正常成人每天尿蛋白排泄量平均为80mg/d，小于150mg/d可视为正常。白蛋白大约占健康人群每天尿蛋白排泄的15%，还有其他血浆蛋白（例如，免疫球蛋白，β2微球蛋白）和Tamm-Horsfall蛋白占85%。蛋白尿中蛋白含量各异，可为一过性或持续存在。[1]Viswanathan G, Upadhyay A. Assessment of proteinuria. Adv Chronic Kidney Dis. 2011;18:243-248.
http://www.ncbi.nlm.nih.gov/pubmed/21782130?tool=bestpractice.com
[2]Montañés Bermúdez R, Gràcia García S, Pérez Surribas D, et al. Consensus document. Recommendations on assessing proteinuria during the diagnosis and follow-up of chronic kidney disease. Nefrologia. 2011;31:331-345.
http://www.ncbi.nlm.nih.gov/pubmed/21780317?tool=bestpractice.com
尿蛋白量排泄异常持续≥3 个月，伴有或不伴有肾小球滤过率 (GFR) 下降，是慢性肾脏病的诊断依据。[3]National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(suppl 1):S1-S266.
http://www.kidney.org/Professionals/Kdoqi/guidelines_ckd/toc.htm
http://www.ncbi.nlm.nih.gov/pubmed/11904577?tool=bestpractice.com
[4]Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011;80:17-28.
http://www.ncbi.nlm.nih.gov/pubmed/21150873?tool=bestpractice.com
尿白蛋白测量是检查慢性肾脏病的重要组成部分。在普通人群和慢性肾脏病患者中，蛋白尿是心血管疾病、死亡和终末期肾病的一个独立危险因素。[5]Chronic Kidney Disease Prognosis Consortium; Matsushita K, van der Velde M, Astor BC, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073-2081.
http://www.ncbi.nlm.nih.gov/pubmed/20483451?tool=bestpractice.com
[6]Astor BC, Matsushita K, Gansevoort RT, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int. 2011;79:1331-1340.
http://www.ncbi.nlm.nih.gov/pubmed/21289598?tool=bestpractice.com
[7]van der Velde M, Matsushita K, Coresh J, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int. 2011;79:1341-1352.
http://www.ncbi.nlm.nih.gov/pubmed/21307840?tool=bestpractice.com
[8]Gansevoort RT, Matsushita K, van der Velde M, et al. Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int. 2011;80:93-104.
http://www.ncbi.nlm.nih.gov/pubmed/21289597?tool=bestpractice.com
[9]British Medical Journal. Low eGFR and high albuminuria predict end stage kidney disease and death at all ages. BMJ. 2012;345:e7478.
http://www.ncbi.nlm.nih.gov/pubmed/23135200?tool=bestpractice.com
危重症患者蛋白尿与高死亡率相关；[10]Han SS, Ahn SY, Ryu J, et al. Proteinuria and hematuria are associated with acute kidney injury and mortality in critically ill patients: a retrospective observational study. BMC Nephrol. 2014;15:93.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072664/
http://www.ncbi.nlm.nih.gov/pubmed/24942179?tool=bestpractice.com
[11]Lin LY, Jenq CC, Liu CS, et al. Proteinuria can predict short-term prognosis in critically ill cirrhotic patients. J Clin Gastroenterol. 2014;48:377-382.
http://www.ncbi.nlm.nih.gov/pubmed/24440941?tool=bestpractice.com
肾脏移植后蛋白尿的程度是移植物和患者存活率的预测指标。[12]Borrego J, Mazuecos A, Gentil MA, et al. Proteinuria as a predictive factor in the evolution of kidney transplantation. Transplant Proc. 2013;45:3627-3629.
http://www.ncbi.nlm.nih.gov/pubmed/24314978?tool=bestpractice.com
药物疗法后蛋白尿的减少可用作针对慢性肾病和许多急性肾小球疾病管理的一项替代标志物，并与肾脏疾病预后的改善有关。[13]Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456-1462.
http://www.nejm.org/doi/full/10.1056/NEJM199311113292004#t=article
http://www.ncbi.nlm.nih.gov/pubmed/8413456?tool=bestpractice.com
[14]The GISEN Group. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349:1857-1863.
http://www.ncbi.nlm.nih.gov/pubmed/9217756?tool=bestpractice.com
[15]Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.
http://www.nejm.org/doi/full/10.1056/NEJMoa011161#t=article
http://www.ncbi.nlm.nih.gov/pubmed/11565518?tool=bestpractice.com
[16]Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860.
http://www.nejm.org/doi/full/10.1056/NEJMoa011303#t=article
http://www.ncbi.nlm.nih.gov/pubmed/11565517?tool=bestpractice.com
[17]Parving HH, Lehnert H, Bröchner-Mortensen J, et al; Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870-878.
http://www.nejm.org/doi/full/10.1056/NEJMoa011489#t=article
http://www.ncbi.nlm.nih.gov/pubmed/11565519?tool=bestpractice.com
[18]Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288:2421-2431.
http://jama.ama-assn.org/cgi/content/full/288/19/2421
http://www.ncbi.nlm.nih.gov/pubmed/12435255?tool=bestpractice.com
[19]Inker LA, Levey AS, Pandya K, et al. Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis. Am J Kidney Dis. 2014;64:74-85.
http://www.ncbi.nlm.nih.gov/pubmed/24787763?tool=bestpractice.com
蛋白尿定义
尿蛋白总量或尿白蛋白均可被测量。尿白蛋白测量值被认为与慢性肾脏病进展和发生心血管事件的风险间的相关性更高。
白蛋白尿
白蛋白尿分级如下：[20]Kidney Disease: Improving Global Outcomes. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. January 2013. http://www.kdigo.org (last accessed 9 August 2017).
http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf
A1(正常至轻度白蛋白尿)
白蛋白排泄率：<30mg/24小时。
白蛋白/肌酐比率（ACR）：＜30mg/g。
A2(中度白蛋白尿)
A3(重度白蛋白尿)
肾病性蛋白尿
肾小球性蛋白尿
肾小管性蛋白尿
溢出性蛋白尿
白蛋白尿对慢性肾脏病预后的影响
白蛋白尿是慢性肾脏病进展的独立危险因素。与轻度GFR下降伴有正常白蛋白尿相比，正常GFR伴有大量蛋白尿对于进展型慢性肾脏病而言更加危险。
[Figure caption and citation for the preceding image starts]: 通过GFR和蛋白尿分类的CKD预后：CKD，慢性肾脏病；GFR，肾小球滤过率；KDIGO，肾病提高全球成果获得麦克米伦出版公司重印许可：Kidney International Supplements (vol 3, issue 1, January 2013), copyright 2013 [Citation ends].
对于晚期 CKD 患者，蛋白尿是终末期肾病的最强预测指标。[21]Grams ME, Li L, Greene TH, et al. Estimating time to ESRD using kidney failure risk equations: results from the African American Study of Kidney Disease and Hypertension (AASK). Am J Kidney Dis. 2015;65:394-402.
http://www.ncbi.nlm.nih.gov/pubmed/25441435?tool=bestpractice.com
流行病学
常见蛋白尿，且其发生率随着肾脏病的进展而增加。有证据表明，与白种人相比，黑种人出现中度和重度白蛋白尿更加常见。GFR 从＞90 mL/分/1.73 m^2 下降到 15-59 mL/分/1.73 m^2，中度升高的白蛋白尿（ACR＜300 mg/g）发生率从 6.0% 上升至 23.2%，重度升高的白蛋白尿（ACR＞300 mg/g）发生率从 0.6% 上升至 8.6%。[22]Astor BC, Hallan SI, Miller ER 3rd, et al. Glomerular filtration rate, albuminuria, and risk of cardiovascular and all-cause mortality in the US population. Am J Epidemiol. 2008;167:1226-1234.
http://aje.oxfordjournals.org/cgi/content/full/167/10/1226
http://www.ncbi.nlm.nih.gov/pubmed/18385206?tool=bestpractice.com
还有证据表明中度白蛋白尿发生率可随体重指数(BMI)的增加而增加。英国谢菲尔德大学的一项人口筛查项目发现白蛋白尿发生率从占 BMI＜25 人群的 3.1% 增加到 BMI＞30 人群的 27.2%。[23]Kawar B, Bello AK, El Nahas AM. High prevalence of microalbuminuria in the overweight and obese population: data from a UK population screening programme. Nephron Clin Pract. 2009;112:c205-c212.
http://www.ncbi.nlm.nih.gov/pubmed/19451722?tool=bestpractice.com
检测：定量测试
实验室蛋白尿常规检测传统上使用多试剂尿液试纸。
尿液白蛋白检测经浸染试剂的试纸条的比色反应完成。
试纸检测法对非白蛋白的敏感性有局限性，因此，当对肾小管性或溢出性蛋白尿存在时常常为假阴性。
尿液试纸条对白蛋白的敏感性是 83%-98%，特异性为 59%-86%。[24]Siedner MJ, Gelber AC, Rovin BH, et al. Diagnostic accuracy study of urine dipstick in relation to 24-hour measurement as a screening tool for proteinuria in lupus nephritis. J Rheumatol. 2008;35:84-90.
http://www.ncbi.nlm.nih.gov/pubmed/18085740?tool=bestpractice.com
[25]White SL, Yu R, Craig JC, et al. Diagnostic accuracy of urine dipsticks for detection of albuminuria in the general community. Am J Kidney Dis. 2011;58:19-28.
http://www.ncbi.nlm.nih.gov/pubmed/21411199?tool=bestpractice.com
此反应依赖于白蛋白浓度，所以对大量、稀释尿液的检测会低估白蛋白尿水平。同理，检测高度浓缩尿液可能高估白蛋白尿水平。
显著碱性PH(>8.0)和碘化放射造影剂的使用也可能产生假阳性结果。
虽然定性试纸检测快速，简洁，且常见，但是它的假阳性和假阴性率限制了其使用。
[Figure caption and citation for the preceding image starts]: 蛋白尿试纸条范围BMJ证据中心，根据作者内容确定 [Citation ends].
检测：半定量检测
更新的试纸条已进入市场，可以在微量白蛋白范围内检测白蛋白/肌酐比率和总蛋白/肌酐比率。
标准化尿蛋白检测以定量尿液中的肌酐来避免稀释或浓缩尿液样本可造成误差。
测量全部蛋白可以用于检出肾小管性和溢出性蛋白尿。根据报告，这些半定量试纸的敏感性是 80%-97%，特异性为 33%-80%。[26]Comper WD, Osicka TM. Detection of urinary albumin. Adv Chronic Kidney Dis. 2005;12:170-176.
http://www.ncbi.nlm.nih.gov/pubmed/15822052?tool=bestpractice.com
检测：定量检测
采用尿白蛋白浓度或尿白蛋白/肌酐比率的白蛋白定量检测，对检测白蛋白尿具有敏感性和特异性。[27]McTaggart MP, Newall RG, Hirst JA, et al. Diagnostic accuracy of point-of-care tests for detecting albuminuria: a systematic review and meta-analysis. Ann Intern Med. 2014;160:550-557.
http://www.ncbi.nlm.nih.gov/pubmed/24733196?tool=bestpractice.com
[28]Wu HY, Peng YS, Chiang CK, et al. Diagnostic performance of random urine samples using albumin concentration vs ratio of albumin to creatinine for microalbuminuria screening in patients with diabetes mellitus: a systematic review and meta-analysis. JAMA Intern Med. 2014;174:1108-1115.
