Introduction

Deterioration in kidney function, whether acute or chronic, can lead to substantial morbidity and mortality. Acute kidney injury (AKI) is a powerful indicator for in-hospital mortality; those who survive face increased length and cost of hospitalization. Some individuals with chronic kidney disease (CKD) develop progressive renal dysfunction and require costly therapy with dialysis, transplant, or both. Even more often, individuals with CKD face high risks for cardiovascular events, anemia, and fractures.

This chapter reviews current data on the epidemiology and trends in the etiology of AKI, CKD, and end-stage renal disease (ESRD), with a focus on low- and middle-income countries (LMICs). We also review management of these conditions, highlighting several interventions—treatment for AKI, screening for CKD, and modality choice for ESRD—with available data on cost or cost-effectiveness.

Acute Kidney Injury

The Condition

Incidence

AKI occurs commonly, although quantifying its exact burden has been challenging. Before 2004, no standardized definition existed. Symptoms do not occur unless severe disease develops. The causes vary widely according to setting—whether AKI is acquired in hospitals or in communities—and establishing practice patterns for screening is difficult. Community-based studies of prevalence illustrate the wide variation in estimates of AKI that are subject to definition and population; studies report annual incidence rates ranging from 22 to 175 per million population (Himmelfarb and Ikizler 2007).

In the mid-2000s, however, the nephrology community began to establish standardized criteria for a case definition of AKI, and evidence indicates that an increasing number of epidemiology reports rely on this definition (Mehta and others 2015). First released in 2004 (Bellomo and others 2004) and updated in 2007 (Mehta and others 2007) and 2012 (Palevsky and others 2013), these definitions emphasize recognizing early signs of kidney injury, with attention to relatively small changes from baseline serum creatinine or expected urine output—since even these small changes are linked with a substantially increased risk for in-hospital mortality (annex 13A) (Chertow and others 2005).

Standardizing 130 studies to the Kidney Disease: Improving Global Outcomes definition of AKI, an extensive global meta-analysis estimates that one in four adults and one in three children throughout the world suffer from AKI during hospitalized care; about 10 percent of these patients develop AKI severe enough to require dialysis (Hoste and Schurgers 2008; Mehta and others 2015; Susantitaphong and others 2013). The overall AKI incidence rate among adults and children was 23.2 percent (95 percent confidence interval [CI] 21.0 to 25.7 percent), with the highest incidence rate of 31.7 percent occurring in the critical care setting (95 percent CI 28.6 to 35.0 percent). The severe AKI incidence rate was 2.3 percent. Data available on the incidence rate of community-acquired AKI—that is, patients presenting to the hospital after developing symptoms of kidney dysfunction, rather than presenting with a systemic illness that during its treatment course is associated with AKI (hospital-acquired AKI)—were scarce (only seven studies reported this data); however, the rate was relatively lower than that of hospital-acquired AKI at 8.3 percent (95 percent CI 1.6 to 33.0 percent) (Susantitaphong and others 2013).

This analysis also includes only two studies from LMICs. However, a recent update capturing more data from Africa, Asia, and Latin America reports incidence of AKI in these regions comparable to that in high-income countries (HICs) (Mehta and others 2015).

Mortality

Mortality from AKI in HICs has traditionally been reported to be higher than in LMICs, but a recent report indicates that, at least among patients with severe AKI requiring dialysis, mortality rates in LMICs are equivalent or higher (Bouchard and others 2015). A prospective study of AKI in patients hospitalized in intensive care units collected data from three middle-income countries (MICs), Brazil, China, and India; findings indicate that patients in MICs experienced twofold higher odds of mortality and nonrecovery of renal function, despite having lower severity of illness, compared with patients in HICs (Bouchard and others 2015). Single-center studies from LMICs have reported large variation in mortality from AKI requiring dialysis, likely reflecting not only the lack of equipment but also variable levels of expertise (table 13.1).

Table 13.1

Selected Studies with Mortality Estimates for Acute Kidney Injury.

