Esame fisico, chimico e morfologico delle urine proposta di Linee Guida per la fase analitica

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Pubblicato il 9 dicembre 2016

Esame delle urine: linee guida per la fase analitica

Urinalysis: guidelines for analytical phase

Esame fisico, chimico e morfologico delle urine proposta di linee guida per la fase analitica del Gruppo Intersocietario Analisi delle Urine (GIAU)

Physical, chemical and morphological urine examination guidelines for the Analytical Phase from the Intersociety Urinalysis Group

Per il Gruppo Intersocietario Analisi delle Urine: Fabio Manoni¹, Gianluca Gessoni², Giovanni Battista Fogazzi³, Maria Grazia Alessio⁴, Alberta Caleffi⁵, Giovanni Gambaro⁶, Maria Grazia Epifani⁶, Barbara Pieretti⁷, Angelo Perego⁷, Cosimo Ottomano⁸, Graziella Saccani⁹, Sara Valverde¹⁰, Sandra Secchiero¹¹

(1) Dipartimento dei Servizi di Diagnosi e Cura Ospedali Riuniti Padova Sud “Madre Teresa di Calcutta” Monselice PD.
(2) Servizio di Medicina di Laboratorio, Ospedale Madonna della Navicella, Chioggia VE
(3) Laboratorio Clinico e di Ricerca sul Sedimento Urinario U.O. Di Nefrologia e Dialisi Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano
(4) Laboratorio Analisi Chimico Cliniche. ASST Papa Giovanni XXIII Piazza OMS Bergamo
(5) U.O Diagnostica Ematochimica, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria Parma
(6) Divisione di Nefrologia e Dialisi, Fondazione Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Roma
(7) Centro di Ricerca Biomedica, U.O.C. Medicina di Laboratorio Azienda Ospedaliera-Università, Padova
(8) Laboratorio Analisi Ospedale S. Croce Fano PU
(9) Divisione di Nefrologia e Dialisi Ospedali Riuniti Padova Sud “Madre Teresa di Calcutta” Monselice PD.
(10) Centro Analisi Monza
(11) Servizio di Medicina di Laboratorio Ospedale Orlandi Bussolengo VR

Il Gruppo Intersocietario (SIPMeL, SIBioC, SIN) Analisi delle Urine è formato da: MG. Alessio (Bergamo), R. Anderlini (Modena), I. Bountis (Monselice), G. Brunori (Trento), A. Caleffi (Parma), D. Coseddu (Torino), B. Creanza (Gravina di Puglia), N. Di Pace Nunzia (Gravina di Puglia), G. Di Rienzo (Gravina di Puglia), MG. Epifani (Padova), GB. Fogazzi (Milano), G. Gambaro (Roma), G. Gessoni (Chioggia), L. Gesualdo (Bari), M. Guida (Gravina di Puglia), A. Liverani (Monselice) F. Manoni (Monselice), C. Ottomano (Monza), M. Parimbelli (Bergamo), A. Perego (Monselice), B. Pieretti (Fano), D. Poz (S. Daniele), G. Saccani (Bussolengo), M. Schinella (Rovereto), S. Secchiero (Padova), F. Sirianni (Palmanova), B. Talento (Nocera Inferiore), S. Valverde (Chioggia), D. Vannoni (Siena), M. Vizzini (Rovereto), T. Zorzan (Monselice).

Corrispondenza a: Dott. Fabio Manoni MD; Dipartimento dei Servizi di Diagnosi e Cura Ospedale Madre Teresa di Calcutta. Monselice PD; Tel: +39 0429 78 82 56; Fax: +39 0429 78 85 60; E-mail: fabio.manoni@ulss17.it

Abstract

Mediante queste linee guida il gruppo intersocietario analisi delle urine (GIAU) mira a stimolare i seguenti aspetti:

