Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville, Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

CKD: Consistency of GFR and Albuminuria as Risk Predictors

Source: Hallan SI, et al. JAMA 2012; 308:2349-2360.

Clinicians have become increasingly aware of the disease burden associated with chronic kidney disease (CKD), especially since the routine inclusion of a calculated estimated glomerular filtration rate (eGFR) within metabolic profile testing. Promulgation of CKD stages by national organizations and encouragement of clinicians to consider referral of patients with CKD at an earlier stage (usually by CKD stage 3-B) has prompted the clinical community to address eGFR as well as the presence, absence, and severity of urinary albumin excretion on a more consistent basis. Because of inherent renal functional decline associated with increased age, accompanied by decrease in muscle mass that contributes to the generation of creatinine, some have questioned whether current stratification of CKD by eGFR, albuminuria, or both holds true throughout the lifespan.

Hallan et al performed a meta-analysis on data from more than 2 million individuals in Asia, Australasia, Europe, and North/South America to investigate whether eGFR and the presence of albuminuria remain consistently predictive of adverse outcomes.

Although at older ages the absolute risk imparted by CKD was greater than in younger folks (simply because a larger absolute number of older individuals die than younger individuals, whether or not they have CKD), overall, the hazard ratio (HR) for mortality decreased with increasing age. For example, at an eGFR of 45 mL/min, the HR for death (when compared to a normal eGFR) was 3.5 for persons ages 18-54, 2.2 for ages 55-64, and 1.35 for ages > 75 years. A similar relationship was noted for albuminuria.

Albuminuria and reduction in eGFR are associated with adverse outcomes throughout the lifespan, although the HR for risk appears to lessen as we age.


Changing Outcomes for Patients with Chronic Hepatitis C

Source: van der Meer AJ, et al. JAMA 2012;308:2584-2593.

Chronic hepatitis C (HEPC) has an increased risk for liver cancer, end-stage liver disease, and all-cause mortality. Fortunately, current antiviral treatments for HEPc (e.g., ribavirin and interferon) are effective in the majority of subjects. As many as 80% of HEPc patients who complete a therapeutic course will obtain what is called a sustained virological response (SVR); that is, no detectible HEPc virus 6 months after completion of therapy. SVR might reasonably be titled “cure,” since indications are that absence of virus at 6 months is indicative of permanent eradication.

Nonetheless, some patients enjoying SVR already have experienced inflammatory hepatic changes resulting in fibrosis. It has not been sufficiently elucidated whether achievement of SVR ultimately reduces risk for mortality, liver cancer, or hepatic failure, especially in a group with already established hepatic fibrosis.

Using an international multicenter database (n = 540), the outcomes of HEPc patients with long-term follow-up (mean 8.4 years), as well as biopsy-proven fibrosis, were investigated to compare those who attained SVR vs those who did not. The mortality rate was essentially three times greater in those who did not attain SVR (26% vs 8.9%); the comparative cumulative incidence rate of liver-related mortality or transplantation was even more dramatic: 1.9% (SVR) vs 27.4% (SVR not attained). The attainment of SVR is associated with substantial longterm reductions in mortality as well as less need for liver transplantation.


Is Fructose a Primary Culprit in Obesity?

Source: Page KA, et al. JAMA 2013; 309:63-70.

Sorting out the causes of the current pandemic of obesity has not been easy and appears to have contributions from various life quadrants: activity, genetics, absolute calorie ingestion, and — most recently — characteristics of the calories we ingest. For instance, whereas in the recent past one might simplistically think that a gram of ice cream and a gram of broccoli should result in similar metabolic impact, recognition of the glycemic index (variation in glucose rate of absorption from different food sources) has taught us that a calorie is not necessarily always a calorie in the grander scope of things.

Fructose, an increasingly commonplace component of fast foods, snacks, etc., has recently come under fire as a potential culprit exacerbating the obesity pandemic. Mechanistically, fructose could be metabolically detrimental because (compared to glucose, that is) it blunts satiety-inducing GLP-1, and fails to shut off appetite-stimulating ghrelin.

Page et al measured regional cerebral blood flow in response to glucose and fructose ingestion. They found that fructose did not produce the same reduction in hypothalamic cerebral blood flow (associated with satiety and fullness) as did glucose. Disproportionate consumption of fructose may be a significant contributor to weight management problems.