Screening, identifying, and treating chronic kidney disease: why, who, when, how, and what?

1 in 7 American adults have chronic kidney disease (CKD); a disease that increases risk for CKD progression, cardiovascular events, and mortality. Currently, the US Preventative Services Task Force does not have a screening recommendation, though evidence suggests that screening can prevent progression and is cost-effective. Populations at risk for CKD, such as those with hypertension, diabetes, and age greater than 50 years should be targeted for screening. CKD is diagnosed and risk stratified with estimated glomerular filtration rate utilizing serum creatinine and measuring urine albumin-to-creatinine ratio. Once identified, CKD is staged according to C-G-A classification, and managed with lifestyle modification, interdisciplinary care and the recently expanding repertoire of pharmacotherapy which includes angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers, sodium-glucose-cotransporter-2 inhibitors, and mineralocorticorticoid receptor antagonists. In this paper, we present the why, who, when, how, and what of CKD screening.

National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical Laboratories.

Recognizing that race is a social and not a biological construct, healthcare professionals and the public have called for removal of race in clinical algorithms. In response, the National Kidney Foundation and the American Society of Nephrology created the Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases to examine the issue and provide recommendations. The final report from the Task Force recommends calculating estimated glomerular filtration rate (eGFR) without a race coefficient using the recently published CKD-EPI 2021 creatinine (cr) and creatinine-cystatin C (cr-cys) equations. The Task Force recommends immediately replacing older eGFRcr equations (MDRD Study and CKD-EPI 2009) with the new CKD-EPI 2021 equation. In a 2019 survey by the College of American Pathologists, 23% of 6200 laboratories reporting eGFRcr used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement. Rapid transition to using the CKD-EPI 2021 equation is an opportunity for laboratories to standardize to a single equation to eliminate differences in eGFRcr due to different equations used by different laboratories, and to report eGFR without use of race. We provide guidance to laboratories for implementing the CKD-EPI 2021 equations for both eGFRcr and eGFRcr-cys.

Missing Care: the Initial Impact of the COVID-19 Pandemic on CKD Care Delivery.

BACKGROUND: Chronic kidney disease (CKD) is a common condition with adverse health outcomes addressable by early disease management. The impact of the COVID-19 pandemic on care utilization for the CKD population is unknown. OBJECTIVE: To examine pandemic CKD care and identify factors associated with a high care deficit. DESIGN: Retrospective observational study PARTICIPANTS: 248,898 insured individuals (95% Medicare Advantage, 5% commercial) with stage G3-G4 CKD in 2018 MAIN MEASURES: Predicted (based on the pre-pandemic period of January 1, 2019-February 28, 2020) to observed per-member monthly face-to-face and telehealth encounters, laboratory testing, and proportion of days covered (PDC) for medications, evaluated during the early (March 1, 2020-June 30, 2020), pre-vaccine (July 1, 2020-December 31, 2020), and late (January 2021-August 2021) periods and overall. KEY RESULTS: In-person encounters fell by 24.1% during the pandemic overall; this was mitigated by a 14.2% increase in telehealth encounters, resulting in a cumulative observed utilization deficit of 10% relative to predicted. These reductions were greatest in the early pandemic period, with a 19.8% cumulative deficit. PDC progressively decreased during the pandemic (range 9-20% overall reduction), with the greatest reductions in hypertension and diabetes medicines. CKD laboratory monitoring was also reduced (range 11.8-43.3%). Individuals of younger age (OR 1.63, 95% CI 1.16, 2.28), with commercial insurance (1.43, 95% CI 1.25, 1.63), residing in the Southern US (OR 1.17, 95% CI 1.14, 1.21), and with stage G4 CKD (OR 1.21, 95% CI 1.17, 1.26) had greater odds of a higher care deficit overall. CONCLUSIONS: The early COVID-19 pandemic resulted in a marked decline of healthcare services for individuals with CKD, with an incomplete recovery during the later pandemic. Increased telehealth use partially compensated for this deficit. The downstream impact of CKD care reduction on health outcomes requires further study, as does evaluation of effective care delivery models for this population.

Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict progression of diabetic kidney disease.

