Estimating glomerular filtration in young people.

Background: Creatinine-based equations are the most used to estimate glomerular filtration rate (eGFR). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the re-expressed Lund-Malmö Revised (r-LMR) and the European Kidney Function Consortium (EKFC) equations are the most validated. The EKFC and r-LMR equations have been suggested to have better performances in young adults, but this is debated. Methods: We collected data (GFR) measured by clearance of an exogenous marker (reference method), serum creatinine, age and sex from 2366 young adults (aged between 18 and 25 years) both from Europe and the USA. Results: In the European cohorts (n = 1892), the bias (in mL/min/1.73 m²) was systematically better for the EKFC and r-LMR equations compared with the CKD-EPI equation [2.28, 95% confidence interval (1.59; 2.91), -2.50 (-3.85; -1.76), 17.41 (16.49; 18.47), respectively]. The percentage of estimated GFR within 30% of measured GFR (P30) was also better for EKFC and r-LMR equations compared with the CKD-EPI equation [84.4% (82.8; 86.0), 87.2% (85.7; 88.7) and 65.4% (63.3; 67.6), respectively]. In the US cohorts (n = 474), the bias for the EKFC and r-LMR equations was better than for the CKD-EPI equation in the non-Black population [0.97 (-1.69; 3.06), -2.62 (-5.14; -1.43) and 7.74 (5.97; 9.63), respectively], whereas the bias was similar in Black US individuals. P30 results were not different between the three equations in US cohorts. Analyses in sub-populations confirmed these results, except in individuals with high GFR levels (GFR ≥120 mL/min/1.73 m²) for whom the CKD-EPI equation might have a lower bias. Conclusions: We demonstrated that both the EKFC and r-LMR creatinine-based equations have a better performance than the CKD-EPI equation in a young population. The only exception might be in patients with hyperfiltration.

Extending the cystatin C based EKFC-equation to children - validation results from Europe.

BACKGROUND: A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. METHODS: Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. RESULTS: The EKFCCysC with the simple QCysC-value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFCCysC with the more complex 4th degree QCysC-value. The arithmetic mean of the EKFCCrea and EKFCCysC with the simple QCysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4th degree QCysC-polynomial. CONCLUSION: Using exactly the same QCysC of 0.83 mg/L, the adult EKFCCysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFCCrea and EKFCCysC results in bias closer to zero and P30 slightly over 90%.

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

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

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

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

Comparison of cystatin C, creatinine, and iohexol clearance in pediatric liver transplantation-a retrospective cohort study.

Impaired renal function after pediatric (LT) is a recognized problem. Accurate monitoring of (GFR) is imperative to detect declining renal function. GFR can be estimated via s-creatinine and/or p-cystatin C or measured by inulin and or/iohexol clearances. We retrospectively compared eGFRcrea and eGFRcyst, to mGFRiohex after LT. Data from 91 children with 312 concomitant measurements of s-creatinine, p-cystatin C, and iohexol clearance, obtained between 2007 and 2015, were analyzed. eGFR was calculated by using the p-cystatin C-based CAPA and CKD-EPI formulas, and the s-creatinine-based Schwartz-LYON, FAS, revised Schwartz and MDRD formulas. Also, the arithmetic means of cystatin C-based and creatinine-based equations were used. Every calculated eGFR was compared to mGFRiohex in statistical correlation, accuracy, precision, bias, and misclassifications. Among the different equations, p-cystatin C-based formulas (CAPA and CKD-EPI) as well as the s-creatinine-based Schwartz-LYON formula showed the most correct estimates regarding accuracy (84-87.5%), bias (0.19-4.0 ml/min/1.73 m2 ), and misclassification rate (24.7-25%). In patients with renal function <75 ml/min/1.73 m2 , cystatin C-based formulas were significantly more accurate and less biased than creatinine-based formulas. In conclusion, S-creatinine could be used in a clinical setting on a regular basis in liver transplanted pediatric patients, with reliable results, if eGFR is calculated by the Schwartz-LYON formula. When suspected renal dysfunction, cystatin C-based eGFR should be calculated, since it gives more accurate and less biased estimates than creatinine-based eGFR, and should be confirmed by mGFR (iohexol).

Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update.

BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children.

BACKGROUND: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. METHODS: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2-17 years. Validated equations included Schwartz-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR, Schwartz-LyonCR, BergCYS, CAPACYS, CKD-EPICYS, AndersenCR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P10) and ± 30% (P30) of mGFR. RESULTS: Three of the cystatin C equations, BergCYS, CAPACYS and CKD-EPICYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPICYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-LyonCR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations. CONCLUSIONS: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.

Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.

BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

New standardized cystatin C and creatinine GFR equations in children validated with inulin clearance.

BACKGROUND: This study compares glomerular filtration rate (GFR) equations in children based on standardized cystatin C (CYSC) and creatinine (CREA) and their combinations with renal clearance of inulin (C-inulin). METHODS: A total of 220 children with different renal disorders were referred for C-inulin (median 84 ml/min/1.73 m(2)). Bias, precision (interquartile range, IQR), and accuracy (percentage of estimates ±30 % of C-inulin; P30) were evaluated for two cystatin C equations, CAPACYSC and BergCYSC, for creatinine equations, SchwartzCREA and GaoCREA, the arithmetic mean of CAPACYSC and SchwartzCREA (MEANCAPA+Schwartz), BergCYSC and SchwartzCREA (MEANBERG+SCHWARTZ) and the composite equation ChehadeCYSC+CREA. RESULTS: Overall results of CAPACYSC, BergCYSC, SchwartzCREA, GaoCREA, MEANCAPA+Schwartz, MEANBERG+SCHWARTZ and ChehadeCYSC+CREA were: median bias -7.6/-4.9/-3.7/-2.3/-4.6/-4.0/-10.1 %, IQR 20.0/19.9/21.7/22.4/21.0/20.9/23.3 ml/min/1.73 m(2) and P30 86/86/80/83/89/91/83 %. The cystatin C equations, MEANCAPA+Schwartz and MEANBERG+SCHWARTZ had a more stable performance across subgroups compared with SchwartzCREA, GaoCREA and ChehadeCYSC+CREA. CONCLUSIONS: Cystatin C was the preferred filtration marker for GFR estimation in children, while the benefit of combining cystatin C and creatinine deserves further investigations.

Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford classification).

BACKGROUND: There has been a lack of international consensus on the classification and the predictive value of the histopathology findings in IgA nephropathy (IgAN). Recently, the International IgA Nephropathy Network has developed the Oxford classification in which four histological variables with the most prognostic importance are identified (MEST score). Our objective was to validate these findings and to assess their predictive power in our cohort and to compare them to identified clinical predictors. METHODS: Ninety-nine children with a follow-up time >5 years were included and investigated with clearances of inulin or iohexol for glomerular filtration rate (GFR), proteinuria and blood pressure at biopsy and during follow-up. Biopsies (90/99) were re-evaluated and scored according to the Oxford classification. RESULTS: Eighteen patients progressed to a poor outcome [end-stage renal disease (ESRD) or GFR reduction >50%]. In the univariate analysis, we found that mesangial hypercellullarity score >0.5, presence of endocapillary hypercellularity or tubular atrophy/interstitial fibrosis of >25% were each associated with a poor outcome, and also presence of cellular or fibrocellular crescents and of global glomerulosclerosis, but segmental glomerulosclerosis did not reach statistical significance. The clinical predictors of a poor outcome were a low GFR, a high mean arterial blood pressure and a high amount of albuminuria (log Ualb/c) at time of biopsy and low GFR and a high log Ualb/c during follow-up. CONCLUSION: We found that three of the four histology lesions identified in the Oxford classification, as well as presence of crescents, were valid in predicting a poor outcome in our cohort of patients.

Maintenance of remission with cyclosporine in paediatric patients with Kimura's disease - two case reports.

UNLABELLED: Here we report two paediatric cases of Kimura's disease, which is a rare, chronic inflammatory disorder with undetermined aetiology. The first patient was a 17-year-old boy presenting with a swelling behind his right ear and a nephrotic syndrome. The second patient was a 9-year-old boy presenting with a left-sided preauricular swelling. Both displayed peripheral blood eosinophilia, raised levels of serum IgE and typical histological findings. Initial response to prednisolone was excellent but both relapsed as medication was tapered or discontinued. Adding cyclosporine to the regimen resulted in prolonged remission in both patients. CONCLUSION: We support the use of cyclosporine for maintaining remission in paediatric patients with Kimura's disease.

Comparison of plasma clearance of iohexol and urinary clearance of inulin for measurement of GFR in children.

BACKGROUND: Very few studies have been published that compare plasma clearance of iohexol (Cio) with renal clearance of inulin (Cin). STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 60 children aged 11.6 ± 4.5 years with different kidney disorders were investigated. INDEX TEST: Plasma Cio calculated from the slope and a single point. REFERENCE TEST: Renal Cin with continuous infusion during water diuresis. Results were compared with the correlation coefficients, bias and precision, accuracy percentage, root mean square error, and intraclass correlation. OTHER MEASUREMENTS: Measured creatinine clearance and estimated glomerular filtration rate based on serum creatinine level and height. RESULTS: Mean Cin was 70.7 ± 41.3 (SD) mL/min/1.73 m². Mean differences between Cio and Cin were 2.65 and 2.00 mL/min/1.73 m² for the slope and single-point methods, respectively. Precision was ±16 mL/min/1.73 m² and intraclass correlation was 0.92 in both methods. Proportions of Cio within 30% of Cin were 83.3% and 86.7% for the slope and single-point methods, respectively. LIMITATIONS: A limited number of patients; no adults were studied. CONCLUSIONS: Plasma Cio shows good agreement with renal Cin.

Predictors of outcome in Henoch-Schönlein nephritis.

Factors predictive of renal outcome were studied in 78 children with Henoch-Schönlein nephritis followed up for as long as 17 (mean 5.2) years. Patients with a good outcome (74%) were healthy or had microalbuminuria or mild proteinuria at the final follow-up (FU), and those with poor outcome (26%) had active renal disease or chronic kidney disease at stages IV-V. Patients with mild symptoms at onset (hematuria + or - mild proteinuria) had a poor outcome in 15% of cases versus 41% of those with severe symptoms (nephritic or nephrotic syndrome or nephritic-nephrotic picture) (p = 0.011). However, among patients with mild proteinuria at onset, 18% showed a poor prognosis; non-nephrotic proteinuria with a urine albumin/creatinine ratio at a cut-off value of >144 mg/mmol at the 1-year FU was predictive of a poor outcome. Among 59 biopsied patients, 37% of those with advanced histological findings [International Study of Kidney Disease in Children (ISKDC) stages III-V] had a poor outcome compared to none of those with mild findings (ISKDC stages I-II) (p = 0.0015). Patients with a poor outcome were older at onset, had more proteinuria, and lower glomerular filtration rate at the 1-year FU compared with patients with a good outcome. Multivariate analysis showed that proteinuria at the 1-year FU and the ISKDC grading score of the renal biopsy were the two most discriminant factors of a poor prognosis.

Treatment of severe Henoch-Schönlein and immunoglobulin A nephritis. A single center experience.

Our aim was to report the effect of two treatment regimens in 43 cases of severe Henoch-Schönlein nephritis (HSN) and immunoglobulin A nephritis (IgAN) (24 HSN, 19 IgAN). Group A, 11 HSN and 7 IgAN, 88% with an International Study of Kidney Disease in Children (ISKDC) biopsy grade > or = III and severe clinical features, were treated with corticosteroids, cyclophosphamide (CYC-P) and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). Group B, 12 HSN and 13 IgAN, 72% with biopsy findings as above and 52% with severe clinical features, were treated with ACEi/ARB +/- corticosteroids. The outcome classification was: (a) healthy; (b) mild proteinuria, normal glomerular filtration rate (GFR); (c) active renal disease; (d) chronic renal failure. Twenty-six patients had a good outcome (a + b). The 17 children with poor outcome (c + d) had lower GFR at onset and at follow-up, higher albumin excretion at follow-up, and higher percentage of segmental glomerulosclerosis in the renal biopsy, than those with good outcome. Treatment with corticosteroids, CYC-P and ACEi/ARB was effective in increasing GFR, reducing proteinuria and decreasing the disease activity index. The proteinuria had decreased at follow-up in both groups. In group A, GFR increased and histopathological activity index declined after treatment. The outcome did not differ between groups A and B. The effects of treatment did not differ between HSN and IgAN.

The effects of candesartan on diabetes glomerulopathy: a double-blind, placebo-controlled trial.

