Guidance document for structured reporting of diuresis renography.

This Guidance Document for structured reporting of diuresis renography in adults was developed by the International Scientific Committee of Radionuclides in Nephro-urology (ISCORN; http://www.iscorn.org). ISCORN chose diuresis renography for its first structured report Guidance Document because suspected obstruction is the most common reason for referral, most radionuclide renal studies are conducted at institutions that perform fewer than 3 studies per week, and a large percentage of studies are interpreted by physicians with limited training in nuclear medicine. Ten panelists were asked to categorize specific reporting elements as essential, recommended, optional (without sufficient data to support a higher ranking), and unnecessary (does not contribute to scan interpretation or quality assurance). The final document was developed through an iterative series of comments and questionnaires with a majority vote required to place an element in a specific category. The Guidance Document recommends a reporting structure organized into indications, clinical history, study procedure, findings and impression and specifies the elements considered essential or recommended in each category. The Guidance Document is not intended to be restrictive but, rather, to provide a basic structure and rationale so that the diuresis renography report will: (1) communicate the results to the referring physician in a clear and concise manner designed to optimize patient care; (2) contain the essential elements required to evaluate and interpret the study; (3) clearly document the technical components of the study necessary for accountability, quality assurance and reimbursement; and (4) encourage clinical research by facilitating better comparison and extrapolation of results between institutions.

Precision and within- and between-day variation of bioimpedance parameters in children aged 2-14 years.

BACKGROUND & AIMS: Bioimpedance spectroscopy (BIS) offers the possibility to perform rapid estimates of fluid distribution and body composition. Few studies, however, have addressed the precision and biological variation in a pediatric population. Our objectives were to evaluate precision, variation within- and between-days for the BIS-determined parameters total body fluid, extra-cellular fluid, intra-cellular fluid, body cell mass, fat-free mass, extra-cellular resistance, intra-cellular resistance and percentage body fat using a Xitron 4200. METHODS: All 133 children (81 boys, 52 girls; 2.4-14.9 years) had one series measured on day one (precision population). Forty-four children had a second series on day one (within-day sub-population). Thirty-two children had a series measured on the next day (between-day sub-population). Each measurement series consisted of three repeated measurements. A linear mixed model was used for statistical analysis. RESULTS: The precision was 0.3-0.8% in children ≥6 years and 0.5-2.4% in children <6 years with a statistically significant difference between the two age-groups (p<0.001). Within-day variation was 1.1-2.8% and between-day variation 2.4-5.7%. Total variation and reference change values are reported. CONCLUSION: The Xitron 4200 has a very good but age-dependent precision. The median value of three repeated measurements is recommended in order to avoid incorrect measurements.

Comparison of within- and between-subject variation of serum cystatin C and serum creatinine in children aged 2-13 years.

BACKGROUND: Previously, data on both the within-subject (SD(I)) and the between-subject (SD(G)) variation of cystatin C in children has not been reported. Thus, this study aimed to determine this biological variation including analytical variation (SD(A)) of both cystatin C and creatinine to characterize the two analytes as renal function markers in children. METHODS: On two consecutive days blood samples for duplicate analysis of cystatin C (nephelometric, Dade Behring) and creatinine (enzymatic, Roche) were obtained from 30 children (11 females and 19 males, mean age 8.3 range 2-13 years) referred for GFR measurements by (51)Cr-EDTA clearance. For determination of the between-subject variation only children with normal GFR (n=21) were included. Data were adjusted for the well known age-related increase in creatinine. RESULTS: The results are given as coefficients of variation. The within-subject variations were identical for both analytes (6.4%). The between-subject variation was 11.1% for cystatin C and 28.4% for creatinine, though decreasing to 20.1% after adjusting for age. The analytical variation was 1.7% and 2.5% for cystatin C and creatinine, respectively. The index of individuality (IOI = SD(I)/SD(G)) was 0.65 for cystatin C and 0.25 for creatinine, though increasing to 0.36 after age-adjustment. CONCLUSION: The within-subject variation was identical and low for cystatin C and creatinine suggesting that the two are equally suitable for serial monitoring of renal function in children. Based on the low IOI neither analyte, however, seems suitable as a screening marker of renal function in a healthy population of children using population-based reference intervals.

[Aprotinin scintigraphy in amyloidosis]. / Aprotininskintigrafi ved amyloidose.

Amyloidosis is a disease characterized by protein deposition (amyloid) in THE extracellular matrix leading to organ dysfunction and death. New treatment modalities have emphasized the need for accurate and early diagnosis. Aprotinin scintigraphy is a radionuclide imaging technique in which the localisation and extent of amyloid deposits are visualized. It is specific and sensitive in detecting cardiac amyloidosis, which is associated with a poor prognosis. In addition, aprotinin scintigraphy appears to be a useful tool for the monitoring of disease progression and treatment efficacy.

Measuring glomerular filtration rate in children; can cystatin C replace established methods? A review.

Our aim was to evaluate published methods that use serum cystatin C (s-CysC) for measuring glomerular filtration rate (GFR) in children and to discuss advantages and limitations of s-CysC and of established GFR methods. A comprehensive literature review of clinical studies in children evaluating s-CysC or CysC-based formulas and plasma creatinine or creatinine-based formulas against an exogenous reference method using receiver operating characteristics (ROC) curves or Bland-Altman plots is presented. The comparison of s-CysC with plasma creatinine indicated that s-CysC was superior to plasma creatinine in five of 13 studies; four studies showed no difference, and, in four studies, no statistical comparison was made. Comparison of s-CysC and the Schwartz formula showed that s-CysC was superior to the Schwartz formula in two of seven studies; two studies demonstrated no difference, and, in one study, the Schwartz formula was superior to s-CysC. In two studies no statistical comparison was made. The CysC-based prediction equations all had high accuracy but low agreement when compared with a reference GFR, in the range of 30-40% at best. S-CysC is most likely superior to plasma creatinine and at least equal to creatinine-based formulas. CysC-based prediction equations are at least as good as creatinine-based formulas but cannot replace exogenous methods.

Normal differential renal function does not indicate a normal kidney after partial ureteropelvic obstruction and subsequent relief in 2-week-old piglets.

PURPOSE: We investigated the functional consequences of relieving ureteric obstruction in young pigs with experimental hydronephrosis (HN) induced by partial unilateral ureteropelvic obstruction. MATERIALS AND METHODS: Three groups of animals were followed from the age of 2 weeks to the age of 14 weeks: Eight animals had severe or grades 3-4 HN throughout the study. Six animals had relief of the obstruction after 4 weeks. Six animals received sham operations at both ages. Morphological and functional examinations were performed at age 6 weeks and again at age 14 weeks and consisted of magnetic resonance imaging (MRI), technetium-diethylenetriaminepentaaceticacid ((99m)Tc-DTPA) renography, renal technetium-dimercaptosuccinicacid ((99m)Tc-DMSA) scintigraphy, and glomerular filtration rate (GFR) measurement. RESULTS: After relief of the partial obstruction, there was reduction of the pelvic diameter and improvement of urinary drainage. Global and relative kidney function was not significantly affected by either obstruction or its relief. Renal (99m)Tc-DMSA scintigraphy showed a change in both the appearance of the kidney and a change in the distribution within kidneys even after relief of obstruction. CONCLUSION: This study shows that partial ureteric obstruction in young pigs may be associated with little effect on global and differential kidney function. However, even after relief of HN, the distribution of (99m)Tc-DMSA in the kidney remains abnormal suggesting that a normal differential renal function may not represent a normal kidney.

Reproducibility and repeatability of differential renal function in 4-week-old piglets.

BACKGROUND: Congenital obstructive renal disease often requires a decision early in the child's life on whether or not surgery is required. Differential renal function (DRF) calculated from the renogram provides important information for the correct decision in this process. A recent publication cast doubt as to the reliability of the renogram in providing DRF in the young child. AIM: To describe the day-to-day variation and reproducibility of the two commonly used agents for estimating DRF. METHODS: Within 1 week, 4-week-old pigs each underwent three examinations with both 99mTc-DTPA and 99mTc-DMSA. DRF values from the 99mTc-DTPA renograms were calculated using both the area under the curve (AUC) and the Rutland-Patlak equation. Day-to-day variations in the results using different background subtraction methods were analysed using the coefficient of variation for each case and the repeatability coefficient for each type of background subtraction. RESULTS: DRF calculated from the 99mTc-DMSA studies showed little variation, with a coefficient of variation of 3.9% in the worst case. The repeatability coefficient calculated from the 99mTc-DTPA studies using the AUC technique combined with the background subtraction method giving the least variation was 14.9% while using the Rutland-Patlak technique with its best background subtraction showed an RC of 9.4%. CONCLUSIONS: The study demonstrates that DRF calculated from 99mTc-DMSA studies have low variability and the results are highly reproducible in immature pigs. The DRF calculated from 99mTc-DTPA renograms failed to show acceptable reproducibility when analysed using either the AUC method or the Rutland-Patlak equation.

AT1 receptor blockade prevents interstitial and glomerular apoptosis but not fibrosis in pigs with neonatal induced partial unilateral ureteral obstruction.

Obstruction-induced fibrosis is a leading cause of end-stage renal failure in children. The pathophysiological mechanisms may involve apoptosis and the renin-angiotensin system. We studied apoptosis and fibrosis in a well-established neonatal pig model with unilateral partial ureteral obstruction (PUUO) induced during ongoing nephrogenesis in 2-day-old piglets. The role of angiotensin II (ANG II) was studied using the AT(1) receptor blocker CV-11974 (0.12 mg/h candesartan from age 23 to 30 days). At day 30 the kidneys were perfusion fixed and fibrosis, apoptosis, and tubular lengths were quantitated using stereological methods, picro Sirius red staining, and immunohistochemical techniques identifying activated caspase 3, aquaporin-2 (AQP2), and von Willebrand factor. The collagen content was assessed by hydroxyproline density. Neonatal induced PUUO increased interstitial and glomerular cell apoptosis and fibrosis. At this stage, PUUO did not increase tubular cell apoptosis or decrease tubular length and cell number. AT(1) receptor blockade prevented the PUUO-induced interstitial and glomerular cell apoptosis but did not attenuate fibrosis. In conclusion, AT(1) receptor blockade after the end of nephrogenesis may prevent interstitial and glomerular cell apoptosis but not fibrosis, suggesting that pathways not involving AT(1) receptor stimulation contribute to neonatal obstruction-induced fibrosis or that prevention of interstitial cell apoptosis counteracts a potential antifibrotic effect of AT(1) receptor blockade in this pig model of congenital obstructive nephropathy. Our results demonstrate that ANG II plays a role in PUUO-induced glomerular cell apoptosis.

Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction.

Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal function and in the present study we examined the effects of chronic AT1 receptor blockade using CV-11974 (0.12 mg/h candesartan from age 23 to 30 days) on kidney function development after PUUO was induced in 2-day-old piglets. Moreover, the effect of superimposed acute NO inhibition using N(G)-nitro-l-arginine methyl ester (l-NAME; 15 mg/kg) was examined to identify if this has diagnostic potential. PUUO significantly increased GFR in the nonobstructed contralateral kidney independent of candesartan. In candesartan-treated piglets, the l-NAME-induced GFR reduction seen in normal and nonobstructed kidneys was absent in the partial obstructed kidneys. Urine output and fractional excretion of water were increased from the partial obstructed kidneys. Consistent with this immunohistochemical analyses showed a reduced aquaporin-2 labeling in the collecting duct principal cells. Moreover, renal sodium handling was compromised by PUUO evidenced by an increased fractional excretion of sodium which was enhanced by candesartan treatment. In conclusion, our findings suggest that the counterbalance between AT1 receptor-mediated vasoconstriction and NO-mediated vasodilatation which maintain GFR in normal young porcine kidneys is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function.

[Prenatal diagnosed hydronephrosis and other urological anomalies]. / Praenatalt diagnosticeret hydronefrose og andre urologiske anomalier.

By renal ultrasound examination, urological anomalies may be demonstrated in 1-2% of fetuses and in about 0.5% of newborns. Boys have about twice the frequency of girls. Surgical treatment is indicated in about one fourth of these urological anomalies. If all pregnant women in Denmark were to have fetal ultrasound examination of the kidneys and the urinary tract, about 70 children would be born each year with a prenatally diagnosed urological anomaly for which surgical procedure is or will be indicated. This paper provides Danish guidelines for prenatal diagnosis, follow-up and intervention in cases of urological anomalies and guidelines for post-natal diagnosis, follow-up and treatment of these anomalies, especially hydronephrosis.

Congenital unilateral hydronephrosis: a review of the impact of diuretic renography on clinical treatment.

PURPOSE: The natural history of and optimal treatment for asymptomatic congenital hydronephrosis is unknown, mainly because most published series are nonrandomized or retrospective with nonstandardized followup regimens. In this survey we provide an overview of the different strategies used for the treatment of congenital unilateral hydronephrosis. MATERIALS AND METHODS: A comprehensive literature review of clinical studies of asymptomatic congenital unilateral hydronephrosis is presented. RESULTS: Different criteria for surgical intervention and different followup regimens have been used. Identification of the population at risk has been attempted but results are ambiguous. Surgery is done in approximately 25% of cases when using deteriorating differential function, symptoms and/or increasing hydronephrosis as criteria for operation. A nonstandardized renographic assessment does not compromise evaluation of the ideal followup but it may compromise the functional outcome. CONCLUSIONS: More studies of kidneys with decreased function, severe hydronephrosis or poor drainage investigated with a standardized protocol are needed to clarify the natural history and establish optimal guidelines for treatment and followup.

Interpretation of the renogram: problems and pitfalls in hydronephrosis in children.

OBJECTIVE: To discuss the main steps of renographic technique and underline some pitfalls related to the acquisition, processing and interpretation of diuretic renography, an important method for guiding the management of asymptomatic congenital hydronephrosis. METHODS: Despite guidelines and consensus protocols, renographic procedures differ among centres, causing difficulties in comparison and controversy in the interpretation of results. Thus we comprehensively assessed published papers on the subject of diuretic renography. RESULTS: Differential renal function (DRF) is a robust measure provided there is adequate background subtraction. Pitfalls are related to the drawing of regions of interest, particularly in infants, to estimating the interval during which DRF is calculated, and to an adequate signal-to-noise ratio. There is no definition of a 'significant' reduction in DRF. The classical variables of the diuretic renogram may not allow an estimate of the best drainage. Poor pelvic emptying may be apparent because the bladder is full and because the effect of gravity on drainage is incomplete. Estimating the drainage as residual activity rather than any parameter on the slope might be more adequate, especially if the time of frusemide administration is changed. Renal function and pelvic volume can influence the quality of drainage. Drainage may be better estimated using new tools. CONCLUSION: Provided the investigation is standardized and potential pitfalls accounted for, the diuretic renogram provides valuable and reproducible quantitative information on DRF and drainage.

Use of plasma clearance of technetium Tc 99m pentetate to estimate renal clearance during postnatal development in pigs.

OBJECTIVE: To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age. ANIMALS: 24 female pigs. PROCEDURE: At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetiumTc 99m pentetate was calculated. Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance (r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight. CONCLUSIONS: Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple biood samples in pigs from 3 to 24 weeks of age.

Reduced number of glomeruli in kidneys with neonatally induced partial ureteropelvic obstruction in pigs.

PURPOSE: We quantify the structural components of the nephron in adult pig kidneys with neonatally induced unilateral hydronephrosis in comparison with nonobstructed kidneys. MATERIALS AND METHODS: The study included 11 pigs with unilateral partial ureteropelvic obstruction induced 2 days after birth and 8 sham operated control pigs. Obstructed kidney glomerular filtration rate was significantly reduced at age 4 weeks but did not differ from control kidneys after 24 weeks. At age 24 weeks the kidneys were perfusion fixed, and the number and volume of glomeruli and tubular lengths were measured using stereological methods. RESULTS: Mean obstructed kidney volume did not differ from that of control kidneys. Mean number plus or minus standard deviation of glomeruli in the obstructed kidneys was reduced by 28% compared to that of control kidneys (502 +/- 163 x 103 versus 697 +/- 161 x 103, p = 0.02), whereas no difference in mean glomerular volume was observed. Mean length of the proximal or distal tubules did not differ between obstructed and control kidneys. Mean number or volume of glomeruli in nonobstructed kidneys contralateral to obstructed kidneys did not differ from that of control kidneys. The individual number of glomeruli in the obstructed kidneys was not associated with function of these kidneys. CONCLUSIONS: Neonatally induced unilateral partial ureteropelvic obstruction causes impaired nephrogenesis with a significant reduction in the number of nephrons, which is not reflected in measurements of kidney function in this model. The reduction in the number of glomeruli suggests that congenital unilateral obstruction impairs nephrogenesis.