Post-operative renal dysfunction has long been considered to be a relatively minor event, since its effect on the immediate prognosis of the patient is not evident. Thus, a transient increase in serum creatinine in the post-operative period was regarded as being of little relevance to clinical outcome. Ronco and Flahault1 highlighted the impact of cumulative renal injuries from various life events, such as nephrotoxic drugs or peri-operative renal insult, which may ultimately lead to irreversible renal injury. Svensson and colleagues2 had suggested previously that a post-operative increase in serum creatinine of above 180 µmol litre1, frequently considered as negligible, was associated with an increase in late mortality from 30% to 50% 5 yr after major aortic surgery. Moreover, a recent study by Chertow and colleagues3 has demonstrated clearly that post-operative acute renal failure, albeit transient, is a risk factor for early mortality following cardiac surgery, even after adjustment for comorbidity and post-operative complications. This large study, which included 42 773 patients, conclusively proved that there is an independent association between post-operative acute renal failure and mortality: dialysis, even if transient, was associated with a 27-fold increase in the odds of death. This contradicts the widely held opinion that acute renal failure is simply a marker of comorbidity.3 The potential for cumulative small renal insults to lead to irreversible renal failure, and the increase in post-operative mortality due to renal failure (at least in some situations), clearly indicates that post-operative renal failure, even if transient, should be of major concern to the anaesthetist.
Numerous tests have been proposed to assess perioperative renal function but none is ideal.4 The easiest technique is to record the requirements for dialysis. The advantages of this method lie in its simplicity and objectivity, and the possibility of collecting data from large cohorts, as in the study of Chertow and colleagues.3 The problem with this technique is its inability to detect lesser degrees of post-operative renal dysfunction, since it only detects a glomerular filtration rate (GFR) of less than approximately 10 ml min1 and thus cannot be recommended to identify moderate renal dysfunction.
An increase in serum creatinine is routinely used to detect perioperative renal impairment and most studies of post-operative renal function have used this variable.5 However, this technique suffers also from a lack of sensitivity. GFR could be reduced by 5070% without leading to an increase in serum creatinine concentration because the decrease in glomerular filtration of creatinine is balanced by increased creatinine secretion by cells in the proximal tubule cells. Also, serum creatinine is affected by a number of extrarenal variables, especially in the post-operative period.6 7 These include fluid loading and the resultant dilution, variable muscle mass and a high metabolic rate, all of which may contribute to misleading information.4 6 7 Although changes in creatinine and urea are widely used for post-operative renal assessment, they detect only 30% of patients with post-operative renal impairment.4 8 9 Urinary volume has been proposed as an alternative measure, but is unreliable10 because oliguria may result also from hypovolaemia or altered concentrations of hormones.
On the other hand, some variables identify a renal abnormality but cannot be used to diagnose renal impairment. Free water clearance, urinary sodium excretion or renal blood flow inform us about renal function but none of them may be used in isolation to define post-operative renal dysfunction. In fact, the strict definition of acute renal failure is a decline in GFR and consequently a retention of nitrogenous waste products such as blood urea nitrogen and creatinine.7 Since the definition of renal insufficiency is a decrease in GFR, definition of post-operative renal dysfunction should be based on measurement of GFR, the gold standard for which is inulin clearance. Inulin was the first substance to meet the criteria of an ideal filtration markerit is freely filterable, non-toxic, pharmacologically inert and neither reabsorbed nor secretedbut it is impractical to use because it must be given by constant infusion.11 Radioactive markers have been proposed because they require only a single infusion to evaluate GFR. The most widely used compounds are [99Tc]DTPA, 125I-labelled iothalamate and [51Cr]EDTA. Methods using labelled agents cannot be recommended for routine use, except when the number of samples is small, because they are invasive and costly. Iodinated contrast agents have been proposed more recently, notably iohexol (omnipaque), whose clearance is well correlated with inulin clearance.12
Creatinine clearance has long been used to assess the ability of the glomeruli to filter creatinine. However, the limitations of creatinine clearance in assessing GFR are well recognized, especially in the post-operative period. The main problems with the technique are overestimation of GFR because of tubular secretion1315 and the need to measure the urine volume accurately. Some authors13 16 have compared a 24 h collection with a 2 h collection to assess GFR. These studies have demonstrated that in critically ill patients, creatinine clearance obtained from a 2 h collection provides the same information as reliably as a 24 h collection. The decision is a balance between the risk of residual urine produced but not collected, which favours 24 h collection, and the risks of collection errors and disruption by other complementary investigations, which favour 2 h collection.
Creatinine clearance could be theoretically calculated from creatinine concentration without urine collection using the Cockroft formula.17 This formula can be used only if the patient has a stable serum creatinine concentration18 and thus cannot be used when serum creatinine is modified by haemodilution. Consequently, the Cockroft formula is useful for screening high renal risk patients in the pre-operative period, but cannot be used to calculate post-operative creatinine clearance because serum creatinine is often reduced by haemodilution.
One of the questions raised by Ryckwaert and colleagues19 in this issue of the journal is the usefulness of improving renal perfusion, and the link between renal blood flow or renal plasma flow and GFR. There is a complex relationship between renal blood flow or renal plasma flow and GFR, including autoregulation of GFR and hormonal control. It cannot be assumed that increasing renal plasma flow, as enalaprilat did in the study by Ryckwaert and colleagues,19 is equivalent to improving renal function. The two variables are connected but there is not a linear relation between them. The increase in effective plasma renal flow is not surprising since it is a fraction of cardiac output, and this was also increased in the study by Ryckwaert and colleagues.19 The most serious adverse effect of angiotensin-converting-enzyme inhibitors during anesthesia is hypotension, especially on induction.20 Hypotension may counterbalance the beneficial effect of improving renal perfusion. It should be noted that Ryckwaert and colleagues failed to demonstrate any improvement in GFR when renal plasma flow increased, except immediately after cardiopulmonary bypass.19 It remains to be determined whether there is an effect of a transient increase in GFR at this time.
In summary, we have to keep in mind the difficulty in assessing renal function in the peri-operative period, because of the difficulty in accurately measuring GFR. In the post-operative period, patients who require dialysis, or whose serum creatinine is increased, have obviously suffered a serious renal insult. However, 6070% of cases of renal impairments go undetected and these patients may have a poor long-term renal prognosis. This point is an argument for the assessment of pre-operative and post-operative GFR in high-risk patients. For small numbers of samples in clinical research, labelled agents could be used and iodinated contrast agents are promising. The Cockroft formula is useful in stable situations, such as the pre-operative period. In other cases, the best evaluation is provided by creatinine clearance, even if this technique remains imperfect. In the future, one of the main questions for anaesthetists will be renal protection, as it was for cardiac events in the past decade. We have to define high-risk populations, what should be considered as significant renal impairment, and its impact on patients health and prognosis.
M. L. Cittanova
Département dAnesthésieRéanimation
Pitié-Salpêtrière University Hospital
4783 Boulevard de lHôpital
F-75651 Paris cedex 13
France
References
1 Ronco PM, Flahault A. Drug-induced end-stage renal disease. New Engl J Med 1994; 331: 171112
2 Svensson LG, Coselli JS, Safi HJ, et al. Appraisal of adjuncts to prevent acute renal failure after surgery on the thoracic or thoracoabdominal aorta. J Vasc Surg 1989; 10: 2309[ISI][Medline]
3 Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998; 104: 3438[ISI][Medline]
4 Kellen M, Aronson A, Roizen MF, et al. Predictive and diagnostic tests of renal failure: a review. Anesth Analg 1994; 78: 13442[Abstract]
5 Novis BK, Roizen MF, Aronson A, et al. Association of preoperative risk factors with postoperative acute renal failure. Anesth Analg 1994; 78: 1439[Abstract]
6 Star RA. Treatment of acute renal failure. Kidney Int 1998; 54: 181731[ISI][Medline]
7 Brady HR, Brenner BM, Lieberthal W. Acute renal failure. In: Brenner BM, ed. Brenner & Rectors The Kidney, 5th Edn. 1996: 120052
8 Charlson ME, MacKenzie CR, Gold JP, Shires GT. Postoperative changes in serum creatinine: when do they occur and how much is important? Ann Surg 1989; 209: 32833[ISI][Medline]
9 Zubicki A, Cittanova ML, Zaier K, et al. Serum creatinine cannot predict renal impairment in the perioperative period. Br J Anaesth 1998; 80 (suppl 1): 7[ISI][Medline]
10 Alpert RA, Roizen MF, Hamilton WK, et al. Intraoperative urinary output does not predict postoperative renal function in patients undergoing abdominal aortic revascularization. Surgery 1984; 95: 70711[ISI][Medline]
11 Mitch WE, Walser M. Nutritional therapy for the uremic patient. In: Brenner BM, ed. Brenner & Rectors The Kidney, 5th Edn. 1996: 2382423
12 Rahn KH, Heidenreich S, Bruckner D. How to assess glomerular function and damage in humans. J Hyperten 1999; 17: 30917[ISI][Medline]
13 Wilson RF, Soullier G. The validity of two-hour creatinine clearance studies in critically ill patients. Crit Care Med 1980; 8: 2814[ISI][Medline]
14 Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28: 8308[ISI][Medline]
15 Lavender S, Hilton P, Jones N. The measurement of glomerular filtration-rate in renal disease. Lancet 1969; i: 12168
16 Sladen RN, Endo E, Harrison T. Two-hour versus 24-hour creatinine clearance in critically ill patients. Anesthesiology 1987; 67: 101316[ISI][Medline]
17 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 3141[ISI][Medline]
18 Shuler C, Golper T, Bennett WM. Prescribing drugs in renal disease. In: Brenner BM, ed. Brenner & Rectors The Kidney, 5th Edn. 1996; 2653702
19 Ryckwaert F, Colson P, Ribstein J, Boccara G, Guillon G. Haemodynamics and renal effects of iv enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction. Br J Anaesth 2000; 86: 169175
20 Coriat P, Richer C, Douraki T, et al. Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction. Anesthesiology 1994; 81: 299307[ISI][Medline]