Publications by authors named "Vidar O Edvardsson"

26 Publications

  • Page 1 of 1

Are conventional stone analysis techniques reliable for the identification of 2,8-dihydroxyadenine kidney stones? A case series.

Urolithiasis 2020 Aug 12;48(4):337-344. Epub 2020 May 12.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

We have recently encountered patients incorrectly diagnosed with adenine phosphoribosyltransferase (APRT) deficiency due to misidentification of kidney stones as 2,8-dihydroxyadenine (DHA) stones. The objective of this study was to examine the accuracy of stone analysis for identification of DHA. Medical records of patients referred to the APRT Deficiency Research Program of the Rare Kidney Stone Consortium in 2010-2018 with a diagnosis of APRT deficiency based on kidney stone analysis were reviewed. The diagnosis was verified by measurement of APRT enzyme activity or genetic testing. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra of pure crystalline DHA and a kidney stone obtained from one of the confirmed APRT deficiency cases were generated. The ATR-FTIR spectrum of the kidney stone matched the crystalline DHA spectrum and was used for comparison with available infrared spectra of stone samples from the patients. Of 17 patients referred, 14 had sufficient data available to be included in the study. In all 14 cases, the stone analysis had been performed by FTIR spectroscopy. The diagnosis of APRT deficiency was confirmed in seven cases and rejected in the remaining seven cases. Comparison of the ATR-FTIR spectrum of the DHA stone with the FTIR spectra from three patients who did not have APRT deficiency showed no indication of DHA as a stone component. Misidentification of DHA as a kidney stone component by clinical laboratories appears common among patients referred to our program. Since current clinical protocols used to interpret infrared spectra for stone analysis cannot be considered reliable for the identification of DHA stones, the diagnosis of APRT deficiency must be confirmed by other methods.
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http://dx.doi.org/10.1007/s00240-020-01187-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395965PMC
August 2020

Stone recurrence among childhood kidney stone formers: results of a nationwide study in Iceland.

Urolithiasis 2020 Oct 27;48(5):409-417. Epub 2020 Feb 27.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland.

Objectives: To examine the stone recurrence rate among childhood kidney stone formers in the Icelandic population.

Materials And Methods: We retrospectively examined kidney stone recurrence in a recently reported population-based sample of 190 individuals who experienced their first stone before 18 years of age in the period 1985-2013. Of these 190 individuals, 112 (59%) were females and the median (range) age at the incident stone diagnosis was 15.0 (0.2-17.9) years. Stone recurrence was defined as an acute symptomatic episode with imaging confirmation or self-reported stone passage, new stone detected by imaging in asymptomatic patients, and suspected clinical stone episode without verification. The Kaplan-Meier method was used to assess stone-free survival and the Chi-square, Fisher's exact, Wilcoxon rank-sum and the log-rank tests to compare groups.

Results: A total of 68 (35%) individuals experienced a second stone event, 1.7 (0.9-18.9) years after the initial diagnosis. The recurrence rate was 26%, 35%, 41% and 46% after 5, 10, 15 and 20 years of follow-up, respectively. The 5-year recurrence rate increased with time and was 9%, 24% and 37% in the periods 1985-1994, 1995-2004 and 2005-2013, respectively (P = 0.005). No difference in stone recurrence was observed between the sexes (P = 0.23).

Conclusions: In our population-based sample of childhood kidney stone formers, the stone recurrence rate is similar to that reported for adults. The observed rise in stone recurrence with time may be related to closer patient follow-up in recent years or increased stone risk in general.
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http://dx.doi.org/10.1007/s00240-020-01179-6DOI Listing
October 2020

Kidney Transplant Outcomes in Patients With Adenine Phosphoribosyltransferase Deficiency.

Transplantation 2020 10;104(10):2120-2128

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD) which is characterized by 2,8-dihydroxyadenine renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients.

