Measuring proteinuria: albumin or total protein?
The Scottish Intercollegiate Guidelines Network (SIGN) produced a guideline on chronic kidney disease in June 2008 (1). The recommendations are similar to the National Institute for Health and Clinical Excellence's (NICE) guideline (2) with one important difference. Both guidelines highlight the importance of formally measuring proteinuria in patients being assessed or monitored for chronic kidney disease. However, NICE recommends measuring proteinuria with an albumin:creatinine ratio in all patients, whereas SIGN recommends using albumin:creatinine ratio in patients with diabetes mellitus, and protein:creatinine ratio in non-diabetic patients. As Crowe and colleagues (3) state, in non-diabetic patients, the evidence of increased renal risk associated with proteinuria (4), and the evidence of reduced risk with interventions (5) is based on total proteinuria, not albuminuria. Protein:creatinine ratio predicts total proteinuria well, but albumin:creatinine ratio does not.
The NICE guideline has extrapolated further from the evidence than the SIGN guideline. It assumes that albuminuria is a more sensitive detector of increased renal risk, but cites weak studies based on estimated glomerular filtration rate in chronic kidney disease stages 1 and 2, which did not measure total proteinuria. The NICE guideline assumes that interventions based on total proteinuria thresholds will apply equally to the albuminuria thresholds chosen, with little supporting evidence. The guideline also assumes that patients with protein:creatinine ratio >50 mg/mmol but albumin:creatinine ratio <_30 mg="mg" mmol="mmol" will="will" not="not" benefit="benefit" from="from" intervention="intervention" again="again" with="with" no="no" evidence.="evidence." it="it" is="is" possible="possible" that="that" these="these" assumptions="assumptions" are="are" correct="correct" but="but" none="none" have="have" been="been" adequately="adequately" tested.="tested." p="p"/>It is also important to note that the p suffix in Scotland denotes patients with a protein-creatinine ratio >100 mg/mmol or 24-hour urinary protein >1 g/day, whereas in England it will denote a group with ACR >30 mg/day, thus identifying two different patient populations. Although important, this technical debate should not distract from the key message of both guidelines that formally measuring proteinuria identifies patients at increased risk of kidney and cardiovascular disease.
1. Scottish Intercollegiate Guidelines Network. Diagnosis and management of chronic kidney disease: a national clinical guideline. SIGN 103. SIGN, Edinburgh, June 2008. www.sign.ac.uk/guidelines/fulltext/103/index.html
2. National Institute for Health and Clnical Excellence. Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care. (Clinical guideline 73) NICE: London, Sept 2008. www.nice.org/Guidance/CG73/NiceGuidance/pdf/English
3. Crowe E, Halpin D, Stevens P. Early identification and management of chronic kidney disease: summary of NICE guidance. BMJ 2008;337:a1530.
4. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, Marcantoni C et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int 2001;60:1131-40.
5. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med 2003;139:244-52.
I was a member of the SIGN CKD Guideline Development Group
Competing interests: No competing interests