Arend Bökenkamp

Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria

ObjectiveThe present study was undertaken to evaluate the practicability of the proposed pediatric RIFLE (pRIFLE) criteria in a patient population at risk for acute kidney injury (AKI) and to analyze the prevalence and association of AKI as defined by pRIFLE with mortality.DesignRetrospective, descriptive cohort study.SettingSingle-center, 9-bed PICU facility.PatientsChildren with respiratory failure requiring mechanical ventilation for more than 4 days admitted between January 2002 and December 2006.InterventionsNone.Measurements and resultsData of 103 patients were studied. Median age was 4.5 years (range 1 month–17 years). Six patients received renal replacement therapy. Seventeen patients (17%) died. Sixty patients (58%) developed AKI by pRIFLE. Mean time to attainment of the first RIFLE stratum was 1.9 ± 1.6 days. By pRIFLE, 34 of the 60 patients fulfilled the maximum AKI criteria on the first day after admission based on the estimated creatinine clearance criterion. Patients with AKI according to the pRIFLE scoring system had five times higher mortality than patients without AKI (25 vs. 5%, P < 0.05).ConclusionsWe observed a high incidence of significant AKI in a PICU population at risk, which was associated with high mortality. Pediatric RIFLE criteria may guide in the early identification of patients at risk for AKI and in the initiation of therapy.

Generation of a New Cystatin C–Based Estimating Equation for Glomerular Filtration Rate by Use of 7 Assays Standardized to the International Calibrator

BACKGROUND Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays. METHODS Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR. RESULTS We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C. CONCLUSIONS A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced.

Renal phenotype in Lowe Syndrome: a selective proximal tubular dysfunction.

BACKGROUND AND OBJECTIVES Lowe syndrome is defined by congenital cataracts, mental retardation, and proximal tubulopathy and is due to mutations in OCRL. Recently, mutations in OCRL were found to underlie some patients with Dent disease, characterized by low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis. This phenotypic heterogeneity is poorly understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The renal phenotype of 16 patients with Lowe syndrome (10.9 +/- 7.0 yr) under care of the authors was characterized to define overlap of symptoms with Dent disease and infer clues about OCRL function. Medical charts of patients were reviewed for data regarding glomerular filtration rate and markers of proximal tubular function. RESULTS All patients had low molecular weight proteinuria and albuminuria. Lysosomal enzymuria was elevated in all 11 patients assessed. Fifteen patients had hypercalciuria, and 14 aminoaciduria. Seven patients required bicarbonate and three required phosphate replacement; all others maintained normal serum values without supplementation. None of the patients had detectable glycosuria, and none had clinically overt rickets. GFR was mildly to moderately impaired and highly variable, with a trend of deterioration with age. CONCLUSIONS Patients with Lowe syndrome do not have renal Fanconi syndrome but a selective proximal tubulopathy, variable in extent and dominated by low molecular weight proteinuria and hypercalciuria, the classical features of Dent disease. These findings suggest that OCRL and ClC-5, the chloride channel mutated in Dent disease, are involved in similar reabsorption pathways in the proximal tubule.

Hypertension and microalbuminuria in children with congenital solitary kidneys.

Aim:  According to the hyperfiltration hypothesis, a low nephron endowment will lead to hyperfiltration in the remaining glomeruli and is associated with systemic hypertension, proteinuria and glomerulosclerosis. Being born with one functioning kidney instead of two, for instance because of unilateral renal agenesis or multicystic dysplastic kidney, is a cause of congenital renal mass reduction.

Renal injury in children with a solitary functioning kidney—the KIMONO study

BACKGROUND Children with a solitary functioning kidney (SFK) have an increased risk of developing hypertension, albuminuria and chronic kidney disease in later life. This renal injury is hypothesized to be caused by glomerular hyperfiltration that follows renal mass reduction in animal studies. Furthermore, children with an SFK show a high incidence of congenital anomalies of the kidney and urinary tract (CAKUT), which could further compromise renal function. METHODS A retrospective study of renal injury markers was performed in 206 children, divided into groups based on the origin of SFK [primary (congenital) SFK (n = 116) and secondary SFK (n = 90)]. Data on ipsilateral CAKUT were stratified separately. For blood pressure, albuminuria and glomerular filtration rate, longitudinal models were additionally developed using generalized estimated equation analysis. RESULTS Renal injury, defined as the presence of hypertension and/or albuminuria and/or the use of renoprotective medication, was present in 32% of all children with an SFK at a mean age of 9.5 (SD 5.6) years. Children with ipsilateral CAKUT had higher proportions of renal injury (48.3 versus 24.6%, P < 0.05). Furthermore, longitudinal models showed a decrease in glomerular filtration rate in both groups from the beginning of puberty onwards. CONCLUSIONS This large cohort study demonstrates that renal injury is present in children with an SFK at a young age, whereas our longitudinal models show an increased risk for chronic kidney disease in adulthood. Renal injury is even more pronounced in the presence of ipsilateral CAKUT. Therefore, we underline that clinical follow-up of all children with an SFK is needed.

Dent-2 Disease: A Mild Variant of Lowe Syndrome

OBJECTIVE To compare the renal and extra-renal phenotypes of patients classified as having Dent disease, Dent-2 disease, or Lowe syndrome. STUDY DESIGN Chart review of data from 93 patients with identified voltage-gated chloride channel and chloride/proton antiporter 5 gene and oculo-cerebro-renal syndrome of Lowe gene mutations observed by the authors, complemented with published data. RESULTS There was a wide overlap of renal symptoms. Nephrocalcinosis was more prevalent in Dent-1 disease, and renal tubular acidosis, aminoaciduria, and renal failure was more prevalent in patients with Lowe syndrome. Patients with Lowe syndrome were shorter than patients with Dent-1 disease, and patients with Dent-2 disease showed an intermediate phenotype. Three patients with Dent-2 disease had mild peripheral cataract, and 9 patients were noted to have some degree of mental retardation. CONCLUSION There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of oculo-cerebro-renal syndrome of Lowe gene function.

Response To Diphtheria And Tetanus Booster Vaccination In Pediatric Renal Transplant Recipients1

BACKGROUND Although inactivated vaccines are recommended for immunocompromized patients, efficacy and safety of diphtheria and tetanus immunization in renal transplant recipients have received little attention so far. The aim of the study was to investigate the response to a standard diphtheria and tetanus booster vaccination in pediatric renal transplant recipients. METHODS Forty-two children, median age 13.2 years (range, 7.8-18.9 years) with complete primary immunization 9.2 years (0.9-15.4 years) before transplantation were enrolled. Immunosuppression consisted of cyclosporine plus prednisolone in 15 (36%), cyclosporine, azathioprine, and prednisolone in 24 (57%), and tacrolimus plus prednisolone in 3 (7%). Antibodies were measured by enzyme-linked immunosorbent assay before and 1, 6, and 12 months after vaccination. RESULTS Before vaccination, protective antibody concentrations exceeding 0.1 IU/ml against diphtheria were found in 16 children (38%). Thirty-eight (90%) had protective antibody concentrations against tetanus. After booster immunization, the protection rate against diphtheria rose to 95% at 1 month with a decline to 93% at 6 and 76% at 12 months. Protection against tetanus was complete after vaccination and persisted over the observation. Antibody concentrations were comparable to those reported for healthy children. Statistical analysis showed no influence of allograft function, immunosuppressive regimen, previous cytotoxic therapy, or time between primary immunization and end-stage renal failure on antibody response. Immunization was well tolerated and kidney function remained unaffected in patients with stable allograft function. CONCLUSIONS Diphtheria and tetanus vaccination can be performed effectively and safely in renal transplant recipients as generally recommended.

Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring

Recently, a new oral microemulsion formulation of cyclosporin A (CsA) — Neoral (Sandoz, Basle, Switzerland) — with a higher bioavailability has become available. Ten stable paediatric renal transplant recipients with excessive variations in CsA trough levels with the original Sandimmun (Sandoz, Basle, Switzerland) preparation were switched to Neoral on a 1∶1 basis. Pharmacokinetic studies revealed impaired absorption of Sandimmun, in six patients. Compared with equal doses of Sandimmun, the 8-h area under the concentration-time curve increased from 1,422 to 2,657 ng×h/ml and the peak concentration rose from 319 to 824 ng/ml (P<0.01). In six patients with Sandimmun malabsorption, conversion on a 1∶1 basis led to a reduction in creatinine clearance which was reversible after dose reduction by 9%–25%. With trough levels at the lower end of the present target range, creatinine clearance stabilised around pre-conversion values.

Effect of Corticosteroid Therapy on Low-Molecular–Weight Protein Markers of Kidney Function

Serum cystatin C, β2-microglobulin, and β-trace protein are endogenous markers of glomerular filtration rate (GFR). Cystatin C, in particular, is a promising alternative to creatinine for the detection of incipient renal failure. However, corticosteroids affect the extrarenal metabolism of cystatin C, which limits the use of cystatin C as a marker of GFR in a variety of clinical settings. Low-molecular–weight (LMW) β-trace protein might be a useful alternative in this respect. The present study set out to compare the effect of corticosteroid therapy on the serum concentrations of cystatin C, β2-microglobulin, and β-trace protein. We studied a group of 108 children being treated or followed for malignancy (n = 41) or renal disease (n = 67). In the former group 14 patients (34%) were treated with glucocorticoids, in the latter 18 (27%). We compared single-injection inulin clearance studies in 76 patients not receiving steroids with 32 in patients receiving corticosteroid treatment (median dose 33.0 mg prednisone-equivalent per m2 body surface area per day, range 1.2–70.4). Mean (SD) age was 9.7 (5.8) years, mean (SD) GFR 92.8 (34.6) mL · min−1 · (1.73 m2)−1. Patients included in the …

Impact of Gestational Age and Birth Weight on Amikacin Clearance on Day 1 of Life

BACKGROUND AND OBJECTIVES Intrauterine growth restriction (IUGR) and prematurity are associated with a low nephron endowment. It can therefore be expected that neonates who are born premature and/or after IUGR have a lower GFR. Measurement of GFR in neonates is difficult, but the clearance of amikacin has been proven to be a reliable marker. We hypothesized that amikacin clearance is lower after IUGR or premature birth as a marker of low nephron endowment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Amikacin clearance was retrospectively analyzed in 161 neonates who received amikacin within the first 24 h of life. Using the MW/Pharm computer program, a population one-compartment model was calculated. The mean population pharmacokinetic parameters were individualized for each patient according to the maximum a posteriori Bayesian fitting method and provided the amikacin clearance. RESULTS Our results show that birth weight z score and gestational age are correlated with the clearance of amikacin (partial correlation coefficient 0.159, P = 0.046, and 0.396, P < 0.001, respectively), after correction for other factors. CONCLUSIONS We conclude that renal clearance on the first day of life is lower in neonates with a lower gestational age and/or birth weight z score. This indicates that both prematurity and IUGR impair GFR on the first day of life.