Proteinuria   how to approach final
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Proteinuria how to approach final

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Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in ...

Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

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Proteinuria   how to approach final Proteinuria how to approach final Presentation Transcript

  • Proteinuria- H T Approach? ow o Dr. Sachin Verma MD, FICM, FCCS, ICFC Fellowship in Intensive Care Medicine Infection Control Fellows Course Consultant Internal Medicine and Critical Care Web:- http://www.medicinedoctorinchandigarh.com Mob:- +91-7508677495References: 1. Brenner’s & Rector’s The Kidney 7th Ed. 2. Harrison’s Internal Medicine 17th Ed. 3. Oxford Textbook Of Clinical Nephrology 4. Internet
  • Problem Statement Proteinuria is a common finding in at least 17% adults in general practice, in routine dip stick screening Fewer than 2% of patients whose urine dipstick is positive for protein have serious and treatable urinary tract disorders
  • Definition 240 years ago, Hippocrates noted the association between “Bubbles on surface of urine” and kidney disease Proteinuria is defined as protein excretion >150mg/day. Most of the positive dip stick test results are due to benign proteinuria, which has no associated morbidity and mortality
  • Causes of Benign Proteinuria Dehydration Emotional stress Fever Heat injury Intense physical activity Most acute illnesses Orthostatic (postural )disorder
  • Composition Of Urinary Protein 70 mg/d 35 mg/d 15 mg/d 10 mg/d 15 mg/d 5 mg/dTamm Horsfall Protein Blood Group Related AntigensAlbumin MucopolysaccaridesHormones and Enzymes Immunoglobulins
  • Mechanism of Proteinuria FILTRATION OF BLOOD OCCURS IN GLOMERULUS GLOMERULAR FILTRATION BARRIER CONSISTS OF: 1. Capillary Endothelium 2.Glomerular Basement Membrane 3.Visceral Epithelium with foot processes forms slit diaphragm GLOMERULAR FILTRATION BARRIER IS SIZE & CHARGE DEPANDENT CHARGE IS ACCOUNTED BY :- Negative charge heparan sulfate present in GBM :- Sialoglycoprotein of epithelium & Endothelium cell
  • Mechanism of Proteinuria SIZE BARRIER IS ACCOUNTED BY: Slit diphragm made up of podocytes of visceral epithelium. Hence structure which is negatively charged and large size is restricted by GFB
  • Classification Of Proteinuria01.ACCORDING TO QUANTITY: MILD : < 500 mg MODERATE : 500 mg -2 gm SEVERE : > 2 gm02.ACCORDING TO NATURE: SELECTIVE NON SELECTIVE
  • 03.ACCORDING T SIT : O E PATHOPHYSIOLOGIC TYPE CAUSES FEATURES Increased glomerular Primary orGlomerular capillary permeability secondary to proteins glomerulopathy Decreased tubular Tubular or resorbtion of proteins interstitial diseaseTubular in glomerular filterate caused by drugs, hypertensive glomerulosclerosis Increased production MonoclonalOverflow of low molecular gammopahy, weight proteins leukemia
  • Causes Of Proteinuria Primary glomerulonephropathy Primary glomerulonephropathy  Minimal change disease  Idiopathic membranous glomerulonephritis  Focal segmental glomerulonephritis  Membranoproliferative glomerulonephritis  IgA nephropathy Secondary glomerulonephropathy  Diabetes mellitus  Collagen vascular disorders (e.g., lupus nephritis)  Amyloidosis  Preeclampsia  Infection (e.g., HIV, hepatitis B and C, poststreptococcal illness, syphilis, malaria and endocarditis)  Gastrointestinal and lung cancers  Lymphoma, chronic renal transplant rejection Glomerulonephropathy associated with the following drugs:  Heroin  NSAIDs  Gold components  Penicillamine  Lithium  Heavy Metal
  • Causes Of Proteinuria Tubular  Hypertensive nephrosclerosis  Tubulointerstitial disease due to  Uric acid nephropathy  Acute hypersenstivity  Interstitial nephritis  Fanconi syndrome  Heavy metals & Drugs  Sickle cell disease Overflow  Hemoglobinuria  Myoglobinuria  Multiple myeloma  Amyloidosis
