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OBJECTIVE: The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. METHODS: The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. RESULTS AND CONCLUSIONS: These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney-related sequelae after STEC-HUS occur in 20-40% of patients. Hyperuricemia (HU) may cause acute and chronic toxicity involving the kidneys. We retrospectively assessed if there was an association between the presence of HU during the acute illness and that of kidney-related sequelae in children with STEC-HUS., Methods: Children with STEC-HUS who had clinical and laboratory data at 2 years of follow-up were included in this case-control study. Univariate and multivariate analyses were performed between patients with (cases) or without (controls) kidney-related sequelae to identify factors associated with outcomes, including different measures of serum uric acid (sUA) (baseline level, peak, and duration of HU). HU was defined as sUA > 8 mg/dL., Results: Of 86 patients included, 77.9% had HU. Patients with sequelae (n = 41) had a higher prevalence of HU (41/41 vs. 26/45, p < 0.01), higher baseline leukocyte count, serum creatinine (sCr), and sUA levels as well as lower sodium than controls. During hospitalization, cases also had higher sCr peak, sUA peak and duration of HU, requirement and duration of dialysis, extrarenal complications, and hypertension. By multivariate analysis, after adjusting for length of dialysis, only duration of HU (p = 0.0005; OR 1.7, 95% CI 1.27-2.36) remained as an independent predictor of sequelae, with a best cutoff of 5.5 days (AUC 0.95, specificity 80%, sensitivity 100%)., Conclusions: The presence of HU is a common finding in children with STEC-HUS and its duration during the acute stage was associated with kidney-related sequelae, regardless of the duration of dialysis. A higher resolution version of the Graphical abstract is available as Supplementary Information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Studies have shown that losartan reduces serum uric acid in adults, unlike angiotensin-converting enzyme inhibitors. A previous study demonstrated that losartan and enalapril had comparable effects on proteinuria in children., Methods: We conducted a post hoc analysis of results from a prospective trial in which the proteinuria-reducing effects of losartan and enalapril were compared. We have now evaluated (a) the effects of these medications on SUA in 248 children with proteinuria and (b) the correlation between changes in SUA and eGFR., Results: SUA levels after 36 months were found to be increased when compared to baseline in both losartan and enalapril groups. The mean change in SUA from baseline was significantly different at 12 months between 23 hypertensive patients randomised to losartan (3.69% decrease [95% CI 11.31%, 3.93%]) and 24 randomised to enalapril (12.57% increase [95% CI 3.72%, 21.41%]), p = 0.007. This significant difference remained after 24, 30 and 36 months but was observed in the entire group of 248 patients only at 12 months. There was a statistically significant negative correlation between changes in SUA and changes in eGFR at each time point over 36 months., Conclusions: Losartan may have long-term beneficial effects on SUA and eGFR in children with proteinuria., (© 2021. The Author(s).)

Introduction: There is a high degree of inter-individual variability among people in response to intervention with omega-3 fatty acids (FA), which may partly explain conflicting results on the effectiveness of omega-3 FA for the treatment and prevention of chronic inflammatory diseases. In this study we sought to evaluate whether part of this inter-individual variability in response is related to the regulation of key oxylipin metabolic genes in circulating peripheral blood mononuclear cells (PBMCs)., Methods: Plasma FA and oxylipin profiles from 12 healthy individuals were compared to PBMC gene expression profiles following six weeks of supplementation with fish oil, which delivered 1.9 g/d eicosapentaenoic acid (EPA) and 1.5 g/d docosahexaenoic acid (DHA). Fold changes in gene expression were measured by a quantitative polymerase chain reaction (qPCR)., Results: Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), and interleukin 8 (IL-8) gene expression in isolated PBMCs. In those individuals for whom plasma arachidonic acid (ARA) in the phosphatidylethanolamine (PE) lipid class decreased in response to omega-3 intervention, there was a corresponding decrease in gene expression for PTGS1 and ALOX12. Several oxylipin product/FA precursor ratios (e.g. prostaglandin E2 (PGE2)/ARA for PTGS1 and 12-hydroxyeicosatetraenoic acid (12-HETE)/ARA for ALOX12) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in PTGS1 gene expression was highly positively correlated with ALOX12 gene expression but not with PTGS2, whereas IL-8 and PTGS2 were positively correlated., Conclusions: The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of PTGS1 and ALOX12 regulation. PBMC gene expression changes in response to omega-3 supplementation varied among healthy individuals, and were associated with changes in plasma FA and oxylipin composition to different degrees in different individuals., Trial Registration: clinicaltrials.gov NCT01838239.

Background: Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results., Study Design: Double-blind placebo-controlled randomized controlled trial., Setting & Participants: 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6g/g (males) or ≥0.8g/g (females); and estimated glomerular filtration rate ≥ 50mL/min/1.73m(2) (≥40mL/min/1.73m(2) if receiving angiotensin-converting enzyme inhibitor). Mean age, 32±12 (SD) years; 62% men; and 73% white., Intervention: Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR≥0.6g/g (males) and ≥0.8g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36mg/kg/d) in addition to lisinopril/losartan plus Omacor., Outcomes: Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment., Measurements: UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula., Results: 44 patients completed 6 months of treatment with MMF (n=22) or placebo (n=22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR<0.2g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was -0.22 (95% CI, -0.75 to 0.31; P=0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew., Limitations: Low patient enrollment and short follow-up., Conclusions: MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of ω3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined ω3 intervention., Methods: The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of ω3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA])., Results: Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r(2)=0.93). However, strikingly divergent responses among individuals were also observed. Both ω3 and ω6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase., Conclusions: Our results show that certain defined responses to ω3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to ω3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of ω3 interventions in modifying disease risk and determining metabolic phenotype.

Background and Objectives: In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined., Design, Setting, Participants, and Measurements: The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2-40 years, with eGFR ≥40 ml/min per 1.73 m(2) and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks., Results: The median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at 78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively, in the two groups from 52 to 78 weeks., Conclusions: In this subset of responding FSGS patients, the improvement in UP/C after cyclosporine or mycophenolate/dexamethasone treatment was largely sustained for 6 months after therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after cyclosporine was stopped although the levels were lower than baseline in seven patients who entered the study with decreased eGFR.

Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease, frequently associated with hypertension and renal inflammation. ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil (FO) improve kidney function in animal models, but have inconsistent metabolic effects in humans. Oxylipin profiles in serum from IgAN patients supplemented with either FO or corn oil (CO) placebo were analyzed by liquid chromatography coupled to tandem mass spectrometry. EPA cyclooxygenase and lipoxygenase metabolites, and EPA and DHA epoxides and diols were increased in response to FO supplementation, as were total epoxides and epoxide/diol ratios. Several of these metabolites were drivers of separation as assessed by multivariate analysis of FO patients pre- vs. post-supplementation, including 17,18-dihydroxyeicosatrienoic acid, prostaglandin D 3 , prostagalandin E 3 , Resolvin E1, 12-hydroxyeicosapentaenoic acid, and 10(11)-epoxydocosapentaenoic acid. In patients whose proteinuria improved, plasma total oxylipins as well as several hydroxyoctadecadienoic acids, hydroxyeicosatetraenoic acids, and leukotriene B 4 metabolites were among the metabolites that were significantly lower than in patients whose proteinuria either did not improve or worsened. These data support the involvement of oxylipins in the inflammatory component of IgAN as well as the potential use of oxylipin profiles as biomarkers and for assessing responsiveness to ω-3 fatty acid supplementation in IgAN patients.

Background: Acute kidney injury (AKI) with elevated serum uric acid (UA) levels has been reported in patients with hemolytic uremic syndrome (HUS). AKI is thought to result from tubular obstruction by UA crystals. Inducing a diuresis may ameliorate the oligoanuria in such patients. We describe a child with HUS in whom reducing UA with fluids and rasburicase appeared to accelerate the recovery of renal function., Case-Diagnosis/treatment: A 9-month-old Caucasian male infant presented with 6 days of diarrhea, 3 days of vomiting, and 24 h of oliguria. On admission, hemoglobin was 8.3 g/dL, platelet count 36,000/L, blood urea nitrogen 73 mg/dL, and serum creatinine (SCr) 2.7 mg/dL. Diarrhea-associated HUS was diagnosed. The day after admission, SCr was 2.9 mg/dL and UA 12.3 mg/dL. On hospital day 2, he received a dose of intravenous rasburicase 0.18 mg/kg, and less than 12 h later, the UA had fallen to 0.3 mg/dL. The SCr level also started to fall, and urine output progressively increased without the use of diuretics. Renal function continued to improve, and the UA level remained normal despite ongoing hemolysis requiring a second red blood cell transfusion on hospital day 5. The patient was discharged on hospital day 7 in good physical condition. Two months later, he was in good health, with a SCr level of 0.2 mg/dL and UA of 4.2 mg/dL., Conclusions: We postulate that aggressive management of the high serum UA level with rasburicase and fluid hydration accelerated the recovery of our patient. Further studies are needed to determine the role of rasburicase in the treatment of hyperuricemia in patients with HUS.

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect.

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40 years, with an estimated glomerular filtration rate > 40 ml/min per 1.73 m², a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m², and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials.

To study the predictive value of biopsy lesions in IgA nephropathy in a range of patient ages we retrospectively analyzed the cohort that was used to derive a new classification system for IgA nephropathy. A total of 206 adults and 59 children with proteinuria over 0.5 g/24 h/1.73 m(2) and an eGFR of stage-3 or better were followed for a median of 69 months. At the time of biopsy, compared with adults children had a more frequent history of macroscopic hematuria, lower adjusted blood pressure, and higher eGFR but similar proteinuria. Although their outcome was similar to that of adults, children had received more immunosuppressants and achieved a lower follow-up proteinuria. Renal biopsies were scored for variables identified by an iterative process as reproducible and independent of other lesions. Compared with adults, children had significantly more mesangial and endocapillary hypercellularity, and less segmental glomerulosclerosis and tubulointerstitial damage, the four variables previously identified to predict outcome independent of clinical assessment. Despite these differences, our study found that the cross-sectional correlation between pathology and proteinuria was similar in adults and children. The predictive value of each specific lesion on the rate of decline of renal function or renal survival in IgA nephropathy was not different between children and adults.

Immunoglobulin A nephropathy is now recognized as the glomerular disease most often associated with progressive renal failure in patients around the world. In many cases it is not known when the disease starts to inflict glomerular injury, but recent studies that have shown genetically determined abnormalities in glycosylation of the IgA molecule suggest that this may begin in early life. This review focuses on recent advances in our understanding of IgA nephropathy, with special emphasis on clinical aspects of the disease when it presents in children and adolescents. In addition, the sections dealing with therapeutic options for patients with IgA nephropathy concentrate on studies that have been carried out on children. Whenever possible, data from randomized controlled clinical trials have formed the basis for recommendations. Unfortunately, this is not always possible, because of the lack of such trials in patients with IgA nephropathy.

IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

This review addresses the relevance of urinary screening for chronic kidney disease (CKD) in children. Ambiguity about screening children exists because of the uncertainty as to whether early detection of renal disorders in childhood will lead to effective interventions and reduction in the number of individuals who subsequently progress to ESRD. A related concern is whether the adoption of urinary screening programs is cost effective. The most common method that is used for screening children for CKD involves the measurement of spot samples of urine for hematuria and or proteinuria. Although mass screening is now well established in Japan, Taiwan, and Korea, there appears to be movement away from mass screening to detect CKD in children and adolescents in North America and Europe. In December 2007, the American Academy of Pediatrics published their latest recommendations, in which no urinalyses were recommended at any age during childhood. The second issue addressed in this review is the reporting of estimated glomerular filtration rates (GFR) in children by clinical laboratories.

IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are related diseases characterized by deposits of IgA1-containing immune complexes in the renal mesangium. Adult patients with IgA nephropathy have aberrantly glycosylated IgA1 (galactose-deficient O-linked glycans) in the circulation and renal deposits. However, IgA1 glycosylation has not been studied in pediatric patients with IgA nephropathy. Using our quantitative lectin enzyme-linked immunosorbent assay (ELISA) test, we measured serum levels of galactose-deficient IgA1 of children with IgA nephropathy and HSPN and controls. Children with IgA nephropathy and HSPN had serum levels higher than those of healthy children or renal-disease controls with C1q nephropathy. Furthermore, lectin ELISA identified patients with HSPN whose clinical course mimicked that of IgA nephropathy. In summary, pediatric patients with IgA nephropathy and HSPN have an aberrancy in the glycosylation in IgA1 O-linked glycans that is similar to that in adults with IgA nephropathy.