Etiology

Although rigorous registry data are lacking, experts suggest that the incidence of community-acquired AKI is higher in LMICs than in HICs. Severe systemic diseases, such as sepsis or major surgical procedures, cause the majority of cases of AKI in HICs and in urban areas of LMICs. Some community-acquired reasons for AKI are more common in LMICs: obstetric complications; toxins, including snake venom; diarrheal illness; advanced human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS); leptospirosis; and malaria.

In Africa, nephrologists report that major causes of AKI are related to the burden of HIV/AIDS, malaria, leptospirosis, and diarrheal diseases (Lameire and others 2013; Naicker, Aboud, and Gharbi 2008; Prakash and others 2015). More than 50 percent of adults with advanced HIV/AIDS or severe malaria develop AKI (Lameire and others 2013). Noninfectious causes specific to LMICs include obstetric and surgical complications, such as severe hemorrhage or late diagnosis of eclampsia, as well as widespread use of traditional herbal remedies or nonsteroidal anti-inflammatory agents (Luyckx and Naicker 2008; Naicker, Aboud, and Gharbi 2008). Such community-acquired AKI more likely afflicts a younger age group and, especially in cases of malaria or diarrheal illness, exhibits seasonal peaks during rainy seasons (Cerda and others 2008; Lameire and others 2013).

Effectiveness of Interventions

AKI management largely depends on etiology and severity. Treatment algorithms in HICs recommend optimizing volume using crystalloid solutions until clinical dehydration is corrected followed by vasopressor support to maintain perfusion pressure (Kellum, Lameire, and KDIGO AKI Guideline Work Group 2013). In conjunction with this approach, treatment of the underlying cause of AKI, such as antibiotics for infection and avoidance of nephrotoxic medications or procedures, often leads to resolution of mild-to-moderate AKI. In HICs, availability of intensive care units, adequate nursing staffing, and rapid-turnaround laboratory facilities allow for frequent and close monitoring of urine output and serum creatinine. Relatively prompt interventions to ameliorate AKI are performed. If AKI progresses to severe renal failure despite these measures, temporary dialysis may be initiated, either to treat volume and electrolyte imbalances or to remove toxins. Continuous hemodiafiltration and intermittent hemodialysis (HD) are the modalities of choice in HICs, although a meta-analysis highlights equivalent survival in patients receiving peritoneal dialysis (PD) versus HD or continuous hemodiafiltration (Chionh and others 2013).

This level of care is not available in most LMICs. The limitations of diagnosis and treatment for advanced AKI are particularly stark in rural areas, but they are also demonstrated in urban university-based hospitals (Bouchard and others 2015; Cerda and others 2008). Data on missed or delayed diagnosis of AKI in LMICs are nonexistent; by their nature, reports on epidemiology of AKI must apply screening criteria that may not be used in standard practice in LMICs. However, studies have confirmed not only a lack of provision of dialysis or transplant but also a lack of intensive care units as crucial gaps in care (Bagasha and others 2015); the infrastructure and budget required to develop renal replacement therapy (RRT) programs to support AKI are often lower priorities in LMICs still struggling with other pressing public health issues, such as infectious diseases, maternal and perinatal health, and nutrition management (Mushi, Marschall, and Flessa 2015). To address such gaps, the International Society of Nephrology has developed an initiative called “0by25.” The objective of the initiative is to eliminate preventable deaths from AKI by 2025 by calling for global strategies that permit timely diagnosis and treatment (including dialysis) of potentially reversible AKI, with particular emphasis on LMICs (Mehta and others 2015; Remuzzi and Horton 2013) (see box 13.1 for an example of a dialysis provision program in AKI in LMICs).

Box 13.1

Case Study: Acute Kidney Injury (AKI) Treatment with Peritoneal Dialysis (PD) in Tanzania.

Recommendations for Policy Makers in LMICs

Although the current understanding of AKI in LMICs is limited, the nephrology community generally agrees on the following (Mehta and others 2015):

• Known incidence is similar to that in HICs.
• Community-acquired causes are more common than in HICs.
• Affected patients are younger than in HICs.
• Lack of intensive care units and access to acute dialysis results in high mortality rates.

This consensus is largely drawn from expert opinions or single-center studies; additional studies are required to estimate the burden, etiology, and mortality of AKI in LMICs.

Based on current consensus, however, the prevention of community-acquired AKI (table 13.2) may play a more crucial role in LMICs. Management algorithms that take the most common region-specific causes into account are crucial in areas with limited staffing of trained physicians. When the need for dialysis arises, temporary PD—a less technologically demanding and less costly modality—can be used for both pediatric and adult acute cases. The International Society of Peritoneal Dialysis has published guidelines to standardize the provision of acute PD (Cullis and others 2014). Successful programmatic implementation of PD—training staff, acquiring dialysis equipment, and prescribing dialysis appropriately—has occurred in third-level centers in Benin, Cambodia, Ghana, Sudan, and Tanzania (Finkelstein and others 2014; Wilkie 2014). However, the challenges of scalability and managing patients who do not recover renal function and require long-term dialysis remain (Kilonzo and others 2012).

Table 13.2

Prevention and Management of Acute Kidney Injury in LMICs.

Chronic Kidney Disease and End-Stage Renal Disease

The Condition

Epidemiology of CKD

CKD is diagnosed when an individual has evidence of persistent kidney dysfunction, as reflected by albuminuria, reduction in estimated glomerular filtration rate (eGFR), or both. Identifying individuals with CKD arguably facilitates treatment to reduce cardiovascular events and slow the progression to ESRD (Levey and Coresh 2012).

However, guidelines for streamlining CKD diagnosis have generated controversy because of their reliance on the glomerular filtration rate (GFR) (annex 13B) (Kidney Disease: Improving Global Outcomes Work Group 2012; Levey and others 2003). Older adults who have isolated modest eGFR reductions may have kidney function at the lower end of the normal-for-age range (Wetzels and others 2007), creating the potential for false positives and overutilization of medical resources (Moynihan, Glassock, and Doust 2013; Poggio and Rule 2009). Most cross-sectionally obtained prevalence estimates fail to fulfill the criteria of repeating assessment at three months to determine persistence (Plata and others 1998). Finally, interpretation of albuminuria requires caution in LMICs, where hygiene, malnutrition, and dietary habits may affect urinary excretion of albumin and creatinine.

With these caveats in mind, we make the following interpretation from available population-based prevalence studies (annex 13C):

• CKD prevalence is understudied in LMICs.
• CKD prevalence in LMICs approaches that of HICs.
• Earlier stages of CKD—albuminuria alone—are common in LMICs, unlike HICs, where modest eGFR reductions with or without albuminuria (CKD stage 3) predominate.

At the same time, individuals with CKD in LMICs remain at high risk of adverse events. Notably, albuminuria has been associated with a linear and sizable increase in risk for all-cause mortality and cardiovascular events, starting at urine albumin-to-creatinine ratios above 10 milligrams/gram (Chronic Kidney Disease Prognosis Consortium and others 2010). Risk for ESRD is 4–11 times higher among individuals with albuminuria (Chronic Kidney Disease Prognosis Consortium and others 2010).

Epidemiology of ESRD

ESRD is rare. About 2 million people are undergoing RRT (either dialysis or kidney transplant) worldwide, with a prevalence of 300 per million adult population or 0.03 percent, compared with prevalence estimates in the range of 7 percent to 15 percent for earlier stages of CKD (Anand, Bitton, and Gaziano 2013; Grassman and others 2005; Thomas and others 2015). While the number of people on RRT has nearly doubled since 1990, 80 percent of the individuals receiving RRT live in HICs (Grassmann and others 2005). The latest Global Burden of Disease estimates from the World Health Organization note that 1.8 percent and 1.1 percent to 1.8 percent of deaths in HICs and LMICs, respectively, are attributable to kidney disease; the cause of death is presumably complications of ESRD.

Currently available data only capture information on patients who have access to RRT, not all those who develop ESRD. In HICs, these numbers are roughly equal because most patients who develop ESRD are diagnosed and offered therapy. In LMICs, however, RRT incidence is not a proxy for ESRD incidence, because individuals may die before or immediately after diagnosis, or they may withdraw from therapy because they cannot pay for it (Couser and others 2011).