  • Selectivity of Proteinuria It is a relative glomerular selectivity for proteins, although it is of little significance It is the ratio of clearance of larger molecule with that of smaller i.e., IgG, IgM against that of albumin  >20% to that of albumin, represents nonselective proteinuria  <10%is highly selective  10 %to 20% is of little discriminatory value This is of little importance ,except to distinguish between minimal change disease from other forms of nephritis or glomerular disease
  • Method Description Detection Comments limit (mg/l) Remove non-protein nitrogen, digest Reference and research method protein, measure protein nitrogenKjeldahl 10–20 Copper reagent, measures peptide Requires precipitation of proteins, bonds used for 24-h measurement inBiuret 50 some laboratories Addition of trichloracetic or Imprecise, different readings for sulfosalicylic acids alters colloid albumin and globulin properties and produces turbidity toTurbidimetric be read in densitometer. 50–100 Benzethomecin also used Indicator changes color in presence Different proteins bind differently; of protein (e.g. Coomassie brilliant several different dyes in use; usedDye-binding blue) 50–100 in many laboratories for 24-h excretion Specific antialbumin antibody used Measures albumin excretion not total protein. Does not detectNephelometric globulins Impregnated with indicator dye Reacts poorly with globulins. UsualStick tests (bromocresol green) which changes 100 mg/l clinical screening test color in the presence of protein
  • Detecting And Quantifying Proteinuria  Dipstick analysis is used in most patients in out door setting  False positive results  Alkaline urine (pH>7.5)  When dipstick is immersed too long  With highly concentrated urine  With gross hematuria  In presence of penicillins, sulfonamide or tolbutamide  With pus, semen or vaginal secretions  False negative results  Dilute urine (sp. gravity >1.015)  Urinary protein are of low molecular weight  The resuts are graded as –  Negative ( <10 mg /dl )  2+ ( 100 mg /dl )  Trace ( 10 to 20mg/dl )  3+ ( 300 mg/dl )  1+ ( 30mg /dl )  4+ ( >1000mg/dl )  The SULFOSALICYLIC ACID (SSA) turbidity test and IMMUNOELECTROPHORESIS qualitatively screens for proteinuria especially Bence Jones proteinuria
  • Detecting And Quantifying Proteinuria  As urine dipstick and SSA tests are crude methods and value depends upon amount of urine produced, they correlate poorly with quantitative urine protein determination  Patients with persistent proteinuria should undergo 24-hr urine protein estimation. The urinary creatinine concentration should be included in 24-hr measurement to determine adequacy of specimen (normal excretion in men=16 to 26mg/kg/day and in women =12 to24 mg/kg/day as it depend on muscle mass)  24- hr urine should be collected by instructing the patient to discard first morning void; specimen of all subsequent voiding should be collected including the first morning sample on second day
  • Detecting And Quantifying Proteinuria Spot Urinary Protein To Creatinine Ratio (Upr/Cr)  It is an alternative to 24-hr urine protein estimation  Correlation between UPr/Cr ratio has been demonstrated in various diseases like diabetes mellitus, pre-ecclampsia, rheumatic disease  Normal value is < 0.2 which corresponds to proteinuria < 200 mg/24hrs  Benefit of it is- 01.Ease of collection. 02. Lack of error from over & under collection
  • Diagnostic Evaluation When proteinuria is found on a dipstick analysis, the urinary sediment should be examined microscopically for- Fatty casts, free fat or oval fat bodies Nephrotic range proteinuria (>3.5 g /24 hours) Leukocytes, leukocyte casts with bacteria Urinary tract infection Leukocytes, leukocyte casts without bacteria Renal interstitial disease Normal-shaped erythrocytes Suggestive of lower urinary tract lesion Dysmorphic erythrocytes Suggestive of upper urinary tract lesion Erythrocyte casts Glomerular disease Waxy, granular or cellular casts Advanced chronic renal disease Eosinophiluria Drug-induced acute interstitial nephritis Hyaline casts No renal disease; present with dehydration
  • RBC Cast Hyaline cast
  • Hyaline and granular castCoarse granular cast adjacent WBCs
  • Final coarse granular castOval fat body with adjacent WBC cast hyaline cast