The pharmacokinetic (PK) parameters of lisinopril were obtained in 46 children aged 6 months to 15 years. A lisinopril suspension (0.15 mg/kg per day) was administered to patients <6 years of age; the remaining children received lisinopril tablets, the daily dose being adjusted according to body weight, i.e., 2.5 mg if <25 kg, 5 mg if 25-45 kg, and 10 mg if >45 kg. Blood was drawn predose and on eight occasions postdose in children aged 4-15 years, and on five occasions in those aged <4 years. PK data are reported for the 46 children in terms of age groups: Group I (n=9), aged 6-23 months; Group II (n=8), aged 2-5 years; Group III (n=12), aged 6-11 years; Group IV (n=17), aged 12-15 years. The dose of lisinopril ranged from 3.07 mg/m(2) per day in Group I to 4.78 mg/m(2) per day in Group IV. C(max) of lisinopril, which occurred 5-6 h postdose, varied from 22 ng/ml in Groups I and II to 44 ng/ml in Groups III and IV; AUC(0-24 h) ranged from 301-311 ng.h/ml in Groups I and II to 550-570 ng.h/ml in Groups III and IV. No serious adverse events related to lisinopril were reported.

Previous studies that have evaluated fish oil preparations in patients with IgA nephropathy (IgAN) have produced a wide range of conclusions. Proposed explanations for these discordant results have not provided a unifying hypothesis. Results from two clinical trials were analyzed to examine whether there is a dosage-dependent effect of Omacor, a purified preparation of omega-3 fatty acids, in patients with IgAN. Whether changes in the level of proteinuria and plasma phospholipid fatty acid profiles were dependent on the dose of Omacor factored by body size was determined. In a post hoc analysis of the first trial results, correlations were found between (1) phospholipid eicosapentaenoic acid (EPA)/arachidonic acid (AA) and docosahexaenoic acid (DHA)/AA ratios and the dosage of Omacor, expressed as milligrams per kilogram of body weight (r = 0.78, P < 0.001 for EPA/AA; r = 0.86, P < 0.001 for DHA/AA), (2) phospholipid EPA/AA and DHA/AA levels and percentage change in urine protein/creatinine ratio after 21 to 24 mo of therapy (r = -0.50, P = 0.02 for EPA/AA; r = -0.52, P = 0.01 for DHA/AA), and (3) dosage of Omacor per kilogram of body weight and change in proteinuria after 21 to 24 mo (r = -0.50, P = 0.02). A similar relationship was observed between urine protein/creatinine ratio and dosage of Omacor per kilogram of body weight in trial 2 (r = -0.38, P < 0.001). It is concluded from these data that the effect of Omacor on proteinuria in patients with IgAN is dosage dependent and is associated with a dosage-dependent effect of Omacor on plasma phospholipid EPA and DHA levels.

Children with frequently relapsing nephrotic syndrome (FRNS) often develop adverse effects from prednisone. Attempts to induce long-term remission in such patients have had varying levels of success. In this multicenter, prospective, open-label study, 14 centers enrolled 33 patients with FRNS, all of whom were in remission at the time of entry. Six of the patients were steroid dependent. The patients received mycophenolate mofetil (MMF) 600 mg/m(2) twice daily (maximum 1 g twice daily) for 6 mo. A tapering dosage of alternate-day prednisone was given to each patient during the first 16 wk of MMF therapy. Patients were monitored for relapses of NS during and after MMF therapy. Treatment failure was defined as a relapse of NS. The patients had the following features at study entry: Age 6.8 +/- 2.7 yr (range 2 to 15 yr); 56% male, 44% female; and 50% white; 25% black, and 25% other. Estimated GFR at entry was 138 +/- 42 ml/min per 1.73 m(2). Twenty-four (75%) of 32 patients stayed in remission throughout the 6 mo of MMF therapy. The relapse rate in these patients improved from one episode every 2 mo before MMF to one every 14.7 mo after MMF. Eight patients stayed in remission during the post-MMF period, for periods of 18 to 30 mo, whereas 16 relapsed after stopping MMF. Eight (25%) of 32 patients relapsed while taking MMF. It is concluded that MMF is effective for maintaining remission in patients who have FRNS and receive treatment for at least 6 mo and is associated with a low incidence of adverse events.

