Publications by authors named "Nina Battelino"

14 Publications

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Kidney Transplantation in Small Children: Association Between Body Weight and Outcome - A Report From the ESPN/ERA-EDTA Registry.

Transplantation 2021 Mar 26. Epub 2021 Mar 26.

Division of Pediatric Nephrology and Gastroenterology, Medical University Vienna, Austria ESPN/ERA-EDTA Registry, Amsterdam UMC, University of Amsterdam, Department of Medical Informatics, Amsterdam Public Health research institute, Meibergdreef 9, Amsterdam, the Netherlands; Department of Pediatric Nephrology, University Medical Center Ljubljana, Slovenia; Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway; Children's Medical Center, Landspitali-The National University Hospital of Iceland, and Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Karolinska Institutet- Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Pediatrics, Medical University Graz, Graz, Austria; Department of Pediatric Nephrology and Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Pediatric Nephrology, Erasmus MC- Sophia Children's Hospital, Rotterdam, the Netherlands; Nephrology Unit, University Children's Hospital, Zürich, Switzerland; S.C. Nefrologia e Dialisi, Azienda Ospefaliero-Universitaria di Perugia, Perugia, Italy; Department of Kidney Transplantation, Russian Children's Federal Clinical Hospital of Pirogov Russian National Research Medical University, Moscow, Russia; Department of Pediatric Nephrology, University Hospital Vall d'Hebron, Barcelona, Spain; Faculty of Medicine Seyhan, Adana Dr. Turgut Noyan Training and Research Center, Department of Pediatric Nephrology, Başkent University, Adana, Turkey; Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany; 1st Pediatric Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 1st Department of Pediatrics, Semmelweis University Budapest, Budapest, Hungary; Pediatric Nephrology Unit, University Hospital of Nantes, Nantes, France; Department ofNephrology, Kidney Transplantation & Hypertension, The Children's Memorial Health Institute, Warsaw, Poland; Department of Nephrology, University Children's hospital, Belgrade, Serbia; Department of Pediatrics, University Hospital Motol, 2nd Medical Faculty and Faculty of Medicine in Plzen, Charles University Prague and Biomedical Centre, Prague, Czech Republic; Department of Pediatric Nephrology, Evelina London Children's Hospital, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Division of Pediatrics, Department of Medicine, University of Udine, Udine, Italy; Pediatric Nephrology Unit, Bordeaux University Hospital, Bordeaux, France; Amsterdam UMC, University of Amsterdam, Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, Amsterdam, the Netherlands.

Background: Many centers accept a minimum body weight of 10 kg as threshold for kidney transplantation (Tx) in children. As solid evidence for clinical outcomes in multinational studies is lacking, we evaluated practices and outcomes in European children weighing below 10 kg at Tx.

Methods: Data were obtained from the ESPN/ERA-EDTA Registry on all children who started kidney replacement therapy (KRT) at <2.5 years of age and received a Tx between 2000 and 2016. Weight at Tx was categorized (<10 kg versus ≥10 kg) and Cox regression analysis was used to evaluate its association with graft survival.

Results: One hundred of the 601 children received a Tx below a weight of 10 kg during the study period. Primary renal disease groups were equal, but Tx <10 kg patients had lower pre-Tx weight gain per year (0.2 kg versus 2.1 kg; p<0.001) and had a higher preemptive Tx rate (23% versus 7%; p<0.001). No differences were found for posttransplant estimated glomerular filtration rates (eGFR) trajectories (p=0.23).The graft failure risk was higher in Tx <10 kg patients at 1 year (graft survival: 90% versus 95%; aHR: 3.84, 95% CI: 1.24-11.84), but not at 5 years (aHR: 1.71, 95% CI: 0.68-4.30).

Conclusions: Despite a lower 1-year graft survival rate, graft function and survival at 5 years were identical in Tx <10 kg patients when compared with Tx ≥10 kg patients. Our results suggest that early transplantation should be offered to a carefully selected group of patients weighing <10 kg.
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http://dx.doi.org/10.1097/TP.0000000000003771DOI Listing
March 2021

Citrate-induced local ionized calcium decrease in pediatric hemodialysis settings: An in-vitro study.

J Vasc Access 2021 Mar 22:11297298211002576. Epub 2021 Mar 22.

Pediatric Nephrology Department, Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Background: Citrate is instilled into the dialysis catheter to prevent clotting and to maintain patency between dialysis sessions. A significant amount of citrate leaks from the catheter at the injection time, which decreases the blood ionized calcium concentration (Ca) due to chelation. We aimed to evaluate the local impact of concentrated (i.e. 30%) citrate spilling on Ca at the catheter tip in real-time pediatric conditions.

Methods: An in-vitro model was constructed, involving an ion-selective electrode (Ca-ISE). A pre-curved catheter and the Ca-ISE were submerged in a glass vessel with the tips positioned adjacent to each other. The vessel was filled with 30 and 80 ml of normal saline with added calcium to simulate normal right atrium size in children and adults, respectively, and normal blood Ca. The amount of instilled citrate matched the filling volume of the catheter. Measurements were performed with 4% and 30% citrate solutions.

Results: The mean Ca measured at the tip of the catheter was 0.457 and 0.058 mmol/l when using 4% and 30% citrate, respectively ( < 0.001). The mean Ca recorded in 30 and 80 ml after instilling 30 % citrate was 0.058 and 0.055 mmol/l, respectively ( = 0.878).

Conclusions: The spilling of 30% citrate caused a strikingly greater decrease of Ca at the catheter tip than the standard 4% citrate. The atrial volume did not influence the test results implying similar safety concerns for pediatric and adult patients. The used static experimental setting might have overestimated the spilling effect.
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http://dx.doi.org/10.1177/11297298211002576DOI Listing
March 2021

Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome.

Pediatr Transplant 2021 May 30;25(3):e13955. Epub 2020 Dec 30.

Department of Pediatrics II, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.
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http://dx.doi.org/10.1111/petr.13955DOI Listing
May 2021

Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study.

Transplantation 2020 01;104(1):137-144

Pediatric Nephrology Unit, Bordeaux University Hospital, Bordeaux, France.

Background: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry.

Methods: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS.

Results: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children <6 years were shortest at KT and showed the greatest increase in height, whereas there was no catch-up growth in children transplanted >12.

Conclusions: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.
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http://dx.doi.org/10.1097/TP.0000000000002726DOI Listing
January 2020

Does Guidewire Exchange Influence Infection Rate Related to Catheters Used for Vascular Access in Children on Chronic Hemodialysis?

Ther Apher Dial 2017 Feb 27;21(1):57-61. Epub 2016 Oct 27.

Department of Pediatric Nephrology, Children's hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.

A central venous catheter (CVC) can either be inserted "de novo" or placed by guidewire exchange (GWE). From September 1998 to September 2015, 32 children (19 boys, 13 girls) were hemodialyzed in our unit by using a CVC. The mean age at CVC insertion was 12.6 ± 0.5 years. A total of 121 uncuffed catheters were placed, either "de novo" or by GWE in 64 (52.9%) and 57 (47.1%) cases, respectively. The most frequent cause for line revision was catheter dysfunction in 40/121 (33.1%) patients. The overall incidence of bacteremia was 1.5/1000 catheter-days. The incidence in newly inserted and GWE catheters was 1.4 and 1.7/1000 catheter-days, respectively. The difference did not reach statistical significance (P = 0.939). The infection rate correlated with patient age, and was higher in younger children (P = 0.006). GWE is an effective option of line revision, and did not influence the infection rate in our study.
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http://dx.doi.org/10.1111/1744-9987.12481DOI Listing
February 2017

End-Stage Renal Disease in an Infant With Hajdu-Cheney Syndrome.

Ther Apher Dial 2016 Jun;20(3):318-21

Department of Pediatric Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Hajdu-Cheney syndrome (HJCYS) is a rare, autosomal dominant, skeletal disorder caused by mutations in the NOTCH2 signaling pathway for which genetic testing has recently become available. Renal abnormalities are associated in at least 10% of cases. We present an 8-year-old Caucasian boy, born with multiple dysmorphic features consistent with HJCYS. Imaging of the urinary tract revealed bilateral cystic dysplastic kidneys with associated vesicoureteral reflux. Renal function has been impaired since birth and deteriorated progressively to end-stage renal disease (ESRD) by the age of two and a half years, when peritoneal dialysis was initiated and only recently renal transplantation was performed. Additional congenital abnormalities and multisystem involvement in HJCYS further complicated management, and he developed refractory anemia. Molecular diagnosis was confirmed by identification of a truncating mutation in exon 34 of NOTCH2. Although, renal abnormalities are considered an integral part of the HJCYS, published reports on ESRD are scarce. In those few published cases, where ESRD was recognized, renal failure developed either in late adolescence or adulthood. This is the first report of early ESRD occurring in a child. Patients with HJCYS may need chronic renal replacement therapy even in early childhood. The management of these children can be challenging given the multisystemic manifestations of HJCYS.
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http://dx.doi.org/10.1111/1744-9987.12444DOI Listing
June 2016

Post-Transplant Recurrence of Focal Segmental Glomerulosclerosis in a Child With Heterozygous Mutations in NPHS1 and NPHS2.

Ther Apher Dial 2016 Jun;20(3):312-7

Department of Pediatric Nephrology, University Medical Centre Ljubljana, Slovenia.

Renal transplantation is the optimal renal replacement therapy (RRT) in children, but some primary diseases can recur after transplantation, and recurrence accounts for a significant proportion of graft losses, being second only to acute rejection. The risk of disease recurrence is highest among patients with idiopathic focal segmental glomerulosclerosis (FSGS), presumably due to a circulating permeability factor. Less is clear about the genetic forms of FSGS, where the data regarding the frequency of recurrence are rather conflicting. We present a 12-year-old girl with rapidly progressive FSGS and end-stage renal disease in her native kidneys associated with heterozygous mutations in NPHS1 and in NPHS2, suffering from early post-transplant recurrence. On the basis of reviewed literature, and until further and more conclusive evidence considering pathogenicity is provided, we propose that FSGS patients with heterozygous mutations in NPHS1 or NPHS2 should be considered as having idiopathic FSGS, and post-transplant recurrence should be anticipated.
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http://dx.doi.org/10.1111/1744-9987.12443DOI Listing
June 2016

Chronic Hemodialysis in Small Children.

Ther Apher Dial 2016 Jun;20(3):302-7

Department of Pediatric Nephrology, Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.

When peritoneal dialysis is inapplicable, chronic hemodialysis (HD) becomes the only available treatment option in small children. Due to small patient size, central venous catheters (CVC) are mainly used for vascular access. Over the past 4 years, four children weighing less than 15 kg received chronic HD in our unit. A total of 848 dialysis sessions were performed. Altogether, 21 catheters were inserted. In all but one occasion, uncuffed catheters were used. Catheter revision was performed 15 times during the study period, either due to infection or catheter malfunction. The median number of catheter revisions and the median line survival was 3.0/patient-year and 53 days (range; 6-373 days), respectively. There were 14 episodes of catheter related infections requiring 11 CVC revisions (78.6%). The median rate of line infections was 2.8/patient-year. Chronic HD in small children is demanding and labor intensive. Issues pertain mainly to CVCs and limit its long-term use.
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http://dx.doi.org/10.1111/1744-9987.12441DOI Listing
June 2016

Vesicoureteral refux detection in children: a comparison of the midline-to-orifice distance measurement by ultrasound and voiding urosonography.

Pediatr Nephrol 2016 Jun 18;31(6):957-64. Epub 2016 Jan 18.

Department of Pediatric Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Background: Due to the questionable clinical role of vesicoureteral reflux (VUR) and the search for noninvasive, radiation-free procedures sufficiently reliable to detect VUR, we compared the correlation between the midline-to-orifice distance (MOD) measured by ultrasonography (US) and echo-enhanced voiding urosonography (VUS) for detecting VUR in children. The aim of the study was to determine whether measuring MOD by US could be a reliable predictor of VUR in children.

Methods: A total of 116 children, aged 0.25-84 months, with 232 potentially refluxing units were investigated simultaneously by measuring the MOD and performing VUS. Indications for cystography were urinary tract infection and follow-up of a previously detected VUR. VUS was performed after the MOD measurement. The results were analyzed with VUS as the reference method.

Results: The MOD was significantly larger in VUR grade III (10.7 mm; p = 0.003) and VUR grade II (9.9 mm; p = 0.001) refluxing units than in non-refluxing units (7.8 mm), even when controlling for the estimated volume/expected maximal capacity (Vest/Vmax) ratio. A MOD cutoff value of 7.4 mm was chosen as a predictor of either the presence or absence of VUR; the sensitivity and specificity of this cutoff measurement for VUR detection were found to be 89 and 24%, respectively.

Conclusions: Despite the statistically significant difference between the MOD of refluxing versus non-refluxing units identified in our study, the MOD measurement needs further evaluation to determine its potential value as a diagnostic tool for the detection of VUR.
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http://dx.doi.org/10.1007/s00467-015-3301-5DOI Listing
June 2016

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study.

Clin J Am Soc Nephrol 2015 May 20;10(5):767-75. Epub 2015 Feb 20.

Due to the number of contributing authors,the affiliations are provided in the Supplemental Material.

Background And Objectives: Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients.

Design, Setting, Participants, & Measurements: This study included 1237 children (0-17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure.

Results: Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR.

Conclusions: Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction.
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http://dx.doi.org/10.2215/CJN.06200614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422235PMC
May 2015

Adult height in patients with advanced CKD requiring renal replacement therapy during childhood.

Clin J Am Soc Nephrol 2014 Jan 31;9(1):92-9. Epub 2013 Oct 31.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Growth and final height are of major concern in children with ESRD. This study sought to describe the distribution of adult height of patients who started renal replacement therapy (RRT) during childhood and to identify determinants of final height in a large cohort of RRT children.

Design, Setting, Participants, & Measurements: A total of 1612 patients from 20 European countries who started RRT before 19 years of age and reached final height between 1990 and 2011 were included. Linear regression analyses were performed to calculate adjusted mean final height SD score (SDS) and to investigate its potential determinants.

Results: The median final height SDS was -1.65 (median of 168 cm in boys and 155 cm in girls). Fifty-five percent of patients attained an adult height within the normal range. Adjusted for age at start of RRT and primary renal diseases, final height increased significantly over time from -2.06 SDS in children who reached adulthood in 1990-1995 to -1.33 SDS among those reaching adulthood in 2006-2011. Older age at start of RRT, more recent period of start of RRT, cumulative percentage time on a functioning graft, and greater height SDS at initiation of RRT were independently associated with a higher final height SDS. Patients with congenital anomalies of the kidney and urinary tract and metabolic disorders had a lower final height than those with other primary renal diseases.

Conclusions: Although final height remains suboptimal in children with ESRD, it has consistently improved over time.
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http://dx.doi.org/10.2215/CJN.00890113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878688PMC
January 2014

Fulminant peritonitis presumably caused by Panton-Valentine leukocidin-positive Staphylococcus aureus in a girl on peritoneal dialysis.

