Overcoming barriers to implementing new guideline-directed therapies for chronic kidney disease.

For the first time in many years, guideline-directed drug therapies have emerged that offer substantial cardiorenal benefits, improved quality of life and longevity in patients with chronic kidney disease (CKD) and type 2 diabetes. These treatment options include sodium-glucose cotransporter-2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists. However, despite compelling evidence from multiple clinical trials, their uptake has been slow in routine clinical practice, reminiscent of the historical evolution of angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use. The delay in implementation of these evidence-based therapies highlights the many challenges to optimal CKD care, including: (i) clinical inertia; (ii) low CKD awareness; (iii) suboptimal kidney disease education among patients and providers; (iv) lack of patient and community engagement; (v) multimorbidity and polypharmacy; (vi) challenges in the primary care setting; (vii) fragmented CKD care; (viii) disparities in underserved populations; (ix) lack of public policy focused on health equity; and (x) high drug prices. These barriers to optimal cardiorenal outcomes can be ameliorated by a multifaceted approach, using the Chronic Care Model framework, to include patient and provider education, patient self-management programs, shared decision making, electronic clinical decision support tools, quality improvement initiatives, clear practice guidelines, multidisciplinary and collaborative care, provider accountability, and robust health information technology. It is incumbent on the global kidney community to take on a multidimensional perspective of CKD care by addressing patient-, community-, provider-, healthcare system- and policy-level barriers.

Need for a Judicious Use of Nonsteroidal Anti-inflammatory Drugs to Avoid Community-Acquired Acute Kidney Injury.

Millions of Americans use over-the-counter analgesics on a daily basis, and nearly 100 million nonsteroidal anti-inflammatory drug (NSAID) prescriptions are filled per year. In high-risk patients, these medications can disrupt kidney hemodynamics and precipitate community-acquired acute kidney injury (CA-AKI). The risk of NSAID-associated CA-AKI increases 3- to 5-fold in patients taking renin-angiotensin system inhibitors and diuretics concurrently. CA-AKI increases the risk of developing chronic kidney disease (CKD) or accelerating progression of pre-existing CKD. Importantly, many cases of NSAID-induced CA-AKI may be avoided by identifying high-risk patients and providing patient and provider education on when to avoid these medications and minimize risk.

Vital Signs: Decrease in Incidence of Diabetes-Related End-Stage Renal Disease among American Indians/Alaska Natives - United States, 1996-2013.

BACKGROUND: American Indians and Alaska Natives (AI/AN) have the highest diabetes prevalence among any racial/ethnic group in the United States. Among AI/AN, diabetes accounts for 69% of new cases of end-stage renal disease (ESRD), defined as kidney failure treated with dialysis or transplantation. During 1982-1996, diabetes-related ESRD (ESRD-D) in AI/AN increased substantially and disproportionately compared with other racial/ethnic groups. METHODS: Data from the U.S. Renal Data System, the Indian Health Service (IHS), the National Health Interview Survey, and the U.S. Census were used to calculate ESRD-D incidence rates by race/ethnicity among U.S. adults aged ≥18 years during 1996-2013 and in the diabetic population during 2006-2013. Rates were age-adjusted based on the 2000 U.S. standard population. IHS clinical data from the Diabetes Cares and Outcomes Audit were analyzed for diabetes management measures in AI/AN. RESULTS: Among AI/AN adults, age-adjusted ESRD-D rates per 100,000 population decreased 54%, from 57.3 in 1996 to 26.5 in 2013. Although rates for adults in other racial/ethnic groups also decreased during this period, AI/AN had the steepest decline. Among AI/AN with diabetes, ESRD-D incidence decreased during 2006-2013 and, by 2013, was the same as that for whites. Measures related to the assessment and treatment of ESRD-D risk factors also showed more improvement during this period in AI/AN than in the general population. CONCLUSION AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Despite well-documented health and socioeconomic disparities among AI/AN, ESRD-D incidence rates among this population have decreased substantially since 1996. This decline followed implementation by the IHS of public health and population management approaches to diabetes accompanied by improvements in clinical care beginning in the mid-1980s. These approaches might be a useful model for diabetes management in other health care systems, especially those serving populations at high risk.

Social Determinants of Racial Disparities in CKD.

Significant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.

