Urinary proteome analysis and the management
of ureteropelvic junction obstruction
Hrair-George O. Mesrobian
Received: 24 December 2009 / Revised: 12 March 2010 / Accepted: 15 March 2010 / Published online: 21 April 2010
# IPNA 2010
Abstract Ureteropelvic junction obstruction (UPJO) detected prenatally may over time deteriorate and require surgery, improve, or remain stable, and it may take upwards of 3 years for its natural history to unfold. Clinical decisions for or against operative corrections are usually based on scintigraphy followup
studies. A non-invasive method for facilitating clinical decisions has recently been presented: urinary proteome analysis utilizing capillary electrophoresis mass spectrometry (CE-MS) has been shown to predict the outcome of UPJO in newborns. The group that developed this assay has now validated their seminal findings and extended the investigations to older age groups (this issue). The results of the linded
analysis correctly identified patients with UPJO who underwent surgery with a sensitivity of 83% (5 of 6 patients) and a specificity of 92% (12 of 13 patients) in infants up to 1 year of age. The validity of the analysis was poor in children >1 year of age with unilateral UPJO. A large number of patients will be
needed to answer the question of to what extent the normal variability of urinary proteomes overlap with the variability of the pattern in UPJO beyond early infancy.
Vitamin D insufficiency: implications for the immune system
Femke Baeke Conny Gysemans Hannelie Korf Chantal Mathieu
Received: 26 September 2009 / Revised: 15 December 2009 / Accepted: 4 January 2010 / Published online: 24 February 2010
# IPNA 2010
Abstract Chronic kidney disease (CKD) is characterized by a loss of kidney function and dysregulation of vitamin D metabolism. Well known are the defects in final activation of vitamin D to 1,25- Hihydroxyvitamin D3 [1,25(OH)2D3], resulting in renal osteodystrophy. However, in recent years,
1,25(OH)2D3 has been identified as having effects far beyond calcium and bone metabolism. In this review, specific attention is given to the effects of 1,25(OH)2D3 on the immune system and the implications of vitamin D deficiency, a feature of many patients with CKD, on immune function
The virtues of vitamin D—but how much is too much?
Rukshana Shroff Craig Knott Lesley Rees
Received: 13 January 2010 / Revised: 6 February 2010 / Accepted: 16 February 2010 / Published online: 15 April 2010
# IPNA 2010
Abstract Vitamin D deficiency is common in healthy adults and children as well as in the chronic kidney disease (CKD) population.Whatwas once a disease of malnourished children in the developing world has re-emerged and reached pandemic proportions. In parallel with this development, there is a growing awareness that vitamin D is not simply a ‘calcaemic hormone’ but plays an important role in the prevention of cardiovascular disease, infectious and autoimmune conditions, renoprotection, glycaemic control and prevention of some common cancers. Most tissues in the body have a vitamin D receptor and the enzymatic machinery to convert ‘nutritional’ 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D; it is estimated that 3% of the human genome is regulated by the vitamin D endocrine system. Although there are few well-conducted studies on the benefits of vitamin D therapy, an exuberant use of vitamin D is now seen in the general population and at all stages of CKD. There is emerging evidence that vitamin D may in fact have a therapeutic window, and at least from the effects on the cardiovascular system, more is not necessarily better. In this review, we discuss the role of nutritional vitamin D (ergocalciferol or cholecalciferol) supplementation in CKD patients, interpreting the clinical studies in the light of the vitamin D metabolic pathway and its pluripotent effects. While nutritional vitamin D compounds clearly have numerous beneficial effects, randomised controlled studies are
required to determine the effectiveness and optimal dose at different stages of CKD, its concurrent use with activated vitamin D compounds and its safety profile
Hereditary nephrotic syndrome: a systematic approach
for genetic testing and a review of associated podocyte
gene mutations
Geneviève Benoit Eduardo Machuca Corinne Antignac
Received: 17 December 2009 / Revised: 4 February 2010 / Accepted: 8 February 2010 / Published online: 24 March 2010
# IPNA 2010
Abstract Several genes have been implicated in genetic forms of nephrotic syndrome occurring in children. It is now known that the phenotypes associated with mutations in these genes display significant variability, rendering genetic testing and counselling a more complex task. This review will focus on the recent clinical findings associated with those genes known to be involved in isolated steroidresistant
nephrotic syndrome in children and, thereby, propose an approach for appropriate mutational screening.
The recurrence of proteinuria after transplantation in patients with hereditary forms of nephrotic syndrome will also be discussed.
The “other” vasculitis syndromes and kidney involvement
Seza Ozen
Received: 25 July 2009 / Revised: 3 September 2009 / Accepted: 3 September 2009 / Published online: 7 November 2009
# IPNA 2009
Abstract There are a number of vasculitides that are not confined to a specific vessel size, do not have characteristic features, and/or are not secondary to another disease. Most of these vasculitides are rare in childhood. Behçet disease is representative of this group as it involves vessels of any size on both the arterial and venous side. In addition to renal vascular involvement, Behçet disease may involve the kidney through glomerulonephritis, secondary amyloidosis and, rarely, tubulointerstital involvement. Vasculitis secondary to infections, malignancy, and drugs are not common among children. However, vasculitis may be associated with a number of rheumatic diseases in childhood and the auto-inflammatory syndromes (periodic fever syndromes). Auto-inflammatory syndromes are diseases characterized by periodic attacks of clinical and laboratory inflammation. Studies carried out during the past decade have provided valuable information on the mechanism of inflammation and innate immunity in general. This group of vasculitides is associated with secondary amyloidosis of the kidney if not treated. Hypocomplementemic
urticarial vasculitis is an interesting vasculitic disease with frequent kidney involvement. Here, we introduce the reader to the wide scope of these diseases; although rare, such diseases represent a challenge to the nephrologist.
Medium-size-vessel vasculitis
Michael J. Dillon Despina Eleftheriou Paul A. Brogan
Received: 7 July 2009 / Revised: 10 September 2009 / Accepted: 11 September 2009 / Published online: 28 November 2009
# IPNA 2009
Abstract Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder
disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better longterm follow-up data will lead
ORIGINAL ARTICLE
No juvenile arterial hypertension in sheep multiples despite
reduced nephron numbers
Anja Mühle Christiane Mühle Kerstin Amann Jörg Dötsch Kai-Dietrich Nüsken Johannes Boltze Holm Schneider
Received: 17 November 2009 / Revised: 15 March 2010 / Accepted: 16 March 2010 / Published online: 13 April 2010
# IPNA 2010
Abstract Low birth weight is associated with an increased risk of metabolic dysfunction and arterial hypertension in later life. Because of their reduced birth weight twins have been used repeatedly as a natural model to investigate prenatal programming of hypertension. To reveal an early impact of lower nephron endowment on blood pressure, we performed a longitudinal study on lambs from single, twin
and triplet pregnancies. The lambs were studied from birth until adulthood, including regular blood analyses, measurements of body weight and blood pressure and post-mortem estimation of glomerular numbers. Relative weight differences between multiples and singletons at birth were −28% for twins and −44% for triplets, respectively. Some lambs showed rapid catch-up growth. Total nephron number of
twins and triplets was reduced by 21 and 37% with respect to that of singletons (p<0.01). However, multiples did not show increased blood pressure within the time frame of this study. No gender-specific effect was observed. Plasma concentrations of creatinine, urea, electrolytes or osmolality also did not differ. Our data indicate that the previously reported postnatal blood pressure differences between sheep multiples and singletons are a time-limited phenomenon. During infancy and adolescence, a reduced nephron number in sheep multiples is neither associated with increased blood pressure nor reflected by plasma parameters.
ORIGINAL ARTICLE
Phosphodiesterase-5 gene (PDE5A) polymorphisms
are associated with progression of childhood
IgA nephropathy
Won-Ho Hahn Jin-Soon Suh Byoung-Soo Cho
Received: 22 February 2010 / Revised: 20 May 2010 / Accepted: 25 May 2010 / Published online: 20 June 2010
# IPNA 2010
Abstract The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimentalstudies have shown that the nitric oxide/cGMP pathwayplays an important role in the pathogenesis of glomerulonephritis,including IgA nephropathy (IgAN). The presentstudy was conducted to investigate the association among16 single nucleotide polymorphisms (SNPs) of PDE5A andchildhood IgAN. The genotyping data from 160 patientswith childhood IgAN and 454 controls showed a significantdifference in rs13124532 (codominant, P=0.005; dominant,P=0.005). Furthermore, patient subgroup analysis revealedan association between the development of proteinuria (>4and ≤4 mg/m2/h) and rs13124532 (codominant, P=0.008;dominant, P=0.011), and between the nephrotic rangeproteinuria (> 40 mg/m2/h) and rs11734241 (dominant, P= 0.035), rs12510138 (dominant, P=0.028), rs13134665
(dominant, P=0.025), rs3822192 (dominant, P= 0.027),rs10013305 (dominant, P=0.020), rs1480940 (dominant,P=0.020), rs1480936 (dominant, P=0.019), rs11947234(dominant, P=0.019), and rs2127823 (dominant, P=0.026).The pathological findings showed that rs13124532 had anassociation with podocyte foot process effacement (codominant,P=0.035; dominant, P=0.044) and with pathological
progression (codominant, P=0.046). Our results suggest thatPDE5A is associated with increased disease susceptibility,pathological progression, and development of proteinuria inchildhood IgAN.
