ORIGINAL ARTICLE Comparison of YD URiSCAN PluScope Urine Microscopic Analyzer and Sysmex UF-1000i Flow Cy

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1 ORIGINAL ARTICLE Comparison of YD URiSCAN PluScope Urine Microscopic Analyzer and Sysmex UF-1000i Flow Cytometry Systems Jae Won Jung, Ae- Chin Oh, Yoon Hwan Chang, Jin Kyung Lee, and Young Jun Hong Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea Corresponding author: Young Jun Hong Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowonro, Nowon-gu, Seoul 01812, Korea Tel: Fax: Background: Urinalysis is one of the most commonly performed tests in clinical laboratories. In this study, we compared YD URiSCAN PluScope (PluScope; YD Diagnostics Corp., Korea) and Sysmex UF-1000i (UF-1000i; Sysmex Corp., Japan) for urine microscopic sediment analysis. Methods: A total of 404 fresh urine samples were collected and analyzed using PluScope, UF-1000i, and manual microscopy. Quantitative correlation analyses for red blood cells (RBCs), white blood cells (WBCs), epithelial cells (EC), and casts were performed using Spearman s correlation. We evaluated agreement among the three systems by using weighted Cohen s κ and calculating concordance rates within one grade of difference for semiquantitative and qualitative parameters. Results: There were moderate-high correlations between PluScope and UF-1000i for RBCs, WBCs, and ECs (r=0.542, 0.714, and 0.571, respectively) but negligible correlation for casts (r=0.186). There were moderate-high correlations between manual microscopy and automated devices for RBCs, WBCs, and ECs (r= ) but negligible correlations for casts (PluScope: r=0.247; UF-1000i: r=0.223). The pairwise concordance rates within one grade difference among the three methods were good for RBCs, WBCs, and ECs (95.0% 99.0%, κ= ). For casts, the concordance rate between PluScope and manual microscopy was fair (96.8%, κ=0.25), but concordance rates between UF-1000i and manual microscopy and between the two automated devices were poor (81.2% and 81.7%; κ=0.04 and 0.06, respectively). Conclusions: The two automated urine sediment analyzers showed a moderate-high correlation and concordance rate. They showed good correlations and concordance rates for RBCs, WBCs, and ECs. However, manual microscopic examinations are still needed for reviewing and confirming the presence of pathologic particles in urine, such as casts and crystals. (J Lab Med Qual Assur 2018;40: ) Key Words: Automated urine sediment analyzer, Urinalysis, Urine sediment, URiSCAN PluScope, UF-1000i pissn: eissn: Received September 24, 2018, Revision received October 19, 2018, Accepted October 24, 2018 서론 요검사는임상영역에서흔하게시행하는검사로, 검체의채집이용이하고비침습적인검사며, 신장, 요로계질환에서부터내분비및대사성질환등의전신성질환에이르기까지다양한질환에대한정보를얻을수있는장점이있다 [1]. 요검사중수기법을이용하는요침사검사는노동집약적이며시간이많이소요되고, 검사자의전문적인판독능력이필요하다. 또한검체준비과정의차이에따라검사결과가달라질수있으며, 검사자간숙련도에따라서도판독에차이가있을수있다 [2-5]. 이러한수기법의단점을극복하기위해자동요침사장비의필요성이대두되어왔으며, 현재여러장비들이대 Copyright 2018 Korean Association of External Quality Assessment Service 223

2 다수의검사실에도입되어사용중이다. 자동요침사장비의검사방법은크게유세포분석 (flow cytometry) 을이용한방법과디지털이미지를촬영하여분석하는방법으로나눌수있으며, 지금까지여러장비들에대한검사수행능및장비간상관성이보고되고있다 [6-14]. YD URiSCAN PluScope (PluScope; YD Diagnostics Corp., Yongin, Korea) 는국산장비로는최초로개발된이미지기반자동요침사장비로서현재까지 PluScope에대한장비평가는거의없었다. 본연구에서는환자의소변검체를대상으로이미지촬영및분석기술을이용하는 PluScope와유세포분석기술을이용하는 Sysmex UF-1000i (UF-1000i; Sysmex Corp., Kobe, Japan) 의검사수행능을비교하였고, 각각수기법과의상관성에대해서도분석하였다. 재료및방법 1. 대상검체원자력병원진단검사의학과에검사가의뢰된검체중잔여소변검체 404개를무작위로선정하였다. 연구대상검체는채취후 1시간이내의신선한검체이며, 잔여검체의양이평가를수행하는데필요한 20 ml 이상남아있는것들을기준으로하였다. 본연구는한국원자력의학원임상연구심의위원회의심의를통과하였다 (IRB approval no., ). 2. 검사방법 1) YD URiSCAN PluScope PluScope 장비는원심분리하지않은소변검체 2.5 ml를이용하여 4개의 counting chamber system에검체를주입하여빠른시간안에효율적으로디지털이미지를촬영함으로써요침사의계수및형태학적분석을시행하는자동화장비다. 적혈구 (red blood cell), 백혈구 (white blood cell), 백혈구응괴 (WBC clumping), 상피세포 (epithelial cell), 초자원주 (hyaline cast), 결정 (crystal), 진균 (fungus), 미분류 (unclassified), 소원형세포 (small round cell) 의 9개분석대상에대해정량적으로측정하였으며, 박테리아 (bacteria) 와점액질 (mucus) 에대해서는반정량적으로결과를측정하였다. 2) Sysmex UF-1000i UF-1000i 장비는유세포분석기술을기반으로하며, 두가지의형광염색과 635 nm의반도체레이저를이용하여검체를분석한다. 원심분리하지않은검체 4 ml를사용하며, 요침사 의구성성분에따라전반산란광, 측방산란광, 측방산란형광이 다르게측정된정보를바탕으로각검사항목별결과를얻을수 있다. 적혈구, 백혈구, 상피세포, 원주, 박테리아의 5 개분석대 상에대해정량적으로측정하였으며, flag 로확인되는결정, 진 균, 병적원주 (pathologic cast), 점액질, 정자 (spermatozoa), 소원형세포에대해서는 count/μl 로결과를기록하였다. 3) 수기법 수기요침사검사는 Clinical and Laboratory Standards Institute (CLSI) 에서제시한지침에따라시행하였다 [15,16]. 현미경계수는표준화된 KOVA cell chamber system 을이용하였다. 12 ml 의소변검체를 1,500 rpm 에서 ( 400 g) 5 분간원심분리하여상층액은버리고 1 ml 를남겨 재부유한후 6.6 μl 를 slide 에떨어뜨리고염색하지않은상태 에서현미경으로관찰하였다. 현미경경검은고배율 (400 배 ) 에 서 10 시야이상관찰하여백혈구, 적혈구, 상피세포의개수를 계수하고각각의평균치를 count/high-power field (HPF) 로 기록하였고, 저배율 (100 배 ) 에서 10 시야이상관찰하여박테리 아, 진균, 결정, 원주, 점액질에대한각각의평균치를 count/ low-power field (LPF) 로기록하였다. 3. 평가방법 1) 정밀도및 carryover 평가 정밀도를평가하기위해 2 가지농도의 pooled urine 검체 에대해 PluScope 와 UF-1000i 에서하루, 5 회반복측정하여 각각변이계수를구하였다. Carryover 평가를위해고농도 검체 4 개 (H1, H2, H3, H4) 와저농도검체 4 개 (L1, L2, L3, L4) 를 PluScope 와 UF-1000i 각장비별로연속측정한결과 로다음의식을이용하여계산하였다 : carryover %={L1 (L3+L4)/2}/{(H2+H3)/2-(L3+L4)/2} ) 단위의통일 두자동화장비를통해수집된검사결과들의단위 (count/ μl) 를수기법과의비교를위해종목별로통일하였다. 적혈구, 백혈구, 상피세포는 count/hpf 로, 원주, 박테리아, 진균, 결 정, 점액질에대해서는 count/lpf 로단위를변환하였다. 단위 간변환에사용된공식은다음과같다 : count 10 6 /L=(10 시 야계수한세포의총합 ) ( 원심분리후남은부피, 1 ml)/( 관 찰한 10 개시야의부피, μl) ( 검체의부피, 12 ml) [17]. 224 J Lab Med Qual Assur 2018;40:

3 3) 정량적상관성비교 PluScope와 UF-1000i 장비간, 그리고자동화장비와수기법간의정량적비교를위한검사종목으로적혈구, 백혈구, 상피세포, 원주를선정하였다. 총 404개의잔여소변검체를대상으로분석하였다. 통계프로그램으로 IBM SPSS ver (IBM Corp., Armonk, NY, USA) 소프트웨어를사용하였고, 데이터의정규성검정을위해 Kolmogorov-Smirnov test 를시행한결과모든분석데이터는정규분포를이루지않았다. 비모수적데이터에대한상관성분석을위해 Spearman s correlation 분석을사용하였으며, 상관계수 (correlation coefficient, r) 값이 0.9 이상이면매우높은 (very high) 상관성을, 일경우높은 (high) 상관성을, 일경우중등도 (moderate) 의상관성, 의경우낮은 (low) 상관성, 을매우낮은 ( 무시할수준, negligible) 상관성을보이는것으로판정하였다 [18]. 통계분석결과는 P값이 0.05 미만일때유의한것으로간주하였다. 4) 반정량적또는정성적일치도비교 PluScope와 UF-1000i 장비간, 그리고자동화장비와수 기법간서로비교가능한 8개의검사종목에대한분석결과를반정량적또는정성적으로분류하여 Table 1과같이등급 (grade) 을나누었다. 하나의장비에서만측정되는검사항목은분석에서제외되었다. 통계학적비교방법으로 weighted Cohen s kappa 분석을이용하여총 404개의잔여소변검체에대해 kappa 계수 (κ) 와일치도 (concordance rate) 를계산하였으며, 적혈구와백혈구, 상피세포, 원주, 박테리아에대해서는 1등급차이내의일치도를구하였다. 일치의정도는 κ값이 일때매우좋은 (very good) 일치, 일때좋은 (good) 일치, 일때중등도 (moderate) 의일치, 일때약간의 (fair) 일치, 0.20 미만일때좋지않은 (poor) 일치를보이는것으로해석하였고 [19], P값이 0.05 미만의경우유의한것으로간주하였다. 결과 1. 정밀도및 carryover 평가정밀도평가결과 PluScope의적혈구에대한검사내변이계수는적혈구에서 2.8%, 2.3% ( 각각고농도, 저농도 ) 였 Table 1. Semi-quantitative and qualitative range classification of urine sediment results of three different examination methods Grade Red blood cell (counts/hpf) < White blood cell (counts/hpf) < Epithelial cell (counts/hpf) < Casts (counts/lpf) < Bacteria Rare A few Some Many Fungus ( ) (+) Crystal ( ) (+) Mucus ( ) (+) Abbreviations: HPF, high-power field; LPF, low-power field. Table 2. Within-run imprecision of two automated urine sediment analyzers (N=404) Level 1 (low) Level 2 (high) Mean±SD (counts/μl) CV (%) Mean±SD (counts/μl) CV (%) URiSCAN PluScope RBC ± ± WBC 40.40± ± UF-1000i RBC ± ± WBC 56.14± ± Abbreviations: SD, standard deviation; CV, coefficient of variation; RBC, red blood cell; WBC, white blood cell. J Lab Med Qual Assur 2018;40:

4 고, 백혈구에대해 7.0%, 2.8% 였다. UF-1000i 의적혈구에대한검사내변이계수는 2.8%, 1.5% 였고, 백혈구에대해 1.4%, 3.3% 였다 (Table 2). Carryover 평가결과 PluScope의 carryover는적혈구와백혈구모두에서 0.0% 였고, UF-1000i 의 carryover는적혈구와백혈구에대해각각 0.1% 와 0.2% 였다. 2. 상관성분석 Spearman correlation을이용하여분석한상관성결과는 Table 3와같다. PluScope와 UF-1000i 두장비간상관성분석결과백혈구에대해서는 r값이 0.714로높은상관관계를, 적혈구와상피세포에대해서는각각 r값이 0.542와 0.571로중등도의상관관계를보였으며, 원주에대해서는 r값은 0.186으로매우낮은상관관계를보였다. 