Methods: Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France. The CKD-EPI and CKiD equations were used to calculate glomerular filtration rate estimates. Allograft survival was analyzed employing the Kaplan-Meier method. The Wilcoxon-Mann-Whitney test was used to compare alllograft outcomes according to xanthine oxidoreductase (XOR) inhibitor treatment status at transplantation.

Results: Seventeen patients (9 females) received 22 kidney transplants. Age at first transplantation was 47.2 (14.9-67.0) years. Ten patients received XOR inhibitor therapy pretransplant (11 allografts), while 8 patients did not receive such treatment before transplantation (11 allografts). Two-year allograft survival was 91% and 55% in the 2 groups, respectively (P = 0.16). The median (range) estimated glomerular filtration rate at 2 years posttransplant was 61.3 (24.0-90.0) mL/min/1.73 m when XOR inhibitor therapy was initiated before transplantation, and 16.2 (10.0-39.0) mL/min/1.73 m (P = 0.009) when such treatment was not administered pretransplant.

Conclusions: Kidney allograft outcomes are good in APRT deficiency patients beginning XOR inhibitor therapy pretransplant. Delay in such treatment is a major cause of premature graft loss in these patients. Increased awareness among clinicians is imperative, promoting early diagnosis of APRT deficiency and pharmacotherapy initiation before kidney transplantation.
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http://dx.doi.org/10.1097/TP.0000000000003088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316615PMC
October 2020

Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.

Mol Genet Metab 2019 Sep - Oct;128(1-2):144-150. Epub 2019 May 28.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address:

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay.

Methods: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (r).

Results: The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (r = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls.

Conclusions: High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.
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http://dx.doi.org/10.1016/j.ymgme.2019.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864267PMC
April 2020

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

Nephrol Dial Transplant 2019 11;34(11):1932-1940

Department of Pediatric Nephrology, Gazi University, Ankara, Turkey.

Background: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment.

Methods: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias.

Results: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings.

Conclusions: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.
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http://dx.doi.org/10.1093/ndt/gfz069DOI Listing
November 2019

Genetics of common complex kidney stone disease: insights from genome-wide association studies.

Urolithiasis 2019 Feb 6;47(1):11-21. Epub 2018 Dec 6.

Department of Statistics, deCODE genetics, Reykjavik, Iceland.

Kidney stone disease is a common disorder in Western countries that is associated with significant suffering, morbidity, and cost for the healthcare system. Numerous studies have demonstrated familial aggregation of nephrolithiasis and a twin study estimated the heritability to be 56%. Over the past decade, genome-wide association studies have uncovered several sequence variants that confer increased risk of common complex kidney stone disease. The first reported variants were observed at the CLDN14 locus in the Icelandic population. This finding has since been replicated in other populations. The CLDN14 gene is expressed in tight junctions of the thick ascending limb of the loop of Henle, where the protein is believed to play a role in regulation of calcium transport. More recent studies have uncovered variants at the ALPL, SLC34A1, CASR, and TRPV5 loci, the first two genes playing a role in renal handling of phosphate, while the latter two are involved in calcium homeostasis. Although genetic data have provided insights into the molecular basis of kidney stone disease, much remains to be learned about the contribution of genetic factors to stone formation. Nevertheless, the progress made in recent years indicates that exciting times lie ahead in genetic research on kidney stone disease.
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http://dx.doi.org/10.1007/s00240-018-1094-2DOI Listing
February 2019

Long-term renal outcomes of APRT deficiency presenting in childhood.

Pediatr Nephrol 2019 03 15;34(3):435-442. Epub 2018 Nov 15.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary purine metabolism disorder that causes kidney stones and chronic kidney disease (CKD). The purpose of this study was to examine the course of APRT deficiency in patients who presented in childhood.

Methods: The disease course of 21 (35%) patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, who presented with manifestations of APRT deficiency and/or were diagnosed with the disorder before the age of 18 years, was studied. The effect of pharmacotherapy on renal manifestations and outcomes was thoroughly assessed.

Results: Fourteen children were placed on allopurinol, 100 (25-200) mg/day, at the age of 2.6 (0.6-16.5) years. Six of these patients had experienced kidney stone events and three had developed acute kidney injury (AKI) prior to allopurinol treatment. During 18.9 (1.7-31.5) years of pharmacotherapy, stones occurred in two patients and AKI in three. Six adult patients started allopurinol treatment, 200 (100-300) mg/day, at age 29.8 (20.5-42.4) years. Five of these patients had experienced 28 stone episodes and AKI had occurred in two. Stone recurrence occurred in four patients and AKI in two during 11.2 (4.2-19.6) years of allopurinol therapy. Lack of adherence and insufficient dosing contributed to stone recurrence and AKI during pharmacotherapy. At latest follow-up, estimated glomerular filtration rate (eGFR) was 114 (70-163) and 62 (10-103) mL/min/1.73 m in those who initiated treatment as children and adults, respectively. All three patients with CKD stages 3-5 at the last follow-up were adults when pharmacotherapy was initiated.

Conclusion: Timely diagnosis and treatment of APRT deficiency decreases renal complications and preserves kidney function.
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http://dx.doi.org/10.1007/s00467-018-4109-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349544PMC
March 2019

Incidence of kidney stone disease in Icelandic children and adolescents from 1985 to 2013: results of a nationwide study.

Pediatr Nephrol 2018 08 6;33(8):1375-1384. Epub 2018 Apr 6.

Division of Nephrology, Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.

Background: An increase in the incidence of kidney stone disease has been reported for all age groups worldwide. To examine this trend, we conducted a nationwide study of the epidemiology of kidney stones in Icelandic children and adolescents over a 30-year period.

Methods: Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases and radiologic and surgical procedure codes indicative of kidney stones in patients aged < 18 years, followed by a thorough medical record review. Age-adjusted incidence was calculated for the time intervals 1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, and 2010-2013. Time trends in stone incidence were assessed by Poisson regression. The prevalence of stone disease for the years 1999-2013 was also determined.

Results: Almost all the 190 patients (97%) that we identified had symptomatic stones, and acute flank or abdominal pain and hematuria were the most common presenting features. The total annual incidence of kidney stones increased from 3.7/100,000 in the first 5-year interval to 11.0/100,000 during the years 1995-2004 (p < 0.001) and decreased thereafter to 8.7/100,000 in 2010-2013 (p = 0.63). The incidence rise was highest in girls aged 13-17 years, in whom it rose from 9.8/100,000 in 1985-1989 to 39.2/100,000 in 2010-2013 (p < 0.001), resulting in an overall female predominance in this age group. The mean annual prevalence of stone disease in 1999-2013 was 48/100,000 for boys and 52/100,000 for girls.

Conclusion: We found a significant increase in the incidence of childhood kidney stone disease, driven by a dramatic increase of stone frequency in teenage females which is poorly understood and warrants further study.
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http://dx.doi.org/10.1007/s00467-018-3947-xDOI Listing
August 2018

Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with Adenine phosphoribosyltransferase deficiency (APRTd): A clinical trial.

Eur J Intern Med 2018 02 12;48:75-79. Epub 2017 Dec 12.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Division of Nephrology, Internal Medicine Services, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address:

Introduction: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, but significant, cause of kidney stones and progressive chronic kidney disease. The optimal treatment has not been established. The purpose of this pilot study was to compare the effect of the xanthine oxidoreductase inhibitors allopurinol and febuxostat on urinary 2,8-dihydroxyadenine (DHA) excretion in APRT deficiency patients.

Materials And Methods: Patients listed in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, currently receiving allopurinol therapy, were invited to participate. The trial endpoint was the 24-h urinary DHA excretion following treatment with allopurinol (400mg/day) and febuxostat (80mg/day). Urinary DHA was measured using a novel ultra-performance liquid chromatography - electrospray tandem mass spectrometry assay.

Results: Eight of the 10 patients invited completed the study. The median (range) 24-h urinary DHA excretion was 116 (75-289) mg at baseline, and 45 (13-112) mg after 14days of allopurinol therapy (P=0.036). At the end of the febuxostat treatment period, 4 patients had urinary DHA below detectable limits (<20ng/mL) compared with none of the participants following allopurinol treatment (P=0.036). The other 4 participants had a median 24-h urinary DHA excretion of 13.2 (10.0-13.4) mg at the completion of febuxostat therapy (P=0.036).

Conclusion: Urinary DHA excretion in APRT deficiency patients decreased with conventional doses of both allopurinol and febuxostat. Febuxostat was, however, significantly more efficacious than allopurinol in reducing DHA excretion in the prescribed doses. This finding, which may translate into improved outcomes of patients with APRT deficiency, should be confirmed in a larger sample.
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http://dx.doi.org/10.1016/j.ejim.2017.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817015PMC
February 2018

Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency.

J Chromatogr B Analyt Technol Biomed Life Sci 2016 Nov 14;1036-1037:170-177. Epub 2016 Sep 14.

University of Iceland, Reykjavik, Iceland; Division of Nephrology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address:

Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA. The UPLC-MS/MS assay was optimized by a chemometric approach for absolute quantification of DHA, utilizing isotopically labeled DHA as an internal standard. Experimental screening was conducted with D-optimal design and optimization of the DHA response was performed with central composite face design and related to the peak area of DHA using partial least square regression. Acceptable precision and accuracy of the DHA concentration were obtained over a calibration range of 100 to 5000ng/mL on three different days. The intra- and inter-day accuracy and precision coefficients of variation were well within ±15% for quality control samples analyzed in replicates of six at three concentration levels. Absolute quantification of DHA in urine samples from patients with APRT deficiency was achieved wihtin 6.5min. Measurement of DHA in 24h urine samples from three patients with APRT deficiency, diluted 1:15 (v/v) with 10mM ammonium hydroxide (NHOH), yielded a concentration of 3021, 5860 and 10563ng/mL and 24h excretion of 816, 1327 and 1649mg, respectively. A rapid and robust UPLC-MS/MS assay for absolute quantification of DHA in urine was successfully developed. We believe this method will greatly facilitate diagnosis and management of patients with APRT deficiency.
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http://dx.doi.org/10.1016/j.jchromb.2016.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445224PMC
November 2016

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

Am J Kidney Dis 2016 Nov 21;68(5):782-788. Epub 2016 Aug 21.

Department of Pediatric, Academic Medical Center, Amsterdam, the Netherlands.

Background: The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults.

Study Design: Cohort study.

Setting & Participants: We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries.

Factor: Liver transplantation.

Outcomes & Measurements: Transplantation and patient survival.

Results: 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4).

Limitations: No data for liver disease of kidney therapy recipients.

Conclusions: Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy.
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http://dx.doi.org/10.1053/j.ajkd.2016.06.019DOI Listing
November 2016

Kidney Disease in Adenine Phosphoribosyltransferase Deficiency.

Am J Kidney Dis 2016 Mar 25;67(3):431-8. Epub 2015 Dec 25.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address:

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a purine metabolism disorder causing kidney stones and chronic kidney disease (CKD). The course of nephrolithiasis and CKD has not been well characterized. The objective of this study was to examine long-term kidney outcomes in patients with APRT deficiency.

Study Design: An observational cohort study.

Setting & Participants: All patients enrolled in the APRT Deficiency Registry of the Rare Kidney Stone Consortium.

Outcomes: Kidney stones, acute kidney injury (AKI), stage of CKD, end-stage renal disease, estimated glomerular filtration rate (eGFR), and changes in eGFR.

Measurements: Serum creatinine and eGFR calculated using creatinine-based equations.

Results: Of 53 patients, 30 (57%) were females and median age at diagnosis was 37.0 (range, 0.6-67.9) years. Median duration of follow-up was 10.3 (range, 0.0-31.5) years. At diagnosis, kidney stones had developed in 29 (55%) patients and 20 (38%) had CKD stages 3 to 5, including 11 (21%) patients with stage 5. At latest follow-up, 33 (62%) patients had experienced kidney stones; 18 (34%), AKI; and 22 (42%), CKD stages 3 to 5. Of 14 (26%) patients with stage 5 CKD, 12 had initiated renal replacement therapy. Kidney stones recurred in 18 of 33 (55%) patients. The median eGFR slope was -0.38 (range, -21.99 to 1.42) mL/min/1.73m(2) per year in patients receiving treatment with an xanthine dehydrogenase inhibitor and -5.74 (range, -75.8 to -0.10) mL/min/1.73m(2) per year in those not treated prior to the development of stage 5 CKD (P=0.001).

Limitations: Use of observational registry data.

Conclusions: Progressive CKD and AKI episodes are major features of APRT deficiency, whereas nephrolithiasis is the most common presentation. Advanced CKD without a history of kidney stones is more prevalent than previously reported. Our data suggest that timely therapy may retard CKD progression.
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http://dx.doi.org/10.1053/j.ajkd.2015.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819988PMC
March 2016

Impact of nephrolithiasis on kidney function.

BMC Nephrol 2015 Aug 28;16:149. Epub 2015 Aug 28.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

Background: Kidney stone disease has been associated with reduced kidney function and chronic kidney disease (CKD). The objective of the study was to examine kidney function, body mass index (BMI) and the prevalence of cardiovascular disease, hypertension and diabetes in recurrent kidney stone formers.

Methods: A cross-sectional, case-control study comparing measures of kidney function, BMI and comorbid conditions was conducted in 195 kidney stone patients aged 18 to 70 years with recurrent clinical stone events and 390 age- and gender-matched controls. Wilcoxon-Mann-Whitney, chi-square tests and analysis of covariance were used to compare serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) between the groups.

Results: The median age of stone formers was 51 (range, 19-70) years and 108 (55 %) were males. Seventy patients (36 %) had experienced 2-4 clinical stone events, 41 (21 %) 5-10 episodes and 84 (43 %) more than 10. The median SCr was 75 (41-140) μmol/L in the stone formers and 64 (34-168) μmol/L in the control group (p < 0.001). The mean eGFR was 87 ± 20 and 104 ± 22 mL/min/1.73 m(2) in the stone formers and controls, respectively (p < 0.001). After adjustment for body size and comorbid conditions, the difference in SCr and eGFR between cases and controls remained highly significant (p < 0.001). The prevalence of CKD was 9.3 % among stone formers compared with 1.3 % in the control group (P < 0.001). Hypertension and diabetes were significantly more prevalent among the cases that also had higher BMI than controls.

Conclusions: Recurrent kidney stone formers have a significantly lower level of kidney function and a markedly higher prevalence of CKD than age- and gender-matched control subjects. The observed deleterious effect of kidney stones on kidney function appears to be independent of comorbid conditions.
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http://dx.doi.org/10.1186/s12882-015-0126-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551564PMC
August 2015

Common and rare variants associated with kidney stones and biochemical traits.

Nat Commun 2015 Aug 14;6:7975. Epub 2015 Aug 14.

1] deCODE genetics/Amgen, Inc., Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.

Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 × 10(-10)) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 × 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 × 10(-5)) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 × 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism.
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http://dx.doi.org/10.1038/ncomms8975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557269PMC
August 2015

An unusual cause of "pink diaper" in an infant: Answers.

Pediatr Nephrol 2016 Apr 1;31(4):577-80. Epub 2015 Apr 1.

Division of Pediatric Nephrology, Children's National Health System, 111 Michigan Avenue NW, Washington, DC, 20010, USA.

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http://dx.doi.org/10.1007/s00467-015-3073-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591240PMC
April 2016

An unusual cause of pink diapers in an infant: Questions and Answers.

Pediatr Nephrol 2016 Apr 1;31(4):575, 577-80. Epub 2015 Apr 1.

Division of Pediatric Nephrology, Children's National Health System, 111 Michigan Avenue NW, Washington, DC, 20010, USA.

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http://dx.doi.org/10.1007/s00467-015-3072-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591217PMC
April 2016

Comparison of aneroid and oscillometric blood pressure measurements in children.

J Clin Hypertens (Greenwich) 2013 Nov 20;15(11):776-83. Epub 2013 Sep 20.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

Limited data exist on the comparison of blood pressure (BP) measurements using aneroid and oscillometric devices. The purpose of the study was to investigate the difference in BP obtained using oscillometric and aneroid BP monitors in 9- to 10-year-old children. A total of 979 children were divided into group O, which underwent two oscillometric BP readings followed by two aneroid readings, and group A, which had BP measured in the reverse order. No significant difference was found between the mean (±standard deviation) of the two systolic BP readings obtained using the oscillometric and aneroid devices (111.5±8.6 vs 111.3±8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the oscillometric monitor (61.5±8.0 vs 64.5±6.8 mm Hg; P<.001). A significant downward trend in BP was observed with each consecutive measurement, and agreement between the two monitors was limited. Multiple BP measurements are, therefore, recommended before the diagnosis of elevated BP or hypertension is made with either method.
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http://dx.doi.org/10.1111/jch.12196DOI Listing
November 2013

The relationship between birth weight and blood pressure in childhood: a population-based study.

Am J Hypertens 2013 Jan;26(1):76-82

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

Background: Low birth weight has been associated with increased risk of hypertension later in life. The aim of this study was to evaluate the association between birth weight and blood pressure (BP) in healthy 9- to 10-year-old Icelandic children.

Methods: Each child underwent 4 seated BP measurements, and the BP percentile was calculated from the mean of the 4 measurements. Height and weight were measured and birth weight retrieved from the Icelandic Birth Registry. Birth measures and anthropometric data were correlated with BP and BP percentiles. Multivariable linear regression was employed to examine the association between BP and birth measures.

Results: Of 857 children with complete data, 445 were female (51.9%). The mean BP was 112/64 mm Hg in males and 111/63 mm Hg in females. The mean birth weight was 3714 ± 620 g. No correlation was found between birth weight and absolute BP values. A significant negative correlation between birth weight and both systolic (r = -0.09, P = 0.005) and diastolic (r = -0.08, P = 0.014) BP percentiles was observed. Gestational age did not correlate with BP.

Conclusion: In contrast to many previous studies, we found no association between birth weight and absolute BP in children. However, we observed a statistically significant negative correlation between birth weight and BP percentiles. The lack of standardized BP values may partly explain the conflicting results of previous studies in children, and we suggest that BP percentiles be examined more thoroughly in association with birth weight.
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http://dx.doi.org/10.1093/ajh/hps012DOI Listing
January 2013

Hereditary causes of kidney stones and chronic kidney disease.

Pediatr Nephrol 2013 Oct 20;28(10):1923-42. Epub 2013 Jan 20.

The Rare Kidney Stone Consortium, Mayo Clinic, Rochester, MN, USA.

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment, and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC, and PH, with an emphasis on childhood manifestations.
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http://dx.doi.org/10.1007/s00467-012-2329-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138059PMC
October 2013

Birth weight and childhood blood pressure.

Curr Hypertens Rep 2012 Dec;14(6):596-602

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

A large body of literature suggests an inverse relationship between birth weight and blood pressure in children, adolescents and adults. The most persistent findings have been observed in children with a history of low birth weight or intrauterine growth restriction, while a large number of studies carried out in populations with normally distributed birth weight have shown conflicting results. A recently reported strong direct association between high birth weight and blood pressure, and the significant positive effect of postnatal growth on blood pressure suggests that the fetal origins of adult disease hypothesis should be expanded to include the role of excessive fetal and postnatal growth. In this paper, we review recent studies on the relationship between birth weight and blood pressure in childhood, with a focus on confounding variables that may explain the conflicting results of published work in this field.
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http://dx.doi.org/10.1007/s11906-012-0311-6DOI Listing
December 2012

Temporal trends in the incidence of kidney stone disease.

Kidney Int 2013 Jan 19;83(1):146-52. Epub 2012 Sep 19.

Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.

Recent reports show an increased occurrence of kidney stone disease worldwide. To further evaluate and quantify this observation, we examined recent trends in the incidence of kidney stone disease in the adult population of Iceland over a 24-year period. Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases, radiologic and surgical procedure codes indicative of kidney stones in patients aged 18 years and older. The time trends in stone frequency of 5945 incident patients (63% men) were assessed by Poisson regression analysis. The majority of patients (90.5%) had symptomatic stone disease. The total incidence of kidney stones rose significantly from 108 per 100,000 in the first 5-year interval of the study to 138 per 100,000 in the last interval. The annual incidence of symptomatic stones did not increase significantly in either men or women. There was, however, a significant increase in the annual incidence of asymptomatic stones over time, from 7 to 24 per 100,000 for men and from 7 to 21 per 100,000 for women. The increase in the incidence of asymptomatic stones was only significant for women above 50 years of age and for men older than 40 years. Thus, we found a significant increase in the incidence of kidney stone disease resulting from increased detection of asymptomatic stones. This was largely due to a more frequent use of high-resolution imaging studies in older patients.
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http://dx.doi.org/10.1038/ki.2012.320DOI Listing
January 2013

Prevalence of hypertension in 9- to 10-year-old Icelandic school children.

J Clin Hypertens (Greenwich) 2011 Oct 14;13(10):774-9. Epub 2011 Jul 14.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

The purpose of the study was to investigate blood pressure (BP) distribution, prevalence of hypertension, and correlation between BP and body mass index (BMI) in 9- to 10-year-old Icelandic children. Two manual and two automated BP measurements were performed in 1071 Icelandic children. Children with elevated BP underwent a second BP screening, and a third screening was performed if the BP was elevated at the second visit. Hypertension was defined as BP ≥95th percentile at all three visits. White-coat hypertension was diagnosed in hypertensive children with normal 24-hour ambulatory BP. Of 970 children with complete data, 489 were girls (50.4%). The mean BP was 111/63 mm Hg in girls and 112/64 mm Hg in boys (P<.001). The prevalence of elevated BP was 13.1%, 6.0%, and 3.1% after the first, second, and third screen, respectively. The prevalence of sustained hypertension was 2.5% and an additional 0.6% had white-coat hypertension. A significant correlation between BMI and BP was observed (r=0.338, P<.001) and 8.6% of the obese children had hypertension. The prevalence of hypertension in 9- to 10-year-old Icelandic children is lower than indicated in recent reports and is associated with obesity.
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http://dx.doi.org/10.1111/j.1751-7176.2011.00496.xDOI Listing
October 2011

Blood pressure in children and target-organ damage later in life.

Pediatr Nephrol 2010 Feb 28;25(2):323-8. Epub 2009 Nov 28.

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

The aim of this study was to examine the association between blood pressure (BP) in children and adolescents and cardiovascular and renal disease in adulthood. This was a retrospective study on patients <18 years of age with an elective admission to Landspitali University Hospital in Reykjavik, Iceland, between 1950 and 1967. We recorded baseline variables including BP and invited all patients for a follow-up visit in 2008 for repeat studies. We used chi(2), Fisher's exact test, and logistic regression to examine the association between BP in childhood and outcome variables at follow-up. We identified 126 individuals (54 men) for the study. The median age (range) at childhood admission was 15 (10-17) years and the median BP was 125/80 mmHg. Median age at follow-up was 58 (42-68) years, follow-up time 43 (25-52) years, and median BP 133/75 mmHg. Eleven had died (five men) and 49 had been diagnosed with hypertension (23 men) and 12 with coronary artery disease (ten men). There was a significant correlation between the diagnosis of coronary artery disease at follow-up and childhood systolic BP (odds ratio = 1.052; P = 0.03) as well as systolic BP >/= 95th percentile (P = 0.03). Our results suggest that elevated childhood systolic BP may increase the risk of coronary artery disease in adult life. The sample size is a limiting factor, and the study should be carried out in a larger population.
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http://dx.doi.org/10.1007/s00467-009-1350-3DOI Listing
February 2010

Familiality of kidney stone disease in Iceland.

Scand J Urol Nephrol 2009 ;43(5):420-4

Children's Medical Center, Landspitali University Hospital, Reykjavik, Iceland.

Objective: The aetiology of kidney stones is multifactorial, with environmental and genetic factors contributing to the pathogenesis. The aim of this study was to assess the role of genetic factors in kidney stone disease by examining the heritability of the trait in Icelandic patients.

Material And Methods: Medical records at all major hospitals and imaging centres in Iceland were searched for diagnostic codes indicative of kidney stones, yielding a cohort of 5954 incident patients with kidney stone disease. The list of patients was cross-matched with a genealogy database that covers the entire Icelandic nation. The risk ratio (RR) and kinship coefficient (KC) were calculated to determine the risk of kidney stones in relatives of stone formers and the relatedness among kidney stone patients.

Results: The risk of kidney stones among family members of stone formers was significantly higher than in the general population. In 2959 patients with radiopaque stones, the RR ranged from 2.25 (p<0.001) for first degree relatives of probands (such as parents or siblings) to 1.07 (p<0.01) in fifth degree relatives. Moreover, for confirmed recurrent stone formers the RR of kidney stones in parents and offspring was in excess of 10 (p<0.001). The KC analysis shows that Icelandic patients with kidney stone disease are significantly more related to each other than is the average Icelander, even when considering only relatives separated by four meioses or more (p<0.05).

Conclusions: The results suggest that genetic factors may substantially influence the risk of kidney stone disease in Iceland.
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http://dx.doi.org/10.3109/00365590903151479DOI Listing
February 2010

Epidemiology of kidney stones in Iceland: a population-based study.

Scand J Urol Nephrol 2006 ;40(3):215-20

Division of Nephrology, Department of Medicine, Children's Medical Center, Landspitali University Hospital, Reykjavik, Iceland.

Objective: The prevalence of kidney stones varies greatly between ethnic groups and geographic locations, ranging from 8% to 19% in males and from 3% to 5% in females in Western countries. The aim of this study was to examine the epidemiology of kidney stones in Iceland.

Material And Methods: Data were derived from the Reykjavik Study, a population-based cohort study carried out between 1967 and 1991. All subjects answered a thorough questionnaire concerning their medical history at each visit. The lifetime prevalence of kidney stones was calculated based on the answer to the question "Have you ever been diagnosed with a kidney stone?" at each person's first visit. Incidence was calculated based on answers from subjects who had made two or more visits. Prevalence and incidence were age-standardized to the truncated world population. Family history of kidney stones was also evaluated.

Results: A total of 9039 men aged 33-80 years and 9619 women aged 33-81 years participated. Of these, 423 males and 307 females had a history of kidney stones (p=0.001). Prevalence increased significantly with age for both genders. Men aged 30-34 years had a prevalence of 2.9%, compared to 8.8% for those aged 65-69 years, whereas corresponding values for women were 2.5% and 5.0%. The age-standardized prevalence for the 30-79 years age group was 4.3% for men and 3.0% for women. No significant increase in prevalence was observed over time. The incidence was 562 per 100 000 per year among men and increased significantly with age. The incidence among women was 197 per 100 000 per year and did not differ between age groups. A family history of nephrolithiasis was present in 25% of subjects with a history of kidney stones, and in 4% of those without.

Conclusions: The incidence and prevalence of kidney stones in Icelandic women are similar to those that have been reported in other Western countries. The prevalence among men is lower that in neighboring countries but the incidence is similar. A strong family history of kidney stones suggests a genetic predisposition.
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http://dx.doi.org/10.1080/00365590600589898DOI Listing
December 2006