Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa.

BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.

Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment.

AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages. RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR <60 mL/min and at BMI 18.5-25 kg/m2 , all equations performed similarly, and for BMI < 18.5 kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2 ). The four more recent equations also classified mGFR stages better than CG. CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

Living kidney donor evaluation for all candidates with normal estimated GFR for age.

Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is <90 ml/min/1.73 m2 (KDIGO guidelines) or 80 ml/min/1.73 m2 (most US centres). However, age-related GFR decline results in a lower eGFR for older candidates. That may limit the number of older kidney donors. Yet, continuing the screening with a GFR measure increases the number of eligible donors. We hypothesized that in-depth screening should be proposed to all candidates with a normal eGFR for age. We compared the evolution of eGFR after donation between three groups of predonation eGFR: normal for age (Sage ) higher than 90 or 80 ml/min/1.73 m2 (S90 and S80, respectively); across three age groups (<45, 45-55, >55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.

Resurgence of BK virus following Covid-19 in kidney transplant recipients.

Kidney transplant recipients have been supposed vulnerable to severe Covid-19 infection, due to their comorbidities and immunosuppressive therapies. Mild-term complications of Covid-19 are currently unknown, especially in this population. Herein, we report two cases of BKV replication after non-severe SARS-CoV-2 infection. The first case was a 59-year-old man, transplanted 3 months ago, with recent history of slight BKV viremia (3.3 log10 DNA copies/ml). Despite strong reduction of maintenance immunosuppression (interruption of mycophenolic acid and important decrease of calcineurin inhibitors), BKV replication largely increased after Covid-19 and viremia persisted at 4.5 log copy/ml few months later. The second case was a 53-year-old woman, transplanted 15 years ago. She had a recent history of BKV cystitis, which resolved with a decrease of MPA dosage. Few weeks after SARS-CoV-2 infection, she presented recurrence of lower urinary tract symptoms. Our reports highlight that SARS-CoV-2 infection, even without severity, could disrupt immune system and particularly lymphocytes, thus leading to viral replication. Monitoring of viral replications after Covid-19 in kidney transplant recipients could permit to confirm these preliminary observations.