Diagnostic Accuracy of Urine Protein/Creatinine Ratio Is Influenced by Urine Concentration.
BACKGROUND
The usage of urine protein/creatinine ratio to estimate daily urine protein excretion is prevalent, but relatively little attention has been paid to the influence of urine concentration and its impact on test accuracy. We took advantage of 24-hour urine collection to examine both urine protein/creatinine ratio (UPCR) and daily urine protein excretion, with the latter as the reference standard. Specific gravity from a concomitant urinalysis of the same urine sample was used to indicate the urine concentration.


METHODS
During 2010 to 2014, there were 540 adequately collected 24h urine samples with protein concentration, creatinine concentration, total volume, and a concomitant urinalysis of the same sample. Variables associated with an accurate UPCR estimation were determined by multivariate linear regression analysis. Receiver operating characteristic (ROC) curves were generated to determine the discriminant cut-off values of urine creatinine concentration for predicting an accurate UPCR estimation in either dilute or concentrated urine samples.


RESULTS
Our findings indicated that for dilute urine, as indicated by a low urine specific gravity, UPCR is more likely to overestimate the actual daily urine protein excretion. On the contrary, UPCR of concentrated urine is more likely to result in an underestimation. By ROC curve analysis, the best cut-off value of urine creatinine concentration for predicting overestimation by UPCR of dilute urine (specific gravity ≦ 1.005) was ≦ 38.8 mg/dL, whereas the best cut-off values of urine creatinine for predicting underestimation by UPCR of thick urine were ≧ 63.6 mg/dL (specific gravity ≧ 1.015), ≧ 62.1 mg/dL (specific gravity ≧ 1.020), ≧ 61.5 mg/dL (specific gravity ≧ 1.025), respectively. We also compared distribution patterns of urine creatinine concentration of 24h urine cohort with a concurrent spot urine cohort and found that the underestimation might be more profound in single voided samples.


CONCLUSIONS
The UPCR in samples with low or high specific gravity is more likely to overestimate or underestimate actual daily urine protein amount, respectively, especially in a dilute urine sample with its creatinine below 38.8 mg/dL or a concentrated sample with its creatinine above 61.5 mg/dL. In particular, UPCR results should be interpreted with caution in cases that involve dilute urine samples because its overestimation may lead to an erroneous diagnosis of proteinuric renal disease or an incorrect staging of chronic kidney disease.
Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chih-Yu
CY
Yang
School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan.
Fu-An
FA
Chen
School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan.
Chun-Fan
CF
Chen
School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei City Hospital Zhongxing Branch, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Wen-Sheng
WS
Liu
School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital Yuanshan Branch, Yilan, Taiwan.
Chia-Jen
CJ
Shih
Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Shuo-Ming
SM
Ou
Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Wu-Chang
WC
Yang
Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chih-Ching
CC
Lin
Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
An-Hang
AH
Yang
D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000097:blood / Q000652:urine*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000473:pathology / Q000652:urine*; D013046:Specific Gravity; D016482:Urinalysis
D003404:Creatinine