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      Shrunken Pore Syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting

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          Abstract

          Shrunken Pore Syndrome was recently suggested for the pathophysiologic state in patients characterized by an estimation of their glomerular filtration rate (GFR) based upon cystatin  C, which is lower or equal to 60% of their estimated GFR based upon creatinine, i.e. when eGFR cystatin  C ≤ 60% of eGFR creatinine. Not only the cystatin  C level, but also the levels of other low molecular mass proteins are increased in this condition. The preoperative plasma levels of cystatin  C and creatinine were measured in 1638 patients undergoing elective coronary artery bypass grafting. eGFR cystatin  C and eGFR creatinine were calculated using two pairs of estimating equations, CAPA and LMrev, and CKD-EPI cystatin  C and CKD-EPI creatinine, respectively. The Shrunken Pore Syndrome was present in 2.1% of the patients as defined by the CAPA and LMrev equations and in 5.7% of the patients as defined by the CKD-EPI cystatin  C and CKD-EPI creatinine equations. The patients were studied over a median follow-up time of 3.5 years (2.0–5.0 years) and the mortality determined. Shrunken Pore Syndrome defined by both pairs of equations was a strong, independent, predictor of long-term mortality as evaluated by Cox analysis and as illustrated by Kaplan-Meier curves. Increased mortality was observed also for the subgroups of patients with GFR above or below 60 mL/min/1.73 m 2. Changing the cut-off level from 60 to 70% for the CAPA and LMrev equations increased the number of patients with Shrunken Pore Syndrome to 6.5%, still displaying increased mortality.

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          Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality.

          A triple-marker approach for chronic kidney disease (CKD) evaluation has not been well studied. To evaluate whether combining creatinine, cystatin C, and urine albumin-to-creatinine ratio (ACR) would improve identification of risks associated with CKD compared with creatinine alone. Prospective cohort study involving 26,643 US adults enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from January 2003 to June 2010. Participants were categorized into 8 groups defined by estimated glomerular filtration rate (GFR) determined by creatinine and by cystatin C of either <60 or ≥60 mL/min/1.73 m(2) and ACR of either <30 or ≥30 mg/g. All-cause mortality and incident end-stage renal disease with median follow-up of 4.6 years. Participants had a mean age of 65 years, 40% were black, and 54% were women. Of 26,643 participants, 1940 died and 177 developed end-stage renal disease. Among participants without CKD defined by creatinine, 24% did not have CKD by either ACR or cystatin C. Compared with those with CKD defined by creatinine alone, the hazard ratio for death in multivariable-adjusted models was 3.3 (95% confidence interval [CI], 2.0-5.6) for participants with CKD defined by creatinine and ACR; 3.2 (95% CI, 2.2-4.7) for those with CKD defined by creatinine and cystatin C, and 5.6 (95% CI, 3.9-8.2) for those with CKD defined by all biomarkers. Among participants without CKD defined by creatinine, 3863 (16%) had CKD detected by ACR or cystatin C. Compared with participants who did not have CKD by any measure, the HRs for mortality were 1.7 (95% CI, 1.4-1.9) for participants with CKD defined by ACR alone, 2.2 (95% CI, 1.9-2.7) for participants with CKD defined by cystatin C alone, and 3.0 (95% CI, 2.4-3.7) for participants with CKD defined by both measures. Risk of incident end-stage renal disease was higher among those with CKD defined by all markers (34.1 per 1000 person-years; 95% CI, 28.7-40.5 vs 0.33 per 1000 person-years; 95% CI, 0.05-2.3) for those with CKD defined by creatinine alone. The second highest end-stage renal disease rate was among persons missed by the creatinine measure but detected by both ACR and cystatin C (rate per 1000 person-years, 6.4; 95% CI, 3.6-11.3). Net reclassification improvement for death was 13.3% (P < .001) and for end-stage renal disease was 6.4% (P < .001) after adding estimated GFR cystatin C in fully adjusted models with estimated GFR creatinine and ACR. Adding cystatin C to the combination of creatinine and ACR measures improved the predictive accuracy for all-cause mortality and end-stage renal disease.
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            The revised Lund-Malmö GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population.

            The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately.
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              Non-invasive estimation of glomerular filtration rate (GFR). The Lund model: Simultaneous use of cystatin C- and creatinine-based GFR-prediction equations, clinical data and an internal quality check

              Abstract Knowledge of glomerular filtration rate (GFR) is required to detect and follow impairment of renal function, to allow correct dosage of drugs cleared by the kidneys, and for the use of nephrotoxic contrast media. Correct determination of GFR requires invasive techniques, which are expensive, slow and not risk-free. Therefore, GFR-prediction equations based solely upon cystatin C or creatinine and anthropometric data or upon cystatin C, creatinine and anthropometric data have been developed. The combined prediction equations display the best diagnostic performance, but in several easily identifiable clinical situations (e.g. abnormal muscle mass, treatment with large doses of glucocorticoids) prediction equations based upon either cystatin C or creatinine are better than the combined equations. In Lund, where cystatin C has been used as a GFR-marker in the clinical routine since 1994, a strategy based upon this knowledge has therefore been developed. This comprises simultaneous use of a cystatin C-based and a creatinine-based GFR-prediction equation. If the GFRs predicted agree, the mean value is used as a reliable GFR-estimate. If the GFRs predicted do not agree, clinical data is evaluated to identify reasons for not using one of the two prediction equations and the GFR predicted by the other one is used. If no reasons for the difference in predicted GFRs are found, an invasive gold standard determination of GFR is performed. If the GFRs predicted agree for a patient, the creatinine value is reliably connected to a specific GFR and can be used to follow changes in GFR of that patient.
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                Author and article information

                Journal
                Scand J Clin Lab Invest
                Scand. J. Clin. Lab. Invest
                ICLB
                iclb20
                Scandinavian Journal of Clinical and Laboratory Investigation
                Informa Healthcare
                0036-5513
                1502-7686
                2 January 2016
                13 January 2016
                : 76
                : 1
                : 74-81
                Affiliations
                [ a ]Departments of Cardiothoracic Surgery
                [ b ]Clinical Chemistry, Lund University and Skåne University Hospital , LundSweden
                Author notes
                CONTACT Anders Grubb, anders.grubb@ 123456med.lu.se , Department of Clinical Chemistry, Lund University and Skåne University Hospital , SE-22185 LundSweden.
                Article
                1099724
                10.3109/00365513.2015.1099724
                4720044
                26647957
                5d62e1d2-6f50-4f5c-8169-677f3e639bb4
                © 2015 Taylor & Francis

                This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.

                History
                : 26 July 2015
                : 11 September 2015
                : 21 September 2015
                Page count
                Pages: 8
                Categories
                Article
                Research Article

                Clinical chemistry
                coronary artery bypass,creatinine,cystatin  c,glomerular filtration rate,mortality determinants

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