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In the past decade, advances in the validation of surrogate end points for chronic kidney disease (CKD) progression have heightened interest in evaluating therapies in early CKD. In December 2020, the National Kidney Foundation sponsored a scientific workshop in collaboration with the US Food and Drug Administration (FDA) to explore patient, provider, and payor perceptions of the value of treating early CKD. The workshop reviewed challenges for trials in early CKD, including trial designs, identification of high-risk populations, and cost-benefit and safety considerations. Over 90 people representing a range of stakeholders including experts in clinical trials, nephrology, cardiology and endocrinology, patient advocacy organizations, patients, payors, health economists, regulators and policy makers attended a virtual meeting. There was consensus among the attendees that there is value to preventing the development and treating the progression of early CKD in people who are at high risk for progression, and that surrogate end points should be used to establish efficacy. Attendees also concluded that cost analyses should be holistic and include aspects beyond direct savings for treatment of kidney failure; and that safety data should be collected outside/beyond the duration of a clinical trial. Successful drug development and implementation of effective therapies will require collaboration across sponsors, patients, patient advocacy organizations, medical community, regulators, and payors.

Background: The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown. Purpose: To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. Data Sources: MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events. Study Selection: 61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients. Data Extraction: A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes. Data Synthesis: ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified. Limitations: Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing. Conclusion: Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.

Current classification of chronic kidney disease (CKD) into stages using indirect systemic measures (estimated glomerular filtration rate (eGFR) and albuminuria) is agnostic to the heterogeneity of underlying molecular processes in the kidney thereby limiting precision medicine approaches. To generate a novel CKD categorization that directly reflects within kidney disease drivers we analyzed publicly available transcriptomic data from kidney biopsy tissue. A Self-Organizing Maps unsupervised artificial neural network machine-learning algorithm was used to stratify a total of 369 patients with CKD and 46 living kidney donors as healthy controls. Unbiased stratification of the discovery cohort resulted in identification of four novel molecular categories of disease termed CKD-Blue, CKD-Gold, CKD-Olive, CKD-Plum that were replicated in independent CKD and diabetic kidney disease datasets and can be further tested on any external data at kidneyclass.org. Each molecular category spanned across CKD stages and histopathological diagnoses and represented transcriptional activation of distinct biological pathways. Disease progression rates were highly significantly different between the molecular categories. CKD-Gold displayed rapid progression, with significant eGFR-adjusted Cox regression hazard ratio of 5.6 [1.01-31.3] for kidney failure and hazard ratio of 4.7 [1.3-16.5] for composite of kidney failure or a 40% or more eGFR decline. Urine proteomics revealed distinct patterns between the molecular categories, and a 25-protein signature was identified to distinguish CKD-Gold from other molecular categories. Thus, patient stratification based on kidney tissue omics offers a gateway to non-invasive biomarker-driven categorization and the potential for future clinical implementation, as a key step towards precision medicine in CKD.

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The interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear.

Early detection and treatment of chronic kidney disease (CKD) is important for slowing progression to renal failure and preventing cardiovascular events, but CKD is often not recognized and patients are referred to nephrologists too late for timely management. Automated laboratory reporting of estimated glomerular filtration rate (eGFR) has been introduced in many health systems to improve CKD recognition, but its impact on large, US-based health systems remains unclear.

Previous studies demonstrate that graft survival from older living kidney donors (LD; age >60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD.

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.

Well-designed trials are of paramount importance in improving the delivery of care to patients with kidney disease. However, it remains unknown whether contemporary clinical trials within nephrology are of sufficient quality and quantity to meet this need.

Diabetic nephropathy is the most common cause of CKD and represents a large and ominous public health problem. Patients with diabetic kidney disease have exceptionally high rates of cardiovascular morbidity and mortality. In fact, the excess mortality among patients with diabetes appears to be largely limited to the subgroup with kidney disease and explained by their high burden of cardiovascular disease. The mechanisms underlying the strong association between diabetic kidney disease and various forms of cardiovascular disease are poorly understood. Traditional risk factors for cardiovascular disease, although prevalent among those with diabetes, do not fully account for the heightened risk observed. Despite their susceptibility to cardiovascular disease, patients with CKD are less likely to receive appropriate risk factor modification than the general population. Moreover, because patients with CKD have commonly been excluded from major cardiovascular trials, the evidence for potential treatments remains limited. The mainstays of treatment for diabetic kidney disease currently include blockade of the renin-angiotensin-aldosterone system and control of hypertension, hyperglycemia, and dyslipidemia. Increased awareness of the vulnerability of this patient population and more timely interventions are likely to improve outcomes while large evidence gaps are filled with newer studies.

Patients with chronic kidney disease (CKD) are complex, have many medication-related problems (MRPs) and high rates of medication nonadherence, and are less adherent to some medications than patients with higher levels of kidney function. Nonadherence in CKD patients increases the odds of uncontrolled hypertension, which can increase the risk of CKD progression. This review discusses reasons for gaps in medication-related care for CKD patients, pharmacy services to reduce these gaps and successful models that incorporate pharmacist care.

In renal allograft recipients presenting with graft dysfunction, it is critical to determine the patency of the transplant vasculature to guide clinical management. Conventional modalities such as Doppler ultrasound, contrast-enhanced computed tomography, magnetic resonance angiography (MRA), and noncontrast MRA are each of limited use because of technical factors and toxicity of standard contrast agents. The purpose of this study was to retrospectively review our institutional experience with renal transplant MRA using ferumoxytol (a nonnephrotoxic medication) as a contrast agent and evaluate its use in the assessment of allograft vascular patency in patients with graft dysfunction, either delayed or slow graft function within hours to days after kidney transplantation or acute kidney injury weeks to months after kidney transplantation.

Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level.

The primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery.

Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

Elderly patients with advanced kidney disease experience considerable disability, morbidity, and mortality. Little is known about the impact of physician-patient interactions on patient preparation for the illness trajectory. We sought to describe how nephrologists and older patients discuss and understand the prognosis and course of kidney disease leading to renal replacement therapy.

Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes, but is challenging to predict from information available before surgery.

Many laboratories now report estimated glomerular filtration rate (eGFR) when a serum creatinine measurement is ordered. A summary of the impact of eGFR reporting in health care systems around the world for which it has been adopted is lacking.

Epidemiologic studies of populations continue to emerge showing that early-life factors influence the risk of developing several chronic diseases of adulthood. Susceptibility to environmental factors is particularly problematic during renal development, which is not complete until 36 weeks of gestation. Environmental deprivation may lead to adaptations including early growth restriction, whereas late insults may alter the kidney during the final stages of development. Because disparities among those who are more likely to have low birth weight mirrors the disparities observed among those more likely to develop kidney-related disorders, fetal origins have been presumed to explain some of the observed disparities. Although current empiric evidence supports a link between fetal programming and childhood/adult kidney disease, affected pathways may vary by race.

Kidney dysfunction is common after cardiac surgery and predicts mortality risk and poorer long-term outcome, particularly when acute injury superimposes upon chronic kidney disease. Numerous insults contribute to perioperative renal impairment including major surgical trespass, procedure-specific interventions (eg, deep hypothermic circulatory arrest), and postoperative complications. Regardless of cause, evidence supports a role for renal impairment and accumulation of “uremic toxins” as direct contributors to adverse outcome. No one has yet characterized a loss of renal function small enough to be insignificant. Despite considerable research focus, progress in development of interventions aimed at perioperative renoprotection has been disappointing. However, practice modifications can influence the likelihood of acute kidney injury, and several recent advances provide hope for the future. We review pathophysiologic understanding of this disorder; evaluate the confusing relationship (causal vepiphenomena) among acute kidney injury, chronic kidney disease, and adverse outcome after cardiac surgery; and provide an evidence-based assessment of the conduct of cardiac surgery and renoprotection strategies.

Background:Chronic kidney disease (CKD) is clearly associated with an increased risk for adverse outcomes; however, the cumulative impact of renal and cardiac complications in high-risk populations is not known. In addition, little is known about patterns of nephrology care in patients with CKD. Methods:We conducted a retrospective longitudinal cohort study assessing CKD prevalence and progression, associations with all-cause mortality, and variations in patterns of nephrology consultation in older patients with diabetes in a vertically integrated health care system. Results:A total of 12,570 patients within a 7–Veterans Affairs hospital service network in 1998 to 1999 were identified by means of computerized records. Nearly half (48%) were affected with CKD; most had mild to moderate CKD. After an observation period of 3 years, mortality rates in those unaffected with CKD were high (4.7 deaths/100 person-years) and increased substantially with progressive CKD (eg, 20.1 deaths/100 person-years with an estimated glomerular filtration rate [GFR] of 15 to 29 mL/min/1.73 m2[0.25 to 0.48 mL/s/1.73 m2]). Only 7.2% of patients with CKD had a nephrology visit during the entire 5-year study period. Although visits increased with more advanced CKD, only 32% of patients with an estimated GFR of 15 to 29 mL/min/1.73 m2had been seen in a nephrology clinic. We also found that nephrology referrals were driven preferentially by elevations in serum creatinine levels, rather than low GFRs. Conclusion:Many in this cohort of older patients with diabetes are affected with CKD. Mortality rates are high, and mortality risks associated with CKD amplify those of other risk factors. Nephrology visits are low and may represent an unexploited resource for improving CKD management. Underrecognition of CKD likely is related to overestimation of kidney function by relying on serum creatinine level in elderly patients.