Dr. Salwa Al-ansari

Renal Diagnostic and Renal Diagnostic and Laboratory TestsLaboratory Tests

ByByDr Salwa Alansari; PhDDr Salwa Alansari; PhD

Dr. Salwa Al-ansari

IntroductionIntroductionKidneys and urinary tractKidneys and urinary tract1- Control the quantity and quality of fluids 1- Control the quantity and quality of fluids

within the bodywithin the body.. 2- Produce hormones and vitamins2- Produce hormones and vitamins

Diseases and conditions affecting the Diseases and conditions affecting the kidneykidney

1-Diseases that affect the blood vessels 1-Diseases that affect the blood vessels 2-Disease and infection in other parts of the body2-Disease and infection in other parts of the body

Dr. Salwa Al-ansari

3-kidney diseases:• Obstruction Obstruction • Infection Infection • Glomerular diseases Glomerular diseases • Other factors Other factors

Signs and symptomsSigns and symptoms

• Swelling or puffinessSwelling or puffiness • Urine character or amountUrine character or amount

Dr. Salwa Al-ansari

• Problems urinating

• Mid-back pain

• High blood pressure

Dr. Salwa Al-ansari

Guidelines for proper test Guidelines for proper test preparation and performancepreparation and performance

To ensure the use of correct diagnostic tests To ensure the use of correct diagnostic tests can confirm or eliminate the presence of can confirm or eliminate the presence of

disease and improve the cost efficiency of disease and improve the cost efficiency of screening testsscreening tests.

1.Universal Precautions1.Universal Precautions• All patients considered potentially infectious.All patients considered potentially infectious.

Dr. Salwa Al-ansari

• Use of protective barriersUse of protective barriers.2-Proper sequencing and scheduling of 2-Proper sequencing and scheduling of

the tests.the tests.• Affect ability to perform tests in limited time Affect ability to perform tests in limited time

period.period.• Patient preparation before the test.Patient preparation before the test.3-Patient Identification & Education3-Patient Identification & Education• Safety Factor.Safety Factor.• More cooperationMore cooperation• Better test results.Better test results.

Dr. Salwa Al-ansari

4-Variables Affecting Test result4-Variables Affecting Test result• AgeAge• GenderGender• RaceRace• PregnancyPregnancy• Food IngestionFood Ingestion• PosturePosture5- Specimen Collection e.g.:5- Specimen Collection e.g.:• Tubes Tubes • 24 hour urine collection24 hour urine collection

Dr. Salwa Al-ansari

6-Trasnsport and Processing of the 6-Trasnsport and Processing of the SampleSample..

• As soon as possibleAs soon as possible7-SI Units7-SI Units• Standardized International MeasuresStandardized International Measures.8-Reporting Test Result8-Reporting Test Result• Clear and easy to interpret.Clear and easy to interpret.

Dr. Salwa Al-ansari

Clinical Examination testsClinical Examination tests• Assessment of cardiovascular and volume Assessment of cardiovascular and volume

statusstatus• Pulse rate and blood pressurePulse rate and blood pressure • Abdominal examination:Abdominal examination:e.g. Obstructione.g. ObstructionEpigastric bruit: Epigastric bruit: renal vascular hypertensionrenal vascular hypertension

• Blood pressure recordingsBlood pressure recordings

Dr. Salwa Al-ansari

Clinical Laboratory TestsClinical Laboratory TestsUrine-analysisUrine-analysis :DM, glomerulonephritis, chronic UTI.

• A paper or plastic dipstickA paper or plastic dipstick or Microchemistry system. or Microchemistry system.• Macroscopic analysisMacroscopic analysisNormal urine volume is 750 to 2000 mlNormal urine volume is 750 to 2000 ml//24hr24hr

Types:Types:11stst morning specimen morning specimenRandomRandomTimed urine collectionTimed urine collection

Appearance ; Color ; Odor; pHAppearance ; Color ; Odor; pH1-RBC1-RBC2-WBC2-WBC3-Nitrite3-Nitrite

Dr. Salwa Al-ansari

4-Protein4-Protein5-Specific Gravity5-Specific Gravity6-Glucose6-Glucose7-Ketones7-Ketones8-Bilirubin8-Bilirubin9-Leukocyte esterase?9-Leukocyte esterase?10-Urobilinogen10-Urobilinogen11-Casts11-Casts12-Crystals12-Crystals

EnzymesEnzymesSCPL & Alkaline PhosphataseSCPL & Alkaline Phosphatase

Dr. Salwa Al-ansari

Cystatin C & Creatinine clearance:Cystatin C & Creatinine clearance: GFRGFR

��S.IgA & S.IgA/C3 ratio :S.IgA & S.IgA/C3 ratio : IgA nephropathyIgA nephropathy

Urinary Cytokines(MCP-1):Urinary Cytokines(MCP-1): IgA nephropathy PrognosisIgA nephropathy Prognosis ??? ???