AIM: Predicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX™) combining electronic health records (EHR) and biomarkers. METHODS: This is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for predicting a composite outcome of eGFR decline of ≥5 ml/min per year, ≥40% sustained decline, or kidney failure within 5 years. RESULTS: In 1146 patients, the median age was 63 years, 51% were female, the baseline eGFR was 54 ml min-1 [1.73 m]-2, the urine albumin to creatinine ratio (uACR) was 6.9 mg/mmol, follow-up was 4.3 years and 21% had the composite endpoint. On cross-validation in derivation (n = 686), KidneyIntelX had an AUC of 0.77 (95% CI 0.74, 0.79). In validation (n = 460), the AUC was 0.77 (95% CI 0.76, 0.79). By comparison, the AUC for the clinical model was 0.62 (95% CI 0.61, 0.63) in derivation and 0.61 (95% CI 0.60, 0.63) in validation. Using derivation cut-offs, KidneyIntelX stratified 46%, 37% and 17% of the validation cohort into low-, intermediate- and high-risk groups for the composite kidney endpoint, respectively. The PPV for progressive decline in kidney function in the high-risk group was 61% for KidneyIntelX vs 40% for the highest risk strata by KDIGO categorisation (p < 0.001). Only 10% of those scored as low risk by KidneyIntelX experienced progression (i.e., NPV of 90%). The NRIevent for the high-risk group was 41% (p < 0.05). CONCLUSIONS: KidneyIntelX improved prediction of kidney outcomes over KDIGO and clinical models in individuals with early stages of DKD.

A qualitative study documenting unmet needs in the management of diabetic kidney disease (DKD) in the primary care setting.

BACKGROUND: A majority of diabetic kidney disease (DKD) patients receive medical care in the primary care setting, making it an important opportunity to improve patient management. There is limited evidence evaluating whether primary care physicians (PCPs) are equipped to effectively manage these patients in routine clinical practice. The present study was undertaken to identify gaps in primary care and unmet needs in the diagnosis and monitoring of DKD in type 2 diabetes (T2D) patients among PCPs. METHODS: This was a qualitative analysis based on 30-45-min interviews with PCPs treating T2D patients. PCPs were recruited via email and were board-certified, in practice for more than 3 years, spent most of their time in direct clinical care, and provided care for more than three T2D patients in a week. Descriptive data analysis was conducted to identify and examine themes that were generated by interviews. Two reviewers evaluated interview data to identify themes and developed consensus on the priority themes identified. RESULTS: A total of 16 PCPs satisfying the inclusion criteria were recruited for qualitative interviews. Although the PCPs recognized kidney disease as an important comorbidity in T2D patients, testing for kidney disease was not consistently top of mind, with 56% reportedly performing kidney function testing in their T2D patients. PCPs most frequently reported using estimated glomerular filtration rate (eGFR) alone to monitor and stage DKD; only 25% PCPs reported testing for albuminuria. Most PCPs incorrectly believed that a majority of DKD patients are diagnosed in early stages. Also, early stages of DKD emerged as ambiguous areas of decision-making, wherein treatments prescribed greatly varied among PCPs. Lastly, early and accurate risk stratification of DKD patients emerged as the most important unmet need; which, if it could be overcome, was consistently identified by PCPs as a key to monitoring, appropriate nephrologist referrals, and intervening to improve outcomes in patients with DKD. CONCLUSIONS: Our study highlights important unmet needs in T2D DKD testing, staging, and stratification in the PCP setting that limit effective patient care. Health systems and insurers in the U.S. should prioritize the review and approval of new strategies that can improve DKD staging and risk stratification.

Implementation of a quality improvement strategy to increase outpatient kidney transplant referrals.