This randomized, placebo-controlled, double-blind trial evaluated the role of prednisone and omega 3 fatty acids (O3FA) in patients with IgA nephropathy. Entry criteria were (1) biopsy-proven IgA nephropathy, (2) estimated GFR > or = 50 ml/min per 1.73 m2, and (3) moderate to severe proteinuria. Thirty-three patients were randomly assigned to receive prednisone 60 mg/m2 every other day for 3 mo, then 40 mg/m2 every other day for 9 mo, then 30 mg/m2 every other day for 12 mo (prednisone group); 32 were randomly assigned to receive O3FA 4 g/d for 2 yr (1.88 g eicosapentaenoic acid, 1.48 g docosahexaenoic acid; O3FA group); and 31 were randomly assigned to receive placebo (placebo group). Most (73%) patients completed 2 yr of treatment. Randomly assigned patients who were hypertensive were given enalapril 2.5 to 40 mg/d. The primary end point was time to failure, defined as estimated GFR <60% of baseline. An overall significance level of 0.10 was used. The three groups were comparable at baseline except that the O3FA group had higher urine protein to creatinine (UP/C) ratios than the placebo group (P = 0.003). Neither treatment group showed benefit over the placebo group with respect to time to failure, with 14 patient failures overall (two in the prednisone group, eight in the O3FA group, and four in the placebo group). The primary factor associated with time to failure was higher baseline UP/C ratios (P = 0.009). Superiority of prednisone or O3FA over placebo in slowing progression of renal disease was not demonstrated in this study. However, the relatively short follow-up period, inequality of baseline UP/C ratios, and small numbers of patients precludes definitive conclusions.

Persistent proteinuria of various degrees of severity in adolescents should be regarded seriously, because recent evidence points to this abnormality's being associated with chronic kidney disease. However, it is also important for primary care physicians to be aware that most adolescents who are found to have proteinuria on a screening urinalysis do not have renal disease, and the proteinuria will usually resolve on repeat testing. Appropriate measures to determine whether the proteinuria is fixed and not orthostatic can and should be conducted expeditiously, because they will allay stress for most patients. For the minority of patients in whom more serious forms of proteinuria exist, timely consultation with a pediatric nephrologist is recommended.

Objectives: Evaluation of the efficacy and safety of amlodipine in hypertensive children., Study Design: A randomized, double blinded, placebo-controlled, parallel-group, dose-ranging study was conducted at 49 centers in North and South America. The primary end point was the effect of amlodipine on systolic blood pressure (BP); secondary end points included the effect of amlodipine on diastolic BP, the effect of amlodipine as a function of dose and body size, and evaluation of safety., Results: We enrolled 268 hypertensive children (mean age, 12.1 +/- 3.3 years); 84 (31.3%) had primary hypertension, and 177 (66%) were boys. Amlodipine produced significantly greater reductions in systolic BP than placebo; these were -6.9 mm Hg for 2.5 mg daily (P=.045 vs placebo) and -8.7 mm Hg for 5 mg daily (P=.005 vs placebo). The underlying cause of hypertension had no effect on the response to amlodipine. There was a significant dose-response effect of amlodipine on both systolic and diastolic BP beginning at doses > or =0.06 mg/kg per day. Systolic BP < or =95(th) percentile was achieved in 34.6% of subjects with systolic hypertension. Amlodipine was well tolerated, with just 6 children withdrawn from treatment because of drug-related adverse events., Conclusions: Amlodipine effectively lowers systolic BP in a dose-dependent manner in hypertensive children who require drug treatment.

Background: IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity., Objective of the Study: The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF., Design: After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor, 100 (2 x 50) patients with IgAN and a urinary P/C ratio > or = 0.6 (males) and > or = 0.8 (females) and an estGFR > or = 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two.

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Objectives: A series of new guidelines has been developed by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative to improve the detection and management of chronic kidney disease (CKD). In most instances of CKD, the earliest manifestations of the disorder may be identified by relatively simple tests. Unfortunately, CKD is often "underdiagnosed," in part because of the absence of a common definition of CKD and a classification of the stages in its progression. The Kidney Disease Outcomes Quality Initiative clinical practice guidelines for CKD evaluation, classification, and stratification provide a basis to remedy these deficits. The specific goals of the guidelines described in this review are to provide: 1) an overview of the clinical practice guidelines as they pertain to children and adolescents, 2) a simple classification of the stages of CKD, and 3) a practical approach to the laboratory assessment of kidney disease in children and adolescents., Methods: The guidelines were developed as part of an evidence-based evaluation of CKD and its consequences in patients of all ages. The data that were used to generate the guidelines in this article were extracted from a structured analysis of articles that reported on children with CKD., Results and Conclusions: This review presents the definition and 5-stage classification system of CKD developed by the work group assigned to develop the guidelines, and summarizes the major recommendations regarding the early detection of CKD. Major emphasis is placed on the identification of children and adolescents with CKD by measuring the protein-to-creatinine ratio in spot urine specimens and by estimating the glomerular filtration rate from serum creatinine using prediction equations.