Miglioramento e standardizzazione dell'approccio analitico all'esame chimico fisico e morfologico delle urine (ECMU).
Sottolineare il valore aggiunto all'ECMU dalla introduzione analizzatori automatizzati per lo studio della morfologia delle frazione corpuscolata delle urine.
Miglioramento della analisi chimica delle urine con particolare riguardo al riesame del significato diagnostico dei parametri che vengono tradizionalmente valutati nell'analisi mediante dip-stik insieme con una crescente consapevolezza dei limiti di sensibilità e specificità di questo metodo analitico.
Aumentare la consapevolezza dell'importanza delle competenze professionali nel campo della morfologia urinaria della importanza della interazione con i clinici.
Implementare una politica di valutazione della qualità analitica utilizzando, oltre ai tradizionali controlli interni ed esterni, un programma per la valutazione della competenza morfologica.
Stimolare l'industria diagnostica del settore a concentrare gli sforzi sulla ricerca e sullo sviluppo di metodologie strumentali sempre più idonee alle esigenze di diagnosi clinica.

La speranza è quella di rivalutare l'enorme potenziale diagnostico di 'ECMU, attraverso la esecuzione di un esame delle urine personalizzato in base alle esigenze diagnostiche di ogni paziente.

Abstract

With these guidelines the Intersociety Urinalysis Group (GIAU) aims to stimulate the following aspects:

Improvement and standardization of the analytical approach to physical, chemical and morphological urine examination (ECMU).
Improvement of the chemical analysis of urine with particular regard to the reconsideration of the diagnostic significance of the parameters that are traditionally evaluated in dipstick analysis together with an increasing awareness of the limits of sensitivity and specificity of this analytical method.
Increase the awareness of the importance of professional skills in the field of urinary morphology and the relationship with the clinicians.
Implement a policy of evaluation of the analytical quality by using, in addition to traditional internal and external controls, a program for the evaluation of morphological competence.
Stimulate the diagnostics industry to focus research efforts and development methodology and instrumental catering on the needs of clinical diagnosis.
The hope is to revalue the enormous diagnostic potential of 'ECMU, implementing a urinalysis on personalized diagnostic needs for each patient.
Emphasize the value added to ECMU by automated analyzers for the study of the morphology of the corpuscular fraction urine.

The hope is to revalue the enormous potential diagnostic of 'ECMU, implementing a urinalysis on personalized diagnostic needs that each patient brings with it.

Tabella 1. Principali alterazioni del colore delle urine e loro possibili cause

Colore	Patologia	Farmaci	Alimenti
ROSSO	Ematuria Porfirinuria Mononucleosi Emoglobinuria Mioglobinuria	Cascara Desferroxamina Doxorubicina Levodopa Fenotiazine Fenitoina Rifampicina Senna (urine alcaline) Epirubucina Sulfametossazolo Ibuprofene	Barbabietole More Rabarbaro
ARANCIONE	Disidratazione	Warfarin Rifampicina Sulfasalanzina (urine alcaline) Fluorescina	Peperoncino Rabarbaro
VERDE-BLU	Ittero (verdi) Tifo Infezioni urinarie da Pseudomonas (verdi) Blue diaper sindrome	Amitriptilina Indometacina Blu di metilene Triamterene
MARRONE	Alkaptonuria Tirosinosi Porfirinuria Ittero	Cascara Ferro Levodopa Metronidazolo Metildopa Nitrofurantoina Fenotiazine Fenitoina Chinino Senna (urine alcaline)
NERO	Black water fever (febbre emoglobinurica in corso di alcune malattie infettive quali malaria, dengue, coinfezione acuta da HBV + HDV) Melanoma maligno	Cascara Ferro Metildopa Chinino
VIOLA	Porfirinuria Sindrome da catetere vescicale (Purple urine bag syndrome)	Senna

Colore

Patologia

Farmaci

Alimenti

ROSSO

Ematuria

Porfirinuria

Mononucleosi

Emoglobinuria

Mioglobinuria

Cascara

Desferroxamina

Doxorubicina

Levodopa

Fenotiazine

Fenitoina

Rifampicina

Senna (urine alcaline)

Epirubucina

Sulfametossazolo

Ibuprofene

Barbabietole

Rabarbaro

ARANCIONE

Disidratazione

Warfarin

Rifampicina

Sulfasalanzina (urine alcaline)

