaluation of Kidney Disease (SEEK). This is a multicenter study involving more than 15 academic centers across India. SEEK aims to determine the prevalence of CKD and to increase awareness of it.
In the initial phase of SEEK, we have examined the prevalence of CKD in an at-risk population using the modified MDRD-3 abbreviated equation. We have used a central laboratory to measure creatinine with an analyzer standardized using the Cleveland Clinic Foundation creatinine panel. We have also standardized urine protein measurement by using Bayer Multistix 10 SG throughout our study. These methods have allowed us to benchmark our numbers to measurements in the United States and Europe. The prevalence of CKD in this Indian cohort using standardized eGFR methodology is 13%, which is 13-fold higher than previous reports from India and is similar to prior U.S. data from the National Health and Nutrition Examination Survey. These data are expected to be discussed more extensively at the 2006 annual meeting of the American Society of Nephrology in San Diego.
Our report of much higher prevalence is relevant because of the public health implications of this high prevalence rate if it were generalized to a population of more than 1 billion people. SEEK also has embarked on education and awareness initiatives that pivot around “world disease days”—for example, “world kidney day” and “world hypertension day.” CME symposia and lectures target physicians whereas “health days” target the general population. The success of these programs is hard to evaluate but the media attention so far indicates tremendous interest. The SEEK program also is important because represents the first foray by a major health-care company (Johnson & Johnson) into the arena of CKD screening and education at a global level.
A screening strategy for developing nations should bridge the need to identify people with CKD at an early stage with the need to craft programs targeted at early and cost-effective treatment. Paying for treatment is perhaps an even steeper hill to climb than documenting the extent of the problem. The cataclysm of the HIV/AIDS crisis in the developing world, however, has provided one overarching lesson to all of us: Ignoring the problem will not make it go away.
Drs. Singh and Mittal are at the Brigham and Women’s Hospital in Boston. Dr. Singh is clinical
director of the hospital’s renal division and is associate professor of medicine at HarvardMedicalSchool in Boston. Dr. Mittal is senior research associate in the renal division.