A retrospective cohort study was conducted by the Southwest Pediatric Nephrology Study Group (SPNSG) to address whether a longer initial course of corticosteroids in patients with idiopathic nephrotic syndrome (INS) provides superior protection against relapse without increased adverse effects. In order to be included in the evaluation, patients with INS must have responded to an initial steroid course, either standard or long regimen as defined here, and completed at least 1 year of follow-up. The standard regimen consisted of prednisone 2.0+/-0.3 mg/kg per day or 60+/-10 mg/m(2) per day for 28+/-4 days, followed by alternate-day prednisone for 4-12 weeks. The long regimen consisted of daily prednisone 2.0+/-0.3 mg/kg per day or 60+/-10 mg/m(2) per day for 42+/-6 days, followed by alternate-day prednisone for 6-14 weeks. The primary outcome measure was relapse of NS within 12 months of discontinuing the initial course of prednisone. There were 151 children who met the criteria for the study; 82 received the standard regimen and 69 the long regimen. The two groups did not differ in age, race, blood pressure, serum albumin, or serum cholesterol prior to the initial steroid course. The cumulative prednisone dose was 49% higher in the long regimen group than in the standard regimen group. Relapse within 12 months was reported in 72.5% of patients who received the long regimen versus 84.1% of those who received the standard regimen. The odds ratio for relapse within 12 months was 0.496 (95% confidence interval 0.22, 1.088), long versus standard regimen. This did not reach statistical significance ( chi(2)=3.058, P=0.08). The odds ratio of experiencing at least one side effect was 3.76, long relative to standard regimen ( n=133, P<0.001). Our data suggest that prolongation of the steroid treatment for the initial episode of steroid-sensitive NS may have a beneficial effect, but at the cost of increased side effects. However, definitive conclusions are limited by the retrospective design of the study and the number of patients. This may have caused failure to achieve statistical significance on the basis of a type II error.

Children with kidney disease are at risk for serious varicella-related complications. To evaluate the safety and immunogenicity of a two-dose regimen of varicella vaccine in children (aged 1-19 years) with chronic renal insufficiency and on dialysis, the Southwest Pediatric Nephrology Study Group (SPNSG) undertook an open-label, multi-center, prospective 3-year clinical trial. Ninety-six patients without history of varicella were enrolled. Fifty (mean age 4.2 years) had no detectable varicella zoster virus (VZV) antibody; 98% seroconverted after the two-dose regimen. At 1, 2, and 3 years' follow-up, all patients studied maintained VZV antibody, including 16 who received a transplant. No significant vaccine-associated adverse events were seen. One subject developed mild varicella (10-50 maculopapular lesions) 16 months post transplant. In multivariate regression analysis, patients vaccinated after age 6 years had VZV antibody levels 73% (95% confidence interval 33%-89%) lower than patients vaccinated before age 6 years after controlling for gender, estimated glomerular filtration rate, and dialysis treatment. Adjusted analysis also showed that VZV antibody levels were lower after kidney transplantation, but this appeared to be a transient phenomenon. In this study, varicella vaccination with a two-dose regimen of varicella vaccine was generally well tolerated and highly immunogenic in children with chronic kidney disease.

Background: Diminished antibody responses to the dosage of hepatitis B (HB) vaccine indicated for healthy adults has led to a greater dosage recommendation (40 microg of HB surface antigen [HBsAg]) for adults with chronic renal failure (CRF), but an appropriate dosage for children with CRF has not been established., Methods: Seventy-eight children and adolescents with CRF (22 patients, predialysis; 42 patients, chronic dialysis therapy; 14 renal transplant recipients) aged 1 to 19 years (mean, 10.1 years) were enrolled onto a study to test a three 20-microg dose course of the HB vaccine Recombivax HB (Merck & Co, Inc, West Point, PA)., Results: The vaccine was well tolerated; no patient had a serious adverse event attributable to vaccine, and no patient withdrew from the study because of an adverse event. Overall, 91% of 66 patients administered three doses had a protective titer of 10 mIU/mL or greater for antibody against HBsAg (anti-HBs) and a geometric mean titer (GMT) of 733 mIU/mL, with seroprotection rates and GMTs among predialysis, dialysis, and renal transplant patients of 100% (4,140 mIU/mL), 94% (419 mIU/mL), and 64% (152 mIU/mL), respectively. All (100%) predialysis patients had a 10-mIU/mL or greater anti-HBs titer after only two doses of vaccine compared with 64% of dialysis patients and 50% of transplant recipients. Eighty-eight percent of 57 fully vaccinated patients tested 12 months after the first dose retained a 10-mIU/mL or greater anti-HBs titer., Conclusion: A regimen of three 20-microg doses of Recombivax HB is suitably immunogenic for children with CRF not administered immunosuppressive medication. When possible, at least two, and preferably all three, doses of vaccine should be administered before progression to end-stage renal disease., (Copyright 2002 by the National Kidney Foundation, Inc.)