BACKGROUND: Kidney transplantation remains the optimal therapy for patients with end stage kidney disease (ESKD), though a small fraction of patients on dialysis are on organ waitlists. An important barrier to both preemptive kidney transplantation and successful waitlisting is timely referral to a kidney transplant center. We implemented a quality improvement strategy to improve outpatient kidney transplant referrals in a single center academic outpatient nephrology clinic. METHODS: Over a 3 month period (July 1-September 30, 2016), we assessed the baseline kidney transplantation referral rate at our outpatient nephrology clinic for patients 18-75 years old with an estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73m2 (2 values over 90 days apart). Charts were manually reviewed by two reviewers to look for kidney transplant referrals and documentation of discussions about kidney transplantation. We then performed a root cause analysis to explore potential barriers to kidney transplantation. Our intervention began on July 1, 2017 and included the implementation of a column in the electronic medical record (EMR) which displayed the patient's last eGFR as part of the clinic schedule. In addition, physicians were given a document listing their patients to be seen that day with an eGFR of < 20 mL/min/1.73m2. Annual education sessions were also held to discuss the importance of timely kidney transplant referral. RESULTS: At baseline, 54 unique patients with eGFR ≤20 ml/min/1.73 m2 were identified who were seen in the Clinic between July 1, 2016 and September 30, 2016. 29.6% (16) eligible patients were referred for kidney transplantation evaluation. 69.5% (37) of these patients were not referred for kidney transplant evaluation. 46.3% (25) did not have documentation regarding kidney transplant in the EMR. nephrologist's most recent note. Following the intervention, 66 unique patients met criteria for eligibility for kidney transplant evaluation. Kidney transplant referrals increased to 60.6% (p <  0.001). CONCLUSIONS: Our pilot implementation study of a strategy to improve outpatient kidney transplant referrals showed that a free, simple, scalable intervention can significantly improve kidney transplant referrals in the outpatient setting. This intervention targeted the nephrologist's role in the transplant referral, and facilitated the process of patient recognition and performing the referral itself without significantly interrupting the workflow. Next steps include further investigation to study the impact of early referral to kidney transplant centers on preemptive and living donor kidney transplantation as well as successful waitlisting.

Primary Care Physicians' Perceived Barriers to Nephrology Referral and Co-management of Patients with CKD: a Qualitative Study.

BACKGROUND: Effective co-management of patients with chronic kidney disease (CKD) between primary care physicians (PCPs) and nephrologists is increasingly recognized as a key strategy to ensure the delivery of efficient and high-quality CKD care. However, the co-management of patients with CKD remains suboptimal. OBJECTIVE: We aimed to identify PCPs' perceptions of key barriers and facilitators to effective co-management of patients with CKD at the PCP-nephrology interface. STUDY DESIGN: Qualitative study SETTING AND PARTICIPANTS: Community-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC; and San Francisco, CA APPROACH: We conducted four focus groups of PCPs. Two members of the research team coded transcribed audio-recorded interviews and identified major themes. KEY RESULTS: Most of the 32 PCPs (59% internists and 41% family physicians) had been in practice for > 10 years (97%), spent ≥ 80% of their time in clinical care (94%), and practiced in private (69%) or multispecialty group practice (16%) settings. PCPs most commonly identified barriers to effective co-management of patients with CKD focused on difficulty developing working partnerships with nephrologists, including (1) lack of timely adequate information exchange (e.g., consult note not received or CKD care plan unclear); (2) unclear roles and responsibilities between PCPs and nephrologists; and (3) limited access to nephrologists (e.g., unable to obtain timely consultations or easily contact nephrologists with concerns). PCPs expressed a desire for "better communication tools" (e.g., shared electronic medical record) and clear CKD care plans to facilitate improved PCP-nephrology collaboration. CONCLUSIONS: Interventions facilitating timely adequate information exchange, clear delineation of roles and responsibilities between PCPs and nephrologists, and greater access to specialist advice may improve the co-management of patients with CKD.

Identifying High-Risk Individuals for Chronic Kidney Disease: Results of the CHERISH Community Demonstration Project.

BACKGROUND: Most people with chronic kidney disease (CKD) are not aware of their condition. OBJECTIVES: To assess screening criteria in identifying a population with or at high risk for CKD and to determine their level of control of CKD risk factors. METHOD: CKD Health Evaluation Risk Information Sharing (CHERISH), a demonstration project of the Centers for Disease Control and Prevention, hosted screenings at 2 community locations in each of 4 states. People with diabetes, hypertension, or aged ≥50 years were eligible to participate. In addition to CKD, screening included testing and measures of hemoglobin A1C, blood pressure, and lipids. -Results: In this targeted population, among 894 people screened, CKD prevalence was 34%. Of participants with diabetes, 61% had A1C < 7%; of those with hypertension, 23% had blood pressure < 130/80 mm Hg; and of those with high cholesterol, 22% had low-density lipoprotein < 100 mg/dL. CONCLUSIONS: Using targeted selection criteria and simple clinical measures, CHERISH successfully identified a population with a high CKD prevalence and with poor control of CKD risk factors. CHERISH may prove helpful to state and local programs in implementing CKD detection programs in their communities.

