Preventive nephrology in the era of “I” evidence: should we screen for chronic kidney disease?
Authors: Carmen A. Peralta, Michelle M. Estrella
Journal: Kidney International (2017)

In this issue, Ferguson and colleagues demonstrate that chronic kidney disease (CKD) screening in populations burdened with CKD may be cost effective. Whether we should screen for CKD, however, continues to be debated despite the availability of effective clinical strategies that mitigate the risks of CKD progression. This study highlights the need for pragmatic trials to test the effectiveness of early CKD detection combined with optimization of clinical management and calls for innovation to tackle CKD. In this issue, Ferguson and colleagues demonstrate that chronic kidney disease (CKD) screening in populations burdened with CKD may be cost effective. Whether we should screen for CKD, however, continues to be debated despite the availability of effective clinical strategies that mitigate the risks of CKD progression. This study highlights the need for pragmatic trials to test the effectiveness of early CKD detection combined with optimization of clinical management and calls for innovation to tackle CKD. Lessons from cardiovascular epidemiology and public health initiatives suggest that early detection and prevention could be an effective strategy to reduce the burden of chronic kidney disease (CKD). Yet in developed countries like the United States and Canada, there is no systematic approach to early detection of CKD. This is largely due to a dearth of evidence. In the United States, which spends over $30 billion annually in Medicare funding for the end-stage renal disease program, we still cannot answer the fundamental question: “Should we screen for CKD?” In fact, the United States Preventive Services Task Force1Fink H.A. Ishani A. Taylor B.C. et al.Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline.Ann Int Med. 2012; 156: 570-581Crossref PubMed Scopus (144) Google Scholar graded the effectiveness of CKD screening as “I,” insufficient evidence to make a recommendation. Guidelines from professional societies have created confusion for providers. We believe that this lack of evidence and confusion lead to missed opportunities to reduce CKD progression and cardiovascular disease morbidity and mortality. Fellow nephrologists and generalists have apathetically asked: “Why does accurate CKD diagnosis matter in clinical practice?” Admittedly, we do not yet have a “CKD pill.” However, we can turn to epidemiology principles to understand the requisites for an asymptomatic condition, like CKD, to be considered suitable for screening. First, CKD is highly prevalent and is associated with major cardiovascular morbidity and mortality and progression to end-stage renal disease. Second, CKD is often asymptomatic at early stages and therefore goes undetected. Third, suitable testing strategies are available in clinical practice and can identify persons at highest risk for complications. Finally, effective clinical management exists to mitigate the risks of CKD progression and related complications, once CKD is recognized. For example, CKD status determines choice of antihypertensive therapy, and blood pressure is harder to control in persons with CKD compared with the general population. Persons with CKD benefit from cholesterol-lowering medications, and guidelines recommend statins for all persons > 50 years of age with CKD. CKD status can influence risks and benefits of treatment of diabetes, HIV infection, and viral hepatitis, and use of nonsteroidal anti-inflammatory drugs. CKD status is an important consideration for drug dosing and patient safety, such as during anticoagulation therapy or use of novel SGLT2 inhibitors for treatment of diabetes.2Shroff G.R. Renal function in patients with atrial fibrillation receiving anticoagulants: the canaries in the coal mine.JAMA Cardiol. 2016; 1: 375-376Crossref PubMed Scopus (9) Google Scholar, 3Wanner C. Inzucchi S.E. Lachin J.M. et al.Empagliflozin and progression of kidney disease in type 2 diabetes.N Engl J Med. 2016; 375: 1799-1800Crossref PubMed Scopus (2042) Google Scholar A review by Gansevoort et al. suggests that, as CKD progresses, treatment optimization may require a transition from an initial focus on control of traditional cardiovascular disease (CVD) risk factors, followed by a focus on control of kidney-specific factors and prevention of CKD progression.4Gansevoort R.T. Correa-Rotter R. Hemmelgarn B.R. et al.Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention.Lancet. 2013; 382: 339-352Abstract Full Text Full Text PDF PubMed Scopus (1253) Google Scholar Therefore, early detection of CKD, followed by treatment optimization, has the potential to reduce CVD complications (primary and secondary prevention) and attenuate CKD progression (secondary prevention) (Figure 1). Continuing to adhere to the nihilistic notion that a CKD diagnosis does not matter or does not add to clinical care is a barrier to innovation. The paper by Ferguson et al.5Ferguson T.W. Tangri N. Tan Z. et al.Screening for chronic kidney disease in Canadian indigenous peoples is cost-effective.Kidney Int. 2017; 92: 192-200Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar (2017) in this issue of Kidney International adds to the body of evidence showing that there are populations at disproportionately higher risk for development of CKD, progression to end-stage renal disease, and CVD where screening may be cost effective.6Hallan S.I. Matsushita K. Sang Y. et al.Age and association of kidney measures with mortality and end-stage renal disease.JAMA. 2012; 308: 2349-2360Crossref PubMed Scopus (428) Google Scholar, 7Manns B. Hemmelgarn B. Tonelli M. et