수기법과각자동화장비간상관성분석결과적혈구에대해서는 PluScope와 UF-1000i의 r값은각각 0.586과 0.644로중등도의상관관계를보였고, 백혈구에대해서는 PluScope 에서중등도 (r=0.599) 의상관관계, UF-1000i에서는높은 (r=0.745) 상관관계를보였다. 상피세포에서 PluScope와 UF-1000i의 r값은각각 0.585와 0.550으로중등도의상관관계를보였으며, 원주에대한 PluScope와 UF-1000i의 r값은 각각 r=0.247와 0.223으로매우낮은상관관계를보였다. 3. 분석종목별일치도비교두장비간, 그리고장비와수기법간의일치도분석과 weighted Cohen s kappa 분석결과는 Table 4와같다. 적혈구에대한일치도분석결과 PluScope 장비와수기법간의 1등급내일치도는 98.5% (398/404) 였고 (κ=0.65), 6개의검체에서 2등급이상의불일치를보였다. UF-1000i 장비와수기법간의 1등급내일치도는 96.3% (389/404) 였으며 (κ=0.50), 15 개의검체에서수기법에비하여 2등급이상높게측정되었다. PluScope와 UF-1000i 두장비간 1등급내일치도는 95.0% (384/404) 였고 (κ=0.51), 2등급이상차이를보인 20개의검체중 16개에서 UF-1000i의검사결과가 PluScope의결과보다높게측정되었다. 백혈구에대한일치도분석결과 PluScope 장비와수기법간일치도는 97.0% (392/404) 였으며 (κ=0.69), 2등급이상차이를보인 12개의검체중 10개에서수기법결과가 PluScope의검사결과보다높게측정되었다. UF-1000i와수기법간일치도는 98.0% (396/404) 였고 (κ=0.74), 2등급이상차이를보인 8개의검체중 7개에서수기법보다높게측정되었다. 두자동화장비간일치도는 95.5% 였고 (κ=0.64), UF-1000i의검 Table 3. Spearman correlation analysis of pairwise results among URiSCAN PluScope, UF-1000i, and manual microscopy (N=404) URiSCAN PluScope vs. UF-1000i URiSCAN PluScope vs. manual microscopy UF-1000i vs. manual microscopy r P-value r P-value r P-value Red blood cell < < <0.001 White blood cell < < <0.001 Epithelial cell < < <0.001 Casts < < <0.001 Abbreviation: r, Spearman correlation of coefficient. Table 4. Pairwise concordance rates within one grade difference and kappa coefficients (κ) for comparison among the three methods (N=404) URiSCAN PluScope vs. UF-1000i URiSCAN PluScope vs. manual microscopy UF-1000i vs. manual microscopy Red blood cell White blood cell Abbreviations: κ, kappa coefficient; NS, not significant. P>0.05. Concordance rates within one grade difference % (κ) Epithelial cell Casts Bacteria Yeast Crystal Mucus 95.0 (0.51) 95.5 (0.64) 98.8 (0.41) 81.7 (0.06) 95.0 (0.44) 98.0 (NS) 98.5 (0.56) 66.1 (0.03) 98.5 (0.65) 97.0 (0.69) 99.0 (0.50) 96.8 (0.25) 96.5 (0.51) 99.5 (NS) 97.3 (0.41) 79.7 (0.56) 96.3 (0.50) 98.0 (0.74) 99.0 (0.47) 81.2 (0.04) 96.8 (0.56) 98.5 (NS) 97.8 (0.39) 61.1 (NS) 226 J Lab Med Qual Assur 2018;40:

5 사결과가 PluScope보다높게측정되는경향이관찰되었다. 상피세포에대한일치도분석결과 PluScope와수기법간, UF-1000i 와수기법간및 PluScope 와 UF-1000i 간의일치도는각각 99.0% (400/404), 99.0% (400/404), 98.8% (399/404) 였으나 ( 각각 κ=0.50, 0.47, 0.41), 대부분의검체결과들이 10-29/HPF 미만으로 grade 1, 2, 3 내의편향적인분포를보이고있었다. 원주에대한일치도분석결과 PluScope와수기법간일치도가 96.8% (391/404) 였으며 (κ=0.25), 2등급이상차이를보인 13개의검체에서 PluScope의검사결과가수기법보다낮게측정되었다. UF-1000i와수기법간일치도는 81.2% (328/404) 였고 (κ=0.04), 2등급이상의차이를보인 76개의검체중 71개에서 UF-1000i의검사결과가수기법보다높게측정되었다. 두자동화장비간일치도는 81.7% (330/404) 였으며 (κ=0.06), UF-1000i의검사결과가 PluScope에비해높게측정되었다. 박테리아에대한일치도분석결과장비간일치도는 95.0% (384/404) 였고 (κ=0.44), 장비와수기법간일치도는 PluScope와 UF-1000i 각각 96.5% (390/404) 와 96.8% (391/404) 였다 ( 각각 κ=0.51, 0.56). 진균에대한일치도분석에서의장비간일치도는 98.0% (396/404), 장비와수기법간일치도는 PluScope와 UF-1000i 각각 99.5% (402/404), 98.5% (398/404) 였으나, kappa 분석에서는 κ값은모두 0으로나타났고통계적으로도유의하지않았다 (P>0.05). 결정에대한일치도분석에서의장비간일치도는 98.5% (398/404) 였고 (κ=0.56), 장비와수기법간일치도는 PluScope와 UF-1000i 각각 97.3% (393/404), 97.8% (395/404) 였다 ( 각각 κ=0.41, 0.39). 점액질에대한일치도분석결과장비간일치도는 66.1% (267/404) 였고 (κ=0.03), 장비와수기법간일치도는 PluScope와수기법간일치도는 79.7% (322/404) 였으며 (κ=0.56), UF-1000i와수기법간일치도는 61.1% (247/404) 였다 (κ=0.01, P>0.05로통계적으로유의하지않음 ). 고찰 수기요침사검사는검사실에따라최초검체량, 원심분리의정도, 검체농축정도, 슬라이드에떨어뜨리는검체량, 관찰및기록방법등에따라검사결과가달라질수있다. 요침사수기법에대한국제적인가이드라인도여러개가존재하여검사방법에차이가있고 [15,16,20,21], 여러검사실마다고유의프로토콜에따라요침사검사를진행하여방법과해석에차이가있 을수있기때문에표준화된외부정도관리에어려움이있다 [2-5]. 이러한검사방법의다양성을줄이고, 검사소요시간과번거로운수작업을줄여효율적인검사수행을할수있는장점이있어자동요침사장비가점점많은임상검사실에도입되고있다. 본연구에서는최초의국산이미지기반장비인 PluScope 와유세포분석기반의 UF-1000i 장비에대하여정밀도와 carryover, 장비간및수기법과의상관성과일치도에대해분석하였다. 적혈구, 백혈구, 상피세포에대한상관성분석에서는 PluScope 와 UF-1000i 간, 그리고자동화장비와수기법간에모두중등도이상의상관성을보였지만 UF-1000i 에서적혈구, 백혈구가 PluScope 에비해다소높게측정되는경향을보였다. 이에대한원인은명확하지않지만, 아마도검사방법간측정원리의차이때문에발생한것으로생각된다. PluScope와수기법검사는공통적으로현미경적형태 (morphology) 를바탕으로요침사를분류하는반면, UF- 1000i의경우유세포분석을이용하여요침사입자를분류하며, 흔하지는않지만유사한크기와세포복잡도를가진입자를적혈구또는백혈구로잘못인식할수있기때문이다. Chien 등 [6] 의유세포분석장비 UF-100과이미지분석장비 iq-200 의비교연구에서는 UF-100의적혈구및백혈구측정결과가 iq-200에비해조금높았고, Lee 등 [10] 의연구에서유세포분석장비 UF-1000i와이미지분석장비 cobas u 701를비교한결과적혈구및백혈구측정에서 UF-1000i가 cobas u 701보다약간높은경향을보였으나그이유는명확하지않았다. 원주에서는모두낮은상관성을보였고일치도비교에서도원주에서낮은일치를보였다. 원주에서관찰되는낮은상관성, 나쁜일치도의원인으로먼저장비간원주측정의원리와계수방법의차이에의한것을생각해볼수있다. UF- 1000i는원주에대해서는정량적측정을하고병적원주에대해서는정해진 cut-off에따라 flag를띄워존재유무를확인하는반면, PluScope는주로초자원주의형태를인식하여측정하기때문에계수대상의차이로인해낮은일치도와상관성을보였을가능성이있다. 본분석에서는 UF-1000i의원주와병적원주의측정결과를구분하지않고합쳐서분석하였고, UF- 1000i 의병적원주에대한 flag의 cut-off 가상대적으로낮게설정되어전체원주에대한계수가 PluScope와수기법의결과보다상대적으로더높게측정되었을수있다고생각된다. 다른원인으로는수기요침사검사의검체준비과정중하나인원심분리과정에서불안정한원주가파괴되어수기법의결과에서상대적으로낮게계수되었을수도있다. 또다른원인으로는 PluScope와수기법장비모두현미경관찰또는디지털이미 J Lab Med Qual Assur 2018;40:

6 지분석으로형태학적구분을통해계수하는데, 초자원주의경우광학현미경에서투명하게관찰되므로계수가되지않았을수있다. 일치도분석결과박테리아, 결정에대해서는양호한일치를보였으나진균과점액질에대해서는일치도가매우좋지않았다. 진균의경우일치도는높았지만 Cohen s kappa 분석에서통계적유의성이없었는데, 이는분석검체의대다수가진균에대해음성검체들이었고, kappa 분석에서는우연에의한일치도를배제하여평가하기때문일것으로생각된다. PluScope 장비에서 미분류 (unclassified) 로나온결과와 UF-1000i에서 flag가표시된결과에대해서는이미지재확인또는수기법을통한검토 (review) 가필요하다. 검토가필요한경우 UF-1000i 장비에서는원심분리, 슬라이드제작등의번거로운검체준비과정이있어야하나, PluScope의경우미분류로분류된사진이디지털이미지로촬영되어저장되기때문에불필요한검체준비과정을피하고촬영한이미지를확인함으로써직접검토가가능하다는장점이있다. 원주, 결정등드물게관찰되는병적인소견들이자동화장비에서확인되지않을수있기때문에검토및확인검사로서수기로시행하는요경검검사가반드시필요하다고여러논문에서언급하였으며 [6,8-12], 일부연구에서는검토율 (review rate) 을요화학검사와요침사검사와의비교 ( 예를들어, 적혈구와잠혈반응, 백혈구와 leukocyte esterase, 박테리아와 nitrite 등 ) 를통해줄일수있다고주장하였다 [8,10,11,22]. 임상검사실에서환자의요검사결과를자동화장비로보고할때, 병적인상태를반영하는원주나결정등의경우 미분류 로보고되는항목들의유무를주의깊게확인하고검토하여야한다. 이런이유들로인해수기법을통한현미경판독은현재로서는아직자동화기기가완전히대체할수없다. 본연구의제한점은다음과같다. 첫째, 자동화장비의정밀도평가에서상품화된정도관리물질대신 pooled urine 검체를사용하였다. 그이유는두장비간비교평가연구를위해서는공통물질을통해장비의성능평가를하고자하는것이본연구의목적인데, 연구준비과정에서각장비에서별도로사용가능한정도관리물질은구할수있었으나공통으로사용가능한정도관리물질은구할수가없었기때문이다. 이에저자들은정밀도평가를위한정도관리물질로서 pooled urine을이용하였으며, CLSI에서제시한지침 [23] 에맞게정밀도평가를수행하려했으나요검체의특성상검체의불안정성으로 5일간분석을하지못하고부득이하게하루 5회측정한결과로변이계수를산출하여정밀도평가에부족한부분이있었다. 향후두장비에공통으로사용가능한정도관리물질을이용하여정 밀도를평가하면더나은결과를얻을수있을것으로기대된다. 두번째로, 상피세포및진균, 결정에대한일치도비교에서검사결과가대부분음성또는낮은결과를보여, 분포가편중되고고농도에서의일치도는평가되지못하였다. 향후병리적변화가있는비뇨기계및신장내과환자의검체를추가하여분석한다면더좋은비교분석을할수있을것이다. 감사의글 이연구는과학기술정보통신부한국원자력의학원연구운영비지원사업의지원을받아수행하였다 ( ). REFERENCES 1. Riley RS, McPherson RA. Basic examination of urine. In: McPherson RA, Pincus MR, editors. Henry s clinical diagnosis and management by laboratory methods. 23th ed. St. Louis (MO): Elsevier, 2017: Delanghe JR, Speeckaert MM. Preanalytics in urinalysis. Clin Biochem 2016;49: Wald R, Bell CM, Nisenbaum R, Perrone S, Liangos O, Laupacis A, et al. Interobserver reliability of urine sediment interpretation. Clin J Am Soc Nephrol 2009;4: Broeren MA, Bahceci S, Vader HL, Arents NL. Screening for urinary tract infection with the Sysmex UF-1000i urine flow cytometer. J Clin Microbiol 2011;49: Lee AJ, Park CG, Bae YC, Jeon CH. Quality improvement of urinalysis results based on automatic sediment urinalysis and urine strip results. J Lab Med Qual Assur 2017;39: Chien TI, Kao JT, Liu HL, Lin PC, Hong JS, Hsieh HP, et al. Urine sediment examination: a comparison of automated urinalysis systems and manual microscopy. Clin Chim Acta 2007;384: Zaman Z, Fogazzi GB, Garigali G, Croci MD, Bayer G, Kranicz T. Urine sediment analysis: analytical and diagnostic performance of sedimax - a new automated microscopy image-based urine sediment analyser. Clin Chim Acta 2010;411: Jiang T, Chen P, Ouyang J, Zhang S, Cai D. Urine particles analysis: performance evaluation of Sysmex UF-1000i 228 J Lab Med Qual Assur 2018;40:

7 and comparison among urine flow cytometer, dipstick, and visual microscopic examination. Scand J Clin Lab Invest 2011;71: Yuksel H, Kilic E, Ekinci A, Evliyaoglu O. Comparison of fully automated urine sediment analyzers H800-FUS100 and LabUMat-UriSed with manual microscopy. J Clin Lab Anal 2013;27: Lee W, Ha JS, Ryoo NH. Comparison of the automated cobas u 701 urine microscopy and UF-1000i flow cytometry systems and manual microscopy in the examination of urine sediments. J Clin Lab Anal 2016;30: Wesarachkitti B, Khejonnit V, Pratumvinit B, Reesukumal K, Meepanya S, Pattanavin C, et al. Performance Evaluation and comparison of the fully automated urinalysis analyzers UX-2000 and Cobas Lab Med 2016;47: Bakan E, Ozturk N, Baygutalp NK, Polat E, Akpinar K, Dorman E, et al. Comparison of Cobas 6500 and Iris IQ200 fully-automated urine analyzers to manual urine microscopy. Biochem Med (Zagreb) 2016;26: Bogaert L, Peeters B, Billen J. Evaluation of a new automated microscopy urine sediment analyser: sedimax contrust. Acta Clin Belg 2017;72: Ince FD, Ellidag HY, Koseoglu M, Simsek N, Yalcin H, Zengin MO. The comparison of automated urine analyzers with manual microscopic examination for urinalysis automated urine analyzers and manual urinalysis. Pract Lab Med 2016;5: Clinical and Laboratory Standards Institute. Urinalysis: approved guideline: GP16-A3. 3rd ed. Wayne (PA): Clinical and Laboratory Standards Institute, Clinical and Laboratory Standards Institute. Physician and nonphysician provider-performed microscopy testing: approved guideline: POCT10-A2. 2nd ed. Wayne (PA): Clinical and Laboratory Standards Institute, Ottiger C, Huber AR. Quantitative urine particle analysis: integrative approach for the optimal combination of automation with UF-100 and microscopic review with KOVA cell chamber. Clin Chem 2003;49: Mukaka MM. Statistics corner: a guide to appropriate use of correlation coefficient in medical research. Malawi Med J 2012;24: Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33: European Confederation of Laboratory Medicine. European urinalysis guidelines. Scand J Clin Lab Invest Suppl 2000;231: Japanese Association of Medical Technologists. Aims of the guidelines on urinary sediment examination procedures proposed by the Japanese committee for clinical laboratory standards (JCCLS). Jpn J Med Technol 2017; 66: Khejonnit V, Pratumvinit B, Reesukumal K, Meepanya S, Pattanavin C, Wongkrajang P. Optimal criteria for microscopic review of urinalysis following use of automated urine analyzer. Clin Chim Acta 2015;439: Clinical and Laboratory Standards Institute. User verification of precision and estimation of bias: approved guideline: EP15-A3. 3rd ed. Wayne (PA): Clinical and Laboratory Standards Institute, J Lab Med Qual Assur 2018;40:

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