Laboratory Assessment of Diabetic Kidney Disease.

IN BRIEF Regardless of etiology, chronic kidney disease (CKD) is identified by two laboratory tests: 1) estimated glomerular filtration rate (eGFR), a measure of kidney function, and 2) urine albumin-to-creatinine ratio (UACR), a measure of kidney damage. It is crucial for all health professionals to understand the significance and limitations of these tests to appropriately identify CKD patients, guide therapy, and determine prognosis. This article provides information that will enable diabetes educators and other clinicians to properly interpret eGFR and UACR laboratory results in the identification and management of CKD.

Diabetic kidney disease: a report from an ADA Consensus Conference.

The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included (1) identification and monitoring, (2) cardiovascular disease and management of dyslipidemia, (3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, (4) glycemia measurement, hypoglycemia, and drug therapies, (5) nutrition and general care in advanced-stage chronic kidney disease, (6) children and adolescents, and (7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD.

Survival on dialysis among American Indians and Alaska Natives with diabetes in the United States, 1995-2010.

OBJECTIVES: We assessed survival in American Indians and Alaska Natives (AI/ANs) with end-stage renal disease attributed to diabetes who initiated hemodialysis between 1995 and 2009. METHODS: Follow-up extended from the first date of dialysis in the United States Renal Data System until December 31, 2010, kidney transplantation, or death. We used the Kaplan-Meier method to compute survival on dialysis by age and race/ethnicity and Cox regression analysis to compute adjusted hazard ratios (HRs). RESULTS: Our study included 510,666 persons-48% Whites, 2% AI/AN persons, and 50% others. Median follow-up was 2.2 years (interquartile range = 1.1-4.1 years). At any age, AI/AN persons survived longer on hemodialysis than Whites; this finding persisted after adjusting for baseline differences. Among AI/AN individuals, those with full Indian blood ancestry had the lowest adjusted risk of death compared with Whites (HR = 0.58; 95% confidence interval = 0.55, 0.61). The risk increased with declining proportion of AI/AN ancestry. CONCLUSIONS: Survival on dialysis was better among AI/AN than White persons with diabetes. Among AI/AN persons, the inverse relationship between risk of death and level of AI/AN ancestry suggested that cultural or hereditary factors played a role in survival.

2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

Albuminuria prevalence in first morning void compared with previous random urine from adults in the National Health and Nutrition Examination Survey, 2009-2010.

BACKGROUND: Albuminuria, defined as urine albumin/creatinine ratio (ACR) ≥30 mg/g, is a diagnostic component of chronic kidney disease (CKD). National estimates of ACR and CKD prevalence have been based on single random urine samples. Although 2 urine samples or a first morning void are known to produce different estimates of ACR, the impact of differing urine sampling schemes on nationally estimated rates of CKD is unknown. METHODS: In 2009-2010, the National Health and Nutrition Examination Survey (NHANES) participants provided 2 untimed urine samples for sequential ACR measurement: an initial random urine collected in the NHANES mobile examination center and a subsequent first morning void collected at home. Rates of albuminuria were calculated in the overall population and broken down by demographics, diagnosed diabetes and hypertension status, and estimated glomerular filtration rate (eGFR). RESULTS: Overall, 43.5% of adults with increased ACR (≥30 mg/g) in a random urine also had increased ACR in a first morning urine. This percentage was higher among individuals ≥50 years old (48.9%), males (53.3%), participants with diagnosed diabetes (56.3%) and hypertension (51.5%), and eGFR <60 mL/min/1.72m(2) (56.9%). The use of confirmed increased ACR (defined as the presence of ACR ≥30 mg/g in both samples taken within 10 days) to define CKD resulted in a lower overall prevalence (11.6%) than first morning urine (12.7%) or random spot urine only (15.2%). CONCLUSIONS: ACR measured on random urine samples appears to overestimate the prevalence of albuminuria compared to first morning urine collections.

A reference system for urinary albumin: current status.

