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

Alain Dardashti, Shahab Nozohoor, Anders Grubb, Henrik Bjursten, Alain Dardashti, Shahab Nozohoor, Anders Grubb, Henrik Bjursten

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.

Keywords: Coronary artery bypass; creatinine; cystatin  C; glomerular filtration rate; mortality determinants.

Figures

Figure 1.
Figure 1.
Calculations using the CKD-EPI formulas based on cystatin C or creatinine. Survival after coronary artery bypass surgery for patients with eGFR > 60 mL/min/1.73 m2 (A) with Shrunken Pore Syndrome (SPS, red broken line) and without (blue solid line). Patients with eGFR< 60 mL/min/1.73 m2 are seen in (B). The cut-off level for SPS was 0.6. For both levels of eGFR: p < 0.001 with log-rank test.
Figure 2.
Figure 2.
Calculations using the CAPA and LMrev formulas based on cystatin C or creatinine. Survival after coronary artery bypass surgery for patients with eGFR > 60 mL/min/1.73 m2 (A) with Shrunken Pore Syndrome (SPS, red broken line) and without (blue solid line). Patients with eGFR < 60 mL/min/1.73 m2 are seen in (B). The cut-off level for SPS was 0.6. For both levels of eGFR: p < 0.001 with log-rank test.
Figure 3.
Figure 3.
Calculations using the CAPA and LMrev formulas based on cystatin C or creatinine. Survival after coronary artery bypass surgery for patients with eGFR > 60 mL/min/1.73 m2 (A) with Shrunken Pore Syndrome (SPS, red broken line) and without (blue solid line). Patients with eGFR < 60 mL/min/1.73 m2 are seen in (B). The cut-off level for SPS was 0.7. For both levels of eGFR: p < 0.001 with log-rank test.

References

    1. Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med. 2005;352:2049–60.
    1. Peralta CA, Shlipak MG, Judd S, Cushman M, McClellan W, Zakal NA, Safford MM, Zhan X, Muntner P. 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. JAMA. 2011;305:1545–52.
    1. Shlipak MG, Matsushita K, Ärnlöv J, Inker LA, Katz R, Polkinghorne KR, Rothenbacher D, Sarnak MJ, Astor BC, Coresh J, Levey S, Gansevoort RT. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369:932–43.
    1. Knight EL, Verhave JC, Spiegelman D, Hillege HL, deZeeuw D, Curhan GC, deJong PE. Factors influencing cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int. 2004;65:1416–21.
    1. Grubb A, Björk J, Nyman U, Pollak J, Bengzon J, Östner G, Lindström V. Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation. Scand J Clin Lab Invest. 2011;71:145–19.
    1. Grubb A, Lindström V, Kristensen K, Christensson A, Wide-Swensson D, Strevens H, Schmidt C, Blirup-Jensen S. Filtration quality: a new measure of renal disease. Clin Chem Lab Med. 2007;45(Suppl):S273–4.
    1. Strevens H, Wide-Swensson D, Torffvit O, Grubb A. Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy. Scand J Clin Lab Invest. 2002;62:141–7.
    1. Kristensen K, Lindström V, Schmidt C, Blirup-Jensen S, Grubb A, Wide-Swensson D, Strevens H. Temporal changes of the plasma levels of cystatin C, beta-trace protein, β2-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process. Scand J Clin Lab Invest. 2007;67:612–8.
    1. Strevens H, Wide-Swensson D, Grubb A. Serum cystatin C is a better marker for preeclampsia than serum creatinine or serum urate. Scand J Clin Lab Invest. 2001;61:575–80.
    1. Kristensen K, Wide-Swensson D, Schmidt C, Blirup-Jensen S, Lindström V, Strevens H, Grubb A. Cystatin C, beta-2-microglobulin and beta-trace protein in pre-eclampsia. Acta Obstet Gynecol Scand. 2007;86:921–6.
    1. Grubb A, Lindström V, Jonsson M, Bäck SE, Åhlund T, Rippe B, Christensson A. Reduction in glomerular pore size is not restricted to pregnant women. Evidence for a new syndrome: “Shrunken pore syndrome”. Scand J Clin Lab Invest. 2015;75:333–40.
    1. Grubb A, Horio M, Hansson LO, Björk J, Nyman U, Flodin M, Larssson A, Bökenkamp A, Yasuda Y, Blufpand H, Lindström V, Zegers I, Althaus H, Blirup-Jensen S, Itoh Y, Sjöström P, Nordin G, Christensson A, Klima H, Sunde K, Hjort-Christensen P, Armbruster D, Ferrrero C. Generation of a new cystatin C-based estimating equation for glomerular filtration rate using seven assays standardized to the international calibrator. Clin Chem. 2014;60:974–86.
    1. Nyman U, Grubb A, Larsson A, Hansson L-O, Flodin M, Nordin G, Lindström V, Björk J. The revised Lund-Malmö GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population. Clin Chem Lab Med. 2014;52:815–24.
    1. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YP, Coresh J, Levey AS. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367:20–9.
    1. Nyman U, Grubb A, Sterner G, Björk J. Different equations to combine creatinine and cystatin C to predict GFR. Arithmetic mean of existing equations performs as well as complex combinations. Scand J Clin Lab Invest. 2009;69:619–27.
    1. Grubb A. 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. Scand J Clin Lab Invest. 2010;70:65–70.
    1. Grubb A, Nyman U, Björk J. Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine. Scand J Clin Lab Invest. 2012;72:73–7.
    1. Dardashti A, Ederoth P, Algotsson L, Brondén B, Bjursten H. Incidence, dynamics, and prognostic value of acute kidney injury for death after cardiac surgery. J Thorac Cardiovasc Surg. 2014;147:800–7.
    1. Arturson G, Groth T, Grotte G. Human glomerular membrane porosity and filtration pressure: dextran clearance data analysed by theoretical models. Clin Sci. 1971;40:137–58.
    1. Carrie BJ, Myers BD. Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy. Kidney Int. 1980;17:669–76.
    1. Scandling JD, Myers BD. Glomerular size-selectivity and microalbuminuria in early diabetic glomerular disease. Kidney Int. 1992;41:840–6.
    1. Deckert T, Kofoed-Enevoldsen A, Vidal P, Nørgaard K, Andreasen HB, Feldt-Rasmussen B. Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria. Diabetologia. 1993;36:244–51.
    1. Roberts M, Lindheimer MD, Davison JM. Altered glomerular permselectivity to neutral dextrans and heteroporous membrane modeling in human pregnancy. Am J Physiol. 1996;270:F338–43.
    1. Blouch K, Deen WM, Fauvel JP, Bialek J, Derby G, Myers BD. Molecular configuration and glomerular size selectivity in healthy and nephrotic humans. Am J Physiol. 1997;273:F430–7.
    1. Zayas CF, Guasch A. Early glomerular dysfunction in human renal allografts. Kidney Int. 2001;60:1938–47.
    1. Oberbauer R, Nenov V, Weidekamm C, Haas M, Szekeres T, Mayer G. Reduction in mean glomerular pore size coincides with the development of large shunt pores in patients with diabetic nephropathy. Exp Nephrol. 2001;9:49–53.
    1. Sasser JM, Murphy SR, Granger JP. Emerging drugs for preeclampsia – the endothelium as a target. Expert Opin Emerg Drugs. 2015

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere