The EFLM European Urinalysis Guideline 2023.

BACKGROUND: The EFLM Task and Finish Group Urinalysis has updated the ECLM European Urinalysis Guidelines (2000) on urinalysis and urine bacterial culture, to improve accuracy of these examinations in European clinical laboratories, and to support diagnostic industry to develop new technologies. RECOMMENDATIONS: Graded recommendations were built in the following areas. MEDICAL NEEDS AND TEST REQUISITION: Strategies of urine testing are described to patients with complicated or uncomplicated urinary tract infection (UTI), and high or low-risk to kidney disease. SPECIMEN COLLECTION: Patient preparation, and urine collection are supported with two quality indicators: contamination rate (cultures), and density of urine (chemistry, particles). CHEMISTRY: Measurements of both urine albumin and α1-microglobulin are recommended for sensitive detection of kidney disease in high-risk patients. Performance specifications are given for urine protein measurements and quality control of multiproperty strip tests. PARTICLES: Procedures for microscopy are reviewed for diagnostic urine particles, including urine bacteria. Technologies in automated particle counting and visual microscopy are updated with advice how to verify new instruments with the reference microscopy. BACTERIOLOGY: Chromogenic agar is recommended as primary medium in urine cultures. Limits of significant growth are reviewed, with an optimised workflow for routine specimens, using leukocyturia to reduce less important antimicrobial susceptibility testing. Automation in bacteriology is encouraged to shorten turn-around times. Matrix assisted laser desorption ionization time-of-flight mass spectrometry is applicable for rapid identification of uropathogens. Aerococcus urinae, A. sanguinicola and Actinotignum schaalii are taken into the list of uropathogens. A reference examination procedure was developed for urine bacterial cultures.

Verifying measurements on Siemens Atellica® instruments using clinically acceptable analytical performance specifications.

Measurements on clinical chemistry analysers must be verified to demonstrate applicability to their intended clinical use. We verified the performance of measurements on the Siemens Atellica® Solution chemistry analysers against the clinically acceptable analytical performance specifications, CAAPS, including the component of intra-individual biological variation, CVI. The relative standard uncertainty of measurement, i.e. analytical variation, CVA, was estimated for six example measurands, haemoglobin A1c in whole blood (B-HbA1c), albumin in urine (U-Alb), and the following measurands in plasma: sodium (P-Na), pancreatic amylase (P-AmylP), low-density lipoprotein cholesterol (P-LDL-C), and creatinine (P-Crea). Experimental CVA was calculated from single-instrument imprecision using control samples, variation between measurements on parallel instruments, and estimation of bias with pooled patient specimens. Each obtained CVA was compared with previously developed CAAPS. The calculated CVA was 1.4% for B-HbA1c (CAAPS 1.9% for single diagnostic testing, CAAPS 2.0% for monitoring after duplicate tests; IFCC units), 10.9% for U-Alb (CAAPS 44.9%), 1.2% for P-Na (CAAPS 0.6%, after triplicate testing 1.5%), 8.2% for P-AmylP (CAAPS 22.9%). The CVA was 4.9% for P-LDL-C (CAAPS for cardiovascular risk stratification 4.9% after four replicates), and 4.2% for P-Crea (CAAPS 8.0%). Three of the six measurands fulfilled the estimated clinical need. Results from P-Na measurements indicate a general need for improving the P-Na assays for emergency patients. It is necessary to consider CVI when creating diagnostic targets for laboratory tests, as emphasised by the CAAPS estimates of B-HbA1c and P-LDL-C.

Clinical decision limits as criteria for setting analytical performance specifications for laboratory tests.

BACKGROUND: The biological (CVI), preanalytical (CVPRE), and analytical variation (CVA) are inherent to clinical laboratory testing and consequently, interpretation of clinical test results. METHODS: The sum of the CVI, CVPRE, and CVA, called diagnostic variation (CVD), was used to derive clinically acceptable analytical performance specifications (CAAPS) for clinical chemistry measurands. The reference change concept was applied to clinically significant differences (CD) between two measurements, with the formula CD = z*√2* CVD. CD for six measurands were sought from international guidelines. The CAAPS were calculated by subtracting variances of CVI and CVPRE from CVD. Modified formulae were applied to consider statistical power (1-ß) and repeated measurements. RESULTS: The obtained CAAPS were 44.9% for urine albumin, 0.6% for plasma sodium, 22.9% for plasma pancreatic amylase, and 8.0% for plasma creatinine (z = 3, α = 2.5%, 1-ß = 85%). For blood HbA1c and plasma low-density lipoprotein cholesterol, replicate measurements were necessary to reach CAAPS for patient monitoring. The derived CAAPS were compared with analytical performance specifications, APS, based on biological variation. CONCLUSIONS: The CAAPS models pose a new tool for assessing APS in a clinical laboratory. Their usability depends on the relevance of CD limits, required statistical power and the feasibility of repeated measurements.

