Patient-Centered Quality Measures for Dialysis Care: A Report of a Kidney Disease Outcomes Quality Initiative (KDOQI) Scientific Workshop Sponsored by the National Kidney Foundation.

Providing high-quality patient-centered care is the central mission of dialysis facilities. Assessing quality and patient-centeredness of dialysis care is necessary for continuous dialysis facility improvement. Based predominantly on readily measured items, current quality measures in dialysis care emphasize biochemical and utilization outcomes, with very few patient-reported items. Additionally, current metrics often do not account for patient preferences and may compromise patient-centered care by limiting the ability of providers to individualize care targets, such as dialysis adequacy, based on patient priorities rather than a fixed numerical target. Developing, implementing, and maintaining a quality program using readily quantifiable data while also allowing for individualization of care targets that emphasize the goals of patients and their care partners provided the motivation for a September 2022 Kidney Disease Outcomes Quality Initiative (KDOQI) Workshop on Patient-Centered Quality Measures for Dialysis Care. Workshop participants focused on 4 questions: (1) What are the outcomes that are most important to patients and their care partners? (2) How can social determinants of health be accounted for in quality measures? (3) How can individualized care be effectively addressed in population-level quality programs? (4) What are the optimal means for collecting valid and robust patient-reported outcome data? Workshop participants identified numerous gaps within the current quality system and favored a conceptually broader, but not larger, quality system that stresses highly meaningful and adaptive measures that incorporate patient-centered principles, individual life goals, and social risk factors. Workshop participants also identified a need for new, low-burden tools to assess patient goals and priorities.

A National Registry for People With All Stages of Kidney Disease: The National Kidney Foundation (NKF) Patient Network.

RATIONALE & OBJECTIVE: The National Kidney Foundation (NKF) launched the first national US kidney disease patient registry, the NKF Patient Network, that is open to patients throughout the continuum of chronic kidney disease (CKD). The Network provides individualized education and will facilitate patient-centered research, clinical care, and health policy decisions. Here, we present the overall design and the results of a feasibility study that was conducted July through December 2020. STUDY DESIGN: Longitudinal observational cohort study of patient-entered data with or without electronic health care record (EHR) linkage in collaboration with health systems. SETTING & PARTICIPANTS: People with CKD, age≥18 years, are invited through their provider, NKF communications, or national outreach campaign. People self-enroll and share their data through a secure portal that offers individualized education and support. The first health system partner is Geisinger. EXPOSURE: Any cause and stage of CKD, including dialysis and kidney transplant recipients. OUTCOME: Feasibility of the EHR data transfer, participants' characteristics, and their perspectives on usability and content. ANALYTICAL APPROACH: Data were collected and analyzed through the registry portal powered by the Pulse Infoframe healthie 2.0 platform. RESULTS: During the feasibility study, 80 participants completed their profile, and 42 completed a satisfaction survey. Mean age was 57.5 years, 51% were women, 83% were White, and 89% were non-Hispanic or Latino. Of the participants, 60% were not aware of their level of estimated glomerular filtration rate and 91% of their urinary albumin-creatinine ratio. LIMITATIONS: Challenges for the Network are lack of awareness of kidney disease for many with CKD, difficulty in recruiting vulnerable populations or those with low digital readiness, and loss to follow-up, all leading to selection bias. CONCLUSIONS: The Network is positioned to become a national and international platform for real-world data that can inform the development of patient-centered research, care, and treatments.

Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration.

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.

Treating Early-Stage CKD With New Medication Therapies: Results of a CKD Patient Survey Informing the 2020 NKF-FDA Scientific Workshop on Clinical Trial Considerations for Developing Treatments for Early Stages of Common, Chronic Kidney Diseases.

Rationale & Objective: With a growing number of medications and therapies available to treat chronic kidney disease (CKD), risk-versus-benefit discussions are increasingly critical. Balancing risks and benefits requires assessing patients' understanding of these, as well as incorporating patient preferences and tolerance for side effects into shared decision making. Study Design: A 26-question online survey was sent to people in the National Kidney Foundation patient email list and posted on associated social media pages to assess the respondents' willingness and comfort with taking preventative medications during earlier-stage CKD to inform a December 2020 scientific workshop co-sponsored by the National Kidney Foundation and the US Food and Drug Administration on clinical trial considerations in developing treatments for individuals with early stages of CKD. Setting & Population: Online survey of CKD patients, including broad demographic data and responses to risk-benefit scenarios, with surveys emailed to 20,249 people not identified as currently receiving kidney replacement therapy. Analytical Approach: Survey results are presented as descriptive data. Results: Of 1,029 respondents, 45 self-identified as at risk for CKD, 566 had CKD, 267 had received kidney transplants, 51 were receiving dialysis, and 100 replied other or did not answer. Respondents reported being willing to assume some risk with the goal of preventing the progression of CKD, with a greater willingness to assume risk and treatment burdens the closer they came to late-stage disease. Clinician recommendations regarding kidney therapies and clinician willingness to work with patients to address any side effects were important in respondents' willingness to initiate and persevere with a new medication. Limitations: Approximately 10% response rate with limited data on respondents. Conclusions: Risk-versus-benefit discussions appear key to patients and their care partners making well-informed decisions about taking a new medication that may or may not help the progression of their kidney disease. Future tools and strategies are needed to facilitate informed discussions of treatment in early-stage kidney disease.

Change in Albuminuria and GFR as End Points for Clinical Trials in Early Stages of CKD: A Scientific Workshop Sponsored by the National Kidney Foundation in Collaboration With the US Food and Drug Administration and European Medicines Agency.

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, these end points may not be practical for early stages of kidney disease. In March 2018, the National Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were presented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simulations of trial design. In cohorts, after accounting for measurement error, relationships between change in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of kidney disease progression were strong and consistent. In trials, the posterior median R2 of treatment effects on the candidate surrogates with the clinical outcome was 0.47 (95% Bayesian credible interval [BCI], 0.02-0.96) for early change in UACR and 0.72 (95% BCI, 0.05-0.99) when restricted to baseline UACR>30mg/g, and 0.97 (95% BCI, 0.78-1.00) for total eGFR slope at 3 years and 0.96 (95% BCI, 0.63-1.00) for chronic eGFR slope (ie, the slope excluding the first 3 months from baseline, when there might be acute changes in eGFR). The magnitude of the relationships of changes in the candidate surrogates with risk for clinical outcome was consistent across cohorts and trials: a UACR reduction of 30% or eGFR slope reduction by 0.5 to 1.0mL/min/1.73m2 per year were associated with an HR of ∼0.7 for the clinical outcome in cohorts and trials. In simulations, using GFR slope as an end point substantially reduced the required sample size and duration of follow-up compared with the clinical end point when baseline eGFR was high, treatment effects were uniform, and there was no acute effect of the treatment. We conclude that both early change in albuminuria and GFR slope fulfill criteria for surrogacy for use as end points in clinical trials for chronic kidney disease progression under certain conditions, with stronger support for change in GFR than albuminuria. Implementation requires understanding conditions under which each surrogate is likely to perform well and restricting its use to those settings.

Confluence of Epidemics of Hepatitis C, Diabetes, Obesity, and Chronic Kidney Disease in the United States Population.