Two analyses comparing RRT use with projected ESRD prevalence highlight a large disparity (Anand, Bitton, and Gaziano 2013; Liyanage and others 2015); fewer than 5 percent of patients projected to have ESRD actually access therapy in China, India, and Nigeria (Anand, Bitton, and Gaziano 2013). The provision of RRT closely tracks a country’s gross national product rather than the prevalence of risk factors.

Trends in Prevalence and Etiology of CKD and ESRD

Despite concerns about accurate diagnosis, most experts agree that CKD is a growing concern worldwide because of the skyrocketing prevalence of its major correlates: diabetes and hypertension. As noted in chapter 2 in this volume (Ajay, Watkins, and Prabhakaran 2017), LMICs are projected to experience the largest percentage increases in the prevalence of diabetes and hypertension (Hossain, Kawar, and El Nahas 2007). Individuals in LMICs are more likely to develop end-organ damage, including progressive CKD, because of delayed diagnosis and poor management of diabetes and hypertension. In a study of individuals with diabetes in Cambodia, more than 50 percent had CKD (Thomas and others 2014), compared with about one-third in the United States (de Boer and others 2011). Not surprisingly, these diseases are an increasingly common cause of ESRD in LMICs. In 2011, 28 percent of cases of ESRD in Brazil were attributed to diabetes, compared with 8 percent in the mid-1990s; 35 percent were attributed to hypertension, compared with 15 percent in 2002 (Oliveira, Romao, and Zatz 2005; Sesso Rde and others 2012).

Although the prevalence of CKD and ESRD related to diabetes and hypertension will increase across the world, HIV nephropathy—a disease of untreated HIV/AIDS resulting in proteinuric kidney disease—will potentially decline. As more individuals with HIV/AIDS have received treatment with antiretroviral drugs, CKD related to side effects of antiretrovirals, comorbid diabetes, or hypertension has already become more common in HICs, a trend that LMICs may follow (Mallipattu, Salem, and Wyatt 2014).

However, kidney diseases related to other infectious diseases—malaria, hepatitis B or C, leptospirosis, and dengue—continue to disproportionately affect individuals in LMICs (Soderland and others 2010). Unusual causes of CKD, including stones and environmental toxins, are also concentrated in LMICs. Stone-related kidney disease is relatively more important in certain regions. In HICs, 3 percent of cases of ESRD are attributed to obstructive uropathy (Jungers and others 2004); in countries along the “stone belt” (a region encompassing North Africa and South and Southeast Asia), up to 6 percent to 11 percent of cases of ESRD are attributed to obstructive uropathy (Jha 2009). Hot climates that predispose individuals to volume depletion or low urine output, low potassium diets, and chewing of calcium hydroxide containing betel leaf all increase the risk for stone formation (Lopez and Hoppe 2010). Limited access to treatment increases the risk for CKD and ESRD.

Individuals in LMICs may experience higher risk for CKD related to environmental toxins, such as lead, arsenic, cadmium, and aristolochic acid. Public health experts from Sri Lanka and the west coast of Central America report that scores of agricultural workers are being diagnosed with CKD unaccompanied by diabetes or hypertension (box 13.2) As yet, there are many unknowns about this phenomenon, including whether the same disease entity is afflicting workers in both regions, and whether strenuous work in high heat may be a major contributing factor.

Box 13.2

Case Study: Investigating Kidney Disease in Farm Workers.

In summary, while the majority of cases of CKD in both HICs and LMICs is likely to be associated with diabetes or vascular disease, kidney disease from rarer etiologies—from HIV/AIDS to environmental toxins—is much more likely to occur in LMICs than in HICs. It is increasingly apparent that CKD in LMICs is a multifactorial condition caused by interacting factors such as poverty and social deprivation, poor sanitation and hygiene, exposure to water- and food-borne toxins, pollution, and infectious diseases. Accordingly, the epidemiology and treatment of CKD should be studied in LMICs as an entity separate from the end-organ consequence of diabetes or vascular disease.