  • Transient Proteinuria If results of microscopic analysis are inconclusive and the dipstick analysis shows trace to 2+protein, the dipstick test should be repeated on morning specimen at least twice during next month If subsequent dipstick test are negative the patient has transient proteinuria It is not associated with increased mortality or morbidity,and specific follow-up is not required
  • Persistent Proteinuria When diagnosis of persistent proteinuria is established, a detailed history and physical examination should be performed, looking for systemic disease with renal involvement A medication history is important A 24-hr urine protein or a UPr/Cr ratio on random urine sample should be obtained An adult with proteinuria >2gm /24 hr requires aggressive work up If creatinine clearance is normal and if diagnosis is clear as diabetes or uncompensated CHF, treat underlying medical condition with regular follow up If there is decreased creatinine clearance or an unclear cause, further investigations should be done in consultation with nephrologist
  • Orthostatic Proteinuria Persons younger than 30 yrs who excrete <2gm of protein /day with normal creatinine clearance should be tested for orthostatic or postural proteinuria This benign condition occur in 3 to 5 %of adolescent and young adults, it is characterized by increased protein excretion in upright position but normal excretion in supine Diagnosis is made by split urine specimen collection
  • Orthostatic Proteinuria The first morning void is discarded , a 16 hr daytime specimen is obtained with patient performing normal activities and finishing the collection by voiding before bed time, an overnight 8 hr. specimen is then collected The day time specimen typically has an increased concentration of protein, while night time specimen has having normal concentration It is a benign condition associated with normal renal function after as long as 20 to 50 yrs of follow up Annual blood pressure measurement is recommended in these patients
  • Isolated Proteinuria A proteinuric patient with normal renal function, no evidence of systemic disease, normal urinary sediments and normal blood pressure is considered to have isolated proteinuria Protein excretion is usually <2 gm/day 20%of these patients have risk for renal insufficiency after 10years and should be followed with blood pressure measurement, urinalysis and creatinine clearance every 6 month Isolated proteinuria with excretion >2 gm /day usually signifies glomerular disease and needs further evaluation.
  • ALGORIT M FOR E H VALUATING A P INT W H P AT IT ROT INURIA E
  • SELECTED INVESTIGATIONS TO BE CONSIDERED IN PROTEINURIA TEST INTERPRETATIONAntinuclear Antibody Elevated in SLEAntistreptolysin O Titre Elevated after streptococcal GNComplement C3 & C4 Levels low in RPGNESR If normal help to rule out infection or inflammationFasting Blood sugar Elevated in Diabetes MellitusHemoglobin, Hct Low in CRFHIV, VDRL & Hepatitis serology All are associated with glomerular proteinuriaS. Electrolytes( Na+, K+ ) Screening for any abnormalities consequent to renal diseaseSerum & Urine protein Abnormal in multiple myelomaElectrophoresisSerum Urate Elevated urates can lead to tubulointerstitial disease and stonesUSG KUB For structural renal diseaseChest X Ray Systemic diseases like sarcoidosis
  • Microalbuminuria It is defined as presence of albumin in urine above normal range of <30 mg/day but below detectable range with conventional dipstick methodology i.e.30-299 mg/day It is estimated by Radioimmunoassay. Recent data have established that MA is not only a predictor of diabetic complication but also a powerful independent risk factor of CVD While the contribution of MA as a prognostic indicator of cardiovascular events in people with diabetes is clear it is still debatable in nondiabetic population. Present in Diabetic nephropathy, hypertension, Cardiac failure & Viral illnesses
  • FINAL COM E M NTA systematic approach to the patientwith proteinuria will allow theclinician to efficiently distinguishbetween benign and pathologicalcauses.
  • T ANK YOU H