Kerry Willis

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.

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.

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.