Synthetic DDAVP for nocturnal enuresis and the risk of symptomatic hyponatremia: which treatment now? Which form?

Recently, several cases of seizure secondary to hyponatremia have been reported in children treated with intranasal DDAVP1), 2). This has rarely been reported with the oral form. Should the intranasal form be banned for the treatment of nocturnal enuresis (NE)? Or should any form of DDAVP be banned? What are the precautions to take to avoid such an event? We hereunder summarize the literature on the subject, and present the recommendations of the Swiss Group for Pediatric Nephrology and the current position of Swiss medic

Spurious hyperphosphatemia in a patient with alteplase-locked central venous catheter

Alteplase has been shown to be effective in preventing central venous access clotting in patients on hemodialysis. Because of a high phosphorus content in its excipient, it can inadvertently contaminate blood samples, leading the physician in care of the patient to erroneously increase dialysis time or change diet in order to control the pseudo-hyperphosphatemi

Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice11See Editorial by Kipari and Hughes, p. 760.

Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice.BackgroundUrinary tract obstruction during development leads to tubular atrophy and causes interstitial fibrosis. Macrophage infiltration into the interstitium plays a central role in this process. Selectins, a family of three adhesion molecules, are involved in leukocyte recruitment to sites of inflammation and immune activity. We investigated the role of selectins in obstructive nephropathy in newborn mice.MethodsTriple selectin-deficient mice (EPL-/-), L-selectin deficient mice (L-/-) and wild type mice (WT) were subjected to complete unilateral ureteral obstruction (UUO) or sham operation within the first 48 hours of life, and were sacrificed 5 and 12 days later. Kidneys were removed, and sections were stained for macrophage infiltration (mAb F4/80), apoptosis (TUNEL), tubular atrophy (periodic acid-Schiff) and interstitial fibrosis (Masson trichrome).ResultsSelectin deficient mice showed a marked reduction in macrophage infiltration into the obstructed kidney compared to WT at day 5 and day 12 after UUO. Tubular apoptosis was strongly reduced in EPL-/- at day 5 after UUO, and in EPL-/- and L-/- at day 12 after UUO when compared to WT. The number of apoptotic tubular cells was correlated with macrophage infiltration, suggesting that macrophages stimulate tubular apoptosis in obstructive nephropathy. In addition, tubular atrophy and interstitial fibrosis were significantly diminished in EPL-/- and L-/- compared to WT at day 12 after UUO.ConclusionFollowing UUO, selectins mediate macrophage infiltration into the obstructed kidney, which in turn may induce tubular apoptosis, tubular atrophy and interstitial fibrosis

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

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

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