Browsing by Subject "NEPHROPATHY"

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  • Wang, Yilin; Strassl, Robert; Helanterä, Ilkka; Aberle, Stephan W.; Bond, Gregor; Hedman, Klaus; Weseslindtner, Lukas (2019)
    Background: While the pathogenicity of the two initially identified Human Polyomaviruses (HPyVs), BK Virus (BKPyV) and JC Virus (JCPyV) has been intensely studied, there is only limited data, on whether the occurrence of the recently discovered HPyVs correlates with high level BKPyV replication and progression towards Polyomavirus associated nephropathy (PVAN). Methods: Therefore, we performed a comprehensive longitudinal genoprevalence analysis of 13 HPyVs using a novel multiplex assay including 400 serum and 388 urine samples obtained from 99 kidney transplant recipients (KTRs), grouped by quantitative BKPyV DNA loads and evidence of manifest BKPyV associated disease (histologically verified PVAN, high urinary decoy cell levels and concurrent decrease of renal function). Results: In total, 3 different non-BKPyV/JCPyV HPyVs, Human Polyomavirus 9, Merkel Cell Polyomavirus (MCPyV) and Trichodysplasia Spinulosa associated Polyomavirus were detected in 11 blood and 21 urine samples from 21 patients. Although DNAemia of these viruses occurred more frequently during high level BKPyV DNAemia and PVAN, the increase of the detection frequency due to progression of BKPyV replication did not reach statistical significance for blood samples. The positive detection rate of MCPyV in urine, however, was significantly higher during BKPyV DNAemia in 19 KTRs of our cohort who suffered from histologically verified PVAN (p=0.005). In one individual with PVAN, continuous long-term shedding of MCPyV in urine was observed. Conclusion: In our cohort the recently discovered HPyVs HPyV9, TSPyV and MCPyV emerged in blood from KTRs with variable kinetics, while detection of MCPyV DNAuria occurred more frequently during BKPyV DNAemia in patients with PVAN.
  • Strausz, Satu; Havulinna, Aki S.; Tuomi, Tiinamaija; Bachour, Adel; Groop, Leif; Mäkitie, Antti; Koskinen, Seppo; Salomaa, Veikko; Palotie, Aarno; Ripatti, Samuli; Palotie, Tuula (2018)
    Objective To evaluate if obstructive sleep apnoea (OSA) modifies the risk of coronary heart disease, type 2 diabetes (T2D) and diabetic complications in a gender-specific fashion. Design and setting A longitudinal population-based study with up to 25-year follow-up data on 36 963 individuals (>500 000 person years) from three population-based cohorts: the FINRISK study, the Health 2000 Cohort Study and the Botnia Study. Main outcome measures Incident coronary heart disease, diabetic kidney disease, T2D and all-cause mortality from the Finnish National Hospital Discharge Register and the Finnish National Causes-of-Death Register. Results After adjustments for age, sex, region, high-density lipoprotein (HDL) and total cholesterol, current cigarette smoking, body mass index, hypertension, T2D baseline and family history of stroke or myocardial infarction, OSA increased the risk for coronary heart disease (HR=1.36, p=0.0014, 95% CI 1.12 to 1.64), particularly in women (HR=2.01, 95% CI 1.31 to 3.07, p=0.0012). T2D clustered with OSA independently of obesity (HR=1.48, 95% CI 1.26 to 1.73, p=9.11x10(-7)). The risk of diabetic kidney disease increased 1.75-fold in patients with OSA (95% CI 1.13 to 2.71, p=0.013). OSA increased the risk for coronary heart disease similarly among patients with T2D and in general population (HR=1.36). All-cause mortality was increased by OSA in diabetic individuals (HR=1.35, 95% CI 1.06 to 1.71, p=0.016). Conclusion OSA is an independent risk factor for coronary heart disease, T2D and diabetic kidney disease. This effect is more pronounced even in women, who until now have received less attention in diagnosis and treatment of OSA than men.
  • Barlovic, Drazenka Pongrac; Tikkanen-Dolenc, Heidi; Groop, Per-Henrik (2019)
    Purpose of Review Physical activity is a fundamental part of lifestyle management in diabetes care. Although its benefits are very well recognized in the general population and in people with type 2 diabetes, much less is known about the effects of exercise in type 1 diabetes. In particular, exercise effects in relation to diabetic kidney disease (DKD) are understudied. Some uncertainties about physical activity recommendations stem from the fact that strenuous exercise may worsen albuminuria immediately after the activity. However, in middle-aged and older adults without diabetes, observational studies have suggested that physical activity is associated with a decreased risk of rapid kidney function deterioration. In this review, we focus on the role of physical activity in patients with DKD and type 1 diabetes.\ Recent Findings Hereby, we present data that show that in individuals at risk of DKD or with established DKD, regular moderate-to-vigorous physical activity was associated with reduced incidence and progression of DKD, as well as reduced risk of cardiovascular events and mortality. Summary Therefore, regular moderate-to-vigorous exercise should become a central part of the management of individuals with type 1 diabetes, in the absence of contraindications and accompanied with all needed educational support for optimal diabetes management.
  • The FinnDiane Study Group; Jansson, Fanny J.; Forsblom, Carol; Harjutsalo, Valma; Thorn, Lena M.; Wadén, Johan; Elonen, Nina; Ahola, Aila J.; Saraheimo, Markku; Groop, Per-Henrik (2018)
    Aims/hypothesis Our aim was to assess regression of albuminuria and its clinical consequences in type 1 diabetes. Methods The analysis included 3642 participants from the Finnish Diabetic Nephropathy (FinnDiane) Study with a 24 h urine sample and a history of albuminuria available at baseline. A total of 2729 individuals had normal AER, 438 a history of microalbuminuria and 475 a history of macroalbuminuria. Regression was defined as a change from a higher category of albuminuria pre-baseline to a lower category in two out of the three most recent urine samples at baseline. The impact of regression on cardiovascular events (myocardial infarction, stroke, coronary procedure) and mortality was analysed over a follow-up of 14.0 years (interquartile range 11.9-15.9). Results In total, 102 (23.3%) individuals with prior microalbuminuria and 111 (23.4%) with prior macroalbuminuria had regressed at baseline. For individuals with normal AER as a reference, the age-adjusted HRs (95% CI) for cardiovascular events were 1.42 (0.75, 2.68) in individuals with regression from microalbuminuria, 2.62 (1.95, 3.54) in individuals with sustained microalbuminuria, 3.15 (2.02, 4.92) in individuals with regression from macroalbuminuria and 5.49 (4.31, 7.00) in individuals with sustained macroalbuminuria. Furthermore, for all-cause and cardiovascular mortality rates, HRs in regressed individuals were comparable with those with sustained renal status at the achieved level (i.e. those who did not regress but remained at the most advanced level of albuminuria noted pre-baseline). Conclusions/interpretation Progression of diabetic nephropathy confers an increased risk for cardiovascular disease and premature death. Notably, regression reduces the risk to the same level as for those who did not progress.
  • Finndiane Study Grp; Lithovius, Raija; Harjutsalo, Valma; Mutter, Stefan; Gordin, Daniel; Forsblom, Carol; Groop, Per-Henrik (2020)
    OBJECTIVE To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in individuals with type 1 diabetes stratified by stages of DN, renal function, and sex. RESEARCH DESIGN AND METHODS This prospective study included a nationally representative cohort of individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (+/- 6 months) baseline visit (1995-2008). Individuals (N= 1,103) were divided into three groups:1) RH,2) uncontrolled blood pressure (BP) but no RH, and3) controlled BP. DN progression, cardiovascular events, and deaths were identified from the individuals' health care records and national registries until 31 December 2015. RESULTS At baseline, 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (hazard ratio 1.95 [95% CI 1.37, 2.79],P= 0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44],P= 0.8) compared with those who had controlled BP. The risk of incident CHD, incident stroke, and all-cause mortality was higher in individuals with RH compared with those who had controlled BP but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria, the risk of stroke remained higher in the RH compared with the controlled BP group (3.49 [81.20, 10.15],P= 0.02). CONCLUSIONS Our findings highlight the importance of identifying and providing diagnostic and therapeutic counseling to these very-high-risk individuals with RH.
  • Finndiane Study Grp; Pongrac Barlovic, Drazenka; Harjutsalo, Valma; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik (2020)
    Aims/hypothesis Lipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes. Methods Individuals (n = 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria. Results During a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median [IQR] for eGFR change:
  • Ahola, Aila J.; Harjutsalo, Valma; Thorn, Lena; Freese, Riitta; Forsblom, Carol; Mäkimattila, Sari; Groop, Per-Henrik; FinnDiane Study Grp (2017)
    Diet is a major modifiable lifestyle factor that may affect the components of the metabolic syndrome. We aimed to investigate the association between relative proportions of macronutrients and the components of the metabolic syndrome in a population of individuals with type 1 diabetes. In all, 791 individuals without nephropathy, with plausible energy intake and known metabolic syndrome status, taking part in the Finnish Diabetic Nephropathy Study were included in the analyses. Dietary data were collected with a diet record. The association between the relative macronutrient intake and the outcome variables were analysed using multivariable nutrient density substitution models. The relative proportions of dietary macronutrients or fatty acids were not associated with the presence of the metabolic syndrome. In men, however, favouring carbohydrates over fats was associated with lower odds of the waist component, whereas favouring either carbohydrates or fats over proteins was associated with lower odds of the blood pressure component of the metabolic syndrome. In women, substituting carbohydrates for fats was associated with lower HDL-cholesterol concentration. Substituting carbohydrates or fats for alcohol or protein was, in men, associated with lower systolic blood pressure. To conclude, the relative distribution of macronutrients may have some relevance for the metabolic syndrome.