Background: The FDA Modernization Act has resulted in an increase in pediatric trials of antihypertensive medications. As experience is limited in children to guide the planning of these studies, we reviewed data from the Ziac Pediatric Hypertension Study to determine patterns of early study termination to help future studies., Methods: For inclusion, subjects aged 6 to 17 years were required to have an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile at the last of three visits during 2 weeks of single-blind placebo screening. Early study termination was defined as early termination for any reason. Screening termination was defined as normalization of blood pressure (BP) during the placebo screening phase., Results: Early study termination rate was 27% (38 of 140 subjects). The most common reason was screening termination due to normalization of BP, accounting for 63% of all early study terminations. Among screening termination subjects who completed three screening visits, SBP was higher (P < .001) at visit 1 (129+/-8 mm Hg) than at visit 2 (123+/-7 mm Hg) or visit 3 (121+/-8 mm Hg), but did not differ between visits 2 and 3. Screening termination occurred in 15% with isolated SBP hypertension, and 21% with isolated DBP hypertension. At randomization, 83% had SBP hypertension and 53% had DBP hypertension., Conclusions: These data suggest that SBP hypertension should be part of inclusion criteria to increase enrollment and reduce the rate of screening termination, and that 1-week placebo screening is necessary and sufficient to minimize inclusion of transiently hypertensive subjects.

We present an evidence-based evaluation of published data on therapy for children with various presentations of the IgA nephropathies--idiopathic IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN). Particular attention has been paid to the outcome markers used in the studies reviewed, with the best evidence provided by markers highly associated with progressive renal failure. No treatment modality for either IgAN or HSPN in pediatric patients has been shown to be effective by a properly designed and administered randomized controlled trial (i.e., the highest level of evidence--level 1). Lower levels of evidence support the use of a variety of corticosteroid regimens, often in combination with other agents, although there are some conflicting studies in this area. No convincing evidence has been published to date to support the use of fish oil, angiotensin-converting enzyme inhibitors or tonsillectomy for the treatment of children with IgAN or HSPN. Well designed randomized controlled trials in children with the IgA nephropathies need to be undertaken.

Purpose: To determine the incidence of avascular necrosis (AVN) of the femoral head in children with chronic renal failure., Materials and Methods: Pelvic radiographs in 205 children (age range, 6 months to 16 years; mean age, 6 years +/- 3.5 [SD]) with chronic renal failure were reviewed. Serial radiographs were obtained every 6 months for 1-7 years (mean, 3 years +/- 2) to assess the presence of AVN of the femoral head; six children had metabolic renal disease, 21 had acquired renal disease, and 178 had structural renal lesions., Results: Radiographic findings of AVN were seen in 14 of 205 patients (approximately one in every 15). The frequency of AVN was similar in boys and girls; AVN was observed in 11 (6.9%) of 159 boys and in three (6.5%) of 46 girls and was not related to the duration of renal disease, type of renal disease, or growth hormone therapy. Affected children were frequently asymptomatic, and, when present, the clinical complaints were mild. In two instances, AVN developed while the patients were receiving corticosteroids before entering this study., Conclusion: The results of this study indicate that AVN of the femoral head is a frequent complication in children with chronic renal failure, occurring in approximately 7% of this population. Unlike Legg-Calvé-Perthes disease, AVN in children with chronic renal failure is frequently asymptomatic and has no sex predilection.

Multicenter studies in pediatric nephrology have been acknowledged in recent years to be an important means of studying renal disease in children. This review examines a number of issues that are important in the design and performance of a successful trial, with special emphasis on their significance for prospective clinical trials of antihypertensive medications in children and adolescents. Some issues to be covered include the most frequent difficulties that are encountered with multicenter studies, an historical perspective, specific design problems, the importance of close networking and communication, and the problems that may be anticipated with regards to authorship and financial reimbursement for time and effort. The paper concludes with a brief analysis of how multicenter studies involving hypertension protocols in children and adolescents might be conducted during the next few years.