BACKGROUND: Increased urinary excretion of albumin reflects kidney damage and is a recognized risk factor for progression of renal and cardiovascular disease. Considerable inter-method differences have been reported for both albumin and creatinine measurement results, and therefore the albumin-to-creatinine ratio. Measurement accuracy is unknown and there are no independent reference measurement procedures for albumin and no reference materials for either measurand in urine. METHODS: The National Kidney Disease Education Program (NKDEP) Laboratory Working Group and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have initiated joint projects to facilitate standardization of urinary albumin and creatinine measurement. RESULTS: A candidate LC-MS/MS reference measurement procedure for urinary albumin and candidate reference materials for urinary albumin and creatinine has been developed. The status of validations of these reference system components is reported. CONCLUSIONS: The development of certified reference materials and reference measurement procedures for urinary albumin will enable standardization of this important measurand.

Racial and Socioeconomic Disparities in CKD in the Context of Universal Health Care Provided by the Military Health System.

RATIONALE & OBJECTIVE: Health-impeding social determinants of health-including reduced access to care-contribute to racial and socioeconomic disparities in chronic kidney disease (CKD). The Military Health System (MHS) provides an opportunity to assess a large, diverse population for CKD disparities in the context of universal health care. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: MHS beneficiaries aged 18 to 64 years receiving care between October 1, 2015, and September 30, 2018. PREDICTORS: Race, sponsor's rank (a proxy for socioeconomic status and social class), median household income by sponsor's zip code, and marital status. OUTCOME: CKD prevalence, defined by International Classification of Diseases, Tenth Revision codes and/or a validated, laboratory value-based electronic phenotype. ANALYTICAL APPROACH: Multivariable logistic regression compared CKD prevalence by predictors, controlling separately for confounders (age, sex, active-duty status, sponsor's service branch, and depression) and mediators (hypertension, diabetes, HIV, and body mass index). RESULTS: Of 3,330,893 beneficiaries, 105,504 (3.2%) had CKD. In confounder-adjusted models, the CKD prevalence was higher in Black versus White beneficiaries (OR, 1.67; 95% CI, 1.64-1.70), but lower in single versus married beneficiaries (OR, 0.77; 95% CI, 0.76-0.79). The prevalence of CKD was increased among those with a lower military rank and among those with a lower median household income in a nearly dose-response fashion (P < 0.0001). Associations were attenuated when further adjusting for suspected mediators. LIMITATIONS: The cross-sectional design prevents causal inferences. We may have underestimated the CKD prevalence, given a lack of data for laboratory tests conducted outside the MHS and the use of a specific CKD definition. The transient nature of the MHS population may limit the accuracy of zip code-level median household income data. CONCLUSIONS: Racial and socioeconomic CKD disparities exist in the MHS despite universal health care coverage. The existence of CKD disparities by rank and median household income suggests that social risks may contribute to both racial and socioeconomic disparities despite access to universal health care coverage.

CKD Prevalence in the Military Health System: Coded Versus Uncoded CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is common but often goes unrecorded. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: Military Health System (MHS) beneficiaries aged 18 to 64 years who received care during fiscal years 2016 to 2018. PREDICTORS: Age, sex, active duty status, race, diabetes, hypertension, and numbers of kidney test results. OUTCOMES: We defined CKD by International Classification of Diseases, Tenth Revision (ICD-10) code and/or a positive result on a validated electronic phenotype that uses estimated glomerular filtration rate and measures of proteinuria with evidence of chronicity. We defined coded CKD by the presence of an ICD-10 code. We defined uncoded CKD by a positive e-phenotype result without an ICD-10 code. ANALYTICAL APPROACH: We compared coded and uncoded populations using 2-tailed t tests (continuous variables) and Pearson χ2 test for independence (categorical variables). RESULTS: The MHS population included 3,330,893 beneficiaries. Prevalence of CKD was 3.2%, based on ICD code and/or positive e-phenotype result. Of those identified with CKD, 63% were uncoded. Compared with beneficiaries with coded CKD, those with uncoded CKD were younger (aged 45 ± 13 vs 52 ± 11 years), more often women (54.4% vs 37.6%) and active duty (20.2% vs 12.5%), and less often of Black race (18.5% vs 31.5%) or with diabetes (23.5% vs 43.5%) or hypertension (46.6% vs 77.1%; P < 0.001). Beneficiaries with coded (vs uncoded) CKD had greater numbers of kidney test results (P < 0.001). LIMITATIONS: Use of cross-sectional administrative data prevents inferences about causality. The CKD e-phenotype may fail to capture CKD in individuals without laboratory data and may underestimate CKD. CONCLUSIONS: The prevalence of CKD in the MHS is ~3.2%. Beneficiaries with well-known CKD risk factors, such as older age, male sex, Black race, diabetes, and hypertension, were more likely to be coded, suggesting that clinicians may be missing CKD in groups traditionally considered lower risk, potentially resulting in suboptimal care.

