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Marc E. De Broe

Bio: Marc E. De Broe is an academic researcher from University of Antwerp. The author has contributed to research in topics: Kidney disease & Kidney. The author has an hindex of 55, co-authored 173 publications receiving 8235 citations. Previous affiliations of Marc E. De Broe include Rafael Advanced Defense Systems & UCLA Medical Center.


Papers
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Journal ArticleDOI
TL;DR: After severe warm I/R renal injury, a pronounced acute tubular necrosis occurs during the first 12-24 h in the absence of a marked cellular infiltrate, but with an important renal MPO activity, reflecting the activation of the adhering inflammatory cells (polymorphonuclear cells (PMNs) and mainly monocytes/macrophages).
Abstract: (P<0.05)), became prominent at day 5 (1034±161 cells/mm2 vs sham=18±18 cells/mm2 (P<0.05)), and Background. Leukocyte adhesion/infiltration in response to renal ischaemia/reperfusion (I/R) injury is almost disappeared after 10 days. CD4+ cells ( W3/25) gradually increased from day 5, reaching a maximum a well-known but poorly understood phenomenon. The identification, kinetics, and exact role of these at day 10. A few CD8+ cells (OX-8) were apparent from days 3 until 10, but no B-cells (OX-33) were inflammatory cells in I/R injury and regeneration are still matters of debate. observed. Conclusions. After severe warm I/R renal injury, a Methods. Uninephrectomized rats were submitted to 60 min renal ischaemia by clamping of renal vessels. pronounced acute tubular necrosis occurs during the first 12–24 h in the absence of a marked cellular Results. Severe acute renal failure was observed, with maximum functional impairment on day 2. By 12 h infiltrate, but with an important renal MPO activity, reflecting the activation of the adhering inflammatory after the ischaemic event, up to 80% of proximal tubular cells in the outer stripe of outer medulla cells (polymorphonuclear cells (PMNs) and mainly monocytes/macrophages). Only later at the time and (OSOM ) were already severely damaged. Proliferation (proliferating cell nuclear antigen (PCNA) staining) site (OSOM ) of regeneration a sequential accumulation of monocytes/macrophages and T cells becomes promstarted after 24 h, reaching maximum activity on day 3. Regeneration of tubular morphology started on the inent, in contrast with the low number of neutrophils found in the kidney during the 10-day post-ischaemic 3rd day, and after 10 days 50% of tubules had regenerated completely. Interstitial leukocytes (OX-1 immuno- period. The non-specificity of the so-called neutrophilspecific identification methods (MPO activity, naphhistochemical staining) were already prominent at day 1, thereafter gradually increasing with time. The thol AS-D chloroacetate esterase, or mAb HIS-48 staining), cross-reacting with monocytes/macrophages, so-called neutrophil-specific identification methods (myeloperoxidase (MPO), chloroacetate esterase, mAb explains the controversy in literature concerning the number of PMNs in post-ischaemic injury. HIS-48) proved to be non-specific, since they also stained for macrophages, as demonstrated by flow Keywords: damage; kidney; macrophages; myelocytometry and the combination of these stainings with peroxidase; neutrophils; rat; regeneration the macrophage-specific ED-1 staining. MPO activity was already significantly increased at 1 h post-I/R (439±34%, P<0.005), reaching its maximum activity after 12 h of I/R (1159±138%, P<0.0005), declining Introduction thereafter. On the other hand, neutrophil presence investigated by H&E staining revealed only a few Ischaemia/reperfusion (I/R) injury is a common clinneutrophils in glomeruli, medullary rays, and OSOM ical event, still associated with high mortality and at 24 h after the ischaemic event (4.7±4.2 cells/mm2 morbidity [1], and lacking a specific therapy. Postvs controls=2.3±2.0 cells/mm2 (n.s.)), and remained ischaemic acute tubular necrosis (ATN ) is observed unchanged over the next 10 days. In contrast, signific- most frequently in patients after major surgery (cardiac ant monocyte/macrophage adhesion/infiltration ( ED-1 and aortic operations), trauma, severe hypovolaemia, staining) occurred at the OSOM at 24 h post-ischaemia burns, and others [2]. In addition, delayed graft func(at 24 h, 120±46 cells/mm2 vs sham=18±4 cells/mm2 tion of renal allografts is mainly caused by postischaemic ATN, with significant long-term graft

369 citations

Journal ArticleDOI
TL;DR: LC is a poorly absorbed, well-tolerated, and efficient phosphate binder in dialysis patients, who show almost no evolution toward low bone turnover over one year (unlike CC-treated patients), nor do they experience any aluminum-like effects on bone.