Current State and Future Trends to Optimize the Care of Chronic Kidney Disease in African Americans.

BACKGROUND: African Americans (AAs) suffer the widest gaps in chronic kidney disease (CKD) outcomes compared to Caucasian Americans (CAs) and this is because of the disparities that exist in both health and healthcare. In fact, the prevalence of CKD is 3.5 times higher in AAs compared to CAs. The disparities exist at all stages of CKD. Importantly, AAs are 10 times more likely to develop hypertension-related kidney failure and 3 times more likely to progress to kidney failure compared to CAs. SUMMARY: Several factors contribute to these disparities including genetic and social determinants, late referrals, poor care coordination, medication adherence, and low recruitment in clinical trials. Key Messages: The development and implementation of CKD-related evidence-based approaches, such as clinical and social determinant assessment tools for medical interventions, more widespread outreach programs, strategies to improve medication adherence, safe and effective pharmacological treatments to control or eliminate CKD, as well as the use of health information technology, and patient-engagement programs for improved CKD outcomes may help to positively impact these disparities among AAs.

Current State and Future Trends to Optimize the Care of African Americans with End-Stage Renal Disease.

BACKGROUND: Chronic kidney disease is a progressive disease, which terminates in end-stage renal diseases (ESRD) that requires either dialysis or kidney transplantation for the patient to survive. There is an alarming trend in the disparities of ESRD in African Americans (AAs). Currently, AAs represent more than 30% of incident ESRD cases, yet they constitute 15% of the overall US population. Despite the reductions in mortality, increases in access to patient-centered home dialysis and preemptive kidney transplantation for the overall US ESRD population over the last decade, disparities in the care of AAs with ESRD remain largely unaffected. SUMMARY: This review discusses patient-, community-, and practitioner-related factors that contribute to disparities in ESRD care for AAs. In particular, the review addresses issues related to end-of-life support, the importance of Apolipoprotein-1 gene variants, and the advent of pharmacogenomics toward achieving precision care. The need for accessible clinical intelligence for the ESRD population is discussed. Several interventions and a call to action to address the disparities are presented. Key Messages: Significant disparities in ESRD care exist for AAs. Strategies to enhance patient engagement, education, accountable partnerships, and clinical intelligence may reduce these disparities.

Health Disparities in Kidney Transplantation for African Americans.

BACKGROUND: The persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system. SUMMARY: There are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

We still go for the jugular: implications of the 3SITES central venous catheter study for nephrology.

The 3SITES study randomly assigned a nontunneled central venous catheter site in over 3000 adults treated in intensive care units. The subclavian site was associated with a lower rate of short-term complications, including catheter-related bloodstream infection and deep venous thrombosis, compared to the femoral or internal jugular site. Nephrologists should be aware of this study and should continue to advocate for alternatives to subclavian vein catheter placement in patients with chronic kidney disease who are expected to require arteriovenous access for dialysis in the future.

North American experience with Low protein diet for Non-dialysis-dependent chronic kidney disease.

Whereas in many parts of the world a low protein diet (LPD, 0.6-0.8 g/kg/day) is routinely prescribed for the management of patients with non-dialysis-dependent chronic kidney disease (CKD), this practice is infrequent in North America. The historical underpinnings related to LPD in the USA including the non-conclusive results of the Modification of Diet in Renal Disease Study may have played a role. Overall trends to initiate dialysis earlier in the course of CKD in the US allowed less time for LPD prescription. The usual dietary intake in the US includes high dietary protein content, which is in sharp contradistinction to that of a LPD. The fear of engendering or worsening protein-energy wasting may be an important handicap as suggested by a pilot survey of US nephrologists; nevertheless, there is also potential interest and enthusiasm in gaining further insight regarding LPD's utility in both research and in practice. Racial/ethnic disparities in the US and patients' adherence are additional challenges. Adherence should be monitored by well-trained dietitians by means of both dietary assessment techniques and 24-h urine collections to estimate dietary protein intake using urinary urea nitrogen (UUN). While keto-analogues are not currently available in the USA, there are other oral nutritional supplements for the provision of high-biologic-value proteins along with dietary energy intake of 30-35 Cal/kg/day available. Different treatment strategies related to dietary intake may help circumvent the protein- energy wasting apprehension and offer novel conservative approaches for CKD management in North America.