Fluorescina

Peperoncino

Rabarbaro

VERDE-BLU

Ittero (verdi)

Tifo

Infezioni urinarie da Pseudomonas (verdi)

Blue diaper sindrome

Amitriptilina

Indometacina

Blu di metilene

Triamterene

MARRONE

Alkaptonuria

Tirosinosi

Porfirinuria

Ittero

Cascara

Ferro

Levodopa

Metronidazolo

Metildopa

Nitrofurantoina

Fenotiazine

Fenitoina

Chinino

Senna (urine alcaline)

NERO

Black water fever (febbre emoglobinurica in corso di alcune malattie infettive quali malaria, dengue, coinfezione acuta da HBV + HDV)

Melanoma maligno

Cascara

Ferro

Metildopa

Chinino

VIOLA

Porfirinuria

Sindrome da catetere vescicale (Purple urine bag syndrome)

Senna

Tabella 2. Valutazione comparativa della sensibilità analitica di alcune strisce reattive del commercio per albumina, glucosio, emazie/emoglobina, esterasi, nitriti e chetoni

	Albumina	Glucosio	Emazie Emoglobina	Esterasi	Nitriti	Chetoni
AimStick	15 mg/dL	50 mg/dL	5 RBC/microL 0.3 mg/dL	5 WBC/microL	0.09 mg/dL	Ad 5 mg/dL Ac 48 mg/dL
AutionSticks	15 mg/dL	50 mg/dL	20 RBC/microL 0.06 mg/dL	5 WBC/microL	0.09 mg/dL	Ad 5 mg/dL -
Chemistrip	6 mg/dL	40 mg/dL	5 RBC/microL -	20 WBC/microL	0.05 mg/dL	Ad 9 mg/dL Ac 70 mg/dL
CombiScreen plus	15 mg/dL	40 mg/dL	5 RBC/microL -	10 WBC/microL	0.05 mg/dL	Ad 5 mg/dL Ac 50 mg/dL
DiaScreen	5 mg/dL	50 mg/dL	5 RBC/microL 0.02 mg/dL	20 WBC/microL	0.05 mg/dL	Ad 5 mg/dL -
Dirui Serie H	15 mg/dL	50 mg/dL	5 RBC/microL -	5 WBC/microL		Ad 0.5 mmol/LL -
MediTest C9	30 mg/dL	50 mg/dL	10 RBC/microL -	-	0.05 mg/dL	- -
Mission	18 mg/dL	25 mg/dL	- 0.018 mg/dL	9 WBC/microL	0.05 mg/dL	Ad 2.5 mg/dL -
Multistix	15 mg/dL	75 mg/dL	5 RBC/microL 0.015 mg/dL	5 WBC/microL	0.06 mg/dL	Ad 5 mg/dL -
Self Stick	5 mg/dL	50 mg/dL	5 RBC/microL -	-	0.05 mg/dL	Ad 5 mg/dL Ac 100 mg/dL
Uriflet S2	5 mg/dL	10 mg/dL	10 RBC/microL 0.03 mg/dL	20 WBC/microL	0.08 mg/dL	Ad 5 mg/dL -
Uriscan	10 mg/dL	50 mg/dL	5 RBC/microL 0.015 mg/dL	2 WBC/microL	0.05 mg/dL	Ad 5 mg/dL Ac 70 mg/dL
Uritest 13G	10 mg/dL	40 mg/dL	- 0.3 mg/dL	15 WBC/microL	0.06 mg/dL	Ad 0.5 mmol/L
Uro-Dip 10C	-	100 mg/dL	- 0.05 mg/dL	-	0.05 mg/dL	Ad 5 mg/dL Ac 100 mg/dL
Uropaper alfa 3-9L	15 mg/dL	50 mg/dL	10 RBC/microL 0.3 mg/dL	25 WBC/microL	0.1 mg/dL	Ad 10 mg/dL -
URS	15 mg/dL	100 mg/dL	5 RBC/microL 0.3 mg/dL	10 WBC/microL	0.075 mg/dL	Ad 5 mg/dL -
vChem	15 mg/dL	45 mg/dL	5 RBC/microL 0.2 mg/dL	20 WBC/microL	0.05 mg/dL	Ad 5 mg/dL Ac 48 mg/dL

Modificata Da Graff’ Textbook of Urinalysis and body Fluids II eds. Mundt L, Shanan K. Lippicot Williamds and Wilkins 2010

Tabella 3. Principali interferenti con i DIP-STIK

Parametro	Metodo / Sensibilità	Specificità / Interferenze
Densità Relativa	Reattivo polielettrolitico ed indicatore di pH Da 1010 a 1030	Solo soluti ionici Interferenza in riduzione: pH alcalino, Glucosio ed Urea >1 g/L Interferenza in aumento: Proteine 500 mg/dL, Chetoacidosi
pH	Due indicatori di pH Da 5.0 a 9.0 incrementi di 0.5 unità	Interferenza in riduzione: Formaldeide
Sangue / Emoglobina	Attività pseudoperossidasica Da 0.02 a 0.06 mg/dL Da 5 a 10 RBC/mL	Falsi positivi: Perossidasi batteriche, Agenti ossidanti, Acido cloridrico Falsi negativi: Ascorbato, Alta densità relativa, Agenti riducenti, Formalina, Nitriti, Farmaci
Esterasi leucocitaria	Attività Indoxil esterasica 5-25 WBC/microL	Presente solo nei granulociti Falsi positivi: Urine ipercromiche, Formalina, Farmaci, Sodio azide, Detergenti Falsi negativi: Ascorbato, Borato, Glucosio >3g/dL, Proteine >05g/dL, Elevata densità relativa, Agenti ossidanti, Saponi e detergenti, Farmaci
Nitriti	Reazione di Greiss 0.05 mg/dL	Falsi positivi: Urine ipercromiche, Farmaci, Malconservazione campione Falsi negativi: Batteri non formanti nitriti, Dieta povera in nitrati, Urine che non hanno soggiornato in vescica , Ascorbato
Proteine	Legame non specifico ad un indicatore Sensibili alla albumina 6-15 mg/dL	Falsi negativi: Presenza di globuline, Urine ipercromiche Falsi positivi: Urine fortemente alcaline, Urine ipercromiche, Farmaci, Ammonio quaternario, Plasma expander
Glucosio	Glucosio ossidasi perossidasi 40 mg/dl	Metodo specifico per il glucosio ma interferenze da bassa temperatura e/o elevata densità relativa Falsi positivi: Agenti ossidanti, Perossidi, Acido cloridrico Falsi negativi: Ascorbato, Malconservazione
Chetoni	Reazione al nitroprussiato 5-10 mg/dL per aceto acetato 50-70 mg/dL per acetone	Non evidenzia l’acido idrossi butirrico Falsi positivi: Gruppi sulfidrilici liberi (N-acetil cisteina), Urine ipercromiche, Metaboliti del levodopa, Fenolftaleina Falsi negativi: Malconservazione
Bilirubina	Azoreazione con sali di diazonio 0.4-0.8 mg/dL bilirubina coniugata	Falsi positivi: Urine ipercromiche, Cloropromazina Falsi negativi: Ascorbato, Nitriti, Malconservazione, Luce solare diretta
Urobilinogeno	Azoreazione con aldeide di Erlich 0.2 – 1.0 mg/dL	Falsi positivi: Urine ipercromiche, Sulfonamidi, Acido para aminosalilico Falsi negativi: Formalina, Agenti ossidanti, Malconservazione
Ascorbato	Riduzione dell’indolo 20 mg/dL	Falsi positivi: Gruppi sulfidrilici liberi (N-acetil cisteina), Agenti riducenti
Creatinina	Reazione ossidativa con complessi di rame	Falsi negativi: EDTA Falsi positivi: Emoglobina, mioglobina

Parametro

Metodo / Sensibilità

Specificità / Interferenze

Densità Relativa

Reattivo polielettrolitico ed indicatore di pH

Da 1010 a 1030

Solo soluti ionici

Interferenza in riduzione: pH alcalino, Glucosio ed Urea >1 g/L

Interferenza in aumento: Proteine 500 mg/dL, Chetoacidosi

Due indicatori di pH

Da 5.0 a 9.0 incrementi di 0.5 unità

Interferenza in riduzione: Formaldeide

Sangue / Emoglobina

Attività pseudoperossidasica

Da 0.02 a 0.06 mg/dL

Da 5 a 10 RBC/mL

Falsi positivi: Perossidasi batteriche, Agenti ossidanti, Acido cloridrico

Falsi negativi: Ascorbato, Alta densità relativa, Agenti riducenti, Formalina, Nitriti, Farmaci

Esterasi leucocitaria

Attività Indoxil esterasica

5-25 WBC/microL

Presente solo nei granulociti

Falsi positivi: Urine ipercromiche, Formalina, Farmaci, Sodio azide, Detergenti

Falsi negativi: Ascorbato, Borato, Glucosio >3g/dL, Proteine >05g/dL, Elevata densità relativa, Agenti ossidanti, Saponi e detergenti, Farmaci

Nitriti

Reazione di Greiss

0.05 mg/dL

Falsi positivi: Urine ipercromiche, Farmaci, Malconservazione campione

Falsi negativi: Batteri non formanti nitriti, Dieta povera in nitrati, Urine che non hanno soggiornato in vescica , Ascorbato

Proteine

Legame non specifico ad un indicatore

Sensibili alla albumina

6-15 mg/dL

Falsi negativi: Presenza di globuline, Urine ipercromiche

Falsi positivi: Urine fortemente alcaline, Urine ipercromiche, Farmaci, Ammonio quaternario, Plasma expander

Glucosio

Glucosio ossidasi perossidasi

40 mg/dl

Metodo specifico per il glucosio ma interferenze da bassa temperatura e/o elevata densità relativa

Falsi positivi: Agenti ossidanti, Perossidi, Acido cloridrico

Falsi negativi: Ascorbato, Malconservazione

Chetoni

Reazione al nitroprussiato

5-10 mg/dL per aceto acetato

50-70 mg/dL per acetone

Non evidenzia l’acido idrossi butirrico

Falsi positivi: Gruppi sulfidrilici liberi (N-acetil cisteina), Urine ipercromiche, Metaboliti del levodopa, Fenolftaleina

