Online Risk Estimator for Kidney Failure Is Accurate Across Diverse, Multi-national Populations

An international consortium of researchers has determined that an online tool for estimating risk of kidney failure accurately predicts the 2- and 5-year risk of developing kidney failure in diverse populations across a range of ages and races, as well as both men and women (JAMA 2016;315:164–74). The findings could help patients with chronic kidney disease (CKD) at high risk of kidney failure prepare for dialysis or transplant, while giving peace of mind to others with CKD who are not at significant risk of kidney failure, according to the authors.

This study builds on initial work by Canadian researchers who developed and validated the risk tool in a Canadian population. The tool, which is available online at, includes four- and eight-variable equations. The four-variable equation considers estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, along with age, sex, and urinary albumin tocreatinine ratio (ACR). The eight-variable equation incorporates all the four-variable equation elements plus measurements for calcium, phosphate, bicarbonate, and albumin.

While the tool has been validated in some other countries and health systems, the researchers believed that in order for it to be adopted widely it needed to be validated in diverse populations, including non-white patients and individuals living outside North America.

The investigators tapped into 31 cohorts participating in the CKD Prognosis Consortium, with data collected from 1982 through 2014. In all, the study included 721,357 participants with CKD stages 3 to 5 in 30 countries spanning four continents. The researchers calculated cohort-specific hazard ratios and combined them in a meta-analysis to develop new pooled kidney failure risk equations. They then compared the original and pooled risk equations.

Out of all participants, 23,829 developed kidney failure, with an average follow-up time of 4.2 years. The investigators found that the original four- and eight-variable equations “achieved excellent discrimination…across all cohorts.” They did not see improved discrimination with their new pooled equations. They did find, however, that the original risk equations over-estimated risk in some non-North American cohorts. By adding a calibration factor, they lowered the 2- and 5-year risk and improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively.

“We’ve known which were the important tests to consider in determining the risk of kidney failure, but we didn’t know exactly how to put them together and we didn’t have a high level of confidence that this tool could be used widely,” said one of the study’s co-authors, Josef Coresh, MD, PhD, in a prepared statement. “Now we do.”

Fecal Immunochemical Testing Is Feasible and Effective for Population-Level Colorectal Cancer Screening

Given its sensitivity for detecting colorectal cancer (CRC) and “high adherence” to annual follow-up screening, annual fecal immunochemical testing (FIT) is “feasible and effective” for population-level CRC screening (Ann Intern Med 2015; doi:10.7326/M15-0983). The findings are from a retrospective cohort study conducted by Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Southern California (KPSC).

The study involved 670,841 KPNC and KPSC member participants in the organizations’ respective CRC screening programs. These included individuals ages 50 to 75 without a record of colonoscopy within 10 years, sigmoidoscopy within 5 years, or fecal blood testing within the past year who were mailed and subsequently returned FIT tests. Overall, 48.2% of member participants returned FIT tests. The researchers subsequently tracked these participants through up to four rounds of testing. Participation ranged from 75.3% to 86.1% in subsequent rounds.

Using the OC FIT-CHEK kit with a cutoff of 20 µg hemoglobin/g for positivity, the investigators observed 5%, 3.7%, and 4.3% FIT positivity rate in the first, second, and third rounds of testing, respectively. More than three-quarters of participants with a positive FIT underwent colonoscopy within 1 year, and more than 96% had some type of follow-up within 12 months of their initial positive result.

FIT detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round 1 and 73.4% and 78% in subsequent rounds.

The lower but stable FIT performance characteristics after the first round of testing, high adherence to repeated rounds of FIT testing, and high levels of follow-up colonoscopy after positive FIT results argue for the cost-effectiveness and efficacy of FIT screening for CRC, according to the researchers.

 SFlt-1:PlGF Ratio Useful for Ruling Out Risk of Preeclampsia

A soluble fms-like tyrosine kinase 1 (sFlt-1):placental growth factor (PlGF) ratio ≤38 has a negative predictive value of 99.3% for developing preeclampsia within the next week (N Engl J Med 2016; 374:13–22). The findings indicate that sFlt-1:PlGF ratio is a promising tool for monitoring women at high-risk for developing preeclampsia, but the investigators and an accompanying editorial suggest more research is needed to better explore use of the ratio in comparison to standard care.

The authors conducted a prospective, multicenter, observational study to derive and validate an sFlt-1:PlGF ratio that would predict, over the near term, the presence or absence of preeclampsia in women with singleton pregnancies at 24 to 36 weeks suspected of having preeclampsia. In the development cohort of 500 women, they found an sFlt-1:PlGF ratio of 38 to be the optimal cutoff. In the validation study, which also involved 500 women, an sFlt-1:PlGF ratio ≤38 had 80% sensitivity and 78.3% specificity.

An sFlt-1:PlGF ratio >38 had a 35.7% positive predictive value for preeclampsia within 4 weeks, with 66.2% sensitivity and 83.1% specificity.

According to the authors of an accompanying editorial, a caveat to these findings is that all tests were run in a single laboratory using only Roche Elecsys sFlt-1 and PlGF immunoassays. In addition, all the study participants were expecting single, rather than multiple babies, but women with multiple gestations are at higher risk for preeclampsia.

Guideline: Patients With Amyloidosis, HIV OK for Heart Transplant

Updated International Society for Heart Lung Transplantation guidelines for listing patients as heart transplant candidates suggest that persistent poor glycemic control—defined as hemoglobin A1c >7.5% despite efforts to control it—should be a relative contraindication for transplant (J Heart Lung Transplant 2016;35:1–23). The guideline, a major update after 10 years, focuses on evolving areas of importance not fully addressed previously, and also reflects evolutions in clinical practice that demanded significant changes.

Several conditions that previously would have excluded patients from heart transplant are now acceptable, given appropriate diagnostic work-ups and management, including amyloidosis, HIV, Chagas disease, and tuberculosis. In the case of amyloid light-chain amyloidosis, the guideline outlines criteria for risk-stratifying cardiac involvement based on N-terminal pro-brain natriuretic peptide (NT-pro BNP), cardiac troponin (cTn), and systolic blood pressure (SBP) ranging from Stage I (NT-pro BNP <332 ng/L and cTn <0.035 µg/L) to high risk stage III (NT-pro BNP >8500 ng/L and SBP <100 mm Hg).

The guideline also outlines screening tests to evaluate extra-cardiac organ involvement from amyloid light-chain amyloidosis, including serum alkaline phosphatase, bilirubin, measured creatinine clearance or estimated glomerular filtration rate, and 24-hour urinary protein excretion.