Browsing by Subject "Renin"

Now showing 1 - 4 of 4
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    Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families
    (American Heart Association, 2016-05) Kuipers, Allison L.; Kammerer, Candace M.; Pratt, J. Howard; Bunker, Clareann H.; Wheeler, Victor W.; Patrick, Alan L.; Zmuda, Joseph M.; Medicine, School of Medicine
    Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension.
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    An International Cohort Study of Autosomal Dominant Tubulointerstitial Kidney Disease due to REN Mutations Identifies Distinct Clinical Subtypes
    (Elsevier, 2020-12) Živná, Martina; Kidd, Kendrah; Zaidan, Mohamad; Vyleťal, Petr; Barešová, Veronika; Hodaňová, Kateřina; Sovová, Jana; Hartmannová, Hana; Votruba, Miroslav; Trešlová, Helena; Jedličková, Ivana; Sikora, Jakub; Hůlková, Helena; Robins, Victoria; Hnízda, Aleš; Živný, Jan; Papagregoriou, Gregory; Mesnard, Laurent; Beck, Bodo B.; Wenzel, Andrea; Tory, Kálmán; Häeffner, Karsten; Wolf, Matthias T.F.; Bleyer, Michael E.; Sayer, John A.; Ong, Albert C.M.; Balogh, Lídia; Jakubowska, Anna; Łaszkiewicz, Agnieszka; Clissold, Rhian; Shaw-Smith, Charles; Munshi, Raj; Haws, Robert M.; Izzi, Claudia; Capelli, Irene; Santostefano, Marisa; Graziano, Claudio; Scolari, Francesco; Sussman, Amy; Trachtman, Howard; Decramer, Stephane; Matignon, Marie; Grimbert, Philippe; Shoemaker, Lawrence R.; Stavrou, Christoforos; Abdelwahed, Mayssa; Belghith, Neila; Sinclair, Matthew; Claes, Kathleen; Kopel, Tal; Moe, Sharon; Deltas, Constantinos; Knebelmann, Bertrand; Rampoldi, Luca; Kmoch, Stanislav; Bleyer, Anthony J.; Medicine, School of Medicine
    There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.
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    Renin as a Biomarker of Acute Kidney Injury and Mortality in Children With Severe Malaria or Sickle Cell Disease
    (Springer Nature, 2023-09-12) Adan, Daniel, Jr.; Batte, Anthony; Namazzi, Ruth; Mufumba, Ivan; Kazinga, Caroline; Mellencamp, Kagan A.; Bond, Caitlin; Opoka, Robert O.; John, Chandy C.; Conroy, Andrea L.; Pediatrics, School of Medicine
    Background: Globally, a very high percentage of acute kidney injury (AKI) occurs in low- and middle-income countries (LMICs) where late recognition contributes to increased mortality. There are challenges with using existing biomarkers of AKI in LMICs. Emerging evidence suggests renin may serve as a biomarker of kidney injury that can overcome limitations in creatinine-based diagnostics. Methods: Two study populations in Uganda were assessed. Cohort #1 was a two-site, prospective cohort study enrolling 600 children with severe malaria (SM). Cohort #2 was a prospective cohort study enrolling 185 children with sickle cell disease (SCD) hospitalized with a vaso-occlusive crisis. Plasma or serum renin concentrations were measured in both cohorts of children at the time of hospital admission using Luminex® (Luminex Corporation, Austin, Texas, United States) or enzyme-linked immunosorbent assay (ELISA), respectively. We assessed the ability of renin to discriminate between children with or without AKI and between children who survived and children who died using receiver operating characteristic curves. Results: In both cohorts, renin concentrations were strongly associated with AKI and mortality. Renin was able to discriminate between children with or without AKI with an area under the curve (AUC) of 0.70 (95%CI, 0.65-0.74) in children with SM and 0.72 (95%CI, 0.6co3-0.81) in children with SCD. Renin was able to discriminate between children who survived and children who died with an AUC of 0.73 (95%CI, 0.63-0.83) in children with SM and 0.94 (95%CI, 0.89-0.99) in children with SCD. In Cohort #2, we compared renin against urine neutrophil gelatinase-associated lipocalin (NGAL) as the leading biomarker of AKI, and it had comparable performance in discriminating AKI and predicting mortality. Conclusions: In two independent populations of children at risk of AKI with key differences in the etiology of kidney injury, renin was strongly associated with AKI and mortality and had moderate to good diagnostic performance to predict mortality.