Effectiveness of Interventions

Screening for CKD

Major primary care and nephrology guidelines in HICs do not advocate universal screening for CKD. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommends first evaluating individuals for risk factors for CKD during routine clinical encounters; if risk is determined, individuals should be further evaluated for serum creatinine and urine abnormalities. The risk factors include age; diabetes; hypertension; autoimmune disease, such as lupus; urinary tract abnormalities, such as infections, stones, and neoplasia; low birth weight; and exposure to toxins, such as drugs, environmental agents, or infections. In practice, physicians target screening to individuals with diabetes or hypertension. Because serum creatinine and automated reporting of eGFR are often part of routine studies in primary care, even individuals without specific risk factors for CKD are recognized at an early stage (Wyatt and others 2007).

The adoption of a targeted screening strategy in LMICs needs to be reassessed, given the lack of self-awareness of underlying risk factors for CKD. For example, in a community-based sample from urban India, individuals with and without knowledge of diabetes had similar prevalence of CKD (Anand and others 2015). Accordingly, selecting high-risk individuals for CKD screening may not be feasible.

Prevention of ESRD

Pharmacotherapy for CKD associated with diabetes or hypertension. Nephrologists use angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) as the primary medical therapies for delaying the progression to ESRD. Data from several randomized clinical trials have shown that these medications can slow the progression of CKD among individuals with proteinuric (diabetic and nondiabetic) kidney disease, with risk reduction approaching 40 percent for a composite endpoint of doubling of serum creatinine or ESRD (Kshirsagar and others 2000). A trial in China replicated these findings for individuals with proteinuria and advanced renal disease (Hou and others 2006). Some evidence indicates that even among individuals with CKD and hypertension without significant proteinuria, the use of ACE inhibitors may delay the progression of CKD beyond the effects achieved by other standard antihypertensive agents (Wright and others 2002). Whether the effect of ACE inhibitors is totally independent of improved blood pressure control has been debated. These medications, which are relatively inexpensive in their generic form, are well tolerated but require laboratory monitoring for hyperkalemia or significant change in serum creatinine among older patients and those with advanced CKD because of associated risk for AKI.

Pharmacotherapy for glomerular diseases. CKD associated with diabetes or renovascular disease is often diagnosed only with screening. Individuals with glomerulonephritis, in contrast, often have classic symptoms, such as edema, hematuria, or arthralgias, and are referred to nephrologists for immunotherapy. Steroids are the initial choice of therapy for many glomerular processes: minimal change disease, membranous nephropathy, focal segmental glomerulonephritis, and IgA nephropathy. Newer steroid-sparing therapies, such as calcineurin inhibitors, are used in individuals at serious risk for adverse events related to steroids or for maintenance therapy. Cyclophosphamide had been the mainstay of therapy for severe glomerulonephritis resulting from lupus or vasculitis. Mycophenolate mofetil (Ginzler and others 2005) and rituximab (Stone and others 2010) have been shown to be equally efficacious in treating severe glomerulonephritis resulting from lupus or vasculitis, respectively.

Race or ethnicity may affect the efficacy of immunotherapy. African-American and Hispanic individuals with lupus reportedly respond better to mycophenolate mofetil than to cyclophosphamide (Isenberg and others 2010). Initial clinical trials from China report the efficacy of mycophenolate mofetil in individuals with IgA nephropathy, but these results have not been replicated in clinical trials in Belgium and the United States (Floege and Eitner 2011).

Data on availability and appropriate use of these pharmacotherapies in LMICs are limited. One study from Mexico reports that one-third of primary care physicians working in the public sector scored in the “very low knowledge” category in a competence evaluation of diabetic kidney disease (Martinez-Ramirez and others 2006). Only 50 percent of patients with diabetes underwent simple screening for kidney disease; fewer than 20 percent of patients with proteinuria had been placed on ACE inhibitors in a third-level center in Nigeria (Agaba and others 2009).

CKD-specific programs in LMICs. We conducted a PUBMED and EMBASE systematic search to capture any programs designed specifically to improve care of patients with CKD or ESRD in LMICs. Of the 292 articles captured by the search, we culled 18 with available full text in English for further review; articles were excluded if they were not applicable to LMICs, if they were presented in abstract only at conferences, or if they did not describe a specific intervention. After excluding reports that were too general or did not capture any outcomes, we found 11 studies that described CKD care programs in LMICs (table 13.3). Although the data on evaluation of these programs were of poor to fair quality, an emerging theme in these reports is the importance of education of primary care physicians in identifying and treating patients at risk for CKD progression.