Racial and ethnic differences in albuminuria in individuals with estimated GFR greater than 60 mL/min/1.73 m(2): results from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors. METHODS: This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000-2008, with estimated glomerular filtration rate > or = 60 mL/min/1.73 m(2), not on regular dialysis therapy, and without a previous kidney transplant. Albuminuria (urine albumin-creatinine ratio > or = 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region. RESULTS: Albuminuria prevalences were 8% (n = 2,303) in whites, 11% (n = 2,310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted OR, 1.93; 95% CI, 1.70-2.20), then Asians (adjusted OR, 1.42; 95% CI, 1.26-1.61), African Americans (adjusted OR, 1.38; 95% CI, 1.29-1.47), and Hispanics (adjusted OR, 1.19; 95% CI, 1.08-1.31). CONCLUSIONS: In the KEEP study population, albuminuria prevalence was higher in African Americans, Hispanics, Asians, and American Indians/Alaska Natives than in non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially in people at increased risk, in the community primary care setting.

Current issues in measurement and reporting of urinary albumin excretion.

BACKGROUND: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement. CONTENT: The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion. DISCUSSION: Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.

The National Kidney Disease Education Program: improving understanding, detection, and management of CKD.

The National Kidney Disease Education Program (NKDEP), an initiative of the National Institute of Diabetes and Digestive and Kidney Diseases, works to reduce the morbidity and mortality caused by chronic kidney disease (CKD) and its complications. Established in 2000, the NKDEP initially focused on increasing awareness in at-risk populations and helping the laboratory community recalibrate serum creatinine measurement methods and begin using a revised equation to estimate glomerular filtration rate. Expanding its focus in recent years, the NKDEP now works to improve provider practices by collaborating with health systems, community health centers, and professional associations to encourage testing and treatment of patients. Among its top priorities is to develop such resources as clinical encounter tools, patient education aids, and training programs that help primary care professionals better identify and care for patients with CKD. Other priorities include improving the coordination of federal responses to CKD and addressing the standardization of measurement and reporting of urine albumin. Improving CKD detection and management is an important challenge. To succeed, the NKDEP must work in close partnership with the renal community, public health agencies, professional associations, and voluntary organizations that serve at-risk and patient communities.

Individuals with a family history of ESRD are a high-risk population for CKD: implications for targeted surveillance and intervention activities.

Activities intended to improve the detection, treatment, and control of chronic kidney disease (CKD) should be incorporated into existing health care systems and targeted to high-risk populations to avoid redundancy and waste of resources. One high-risk population consists of first- or second-degree family members of patients with end-stage renal disease (ESRD), who are 2 to 3 times as likely to have incident ESRD, have high rates of impaired kidney function and undetected and uncontrolled high blood pressure, and are more likely to be obese. These individuals usually are unaware of their underlying CKD and may discount their own risk of ESRD. The ESRD Network 6 Family History Project shows that the ESRD Networks, which constitute a national CKD surveillance system for patients with stage 5 CKD, may be an existing resource that can be used to identify relatives of incident patients with ESRD and provide these families with information about CKD. Nationally available resources have been developed by the National Kidney Disease Education Program for use with these at-risk families. Individuals interested in population-based CKD control activities should be aware of and use these resources.

Risk factors for chronic kidney disease among American Indians and Alaska Natives--findings from the Kidney Early Evaluation Program.

BACKGROUND: American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR. METHODS: Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, <60 ml/min/1.73 m(2), or albuminuria, a urine albumin/creatinine ratio > or =30 mg/g. RESULTS: The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% CI 5.92-11.98), followed by hypertension (OR 2.38, 95% CI 1.74-3.26). In contrast, diabetes (OR 2.04, 95% CI 1.57-2.64) and hypertension (OR 2.63, 95% CI 1.93-3.59) were the only predictors of albuminuria among persons with a normal eGFR. CONCLUSION: The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN.