Familial Risks of Kidney Failure in Sweden: A Nationwide Family Study

PLOS ONE, Nov 2014

Background The value of family history as a risk factor for kidney failure has not been determined in a nationwide setting. Aim This nationwide family study aimed to determine familial risks for kidney failure in Sweden. Methods The Swedish multi-generation register on 0–78-year-old subjects were linked to the Swedish patient register and the Cause of death register for 1987–2010. Individuals diagnosed with acute kidney failure (n = 10063), chronic kidney failure (n = 18668), or unspecified kidney failure (n = 3731) were included. Kidney failure patients with cystic kidney disease, congenital kidney and urinary tract malformations, urolithiasis, and rare inherited kidney syndromes, and hyperoxaluria were excluded. Standardized incidence ratios (SIRs) were calculated for individuals whose parents/siblings were diagnosed with kidney failure compared to those whose parents or siblings were not. Results The concordant (same disease) familial risks (sibling/parent history) were increased for chronic kidney failure SIR = 2.02 (95% confidence interval, CI 1.90–2.14) but not for acute kidney failure SIR = 1.08 (95% CI 0.94–1.22) and for unspecified kidney failure SIR = 1.25 (95% CI 0.94–1.63). However, the discordant (different disease) familial risk for acute kidney failure SIR = 1.19 (95% CI 1.06–1.32) and unspecified kidney failure SIR = 1.63 (95% CI 1.40–1.90) was significantly increased in individuals with a family history of chronic kidney failure. The familial risk for chronic kidney failure was similar for males SIR = 2.04 (95% CI 1.90–2.20) and females SIR = 1.97 (95% CI 1.78–2.17). Familial risks for chronic kidney failure were highest at age of 10–19 years SIR = 6.33 (95% CI 4.16–9.22). Conclusions The present study shows that family history is an important risk factor for chronic kidney failure but to a lower degree for acute kidney failure and unspecified kidney failure.

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Familial Risks of Kidney Failure in Sweden: A Nationwide Family Study

November Familial Risks of Kidney Failure in Sweden: A Nationwide Family Study Delshad Saleh Akrawi * 0 2 Xinjun Li 0 2 Jan Sundquist 0 1 2 Kristina Sundquist 0 2 Bengt 2 0 Center for Primary Care Research, Lund University/Region Sk a ne , Malm o , Sweden, 1 Stanford Prevention Research Center, Stanford University School of Medicine , Stanford, California , United States of America 2 Editor: Zhanjun Jia, University of Utah School of Medicine , United States of America Background: The value of family history as a risk factor for kidney failure has not been determined in a nationwide setting. Aim: This nationwide family study aimed to determine familial risks for kidney failure in Sweden. Methods: The Swedish multi-generation register on 0-78-year-old subjects were linked to the Swedish patient register and the Cause of death register for 19872010. Individuals diagnosed with acute kidney failure (n510063), chronic kidney failure (n518668), or unspecified kidney failure (n53731) were included. Kidney failure patients with cystic kidney disease, congenital kidney and urinary tract malformations, urolithiasis, and rare inherited kidney syndromes, and hyperoxaluria were excluded. Standardized incidence ratios (SIRs) were calculated for individuals whose parents/siblings were diagnosed with kidney failure compared to those whose parents or siblings were not. Results: The concordant (same disease) familial risks (sibling/parent history) were increased for chronic kidney failure SIR52.02 (95% confidence interval, CI 1.902.14) but not for acute kidney failure SIR51.08 (95% CI 0.94-1.22) and for unspecified kidney failure SIR51.25 (95% CI 0.94-1.63). However, the discordant (different disease) familial risk for acute kidney failure SIR51.19 (95% CI 1.061.32) and unspecified kidney failure SIR51.63 (95% CI 1.40-1.90) was significantly increased in individuals with a family history of chronic kidney failure. The familial risk for chronic kidney failure was similar for males SIR52.04 (95% CI 1.90-2.20) and females SIR51.97 (95% CI 1.78-2.17). Familial risks for chronic kidney failure were highest at age of 10-19 years SIR56.33 (95% CI 4.16-9.22). Conclusions: The present study shows that family history is an important risk factor for chronic kidney failure but to a lower degree for acute kidney failure and unspecified kidney failure. - Introduction Materials and Methods Predictor and outcome variables Individual variables included in the analysis Statistical Analysis (5-year groups), sex, socioeconomic status, time period (5-year groups), geographic region of residence, and comorbidities. 95% confidence intervals (95% CIs) were calculated assuming a Poisson distribution [29]. Data values are accurate to two decimals places. All analyses were performed using SAS version 9.2 (Institute, Cary, NC, USA). Ethical Considerations Familial risk of kidney failure 0, 1, 1, 5, 5, and 7 years. For three children, the diagnosis was unknown (two had ICD diagnosis5Z038 and one had no additional diagnosis). One child was prematurely born (,28 weeks) and/or had a very low birth weight (,1000 g) (ICD-95765A), one had unspecified infectious gastroenteritis (ICD-95009B), and one had gastroenteritis with Escherichia coli (ICD-95008A). No significant increased risk for unspecified kidney failure was observed for any other age groups. However, the familial risk for all kidney failure was increased in all age groups (Table 4). had little effect. Siblings with an age difference of ,5 years showed a SIR for all kidney failure of 1.64 (95% CI, 1.50 to 1.79) compared with 1.72 (95% CI, 1.59 to 1.86) for those with an age difference of >5 years. The concordant sibling risk for chronic kidney failure was 2.36 (95% CI 2.072.67) for siblings with an age difference of ,5 years, compared with 2.65 (95% CI, 2.38 to 2.95) for those with an age difference of >5 years. Additional analyses Unspecified kidney failure All kidney failure Subtype of kidney failure in offspring/ sibling Acute kidney failure Familial risks were adjusted for age, sex, time period, region of residence, socioeconomic status, and comorbidities. Bold type: 95% CI does not include 1.00. O5observed number of cases with family history of kidney failure; SIR5standardized incidence ratio; CI5confidence interval. Sensitivity analysis Table S4 presents concordant and discordant familial risks (parent/siblings) after exclusion of patients with kidney cancer in parents/offspring. This did not change the results to any major degree. Probands with any type of kidney failure Family history (parent/sibling) Parents history Paternal history Maternal history Sibling history Subtype of kidney failure in offspring/ siblings Acute kidney failure Familial risks were adjusted for age, sex, time period, region of residence, socioeconomic status, and comorbidities. Bold type: 95% CI does not include 1.00. O5observed number of cases with family history of kidney failure; SIR5standardized incidence ratio; CI5confidence interval. Discussion The present study is the first nationwide follow-up study to evaluate the familial risks of chronic, acute, and unspecified kidney failure among offspring/siblings of affected individuals. The results confirm previous case-series and case-control studies, which showed that familial factors are important for chronic kidney failure [918]. The present study adds follow-up data for a whole country. Previously a follow-up study only showed moderately increased familial risk Familial risks were adjusted for age, sex, time period, region of residence, socioeconomic status, and comorbidities. Bold type: 95% CI does not include 1.00. O5observed number of cases with family history of kidney failure; SIR5standardized incidence ratio; CI5confidence interval. Supporting Information Table S1. Familial risk of concordant kidney failure among siblings by age at difference in siblings. doi:10.1371/journal.pone.0113353.s001 (DOCX) Table S2. Familial risk of concordant and discordant kidney failure in men and women. doi:10.1371/journal.pone.0113353.s002 (DOCX) Table S3. Familial risk (sibling/parent history) of concordant and discordant kidney failure in males and females by age at diagnosis. doi:10.1371/journal.pone.0113353.s003 (DOCX) Table S4. Familial risk (sibling/offspring) of concordant and discordant kidney failure in males and females, after excluding kidney cancer in parents/offspring. doi:10.1371/journal.pone.0113353.s004 (DOCX) Table S5. Familial risk of concordant and discordant kidney failure in males and females, follow-up 20012010. doi:10.1371/journal.pone.0113353.s005 (DOCX) Acknowledgments Author Contributions Conceived and designed the experiments: DSA BZ KS JS XL. Performed the experiments: DSA BZ XL. Analyzed the data: DSA BZ KS JS XL. Contributed reagents/materials/analysis tools: DSA BZ JS KS XL. Wrote the paper: DSA. 1. Levey AS , Coresh J ( 2012 ) Chronic kidney disease . Lancet 379 : 165 - 180 . 2. Levey AS , Atkins R , Coresh J , Cohen EP , Collins AJ , et al. ( 2007 ) Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes . Kidney Int 72 : 247 - 259 . 3. Weiner DE , Tighiouart H , Amin MG , Stark PC , Macleod B , et al. ( 2004 ) Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies . J Am Soc Nephrol 15 : 1307 - 1315 . 4. Satko SG , Freedman BI ( 2004 ) The importance of family history on the development of renal disease . Curr Opin Nephrol Hypertens 13 : 337 - 341 . 5. Satko SG , Sedor JR , Iyengar SK , Freedman BI ( 2007 ) Familial clustering of chronic kidney disease . Semin Dial 20 : 229 - 236 . 6. Witasp A , Nordfors L , Carrero JJ , Luttropp K , Lindholm B , et al. ( 2012 ) Genetic studies in chronic kidney disease: interpretation and clinical applicability . J Nephrol 25 : 851 - 864 . 7. Drawz PE , Sedor JR ( 2011 ) The genetics of common kidney disease: a pathway toward clinical relevance . Nat Rev Nephrol 7 : 458 - 468 . 8. O'Seaghdha CM , Fox CS ( 2011 ) Genome-wide association studies of chronic kidney disease: what have we learned ? Nat Rev Nephrol 8 : 89 - 99 . 9. Ferguson R , Grim CE , Opgenorth TJ ( 1988 ) A familial risk of chronic renal failure among blacks on dialysis ? J Clin Epidemiol 41 : 1189 - 1196 . 10. Freedman BI , Spray BJ , Tuttle AB , Buckalew VM Jr ( 1993 ) The familial risk of end-stage renal disease in African Americans . Am J Kidney Dis 21 : 387 - 393 . 11. Lei HH , Perneger TV , Klag MJ , Whelton PK , Coresh J ( 1998 ) Familial aggregation of renal disease in a population-based case-control study . J Am Soc Nephrol 9 : 1270 - 1276 . 12. O'Dea DF , Murphy SW , Hefferton D , Parfrey PS ( 1998 ) Higher risk for renal failure in first-degree relatives of white patients with end-stage renal disease: A population-based study . Am J Kidney Dis 32 : 794 - 801 . 13. Bergman S , Key BO , Kirk KA , Warnock DG , Rostant SG ( 1996 ) Kidney disease in the first-degree relatives of African-Americans with hypertensive end-stage renal disease . Am J Kidney Dis 27 : 341 - 346 . 14. Jurkovitz C , Franch H , Shoham D , Bellenger J , McClellan W ( 2002 ) Family members of patients treated for ESRD have high rates of undetected kidney disease . Am J Kidney Dis 40 : 1173 - 1178 . 15. McClellan W , Speckman R , McClure L , Howard V , Campbell RC , et al. ( 2007 ) Prevalence and characteristics of a family history of end-stage renal disease among adults in the United States population: Reasons for Geographic and Racial Differences in Stroke (REGARDS) renal cohort study . J Am Soc Nephrol 18 : 1344 - 1352 . 16. Jurkovitz C , Hylton TN , McClellan WM ( 2005 ) Prevalence of family history of kidney disease and perception of risk for kidney disease: A population-based study . Am J Kidney Dis 46 : 11 - 17 . 17. Freedman BI , Soucie JM , McClellan WM ( 1997 ) Family history of end-stage renal disease among incident dialysis patients . J Am Soc Nephrol 8 : 1942 - 1945 . 18. Freedman BI , Volkova NV , Satko SG , Krisher J , Jurkovitz C , et al. ( 2005 ) Population-based screening for family history of end-stage renal disease among incident dialysis patients . Am J Nephrol 25 : 529 - 535 . 19. Hsu CY , Iribarren C , McCulloch CE Darbinian J, Go AS ( 2009 ) Risk factors for end-stage renal disease: 25-year follow-up . Arch Intern Med 169 : 342 - 350 . 20. Li PK , Burdmann EA , Mehta RL , World Kidney Day Steering Committee 2013 ( 2013 ) Acute kidney injury: global health alert . Transplantation 95 : 653 - 657 . 21. O'Seaghdha CM , Fox CS ( 2011 ) Genome-wide association studies of chronic kidney disease: what have we learned ? Nat Rev Nephrol 8 : 89 - 99 . 22. K ottgen A , Glazer NL , Dehghan A , Hwang SJ , Katz R , et al. ( 2009 ) Multiple loci associated with indices of renal function and chronic kidney disease . Nat Genet 41 : 712 - 717 . 23. K ottgen A , Pattaro C , B oger CA, Fuchsberger C , Olden M , et al. ( 2010 ) New loci associated with kidney function and chronic kidney disease . Nat Genet 42 : 376 - 384 . 24. Burton PR , Tobin MD , Hopper JL ( 2005 ) Key concepts in genetic epidemiology . Lancet 366 : 941 - 951 . 25. Lawlor DA , Mishra GD ( 2009 ) Family matters. Deigning, analyzing and understanding family based studies in life course epidemiology . New York : Oxford University Press. 26. Rosen M , Hakulinen T ( 2005 ) Use of disease registers . In: Handbook of epidemiology. Berlin: SpringerVerlag . pp. 231 - 251 . 27. Z oller B , Li X , Sundquist J , Sundquist K ( 2011 ) Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden . Circulation 124 : 1012 - 1020 . 28. Hemminki K , Vaittinen P , Dong C , Easton D ( 2001 ) Sibling risks in cancer: clues to recessive or Xlinked genes? Br J Cancer 84 : 388 - 391 . 29. Breslow NE , Day NE ( 1987 ) Statistical methods in cancer research. Volume II-The design and analysis of cohort studies . IARC Sci Publ 82 : 1 - 406 . 30. Jenssen GR , Hovland E , Bangstad HJ , Nyg ard K , Vold L , et al. ( 2014 ) The incidence and aetiology of acute kidney injury in children in Norway between 1999 and 2008 . Acta Paediatr Jul 10 . Epub ahead of print doi: 10.1111/apa.12742 31. The National Board of Health and Welfare ( 2000 ) [Validity of the diagnoses from the Swedish In-Care Register 1987 and 1995] . In Swedish. Stockholm: Epidemiologiskt Centrum, National Board of Health and Welfare . 32. Ludvigsson JF , Andersson E , Ekbom A , Feychting M , Kim JL , et al. ( 2011 ) External review and validation of the Swedish national inpatient register . BMC Public Health 11 : 450 .


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Delshad Saleh Akrawi, Xinjun Li, Jan Sundquist, Kristina Sundquist, Bengt Zöller. Familial Risks of Kidney Failure in Sweden: A Nationwide Family Study, PLOS ONE, 2014, DOI: 10.1371/journal.pone.0113353