Table 13.3

Summary of Programs Targeted to Caring for Patients with CKD in LMICs.

Treatment of ESRD

Survival on dialysis. Survival on dialysis—equivalent for HD and PD—is generally poor in HICs, with annual mortality rates nearing 20 percent to 25 percent (van Dijk and others 2001). Many LMICs report equivalent, if not better, survival on dialysis (Anand, Bitton, and Gaziano 2013). At the same time, several studies have noted poorer provision of long-term care in LMICs: late referral to nephrologists, greater reliance on twice-weekly HD (Bieber and others 2013), less frequent laboratory draws and use of ancillary medications (Bieber and others 2013), and lack of enforcement of standards for water treatment for HD (Braimoh and others 2012). Patient selection factors may explain this incongruity between better survival despite reported poorer quality of care. In South Africa, where government-sponsored dialysis is offered to patients who fulfill the criteria for eventual transplantation, patients older than age 60 years and patients with diabetes are significantly less likely to receive dialysis (Moosa and Kidd 2006). Thus, a rationing process—whether at a societal or familial level—may create artificially better outcomes in LMICs, because a younger, healthier population is most likely to be able to access expensive dialysis therapy; see chapter 21 in this volume (Sakuma and others 2017) for a more detailed discussion.

Survival on transplantation. Compared with dialysis, first-year post–kidney transplant mortality is less than 10 percent in most HICs (van Dijk and others 2001). Better survival after a kidney transplant reflects a combination of selection factors—a healthier group of patients receiving transplants, and greater efficacy of therapy (Wolfe and others 1999). Most individuals in HICs receive cadaveric transplants.

In LMICs, reported outcomes for living donor transplantation are similar to those in HICs (Anand, Bitton, and Gaziano 2013). Cadaveric donation is much less common in LMICs because of the lack of deceased-donor registries; in one center’s report, cadaveric donation was associated with poorer outcomes than in HICs (Medina-Pestana 2006). Reasons behind the poorer transplant outcomes in LMICs should be further studied, especially considering that recipients tend to have fewer comorbidities and are younger. In most LMICs with flourishing transplant centers—such as Brazil, India, the Islamic Republic of Iran, Pakistan, South Africa, and Tunisia—the technical training of surgeons and nephrologists is comparable to that in HICs. However, two factors specific to LMICs may be at play:

• Funding of immunosuppression medication varies; some governments, such as Brazil, pay the full costs; others expect a majority of patients to self-pay. Because immunosuppression medications are expensive, patients might minimize or discontinue use if asked to self-pay.
• Risks for serious posttransplant infection are likely to be higher in LMICs. An estimated 10 percent to 15 percent of individuals with kidney transplants develop tuberculosis in endemic regions (Malhotra 2007; Rizvi and others 2003). Among those who have a co-infection, the mortality rate has been reported to be 75 percent (Chen and others 2008).

Use of modality. Kidney transplant offers the best survival rates and quality of life for individuals with ESRD when transplantation is performed using optimal practice standards. In HICs, kidney transplants meet the needs of 30 percent to 40 percent of prevalent ESRD patients (Grassmann and others 2005). Advances in patient selection, organ suitability, and organ availability have increased transplantation rates. National and regional organ donation chains can maximize adequate donor-recipient pairing over a large geographical area to ensure maximal chance of transplantation rate and allograft survival (Gentry, Montgomery, and Segev 2011). Recent changes to the deceased-donor system in the United States are anticipated to allocate organs more efficiently.

As in HICs, HD is the most commonly used therapy in LMICs. Transplants are relatively more commonly used in the Middle East and North Africa and in South Asia, compared with other LMIC regions (figure 13.1). In the Islamic Republic of Iran, compensation for organ donation may drive this trend (Ghods and Savaj 2006). PD is relatively more commonly used in Latin America and the Caribbean.

Figure 13.1

Use of Renal Replacement Therapy by Modality.

In addition to limits to organ availability, many LMICs struggle with inadequate infrastructure for safe transplantation and postsurgical care (Rizvi and others 2011). Deceased-donor registries do not exist in most countries. Practices such as black market trade and financial compensation are more prevalent and often disproportionally target poorer members of the population as donors (Mendoza 2010).

The preponderance of efficacy data demonstrate equivalent survival for patients on HD compared with PD, but HD predominates as the primary mode of therapy. Approximately 20 percent of patients who receive RRT in HICs receive PD (Anand, Bitton, and Gaziano 2013). Some reasons for this low uptake include skewed provider incentives toward in-center care, lack of patient education about alternate modalities, and patient fear of self-care.

PD, a relatively low-technology technique that requires neither a high ratio of trained nurses and nephrologists nor specialized facilities with water treatment capabilities, can have greater uptake in LMICs. Mexico and Thailand are exceptions to the generally low use of PD. Historically, Mexican clinicians have been trained in PD and disseminated the technique (Riella and Locatelli 2007); internists have been able to prescribe PD (Pecoits-Filho and others 2007). Following the model of Hong Kong SAR, China, the Ministry of Health in Thailand has tied use of PD first (before other interventions) to reimbursement and has supported expansion of PD; see chapter 21 in this volume (Sakuma and others 2017) for a detailed discussion.

Cost and Cost-Effectiveness of Interventions

Screening for CKD

The cost-effectiveness of screening for CKD has been extensively studied in HICs. The accuracy of creatinine-based eGFR alone in predicting outcomes and progression has remained questionable; not surprisingly, its use in the general population resulted in incremental cost-effectiveness ratios (ICERs) exceeding US$100,000 per QALY gained (Komenda and others 2014). Narrowing to the diabetic population, however, the ICER for screening was US$23,680 per QALY gained.

Assessment of proteinuria via urine albumin-to-creatinine ratio is generally considered to be a more reliable test, although Jafar and others (2007) have shown high specificity but moderate sensitivity (46 percent to 60 percent) in an Indo-Asian population. The cost of testing for urine albumin-to-creatinine ratio is significantly higher than that of serum creatinine, but more acceptable ICERs were noted for its application to those ages 50 years and older: US$73,000 per QALY gained if performed annually, to US$22,000 per QALY gained if performed every 10 years, compared with no screening (Hoerger and others 2010). ICERs for individuals with diabetes or hypertension were US$15,000 per QALY gained if urine albumin-to-creatinine testing is performed every 10 years.

Targeted screening may be the most cost-effective strategy for HICs, but identifying high-risk individuals in LMICs is difficult, and the cost of and utility loss from the development of ESRD is higher, given the restrictions on RRT. Two-stage screening may be a strategy worth investigating (box 13.3). When Howard and others (2010) modeled the use of annual dipstick screening for proteinuria in all Australians ages 50–69 years, followed by confirmatory urine protein-to-creatinine ratio and initiation of treatment, the resulting ICERs were US$5,298 per QALY gained. Similarly, a study of elderly patients at Veterans Administration hospitals in the United States finds that the number needed to treat to prevent a case of ESRD over a three-year period was substantially lower among individuals with dipstick proteinuria, compared with those without proteinuria and modest reductions in eGFR (O’Hare and others 2014).

Box 13.3

Case Study: Integrated Screening Program in Tamil Nadu.

Renal Replacement Therapy Program and Modality Choice

No recent studies from HICs have evaluated the cost-effectiveness of supporting an individual’s decision to pursue RRT rather than palliative care. Most HICs include RRT as part of universal health care packages or government-sponsored insurance programs. In 2011, the U.S. Medicare agency paid US$87,945 per patient for HD, US$71,630 for PD, US$99,826 for first year of transplant, and US$12,019 for ongoing posttransplant care (U.S. Renal Data System 2013). Other HICs report similar ranking of costs across modalities.

Despite the high upfront procedural costs, transplantation is the most cost-effective form of therapy in the long term because of its efficacy and low maintenance costs (Winkelmayer and others 2002). Data from LMICs are limited, but these results are likely to be confirmed even in resource-limited settings. However, transplantation has several unmodifiable limitations: it can rarely be preemptive; it is contraindicated in patients with serious comorbidity, such as cardiovascular disease, cancer, or infection; and most important, it faces a limited supply of organs.