BACKGROUND & AIMS: Obesity, kidney disease, and diabetes are common conditions that can affect outcomes of patients with chronic hepatitis C. The authors aimed to quantify the burden of these comorbid conditions among adults with chronic hepatitis C in the United States and to estimate the risk of death among people with chronic hepatitis C and comorbidities. METHODS: The authors conducted cross-sectional and prospective analyses of 13,726 participants in the third National Health and Nutrition Examination Survey (NHANES III) and 23,691 participants of NHANES 1999-2012. Serum samples were analyzed for the presence of antibodies to hepatitis C virus (anti-HCV); in samples found to be positive for anti-HCV, the authors quantified HCV RNA (viral load). Individuals with anti-HCV and detectable HCV RNA were considered to have chronic hepatitis C. Comorbidities were defined using self-reported, physical examination, and laboratory data, as available. The authors used logistic models and predictive margins to estimate the adjusted prevalence of comorbidities in patients with chronic hepatitis C. The authors used Poisson regression models to estimate adjusted mortality rates based on chronic hepatitis C status, with or without comorbidities. Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause, cardiovascular, and cancer mortality according to chronic hepatitis C status, with and without comorbidities. RESULTS: Among persons with chronic hepatitis C, the demographic-adjusted prevalence estimate of diabetes was 17.9% (95% CI, 11.2%-27.5%) and of obesity was 20.9% (95% CI, 12.4%-29.5%). Overall, 69.6% of persons with chronic hepatitis C had at least 1 major cardiometabolic comorbidity (95% CI, 62.1%-76.2%). Only 38% of adults with chronic hepatitis C reported a diagnosis of liver disease. Chronic hepatitis C was associated with a substantially increased risk of death (HR, 2.45), especially in the presence of diabetes (HR, 3.24) or chronic kidney disease (HR, 4.39). CONCLUSION: In an analysis of NHANES data, the authors found that individuals with chronic hepatitis C have a high burden of major cardiometabolic comorbidities. Diabetes and chronic kidney disease, in particular, are associated with substantial excess mortality in persons with chronic hepatitis C.

GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration.

The US Food and Drug Administration currently accepts halving of glomerular filtration rate (GFR), assessed as doubling of serum creatinine level, as a surrogate end point for the development of kidney failure in clinical trials of kidney disease progression. A doubling of serum creatinine level generally is a late event in chronic kidney disease (CKD); thus, there is great interest in considering alternative end points for clinical trials to shorten their duration, reduce sample size, and extend their conduct to patients with earlier stages of CKD. However, the relationship between lesser declines in GFR and the subsequent development of kidney failure has not been well characterized. The National Kidney Foundation and Food and Drug Administration sponsored a scientific workshop to critically examine available data to determine whether alternative GFR-based end points have sufficiently strong relationships with important clinical outcomes of CKD to be used in clinical trials. Based on a series of meta-analyses of cohorts and clinical trials and simulations of trial designs and analytic methods, the workshop concluded that a confirmed decline in estimated GFR of 30% over 2 to 3 years may be an acceptable surrogate end point in some circumstances, but the pattern of treatment effects on GFR must be examined, specifically acute effects on estimated GFR. An estimated GFR decline of 40% may be more broadly acceptable than a 30% decline across a wider range of baseline GFRs and patterns of treatment effects on GFR. However, there are other circumstances in which these end points could lead to a reduction in statistical power or erroneous conclusions regarding benefits or harms of interventions. We encourage careful consideration of these alternative end points in the design of future clinical trials.

Potential effects of reclassifying CKD as a coronary heart disease risk equivalent in the US population.

BACKGROUND: Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. STUDY DESIGN: Nationally representative cross-sectional study. SETTING & PARTICIPANTS: 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. PREDICTORS: Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. OUTCOMES & MEASUREMENTS: Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. RESULTS: Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. LIMITATIONS: CKD and LDL cholesterol defined using a single laboratory value. CONCLUSIONS: Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy.

Cardiovascular risk factor burden, treatment, and control among adults with chronic kidney disease in the United States.

BACKGROUND: Cardiovascular disease is a major concern in persons with chronic kidney disease (CKD). We assessed the current burden of cardiovascular risk factors and differences in risk factor treatment and control in the general US adult population by CKD status. METHODS: A cross-sectional study of 10,741 adults aged 20+ years from the 2007-2010 National Health and Nutrition Examination Survey was performed. Persons were categorized into 3 groups: CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), CKD stages 1 and 2 (urinary albumin-to-creatinine ratio ≥30 mg/g and estimated glomerular filtration rate ≥60 mL/min/1.73 m(2)), and no CKD. RESULTS: The majority of adults with CKD stages 3 to 5 (79.8%) and stages 1 and 2 (59.1%) had ≥2 cardiovascular risk factors, substantially higher than adults without CKD (32.7%, P < .001). Diabetes was the most strongly associated risk factor and was highly specific for CKD stages 1 and 2 (prevalence ratio 2.53, 95% CI 2.21-2.89) and, to a lesser extent, CKD stages 3 to 5 (prevalence ratio 1.59, 95% CI 1.38-1.84). Most adults with diagnosed risk factors reported medication use for risk factor control, and pharmacologic treatment was more common among those with than without CKD. However, poor risk factor control was also common among persons treated for risk factors with CKD compared with those without CKD. CONCLUSIONS: There continues to be a substantial cardiovascular risk factor burden among adults with CKD stages 3 to 5 and, to a lesser extent, adults with CKD stages 1 and 2 when compared with adults without CKD. Overall, optimal risk factor control is low in adults with CKD, highlighting the need for aggressive cardiovascular risk reduction in adults with CKD.

