Aims Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long- term mortality and end -stage renal disease (ESRD) is unknown. Methods and Results We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all–cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long–term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). Conclusion Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients.
References
[1]
Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, et al. (1999) ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery). American College of Cardiology/American Heart Association. J Am Coll Cardiol 34: 1262–1347.
[2]
Cooper WA, O'Brien SM, Thourani VH, Guyton RA, Bridges CR, et al. (2006) Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Database. Circulation 113: 1063–1070.
[3]
Hillis GS, Croal BL, Buchan KG, El-Shafei H, Gibson G, et al. (2006) Renal function and outcome from coronary artery bypass grafting: impact on mortality after a 2.3-year follow-up. Circulation 113: 1056–1062.
[4]
Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, et al. (2004) Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 15: 1597–1605.
[5]
Grams ME, Astor BC, Bash LD, Matsushita K, Wang Y, et al. (2010) Albuminuria and Estimated Glomerular Filtration Rate Independently Associate with Acute Kidney Injury. J Am Soc Nephrol 21: 1757–1764.
[6]
Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, et al. (2004) Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 110: 32–35.
[7]
Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S (2001) Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 134: 629–636.
[8]
Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, et al. (2002) Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 106: 1777–1782.
[9]
Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, et al. (2009) Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 20: 1069–1077.
[10]
Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, et al. (2010) Relation between kidney function, proteinuria, and adverse outcomes. JAMA 303: 423–429.
[11]
James MT, Hemmelgarn BR, Wiebe N, Pannu N, Manns BJ, et al. (2011) Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet 376: 2096–2103.
[12]
Halbesma N, Kuiken DS, Brantsma AH, Bakker SJ, Wetzels JF, et al. (2006) Macroalbuminuria is a better risk marker than low estimated GFR to identify individuals at risk for accelerated GFR loss in population screening. J Am Soc Nephrol 17: 2582–2590.
[13]
Huang TM, Wu VC, Young GH, Lin YF, Shiao CC, et al. (2011) Preoperative Proteinuria Predicts Adverse Renal Outcomes after Coronary Artery Bypass Grafting. J Am Soc Nephrol 22: 156–163.
[14]
DeRose JJ Jr, Toumpoulis IK, Balaram SK, Ioannidis JP, Belsley S, et al. (2005) Preoperative prediction of long-term survival after coronary artery bypass grafting in patients with low left ventricular ejection fraction. J Thorac Cardiovasc Surg 129: 314–321.
[15]
Bove T, Landoni G, Calabro MG, Aletti G, Marino G, et al. (2005) Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial. Circulation 111: 3230–3235.
[16]
Ruggenenti P, Remuzzi G (2006) Time to abandon microalbuminuria? Kidney Int 70: 1214–1222.
[17]
Hsu CY, Ordonez JD, Chertow GM, Fan D, McCulloch CE, et al. (2008) The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 74: 101–107.
[18]
Hobson CE, Yavas S, Segal MS, Schold JD, Tribble CG, et al. (2009) Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 119: 2444–2453.
[19]
Wen CP, Cheng TY, Tsai MK, Chang YC, Chan HT, et al. (2008) All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan. Lancet 371: 2173–2182.
[20]
Orii K, Hioki M, Iedokoro Y, Shimizu KPrognostic factors affecting clinical outcomes after coronary artery bypass surgery: analysis of patients with chronic kidney disease after 5.9 years of follow-up. J Nihon Med Sch 78: 156–165.
[21]
Donadelli R, Abbate M, Zanchi C, Corna D, Tomasoni S, et al. (2000) Protein traffic activates NF-kB gene signaling and promotes MCP-1-dependent interstitial inflammation. Am J Kidney Dis 36: 1226–1241.
[22]
Abbate M, Zoja C, Remuzzi G (2006) How does proteinuria cause progressive renal damage? J Am Soc Nephrol 17: 2974–2984.
[23]
Konta T, Hao Z, Takasaki S, Abiko H, Ishikawa M, et al. (2007) Clinical utility of trace proteinuria for microalbuminuria screening in the general population. Clin Exp Nephrol 11: 51–55.
[24]
James MT, Hemmelgarn BR, Wiebe N, Pannu N, Manns BJ, et al. (2010) Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet 376: 2096–2103.
[25]
Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375: 2073–2081.
[26]
Lauer MS, Blackstone EH, Young JB, Topol EJ (1999) Cause of death in clinical research: time for a reassessment? J Am Coll Cardiol 34: 618–620.
[27]
Wu VC, Ko WJ, Chang HW, Chen YS, Chen YW, et al. (2007) Early renal replacement therapy in patients with postoperative acute liver failure associated with acute renal failure: effect on postoperative outcomes. J Am Coll Surg 205: 266–276.
[28]
Wu VC, Ko WJ, Chang HW, Chen YW, Lin YF, et al. (2008) Risk factors of early redialysis after weaning from postoperative acute renal replacement therapy. Intensive Care Med 34: 101–108.
[29]
Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40: 373–383.
[30]
Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C (2006) An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 34: 1913–1917.
[31]
Wu VC, Huang DM, Ko WJ, Wu KD (2011) Acute-on-chronic kidney injury predicted long-term dialysis and mortality in critical patients after discharge. Kidney Int. in press.
[32]
Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, et al. (2008) Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 359: 7–20.
[33]
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, et al. (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130: 461–470.
[34]
Haase M, Bellomo R, Matalanis G, Calzavacca P, Dragun D, et al. (2009) A comparison of the RIFLE and Acute Kidney Injury Network classifications for cardiac surgery-associated acute kidney injury: a prospective cohort study. J Thorac Cardiovasc Surg 138: 1370–1376.
[35]
Insurance BoNH (2007) National Health Insurance in Taiwan. Available at wwwnhigovtw/english/indexasp accessed 20 August 2009.
[36]
Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, et al. (1989) Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med 320: 143–149.