al.Population based screening for chronic kidney disease: cost effectiveness study.BMJ. 2010; 341: c5869Crossref PubMed Scopus (111) Google Scholar, 8Boulware L.E. Jaar B.G. Tarver-Carr M.E. et al.Screening for proteinuria in US adults: a cost-effectiveness analysis.JAMA. 2003; 290: 3101-3114Crossref PubMed Scopus (317) Google Scholar An important innovation is modeling the use of both estimated glomerular filtration rate and albuminuria assessments for CKD screening. Not surprisingly, cost effectiveness was increased in circumstances where disease prevalence is highest, as seen in Canadian indigenous peoples with limited access. In the United States, a recent report from the Indian Health Service announced a marked reduction in end-stage renal disease after implementation of an early CKD detection program, followed by treatment among Native Americans with diabetes. The current paper also highlights the importance of implementation of established, evidence-based guidelines for treatment among persons with CKD. Specifically, the modeling strategy depends on implementation of basic, evidence-based interventions such as use of inhibitors of the renin-angiotensin system. A major gap not addressed in this study is the potential for CVD risk reduction. The cost effectiveness of a CKD screening program would likely increase if reduction in CVD events were included in the modeling strategy. Despite all this epidemiologic and modeling evidence, there is a need for randomized trials to test the effectiveness of early detection of CKD paired with subsequent optimization of clinical management. These trials are likely to be pragmatic in nature, and set in primary care clinics or community settings where screening is most likely to occur. Some of these trials may heavily rely on electronic health records to identify patients at risk, deliver interventions, and assess outcomes. Once CKD is detected, interventions are likely to require multidisciplinary teams to address the complex needs of CKD patients. Some trials may test interventions that are purely physician-facing, such as decision supports, whereas others may incorporate patient education, activation, and self-management programs. We need them all because we will learn from them all. Although we currently rely on albuminuria and estimated glomerular filtration rate, there is a growing panel of serum and urine biomarkers that can detect kidney injury before the estimated glomerular filtration rate is reduced. These biomarkers promise sufficiently early identification of ongoing kidney injury so clinical management could be implemented before permanent damage ensues. Similar to conventional CKD screening methodologies, however, we need research focused on answering the who, when, and how to screen using these novel biomarkers. Before embarking on this quest for evidence, we must have alignment of several major academic influencers: (i) peer reviewers, (ii) funding agencies, (iii) nephrology thought leaders, (iv) primary care leaders, (v) promotions committees, and, most importantly, (vi) an energetic workforce of budding kidney health investigators. While the field faces a reduced interest in nephrology careers, we must expand our worldview to build and nurture a workforce with the skills to design, plan, and implement these trials. Thus, the field of nephrology will need to train implementation scientists, qualitative researchers, experts in informatics, data scientists, economists, policy advocates, and investigators in community-based participatory research, to name a few. In order for these scientists to have the opportunity to innovate, peer reviewers will need to educate themselves on novel analytics, machine learning, and data science methods to understand how to read applications that may use nontraditional data sources. Funding agencies are already setting the directions for this type of research, as exemplified by recent funding announcements calling for implementation studies using information technology in CKD.9Translational Research to Improve Outcomes in Kidney Diseases (R18). Available at: https://grants.nih.gov/grants/guide/rfa-files/RFA-DK-15-009.html. Accessed May 3, 2015.Google Scholar We need division chiefs and senior nephrology mentors across the country who will open the doors of academic nephrology to physician scientists who may not fit traditional molds. The leadership must understand that innovation comes in many shapes and forms. We are not used to seeing such careers highlighted as successes in academic nephrology. However, our patients cannot afford for the field to produce only nephrology innovators who replicate the glories of nephrology’s past. Nephrology today has a great opportunity to innovate and to partner with health systems, academia, and industry to find creative ways to reduce the CKD burden. For now, early detection and prevention may be our magic pill. CAP is a scientific advisor and owns stock options for Cricket Health, Inc. The other author declared no competing interests. Screening for chronic kidney disease in Canadian indigenous peoples is cost-effectiveKidney InternationalVol. 92Issue 1PreviewCanadian indigenous (First Nations) have rates of kidney failure that are 2- to 4-fold higher than the non-indigenous general Canadian population. As such, a strategy of targeted screening and treatment for CKD may be cost-effective in this population. Our objective was to assess the cost utility of screening and subsequent treatment for CKD in rural Canadian indigenous adults by both estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A decision analytic Markov model was constructed comparing the screening and treatment strategy to usual care. Full-Text PDF Open Archive