UriSed 3 PRO automated microscope in screening bacteriuria at region-wide laboratory organization.

BACKGROUND AND AIMS: We assessed the possibility to rule out negative urine cultures by counting with UriSed 3 PRO (77 Elektronika, Hungary) at Helsinki and Uusimaa Hospital District. MATERIALS AND METHODS: Bacteria counting of the UriSed 3 PRO automated microscope was verified with reference phase contrast microscopy against growth in culture. After acceptance into routine, results of bacteria and leukocyte counting from 56 426 specimens with eight UriSed 3 PRO instruments were compared against results from parallel samples cultured on chromogenic agar. Laboratory data including preanalytical details were accessed through the regional database of the Helsinki and Uusimaa Hospital District. RESULTS: A combined sensitivity of 87-92% and a negative predictive value of 90-96% with a specificity of 54-50% was reached, depending on criteria. Preanalytical data (incubation time in bladder) combined with the way of urine collection would improve these figures if reliable. CONCLUSIONS: Complex patient populations, regional logistics and data interfases, and economics related to increased costs of additional particle counts against costs of screening cultures of all samples, did not support adaptation of a screening process of urine cultures. This conclusion was made locally, and may not be valid elsewhere.

Verification of UriSed 3 PRO automated urine microscope in regional laboratory environment.

BACKGROUND AND AIMS: Ten UriSed 3 PRO automated microscopes (77 Elektronika, Hungary) were verified for nine HUSLAB laboratories with 160 000 annual urine samples. MATERIALS AND METHODS: Particle counting of the primary UriSed 3 PRO instrument (77 Elektronika, Hungary) was verified against reference visual microscopy with 463 urine specimens, and against urine culture on chromogenic agar plates with parallel 396 specimens. Nine secondary instruments were compared pairwise with the primary instrument. RESULTS: Relative imprecisions compared to Poisson distribution, R(CV), were estimated to be 1.0 for white blood cell (WBC) and 1.5 for red blood cell (RBC) counts, respectively. Spearman's correlations against visual microscopy were rS = 0.94 for WBC, rS = 0.87 for RBC, and rS = 0.82 for squamous epithelial cell (SEC) counts. Agreement with visual microscopy (Cohen's weighted kappa) was 0.94 for WBC, 0.89 for RBC, 0.88 for SEC, 0.59 for combined casts, and 0.49 for non-squamous epithelial cells (NEC). Bacteria were detected with a sensitivity of 90% and specificity of 39 against culture at 107 CFB/L (104 CFU/mL). Created flagging limits allowed automated reporting for 70-75% of patient results. CONCLUSIONS: UriSed 3 PRO instruments were adopted into routine use after acceptance of the verification.

External quality assessment of urine particle identification: a Northern European experience.

External quality assessment (EQA) schemes for urinalysis have been provided by Labquality Ltd, the publicly owned EQA service provider in Finland, since the 1980s. In 2014, the scheme on urine particle identification had 329 participating laboratories, out of which 60% from 19 countries were outside Finland. Each of the four annual web-based rounds were distributed with four Sternheimer-stained images from a single patient sample, as viewed both by bright-field and phase-contrast optics. Participants reported classified categories either at the basic or at the advanced level. Participating laboratories received assessment of their analytical performance as compared to their peers, including reflections from clinical data and preanalytical detail of the specimen. In general, reporting of basic urine particles succeeded in the eight schemes during the years 2013-2014 as follows: red blood cells 82%-92%, white blood cells 82%-97%, squamous epithelial cells 92%-98%, casts 84%-94%, and small epithelial cells 73%-83% (minimum and maximum of expected or accepted reports). This basic level of differentiation is used in routine laboratory reports, or as verification of results produced by automated instruments. Considerable effort is needed to standardise national procedures and reporting formats, in order to improve the shown figures internationally. Future technologies may help to alleviate limitations created by single digital images. Despite improvements, degenerating cells and casts always exhibit intermediate forms creating disputable classifications. That is why assessment of performance should encompass justified acceptable categories into the assessed outcomes. Preanalytical and clinical detail provide essential added value to morphological findings.