PD offers similar survival and quality of life compared with HD; based on its cost rankings in HICs, PD could be hypothesized to be more cost-effective than HD (Karopadi and others 2013). Uptake remains low. Efforts to rein in costs related to ESRD led to the 2011 implementation of bundling rules in the United States, which require that several ancillary services be packaged into a fixed payment to dialysis facilities. Although the impact of bundling on patient outcomes has yet to be studied in detail, these measures provide incentives for home-based PD or HD. After only two years of implementation, the number of prevalent individuals on PD had risen by 30 percent for two of the largest dialysis providers in the United States (Golper 2013).

Despite its lower requirements for specialized treatment facilities and nephrology-trained staff, costs associated with PD in LMICs are estimated to be equivalent to or higher than those of HD (figure 13.2) (Karopadi and others 2013). Although further study is required to determine the reason for these cost differences, economies of scale and costs of importing PD solutions and equipment likely play a substantial role. Local manufacturing of PD solutions and equipment in India and Mexico, for example, has resulted in PD costs being lower than those for HD.

Figure 13.2

Association of HD/PD Cost Ratio to the Human Developmental Index.

Recommendations for Policy Makers in LMICs

Although the data on caring for patients with CKD and ESRD in LMICs are limited, some cornerstones of management—such as educating primary care physicians to recognize diabetic CKD or prioritizing kidney transplants in RRT programs—will translate directly, even in low-resource settings (table 13.4). However, others—in particular, CKD screening and innovative ways of maximizing dialysis provision—require research specific to LMICs.

Table 13.4

Recommendations for CKD and ESRD care in LMICs.

Conclusions

Overall, care provision for patients with either AKI or CKD is limited in LMICs, especially since the severe forms of each require the use of expensive RRT. However, several current gaps can be addressed with careful policy consideration.

For AKI, gathering more data on its true incidence and risk factors is crucial. Because the community-based form of AKI may be more prevalent in LMICs, if we can identify the most common etiologies, we can work to prevent them. In addition to identifying regional centers that can accommodate patients who acutely require RRT, protocols that optimize intensive care at first- or second-level hospitals are an initial first step in its management. Use of PD for AKI may be achievable even at second-level hospitals but requires further study.

LMICs are likely to face a growing burden of individuals with CKD and ESRD. Current data indicate that screening a high-risk, older population for CKD is cost-effective, but identifying such a population in countries without first-level health care systems is a key challenge. Low-cost strategies, such as the use of a urine dipstick, can be readily integrated into programs for chronic disease surveillance but also require further study. Most patients with proteinuric and, to a modest extent, hypertensive CKD benefit from initiation of ACE inhibitor and ARB therapy, which are available as low-cost generics.

Finally, although ESRD is rare, large gaps remain between LMICs and HICs in the provision of therapy. Efforts to increase access to RRT need to first focus on increasing the provision of transplantation—the most effective and cost-effective form of RRT. Because transplantation is not appropriate for all individuals with ESRD, dialysis is required for any RRT program. PD—while not clearly more cost-effective in LMICs—holds the most promise in its ability to reach a larger swath of individuals without intensive technical and equipment requirements.

Annexes

The annexes to this chapter are as follows. They are available at http://www.dcp-3.org/CVRD.

• Annex 13A. Kidney Disease Improving Global Outcomes: Criteria for AKI Severity
• Annex 13B. Kidney Disease Improving Global Outcomes: Stages of Chronic Kidney Disease
• Annex 13C. Selected Population-Based Studies Reporting Prevalence of Chronic Kidney Disease

Note

World Bank Income Classifications as of July 2014 are as follows, based on estimates of gross national income (GNI) per capita for 2013:

• Low-income countries (LICs) = US$1,045 or less
• Middle-income countries (MICs) are subdivided:

  1. lower-middle-income = US$1,046 to US$4,125
  2. upper-middle-income (UMICs) = US$4,126 to US$12,745
• High-income countries (HICs) = US$12,746 or more.

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