Albumin Polymerase (urine):Albumin Polymerase (urine): GlomerulonephritisGlomerulonephritis with with Nephrotic syndromeNephrotic syndrome

Liver enzymes?Liver enzymes?

Dr. Salwa Al-ansari

CBCCBC• HbHb• HctHct

Hormonal AnalysisHormonal Analysis1-Renin :1-Renin : evaluate type of hypertensionevaluate type of hypertension2-ADH2-ADH3-Catecholamine &VMA3-Catecholamine &VMA4-Erythropoietin4-Erythropoietin5-PTH5-PTH6-Vt. D6-Vt. D

Dr. Salwa Al-ansari

Renal artery stenosis↓Renal blood flow

Stimulation of juxta-glomerular cells

↑Renin

↑Angiotensin I,IIVasoconstriction

↑Aldosterone

Hypertension

Reabsorption↑ :Na

Water

Renin –Angiotensin system

Dr. Salwa Al-ansari

Iron PanelIron Panel • IronIron• Folic AcidFolic Acid• FerritinFerritin• Vt. BVt. B1212

Prostate MarkersProstate MarkersPSAPSAIndicationIndication1-Infection1-Infection2-Benign hypertrophy2-Benign hypertrophy3- Prostate cancer3- Prostate cancer4-Therapy4-Therapy

Dr. Salwa Al-ansari

• PSA Density ( PSA /gland volume)PSA Density ( PSA /gland volume)• PSA Velocity (PSA/time)PSA Velocity (PSA/time)• %%fPSAfPSA• < 25 high probability of ca.< 25 high probability of ca.• > 25 low probability of ca.> 25 low probability of ca.

Immunology testsImmunology tests• Lupus?Lupus?• ComplementComplement• ASOT; nuclear ABASOT; nuclear AB

Kidney stone analysisKidney stone analysis

Dr. Salwa Al-ansari

Urine Culture &SensitivityUrine Culture &SensitivityUTIUTI

Electrophoresis Electrophoresis (urine)(urine)Protein loosing nephropathiesProtein loosing nephropathies (N.S & Nephrosis) (N.S & Nephrosis)Nephrotic syndromeNephrotic syndrome↓↓↓↓AlbuminAlbumin↑↑↑↑αα22 globulin globulin

N or ↑ N or ↑ ββ globulin globulinSelective Selective : lipoid nephrosis: lipoid nephrosisNon-selectiveNon-selective : glomerulonephritis : glomerulonephritis

Dr. Salwa Al-ansari

ElectrolytesElectrolytesNaNa++

KK++

CLCL--

UAUACaCa+2+2

POPO44

HCO3HCO3--

OsmolalityOsmolality

FNA?FNA?

Dr. Salwa Al-ansari

Injury biomarkers:Injury biomarkers:1-Glutathione S1-Glutathione S--

transferases transferases ((GSTsGSTs))• alpha GST in proximal alpha GST in proximal

tubule (graph 1)tubule (graph 1)• Pi GST in the distal Pi GST in the distal

(graph2).(graph2).

2-Collagen IV2-Collagen IV :Glomerular basement

membrane (graph3)

3-b-trace protein (BTP)3-b-trace protein (BTP)indicator of reduced GFRindicator of reduced GFR

Dr. Salwa Al-ansari

Apolipoprotein A-I Apolipoprotein A-I

Exosomes ? Exosomes ? Proteins profiling in urineProteins profiling in urine

Dr. Salwa Al-ansari

Proteomic approachProteomic approach

Mass spectrophotometerMass spectrophotometer

• Coupled to capillary electrophoresisCoupled to capillary electrophoresis

• 2-Dimensional electrophoresis2-Dimensional electrophoresis

• SELDI: surface enhanced laser desorption /ionization SELDI: surface enhanced laser desorption /ionization protein chip array time of flight mass spectrometryprotein chip array time of flight mass spectrometry

Dr. Salwa Al-ansari

ConditionTests Used in DiagnosisTests Used to Follow

Chronic kidney disease

(chronic renal failure)

Blood urea, creatinine, estimated GFR, urinalysisUrea, creatinine, estimated GFR, electrolytes, calcium, phosphate, alkaline phosphatase, parathyroid hormone, FBC

Urinary tract infections

Urinalysis, urine cultureUrinalysis, urine culture

Kidney stonesImaging (see below), urinalysisUrine sodium, calcium, phosphate, citrate, oxalate, uric acid

Nephrotic syndrome

Urinalysis; serum albumin, total protein, cholesterol; urine total protein; antinuclear antibody (ANA) test, hepatitis

B test, hepatitis C test; complement levels

Urine total protein, serum cholesterol, urea, creatinine, estimated GFR

NephritisUrinalysis, serum urea, creatinine, estimated GFR, serum albumin, urine total protein, antinuclear antibody

(ANA) test, antistreptolysin O, antiglomerular basement membrane antibody, antineutrophil cytoplasmic

antibodies

Urea, creatinine, estimated GFR, urinalysis

Kidney disease due to

diabetes or high blood pressure

MicroalbuminMicroalbumin, urine total protein, urea, creatinine, estimated GFR

SummarySummary

Dr. Salwa Al-ansari

Radiology TestsRadiology Tests

• PyelographyPyelography

• KUB X-ray : KUB X-ray : uric acid stonesuric acid stones

• Prostate ultra sonographyProstate ultra sonography

• MRIMRI

Dr. Salwa Al-ansari

• AngiographyAngiography

• Magnetic resonance angiography (MRA): Magnetic resonance angiography (MRA): newnew

Dr. Salwa Al-ansari

Urologic TestUrologic Test• CystometryCystometry

• CystogrpahyCystogrpahy

• Pelvic floor sphincter electromyographyPelvic floor sphincter electromyography

• Urethral Pressure ProfileUrethral Pressure Profile

Dr. Salwa Al-ansari

• Kidney BiopsyKidney BiopsyIndicationIndication• Unusual depositUnusual deposit• Infecting organismInfecting organism• Speed of failureSpeed of failure• Non functioning transplant Non functioning transplant

kidneykidney• Usually accompanied by Usually accompanied by

urine and blood tests.urine and blood tests.

Dr. Salwa Al-ansari

Nuclear medicine TestsNuclear medicine TestsRenal Blood FlowRenal Blood Flow (Tc99m-DTPA) (Tc99m-DTPA)IndicationIndication1-Renovascular hypertension 1-Renovascular hypertension 2-Obstruction2-Obstruction3-CRF vs. ARF3-CRF vs. ARF4-Renal transplant4-Renal transplantInformationInformation• GFRGFR• ExcretionExcretion• ShapeShape

As shown in graphs:As shown in graphs:

Dr. Salwa Al-ansari

Dr. Salwa Al-ansari

Dr. Salwa Al-ansari

Dr. Salwa Al-ansari

Renal structural scanRenal structural scan ((99m99mTc DTPA or Tc DTPA or 99m99mTc DSMA)Tc DSMA)

IndicationIndication

1-Alteration in anatomic structure1-Alteration in anatomic structure ( (tumor; cyst; tumor; cyst; abscessabscess))

2-Congenital disorders 2-Congenital disorders (hypoplasia; a plasia mal-(hypoplasia; a plasia mal-position of kidney)position of kidney)

3-Transplant rejection3-Transplant rejection

Dr. Salwa Al-ansari

Renal function scanRenal function scan ((RenogramRenogram))

IndicationIndication1- 1- 99m99mTc DTPA: GFRTc DTPA: GFR

2- 2- 99m99mTc DMSA: tubular cell excretionTc DMSA: tubular cell excretion

3- Iodohippurate Na 3- Iodohippurate Na 131131I or Iodohippurate Na I or Iodohippurate Na 133133I: GFR I: GFR & tubular cell excretion.& tubular cell excretion.

Dr. Salwa Al-ansari

Renal hypertension scanRenal hypertension scan ((ACE inhibitor: ACE inhibitor: CaptoprilCaptopril))

IndicationIndication• Renovascular hypertensionRenovascular hypertension

Dr. Salwa Al-ansari

Renal Obstruction scanRenal Obstruction scanIndicationIndication1-Obstruction of the outflow tract1-Obstruction of the outflow tract ( (pelvis; ureter; bladder pelvis; ureter; bladder

outletoutlet) )

2-Arterial Atherosclerosis2-Arterial Atherosclerosis3-Renal tumors3-Renal tumors4-renal or ureteral disease &conditions.4-renal or ureteral disease &conditions.

Renal reflux study (Tc99m - DTPA)Renal reflux study (Tc99m - DTPA) vesicoureteral refluxvesicoureteral reflux

Requires catheterization of bladder.Requires catheterization of bladder.

Dr. Salwa Al-ansari

Genetic TestsGenetic TestsSequencing Genotyping RFLP analysisImmunohistochemistry

1- Hereditary Dis. associated with Renal Cell 1- Hereditary Dis. associated with Renal Cell CancerCancer

• VHL(3p25-26):VHL(3p25-26): Von-Hippel LindanVon-Hippel Lindan• c-MET(7931.3):c-MET(7931.3): Renal Cell Cancer.Renal Cell Cancer.

Dr. Salwa Al-ansari

• BHD:BHD: Birt- Hogg- (17p11.2)?Birt- Hogg- (17p11.2)? • TcF2:TcF2: HNF1HNF1ββ disease disease..

• HaptoglobinHaptoglobin Homozygote:Homozygote: CRFCRFHeterozygote:Heterozygote: Chronic glomerulonephritisChronic glomerulonephritis

2-Pediatric Mitochondrial diseases2-Pediatric Mitochondrial diseasese.g Kearns – Sayer syndrome; Pearson Syndrome & e.g Kearns – Sayer syndrome; Pearson Syndrome &

encephalopathyencephalopathy

Dr. Salwa Al-ansari

3-Tests for genetic diseases associated with 3-Tests for genetic diseases associated with kidney dysfunction (renal transport)kidney dysfunction (renal transport)

e.g Fanconi’s syndrome; cysteinuriae.g Fanconi’s syndrome; cysteinuria

Amino acid quantitationsAmino acid quantitations

Urine ( random ; 24- hours); serum and CSF

Dr. Salwa Al-ansari

MethodMethod High-pressure liquid chromatography (HPLC) High-pressure liquid chromatography (HPLC)

separation with post-column Ninhydrin quantitation separation with post-column Ninhydrin quantitation

Dr. Salwa Al-ansari

 Sample Points1. PER 2. TAU 3. PETN 4. THR 5. GLU 6. GLY 7. ALA 8. MET 9. CYST 10. ILE 11. LEU 12. TYR 13. PHE 14. BALA 15. BABA 16. TRP 17. EIN 18. NH3 19. ORN 20. LYS 21. 1 ME-HIS 22. HIS 23. 3 ME-HIS 24. ANS 25. CARN 26. ARG

2424--hours urine amino hours urine amino acidsacids

Dr. Salwa Al-ansari

Research TestsResearch Tests Clinical trialsClinical trials

• Renal PapillaryRenal Papillary Antigens 1 andAntigens 1 and 22::collecting ducts of collecting ducts of the rat kidney: the rat kidney: Renal Papillary NecrosisRenal Papillary Necrosis

• Ischaemia-Reperfusion Injury /kidney Ischaemia-Reperfusion Injury /kidney transplant:transplant: GST & collagen IVGST & collagen IV

VUR : DNA and immortalized lymphocytes VUR : DNA and immortalized lymphocytes from sibling pairsfrom sibling pairs

peritoneal dialysisperitoneal dialysis

Dr. Salwa Al-ansari

transplant: long term outcometransplant: long term outcome

• fibronectin: scar proteinfibronectin: scar protein

• Studies aimed at DNA vaccinationStudies aimed at DNA vaccinationRCC associated peptides e.g. CA9 antigen derived peptides. RCC associated peptides e.g. CA9 antigen derived peptides.

Detected in peripheral mononuclear cells by INF-Detected in peripheral mononuclear cells by INF-γγ release release assay.assay.

• Podocytes associated proteins (graph)Podocytes associated proteins (graph)Characterization of each proteins and mutations associatedCharacterization of each proteins and mutations associated

Dr. Salwa Al-ansari

Dr. Salwa Al-ansari

Beta 8 integrin in glomerular injuryBeta 8 integrin in glomerular injury

Dr. Salwa Al-ansari

Ephrin A2 regulates ureteric bud branchingEphrin A2 regulates ureteric bud branching

Dr. Salwa Al-ansari

Wilm's tumor interacting protein (WTIP)Wilm's tumor interacting protein (WTIP)

Dr. Salwa Al-ansari

• Lithium clearanceLithium clearance1- Clearance Depend GFR1- Clearance Depend GFR2- Hyponatraemia vs. litium2- Hyponatraemia vs. litium