Adenine phosphoribosyltransferase deficiency as a rare cause of renal allograft dysfunction.

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent CKD. Because of symptom variability and lack of awareness, however, the diagnosis is sometimes extremely deferred. We describe a patient with adenine phosphoribosyltransferase deficiency who was diagnosed during evaluation of a poorly functioning second kidney allograft. This report highlights the risk of renal allograft loss in patients with undiagnosed adenine phosphoribosyltransferase deficiency and the need for improved early detection of this disease.

[Update on current care guidelines: urinary tract infections]. / Käypä hoito -suosituksen päivitystiivistelmä. Virtsatieinfektiot.

This guideline is focused on the diagnostics and treatment of acute, recurrent and relapsing urinary tract infections in adults and children. Sexually transmitted diseases are not addressed, but must be considered in differential diagnostics. The resistance prevalence of the causative microbes and the ecological adverse effects of antimicrobial agents were considered important factors in selecting optimal therapeutic choices for the guideline. Diagnosis and management of cystitis in otherwise healthy women aged 18-65 years can be based on structured telephone interviews. Primary antimicrobiotic drugs are nitrofurantoin, pivmesillinam and trimetoprim for three days.

An interactive two-step training and management model of point-of-care glucose testing in northern Finland.

OBJECTIVES: To assess an interactive 2-step training and management model for nurses in glucose point-of-care testing (POCT). STUDY DESIGN: The training of the nursing staff by the point-of-care coordinator of the laboratory started with interactive sessions with contact persons who subsequently trained their nursing colleagues at the Oulu University Hospital in northern Finland. The 2-step training model was applied in blood glucose testing as a pilot study. METHODS: Functional quality was assessed through interviews with clinical contact persons and a questionnaire was given to the trained nurses. Technical quality was assessed through control measurements by laboratory and nursing staff. RESULTS: Training succeeded because of basic resources (trainers' knowledge and skills, organized contents of training and place), interpersonal communication and high-quality interactions. Nurses were especially satisfied with the prerequisite training of the contact persons (mean score 1.58, Likert scale from -2 to +2, strongly disagree - strongly agree). Day-to-day repeatabilities of less than 3% were achieved in control measurements by both nursing and laboratory staff. CONCLUSIONS: The interactive 2-step training and management model could be implemented in the clinical units using a reasonable amount of laboratory resources. The goal of good functional and technical quality in point-of-care testing in the clinical units was achieved. Despite successful implementation, POCT needs continuous support from the laboratory.

Preanalytical quality improvement: from dream to reality.

Abstract Laboratory diagnostics (i.e., the total testing process) develops conventionally through a virtual loop, originally referred to as "the brain to brain cycle" by George Lundberg. Throughout this complex cycle, there is an inherent possibility that a mistake might occur. According to reliable data, preanalytical errors still account for nearly 60%-70% of all problems occurring in laboratory diagnostics, most of them attributable to mishandling procedures during collection, handling, preparing or storing the specimens. Although most of these would be "intercepted" before inappropriate reactions are taken, in nearly one fifth of the cases they can produce inappropriate investigations and unjustifiable increase in costs, while generating inappropriate clinical decisions and causing some unfortunate circumstances. Several steps have already been undertaken to increase awareness and establish a governance of this frequently overlooked aspect of the total testing process. Standardization and monitoring preanalytical variables is of foremost importance and is associated with the most efficient and well-organized laboratories, resulting in reduced operational costs and increased revenues. As such, this article is aimed at providing readers with significant updates on the total quality management of the preanalytical phase to endeavour further improvement for patient safety throughout this phase of the total testing process.

Health centres' view of the services provided by a university hospital laboratory: use of satisfaction surveys.

Customer orientation has gained increasing attention in healthcare. A customer satisfaction survey is one way to raise areas and topics for quality improvement. However, it seems that customer satisfaction surveys have not resulted in quality improvement in healthcare. This article reports how the authors' university hospital laboratory has used customer satisfaction surveys targeted at the health centres in their hospital district. Closed-ended statements of the questionnaire were planned to cover the essential aspects of laboratory services. In addition, an open-ended question asked what was considered to be the most important problem in services. The questionnaires were sent to the medical directors of the health centres. The open-ended question proved to be very useful because the responses specified the main problems in service. Based on the responses, selected dissatisfied customers were contacted to specify their responses and possible corrective actions were taken. It is concluded that a satisfaction survey can be used as a screening tool to identify topics of dissatisfaction. In addition, further clarifications with selected customers are needed to specify the causes for their dissatisfaction and to undertake proper corrective actions.

Limits of preservation of samples for urine strip tests and particle counting.

BACKGROUND: Preservation of urine samples is important for centralised laboratory services with automated instruments. METHODS: A multicentre evaluation was carried out to assess preservative tubes from BD Diagnostics-Preanalytical Systems and from Greiner Bio-One for test strip reading (documented at the level of remission values), for particle counting by flow cytometers (UF-100) and for visual microscopy. Failures were expressed as percentages of originally positive samples beyond a two-fold change (+100% or -50%) from the original values. RESULTS: The preservative-containing BD Plus C&S plastic, BD Plus UAP and Greiner Stabilur tubes succeeded in preservation of test strip results for 6-24 h (exceptions were glucose and nitrite tests). Greiner boric acid tube showed false negative results in leukocyte, protein and ketone strip tests immediately after adding the preservative. Urine red blood cell counts (with Sysmex UF-100) were preserved for 5 h in BD Plus C&S plastic and Greiner Stabilur tubes (Greiner tubes having clearly larger preservative-related background). Bacteria or white blood cell counting succeeded in BD Plus C&S plastic tubes for 5 or 24 h, respectively, but up to 72 h in Greiner Stabilur tubes. In visual microscopy, the Greiner Stabilur tube was slightly better than the BD Plus C&S plastic tube. CONCLUSIONS: Urine specimens can be transported at +20 degrees C on the day of collection if preserved properly. Longer delays need careful planning with current preservatives. Flow cytometry with UF-100 is sensitive to non-dissolved preservative remnants.

From customer satisfaction survey to corrective actions in laboratory services in a university hospital.

OBJECTIVE: To find out the satisfaction of clinical units with laboratory services in a university hospital, to point out the most important problems and defects in services, to carry out corrective actions, and thereafter to identify the possible changes in satisfaction. SETTING: and STUDY PARTICIPANTS: Senior physicians and nurses-in-charge of the clinical units at Oulu University Hospital, Finland. DESIGN: Customer satisfaction survey using a questionnaire was carried out in 2001, indicating the essential aspects of laboratory services. Customer-specific problems were clarified, corrective actions were performed, and the survey was repeated in 2004. RESULTS: In 2001, the highest dissatisfaction rates were recorded for computerized test requesting and reporting, turnaround times of tests, and the schedule of phlebotomy rounds. The old laboratory information system was not amenable to major improvements, and it was renewed in 2004-05. Several clinical units perceived turnaround times to be long, because the tests were ordered as routine despite emergency needs. Instructions about stat requesting were given to these units. However, no changes were evident in the satisfaction level in the 2004 survey. Following negotiations with the clinics, phlebotomy rounds were re-scheduled. This resulted in a distinct increase in satisfaction in 2004. CONCLUSIONS: Satisfaction survey is a screening tool that identifies topics of dissatisfaction. Without further clarifications, it is not possible to find out the specific problems of customers and to undertake targeted corrective actions. Customer-specific corrections are rarely seen as improvements in overall satisfaction rates.

Analytical performance of the Iris iQ200 automated urine microscopy analyzer.

BACKGROUND: We evaluated the Iris iQ200 Automated Urine Microscopy Analyzer to find out if the instrument performed better than traditional visual bright field microscopy in detecting basic urine particles, as assessed against reference phase contrast microscopy. METHODS: The HUSLAB quality system was followed in planning and completing the evaluation process. The iQ200 instrument results from 167 mid-stream, uncentrifuged urine specimens were compared to those obtained with phase contrast reference microscopy, and to those with routine bright field microscopy. Linearity, carry-over and precision were tested according to well-established protocols. RESULTS: The iQ200 counted erythrocytes (RBC) at r=0.894 (R(2)=0.799) with Automated Particle Recognition (APR) software alone and at r=0.948 (R(2)=0.898) after re-classification. The performance for leukocytes (WBC) was r=0.885 with APR and r=0.978 after re-classification. The correlations of counting after user re-classification were r=0.927 for squamous epithelial cells (SQEP), r=0.856 for casts, and r=0.706 for non-squamous epithelial cells. The iQ200 showed good linearity and precision and no carry-over was detected. CONCLUSIONS: The Iris iQ200 was capable to count reliably RBC, WBC, and SQEP cells and to identify a fraction of bacteria and renal elements. Counting results equalled or exceeded that of routine bright field microscopy or earlier flow cytometric technology. The instrument eliminates manual sample preparation but requires a well-trained technologist for re-grouping of findings.

