Publications by authors named "Sari Aaltonen"

33 Publications

Letermovir treatment for CMV infection in kidney and pancreas transplantation: a valuable option for complicated cases.

Clin Transplant 2021 Nov 19:e14537. Epub 2021 Nov 19.

Department of Transplantation and Liver Surgery Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Cytomegalovirus (CMV) infection remains a major challenge in solid organ transplantation. Ganciclovir has changed the prognosis, but with the expense of possible viral resistance. New antiviral drugs, such as letermovir, have not been studied sufficiently in kidney and pancreas transplant recipients. We reviewed abdominal organ transplants recipients with CMV infection from the national transplant registry and identified patients treated with letermovir from electronic medical records. We report on letermovir treatment in one kidney and three simultaneous pancreas and kidney (SPK) transplant patients with refractory or ganciclovir-resistant CMV infection (UL54/ UL97 mutation). In SPK patients, persistent leukopenia undermined immunosuppressive and antiviral treatment, favoring life-threatening bacterial infections or ganciclovir resistance. All patients achieved viral clearance after letermovir monotherapy of 1.5 to 6 months. Letermovir was well tolerated and leukopenia resolved. Adjustments of calcineurin inhibitor doses were challenging. One acute rejection occurred because of under immunosuppression. After the end of treatment, recurrent low-grade CMV-DNAemia was common requiring reinitiating antiviral therapy to achieve viral clearance. To conclude, letermovir was a well-tolerated valuable option for the treatment of refractory or resistant CMV infection in kidney and pancreas transplantation. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/ctr.14537DOI Listing
November 2021

Genetic and Environmental Effects on the Individual Variation and Continuity of Participation in Diverse Physical Activities.

Med Sci Sports Exerc 2021 Dec;53(12):2495-2502

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FINLAND.

Introduction: Participation in diverse physical activities has beneficial health effects. However, little is known on how genetic and environmental factors affect this trait. Thus, we examined to what extent these factors explain participation in diverse leisure-time physical activities from late adolescence to adulthood using a twin study design.

Methods: The participants were Finnish twins who reported their participation in diverse leisure-time physical activities at ages 17 (n = 5429) and 34 yr (n = 4246). The number of physical activities engaged in was analyzed using applications of structural linear modeling for twin data.

Results: On average, the total number of physical activities engaged in during leisure time was slightly over three at both ages and in both sexes, with moderate heritability estimates (40%-58%) from adolescence to adulthood. Environmental factors shared by co-twins (e.g., childhood family environment) influenced only in adolescence, being higher for women. Environmental influences unique to each co-twin explained the remaining variances (34%-57%), being higher at age 34 yr. Participation in diverse leisure-time physical activities correlated moderately between ages 17 and 34 yr (men: rtrait = 0.30, 95% confidence interval [CI] = 0.25-0.35; women: rtrait = 0.26, 95% CI = 0.22-0.31). In addition, genetic influences on participation in physical activities correlated moderately between adolescence and adulthood (rA = 0.51, 95% CI = 0.39-0.64, and 0.44, 95% CI = 0.34-0.55, respectively). These common genetic influences explained 93% of the trait correlations found in men and 85% in women.

Conclusions: Genetic and unique environmental influences explain a large proportion of variation in the number of leisure-time physical activities. However, the estimates vary by age and sex. Common genetic background mainly explains the continuity of the participation in diverse leisure-time physical activities between adolescence and adulthood.
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http://dx.doi.org/10.1249/MSS.0000000000002744DOI Listing
December 2021

The Associations Between Leisure-Time Physical Activity and Academic Performance: A Twin Study.

J Phys Act Health 2021 Jun 17;18(8):998-1003. Epub 2021 Jun 17.

Background: Both genetic and environmental influences have been shown to contribute to the association between physical activity and overall academic performance. The authors examined whether leisure-time physical activity (LTPA) shares genetic and environmental variances between spelling, essay writing, reading aloud, reading comprehension, and mathematics in early adolescence. Moreover, they investigated whether genetic polymorphisms associated with physical activity behavior affect these academic skills.

Methods: Participants were 12-year-old Finnish twins (n = 4356-4370 twins/academic skill, 49% girls). Academic skills were assessed by teachers, and LTPA was self-reported. Polygenic scores for physical activity behavior were constructed from the UK Biobank. Quantitative genetic modeling and linear regression models were used to analyze the data.

Results: The trait correlations between LTPA and academic skills were significant but weak (r = .05-.08). The highest trait correlation was found between LTPA and mathematics. A significant genetic correlation was revealed between LTPA and essay writing (rA = .14). Regarding polygenic scores of physical activity, the highest correlations were found with reading comprehension, spelling, and essay writing, but these results only approached statistical significance (P values = .09-.15).

Conclusions: The authors' results suggest that reading and writing are the academic skills that most likely share a common genetic background with LTPA.
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http://dx.doi.org/10.1123/jpah.2020-0746DOI Listing
June 2021

Diagnostic Dilemma of Thrombotic Microangiopathy in Pregnancy.

Kidney Int Rep 2021 Feb 13;6(2):529-533. Epub 2020 Nov 13.

Department of Bacteriology and Immunology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.ekir.2020.10.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879120PMC
February 2021

Motives for physical activity in older men and women: A twin study using accelerometer-measured physical activity.

Scand J Med Sci Sports 2020 Aug 20;30(8):1409-1422. Epub 2020 Apr 20.

Faculty of Sport and Health Sciences, University of Jyväskylä, University of Jyväskylä, Jyväskylä, Finland.

Motives for physical activity may vary considerably by age, sex, and the level of physical activity. We aimed to examine motives for physical activity in older men and women with different physical activity levels as well as whether genetic and/or environmental factors explain those motives. Finnish twins (mean age 72.9 years, 262 full twin pairs) self-reported their motives for physical activity. Time spent on moderate-to-vigorous physical activity was monitored using a hip-worn accelerometer. Comparisons between the different physical activity groups of older twins (n = 764-791/motive dimension) were analyzed using the Wald test, and effect sizes were calculated as Cohen's d. Quantitative genetic modeling was used to estimate genetic and environmental contributions. For both sexes, the most frequently reported motives for physical activity were physical fitness, health maintenance, and psychological well-being. Conforming to others' expectations was more important for men than for women (P < .001, Cohen's d = 0.38), while appearance (P = .001 Cohen's d = -0.24) and psychological well-being (P = .02, Cohen's d = -0.17) were highlighted by women. Most of the motive dimensions differed significantly between the physically active and inactive individuals. It was estimated that 5%-42% of the variation in motives was contributed by genetic factors and 58%-95% by environmental factors. The result that environmental factors contribute in a great deal to motives indicates that interventions to motivate physically inactive older individuals to be physically active can be successful. However, personalized interventions are needed because sex and the level of physical activity were found to be associated with older individuals' motives for physical activity.
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http://dx.doi.org/10.1111/sms.13673DOI Listing
August 2020

Cross-sectional associations between the diversity of sport activities and the type of low back pain in adulthood.

Eur J Sport Sci 2020 Oct 4;20(9):1277-1287. Epub 2020 Jan 4.

Department of Public Health, University of Helsinki, Helsinki, Finland.

Leisure-time physical activity has a complex relationship with low back pain (LBP). Thus, we aimed to investigate whether the diversity of sport activities is associated with the type of LBP. In the FinnTwin16 study, 4246 (55% females) Finnish twins at mean age 34.1 years replied to a health behaviour survey in 2010-2012. Based on the participation in different sport activities, we created two measures of diversity: quantity (i.e. the number of sport activities: 1, 2, 3, 4 and ≥5) and quality (i.e. the type of sport activity: endurance, strength, body care, etc.). Based on the frequency, duration and type of LBP, we created three groups: no history of LBP lasting more than one day, radiating LBP and non-radiating LBP. The associations between the quantity and quality of sport activities and the type of LBP were investigated with logistic regression analyses. Participation in ≥5 sport activities associated with less radiating and non-radiating LBP in analyses pooled across sex (odds ratio 0.46, 95% CI 0.30-0.69 and 0.66, 0.44-0.99, respectively). However, the associations attenuated after adjusting for several confounders. Participation in endurance sports was associated with less radiating (0.58, 0.43-0.76) and non-radiating (0.60, 0.44-0.81) LBP, whereas strength sports and body care only with less radiating LBP (0.76, 0.58-1.00 and 0.26, 0.09-0.74, respectively) adjusted for all sport types. On a sport-specific level, running and cycling were associated with less radiating and non-radiating LBP. In adulthood, the diversity of sport activities, particularly participation in endurance sports, may be associated with less radiating and non-radiating LBP.
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http://dx.doi.org/10.1080/17461391.2019.1706642DOI Listing
October 2020

FinnTwin16: A Longitudinal Study from Age 16 of a Population-Based Finnish Twin Cohort.

Twin Res Hum Genet 2019 12 3;22(6):530-539. Epub 2019 Dec 3.

Department of Public Health, University of Helsinki, Helsinki, Finland.

The purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders, weight development, obesity, life satisfaction and personality. To date, five waves of data collection have been completed and the sixth is now planned. Data from the FT16 cohort have contributed to several hundred studies and many substudies, with more detailed phenotyping and collection of omics data completed or underway. FT16 has also contributed to many national and international collaborations.
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http://dx.doi.org/10.1017/thg.2019.106DOI Listing
December 2019

FinnTwin12 Cohort: An Updated Review.

Twin Res Hum Genet 2019 10 23;22(5):302-311. Epub 2019 Oct 23.

Institute for Molecular Medicine FIMM, Helsinki, Finland.

This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983-1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene-environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.
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http://dx.doi.org/10.1017/thg.2019.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108792PMC
October 2019

Outpatient Kidney Biopsy: A Single Center Experience and Review of Literature.

Nephron 2020 2;144(1):14-20. Epub 2019 Oct 2.

Abdominal Center, Nephrology, Helsinki University and Helsinki University Hospital, Helsinki, Finland.

Background: A kidney biopsy is an important tool in managing kidney diseases. Bleeding is the most significant complication. The biopsy can be performed as an inpatient or an outpatient procedure with a shorter post-biopsy bed rest and monitoring period. It is cost-effective, but raises some questions about patient safety. At Helsinki University Hospital, the majority of elective kidney biopsies have been performed as outpatient procedures since 2010. The aim of this study was to retrospectively evaluate the safety and risk factors of this protocol.

Methods: We collected data from all patients undergoing an elective outpatient biopsy of a native or transplanted kidney following the outpatient protocol between January 2011 and February 2016. We recorded the data on the biopsy procedure and complications: bleeding (hematoma or macrohematuria), severe pain, death, or "other" (infection, accidental puncture of another organ). A complication was classified as major, if it required interventions such as transfusion or radiological or surgical intervention.

Results: Over a 5-year period, 824 (448 native and 326 transplant kidney) patients were biopsied. In total, 94 (11.4%) had a complication, but only 4 patients (0.5%) had a major complication; no deaths were recorded. All major and 70 minor complications emerged during post-biopsy monitoring (4-6 h). Patients with complications were younger (p = 0.001), female (p < 0.001), and had lower hemoglobin (p = 0.001) than those without. Transplant biopsies were associated with fewer complications than native kidney biopsies (p= 0.002).

Conclusions: In selected patients, an outpatient kidney biopsy is a relatively safe procedure.
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http://dx.doi.org/10.1159/000503255DOI Listing
March 2021

Physical Activity and Academic Performance: Genetic and Environmental Associations.

Med Sci Sports Exerc 2020 02;52(2):381-390

Department of Social Research, University of Helsinki, Helsinki, FINLAND.

Introduction: Physical activity and academic performance are believed to be associated. Though both traits are partially heritable, it remains unclear whether these traits also share a genetic and/or environmental background in common. We aimed to examine to what extent leisure time physical activity and academic performance share genetic and environmental effects from early adolescence to young adulthood.

Methods: Participants were Finnish twins (2543-2693 individuals/study wave) who reported their leisure-time physical activity at ages 12, 14, 17, and 24 yr. Academic performance was assessed with teacher-reported grade point averages at ages 12 and 14 yr and by self-reported educational levels at ages 17 and 24 yr. Bivariate quantitative genetic modeling at each age and between different ages was performed to decompose the trait correlation between academic performance and physical activity into genetic and environmental components.

Results: The trait correlations between leisure-time physical activity and academic performance were positive, but modest at most (rtrait = 0.08-0.22 in males, and 0.07-0.18 in females). The genetic correlations between leisure-time physical activity and academic performance were higher than the trait correlations (rA = 0.17-0.43 in males, and 0.15-0.25 in females). Common genetic influences explained 43% to 100% of the trait correlations. Environmental influences shared by cotwins between leisure-time physical activity and academic performance were also correlated (rC = 0.27-0.54 in males, and 0.21-0.69 in females) explaining 41% to 100% of the trait correlations. Unique environmental influences were correlated only in females (rE = 0.10-0.15).

Conclusions: Both common genetic background and shared family environment (i.e., familial background) partially account for the associations observed between leisure-time physical activity and academic performance. However, the estimates vary in magnitude by age.
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http://dx.doi.org/10.1249/MSS.0000000000002124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962558PMC
February 2020

Is diversity of leisure-time sport activities associated with low back and neck-shoulder region pain? A Finnish twin cohort study.

Prev Med Rep 2019 Sep 4;15:100933. Epub 2019 Jul 4.

Department of Public Health, P.O. Box 20 (Tukholmankatu 8 B), FI-00014, University of Helsinki, Helsinki, Finland.

This study investigates cross-sectional and longitudinal associations between the diversity of leisure-time sport activities and the frequencies of low back pain (LBP) and neck-shoulder region pain (NSP) in twins, including a cross-sectional within-pair design to adjust for potential familial confounding. Finnish twins born in 1975-79 (FinnTwin16 study) reported participation in leisure-time sport activities at the mean ages of 17 (1992-96) ( = 5096, 54% females) and 34 years (2010-12) ( = 3731, 57% females). Diversity assessed as the number of sport activities was categorized as 1, 2, 3, 4, and ≥ 5, excluding inactive individuals. The frequencies of LBP ( = 3201) and NSP ( = 3207), reported at age 34, were categorized as never/seldom, monthly, or weekly pain. Cross-sectional and longitudinal individual-based associations between the number of sport activities and the frequency of LBP and NSP were investigated with multinomial logistic regression analyses, adjusting for multiple confounders. Cross-sectionally, participation in ≥5 sport activities, compared to 1 sport, was associated with significantly less weekly LBP (OR = 0.63, 95%CI = 0.43-0.90), but not with NSP. Longitudinally, participation in several sport activities in adolescence had no significant association with LBP or NSP in adulthood. Cross-sectional within-pair analyses were conducted among twin pairs discordant for LBP ( = 507) and NSP ( = 579). The associations between monozygotic and dizygotic twin pairs were similar in LBP-discordant pairs but differed within NSP-discordant pairs. Participation in ≥5 sport activities in adulthood may be associated with less weekly LBP, but not with monthly LBP or the frequency of NSP. However, within-pair analyses for NSP suggest confounding due to shared familial factors.
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http://dx.doi.org/10.1016/j.pmedr.2019.100933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626109PMC
September 2019

Parental Education and Genetics of BMI from Infancy to Old Age: A Pooled Analysis of 29 Twin Cohorts.

Obesity (Silver Spring) 2019 05 5;27(5):855-865. Epub 2019 Apr 5.

Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Objective: The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions.

Methods: A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling.

Results: Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia.

Conclusions: Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.
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http://dx.doi.org/10.1002/oby.22451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478550PMC
May 2019

The Interplay between Genes and Psychosocial Home Environment on Physical Activity.

Med Sci Sports Exerc 2018 04;50(4):691-699

Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, FINLAND.

Introduction: Genetic factors contribute to individual differences in physical activity, but it remains uncertain whether the magnitude of the genetic effects is modified by variations in home environments. We aimed to examine to what extent the psychosocial home environment in childhood and adolescence modifies the genetic influences on leisure time physical activity in young adulthood.

Methods: Participants were Finnish twins (N = 3305) who reported their leisure time physical activity at age 24 yr. The psychosocial home environment was assessed by twins at ages 12, 14, and 17 yr, as well as by their parents when the twins were age 12 yr. Gene-environment interaction modeling was performed with OpenMx software.

Results: Parental ratings of positive home atmosphere as well as the twins' ratings of both positive home atmosphere at age 14 yr and lower relational tensions at ages 12 and 14 yr predicted higher leisure time physical activity levels in young adulthood (regression coefficients = 0.33-0.64). Parental perceptions as well as the twins' perceptions of positive home atmosphere at ages 14 and 17 yr increased the additive genetic variation (moderation effects: 0.55, 95% confidence interval [CI] = 0.29-0.80; 0.60, 95% CI = 0.26-1.05; and 0.52, 95% CI = 0.19-0.87, respectively). The twins' ratings of positive home atmosphere at age 12 yr and lower relational tensions at ages 12 and 14 yr increased the unique environmental variation of their subsequent physical activity (moderation effects: 0.46, 95% CI = 0.19-0.60; 0.48, 95% CI = 0.29-0.64; and 0.85, 95% CI = 0.12-0.95, respectively).

Conclusions: A psychosocial home environment that is warm and supportive in childhood and adolescence not only increases the mean level of subsequent leisure time physical activity in young adulthood but also modifies the genetic and environmental variances in leisure time physical activity.
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http://dx.doi.org/10.1249/MSS.0000000000001506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856601PMC
April 2018

Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region: an individual-based pooled analysis of 40 twin cohorts.

Am J Clin Nutr 2017 Aug 5;106(2):457-466. Epub 2017 Jul 5.

The Danish Twin Registry.

Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m)], but factors modifying these variance components are poorly understood. We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
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http://dx.doi.org/10.3945/ajcn.117.153643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525120PMC
August 2017

Leisure-Time Physical Activity and Academic Performance: Cross-Lagged Associations from Adolescence to Young Adulthood.

Sci Rep 2016 12 15;6:39215. Epub 2016 Dec 15.

Department of Social Research, University of Helsinki, P.O. Box 54, FIN-00014 University of Helsinki, Finland.

Physical activity and academic performance are positively associated, but the direction of the association is poorly understood. This longitudinal study examined the direction and magnitude of the associations between leisure-time physical activity and academic performance throughout adolescence and young adulthood. The participants were Finnish twins (from 2,859 to 4,190 individuals/study wave) and their families. In a cross-lagged path model, higher academic performance at ages 12, 14 and 17 predicted higher leisure-time physical activity at subsequent time-points (standardized path coefficient at age 14: 0.07 (p < 0.001), age 17: 0.12 (p < 0.001) and age 24: 0.06 (p < 0.05)), whereas physical activity did not predict future academic performance. A cross-lagged model of co-twin differences suggested that academic performance and subsequent physical activity were not associated due to the environmental factors shared by co-twins. Our findings suggest that better academic performance in adolescence modestly predicts more frequent leisure-time physical activity in late adolescence and young adulthood.
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http://dx.doi.org/10.1038/srep39215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156951PMC
December 2016

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994.

Elife 2016 12 14;5. Epub 2016 Dec 14.

Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, United States.

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
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http://dx.doi.org/10.7554/eLife.20320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156525PMC
December 2016

Genetic and environmental effects on body mass index from infancy to the onset of adulthood: an individual-based pooled analysis of 45 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) study.

Am J Clin Nutr 2016 Aug 13;104(2):371-9. Epub 2016 Jul 13.

Centre of Human Genetics, University Hospitals Leuven, Leuven, Belgium; Department of Obstetrics and Gynaecology, Ghent University Hospitals, Ghent, Belgium;

Background: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking.

Objectives: We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments.

Design: Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling.

Results: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions.

Conclusions: Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity.
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http://dx.doi.org/10.3945/ajcn.116.130252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962159PMC
August 2016

Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts.

Sci Rep 2016 06 23;6:28496. Epub 2016 Jun 23.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.
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http://dx.doi.org/10.1038/srep28496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917845PMC
June 2016

Leisure-time physical activity and intra-abdominal fat in young adulthood: A monozygotic co-twin control study.

Obesity (Silver Spring) 2016 05;24(5):1185-91

Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

Objective: To investigate differences in abdominal fat compartments between young adult monozygotic twin pairs discordant for leisure-time physical activity.

Methods: Ten young adult male monozygotic twin pairs (age range 32-36 years) discordant for leisure-time physical activity during the past 3 years were systematically selected from a population-based Finnish twin cohort. Magnetic resonance image at the level of the L2-L3 intervertebral disc was used to predict intra-abdominal and subcutaneous abdominal fat masses. Dietary intake was assessed with a 4-day food diary.

Results: Inactive twins had 31% more intra-abdominal fat than their active co-twins (mean difference 0.52 kg, 95% CI 0.12 to 0.91, P = 0.016), whereas the difference in subcutaneous abdominal fat was only 13% (P = 0.21) and 3% in body mass index (P = 0.28). Intraperitoneal fat mass was 41% higher among inactive twins compared to their active co-twins (mean difference 0.41 kg, 95% CI 0.11 to 0.70, P = 0.012). Dietary intake did not differ between co-twins.

Conclusions: A lower level of physical activity is related to greater accumulation of intra-abdominal fat among healthy adult males in their mid-30s. The findings highlight the importance of leisure-time physical activity independent of genes and diet in the prevention of intra-abdominal fat accumulation from early adulthood onward.
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http://dx.doi.org/10.1002/oby.21465DOI Listing
May 2016

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

Twin Res Hum Genet 2016 Apr;19(2):112-24

The Hebrew University of Jerusalem,Jerusalem,Israel.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
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http://dx.doi.org/10.1017/thg.2016.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100672PMC
April 2016

Motor Development and Physical Activity: A Longitudinal Discordant Twin-Pair Study.

Med Sci Sports Exerc 2015 Oct;47(10):2111-8

1Department of Public Health, University of Helsinki, Helsinki, FINLAND, 2Department of Social Research, University of Helsinki, Helsinki, FINLAND; 3Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN; 4Department of Psychology, University of Jyvaskyla, Jyvaskyla, FINLAND, 5Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, FINLAND, 6Institute for Molecular Medicine, University of Helsinki, Helsinki, FINLAND; and 7Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, FINLAND.

Introduction: Previous longitudinal research suggests that motor proficiency in early life predicts physical activity in adulthood. Familial effects including genetic and environmental factors could explain the association, but no long-term follow-up studies have taken into account potential confounding by genetic and social family background. The present twin study investigated whether childhood motor skill development is associated with leisure-time physical activity levels in adulthood independent of family background.

Methods: Altogether, 1550 twin pairs from the FinnTwin12 study and 1752 twin pairs from the FinnTwin16 study were included in the analysis. Childhood motor development was assessed by the parents' report of whether one of the co-twins had been ahead of the other in different indicators of motor skill development in childhood. Leisure-time physical activity (MET·h·d) was self-reported by the twins in young adulthood and adulthood. Statistical analyses included conditional and ordinary linear regression models within twin pairs.

Results: Using all activity-discordant twin pairs, the within-pair difference in a sum score of motor development in childhood predicted the within-pair difference in the leisure-time physical activity level in young adulthood (P < 0.001). Within specific motor development indicators, learning to stand unaided earlier in infancy predicted higher leisure-time MET values in young adulthood statistically significantly in both samples (FinnTwin12, P = 0.02; and FinnTwin16, P = 0.001) and also in the pooled data set of the FinnTwin12 and FinnTwin16 studies (P < 0.001). Having been more agile than the co-twin as a child predicted higher leisure-time MET values up to adulthood (P = 0.03).

Conclusions: More advanced childhood motor development is associated with higher leisure-time MET values in young adulthood at least partly independent of family background in both men and women.
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http://dx.doi.org/10.1249/MSS.0000000000000650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576714PMC
October 2015

Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project.

Twin Res Hum Genet 2015 Oct 4;18(5):557-70. Epub 2015 Sep 4.

Istituto Superiore di Sanità - National Center for Epidemiology,Surveillance and Health Promotion,Rome,Italy.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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http://dx.doi.org/10.1017/thg.2015.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605819PMC
October 2015

The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits.

Twin Res Hum Genet 2015 Aug 27;18(4):348-60. Epub 2015 May 27.

Istituto Superiore di Sanità -- National Center for Epidemiology,Surveillance and Health Promotion,Rome,Italy.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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http://dx.doi.org/10.1017/thg.2015.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696543PMC
August 2015

Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

Med Sci Sports Exerc 2015 Mar;47(3):509-18

1Department of Health Sciences, University of Jyväskylä, Jyväskylä, FINLAND; 2Department of Applied Physics, University of Eastern Finland, Kuopio, FINLAND; 3Department of Psychology, University of Jyväskylä, Jyväskylä, FINLAND; 4Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, FINLAND; 5Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, FINLAND; 6Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, FINLAND; and 7Institute for Molecular Medicine, University of Helsinki, Helsinki, FINLAND.

Purpose: The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity.

Methods: From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses.

Results: According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001.

Conclusions: Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.
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http://dx.doi.org/10.1249/MSS.0000000000000437DOI Listing
March 2015

Factors behind leisure-time physical activity behavior based on Finnish twin studies: the role of genetic and environmental influences and the role of motives.

Biomed Res Int 2014 8;2014:931820. Epub 2014 Apr 8.

Department of Public Health, The Hjelt Institute, University of Helsinki, P.O. Box 41, Mannerheimintie 172, 00014 Helsinki, Finland ; Institute for Molecular Medicine, University of Helsinki, P.O. Box 21, Tukholmankatu 8, 00014 Helsinki, Finland ; Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, P.O. Box 30, 00271 Helsinki, Finland.

Different approaches are being taken to clarify the role of various factors in the development of physical activity behaviors. Genetic studies are a new area of physical activity research and also the motives for physical activity have been widely studied. The purpose of this paper is to review the findings emerging from the longitudinal genetic studies on leisure-time physical activity and to evaluate the associations between motivational factors and leisure-time physical activity. The focus is to review recent findings of longitudinal Finnish twin studies. The results of the latest longitudinal Finnish twin studies point to the existence of age-specific genetic and environmental influences on leisure-time physical activity. Variations in environmental factors seem to explain the observed deterioration in leisure-time physical activity levels. A decline in genetic influences is seen first from adolescence to young adulthood and again from the age of thirty to the mid-thirties. In the Finnish twin participants, mastery, physical fitness, and psychological state were the major motivation factors associated with consistent leisure-time physical activity behavior. The results also indicate that intrinsic motivation factors may be important for engagement in leisure-time physical activity.
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http://dx.doi.org/10.1155/2014/931820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997869PMC
December 2014

Interventions to prevent sports related injuries: a systematic review and meta-analysis of randomised controlled trials.

Sports Med 2014 Apr;44(4):473-86

Tampere Research Center of Sports Medicine, UKK Institute, Kaupinpuistonkatu 1, PL 30, 33500, Tampere, Finland,

Background: The effects of methods to prevent injuries have been studied in several systematic reviews. However, no meta-analysis taking into account all randomised controlled intervention trials aiming at the prevention of sports injuries has been published.

Objective: To summarise the effects of sports injury prevention interventions.

Design: Systematic review and meta-analysis of randomised controlled trials.

Data Sources: PubMed, MEDLINE, SPORTDiscus, the Cochrane Central Register of Controlled Trials, CINAHL, PEDro, and Web of Science, searched in September 2013. The reference lists of retrieved articles and reviews were hand searched.

Eligibility Criteria For Selecting Studies: To be selected articles had to examine the effects of any preventive intervention on sports injuries, be randomised/quasi-randomised and controlled trials, published in a peer-reviewed journal. The outcome of the trial had to be injury rate or the number of injured individuals.

Results: Of the 5580 articles retrieved after a search of databases and the relevant bibliography, 68 randomised controlled trials were included in the systematic review and 60 trials were included in the meta-analysis. Insoles (OR 0.51, 95% CI 0.32-0.81), external joint supports (OR 0.40, 95% CI 0.30-0.53), and specific training programmes (OR 0.55, 95% CI 0.46-0.66) appeared to be effective in reducing the risk of sports injuries. Stretching (OR 0.92, 95% CI 0.80-1.06), modified shoes (OR 1.23, 95% CI 0.81-1.87), and preventive videos (OR 0.86, 95% CI 0.44-1.68) seemed not to be effective.

Conclusions: This meta-analysis showed that certain interventions can reduce the risk of sports injuries. There were limitations regarding the quality of the trials, generalisability of the results, and heterogeneity of the study designs. In future, the mechanisms behind effective methods and the most beneficial elements of preventive training programmes need to be clarified.
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http://dx.doi.org/10.1007/s40279-013-0136-8DOI Listing
April 2014

Genetic and environmental influences on longitudinal changes in leisure-time physical activity from adolescence to young adulthood.

Twin Res Hum Genet 2013 Apr 28;16(2):535-43. Epub 2013 Feb 28.

Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

The aim of this study was to estimate genetic and environmental influences on the longitudinal evolution of leisure-time physical activity habits from adolescence to young adulthood. Data were gathered at four time points, at mean ages 16.2, 17.1, 18.6, and 24.5 years. At baseline, the sample comprised 5,216 monozygotic and dizygotic twins, born 1975-1979, and, at the last follow-up point, of 4,531 monozygotic and dizygotic twins. Physical activity volume was assessed as frequency of leisure-time physical activity and participants were categorized into three groups: inactive, moderately active, and active. Genetic and environmental influences were estimated using a multivariate, longitudinal Cholesky decomposition with a 'multifactorial liability threshold' approach. The results suggest that, in both sexes the heritability of leisure-time physical activity remained moderate (~43-52%) during adolescence, declining to ~30% in young adulthood. Shared environmental influences increased from adolescence (~18-26%) to young adulthood (43% in men and 49% in women). Specific environmental influences remained relatively stable during the total follow-up (~20-30%). New genetic, shared, and specific environmental influences at every follow-up point were suggested by the low correlations across occasions. In conclusion, the study demonstrated gender differences in genetic influences in the evolution of leisure-time physical activity habits from adolescence to young adulthood. However, shared environmental influences, especially in women, were crucial in explaining longitudinal changes in leisure-time physical activity. These outcomes emphasize the need of gender-specific measures to promote physical activity habits during young adulthood.
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http://dx.doi.org/10.1017/thg.2013.9DOI Listing
April 2013

Membranoproliferative glomerulonephritis complicating infection.

Clin Kidney J 2013 Feb 9;6(1):35-39. Epub 2012 Dec 9.

Department of Nephrology , Helsinki University Central Hospital , Helsinki , Finland.

Background: () is a common microbe of the skin and mucosal surfaces rarely considered a true pathogen. However, it has been reported to cause serious infections. Subsequent ongoing low-grade antigenaemia may, in turn, lead to an immune-mediated glomerulonephritis with various renal histologies including that of membranoproliferative glomerulonephritis (MPGN).

Methods: Here, we describe two cases of infection-induced MPGN and their treatment.

Results: Both patients were successfully treated by the eradication of the infection. One patient also received immunosuppressive medication prior to the correct diagnosis.

Conclusions: A vigorous exclusion of infection is warranted in MPGN type I or immune-complex-mediated MPGN and may sometimes yield a diagnosis of secondary MPGN.
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http://dx.doi.org/10.1093/ckj/sfs165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094392PMC
February 2013

[The puzzle of glomerulonephritides is closer to be saved].

Duodecim 2012 ;128(16):1663-9

HYKS, medisiininen tulosyksikkö, nefrologian klinikka.

Glomerulonephritides are a mixed group of kidney diseases, the diagnosis and classification of which being based on renal biopsy. Over the last few years revolutionary findings on the pathogenesis of these diseases have been made. Above all the previously obscure immunopathogenesis of focal segmental glomerulosclerosis and membranous nephropathy have begun to unravel. New ideas are bringing new diagnostic methods to the diagnostics and monitoring of these diseases. At the same time their treatments are increasingly focusing on the underlying immunological phenomena.
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October 2012

Outcome of idiopathic membranous nephropathy using targeted stepwise immunosuppressive treatment strategy.

Nephrol Dial Transplant 2011 Sep 21;26(9):2871-7. Epub 2011 Mar 21.

Division of Nephrology, Department of Medicine, Helsinki University Hospital, Helsinki, Finland.

Background: The natural course of idiopathic membranous nephropathy (IMN) is variable and the role of immunosuppressive therapy is controversial. In our centre, the strategy has been conservative: the immunomodulating treatment (glucocorticoids and/or cyclosporine A) has been targeted to patients at high risk of developing progressive renal disease and the cytotoxic drugs have been used cautiously. The aim of this retrospective observational study was to evaluate the efficacy of this strategy.

Methods: We evaluated the clinical course and outcome of IMN patients diagnosed between 1993 and 2003. Risk assessment was done during an observation period of ≥6 months after the initial renal biopsy. Patients were followed up until death, the development of end-stage renal disease (ESRD) or the last clinical visit (before December 2006). Treatments and their side effects were recorded.

Results: One hundred and forty-two patients with membranous nephropathy were diagnosed of which 81 were idiopathic. The clinical course of 76 IMN patients (38 high risk and 38 low risk) were followed up [mean duration 66 ± 40 (median 59) months]. Thirty-five patients were treated with immunosuppressive drugs, and at last follow-up, 71% of them were in complete or partial remission. The overall response rate of this therapy was 83%. 11% of the high-risk patients had reached ESRD. For the high-risk patients, 10-year survival (alive with glomerular filtration rate >10 mL/min/1.73 m(2)) was 79%. No major side effects were observed.

Conclusions: This study suggests that targeted, stepwise, cytotoxic drug-sparing immunosuppressive treatment in IMN was associated with favourable renal, as well as overall survival among patient at risk of developing ESRD.
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http://dx.doi.org/10.1093/ndt/gfq841DOI Listing
September 2011
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