• Urinary transthyretinUrinary transthyretinMutation in the gene gives transthyretin amyloidosisMutation in the gene gives transthyretin amyloidosis

Dr. Salwa Al-ansari

Research involving nuclear material and Research involving nuclear material and production of New tracer:production of New tracer:

• Technologies for real-time, in vivo imaging of Technologies for real-time, in vivo imaging of gene expression in health and disease;gene expression in health and disease;

• Labeling of progenitor cells for non-invasively Labeling of progenitor cells for non-invasively imaging and tracking their behavior and fate in imaging and tracking their behavior and fate in vivo and their overall role in organ and tissue vivo and their overall role in organ and tissue regeneration in disease states; regeneration in disease states;

Dr. Salwa Al-ansari

• In vivo targeting of mutated proteins critical to In vivo targeting of mutated proteins critical to carcinogenesis and tumor cell growth.carcinogenesis and tumor cell growth.

• Enabling in vivo imaging assay of Enabling in vivo imaging assay of neurotransmitter chemistry and brain functionneurotransmitter chemistry and brain function

Dr. Salwa Al-ansari

ReferencesReferences1.1. Yagame, M. et al. (1997). Significance of urinary type IV Yagame, M. et al. (1997). Significance of urinary type IV

collagen in patients with diabetic nephropathy using a highly collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay. Journal of sensitive one-step sandwich enzyme immunoassay. Journal of Clinical and Laboratory Analysis 11. 110-116Clinical and Laboratory Analysis 11. 110-116

2.2. Okinogi et alOkinogi et al. (. (20012001). ). Urinary Type IV Collagen Excretion Urinary Type IV Collagen Excretion Reflects Renal Morphological Alterations and Type IV Reflects Renal Morphological Alterations and Type IV expression in patients with type 2 Diabetesexpression in patients with type 2 Diabetes. . Clinical Nephrology Clinical Nephrology 55, 357-36455, 357-364..

3.3. Maxwell P-R et al. (2004). Differentiation between renal injury Maxwell P-R et al. (2004). Differentiation between renal injury and compensatory responses by the use of specific biomarkers. and compensatory responses by the use of specific biomarkers. Poster presented at the 43rd Annual meeting of the American Poster presented at the 43rd Annual meeting of the American Society of Toxicology, Baltimore March 21-25, 2004.Society of Toxicology, Baltimore March 21-25, 2004.

Dr. Salwa Al-ansari

4. Corrigal, A.V. et al. (1988). Glutathione S-transferase Corrigal, A.V. et al. (1988). Glutathione S-transferase distribution and concentration in human organs. Biochem. distribution and concentration in human organs. Biochem. Int. 16: 443-448.Int. 16: 443-448.

5. Sundberg A.G.M. et al. (1994). Urinary pi class glutathione 5. Sundberg A.G.M. et al. (1994). Urinary pi class glutathione S-transferase as an indicator of tubular damage in the human S-transferase as an indicator of tubular damage in the human kidney. Nephron 67: 308-316.kidney. Nephron 67: 308-316.

6. Daeman, J.W. H.C. et al. (1997). Glutathione S-transferase 6. Daeman, J.W. H.C. et al. (1997). Glutathione S-transferase as predictor of functional outcome in transplantation of as predictor of functional outcome in transplantation of machine preserved non-heart-beating donor kidneys. machine preserved non-heart-beating donor kidneys. Transplantation 63 (1):89-93.Transplantation 63 (1):89-93.

7. Falkenberg, F. et al. (1996). Papillary antigens as markers of 7. Falkenberg, F. et al. (1996). Papillary antigens as markers of papillary toxicity. I Identification and characterisation of rat papillary toxicity. I Identification and characterisation of rat papillary antigens with monoclonal antibodies. Arch. papillary antigens with monoclonal antibodies. Arch. Toxicol. 71, 80-92Toxicol. 71, 80-92

Dr. Salwa Al-ansari

8. Bagley DH, Liu JB: Endoureteral sonography to define the anatomy of the obstructed ureteropelvic junction. Urol Clin North Am 1998 May; 25(2): 271-9.

10. Kathleen & Timothy Pagana. Mosby’s manual of diagnostic and laboratory tests. 2nd edition. 2002.

11. Daniel R, Anjali S, Tibor N, et al. Nature Clinical Practice Nephrology (2007) 3, 287-293 .

12. www.wickpedia.com

Dr. Salwa Al-ansari

The End!!!

Dr. Salwa Al-ansari

( PhD)