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 m2. 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 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2. 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.

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid ( 99m Tc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean 99m Tc-DTPA GFR was 58 ؎ 23 ml/min per 1.73 m 2 . The cystatin C-based equations of Filler and Le Bricon had the lowest bias (؊1.7 and ؊3.8 ml/min per 1.73 m 2 ), greatest precision (11.4 and 11.8 ml/min per 1.73 m 2 ), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m 2 . The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatininebased equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.

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Background: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients (KTRs) is unknown. Methods: We used the plasma clearance of 99mTc–diethylenetriamine pentaacetic acid to measure the GFR in a cohort of 207 stable KTRs and estimated the GFR with the new CKD-EPI equation. Results: The mean bias for the CKD-EPI equation of −4.5 mL · min−1 · (1.73 m2)−1 was lower than that of the 4-variable MDRD Study equation; however, the 2 equations showed similar variation of individual biases around the mean or median bias, so that only modest improvement was seen in the overall percentage of GFR estimates within 30% of the measured GFR (84% vs 77% for the CKD-EPI vs MDRD Study equations, respectively). In the cohort with a GFR &gt;60 mL · min−1 · (1.73 m2)−1 (n = 98), the CKD-EPI bias was much less than that of the MDRD Study equation [−7.4 mL · min−1 · (1.73 m2)−1 vs −14.3 mL · min−1 ·(1.73 m2)−1], and an accuracy of ±30% was seen for 89% of GFR estimates, compared with 77% with the MDRD Study equation. The variation of the individual biases around the mean bias remained substantial [SD = 13.7 mL · min−1 · (1.73 m2)−1]. Conclusions: The CKD-EPI equation shows improved estimation ability, and we recommend that it replace the MDRD Study equation as the currently preferred creatinine-based estimating equation for KTRs. The precision of GFR estimates obtained with the CKD-EPI equation remains suboptimal, however, and we recommend that research on other markers of GFR, such as cystatin C and β-trace protein, be pursued.

Background: Beta-trace protein (BTP) is a low molecular weight glycoprotein that is a more sensitive marker of glomerular filtration rate (GFR) than serum creatinine. The utility of BTP has been limited by the lack of an equation to translate BTP into an estimate of GFR. The objectives of this study were to develop a BTP-based GFR estimation equation. Methods: We measured BTP and GFR by 99mtechnetium-diethylenetriaminepentaacetic acid in 163 stable adult renal transplant recipients. Stepwise multiple regression models were created to predict GFR corrected for body surface area. The following variables were considered for entry into the model: BTP, urea, sex, albumin, creatinine, age, and race. Results: BTP alone accounted for 75.6% of variability in GFR. The model that included all the predictor variables had the largest coefficient of determination (R2) at 0.821. The model with only BTP, urea, and sex had only a slightly lower R2 of 0.81 and yielded the following equation: GFR mL · min−1 · (1.73 m2)−1 = 112.1 × BTP−0.662 × Urea−0.280 × (0.88 if female). A 2nd equation (R2 = 0.79) using creatinine instead of urea was also developed: GFR mL · min−1 · (1.73 m2)−1 = 1.678 × BTP−0.758 × creatinine−0.204 × (0.871 if female). Conclusions: We have shown that BTP can be used in a simple equation to estimate GFR. Further study is needed in other populations to determine accuracy and clinical utility of this equation.

Co-trimoxazole is a frequently prescribed antibiotic worldwide. It is composed of both trimethoprim and sulfamethoxazol (Sfx) and is used in the treatment and prophylaxis of urinary tract and Pneumocystis jirovecii infections. The Sfx component appears to be nephrotoxic at high doses or doses inappropriately adjusted for glomerular filtration rate (GFR). The trimethoprim component, even at recommended doses, inhibits tubular creatinine secretion, leading to a rapid but ultimately reversible increase in serum creatinine independent of any changes in GFR. This translates into a falsely low estimated GFR when creatinine-based equations are used. This review focuses on evidence of the differential effects of trimethoprim and Sfx on serum creatinine concentrations and GFR and their relevance to clinical practice, with particular attention to kidney transplantation.