Assessment of adult formulas for glomerular filtration rate estimation in children

Background: Estimated glomerular filtration rate (eGFR) is an important diagnostic instrument in clinical practice. The National Kidney Foundation-Kidney Disease Quality Initiative (NKF-KDOQI) guidelines do not recommend using formulas developed for adults to estimate GFR in children; however, studies confirming these recommendations are scarce. The aim of our study was to evaluate the accuracy of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, the Modification of Diet in Renal Disease (MDRD) formula, and the Cockcroft-Gault formula in children with various stages of chronic kidney disease (CKD). Methods: A total of 550 inulin clearance (iGFR) measurements for 391 children were analyzed. The cohort was divided into three groups: group 1, with iGFR >90ml/min/1.73m2; group 2, with iGFR between 60 and 90 ml/min/1.73m2; group 3, with iGFR of <60 ml/min/1.73m2. Results: All formulas overestimate iGFR with a significant bias (p < 0.001), present poor accuracies, and have poor Spearman correlations. For an accuracy of 10%, only 11, 6, and 27% of the eGFRs are accurate when using the MDRD, CKD-EPI, and Cockcroft-Gault formulas, respectively. For an accuracy of 30%, these formulas do not reach the NKF-KDOQI guidelines for validation, with only 25, 20, and 70% of the eGFRs, respectively, being accurate. Conclusions: Based on our results, the performances of all of these formulas are unreliable for eGFR in children across all CKD stages and cannot therefore be applied in the pediatric population grou

Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders

Background Microalbuminuria (MA) has been shown to be an early biomarker of renal damage. It is postulated that MA is the early result of hyperfiltration, which could evolve into glomerular sclerosis and renal failure if hyperfiltration is left untreated. We hypothesized that MA is a good indicator of hyperfiltration in children with kidney disorders, obviating the need to calculate the filtration fraction (FF). Methods A total of 155 children or young adults were prospectively included [42 single kidney (SK), 61 vesico-ureteral reflux, 23 obstructive uropathies, 29 other kidney diseases]. We measured inulin, para-aminohippuric acid clearances, FF and MA. Prediction of hyperfiltration was explored by studying the association between the FF and other variables such as urinary albumin (Alb), urinary albumin-creatinine ratio (ACR) and creatinine clearance. Results A significant but weak association between urinary Alb or ACR and FF was found in subjects with an SK (Spearman correlation coefficients 0.32 and 0.19, respectively). Multivariate analysis also showed that urinary Alb and ACR significantly predict FF only in subjects with an SK (r2 = 0.17, P = 0.01 and r2 = 0.13, P = 0.02, respectively). This holds true only in subjects with an SK and inulin clearance >90 mL/min/1.73 m2 (r2 = 0.41, P < 0.001). There was no association between creatinine clearance and FF. Conclusions MA is not associated with FF in our subjects with nephro-urological disorders, except in those with an SK, where the association is weak, indicating that MA is due to other mechanisms than high FF and cannot predict hyperfiltration in such group

Urinary low-molecular-weight protein excretion in pediatric idiopathic nephrotic syndrome

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin (uNGAL), urinary alpha1-microglobulin (uα1M) and urinary N-acetyl-beta-D-glucosaminidase (uβNAG) as markers for differentiating MCD from FSGS. We have also evaluated whether these proteins are associated to INS relapses or to glomerular filtration rate (GFR). Methods: The patient cohort comprised 35 children with MCD and nine with FSGS; 19 healthy age-matched children were included in the study as controls. Of the 35 patients, 28 were in remission (21 MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies of these proteins were assessed by receiver operating characteristic (ROC) curve analyses. Results: The level of uNGAL, indexed or not to urinary creatinine (uCreat), was significantly different between children with INS and healthy children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and between children with MCD and those with FSGS (p = 0.01). It was not significantly correlated to proteinuria or GFR levels. The ROC curve analysis showed that a cut-off value of 17ng/mg for the uNGAL/uCreat ratio could be used to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78. uβNAG was not significantly different in patients with MCD and those with FSGS (p = 0.86). Only uα1M, indexed or not to uCreat, was significantly (p < 0.001) higher for patients in relapse compared to those in remission. Conclusions: Our results indicate that in our patient cohort uNGAL was a reliable biomarker for differentiating MCD from FSGS independently of proteinuria or GFR level

Darbepoetin Alfa in Young Infants With Renal Failure: Single Center Experience, a Case Series and Review of the Literature.

Background: Anemia treatment in infants with advanced or chronic kidney disease (CKD) represents an important challenge to nephrologists. The use of darbepoetin alfa, a novel erythropoiesis stimulating agent, has largely replaced recombinant human erythropoietin in older children and in adults with CKD. However, studies reporting the use of darbepoetin alfa in infants below 1 year of age are rare. Case presentation: We report the data of three infants with advanced stage kidney failure, aged 1, 4, and 7 months, who were treated with darbepoetin alfa and followed for 18-41 months. Hemoglobin levels increased in all three patients, reaching the target levels of 10.7-12 g/dl by 11, 19, and 22 weeks respectively, without any documented adverse effects. Patients younger than 1 year of age required a larger darbepoetin alfa dosage (ranged from 1.2 to 2.9 μg/kg per month) as compared to older children. A review of the literature found only three studies using darbepoetin alfa successfully in such young infants, with similar dosage and clinical success. Conclusion: In these three patients with advanced kidney disease, darbepoetin alfa was effective in correcting anemia with no observed side effects. It reinforces its potential use in very young patients with advanced CKD

Balancing competing needs in kidney transplantation: does an allocation system prioritizing children affect the renal transplant function?

Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors <60 years preferentially to children. The retrospective cohort study included all paediatric transplant patients (<20 years of age) before (n = 19) and after (n = 32) the new SOAS (from 2001 to 2014). Estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio (UPC), need for antihypertensive medication, waiting times to kidney transplantation (KTX), number of pre-emptive transplantations and rejections, and the proportion of living donor transplants were considered as outcome parameters. Patients after the new SOAS had significantly better eGFRs 2 years after KTX (Mean Difference, MD = 25.7 ml/min/1.73 m(2) , P = 0.025), lower UPC ratios (Median Difference, MeD = -14.5 g/mol, P = 0.004), decreased waiting times to KTX (MeD = -97 days, P = 0.021) and a higher proportion of pre-emptive transplantations (Odds Ratio = 9.4, 95% CI = 1.1-80.3, P = 0.018), while the need for antihypertensive medication, number of rejections and living donor transplantations remained stable. The new SOAS is associated with improved short-term clinical outcomes and more rapid access to KTX. Despite lacking long-term research, the study results should encourage other policy makers to adopt the SOAS approach

The inhibition of complement system in formal and emerging indications: results from parallel one-stage pairwise and network meta-analyses of clinical trials and real-life data studies

Producción CientíficaThis manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common “off-label” (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs

Outcomes of renal replacement therapy in boys with prune belly syndrome : findings from the ESPN/ERA-EDTA Registry

As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data. Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD). Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups. This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.Peer reviewe

The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV