Ulla B. Berg

Measuring GFR: A Systematic Review.

BACKGROUND No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. STUDY DESIGN Systematic review with meta-analysis of cross-sectional diagnostic studies. SETTING & POPULATION Published original studies and systematic reviews in any population. SELECTION CRITERIA FOR STUDIES Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. INDEX TESTS Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. REFERENCE TEST Renal inulin clearance measured under continuous inulin infusion and urine collection. RESULTS Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%. LIMITATIONS The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. CONCLUSIONS At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

HENOCH SCHONLEIN 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-Schönlein 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.

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.

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.

Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotension and in treated hypertensive recipients.

Abstract:  Increased carotid IMT was found to be associated with cardiovascular risk factors. As pediatric renal transplants are at high risk for cardiovascular disease, we examined whether there is a relationship between BP and IMT in normotensive and in treated hypertensive recipients after transplantation. Thirty‐one recipients aged 10 ± 3.5 yr (16 M, 15 F) underwent repeated carotid ultrasound examinations 5.4 ± 3.2 yr after transplantation with a 4.1 ± 1 yr interval and were followed with annual ambulatory BP monitoring. Baseline IMT was significantly higher in transplants compared with controls. When recipients were again investigated, follow‐up IMT measurements were similar compared with measurements obtained at baseline. The analysis of variance showed that baseline IMT both in recipients with strict normotension, i.e., ambulatory normotension without antihypertensive therapy at baseline and throughout the study period (n = 9), and in recipients with treated hypertension or newly diagnosed hypertension (n = 22) was significantly higher than in healthy controls (n = 21). Baseline IMT did not differ between these subgroups of recipients. Similarly, pairwise comparisons showed that baseline and follow‐up IMT within each subgroup of recipients were not significantly different. Overall and regardless of time‐point, no significant associations were found between systolic and diastolic 24‐h BP, daytime BP, night‐time BP, ambulatory BP standard deviation scores, BP loads and IMT. Our results suggest that increased IMT in pediatric renal transplants does not seem to be related to BP but more likely to other factor(s) not investigated in this study.

Long-term psychosocial outcome after renal transplantation during childhood.

Abstract:  The aim of this study was to describe long‐term psychosocial outcome after renal transplantation during childhood. Sixty‐eight patients, having reached adulthood (>20 yr of age), were selected for the study. An invitation letter was sent to the patients asking them to participate in an interview performed by telephone and 42 (24 females) agreed. The age at the time of the interview was median 25.7 yr. The age at the transplantation was 1.4–20.5 yr. A total of 9.5% considered themselves as ill (three of four on dialysis), 24% as both ill and well and 67% as well. The school performance did not differ to a great extent from the general population. Fourteen percent were unemployed compared with 5.3% of the general population. Fourteen percent, all under 25 yr, lived with their parents, 52% had independent lodging and 33% were married or lived with a partner. Twenty‐five patients stated that they had felt anxiety or depressed at some time. However, when asking them to score their quality of life on a scale from 1 to 10, they scored median 8.0. Thus, the long‐term psycho‐social outcome after kidney transplantation during childhood seems to be quite good. Most of the interviewed seemed to have a good life according to themselves.

ABO‐incompatible kidney transplantation in children

Tydén G, Kumlien G, Berg UB. ABO‐incompatible kidney transplantation in children. 
Pediatr Transplantation 2011: 15: 502–504.

Use of annual ABPM, and repeated carotid scan and echocardiography to monitor cardiovascular health over nine yr in pediatric and young adult renal transplant recipients

Balzano R, Lindblad YT, Vavilis G, Jogestrand T, Berg UB, Krmar RT. Use of annual ABPM, and repeated carotid scan and echocardiography to monitor cardiovascular health over nine yr in pediatric and young adult renal transplant recipients.
Pediatr Transplantation 2011: 15: 635–641.

Schwartz Formula: Is One k-Coefficient Adequate for All Children?

Background/Objective Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population. Patients/Methods We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort. Results In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient. Conclusions The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance.

Blood pressure control in hypertensive pediatric renal transplants: role of repeated ABPM following transplantation.

BACKGROUND Hypertension in pediatric renal transplants is a widespread condition associated with high mortality risk in early adult life. Ambulatory blood pressure monitoring (ABPM) was found to be superior to office blood pressure (BP) in identifying true hypertensive and responders to treatment. The aim of this study was to investigate the role of repeated ABPM, performed at yearly intervals following transplantation, in the assessment and decision-making processes of post-transplant hypertension. METHODS Thirty-seven recipients (23 males; aged 10.5 +/- 4.3 years) who were followed for 4.3 +/- 2.2 years (range 2-9) after transplantation were eligible for analysis. The mean follow-up time between the baseline (1 year post-transplantation) and the most recent ABPM examination was 3.3 +/- 2.2 years (range 1-8). RESULTS Throughout the follow-up period, antihypertensive therapy was either started or intensified in 27 recipients. These interventions were decided based on ABPM results obtained on 40 of 44 occasions. At last follow-up, 24 of 29 treated hypertensive recipients displayed controlled BP. This figure was significantly higher compared to our historical hypertensive control recipients in whom ABPM was applied for the first time in treatment at 6 +/- 3.3 years (range 2-15) after transplantation, while therapeutic decisions were driven by office BP measurements (95 % confidence interval (95% CI) for the difference between proportions (80.6-32 %) 36-60 %, P = 0.001). CONCLUSIONS Our study shows that, in a population with high risk for hypertension, repeated ABPM may significantly help to improve BP control.