Children with chronic renal failure (CRF) have high serum levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), -2, and -6. The excess IGFBP-2 and -1 may play a role in the growth failure of CRF children by sequestering IGF peptides. In contrast, IGFBP-3 levels rise with GH treatment of CRF children, suggesting a role for IGFBP-3 in their accelerated growth. The present studies used sensitive and specific antisera to characterize levels and forms of IGFBP-4 and -5 in serum from CRF children. By RIA, the mean baseline serum level of IGFBP-4 was high in CRF children compared to that in normal children, but the IGFBP-4 level in CRF serum did not correlate with height SD score; by immunoblot, high CRF levels were associated with increases in both intact and fragmented IGFBP-4. Mean RIA levels of IGFBP-5 were comparable in sera from CRF and normal children. Treating CRF children with GH for 12 months increased serum IGFBP-4 levels by 26% and IGFBP-5 levels by 49%, as determined by RIA; levels of IGFBP-5, but not IGFBP-4, correlated significantly with serum levels of IGF-I, IGF-II, IGFBP-3, and acid-labile subunit and with growth rate in these GH-treated children. In summary, IGFBP-4 levels are high in serum of CRF children, and GH increases serum levels of IGFBP-4 and IGFBP-5 in these children. The data suggest a role for IGFBP-5 in the accelerated growth of GH-treated CRF children, perhaps as part of a ternary complex with acid-labile subunit and IGFs. Additional studies on the relationship between intact IGFBP-4 levels and growth are needed to determine what role IGFBP-4 plays in the linear growth process in vivo.

Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

We report our experience with 11 children treated by continuous veno-venous hemodiafiltration. The median age was 5.0 years (range 3 days to 14 years). Access was via dual-lumen subclavian or femoral vein catheters. Hemofilters were chosen on the basis of patient size and dialysis requirements. Bicarbonate-buffered dialysis solution was prepared shortly before use by supplementation of a specially prepared base solution with commercially available electrolyte solutions. The mean ultrafiltration rate was 37.4 +/- 27 ml/kg body weight per hour. Urea and creatinine clearances were 15.1 +/- 6.4 ml/kg body weight per min and 16.4 +/- 8.4 ml/kg body weight per min, respectively. Metabolic acidosis was readily controlled in all patients. Of the 11 patients, 7 ultimately recovered normal renal function.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nutropin, 0.05 mg/kg/day, and the studies were carried out at baseline and after 3 and 12 months. At baseline, serum insulin-like growth factor binding protein (IGFBP)-1 and -2 levels were, while IGFBP-3 levels were not, higher than those of children with normal renal function. In addition, height SDS at baseline correlated inversely with serum IGFBP-2 levels (r = -0.461, P = 0.0016), but did not correlate significantly with any other factor. After 12 months of study, the 30 children receiving rhGH showed: (i) greater increase in height (9.1 +/- 2.8 vs. 5.5 +/- 1.9 cm, P < 0.0001); (ii) increases in serum levels of IGF-I, IGF-II, free IGF-I, IGFBP-3 and acid labile subunit (ALS); (iii) a greater decrease in serum IGFBP-1 levels; and (iv) no significant difference in serum IGFBP-2 levels, when compared to the 14 control patients. The change in height SDS after 12 months of rhGH (+0.8) in the 30 treated children correlated significantly and positively with serum ALS, IGFBP-3, total IGF, IGF-I, IGF-II and free IGF-I levels measured during treatment. These observations suggest that, in children with growth failure associated with chronic renal failure: (i) IGFBP-2, and not IGFBP-3, is likely to be a growth inhibitor; (ii) rhGH stimulates catch-up growth in part by increasing serum levels of IGF peptides; and (iii) linear growth is influenced by the balance between growth stimulating IGFs and growth inhibitory IGFBPs.

The significance of a positive family history in predicting responsiveness to desmopressin (DDAVP) treatment was evaluated in 71 children with nocturnal enuresis. A good response to treatment was recorded in 91% of those children with a positive family history compared with only 7% of those with a negative family history. A review of the published literature further supports the predictive value of a positive family history and also confirms the importance of a broad definition for family history-including persistent nocturia. The importance of defining the family history is also discussed in terms of response to some other therapies for nocturnal enuresis.

In this article, we consider a number of treatment options for patients with IgA nephropathy. Major emphasis will be placed on the use of corticosteroids and fish oil capsules because these have shown the most promise in recent publications. We also consider the specific management of two patients with severe manifestations of this disease and describe their responses. Finally, we consider future avenues of research into the treatment of IgA nephropathy. This includes a brief description of a three-arm multicenter, placebo-controlled study evaluating alternate-day prednisone and highly purified fish oil concentrate (Omacor) in children and young adults with moderately severe forms of IgA nephropathy.