320 citations

Journal ArticleDOI
TL;DR: For each aminoglycoside, a single short‐term infusion resulted in significantly lower renal drug levels than did a continuous infusion of the same dose, which supports the administration of gentamicin and netilmicin as once‐daily injections.
Abstract: The pathogenesis of aminoglycoside nephrotoxicity is intimately related to the extent of drug accumulated in the renal cortex. In the framework of searching for preventive measures of aminoglycoside-induced nephrotoxicity, we investigated the influence of dosage regimen on the renal cortical accumulation of gentamicin and netilmicin in humans. Patients with a tumor partly involving one kidney, with normal renal function, and scheduled for nephrectomy received one dose of either gentamicin (4.5 mg/kg) or netilmicin (5 mg/kg) as a single short-term infusion or as 24-hour continuous infusion. Treatment started 24 hours before surgery. Serum aminoglycoside pharmacokinetics were examined during treatment and renal cortical tissue was sampled at the moment of operation for drug determination. The short-term infusion schedule yielded cortical concentrations of 103.2 ± 36.3 and 137.4 ± 34.6 µg/gm for gentamicin and netilmicin, respectively. Tissue levels after continuous infusion were 158.1 ± 52.9 and 178.5 ± 21.8 µg/gm for gentamicin and netilmicin, respectively. For each aminoglycoside, a single short-term infusion resulted in significantly lower renal drug levels than did a continuous infusion of the same dose. From the nephrotoxicity point of view, these data support the administration of gentamicin and netilmicin as once-daily injections. This also supports the appropriateness of further studies to determine clinical efficacy of once-a-day dosing for aminoglycosides. Clinical Pharmacology and Therapeutics (1989) 45, 22–27; doi:10.1038/clpt.1989.4

193 citations

Journal ArticleDOI
TL;DR: It is suggested that at low concentrations Sr interferes with the bone formation at the level of cell differentiation, whereas at high concentrations the disturbed mineralization in the presence of an intact nodule formation is indicative for a physicochemical interference of Sr with the hydroxyapatite formation.

193 citations

Journal ArticleDOI
TL;DR: Blocking the b130/CD28 costimulatory pathway by CTLA-4 Ig (recombinant fusion protein) ameliorated renal dysfunction and decreased mononuclear cell infiltration in I/R of the kidney and it seems worthwhile to study a combination therapy using anti-inflammatory/anti-adhesion molecules in the early phase of I-R.

185 citations


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01 Mar 2007
TL;DR: An initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI is described.
Abstract: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

5,467 citations

Journal ArticleDOI
TL;DR: The potential value of using pharmacokinetic/pharmacodynamic parameters as guides for establishing optimal dosing regimens for new and old drugs and for new emerging pathogens and resistant organisms should make the continuing search for the therapeutic rationale of antibacterial dosing of mice and men worthwhile.
Abstract: Investigations over the past 20 years have demonstrated that antibacterials can vary markedly in the time course of antimicrobial activity. These differences in pharmacodynamic activity have implications for optimal dosage regimens. The results of more recent studies suggest that the magnitude of the pharmacokinetic/pharmacodynamic parameters required for efficacy are relatively similar in animal infection models and in human infections. However, there is still much to learn. Additional studies are needed to further correlate pharmacokinetic/pharmacodynamic parameters for many antibacterials with therapeutic efficacy in a variety of animal infection models and in human infections. The potential value of using pharmacokinetic/pharmacodynamic parameters as guides for establishing optimal dosing regimens for new and old drugs and for new emerging pathogens and resistant organisms, for setting susceptibility breakpoints, and for reducing the cost of drug development should make the continuing search for the therapeutic rationale of antibacterial dosing of mice and men worthwhile.

2,719 citations

Journal ArticleDOI
TL;DR: A panel to update the prior position statements on the management of type 2 diabetes in adults includes additional focus on lifestyle management and diabetes self-management education and support and efforts targeting weight loss.
Abstract: The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: 1) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA1c or individualized HbA1c target; 2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and 3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min-1 [1.73 m]-2 or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.

2,592 citations

Journal ArticleDOI
TL;DR: The burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected.

2,370 citations

Journal ArticleDOI
TL;DR: A comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism is presented, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology.
Abstract: The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis an...

2,332 citations