Real-time multi-marker measurement of organic compounds in human breath: towards fingerprinting breath.

The prospects for exploiting proton transfer reaction-time of flight-mass spectrometry (PTR-ToF-MS) in medical diagnostics are illustrated through a series of case studies. Measurements of acetone levels in the breath of 68 healthy people are presented along with a longitudinal study of a single person over a period of 1 month. The median acetone concentration across the population was 484 ppbV with a geometric standard deviation (GSD) of 1.6, whilst the average GSD during the single subject longtitudinal study was 1.5. An additional case study is presented which highlights the potential of PTR-ToF-MS in pharmacokinetic studies, based upon the analysis of online breath samples of a person following the consumption of ethanol. PTR-ToF-MS comes into its own when information across a wide mass range is required, particularly when such information must be gathered in a short time during a breathing cycle. To illustrate this property, multicomponent breath analysis in a small study of cystic fibrosis patients is detailed, which provides tentative evidence that online PTR-ToF-MS analysis of tidal breath can distinguish between active infection and non-infected patients.

Detection of chemical weapon agents and simulants using chemical ionization reaction time-of-flight mass spectrometry.

Chemical ionization reaction time-of-flight mass spectrometry (CIR-TOF-MS) has been used for the analysis of prepared mixtures of chemical weapon agents (CWAs) sarin and sulfur mustard. Detection of the CWA simulants 2-chloroethyl ethyl sulfide, triethyl phosphate, and dimethyl methyl phosphonate has also been investigated. Chemical ionization of all the agents and simulants was shown to be possible using the CIR-TOF-MS technique with a variety of reagent ions, and the sensitivity was optimized by variation of instrument parameters. The ionization process was found to be largely unaffected by sample humidity levels, demonstrating the potential suitability of the method to a range of environmental conditions, including the analysis of CWAs in air and in the breath of exposed individuals.

Differentiation of isobaric compounds using chemical ionization reaction mass spectrometry.

The technique of proton transfer reaction mass spectrometry (PTR-MS) couples a proton transfer reagent, usually H3O+, with a drift tube and mass spectrometer to determine concentrations of volatile organic compounds. Here we describe a first attempt to use chemical ionization (CI) reagents other than proton transfer species inside a PTR-MS instrument. The ability to switch to other types of CI reagents provides an extra dimension to the technique. This capability is demonstrated by focusing on the ability to distinguish several isobaric aldehydes and ketones, including the atmospherically important molecules methacrolein and methyl vinyl ketone. Two CI reagents were selected, H3O+ and NO+, both being cleanly generated in a low intensity radioactive source prior to injection into the drift tube. By recording spectra with both of these reagents, the contributions from different isobaric molecules can be separated by virtue of their unique spectrometric 'fingerprints'. The work demonstrates that this form of instrumentation is not restricted to proton transfer reagents and is the basis of a more general technique, chemical ionization reaction mass spectrometry (CIRMS).

Report of three case studies with olanzapine for chronic pain.

Olanzapine, an atypical antipsychotic, has broad spectrum psychotropic effects, affecting dopamine receptors 1, 2, and 3, 5-hydroxytryptamine 2A, 5-hydroxytryptamine 2C, muscarinic, alpha-adrenergic, alpha-adrenergic, and histamine H-sites. This unique pharmacologic property allows clinicians to use the agent as an adjunct for pain control, particularly when the intensity of the pain is exacerbated by dysregulation of neurotransmitters. Three case studies are presented from a suburban family practice setting in which olanzapine has been successfully used to regulate pain perception in adults with chronic pain.