Ther Apher Dial 2013 Aug;17(4):431-7

Department of Pediatric Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Peritonitis is a significant complication of peritoneal dialysis (PD) and the most common cause of technique failure. Panton-Valentine leukocidin (PVL), a cytotoxin produced by certain strains of Staphylococcus aureus (SA), causes destruction of neutrophils, and is associated with severe invasive infections. We present a 2.5-year-old girl on PD, who presented suddenly with an unusually fulminant and protracted course of peritonitis. Only a few hours after the onset of clinical signs, septic shock developed. PVL-positive methicillin-sensitive SA (MSSA) was grown and initial empiric antibiotic treatment changed to flucloxacillin and rifampicin in order to minimize toxin production. In spite of adequate antibiotic treatment and PD-catheter removal, recovery was slow. No PD-related peritonitis in children associated with PVL-producing strains have been reported so far and no specific recommendation exists for treatment. We speculate that PVL contributed to the severity and outcome of peritonitis in our patient.
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http://dx.doi.org/10.1111/1744-9987.12092DOI Listing
August 2013

A comparison of echo-enhanced voiding urosonography with X-ray voiding cystourethrography in the first year of life.

Acta Paediatr 2012 May 27;101(5):e235-9. Epub 2012 Jan 27.

Paediatric Radiology Unit, University Medical Centre, Ljubljana, Slovenia.

Background: Second-generation echo-enhanced voiding urosonography (VUS) with improved contrast-specific ultrasound (US) techniques is increasingly being used for vesicoureteric reflux (VUR) detection.

Aim: To compare VUS with X-ray voiding cystourethrography (VCUG) and to evaluate the predictive value of pelvicalyceal dilatation for detecting VUR in the first year of life.

Materials And Methods: Sixty-six children younger than one were investigated by US, VUS and VCUG. VCUG represented the reference method for VUR detection.

Results: According to VCUG, VUR was present in 16/132 (12%) renal units. VUS confirmed all these and additionally revealed VUR in 26 renal units (all together 42/132 (32%) renal units with VUR). It should be noted that all VUR detected only with VUS and missed by VCUG were of grades II and III. In 27/92 (29%) US normal and in 15/40 (37%) renal units with pelvicalyceal dilatation, VUR was detected by VUS.

Conclusion: We believe that VUS could safely replace VCUG in VUR detection in infants, with no regard to the degree of abnormality of the upper urinary tract seen on US. VCUG should be limited only to cases where bladder and/or urethra pathology are suspected.
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http://dx.doi.org/10.1111/j.1651-2227.2011.02588.xDOI Listing
May 2012

Endothelial nitric oxide synthase T(-786)C polymorphism in children and adolescents with type 1 diabetes and impaired endothelium-dependent dilatation.

Horm Res Paediatr 2011 10;76(4):248-53. Epub 2011 Sep 10.

Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, UMC, Bohoričeva 20, Ljubljana, Slovenia.

Background/aims: This study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) polymorphisms with impaired endothelium-dependent dilatation (EDD) in a cohort of children and adolescents with type 1 diabetes.

Methods: Ninety-seven children and adolescents with type 1 diabetes underwent ultrasound assessment of EDD. The association of various factors with EDD was analyzed with multivariate linear regression analysis. Genotypes were determined for the eNOS T(-786)C and 4ab polymorphisms, and their association with EDD was tested with logistic regression analysis.

Results: Thirty-three percent of children had impaired EDD. EDD was independently associated with A1c (p = 0.0005) and inversely correlated with A1c (p = 0.0037, OR = 2.14) using logistic regression analysis. The presence of any C allele at eNOS (-786) was significantly more frequent in patients with impaired EDD (OR = 2.97, 95% CI = 1.08-8.87, p = 0.03). Logistic regression analysis revealed OR of 3.09 for impaired EDD for patients with any C allele as compared to TT patients when controlling for all other covariates (p = 0.048).

Conclusion: A third of children and adolescents with type 1 diabetes had impaired EDD independently associated with A1c. The presence of any C at (-786) of the eNOS gene conveyed a significantly increased independent risk for impaired EDD.
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http://dx.doi.org/10.1159/000329549DOI Listing
February 2012