Nordin, Gunnar

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m 2 . This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m 2 , whereas in elderly people it is increased at levels <45 ml/min per 1.73 m 2 . Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

Abstract Background Iohexol is used for measurement of kidney glomerular filtration rate (GFR). Until recently, there have not been available proficiency standards to assist in calibrating a laboratory's results. In view of a shift in calibration at the University of Rochester Medical Center (URMC) laboratory, serving as Central Biochemistry Laboratory for the CKiD study, we performed a multicentered laboratory comparison. Methods Two batches of 30 fortified sera and patient samples from serum or heparinized plasma were sent for duplicate analysis to URMC, University of Minnesota (UMN), Mayo Clinic, and University of Lund. Five proficiency testing materials from Equalis AB were also provided. Iohexol calibration was performed using dilutions of OmnipaqueTM 300 and concentrations measured by HPLC or LC-MS/MS (Mayo). Results The 2 batches sent to UMN and University of Lund agreed well. URMC calibration was 11%–13% lower, and Mayo was 4%–8% lower for fortified samples. URMC corrected calibration was 3%–8% higher for these samples. When measured values were adjusted for the results of the Equalis samples, all laboratories agreed within 1%–2% on all iohexol concentrations. Conclusions For 12 URMC calibrator lots from November 2006 to March 2016, the factor quantifying the underestimation of measured to true iohexol concentration was 0.89. If each concentration was divided by 0.89, the calculated GFRs would be reduced by 10%–11%. GFR results for CKiD were adjusted for this shift in calibration. Regular examination of iohexol proficiency testing materials, free exchange of samples among laboratories, and standardized dilution of the stock iohexol for calibration would help to bring more universal agreement to this assay.

Abstract This paper, prepared by the EFLM Task and Finish Group on Allocation of laboratory tests to different models for performance specifications (TFG-DM), is dealing with criteria for allocating measurands to the different models for analytical performance specifications (APS) recognized in the 1st EFLM Strategic Conference Consensus Statement. Model 1, based on the effect of APS on clinical outcome, is the model of choice for measurands that have a central role in the decision-making of a specific disease or clinical situation and where cut-off/decision limits are established for either diagnosing, screening or monitoring. Total cholesterol, glucose, HbA 1c , serum albumin and cardiac troponins represent practical examples. Model 2 is based on components of biological variation and should be applied to measurands that do not have a central role in a specific disease or clinical situation, but where the concentration of the measurand is in a steady state. This is best achieved for measurands under strict homeostatic control in order to preserve their concentrations in the body fluid of interest, but it can also be applied to other measurands that are in a steady state in biological fluids. In this case, it is expected that the “noise” produced by the measurement procedure will not significantly alter the signal provided by the concentration of the measurand. This model especially applies to electrolytes and minerals in blood plasma (sodium, potassium, chloride, bicarbonate, calcium, magnesium, inorganic phosphate) and to creatinine, cystatin C, uric acid and total protein in plasma. Model 3, based on state-of-the-art of the measurement, should be used for all the measurands that cannot be included in models 1 or 2.