Browsing by Subject "nephropathy"

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  • Manca, Maria Laura; Solini, Anna; Haukka, Jani K.; Sandholm, Niina; Forsblom, Carol; Groop, Per Henrik; Ferrannini, Ele (2021)
    Background: Chronic kidney disease (CKD) shows different clinical features in Types1 (T1D) and 2 diabetes (T2D). Metabolomics have recently provided useful contribution to the identification of biomarkers of CKD progression in either form of the disease. However, no studies have so far compared plasma metabolomics between T1D and T2D in order to identify differential signatures of progression of estimated glomerular filtration rate (eGFR) decline. Methods: We used two large cohorts of T1D (from Finland) and T2D (from Italy) patients followed up to 7 and 3 years, respectively. In both groups, progression was defined as the top quartile of yearly decline in eGFR. Pooled data from the two groups were analysed by univariate and bivariate random forest (RF), and confirmed by bivariate partial least squares (PLS) analysis, the response variables being type of diabetes and eGFR progression. Results: In progressors, yearly eGFR loss was significantly larger in T2D [-5.3 (3.0), median (interquartile range)mL/min/1.73 m2/year] than T1D [-3.7 (3.1) mL/min/1.73 m2/year; P = 0.018]. Out of several hundreds, bivariate RF extracted 22 metabolites associated with diabetes type (all higher in T1D than T2D except for 5-methylthioadenosine, pyruvate and β-hydroxypyruvate) and 13 molecules associated with eGFR progression (all higher in progressors than non-progressors except for sphyngomyelin). Three of the selected metabolites (histidylphenylalanine, leucylphenylalanine, tryptophylasparagine) showed a significant interaction between disease type and progression. Only eight metabolites were common to both bivariate RF and PLS. Conclusions: Identification of metabolomic signatures of CKD progression is partially dependent on the statistical model. Dual analysis identified molecules specifically associated with progressive renal impairment in both T1D and T2D.
  • Lehtonen, Sanna; Lewko, Barbara (2019)
  • Jalonen, Emmi (Helsingin yliopisto, 2019)
    Tyypin 1 diabetesta esiintyy Suomessa eniten maailmassa. Tärkeimmät estettävissä olevat lisäsairastavuutta aiheuttavat tekijät ovat sairauden mikro- ja makrovaskulaariset komplikaatiot. The Finnish Diabetic Nephropathy Study eli FinnDiane -seurantatutkimus selvittää näiden lisäsairauksien syntymekanismeja, erityisesti munuaissairauden (nefropatia) osalta, joka tunnetaan merkittävänä kuolleisuuden riskitekijänä. Diabeettinen nefropatia lisää huomattavasti sydän- ja verisuonisairastavuutta, mikä on diabetesta sairastavien potilaiden johtava kuolinsyy. Pulssipaine on systolisen ja diastolisen verenpaineen erotus. Se on noninvasiivinen tapa mitata valtimoiden jäykkyyttä, ja esimerkiksi valtimoiden keskiverenpaineeseen verrattuna huomioi paremmin sekä systolisen että diastolisen verenpaineen vaihtelun. Aiemmassa tutkimuksessamme on osoitettu diabetesta sairastavien kiihtyneestä valtimoiden jäykistymisestä johtuva varhaisempi pulssipaineen nousu jo nuoremmalla iällä. Tässä tutkimuksessa halusimme selvittää, ennustaako kohonnut pulssipaine kuolleisuutta tyypin 1 diabetesta sairastavilla henkilöillä. Tutkimusaineisto koostui 4439 FinnDiane-tutkimukseen osallistuneesta aikuispotilaasta, joilla diabetes oli todettu alle 40-vuotiaana ja joiden insuliinihoito oli aloitettu vuoden sisään diagnoosista. Tiedot kerättiin kyselylomakkeella, jota täydennettiin vastaanotolla. Tiedot kuolemasta saatiin Tilastokeskuksen kuolinrekisteristä. Tietoa kerättiin vuosien 1994-2014 välisenä aikana. Seuranta-ajan mediaani oli 14 vuotta. 713 kuoli seuranta-aikana. Jaoimme potilaat pulssipaineen suhteen neljänneksiin, joita vertailimme Coxin regressio –menetelmää käyttäen. Kolmen matalimman neljänneksen välillä ei saatu merkittävää eroa kuolleisuudessa, mutta korkeimman pulssipaineen neljänneksessä kuolleisuus oli 1,4-kertainen edellisiin verrattuna. Lisäksi analysoimme aineistoa pulssipaineen mediaanin suhteen kahtia jaettuna. Korkeampi pulssipaine liittyi yhdenmukaisesti suurempaan kuolleisuuteen. Muita pulssipaineeseen liittyvän kuolleisuuden riskitekijöitä olivat nefropatia, miessukupuoli ja huono glukoositasapaino.
  • Vapalahti, K; Virtala, A. M; Joensuu, T. A; Tiira, K; Tahtinen, J; Lohi, H (2016)
  • Keindl, Magdalena; Fedotkina, Olena; du Plessis, Elsa; Jain, Ruchi; Bergum, Brith; Mygind Jensen, Troels; Laustrup Moller, Cathrine; Falhammar, Henrik; Nystrom, Thomas; Catrina, Sergiu-Bogdan; Jorneskog, Gun; Groop, Leif; Eliasson, Mats; Eliasson, Bjorn; Brismar, Kerstin; Nilsson, Peter M.; Berg, Tore Julsrud; Appel, Silke; Lyssenko, Valeriya (2020)
    Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic beta cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naive to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care.
  • Weseslindtner, Lukas; Hedman, Lea; Wang, Yilin; Strassl, Robert; Helanterä, Ilkka; Aberle, Stephan W.; Bond, Gregor; Hedman, Klaus (2020)
    In kidney transplant recipients (KTRs), BK polyomavirus (BKPyV) replication may progress to polyomavirus-associated nephropathy (PVAN). In this retrospective study, we assessed the chemokine CXCL10 in urine and blood samples consecutively acquired from 85 KTRs who displayed different stages of BKPyV replication and eventually developed PVAN. In parallel to progression toward PVAN, CXCL10 gradually increased in blood and urine, from baseline (prior to virus replication) to BKPyV DNAuria (median increase in blood: 42.15 pg/ml, P = 0.0156), from mere DNAuria to low- and high-level BKPyV DNAemia (median increase: 52.60 and 87.26 pg/ml, P = 0.0010 and P = 0.0002, respectively) and peaked with histologically confirmed PVAN (median increase: 145.00 pg/ml, P <0.0001). CXCL10 blood and urine levels significantly differed among KTRs with respect to simultaneous presence of human cytomegalovirus (P <0.001) as well as in relation to the clinical severity of respective BKPyV DNAemia episodes (P = 0.0195). CXCL-10 concentrations were particularly lower in KTRs in whom BKPyV DNAemia remained without clinical evidence for PVAN, as compared to individuals who displayed high decoy cell levels, decreased renal function and/or biopsy-proven PVAN (median blood concentration: 266.97 vs. 426.42 pg/ml, P = 0.0282). In conclusion, in KTRs CXCL10 rises in parallel to BKPyV replication and correlates with the gradual development of PVAN.
  • Parente, Erika B.; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik (2022)
    Context: Obesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown. Objective: To investigate the associations between body composition and SDED in adults with T1D. Methods: From 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic. Results: During a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z= 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z= 2.22).The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR >= 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages. Conclusions: WHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.