Our objective was to study the effects of candesartan on diabetic glomerulopathy in young normoalbuminuric and normotensive patients with type 1 diabetes in a double-blind, placebo-controlled trial. In 13 patients aged 24 years at baseline, we evaluated blood pressure, kidney biopsies and kidney function tests at baseline and after 5 years of treatment. Kidney biopsies were examined with light and electron microscopy, glomerular filtration rate and effective renal plasma flow determined with inulin and para-aminohippuric acid clearances. Two patients in the placebo group needed antihypertensive treatment because they developed microalbuminuria and/or hypertension, but no patient in the candesartan group did. A significant reduction in mesangial matrix volume and mesangial volume occurred in the candesartan group, although changes in morphological parameters were similar between groups. Office blood pressure was significantly lower in the candesartan group at follow-up than in the placebo group. Deterioration in morphological parameters observed in earlier studies of our patients did not become worse during treatment with candesartan or placebo. The effects of candesartan, with reduction in morphological parameters and lowering of blood pressure, might influence future treatment of glomerulopathy in type 1 diabetes patients.

Urinary excretion of endothelin-1 (ET-1), transforming growth factor- beta1 (TGF- beta1) and vascular endothelial growth factor (VEGF165) in paediatric chronic kidney diseases: results of the ESCAPE trial.

UNLABELLED: The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-beta1 and VEGF(165) was evaluated in 303 children with CKD stage II-IV (GFR 48 +/- 22 ml/min/1.73 m(2)) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). RESULTS: The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 +/- 2042 vs 216 +/- 335 fmol/g creatinine for ET-1; 252 +/- 338 vs 155 +/- 158 ng/g for VEGF; 31.6 +/- 37.0 vs 10.9 +/- 9.8 ng/g for TGF-beta1 (each P < 0.0001). The excretion of ET-1 and TGF-beta1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-beta1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P < 0.005) and renal function (r = -0.21, -0.13 and -0.15; P < 0.001; < 0.05; < 0.01; respectively) VEGF and TGF-beta1 excretion rates were positively correlated both in patients and controls. CONCLUSIONS: Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-beta1 and VEGF(165) in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-beta1 and VEGF(165) excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

Gender affects self-evaluation in children with cystic fibrosis and their healthy siblings.

AIM: To determine whether self-esteem among children with cystic fibrosis (CF) and their healthy siblings differs from that of a healthy reference group and whether there are differences within and between sibling pairs. METHODS: All Swedish CF children 6-14 y old with a healthy sibling in the same age range (n=65) were invited to participate, 55 sibling pairs and their parents taking part in the study. Five aspects of the children's self-concept-physical characteristics, skills and talents, mental well-being, relations to parents and family, and relations to others-were assessed by the "I think I am" self-evaluation questionnaire. Severity of illness was assessed by means of the Shwachman Clinical Evaluation System. RESULTS: Whereas self-evaluation did not differ between groups at a general level, healthy girls as well as those with CF scored lower than girls in the reference group on the "mental well-being" and "relations to parents and family" subscales. Comparison of gender combinations (sick girl/healthy boy, sick girl/healthy girl, sick boy/healthy boy, sick boy/healthy girl) suggested that girls pay a cost of a lesser sense of psychological well-being and feelings of inadequacy in relation to their parents and family. The Shwachman score of the sick child was not related to the level of self-esteem. CONCLUSION: When CF is present among siblings, girls seem to carry more of the family pain than boys, a finding that calls for an increased awareness of the girls' situation by members of care teams.

Henoch Schönlein nephritis: clinical findings related to renal function and morphology.

We evaluated the renal hemodynamics and the urine protein excretion rates of 73 children with Henoch-Schonlein nephritis (HSN). In 40 children we also performed a renal biopsy. The glomerular filtration rate (GFR) and effective renal plasma flow were determined by the clearances of inulin and para-aminohippurate during water diuresis. Urine albumin and IgG excretion were assessed in short-term timed samples. The mean GFR at the first examination was reduced in the HSN patients and most reduced in those with nephrotic proteinuria. There was an inverse correlation between the GFR at the first examination and the amount of albuminuria and urinary IgG excretion. Among the 40 patients with some degree of proteinuria who underwent a renal biopsy, 9 of 13 patients with mild to moderate proteinuria had severe morphological changes. GFR correlated inversely and fractional albumin and IgG excretion directly with the severity of the pathological findings on the biopsy, and with segmental and global sclerosis, the grade of mesangial proliferation, and interstitial inflammation. In conclusion, GFR is moderately reduced early in HSN and more reduced in patients with more proteinuria and in those with more advanced morphological changes. Moreover, even mild to moderate proteinuria may indicate severe morphological changes, which increase the indications for early renal biopsy in these patients.