A5032763801- Renal Diseases and Glomerulopathies
- Vasculitis and related conditions
- Renal Transplantation Outcomes and Treatments
- Chronic Kidney Disease and Diabetes
- Acute Kidney Injury Research
- Cell Adhesion Molecules Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Complement system in diseases
- Organ Transplantation Techniques and Outcomes
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Otitis Media and Relapsing Polychondritis
- Renal and Vascular Pathologies
- Systemic Sclerosis and Related Diseases
- Organ Donation and Transplantation
- Biomedical Research and Pathophysiology
- Autoimmune Bullous Skin Diseases
- Pediatric Urology and Nephrology Studies
- Chemotherapy-induced organ toxicity mitigation
- Renal and related cancers
- Neuropeptides and Animal Physiology
- Polyomavirus and related diseases
- Platelet Disorders and Treatments
- Urticaria and Related Conditions
- Organ and Tissue Transplantation Research
- Pregnancy and Medication Impact
University Hospital Dubrava
2016-2025
University of Zagreb
2016-2025
University Hospital Centre Zagreb
2014-2020
RELX Group (United States)
2020
International Society of Nephrology
2020
Research Institute Hospital 12 de Octubre
2019
Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
2018
Hospital Universitario Fundación Jiménez Díaz
2018
University of Colorado Denver
2002-2013
Klinička bolnica Merkur
2010
We have demonstrated that caspase-1-deficient (caspase-1<sup>–/–</sup>) mice are functionally and histologically protected against cisplatin-induced acute renal failure (ARF). Caspase-1 exerts proinflammatory effects via the cytokines interleukin (IL)-1β, IL-18, IL-6, neutrophil recruitment. sought to determine role of IL-1β, IL-6 recruitment in ARF. first examined IL-1β; IL-1β increased nearly 2-fold ARF was reduced caspase-1<sup>–/–</sup> mice. However, inhibition with IL-1 receptor...
Having recently described the injurious role of caspase-1–mediated production proinflammatory cytokine IL-18 in ischemic acute renal failure (ARF), we report here on effect newly developed caspase inhibitor Quinoline-Val-Asp(Ome)-CH2-OPH (OPH-001) caspase-1, IL-18, neutrophil infiltration, and function ARF. C57BL/6 mice with ARF treated OPH-001 had a marked (100%) reduction blood urea nitrogen (BUN) serum creatinine highly significant morphological tubular necrosis (ATN) score compared...
Having recently described the injurious role of caspase-1–mediated production proinflammatory cytokine IL-18 in ischemic acute renal failure (ARF), we report here on effect newly developed caspase inhibitor Quinoline-Val-Asp(Ome)-CH2-OPH (OPH-001) caspase-1, IL-18, neutrophil infiltration, and function ARF. C57BL/6 mice with ARF treated OPH-001 had a marked (100%) reduction blood urea nitrogen (BUN) serum creatinine highly significant morphological tubular necrosis (ATN) score compared...
Abstract Ischemia/reperfusion (I/R) injury of the kidney is a common cause acute renal failure (ARF) and associated with high morbidity mortality in intensive care unit. The mechanisms underlying I/R are complex. Studies have shown that complement activation contributes to pathogenesis kidney, but exact not been defined. We hypothesized this setting occurs via alternative pathway mice deficient factor B, an essential component pathway, would be protected from ischemic ARF. Wild-type suffered...
Inflammation contributes to the pathogenesis of acute kidney injury (AKI). IL-33 is a proinflammatory cytokine, but its role in AKI unknown. Here we observed increased protein expression full-length following induction with cisplatin. To determine whether promotes injury, administered soluble ST2 (sST2), fusion that neutralizes activity by acting as decoy receptor. Compared cisplatin-induced untreated mice, mice treated sST2 had fewer CD4 T cells infiltrate kidney, lower serum creatinine,...
We have demonstrated that caspase-1 is a mediator of both cisplatin-induced acute kidney injury (AKI) and ischemic AKI. As activated in the inflammasome, we investigated inflammasome Mice were injected with cisplatin or subjected to bilateral renal pedicle clamping. Immunoblot analysis whole after AKI revealed: 1) an increase apoptosis-associated Speck-like protein containing caspase recruitment domain (ASC), major complexes nucleotide-binding oligomerization domain, leucine-rich repeat...
Kidney glomerulosclerosis commonly progresses to end-stage kidney failure, but pathogenic mechanisms are still poorly understood. Here, we show that podocyte expression of decay-accelerating factor (DAF/CD55), a complement C3 convertase regulator, crucially controls disease in murine models adriamycin (ADR)-induced focal and segmental (FSGS) streptozotocin (STZ)-induced diabetic glomerulosclerosis. ADR induces enzymatic cleavage DAF from surfaces, leading activation. deficiency or prevention...
Genetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history hematuria or kidney function impairment. Alport syndrome experts now advocate genetic even when heterozygous COL4A3 COL4A4 suspected, and cascade their first-degree members because risk impaired function. The recommend too that heterozygotes do not act as donors. Testing in COL4A3–COL4A5 genes should also be performed proteinuria...
Abstract The recent Chandos House meeting of the Alport Variant Collaborative extended indications for screening pathogenic variants in COL4A5, COL4A3 and COL4A4 genes beyond classical phenotype (haematuria, renal failure; family history haematuria or failure) to include persistent proteinuria, steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis (FSGS), familial IgA glomerulonephritis end-stage kidney failure without an obvious cause. refined ACMG criteria variant...
Fractalkine (CX3CL1) is expressed on injured endothelial cells and a potent chemoattractant adhesion molecule for macrophages carrying the fractalkine receptor (CX3CR1). The aim of this study was to investigate role CX3CL1, its ligand CX3CR1, in ischemic acute renal failure (ARF) mice. On immunoblotting, CX3CL1 protein expression kidney increased markedly ARF. immunofluorescence staining, intensity staining blood vessels significantly more prominent ARF compared with controls. A specific...
Complement activation in the kidney after ischemia/reperfusion (I/R) seems to occur primarily via alternative complement pathway. The ability of an inhibitory mAb mouse factor B, a necessary component pathway, protect mice from ischemic acute renal failure was tested. Treatment with prevented deposition C3b on tubular epithelium and generation systemic C3a I/R. Treated had significantly lower increases serum urea nitrogen developed less morphologic injury For gaining insight into potential...
Cyst expansion in polycystic kidney disease (PKD) results localized hypoxia the that may activate hypoxia-inducible factor-1α (HIF-1α). HIF-1α and autophagy, a form of programmed cell repair, are induced by hypoxia. The purposes were to determine expression autophagy rat mouse models PKD. was detected electrochemiluminescence. Autophagy visualized electron microscopy (EM). LC3 beclin-1, markers immunoblotting. Eight-week-old male heterozygous (Cy/+) 4-wk-old homozygous (Cy/Cy) Han:SPRD rats,...
Glomerular IgM and C3 deposits frequently accompany idiopathic FSGS secondary glomerulosclerosis, but it is unknown whether activates complement, possibly contributing to the pathogenesis of these diseases. We hypothesized that natural antibody binds neoepitopes exposed in glomerulus after nonimmune insults, triggering activation complement system further injury. examined effects depleting B cells, using three different strategies, on adriamycin-induced glomerulosclerosis. First, we treated...
Ischemia/reperfusion (I/R) triggers a robust inflammatory response within the kidney. Numerous components of immune system contribute to resultant renal injury, including complement system. We sought identify whether natural Abs bind postischemic kidney and activation after I/R. depleted peritoneal B cells in mice by hypotonic shock. Depletion prevented deposition IgM glomeruli I/R attenuated injury found that glomerular activates classical pathway complement, but it does not cause...
In 1927 Arthur Cecil Alport, a South African physician, described British family with an inherited form of kidney disease that affected males more severely than females and was sometimes associated hearing loss. 1961, the eponymous name Alport syndrome adopted. late twentieth century three genes responsible for were discovered: COL4A3, COL4A4, COL4A5 encoding α3, α4, α5 polypeptide chains type IV collagen, respectively. These assemble to heterotrimers collagen in glomerular basement...
Caspase-1-deficient (−/−) mice are protected against sepsis-induced hypotension and mortality. We investigated the role of caspase-1 its associated cytokines in a nonhypotensive model endotoxemic acute renal failure (ARF). Mice were injected intraperitoneally with 2.5 mg LPS that induces ARF. On immunoblot analysis whole kidney, there was an increase protein LPS-treated compared vehicle-treated controls. In mice, glomerular filtration rate (GFR) significantly higher −/− vs. wild-type at 16...
Acute kidney injury (AKI) in septic patients drastically increases the mortality to 50-80%. Sepsis is characterized by hemodynamic perturbations as well overwhelming induction of proinflammatory cytokines. Since ghrelin has been shown have anti-inflammatory properties, we hypothesized that may afford renal protection during endotoxemia-induced AKI. Studies were conducted a normotensive AKI model mice intraperitoneal injection 3.5 mg/kg LPS. Serum levels increased endotoxemia accompanied...
IL-18 function is neutralized in binding protein transgenic (IL-18BP Tg) mice. First, we determined whether IL-18BP Tg mice are protected against ischemic acute kidney injury (AKI). Ischemic AKI was induced by bilateral renal pedicle clamping. were functionally and histologically as blood urea nitrogen, serum creatinine, tubular necrosis score. We have demonstrated that the injurious effect of independent neutrophils lymphocytes. Thus inhibition on macrophage infiltration determined. The...
Abstract Background The VALidation of IGA (VALIGA) study investigated the utility Oxford Classification immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed central review Oxford. We had two distinct objectives: to assess how closely pathology findings associated with decision give corticosteroid/immunosuppressive (CS/IS) treatments, and determine impact differences MEST-C scoring between on clinical...