Falsi negativi: Malconservazione

Bilirubina

Azoreazione con sali di diazonio

0.4-0.8 mg/dL

bilirubina coniugata

Falsi positivi: Urine ipercromiche, Cloropromazina

Falsi negativi: Ascorbato, Nitriti, Malconservazione, Luce solare diretta

Urobilinogeno

Azoreazione con aldeide di Erlich

0.2 – 1.0 mg/dL

Falsi positivi: Urine ipercromiche, Sulfonamidi, Acido para aminosalilico

Falsi negativi: Formalina, Agenti ossidanti, Malconservazione

Ascorbato

Riduzione dell’indolo

20 mg/dL

Falsi positivi: Gruppi sulfidrilici liberi (N-acetil cisteina), Agenti riducenti

Creatinina

Reazione ossidativa con complessi di rame

Falsi negativi: EDTA

Falsi positivi: Emoglobina, mioglobina

Tabella 5. Elementi corpuscolati nelle urine e principali associazioni cliniche

Elementi principali	Principali associazioni cliniche
Eritrociti dismorfici e acantociti	Ematuria glomerulare
Eritrociti isomorfi	Ematuria non glomerulare
Leucociti polimorfonucleati	Infezioni urinarie Glomerulonefriti proliferative Nefriti interstiziali acute Contaminazione da secrezioni genitali
Cellule epiteliali renali tubulari	Patologie renali associate a danno tubulare organico (=necrosi tubulare acuta), quali si possono osservare nelle nefropatie tubulotossiche, ischemiche, glomerulonefriti, nefriti intersitiziali ecc.
Cellule transizionali superficiali	Patologie associate a danno dell'epitelio di transizione (strati cellulari superficiali)
Cellule transizionali profonde	Patologie associate a danno dell'epitelio di transizione (strati cellulari profondi)
Cellule squamose	Contaminazione da secrezioni genitali
Lipidi	Patologie glomerulari associate a proteinuria di grado variabile, ma soprattutto di entità nefrosica. Malattia di Fabry (da accumulo lisosomiale di glicosfingolipidi)
Cilindri jalini	Possono essere presenti in piccolo numero negli individui normali. Possono essere presenti in svariate tipologia di patologia renale.
Cilindri jalino-granulosi	Possono essere presenti in piccolo numero negli individui normali. Possono essere presenti in svariate tipologia di patologia renale
Clindri granulosi	Possono essere presenti in svariate tipologia di patologia renale Necrosi tubulare acuta
Cilindri cerei	Patologia renale con significativa perdita di funzione
Cilindri lipidici	Sindrome nefrosica
Cilindri eritrocitari	Ematuria glomerulare Glomerulonefrite proliferativa o necrotizzante
Cilindri leucocitari	Nefrite interstiziale acuta Pielonefrite acuta Glomerulonefrite proliferativa
Cilindri cellulari / epiteliali (cellule epiteliali tubulari)	Necrosi tubulare acuta Nefrite interstiziale acuta Sindrome nefrosica
Cilindri emoglobinici	Ematuria glomerulare Glomerulonefrite proliferativa o necrotizzante Emolisi acuta intravascolare
Cilindri mioglobinici	Rabdomiolisi
Cilindri bilirubinici	Ittero marcato
Cilindri con inclusi batterici o micotici	Infezioni batteriche o micotiche del rene
Cilindri con inclusioni cristalline	Insufficienza renale acuta da cristalluria massiva
Cilindri a composizione mista	Secondo il tipo di inclusione

Modificata Da Graff’ Textbook of Urinalysis and body Fluids II eds. Mundt L, Shanan K. Lippicot Williamds and Wilkins 2010

Modificata Da Fogazzi GB e Garigali G Urinalysis. In Johnson R, Feehally J, Floege J Comprehensive Clinical Nephrology 5^th edition pp 39-52. Elsevier 2015

Tabella 6. Classificazione delle principali cause di ematuria

Cause Urologiche	Cause non Urologiche	Falsa Ematuria
Cistite emorragica	Nefrite interstiziale acuta	Colorazione da Farmaci
Calcolosi	Da anticoagulanti	Colorazione da Alimenti
Neoplasie delle vie urinarie	Glomerulopatie	Mioglobinuria
Neoplasie della prostata		Porfirie
Traumatismi		Emoglobinuria
Ematuria da sforzo fisico intenso
Fistole artero-venose renali
Rottura cisti renali
Manovre diagnostiche invasive
Endometriosi delle vie urinarie

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pubblicata il 09 dicembre 2016
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Parole chiave: analisi delle urine, fase analitica, linee guida

Key words: Analytical Phase, guidelines, Urinalysis

3 Commenti

1	Metodi Rapidi: Microscopia estemporanea del campione nativo (livello 1)
2	Metodi di Routine: Esame microscopico standardizzato del sedimento (livello 2)
3	Metodi di Comparazione: Conta degli elementi corpuscolati delle urine in camera citometrica effettuata su campione non centrifugato. Valutazione della flora batterica dopo centrifugazione fissazione e colorazione secondo Gram. (livello 3)
4	Metodo di Riferimento: Conta di WBC e RBC, cellule epiteliali e cilindri in camera citologia secondo raccomandazione ISLH (livello 4)

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Esame fisico, chimico e morfologico delle urine proposta di Linee Guida per la fase analitica

Esame delle urine: linee guida per la fase analitica

Urinalysis: guidelines for analytical phase

Esame fisico, chimico e morfologico delle urine proposta di linee guida per la fase analitica del Gruppo Intersocietario Analisi delle Urine (GIAU)

Physical, chemical and morphological urine examination guidelines for the Analytical Phase from the Intersociety Urinalysis Group

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Abstract

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