Creatinine-Based Formulae Poorly Match in the Classification of Hypofiltration or Hyperfiltration in a General Population of Adolescents: A Retrospective Analysis of a Cross-Sectional Study

Pediatric formulae to estimate glomerular filtration rate (eGFR) give a broad range of values. Their consistency in assigning the subjects as hypofiltrating or hyperfiltrating is unknown. In 1993 apparently healthy adolescents (53.4% females) aged 14–17 years, we investigated the concordance of six creatinine-based formulae in the classification of the subjects into ≤ 5th or ≥95th percentile of eGFR, and the between-groups difference in the prevalence of cardiometabolic risk factors. Mean eGFR varied between 77 and 121 mL/min/1.73 m2. Arbitrary setting of hypofiltration or hyperfiltration to 5% returned 46 males and 53 females. At least one formula classified 89 males and 99 females as hypofiltrating and 105 males and 114 females as hyperfiltrating. All six formulae concordantly classified 15 males and 17 females as hypofiltrating and 9 and 14, respectively, as hyperfiltrating. Pairwise, formulae consistently classified hypofiltration in 42–87% of subjects with hyperfiltration in 28–94%. According to two out of the six formulae, hyperfiltration was associated with an increased prevalence of obesity and obesity-associated comorbidities. Hypofiltrating subjects did not manifest chronic kidney disease–associated comorbidities. Further studies in different populations of healthy adolescents are needed before it is possible to conclude which creatinine-based formula is appropriate for the classification of hypofiltration and hyperfiltration in nonclinical cohorts.

Estimation of kidney function in patients with primary neuromuscular diseases: is serum cystatin C a better marker of kidney function than creatinine?

Background Using serum creatinine leads to an overestimation of kidney function in patients with primary neuromuscular disorders, and reduced kidney function may remain undetected. Cystatin C (CysC) could provide a better estimation. Aim To evaluate the precision, accuracy, and bias of two creatinine-, one cystatin C-based and one combined equation to estimate glomerular filtration rate (eGFR) in patients with primary neuromuscular disease. Patients and methods Of the 418 patients initially identified at the out-patient clinic, data on kidney function was obtained for 145 adult patients (age 46 ± 14 years, BMI 26 ± 6 kg/m2) with primary neuromuscular disease. Kidney function was measured by iohexol clearance, and blood samples for serum creatinine and CysC were drawn simultaneously. Bias was defined as the mean difference between eGFR and measured iohexol clearance, and accuracy as the proportion of eGFRs within ± 10% (P10) of measured clearance. Results Kidney function (iohexol clearance) was 81 ± 19 (38–134) ml/min/1.73m2. All equations overestimated kidney function by 22–60 ml/min/1.73m2. eGFR CysC had the lowest bias overall 22 (95% CI 20–26) ml/min/1.73m2 also at all levels of kidney function we evaluated (at 30–59 ml/min/1.73m2 bias was 27 (95% CI 21–35), at 60–89 it was 25 (95% CI 20–28) and at ≥ 90 it was 12 (95% CI 7–22)). eGFR CysC also had the best accuracy in patients with reduced kidney function (P10 was 5.9% at 30–59 ml/min/1.73m2). Conclusions Cystatin C-based estimations of kidney function performed better than creatinine-based ones in patients with primary neuromuscular disease, but most importantly, all evaluated equations overestimated kidney function, especially in patients with reduced kidney function. Therefore, kidney function should be measured by gold-standard methods when precision and accuracy are needed. Graphic abstract

Racial Adjustment Adversely Affects Glomerular Filtration Estimates in African Americans Living with HIV

Background The creatinine-based CKD EPI equation is the most widely used method to estimate glomerular filtration rate (eGFRcr) in clinical practice. Here, we focus on African American (AA) participants to determine whether the race eGFRcr calibration factor contributes to poor accuracy and bias in AAs living with HIV. Methods Annually, we measured GFR by iohexol disappearance from plasma (iGFR) and serum concentrations of creatinine and cystatin C. We calculated eGFRcr and the creatinine-cystatin C combination equation (eGFRcr-cys) with and without race adjustment. We used multilevel mixed models to account for the within-visit linked structure of the multiple GFR measures, further nested within repeated observations for individuals. We examined the association between lean mass, HIV status, and eGFRcr bias in a subset with body composition measures. Results 207 HIV-positive and 107 HIV-negative AA participants contributed 781 and 376 study visits, respectively, with valid measures of iGFR, creatinine, and cystatin C. Among PLWH, omitting the race adjustment (compared with retaining it) changed average eGFRcr bias from 9.1 to -3.9 ml/min/1.73 m2. Moreover, estimation accuracy improved significantly when race adjustment was omitted rather than retained: 86% vs. 78% for eGFRcr (P<0.001) and 91% vs. 88% for eGFRcr-cys (P=0.045). Lean mass was correlated with eGFRcr bias and, in adjusted analyses, lean mass was significantly lower in PLWH compared with HIV-negative AAs compatible with not using the race coefficient. Conclusions We found that the standard, widely used eGFRcr equation overestimate iGFR and has poor accuracy in AAs living with HIV.

Clinical Implications of the New Equation to Estimate Glomerular Filtration Rate

Recently, a new full-age spectrum equation was proposed by the European Kidney Function Consortium (EKFC) to overcome the difficulty of using multiple glomerular filtration rate (GFR) estimation equations and problems of implausible changes in GFR during the transition from adolescence to adulthood and address GFR overestimation in young adults and in the older adults. To verify the impact on patient classifications, we applied the new equation to data of 38,188 adult patients, comparing GFR estimation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations. As expected, our data indicate that a significant proportion of patients will be reclassified downward by the EKFC compared to the CKD-EPI equation with a particular reference between CKD stages 1–2 and 2–3 and age categories of 18–30 and ≥61 years, respectively. Clinicians should be aware that any replacement for the EKFC equation will entail a period of different results in estimated GFR during the transition from the previous to the new equation.

The influence of the antithymocyte globulin dose on clinical outcomes of patients undergoing kidney retransplantation

Optimizing antithymocyte globulin (rATG) dosage is critical for high immunological risk patients undergoing a repeat kidney transplant. This natural retrospective cohort study compared clinical outcomes of two successive cohorts of consecutive recipients of retransplants receiving 5 x 1 mg/kg (rATG-5, n = 100) or a single 3 mg/kg (rATG-3, n = 110) dose of rATG induction therapy. All patients had negative complement-dependent cytotoxicity crossmatch and no anti-HLA A, B, DR donor-specific antibodies (DSA). The primary endpoint was efficacy failure (first biopsy-proven acute rejection, graft loss, or death) at 12 months. There was no difference in the cumulative incidence of efficacy failure (18.0% vs. 21.8%, HR = 1.22, 95% CI 0.66–2.25), respectively. There were no differences in 3-years freedom from biopsy proven acute rejection, and patient, graft, and death-censored graft survivals. There were no differences in the incidence of surgical complications (25.0% vs. 18.2%; p 0.151), early hospital readmission (27.8% vs. 29.5%; p = 0.877) and CMV infections (49% vs. 40%; p = 0.190). There were also no differences in the incidence (59.6% vs. 58.7%, p = 0.897) and duration of delayed graft function but a stable difference in estimate glomerular filtration rate was observed from month 1 (54.7±28.8 vs. 44.1±25.3 ml/min/1.73 m2, p = 0.005) to month 36 (51.1±27.7 vs. 42.5±24.5, p = 0.019). Mean urinary protein concentration (month 36: 0.38±0.81 vs. 0.70±2.40 g/ml, p = 0.008) and mean chronic glomerular Banff score in for cause biopsies (months 4–36: 0.0±0.0 vs. 0.04±0.26, p = 0.044) were higher in the rATG-3 group. This cohort analysis did not detect differences in the incidence of efficacy failure and in safety outcomes at 12 months among recipients of kidney retransplants without A, B, and DR DSA, receiving induction therapy with a single 3 mg/kg rATG dose or the traditional 5 mg/kg rATG.

Creatinine-Based Formulae Poorly Match In The Classification of Hypofiltration Or Hyperfiltration In a General Population of Adolescents. A Retrospective Analysis of a Cross-Sectional Study

Pediatric formulae to estimate glomerular filtration rate (eGFR) give a broad range of values. Their consistency in assigning the subjects as hypofiltrating or hyperfiltrating is unknown. In 1,993 apparently healthy adolescents (53.4% females) aged 14-to-17 years, we investigated the concordance of six creatinine-based formulae in the classification of the subjects into ≤ 5th or ≥ 95th percentile of eGFR; and the between-groups difference in the prevalence of cardiometabolic risk factors. Mean eGFR varied between 77-to-121 mL/min/1.73 m2. Arbitrary setting of hypofiltration or hyperfiltration to 5% returned 46 males and 53 females. At least one formula classified 89 males and 99 females as hypofiltrating, and 105 males and 114 females as hyperfiltrating. All six formulae concordantly classified 15 males and 17 females as hypofiltrating; and 9 and 14, respectively, as hyperfiltrating. Pairwise, formulae consistently classified hypofiltration in 42%-to-87% subjects, hyperfiltration in 28%-94%. According to two out of six formulae, hyperfiltration associated with increased prevalence of obesity and obesity-associated comorbidities. Hypofiltrating subjects did not manifest chronic kidney disease-associated comorbidities. Further studies in different populations of healthy adolescents are needed before it is possible to conclude on which creatinine-based formula is appropriate for the classification of hypofiltration and hyperfiltration in non-clinical cohorts.