http://www.ncbi.nlm.nih.gov/pubmed/24798807?tool=bestpractice.com
测定尿白蛋白浓度而不测定尿肌酐浓度时价格较低，并作为糖尿病患者的筛查，表现出与白蛋白肌酐比值类似的敏感性和特异性。[28]Wu HY, Peng YS, Chiang CK, et al. Diagnostic performance of random urine samples using albumin concentration vs ratio of albumin to creatinine for microalbuminuria screening in patients with diabetes mellitus: a systematic review and meta-analysis. JAMA Intern Med. 2014;174:1108-1115.
http://www.ncbi.nlm.nih.gov/pubmed/24798807?tool=bestpractice.com
传统应用的24小时尿液收集法易出现收集量过多或过少的偏差。且收集24小时尿液对患者来说是比较麻烦的。24小时尿蛋白经24小时尿液肌酐校正后（g蛋白/g肌酐）有助于减少收集过程中的偏差。
女性尿肌酐正常范围在15-20mg/kg，男性是20-25mg/kg
或者尿肌酐排泄的估值(g)=（140-年龄）x体重（kg）/5000。女性计算结果需乘以 0.85。[29]Ginsberg JM, Chang BS, Matarese RA, et al. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983;309:1543-1546.
http://www.ncbi.nlm.nih.gov/pubmed/6656849?tool=bestpractice.com
更常见的是，随机尿的尿蛋白/肌酐比率或尿白蛋白/肌酐比率被用来分别估计24小时尿蛋白排泄量和24小时尿白蛋白排泄。
在检测低水平的蛋白尿时，白蛋白肌酐比值比蛋白肌酐比值更敏感。[30]National Institute for Health and Care Excellence. Chronic kidney disease in adults: assessment and management. January 2015. https://www.nice.org.uk/ (last accessed 9 August 2017).
https://www.nice.org.uk/guidance/cg182/
清晨尿标本可以更准确地评估 24 小时尿蛋白排泄，无法采集晨尿时，随机样本也可采用。[3]National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(suppl 1):S1-S266.
http://www.kidney.org/Professionals/Kdoqi/guidelines_ckd/toc.htm
http://www.ncbi.nlm.nih.gov/pubmed/11904577?tool=bestpractice.com
[29]Ginsberg JM, Chang BS, Matarese RA, et al. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med. 1983;309:1543-1546.
http://www.ncbi.nlm.nih.gov/pubmed/6656849?tool=bestpractice.com
[31]Johnson DW, Jones GR, Mathew TH, et al. Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement. Med J Aust. 2012;197:224-225.
https://www.mja.com.au/journal/2012/197/4/chronic-kidney-disease-and-measurement-albuminuria-or-proteinuria-position
http://www.ncbi.nlm.nih.gov/pubmed/22900872?tool=bestpractice.com
由于每日变化，如果需要长期检测患者尿蛋白，最好是连续收集每天相同时间随机尿标本。此外，随机尿样本经24小时排泄量校正与肾病性蛋白尿的相关性较差。尿蛋白＞300 mg 的妊娠妇女的随机尿比率更加缺乏准确性。[32]Papanna R, Mann LK, Kouides RW, et al. Protein/creatinine ratio in preeclampsia: a systematic review. Obstet Gynecol. 2008;112:135-144.
http://www.ncbi.nlm.nih.gov/pubmed/18591319?tool=bestpractice.com
[33]Côté AM, Brown MA, Lam E, et al. Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review. BMJ. 2008 ;336:1003-1006.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364863
http://www.ncbi.nlm.nih.gov/pubmed/18403498?tool=bestpractice.com
每1.73 m^2人体表面积的肌酐排泄量大致是1g。一个平均体表面积的个体每1g尿蛋白/g肌酐比近似于24小时内尿中有1 g的蛋白排泄。认识到这一点很重要，一个身体强壮的人，在24小时内排泄2g，那么如果他的尿蛋白/肌酐比为2.5 g蛋白/g肌酐实际上说明他的蛋白排泄量为5g/天，这已在肾病综合征的范畴。同样，一个老年且身体虚弱的女人可能每天排泄＜1g肌酐，在此状况下，随机比率将高估她的蛋白尿含量。
