Cystatin C as a reliable marker of renal function following heart valve replacement surgery with cardiopulmonary bypass

Abstract

Background

Little is known about serum cystatin C as a marker of renal function in cardiac surgery patients. The aim of this study was to assess its utility post cardiopulmonary bypass (CPB).

Methods

60 heart valve replacement patients were enrolled, and 26 of them had low-dose corticosteroid treatment on the first 3 days postoperatively. Serum creatinine, serum cystatin C and 24-h creatinine clearance rate (CCR) adjusted by body surface area were determined preoperation, days 1, 2, 3, 7 post operation.

Results

Serum creatinine increased and peaked at day 3 postoperatively, while cystatin C peaked at day 2, and the adjusted CCR also reached a minimum at day 2. The inverse of cystatin C correlated better with CCR than that of creatinine (r = 0.751 vs. 0.629). Using adjusted CCR as “golden standard”, cystatin C was superior to creatinine in diagnosing renal dysfunction (area under the curve [AUC] for cystatin C 0.876, 95% confidence interval 81.8–93.4; AUC for creatinine 0.801, 95% confidence interval 72.5–87.7; p = 0.045). Low-dose corticosteroid treatment has no significant effect on cystatin C.

Conclusion

In agreement with many other investigators, the present findings support cystatin C is a reliable marker of renal function. It is superior to creatinine in patients post CPB.

Introduction

Acute renal dysfunction is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). It affects about 7–40% patients and associates with mortality especially in those who require dialysis [1], [2], [3]. Studies have shown that the aetiology of renal injury is multifactorial, including ischemia–reperfusion injury, perioperative renal hypoperfusion, inflammation, nephrotoxins, advanced age and pre-existing renal dysfunction [4]. A recent study concluded that heart valve operation is an independent risk of acute renal failure (ARF) [5]. For those who developed ARF eventually, there are no effective drug treatments till now. So it is of great importance to evaluate perioperative renal function exactly and promptly, and then renal injury can be managed earlier and the risk of ARF will be reduced.

There are a number of available renal function tests, and each examines a different aspect of the kidney's function. Glomerular filtration rate (GFR) is probably the best overall index of renal function. The “gold standard” for determining GFR is to measure the clearance of exogenous substances such as insulin, ⁵¹Cr-EDTA, ⁹⁹mTc-DTPA, iohexol, or ¹²⁵I-labeled iothalamate. But the techniques for determining GFR are time-consuming, labor-intensive and expensive, which make them unpractical for routine monitoring. As a result, the usual rapid-estimation and first-line test of glomerular function has been creatinine clearance rate (CCR), however, it still requires exact urine collection, measurement of urine creatinine and calculation. Serum creatinine is the most widely used assessment of renal function. However, it is a specific marker but not very sensitive. A substantial proportion of patients with a reduced GFR have creatinine values within the normal range, and even a 50% reduction in GFR may be associated with normal creatinine concentrations. Except for this, it can be affected by other factors, such as muscle mass, dietary intake, changes in tubular secretion, and interference by other substances in the serum when measured.

Cystatin C is an alkaline non-glycosylated protein belonging to the cysteine protease inhibitors of the cystatin superfamily. It is produced by all nucleated cells at a constant rate. Due to its low molecular weight (13.3 kDa) and positive charge at physiological pH, cystatin C is freely filtered through the glomerular membrane, which is the major elimination pathway. Then it is nearly completely reabsorbed and degraded by the proximal tubular cells [6], [7], [8]. In addition, its concentration is not affected by sex, age, diet, muscle mass, infections, or inflammation diseases; its assay is less susceptible to methodological interference and has less inter-individual variation than creatinine. These characteristics determine that it is a good endogenous marker of GFR, which has been proven in various experimental and clinical settings [9], [10], [11], [12], [13], [14], [15], [16].

However, there are only a few studies about the use of cystatin C in perioperative patients until now [12], [17], [18], [19], [20], and very few studies of its diagnostic use after cardiac surgery have been performed. CPB is a complicated process, and low-dose glucocorticoids are often used postoperatively for a few days such as dexamethasone and methylprednisolone. These may affect the concentration of cystatin C. The aim of present study was to assess the efficacy of cystatin C as a marker of GFR following cardiac surgery with CPB primarily, and to investigate whether cystatin C is influenced by the low-dose glucocorticoids therapy secondarily.