Urinary proteome analysis identifies infants but not older
children requiring pyeloplasty
Jens Drube Petra Zürbig Eric Schiffer Esther Lau Benno Ure Sylvia Glüer Martin Kirschstein Lars Pape Stéphane Decramer Jean-Loup Bascands Joost P. Schanstra Harald Mischak Jochen H. H. Ehrich
Received: 17 August 2009 / Revised: 23 December 2009 / Accepted: 7 January 2010 / Published online: 24 February 2010
# IPNA 2010
Abstract One out of every five children suffering from ureteropelvic junction obstruction (UPJO) requires pyeloplasty. This prevalence indicates an urgent necessity to identify high-grade UPJO as early as possible to avoid renal damage. A novel non-invasive proteomic urine test has recently been introduced that is able to detect these patients at an early stage. In the study reported here, we tested this approach to assess its use in our centre and to expand its application to older children. Twenty-seven children (median
age 0.4 years, range 0.1–8.8 years) with hydronephrosis who had been scheduled a nuclear diuretic renal
scan (DR) to identify urodynamically relevant UPJO were included in our prospective study. Patients with prior surgery of the urinary tract were excluded. The urinary proteome pattern was analysed using capillary electrophoresis coupled to mass spectrometry. Of the 27 children, 11 had a relevant UPJO diagnosed by the DR. In 19 children <1 year of age, urinary proteome analysis predicted obstruction with a sensitivity of 83% (5/6) and a specificity of 92% (12/13). However, in older patients, the sensitivity
decreased to 20% (1/5) and specificity to 66% (2/3). Based on our results, the proteome pattern established by Decramer and co-workers predicts the need for surgery in infants but not in older children with UPJO.
ORIGINAL ARTICLE
Complications and long-term outcome of primary
obstructive megaureter in childhood
Charlotte Gimpel Liuda Masioniene Nenad Djakovic Jens-Peter Schenk Uwe Haberkorn
Burkhard Tönshoff Franz Schaefer
Received: 21 January 2010 / Revised: 23 February 2010 / Accepted: 1 March 2010 / Published online: 28 April 2010
# IPNA 2010
Abstract We assessed the clinical outcome of 49 children with 56 primary obstructive megaureters (POM) treated with the primarily conservative approach recommended by the 2001 German consensus guidelines. POM occurred more often in boys (71%) and on the left side (67%). Fortythree POM (77%) were treated conservatively. Four kidneys underwent immediate surgery and nine of 52 kidneys managed primarily conservatively worsened subsequently, requiring surgery. Urinary tract infections (UTI) were the most common complication (mean 1.3 per patient), with frequent hospital admission (45%). During
the first year of life, the incidence of UTIs was 55% less during prophylactic antibiotic treatment (0.94 vs.0.42 UTIs per year, p<0.05). Spontaneous regression occurred in 80% of POMs with dilated non-obstructive renogram, but in <20% with intermediate or relevant obstruction. All megaureters with <8.5 mm sonographic diameter regressed, but none over 15 mm. Eight patients had a poor outcome (partial kidney function <40% (n=6), renal atrophy (n=3)), but in seven of the patients, these findings were already present postnatally. In summary, the long-term outcome of POM appears favorable with mainly conservative treatment. UTI as the most common complication was 55% lower with antibiotic prophylaxis in infants. Adverse outcome was more closely related to congenital kidney hypoplasia than to degree of obstruction.
ORIGINAL ARTICLE
Antenatal and postnatal ultrasound in the evaluation
of the risk of vesicoureteral reflux
Serge Grazioli Paloma Parvex Laura Merlini Christophe Combescure Eric Girardin
Received: 21 December 2009 / Revised: 15 April 2010 / Accepted: 16 April 2010 / Published online: 4 June 2010
# IPNA 2010
Abstract Antenatal hydronephrosis (ANH) is a frequent anomaly detected on fetal ultrasound scans. There is no consensus recommendation for the postnatal follow-up and/or the necessity to perform a voiding cystourethrography (VCUG) to diagnose vesicoureteral reflux (VUR). We conducted a cohort/non-randomized trial of 121 patients with ANH, defined as an anterior posterior diameter (APD) ≥5mm
after the 20th week of gestation, to evaluate the ability of the antenatal and postnatal ultrasonography results to predict VUR. All infants had two successive ultrasounds at 5 days and 1 month, respectively, after birth. AVCUG was performed at 6 weeks in children with a persistent APD ≥5 mm and/or an
ureteral dilatation observed on at least one of two postnatal ultrasounds. In total, 88 patients had VCUG and nine had VUR, with five having high-grade reflux (>grade II). The risk of VUR increased significantly with the degree of APD detected on the postnatal ultrasound scan (p=0.03). The odds ratios were 5.0 [95% confidence interval (CI) 0.5– 51.2] for APD = 7–9 mm and 9.1 (95% CI 1.0–80.9) for
APD ≥10 mm. The results of this study show that among our patient cohort antenatal ultrasound was not predictive of reflux. There was, however, a relation between the importance of the postnatal renal pelvis diameter and the risk of VUR. A cut-off of 7 mm showed a fair ability of ultrasonography to predict VUR and a cut-off of 10 mm enabled all severe refluxes in the 88 patients who had a VCUG to be diagnosed.
Bleeding risk for surgical dialysis procedures in children
with hemolytic uremic syndrome
Brent R. Weil Sharon P. Andreoli Deborah F. Billmire
Received: 20 January 2010 / Revised: 23 March 2010 / Accepted: 25 March 2010 / Published online: 27 April 2010
# IPNA 2010
Abstract Children with hemolytic uremic syndrome (HUS) frequently develop acute kidney injury (AKI)
requiring renal replacement therapy (RRT). Peritoneal dialysis (PD) is commonly used. Despite high rates of thrombocytopenia, there is concern that platelet transfusions may worsen HUS by exacerbating microthrombi formation. We evaluated bleeding risk for PD catheter placement with or without central venous catheter (CVC) placement in children with HUS. Records from 1998 to 2007 were searched. Data regarding patient demographics, PD catheter placement, CVC placement, occurrence of procedure-associated bleeding, and time from insertion to removal of PD catheter were collected. Patients were
stratified according to those who received and those who did not receive platelet transfusions. Seventy-three patients were identified. Twenty-two (30%) patients received platelet transfusion while 51 (70%) did not. Mean preoperative platelet counts were 37,600±21,900/mm3 in patients receiving transfusions and 64,800±38,800/mm3 in patients not receiving transfusions. Sixty-seven children (92%) also
underwent CVC placement. There were no bleeding complications related to these procedures in either group. No differences in time to removal of the PD catheter were detected. Although caution and sound clinical judgment must be exercised, our findings suggest that PD catheter and CVC placement can be accomplished safely in most children with HUS, without need for platelet transfusion in spite of the associated thrombocytopenia.
ORIGINAL ARTICLE
Risk for anemia in pediatric chronic kidney disease patients:
a report of NAPRTCS
Meredith A. Atkinson Karen Martz Bradley A. Warady Alicia M. Neu
Received: 11 June 2009 / Revised: 26 March 2010 / Accepted: 30 March 2010 / Published online: 13 May 2010
# IPNA 2010
Abstract Previous studies in children with chronic kidney disease (CKD) have identified low hemoglobin as a risk factor for poor outcomes. A retrospective review of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) CKD registry was performed to identify the prevalence of and risk factors for anemia among children with stage 3 CKD, including both patients with low hemoglobin and those whose hemoglobin normalized with an erythropoiesis-stimulating agent (ESA). At enrollment, 2,792 patients had stage 3 CKD. Mean age was 9.5 (±0.11) years, 62.1% were male, 61.3% were white, and 43.7% had structural/urologic disease. Among 1,640 of those patients with 12 month follow-up data available for multivariate analysis, 73% met the criteria for anemia. Multivariate logistic regression analysis identifying risk factors for anemia at the 12-month follow-up revealed that, after controlling for estimated glomerular filtration rate, age >2 years, male sex, earlier era of study entry, and prescription of anti-hypertensive medications are associated with an increased risk for anemia at 12 months. In addition,
multivariate Cox proportional hazards regression analysis revealed that when patients with ESA-corrected hemoglobin are included in the definition, anemia is not associated with increased risk of progression to end stage renal disease (dialysis initiation or transplantation).