Epidemiology of kidney failure and glomerulonephritis in Sweden. Hereditary and non-hereditary factors

Sammanfattning: AbstractBackground: Kidney disease is recognised as an important worldwide health burden. Kidney failure is the result of acute and chronic kidney disease and is associated with morbidity and mortality. Chronic kidney failure is associated with high-costs for society and low quality of life. Kidney failure may progress to end-stage renal disease (ESRD) that requires dialysis or kidney transplantation with associated high costs for society and low quality of life for the patient. Both genetic and socioeconomic factors are increasingly recognised as important for the development of kidney disease. However, the importance of hereditary and socioeconomic factors has not been studied nationwide in a whole country for kidney failure or glomerulonephritis. Aims: The overall aim was to study the association between familial and non-hereditary factors and kidney failure and glomerulonephritis in Sweden. In the first paper, neighbourhood deprivation and ESRD was studied. In the second paper, familial risks of renal failure was determined. In the third paper, familial risks of glomerulonephritis was studied. In the fourth paper, heritability of ESRD was determined among Swedish adoptees.Methods: The thesis is based on nationwide retrospective cohort studies using Swedish registers such as the Multi-generation register and the National patient register (NPR). In the first paper, data were analysed by multilevel logistic regression, with individual-level sociodemographic factors and comorbidities at the first level and neighbourhood deprivation at the second level. In the second and third papers familial relative risks (FRRs) of kidney failure and glomerulonephritis were determined using standardized incidence ratio (SIR). In study IV logistic regression (OR=odds ratio) and tetrachoric correlation and also Falconers regression were used to determine heritability of ESRD among adoptees in Sweden.Results: In paper I, neighbourhood deprivation was modestly associated with ESRD in the full model after adjusting for individual-level sociodemographic factors and comorbidities in men OR=1.17 (95% confidence interval [CI] 1.07–1.27) and in women OR=1.18 (95% CI 1.06–1.31). In paper II the FRR was significantly increased for chronic kidney failure (SIR= 2.02, 95% 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, i.e. not specified as acute or chronic (SIR=1.25 (95% CI 0.94–1.63). Males and females had similar FRR for chronic kidney failure, (males SIR=2.04 [95% CI 1.90-2.20] versus females SIR=1.97 [95% CI 1.78-2.17]). The highest FRR was observed for chronic kidney failure among individuals aged 10-19 years (SIR=6.33 [95% CI 4.16-9.22]). In paper III FRR for acute glomerulonephritis was 3.57 (95% CI 2.77-4.53), for chronic glomerulonephritis 3.75 (95% CI 2.85-4.83), and 3.75 (95% CI 2.85-4.83) for unspecified glomerulonephritis, i.e. not specified as acute or chronic. An especially high FRR was observed if two or more relatives were affected (SIR=209.83, 95% 150.51-284.87). In paper IV odds ratio (OR) for ESRD was 6.41 (95% CI 2.96-13.89) in adoptees with a biological parent diagnosed with ESRD. The odds ratio for ESRD was not significantly increased in adoptees with an adoptive parent diagnosed with ESRD (OR=2.40, 95% CI 0.76-7.60). The heritability of ESRD was 59.5 ± 18.2 %.Conclusion: Family history of chronic kidney failure and glomerulonephritis are important risk factors for kidney diseases. Heritability of ESRD is high. Familial factors were not associated with acute kidney failure to any major degree. Genetic factors are indicated to be of importance for the burden of glomerulonephritis and chronic kidney failure and in the Swedish population. In contrast, neighbourhood deprivation is only associated with a modestly increased risk of ESRD.