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Three Part Question

In [adults (18+) presenting to the A&E with acute renal failure] is [serum Cystatin C] better at [diagnosing acute renal failure] than creatinine.

Clinical Scenario

A patient presents to your A&E department acutely unwell, and you suspect acute renal failure, however creatinine does not appear deranged enough to account for the symptoms seen.

Search Strategy

({[exp Kidney Failure, Acute OR Acute Kidney Failure.mp] AND [exp Cystatins/ or cystatin.mp.]} LIMIT to [English AND human])
Medline 1950 to June Week 3 2007 and EMBASE 1980 to 2007 Week 26 using the OVID interface.

Search Outcome

54 papers were found, of which 50 were irrelevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Villa P et al 2005 Spain	50 critically ill patients aged 21–86 years who did not have chronic renal failure but were at risk for developing renal dysfunction.	PRCT	25 patients did not have renal dysfunction according to 24 creatinine clearance	100% had normal creatinine, 93% had normal cystatin C	Small patient group. Only analyses critically ill patients.
			25 patients did have renal dysfunction according to 24 creatinine clearance	20% had raised serum creatinine, 76% had raised cystatin C
Herget-Rosenthal S et al. 2004 Germany	85 patients with 2 predisposing factors for ARF and normal GFR at the start of the study. 44 developed ARF, 41 served as control.	PRCT	ARF diagnosed according to RIFLE criteria on the basis of creatinine	44 developed ARF according to creatinine levels	Small number of patients
			ARF diagnosed according to RIFLE criteria on the basis of cystatin C	Cystatin C levels increased by ≥50% 1.5 (± 0.6) days earlier
Åhlström A et al. 2004 Germany	202 consecutive adult patients admitted into the intensive care unit (ICU) during a period of 9 months. 54 went on to develop ARF.	PRCT	Patient did not develop ARF	Serum creatinine and cystatin C remained within normal limits	Small number of patients. Used Apache II score rather than RIFLE criteria.
			Patient developed ARF	Serum creatinine and cystatin C became elevated at the same time (median 3 days). Mortality poorly predicted by either
Bouvet Y et al. 2006 France	100 children or young adults (aged 1.4–22.8 years old), who needed an EDTA clearance test. GFR was then estimated using a number of formulae, which either included or excluded serum creatinine, serum cystatin c, age and body weight.		GFR predicted using all 4 criteria	GFR calculated most accurately by comparison with 24 EDTA clearance.	Small patient group.
			GFR predicted using less than 4 criteria	GFR calculated less accurately than with other criteria added.
Donadio, C. et al. 2001 Italy	110 patients had creatinine, cystatin C, b2-microglobulin, and retinol-binding protein measured and comapred to renal clearance. Only results for creatinine and cystatin C are included.	prospective study	Creatinine measured	raised by a significant amount when GFR fell below 80ml/min/1.73m2	Poor patient selection process, small group of patients.
			Cystatin C measured	raised by a significant amount when GFR fell below 60ml/min/1.73m2

Comment(s)

In all studies, cystatin C was shown to be at least equally diagnostic of ARF as creatinine. In a number of small studies, Cystatin C was found to predict ARF 1.5-2 days earlier than creatinine, however certain other studies found no difference in the time serum creatinine and cystatin C changed. Although Åhlström A et al. found that both creatinine and cystatin C were poor predictors of mortality, they were also the only trial not to use the RIFLE criteria, which has been shown to be a good predictor of mortality. Therefore this finding can be ignored. These differences in finding show great promise but also highlight the need for a large trial into the use of cystatin C as a diagnostic marker for ARF.

Clinical Bottom Line

The full reliability of cystatin C, especially in septic patients, remains unknown. A large enough study to pick up rare erroneous results has not been carried out. As such cystatin C cannot currently be recommended as a replacement for serum creatinine. However, if used in conjunction with serum creatinine, cystatin C can help to predict development of ARF earlier, and aid in initiating therapy.

References

1. Villa P et al Serum cystatin C conc as a marker of acute renal dysfunction in criticially ill patients Crit Care 9(2); R139-43
2. Herget-Rosenthal S et al. Early Detection of Acute Renal Failure by Serum Cystatin C Kidney Int 66(3); 1115-22
3. Åhlström A et al. Evolution and predictive power of serum cystatin C in acute renal failure Clin Nephrol 62(5); 344-50
4. Bouvet Y et al. GFR is better estimated by considering both serum cystatin C and creatinine levels Pediatr Nephrol 21(9); 1299-306
5. Donadio, C. et al. Cystatin C, beta 2-microglobulin, and retinol-binding protein as indicators of glomerular filtration rate: comparison with plasma creatinine J Pharm Biomed Anal 24(5-6); 835-42