Kidney Health for Everyone Everywhere - From Prevention to Detection and Equitable Access to Care

Primary prevention of CKD

The incidence (new cases) and prevalence (cumulative pre-existing cases) of CKD have been rising worldwide.[13] This primary level of prevention requires awareness of modifiable CKD risk factors and efforts to focus healthcare resources on those patients who are at the highest risk of developing new onset or de novo CKD.

Measures to achieve effective primary prevention should focus on the two leading risk factors for CKD including diabetes mellitus and hypertension. Evidence suggests that an initial mechanism of injury is renal hyperfiltration with seemingly elevated glomerular filtration rate, (GFR), above normal ranges. This is often the result of glomerular hypertension that is often seen in patients with obesity or diabetes mellitus, but it can also occur after a high dietary protein intake.[8] Other CKD risk factors include polycystic kidneys or other congenital or acquired structural anomalies of the kidney and urinary tracts, primary glomerulonephritis, exposure to nephrotoxic substances or medications (such as nonsteroidal anti-inflammatory drugs), having one single kidney, e.g., solitary kidney after cancer nephrectomy, high dietary salt intake, inadequate hydration with recurrent volume depletion, heat stress, exposure to pesticides and heavy metals (as has been speculated as the main cause of Mesoamerican Nephropathy), and possibly high protein intake in those at higher risk of CKD.[8] Among non-modifiable risk factors are advancing age and genetic factors such as apolipoprotein 1 (APOL1) gene that is mostly encountered in those with sub-Saharan African ethnicity, especially among African Americans. Certain disease states may cause de novo CKD such as cardiovascular and atheroembolic diseases (also known as secondary cardiorenal syndrome) and liver diseases (hepatorenal syndrome). Table 1 shows some of the risk factors of CKD.

Among measures to prevent emergence of de novo CKD are screening efforts to identify and manage persons at high risk of CKD, especially those with diabetes mellitus and hypertension. Hence, targeting primordial risk factors of these two conditions including metabolic syndrome and overnutrition is relevant to primary CKD prevention as is correcting obesity.[14] Promoting healthier lifestyle is an important means to that end including physical activity and healthier diet. The latter should be based on more plant-based foods with less meat, less sodium intake, more complex carbohydrates with higher fiber intake, and less saturated fat. In those with hypertension and diabetes, optimizing blood pressure and glycemic control has shown to be effective in preventing diabetic and hypertensive nephropathies. A recent expert panel suggested that persons with solitary kidney should avoid high protein intake above 1 gram per kilogram body weight per day.[15] Obesity should be avoided, and weight reduction strategies should be considered.[14]

Secondary prevention in CKD

Evidence suggests that among those with CKD, the vast majority have early-stage of the disease. i.e. CKD Stages 1 and 2 with microalbuminuria (30 to 300 mg/day) or CKD Stage 3B (eGFR between 45 to 60 ml/min/1.73m²).[16] In these persons with preexisting disease, the “secondary prevention” of CKD has the highest priority. For these earlier stages of CKD, the main goal of kidney health education and clinical interventions is how to slow disease progression. Uncontrolled or poorly controlled hypertension is one of the most established risk factors for faster CKD progression. The underlying pathophysiology of faster CKD progression relates to ongoing damage to the kidney structure and loss of nephrons with worsening interstitial fibrosis as it happens with sustained hypertension.

The cornerstone of the pharmacotherapy in secondary prevention is the use of angiotensin pathway modulators, also known as renin-angiotensin-aldosterone system inhibitors (RAASi). These drugs reduce both systemic blood pressure and intraglomerular pressure by opening efferent arterioles of the glomeruli, hence, leading to longevity of the remaining nephrons. Low protein diet appears to have a synergistic effect on RAASi therapy.[17] In terms of the potential effect of controlling glycemic status and correcting obesity on the rate of CKD progression, there are mixed data. However, recent data suggest that a new class of anti-diabetic medications known as sodium-glucose cotransporter-2 Inhibitors (SGLT2i) can slow CKD progression, but this effect may not be related to glycemic modulation of the medication. Whereas acute kidney injury (AKI) may or may not cause de novo CKD, AKI events that are superimposed on preexisting CKD may accelerate disease progression.[18] A relatively recent case of successful secondary prevention that highlights the significance of implementing preventive strategies in CKD is the use of a vasopressin V (2)-receptor antagonists in Adult Polycystic Kidney Disease (ADPKD).[19]

Tertiary prevention in CKD

In patients with advanced CKD, management of uremia and related comorbid conditions such as anemia, mineral and bone disorders, and cardiovascular disease is of high priority, so that these patients can continue to achieve highest longevity. These measures can be collectively referred to as “tertiary prevention” of CKD. In these individuals, cardiovascular disease burden is exceptionally high, especially if they have underlying diabetes or hypertension, while they often do not follow other traditional profile of cardiovascular risk such as obesity or hyperlipidemia. Indeed, in these patients, a so-called “reverse epidemiology” exist, in that hyperlipidemia and obesity appear to be protective at this advanced stage of CKD. This could be due to the overshadowing impact of the “protein-energy wasting” (PEW) that happens more frequently with worsening uremia and which is associated with weight loss and poor outcomes including cardiovascular disease and death. Whereas many of these patients, if they survive ravages of PEW and cardiovascular disease, will eventually receive renal replacement therapy in form of dialysis therapy or kidney transplantation, a new trend is emerging to maintain them longer without dialysis by implementing conservative management of CKD. However, in some with additional comorbidities such as metastatic cancers, palliative measures with supportive care can be considered.

