Browsing by Subject "kidney"

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  • Laine, Outi; Joutsi-Korhonen, Lotta; Lassila, Riitta; Huhtala, Heini; Vaheri, Antti; Makela, Satu; Mustonen, Jukka (2016)
    We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207pg/mL, range 56-1258pg/mL vs. median 58 pg/mL, range 11-241pg/mL, P Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.
  • Li, Hao; Hohenstein, Peter; Kuure, Satu (2021)
    The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) nephrons, and (c) mesangial cells together with connective tissue of the stroma. Extensive interest has been raised towards these embryonic progenitor cells, which are normally lost before birth in humans but remain part of the undifferentiated nephrogenic rests in the pediatric renal cancer Wilms tumor. Here, we discuss the current understanding of kidney-specific embryonic progenitor regulation in the innate environment of the developing kidney and the types of disruptions in their balanced regulation that lead to the formation of Wilms tumor.
  • Hölttä, Tuula; Gordin, Daniel; Rahkonen, Otto; Turanlahti, Maila; Holmström, Miia; Tainio, Juuso; Rönnholm, Kai; Jalanko, Hannu (2020)
    Over the past 30 years, there has been an improvement in both patient and graft survival after pediatric renal transplantation (RTX). Despite this success, these patients still carry an elevated risk for untimely death, partly through premature aging of the vasculature. The aim of this study was thus to investigate the long-term outcome of individuals with RTX in childhood, as well as to explore the cardiovascular health of these adults more than a decade later. We studied 131 individuals who had undergone a RTX between the years 1979 and 2005. Furthermore, left ventricular hypertrophy (LVH), coronary artery calcifications (CAC), and related metabolic factors were investigated in a cross-sectional study including 52 individuals as part of the initial cohort. The mortality rate (n = 131) was 12.2%. The median estimated graft survival was 17.5 years (95% CI 13.6-21.3), being significantly better in children transplanted below the age of 5 years (18.6 vs. 14.3 years, P <0.01) compared with older ones. CAC were found in 9.8% and LVH in 13% of the patients. Those with cardiac calcifications had longer dialysis vintage and higher values of parathyroid hormone (PTH) during dialysis. Left ventricular mass correlated positively with systolic blood pressure, PTH, and phosphate measured at the time of the study.
  • Keltto, Katri (Helsingfors universitet, 2011)
    Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) widely used for the treatment of pain in sheep and swine. Information of correct ketoprofen doses in different animal species is limited. The correct dose cannot be reliably extrapolated based on other species or human. The problem in cases of suspected overdose is knowing whether the given dose was toxic. The objective of the study with sheep was to figure out if the kinetics of ketoprofen is altered by a tenfold overdose, study the effect of the overdose to kidneys and find out a way to diagnose overdose by a simple urine test. The objective of the study with swine was to figure out the bioavailability and pharmacokinetics of ketoprofen after oral, intramuscular and intravenous administration. The most important variables were AUC0-_, Cmax and Tmax. Bioavailability was calculated based on intravascular administration. 30 mg/kg ketoprofen was administered intravenously to six sheep. The concentration of ketoprofen in sheep plasma was followed for 24 hours. Pharmacokinetic parameters were calculated afterwards. Blood and urine samples were analysed to detect enzyme markers indicating possible renal failure. The sheep were finished off 24 hours after the administration and the possible damage to kidneys was evaluated from histological samples. Ketoprofen was also administered to eight swine. The doses were 3 mg/kg of oral, intramuscular and intravascular, and 6 mg/kg of oral ketoprofen. The study was performed as a randomized, cross-over study. The concentration of ketoprofen in swine plasma was followed for 48 hours after administration. Pharmacokinetic parameters were calculated and bioequivalence evaluated afterwards. The in vivo -studies of both of the studies as well as the histological study of the kidneys, and the urine and blood analysis except for the analysis of ketoprofen concentration, were carried out by the researchers of the Faculty of Veterinary Medicine. Plasma ketoprofen concentrations were measured by high-performance liquid chromatography (HPLC). Drug concentration and pharmacokinetic analysis were carried out in the Faculty of Pharmacy. The tenfold dose of ketoprofen was toxic in sheep. Serum concentrations of urea and creatinine increased. Histological samples revealed acute tubular damage. Many urine enzyme concentrations increased. The rise of urine lactate dehydrogenase (LD) concentration was most significant and earliest. LD appears to be a potential marker of a toxic ketoprofen dose. Compared with the therapeutic dose, overdose did not affect ketoprofen elimination rate from plasma, so the kinetics of ketoprofen was not altered. AUC- and Cmax -values were over tenfold compared to the therapeutic dose, so the values did not rise linearly as the dose reached a toxic level. Bioequivalence of ketoprofen in swine was not observed between different routes of administration. The bioavailability was excellent in all routes of administration. Tmax was slightly over one hour after administration. Cmax and AUC were 5,1 mg/l and 32 mg l-1 h after oral 3 mg/kg dose and 7,6 mg/l and 37 mg l-1 h after intramuscular dose. The increases in AUC and Cmax were linear between the different dosages of oral ketoprofen. The difference of the elimination rates between oral and intravascular administration was statistically significant. Ketoprofen distribution volume and clearance did not differ significantly between different routes of administration.
  • Lehtonen, Sanna (2020)
    Metformin is the most commonly prescribed drug for treating type 2 diabetes mellitus (T2D). Its mechanisms of action have been under extensive investigation, revealing that it has multiple cellular targets, either direct or indirect ones, via which it regulates numerous cellular pathways. Diabetic kidney disease (DKD), the serious complication of T2D, develops in up to 50% of the individuals with T2D. Various mechanisms contribute to the development of DKD, including hyperglycaemia, dyslipidemia, oxidative stress, chronic low-grade inflammation, altered autophagic activity and insulin resistance, among others. Metformin has been shown to affect these pathways, and thus, it could slow down or prevent the progression of DKD. Despite several animal studies demonstrating the renoprotective effects of metformin, there is no concrete evidence in clinical settings. This review summarizes the renoprotective effects of metformin in experimental settings. Special emphasis is on the effects of metformin on podocytes, the glomerular epithelial cells that are central in maintaining the glomerular ultrafiltration function.
  • Leppäniemi, A. (2019)
    Background and aims: Today, a significant proportion of solid abdominal organ injuries, whether caused by penetrating or blunt trauma, are managed nonoperatively. However, the controversy over operative versus nonoperative management started more than a hundred years ago. The aim of this review is to highlight some of the key past observations and summarize the current knowledge and guidelines in the management of solid abdominal organ injuries. Materials and Methods: A non-systematic search through historical articles and references on the management practices of abdominal injuries was conducted utilizing early printed volumes of major surgical and medical journals from the late 19th century onwards. Results: Until the late 19th century, the standard treatment of penetrating abdominal injuries was nonoperative. The first article advocating formal laparotomy for abdominal gunshot wounds was published in 1881 by Sims. After World War I, the policy of mandatory laparotomy became standard practice for penetrating abdominal trauma. During the latter half of the 20th century, the concept of selective nonoperative management, initially for anterior abdominal stab wounds and later also gunshot wounds, was adopted by major trauma centers in South Africa, the United States, and little later in Europe. In blunt solid abdominal organ injuries, the evolution from surgery to nonoperative management in hemodynamically stable patients aided by the development of modern imaging techniques was rapid from 1980s onwards. Conclusion: With the help of modern imaging techniques and adjunctive radiological and endoscopic interventions, a major shift from mandatory to selective surgical approach to solid abdominal organ injuries has occurred during the last 30-50 years.
  • Kurtzeborn, Kristen; Cebrian, Cristina; Kuure, Satu (2018)
    Classically, trophic factors are considered as proteins which support neurons in their growth, survival, and differentiation. However, most neurotrophic factors also have important functions outside of the nervous system. Especially essential renal growth and differentiation regulators are glial cell line-derived neurotrophic factor (GDNF), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs). Here we discuss how trophic factor-induced signaling contributes to the control of ureteric bud (UB) branching morphogenesis and to maintenance and differentiation of nephrogenic mesenchyme in embryonic kidney. The review includes recent advances in trophic factor functions during the guidance of branching morphogenesis and self-renewal versus differentiation decisions, both of which dictate the control of kidney size and nephron number. Creative utilization of current information may help better recapitulate renal differentiation in vitro, but it is obvious that significantly more basic knowledge is needed for development of regeneration-based renal therapies.
  • Wasik, Anita A.; Dash, Surjya N.; Lehtonen, Sanna (2019)
    Septins are a conserved family of GTP-binding proteins that assemble into cytoskeletal filaments to function in a highly sophisticated and physiologically regulated manner. Originally septins were discovered in the budding yeast as membrane-associated filaments that affect cell polarity and cytokinesis. In the last decades, much progress has been made in understanding the biochemical properties and cell biological functions of septins. In line with this, mammalian septins have been shown to be involved in various cellular processes, including regulation of cell polarity, cytoskeletal organization, vesicle trafficking, ciliogenesis, and cell-pathogen interactions. A growing number of studies have shown that septins play important roles in tissue and organ development and physiology; yet, little is known about their role in the kidney. In the following review, we discuss the structure and functions of septins in general and summarize the evidence for their presence and roles in the kidney.