Preservation of urine for flow cytometric and visual microscopic testing.

BACKGROUND: Preservatives that could prevent destruction of cells, casts, and bacteria in urine are of great practical importance because they allow centralization and improvement of accuracy of urine particle counting. We compared two in-house mixtures and one commercial solution, as well as refrigeration, for their ability to preserve urine for both automated analysis (flow cytometry) and visual microscopy. METHODS: Urine specimens were preserved by refrigeration at 4 degrees C without preservatives (procedure 1); in a lyophilized solution intended to preserve specimens for bacterial culture (Urine C&S tubes; BD Preanalytical Solutions; procedure 2); in 10 mL/L formalin-0.15 mol/L NaCl (procedure 3); in 80 mL/L ethanol-20 g/L polyethylene glycol (procedure 4); and by storage at 20 degrees C without preservatives (procedure 5). Test strip measurements were used to select specimens positive for leukocyte esterase, hemoglobin, albumin, or nitrite. For 106 consecutive strip-positive specimens, urinalysis was performed by UF-100 (Sysmex) and by phase-contrast microscopy after Sternheimer supravital staining. Automated analysis was performed at arrival in the morning, on the same day in the afternoon, and after 1 and 3 days. Visual microscopy was performed at arrival and 3 days later. RESULTS: Urine bacterial counts were well preserved with procedures 1-3, with a false-positive rate of 0.0-3.4% at day 3 vs 28% without preservation (procedure 5). Erythrocytes were poorly preserved for 3 days (kappa coefficients, 0.24-0.61); after 1 day, fair preservation was seen with procedure 2 (kappa = 0.78), compared with less favorable preservation with procedure 1 (kappa = 0.61) or procedure 5 (kappa = 0.66). Leukocytes were well preserved by all five procedures in the acidic adult urines investigated. Counts of casts and large epithelial cells were artifactually increased by procedure 3. Procedure 2 performed at least as well as refrigeration for specimens analyzed with visual microscopy. CONCLUSIONS: Urine specimens from adults can be stabilized at room temperature for both automated particle analysis and visual microscopy.

Increased glomerular permeability in patients with nephropathia epidemica caused by Puumala hantavirus.

BACKGROUND: Nephropathia epidemica (NE) is the Scandinavian type of haemorrhagic fever with renal syndrome. Usually heavy transient proteinuria is present at the onset of the disease. METHODS: We investigated glomerular permeability in eight patients with acute NE and in eight healthy controls. Six patients were followed for 1 year. The glomerular filtration rate (GFR) was determined by inulin clearance and effective renal plasma flow (ERPF) by para-aminohippurate clearance. RESULTS: GFR and ERPF were significantly reduced in NE patients during the acute phase compared with those in controls (P<0.001 and P<0.001, respectively). The filtration fraction (FF) was thus high, 0.37. The fractional clearances of albumin, IgG, and IgG(4) were markedly increased. As a sign of tubular dysfunction, increased urinary excretion of alpha(1)-microglobulin was observed in all patients. After 1 year, the GFR of the patients no longer differed from that of the controls. ERPF was lower and FF higher than those in controls (P=0.014 and P=0.009, respectively). The fractional clearances of albumin, IgG, and IgG(4) remained increased. The high-molecular fractional dextran clearances in the patients were significantly increased compared with controls during the acute phase. Computed analysis of glomerular membrane-pore structure showed that the "shunt-flow" was increased in the patients during the acute phase compared with the controls. There was a positive correlation between the FF and the shunt (r=0.768, P=0.026). In addition, fractional clearances of albumin and IgG correlated significantly with the shunt (r=0.810, P=0.015 and r=0.762, P=0.028, respectively). CONCLUSIONS: Renal involvement in the acute phase of NE is characterized by a markedly decreased GFR and ERPF. Increased glomerular permeability is associated with impairment of both the size- and charge-selectivity properties of the glomerular filter.