Cost-effectiveness of early detection programs

Universal screening of the general population would be time-consuming, expensive and has been shown to be not cost-effective. Unless selectively directed towards high- risk groups, such as the case of Chronic kidney disease of unknown cause (CKDu) in disadvantaged populations,[32] according to a cost-effectiveness analysis using a Markov decision analytic model, population-based dipstick screening for proteinuria has an unfavorable cost effectiveness ratio.[33] A more recent Korean study confirmed that their National Health Screening Program (NHSP) for chronic kidney disease (CKD) is more cost-effective for patients with diabetes or hypertension than the general population.[34] From an economic perspective, screening CKD by detection of proteinuria was shown to be cost-effective in patients with hypertension or diabetes in a systematic review.[35] The incidence of CKD, rate of progression, and effectiveness of drug therapy were major drivers of cost-effectiveness and thus CKD screening may be more cost-effective in populations with higher incidences of CKD, rapid rates of progression, and more effective drug therapy.

Integration of CKD prevention into national NCD programs

Given the close links between CKD and other NCDs, it is critical that CKD advocacy efforts be aligned with existing initiatives concerning diabetes, hypertension, and cardiovascular disease, particularly in Low middle income countries (LMIC). Some countries and regions have successfully introduced CKD prevention strategies as part of their NCD programs. As an example, in 2003, a kidney health promotion program was introduced in Taiwan, with its key components including a ban on herbs containing aristolochic acid, public-awareness campaigns, patient education, funding for CKD research, and the setting up of teams to provide integrated care.[36] In Cuba, the Ministry of Public Health has implemented a national program for the prevention of CKD. Since 1996 the program has followed several steps: 1) the analysis of the resources and health situation in the country; 2) epidemiological research to define the burden of CKD; and 3); a continuing education for nephrologists, family doctors, and other health professionals. The main goal has been to bring nephrology care closer to the community through a regional redistribution of nephrology services and joint management of CKD patients by primary healthcare physicians and nephrologists.[37] The integration of CKD prevention into NCDs program, has resulted in the reduction of renal and cardiovascular risks in the general population. Main outcomes have been the reduction in the prevalence of risk factors, such as low birth weight, smoking, and infectious diseases. There has been an increased rate of the diagnosis of diabetes and of glycemic control, as well as an increased diagnosis of patients with hypertension, higher prescription use of renoprotective treatment with Angiotensin converting enzyme inhibitor (ACEI) and higher rates of blood pressure control.[38] Recently, the US Department of Health and Human Services has introduced an ambitious program to reduce the number of Americans developing end-stage renal disease by 25 percent by 2030. The program, known as the Advancing American Kidney Health Initiative, has set goals with metrics to measure its success; among them is to put more efforts to prevent, detect, and slow the progression of kidney disease, in part by addressing traditional risk factors like diabetes and hypertension. To reduce the risk of kidney failure, the program contemplates advancing public health surveillance and research to identify populations at risk and those in early stages of kidney disease, and to encourage adoption of evidence-based interventions to delay or stop progression to kidney failure.[39] Ongoing programs, like the Special Diabetes Program for Indians (SDPI) represents an important part of this approach by providing team-based care and care management. Since its implementation, the incidence of diabetes-related kidney failure among American Native populations decreased by over 40 percent between 2000 and 2015.[40]

Online educational programs for CKD prevention and treatment

Whereas it is important to enhance the promotion and implementation of “Prevention” of kidney disease and kidney failure amongst healthcare professionals, it is equally important to promote “Prevention” with education programs for those at risk of kidney disease and kidney failure, and with the general population at large. It is a stepwise process, from awareness, engagement, participation, empowerment and to partnership. As highlighted above, in general, the health literacy of the general population is low. Awareness and understanding of kidney disease are inadequate. Education is key to engaging patients with kidney disease. It is the path to self-management and patient-centered care. Narva found patient education is associated with better patient outcomes.[56] Obstacles include the complex nature of kidney disease information, low baseline awareness, limited health literacy and numeracy, limited availability of CKD information, and lack of readiness to learn. New education approaches should be developed through research and quality improvement efforts. Schatell found Web-based kidney education is helpful in supporting patient self-management.[57] The Internet offers a wealth of resources on education. Understanding the types of Internet sources that CKD patients use today can help renal professionals to point patients in the right direction. It is important that reputable healthcare organizations, preferably at a national level, facilitate users to have easier access to health information on their websites [Appendix 1]. The mode of communication currently used by patients and the population at large is through the internet - websites, portals, and other social media, such as Facebook and Twitter. There are also free apps on popular mobile devices providing education on kidney disease. There is no shortage of information on the internet. The challenge is how to effectively “push” important healthcare information in a targeted manner, and to facilitate users seeking information in their efforts to “pull” relevant and reliable information from the internet. It is important the “pushing” of health information is targeted and specific, relevant for the condition (primary, secondary or tertiary prevention), and is offered at the right time to the right recipient. It is possible with the use of information technology and informatics to provide relevant and targeted information for patients at high risk, coupling the information based on diagnosis and drugs prescribed. Engagement of professional society resources and patient groups is a crucial step to promote community partnership and patient empowerment on prevention. Additional resources may be available from charitable and philanthropic organizations.

Disclosure

This article was originally published in Kidney International, volume 97, pages 226-232, Copyright World Kidney Day Steering Committee (2020), and reprinted concurrently in several journals. The articles cover identical concepts and wording but vary in minor stylistic and spelling changes, detail, and length of manuscript in keeping with each journal's style. Any of these versions may be used in citing this article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.