대한내과학회지 : 제 76 권제 5 호 2009 특집 (Special Review) - 만성콩팥병, 적극적치료가필요하다. 만성콩팥병의진단및검사 순천향대학교의과대학순천향대학교병원현암신장연구소 권순효 한동철 Diagnosis and screening of chronic kidney disease Soon Hyo Kwon, M.D. and Dong Cheol Han, M.D., Ph.D. Hyonam Kidney Laboratory, Soon Chun Hyang University Hospital, Seoul, Korea A simple definition of chronic kidney disease (CKD) is necessary to establish clinical practical guidelines. The Kidney Disease Outcomes Quality Initiative (K/DOQI) defined CKD as kidney damage or a glomerular filtration rate (GFR) <60 ml/min/1.73 m 2 for 3 months or more, irrespective of cause. In addition, the Kidney Disease: Improving Global Outcome (KDIGO), provided evidence-based understanding of CKD and established global consensus while identifying a collaborative research agenda and plan for the practical definition and classification of CKD. To identify CKD, estimation of the GFR from the serum creatinine and the presence of albuminuria are essential. The GFR estimation needs the application of appropriate equations, such as the Modification of Diet in Renal Disease Study equation or the Cockcroft-Gault formula, and calibration of the serum creatinine. Albuminuria can be detected using an albumin-to-creatinine ratio >30 mg/g in two of three spot urine collections. With the CKD guidelines of K/DOQI and KDIGO, the diagnosis and early detection of CKD, which may need a Korean estimation equation, are improving and should help to reduce the prevalence and incidence of end-stage renal disease in Korea. (Korean J Med 76:515-520, 2009) Key Words: Chronic kidney disease; Estimated GFR; Spot urine albuminuria; K/DOQI 만성콩팥병은진행되기전에발견하는것이중요하다. 최근들어급증하고있는새로운검사나치료중에서만성콩팥병환자에게해로운증례가나타나고있으므로더욱그러하다. Solin에의한인산염신증 (phosphate nephropathy) 1,2), gadolinium MRI 에의한 nephrogenic systemic fibrosis 3,4), 골다공증시투여하는 bisphosphonate에의한신독성 5,6), metformin 에의한 lactic acidosis 7) 등이이에해당된다. 이렇게만성콩팥병은그진행의정도에따라시행해야할각종치료와검사에세심한주의를요한다. 국제신장학회에서정의한만성콩팥병은모두가쉽게받아들일수있게단순명료하여조기진단과그에따른치료를가능하게하고있다. 만성콩팥병을조기에진단한다면시간이경과함에따라콩팥손상의정도를예측할수있고, 만성콩팥병단계에따라사용할수있는적절한약물의용량과범위를가늠할수있을것이다. 또한용이하고간편한만성콩팥병진단기준은증가하고있는만성콩팥병발병을억제하기위해서도더욱그러하다. 이에저자들은현재까지의만성콩팥병정의와진단에필요한검사와한계점을정리하고자한다. 만성콩팥병이란? 미국신장재단과국제신장학회의 Kidney disease: Improving global Outcome (KDIGO) group에서는원인에상관없이 3 개월이상평가사구체여과율 (estimated Glomerular Filtration Rate; egfr) 이 60 ml/min/1.73 m 2 미만인경우와콩팥손상의증거가있을때만성콩팥병으로정의하였다. 콩팥손상의증 - 515 -
- The Korean Journal of Medicine: Vol. 76, No. 5, 2009 - Table 1. Criteria for the definition of chronic kidney disease Structural or functional abnormalities of the kidneys for at least 3 months, as manifested by either (1) Kidney damage, with or without a decreased GFR, as defined by: Pathologic abnormalities Markers of kidney damage - Urinary abnormalities (proteinuria) - Blood abnormalities (renal tubular syndromes) - Imaging abnormalities - Kidney transplantation (donors) Kidney transplant recipients or (2) GFR <60 ml/min/1.73m 2, with or without kidney damage Adapted from the National Kidney Foundation KDOQI 9,10). GFR, glomerular filtration rate. Table 2. Chronic kidney disease: A clinical action plan Stage Description GFR (ml/min/1.73 m 2 ) Action At increased risk 60 (with CKD risk factors) 1 Kidney damage with a normal or GFR 90 Diagnosis and treatment, treatment of comorbid conditions, slow progression, reduce CVD risk 2 Kidney damage with a mild FR 60-89 Estimate progression 3 Moderate FR 30-59 Evaluate and treat complications 4 Severe GFR 15-29 Prepare for kidney replacement therapy 5 Kidney failure <15 (or dialysis) Replacement (if uremia present) GFR, glomerular filtration rate; CKD, chronic kidney disease; CVD, cardiovascular disease. Adapted from the National Kidney Foundation K/DOQI Clinical Practice Guidelines for CKD 8). 거는혈액과소변 ( 단백뇨 ) 또는영상의학적, 병리학적검사등에서이상이있을경우이다 ( 표 1) 8,9). 또한 egfr 의수준에따라 1기에서 5기까지정의하고, 각각의단계에따라필요한행동지침을제시하고있다 ( 표 2) 8,9). 이러한기준에따라흔히임상에서사용하고있는용어인만성신부전은 3기에서 5기에해당되고, 말기신부전은 5기에해당된다 10). 만성콩팥병은원인질환, 손상정도, 질환의진행속도그리고동반된질환에따라서다양한임상형태를보인다 10). 여러가지다양한원인에의하여발병되는만성콩팥병의발견은두가지검사즉, 단백뇨측정을위한검사와 egfr 측정을위한혈액검사로가능하다. 이러한명료한정의와간단한검사에의하여의료인뿐만아니라일반인도만성콩팥병진단을쉽게내릴수있다. 만성콩팥병의선별검사 (screening test) 대상자는? 현재까지일반인구전체를대상으로한선별검사가비용 효과면에서효과적인지는확실하지않다 11,12). KDIGO는만성콩팥병이발생할가능성이높은대상자들을상대로만성콩팥병선별검사를시행할것을권고하였다. 선별검사를가장우선적으로고려해야할대상자는고혈압, 당뇨병, 심혈관계질환이있는환자들이다. 또한노인, 만성콩팥병의가족력이있거나, 고지혈증, 비만, 대사증후군, 흡연등의심혈관계위험인자가있는대상, 잠재적으로콩팥독성이있는약물에노출이되거나, 만성감염그리고종양환자들을포함한다 13). 선별검사의빈도는각질환의임상지침을따르며, 만일지침에적절한기준이없다면 1년에한차례시행하는것을추천하였다 13). 미국당뇨병학회에서는 1형당뇨병은진단후 5년부터 2형당뇨병은진단즉시콩팥병에대한선별검사를시행하고, 이후최소 1년에한차례반복적인검사시행을권유하고있다 14). 일본은 1970년대초반부터학교신체검사등에소변검사를포함시켰으며, 1992년이후부터는만성콩팥병발견을위한혈청크레아티닌검사를 40세이상의전국 - 516 -
- Soon Hyo Kwon, et al. Diagnosis and screening of chronic kidney disease - 민을대상으로시행하고있다. 그결과어린이와 45세이하의성인인구에서사구체질환으로인한말기신부전환자의수는감소하였으며, 만성콩팥병환자에서신대체요법의시작나이가늦어지는효과를보고하였다 15). 국내에서는국민보험공단에서전국민을대상으로하는건강검진항목의 1차검사로요단백, 요잠혈, 요혈당이포함되어있다. 그러나 egfr 측정을위한혈청크레아티닌측정은 1차검사이상자에한하여시행되는 2차검사에포함되어있으므로콩팥병환자발견이늦어지고있다. 우리나라에서매년발병되는말기신부전환자의발병빈도가매우높은나라에속하고있으므로 16), 혈청크레아티닌검사를일본과같이 40세이상전국민을대상으로시행해야한다고생각한다. 또한일본오키나와지역의연구결과를보면비만정도가심각하게증가할수록, 만성콩팥병발병빈도가높다고한다 17). 우리나라역시노년인구가급증하고, 비만인구와당뇨병인구역시급증하므로더욱만성콩팥병발병예방에힘을기울어야한다고생각한다. egfr 의측정방법은? egfr 은콩팥기능측정의가장좋은수단이다. 미국신장재단 Kidney Disease Quality Outcome Initiative (K/DOQI) 지침을참조하면만성콩팥병과관련된합병증은 egfr 이 60 Table 3. Equations for estimating the glomerular filtration rate The original MDRD Study equation 21) GFR=186 Scr-1-154 age -0.203 1.212 [if black] 0.742 [if female] The re-expressed: MDRD Study equation for standardized serum creatinine 22) GFR (ml/min/1.73 m 2 )=175 standardized Scr -1.154 age -0.203 1.212 [if black] 0.742 [if female] The Cockcroft-Gault equation 20) Ccr (ml/min)=(140-age) weight 0.85 [if female] 1.73/(72 Scr BSA) BSA, body surface area. ml/min/1.73 m 2 미만에서증가한다. 또한 egfr 이 60 ml/min /1.73 m 2 미만의환자중에서고혈압은 50~75% 에서발병하고 8), 빈혈역시발병이증가한다 8,18). 직접적인 GFR 측정은매우복잡하고비용이많이들기때문에보통의임상상황에서는시행하지않는다. 또한흔히임상에서콩팥손상의측도로응용하는혈청크레아티닌은개인의근육양, 식이습관그리고검사실간의측정방법의차이등으로인하여콩팥손상을밝히는데한계가있다 19). 따라서개인간의차이를보정하기위한계산식이고안되었다. 추정계산식은크레아티닌과함께나이, 성별, 인종그리고신체치수등의변수가포함하고있으므로해서개인간의차이를보정하게된다 ( 표 3) 20-22). 보다정확한콩팥기능을평가하기위해서 egfr 은자동적으로계산하여검사결과보고시참조할수있도록권유하고있다 ( 그림 1) 23,24). K/DOQI 지침은성인의경우 MDRD 또는 Cockcroft- Gault (CG) 공식을이용하여 egfr 을구할것을권유하였으나 8), 최근 KDIGO에서는큰인구집단과다양한인구집단에서연구되어온점을감안하여 MDRD 공식을추천하였다 9). MDRD 공식에의한한국인의 egfr 측정이임상적으로유용한가에대한검정이필요하다. 중국과일본의연구에서보면 MDRD 공식에의한 egfr 측정치가실제여과율과차이가있었다 25,26). 참고로 egfr이 60 ml/min/1.73 m 2 미만인 CKD 환자는한국 5.0% 27), 미국 4.7% 28), 중국 4.9% 29) 였고, 호주와일본은현저히높아서각각 11.2% 30), 19.2% 31) 였다. 이는모두 MDRD 공식에의한유병률이지만보다일본에서의보고처럼 32), 보다더연구가되어야한다고생각한다. 대한신장학회에서는서울대김연수교수를책임자로한국형 egfr 측정에대한 2년간협연연구를의뢰하였으므로, 이에대한연구결과는우리나라만성콩팥병환자진단에유용하리라생각한다. 검사실마다차이가나는크레아티닌측정치역시해결해야할문제점이다. 2006년재발표된 MDRD 공식에서도표준화된크레아티닌값으로표현되고있으며 22), KDIGO도크레아티닌의표준화를강력히권고하고있다 9). 그러므로대한신장학회와대한진단검사학회의협조하에크레아티닌의표 Figure 1. The calculated egfr is shown automatically in the patient s laboratory results. - 517 -
- 대한내과학회지 : 제 76 권제 5 호통권제 585 호 2009 - 준화에대한지침이필요할것으로생각된다. 또한 CG 공식보다정확하다는 MDRD 공식 33) 역시 60 ml/min/1.73 m 2 이상의경우에서는부정확한것으로밝혀졌다 34,33). KDIGO에서는 egfr 60 ml/min/1.73 m 2 이상에서는 60으로표현하고, 그이하에서만숫자로보고하거나또는모든수준에서숫자로보고하되 60 이상에서는부정확하다는보고를같이할것을권고하고있다 9). 알부민뇨, 단백뇨의임상적유효성은? 알부민뇨란소변에서알부민배출이많아진상태로정의된다. 미세알부민뇨 (microalbuminuria) 는정상범위의알부민보다많이배출되지만단백뇨검사에서는검출되지않는상태를말한다 8,10). 알부민뇨는사구체질환그리고당뇨와고혈압에의한만성콩팥병에서민감하고특이적인표지자이다 8). 또한미세알부민뇨는혈관이전반적으로정상기능을하지못하는표지자 ( 혹은내피세포기능부전표지자 ) 로여겨지고있다 35). 성인의만성콩팥병진단은단백뇨보다더욱민감한알부민뇨의측정이더선호된다 8-10). 오랫동안단백뇨정량검사의방법이었던 24시간요검사는현실적으로번거롭고, 소변의수집과정중실수가있을수있어초기미세알부민뇨의선별검사에적합하지않다 8,9,36). 무작위소변알부민뇨검사는 24시간요검사와높은상관관계를보이고있으며, 검사가편리하고검사비용이싸게들므로만성콩팥병의선별검사에적절하다 37,38). 소변의채취는아침첫소변이가장좋으나, 불가능하다면시간에상관없이채취를하는것도무방하다. 무작위소변알부민뇨는탈수정도와상관이있으므로소변크레아티닌과의비율로보정 (albumin to creatinine ratio or protein to creatinine ratio) 하여정량검사를한다 8,10). 2002년 K/DOQI에서정의한미세알부민뇨의기준치는성별에따른기준 ( 남자 17 mg/g; 여자 25 mg/g) 을제시하였으나 8), 미국당뇨병학회, KDIGO 등에서는 30 mg/g 이상으로하고있다 9,14). 이는성별에따른기준은이용하기에복잡하고, 검사정확성이확실하지않으며, 성별이외에도인종, 식사, 체표면적등의여러가지인자들이알부민뇨에영향을미치기때문에간단한기준을제시한것이다 9,39,40). 최근정상알부민뇨수준에서도알부민뇨의정도가높을수록심혈관계질환의위험도가높아진다고한다 35). 또한지난수십년간고혈압과고지혈증, 당뇨진단기준치가낮아지고있는점을감안한다면, 향후적절한미세알부민뇨의정의는중요연구과제가될것이다 36). 마크로알부민뇨 (macroabulminuria) 또는현성단백뇨 (overt proteinuria) 는 300 mg/g 이상의알부민또는총단백뇨가나올때로정의한다 8). 단백뇨는요로감염, 운동, 발열, 케토산혈증등에의해서일시적으로나타날수있다. 따라서지속적인단백뇨를확인하기위해서는 3개월에걸쳐 3번의검사중 2회이상의소변이상을확인할필요가있다 9). 알부민뇨의양이 500 mg~1,000 mg/g 이상으로많이나올경우에는단백뇨의측정으로대신할수있다 8,10). 단백뇨의지속적인관찰이유는콩팥병의진행정도를반영하고치료의목표가되기때문이다 8). 콩팥손상을찾기위한다른인자의유용성은? 만성콩팥병의다른증거는영상의학적방법, 단백뇨이외의소변혈청의표지자, 조직검사등을이용하여판단한다 8). 뇨검사에서의미있는수의적혈구, 백혈구및원주의존재는정밀검사가필요한급, 만성콩팥병이있음을암시한다 8). 콩팥초음파검사는콩팥기능저하환자에있어서급성과만성의감별에도움을줄수있는검사이다. 콩팥의길이가 7~8 cm 정도로측정된다면가역적인원인에의한콩팥손상일경우의가능성은낮다 41). 또한가족력에다낭성신증이있다면초음파검사등을통해확인할수있을것이다. 최근저자들은복부컴퓨터단층촬영으로측정한콩팥크기로만성콩팥병진단과예방에필요한기초적인자료를발표하면서 42), 아직만성콩팥병진단과관련하여간편한임상적도구개발의여지가있다는것을확인하였다. 결론우리나라는다른나라와비교하여말기신부전의발병률이현저히높은나라 16) 에속하기때문에일차진료의에게만성콩팥병의진단과검사는매우중요한임상책무이다. 만성콩팥병이의심되는환자는혈청크레아티닌측정으로 GFR 을평가하고, 소변알부민과크레아티닌을 3회측정해야한다. 또한만성콩팥병의적절한치료를위해서는원인질환의규명과동반된질환, 합병증의확인이선행되어야할것이다 8). 이를위해서는특히 4기의만성콩팥병, 모호한원인콩팥질환, 현저한단백뇨 ( 500 mg/g), egfr 의빠른감소그리고조절되지않는고혈압과고칼륨혈증인경우에는반드시신장내과전문의와협진하는것이올바른환자접근법이라생각한다 9). 중심단어 : 만성콩팥병 ; 평가사구체여과율 ; 무작위소변알부민요 - 518 -
- 권순효외 1 인. 만성콩팥병의진단및검사 - REFERENCES 1) Markowitz GS, Stokes MB, Radhakrishnan J, D Agati VD. Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure. J Am Soc Nephrol 16:3389-3396, 2005 2) Desmeules S, Bergeron MJ, Isenring P. Acute phosphate nephropathy and renal failure. N Engl J Med 349:1006-1007, 2003 3) Cowper SE. Nephrogenic systemic fibrosis: the nosological and conceptual evolution of nephrogenic fibrosing dermopathy. Am J Kidney Dis 46:763-765, 2005 4) Daram SR, Cortese CM, Bastani B. Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: report of a new case with literature review. Am J Kidney Dis 46:754-759, 2005 5) Hirschberg R. Nephrotoxicity of third-generation, intravenous bisphosphonates. Toxicology 196:165-167, author reply 169-170, 2004 6) Smetana S, Michlin A, Rosenman E, Biro A, Boaz M, Katzir Z. Pamidronate-induced nephrotoxic tubular necrosis: a case report. Clin Nephrol 61:63-67, 2004 7) Misbin RI, Green L, Stadel BV, Gueriguian JL, Gubbi A, Fleming GA. Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338:265-266, 1998 8) National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1-S266, 2002 9) Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G. Definition and classification of chronic kidney disease: a position statement from Kidney Disease. Kidney Int 67:2089-2100, 2005 10) Vassalotti JA, Stevens LA, Levey AS. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. Am J Kidney Dis 50:169-180, 2007 11) Atthobari J, Asselbergs FW, Boersma C, de Vries R, Hillege HL, van Gilst WH, Gansevoort RT, de Jong PE, de Jong-van den Berg LT, Postma MJ. Cost-effectiveness of screening for albuminuria with subsequent fosinopril treatment to prevent cardiovascular events: a pharmacoeconomic analysis linked to the prevention of renal and vascular endstage disease (PREVEND) study and the prevention of renal and vascular endstage disease intervention trial (PREVEND IT). Clin Ther 28:432-444, 2006 12) Boulware LE, Jaar BG, Tarver-Carr ME, Brancati FL, Powe NR. Screening for proteinuria in US adults: a cost-effectiveness analysis. JAMA 290:3101-3114, 2003 13) Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 72:247-259, 2007 14) American Diabetes Association. Standards of medical care in diabetes: 2008. Diabetes Care 31(Suppl 1):S12-S54, 2008 15) Imai E, Yamagata K, Iseki K, Iso H, Horio M, Mkino H, Hishida A, Matsuo S. Kidney disease screening program in Japan: history, outcome, and perspectives. Clin J Am Soc Nephrol 2:1360-1366, 2007 16) United States Renal Data System: international comparisons. 2008. Available from: www.usrds.org/adr/htm. 17) Tanaka H, Shiohira Y, Uezu Y, Higa A, Iseki K. Metabolic syndrome and chronic kidney disease in Okinawa, Japan. Kidney Int 69:369-374, 2006 18) Obrador GT, Pereira BJ. Anaemia of chronic kidney disease: an under-recognized and under-treated problem. Nephrol Dial Transplant 17(Suppl 11):44-46, 2002 19) Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function: measured and estimated glomerular filtration rate. N Engl J Med 354:2473-2483, 2006 20) Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 16:31-41, 1976 21) Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461-470, 1999 22) Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, van Lente F. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247-254, 2006 23) Thorp ML, Eastman L. Potential application of the National Kidney Foundation s chronic kidney disease guidelines in a managed care setting. Am J Manag Care 10:417-422, 2004 24) Yeoh HH, Rasgon S, Rutkowski M, Crooks P, Idroos M, Diesto J. Management of patients with chronic kidney disease at Kaiser Permanente. Nephrol News Issues 17:25-27, 30, 2003 25) Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, Ura N, Kiyohara Y, Hirakata H, Watanabe T, Moriyama T, Ando Y, Inaguma D, Narita I, Iso H, Wakai K, Yasuda Y, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol 11:41-50, 2007 26) Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, Xu JS, Huang SM, Wang LN, Huang W, Wang M, Xu GB, Wang HY. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 17:2937-2944, 2006 27) Kim S, Lim CS, Han DC, Kim GS, Chin HJ, Kim SJ, Cho WY, Kim YH, Kim YS. The prevalence of chronic kidney disease (CKD) and the associated factors to CKD in urban Korea: a population-based cross-sectional epidemiologic study. J Korean Med - 519 -
- The Korean Journal of Medicine: Vol. 76, No. 5, 2009 - Sci 24(Suppl):S11-S21, 2009 28) Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis 41:1-12, 2003 29) Li ZY, Xu GB, Xia TA, Wang HY. Prevalence of chronic kidney disease in a middle and old-aged population of Beijing. Clin Chim Acta 366:209-215, 2006 30) Chadban SJ, Briganti EM, Kerr PG, Dunstan DW, Welborn TA, Zimmet PZ, Atkins RC. Prevalence of kidney damage in Australian adults. J Am Soc Nephrol 14(7 Suppl 2):S131-S138, 2003 31) Imai E, Horio M, Iseki K, Yamagata K, Watanabe T, Hara S, Ura N, Kiyohara Y, Hirakata H, Moriyama T, Ando Y, Nitta K, Inaguma D, Narita I, Iso H, Wakai K, Yasuda Y, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S. Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modified by a Japanese coefficient. Clin Exp Nephrol 11:156-163, 2007 32) Imai H, Yasuda T, Satoh K, Miura AB, Sugawara T, Nakamoto Y. Pan-nephritis (glomerulonephritis, arteriolitis, and tubulointerstitial nephritis) associated with predominant mesangial C1q deposition and hypocomplementemia: a variant type of C1q nephropathy? Am J Kidney Dis 27:583-587, 1996 33) Poggio ED, Wang X, Greene T, van Lente F, Hall PM. Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol 16:459-466, 2005 34) Stevens LA, Coresh J, Feldman HI, Greene T, Lash JP, Nelson RG, Rahman M, Deysher AE, Zhang YL, Schmid CH, Levey AS. Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol 18:2749-2757, 2007 35) Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 108:2154-2169, 2003 36) de Jong PE, Curhan GC. Screening, monitoring, and treatment of albuminuria: public health perspectives. J Am Soc Nephrol 17:2120-2126, 2006 37) Zelmanovitz T, Gross JL, Oliveira J, de Azevedo MJ. Proteinuria is still useful for the screening and diagnosis of overt diabetic nephropathy. Diabetes Care 21:1076-1079, 1998 38) Zelmanovitz T, Gross JL, Oliveira JR, Paggi A, Tatsch M, Azevedo MJ. The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care 20:516-519, 1997 39) Jacobs DR Jr, Murtaugh MA, Steffes M, Yu X, Roseman J, Goetz FC. Gender- and race-specific determination of albumin excretion rate using albumin-to-creatinine ratio in single, untimed urine specimens. Am J Epidemiol 155:1114-1119, 2002 40) Mattix HJ, Hsu CY, Shaykevich S, Curhan G. Use of the albumin/creatinine ratio to detect microalbuminuria: implications of sex and race. J Am Soc Nephrol 13:1034-1039, 2002 41) Graves JW. Diagnosis and management of chronic kidney disease. Mayo Clin Proc 83:1064-1069, 2008 42) Kwon SH, Lee HY, Kim NR, Jeon JS, Noh H, Kim Y, Kim JH, Han DC. Normal kidney volume and length in Korean adults as measured by multidetector-row computerized tomography imaging. Korean J Nephrol 27:659-665, 2008-520 -