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- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 2. |
- Ederoth, Per, et al.
(författare)
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Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) : A study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study
- 2016
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Ingår i: BMJ Open. - 2044-6055. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia-reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia- reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI. Methods and analysis: Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15-90 mL/min/ 1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury. Ethics and dissemination: The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study.
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| 4. |
- Grins, Edgars, et al.
(författare)
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Effect of Cyclosporine on Cytokine Production in Elective Coronary Artery Bypass Grafting : A Sub-Analysis of the CiPRICS (Cyclosporine to Protect Renal Function in Cardiac Surgery) Study
- 2022
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770. ; 36:7, s. 1985-1994
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The augmented inflammatory response to cardiac surgery is a recognized cause of postoperative acute kidney injury. The present study aimed to investigate the effects of preoperative cyclosporine treatment on cytokine production and delineate factors associated with postoperative kidney impairment. Design: A randomized, double-blind, placebo-controlled, single-center study. Setting: At a tertiary care, university hospital. Participants: Patients eligible for elective coronary artery bypass grafting surgery; 67 patients were enrolled. Interventions: Patients were randomized to receive 2.5 mg/kg cyclosporine or placebo before surgery. Cytokine levels were measured after the induction of anesthesia and 4 hours after the end of cardiopulmonary bypass. Measurements and Main Results: Tissue-aggressive (interleukin [IL]-1β, macrophage inflammatory protein [MIP]-1β, granulocyte colony-stimulating factor [G-CSF], IL-6, IL-8, IL-17, MCP-1), as well tissue-lenient (IL-4) cytokines, were significantly elevated in response to surgery. Changes in cytokine levels were not affected by cyclosporine pretreatment. Conclusions: Elective coronary artery bypass grafting surgery with cardiopulmonary bypass triggers cytokine activation. This activation was not impacted by preoperative cyclosporine treatment.
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