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Prof. e. sarhan.work up of_proteinuric_patients
 

Prof. e. sarhan.work up of_proteinuric_patients

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    Prof. e. sarhan.work up of_proteinuric_patients Prof. e. sarhan.work up of_proteinuric_patients Presentation Transcript

    • Iman SarhanProf of Internal Medicineand Nephrology, Ain Shams UniversityESNT 2012 Mars Alem
    • Protein excretion ratePlasma protein the proximal tubule 50% 50% The ability of( if low mol wt the proximalprotein) tubule toOverflow excrete ,proteinuria metabolize and reabsorb any filtered proteins GFRPermeability Tubular proteinuriaGBMGlomerular proteinuriaThe permeability of the glomerular N urinary protein < 0.15 g per daybasement membrane (15% albumin)Primary or secondary glomerulopathy N urinary albumin <30mg/gm creatinine >0.2 gm proteinuria
    • Normal Glomerular Capillary  The normal thickness of the basement membrane equals about 250–300 nm.  The spaces between foot processes, with diameters of 20–60 nm, are called filtration pores, by which filtered fluid reaches the urinary space Podocytes Endothelial cells on the luminal aspect of the basement membrane are fenestrated (diameter 70–100 nm). The GBM.
    • Pathophysiologic classification of proteinuria 1. Functional 2. Orthostatic 3. Overflow proteinuria transient proteinuria Multiple myeloma Account for 50% of isolated proteinuria 5. Glomerular lesionCHF, Strenuousexercise, fever 4. Tubular proteinuria Tubulointerstial injury
    • Differential diagnosis of glomerular diseasesDiseases presented by either nephrotic and nephritic can beidiopathic or secondary to other causes.
    • 1st Work up of proteinuria Glucose.  Urinalysis Urobilinogen. Bilirubin. Ketones.  Urine sample Specific gravity.  Urine protein by dipsticks pH. Nitrite. Leukocyte esterase.False +ve blood. Protein.High urine PH>8 with gross hematuria. in the presence of penicillin, False –vesulfonamides or tolbutamide. Small amount of albumin: microalbuminuria with pus, semen or vaginal secretions. Large amount of non albumin protein This method preferentially detects albumin and is less sensitive to globulins or parts of globulins or (heavy or light chains or Bence Jones proteins). Laffeyette et al., 1996
    • Overflow proteinuriaCauses of Overflow Multiple myeloma  In overflow proteinuria, low- Amyloidosis molecular-weight proteins Hemoglobinuria overwhelm the ability of the Myoglobinuria proximal tubules to reabsorb filtered proteins. Diagnosis: urinary protein electrophoresis
    • Urinalysis Urinary sediment Negative Bland urinary sediment Trace to 2+ on dipstick test Repeat urinalysis2-3 times in next month -veTransient occur in CHF, Strenuous exercise, feverproteinuria
    • Urinalysis Urinary sediment Negative Bland urinary sediment Trace to 2+ on dipstick test +ve 3+-4+ on dipstick test Repeat urinalysis2-3 times in next month Quantatitive 24 h urinary protein , pr/cr ratio -ve 24 h urinary protein Protein /creatinine ratio.Transient albumin/creatinine ratio Timed urine collection
    • Quantitative test Protein creatinine Vs Albumin creatinine Equivalent to 24h urinary protein Equivalent to 24h urinary albumin.Normally <150 mg/gm, Or 0.15 mg/mg. Normally <30mg/gm>0.2 mg/mg considered proteinuria Microalbuminuria: 30-299 (false –ve test) Macroalbuminuria:>300 Unites is important, if creatinine mmol x 0.088
    • Urinalysis Urinary sediment Negative Bland urinary sediment Trace to 2+ on dipstick test +ve 3+-4+ on dipstick test Repeat urinalysis2-3 times in next month Quantatitive 24 h urinary protein , pr/cr ratio GFR -ve Normal lowTransient Nephrological <30 y >30y Symptomatic P Unknown cause consultation Orthostatic P Isolated
    • Cause of Proteinuria (bland urinary sediment )Relatedto Quantity Daily protein cause excretion 0.15 to 2.0 g Mild glomerulopathies Orthostatic proteinuria (0.15- <2gm) Tubular proteinuria Overflow proteinuria 2.0 to 4.0 g Usually glomerular >4.0 g Always glomerular Adapted with permission from McConnell KR, Bia MJ. Evaluation of proteinuria: an approach for the internist. Resident Staff Phys 1994;40:41-8.
    • Orthostatic Proteinuria Young tall Must be tested  <30 years for orthostatic  < 2 g of protein per day proteinuria  Normal GFR Split urine specimens A 16-hour daytime specimen is obtainedHow to diagnose with the patient performing normal activities and finishing the collection by voiding just before bedtime. An eight-hour overnight specimen is then collected. Which is less than 50 mg per eight hours)
    • Isolated Proteinuria A proteinuria usually <2 g per day With normal renal function. No evidence of systemic disease that might cause renal malfunction. Normal urinary sediment. Normal blood pressures
    • Tubular proteinuria Tubular proteinuria occurs when tubulointerstitial disease prevents the proximal tubule from reabsorbing low-molecular- weight proteins (part of the normal glomerular ultrafiltrate). When a patient has tubular disease, usually less than 2 g of protein is excreted in 24 hours. Tubular proreinuria  Hypertensive nephrosclerosis  Tubulointerstitial disease due to:  Uric acid nephropathy  Acute hypersensitivity interstitial nephritis History of HTN  Fanconi syndrome Drug intake  Heavy metals Esinophilluria  Sickle cell disease  NSAIDs, antibiotics
    • Urinalysis Urinary sediment Negative Bland urinary sediment Trace to 2+ on dipstick test +ve 3+-4+ on dipstick test Repeat urinalysis2-3 times in next month Quantatitive 24 h urinary protein , pr/cr ratio GFR GFR -ve Normal low low NormalTransient Nephrological <30 y >30y Symptomatic P consultation Unkown cause Orthostatic P Isolated
    • Urinalysis Urinary sediment Negative Positive Bland urinary sediment Active urinary sediment Trace to 2+ on dipstick test +ve 3+-4+ on dipstick test Repeat urinalysis2-3 times in next month Quantatitive 24 h urinary protein , pr/cr ratio GFR GFR -ve Normal low low NormalTransient Nephrological <30 y >30y Symptomatic P consultation Unkown cause Orthostatic P Isolated
    • DD of castEpithelial cells casts White cell casts +Acute tubular necrosis, pyuria Fatty cast Red cell casts tubulointerstitial Pyelonephritis. proteinuria glomerulonephritis disease Nephrotic syndrome. or vasculitis acute pyelonephritis. Advanced renal failure Granular cast Waxy cast Dysmorphic
    •  Non nephrotic rang proteinuria if the cause is unknown Nephrotic range proteinuria with normal GFR or low GFR. Patient with active urinary sedimentRecognize the Laboratoryglomerular investigation tosyndrome Renal recognize the biopsy underlying causes
    • Approach to patient with glomerular diseases  Investigation to recognize the glomerular syndrome  History taking and examination.  Urinalysis : RBCs, RBCs cast, proteinuria.1st  Quantitative urinary protein. Nephrotic range proteinuria (>3.5 gm/24h), subnephrotic range.  Renal function tests: blood urea, creatinine, estimated GFR, creatinine clearance.  Renal imaging ( to differentaite between acute and chronic and to exclude obstructive uropathy)2nd •Renal biopsy: Investigation to recognize histopathological diagnosis • Investigation to recognize the underlying causes: • ANA (antinuclear antidoy) Anti-ds DNA positive in systemic lupus erythromatosis (SLE). • C3, C4 (complement) may be comsumed. • ASOT (anti-streptolysin O titre) positive in post streptococcal GN.3rd • ANCA (antineutrophilic antibody) positive in Wagner granulomatosis. • Antiglomerular basement membrane (AGBM) positive in Goodpasuture syndrome.
    • All cases of In non nephrotic Hematuria nephrotic syndrome range proteinuria RPGN If Unexplained <2gm only if low +proteinuria AKI ExceptExcept GFR OR low +ve Anti-GBM,Children with INS GFR +ve ANCA Post txDiabetic CADnephropathySome cases lightchain dis Result of renal biopsy
    • Minimal change diseaseFSGS MN MN
    • Pathological terms in glomerular disease Normal Global Segmental if the whole glomerular tuft is only a part of the glomerulus is involved affected Focal Normal Diffuse some but not all the most of the glomeruli (> glomeruli contain the 75%) contain the lesion. lesion.
    • Glomerular proteinuria 2-4 gm >4gm Renal biopsy Isolated proteinuria MCD FSGS Proteinuric Syndromes Membranous nephropathy < nephrotic range— Diabetic glomerulosclerosis nephrotic range Amyloidosis proteinuria without RBCs Light-chain deposition disease Secondary cause
    • Proteinuria + active urinary sediment  Mesangial proliferative GN,Membranoproliferative GN  IgA nephropathy)  Focal and segmental GNFibrillary glomerulopathies  class III lupus N.  Infective endocarditis)Hereditary nephritis (Alport  Diffuse proliferative GNsyndrome)  post- streptococcal GN,  Class IV lupus N  Crescentic GN  Anti-GBM nephritis, Pauci-immune nephritis ) Both Nephritic and Nephrotic Hematuric Features Syndromes >nephrotic range+ RBCs cast <nephrotic range+ RBCs cast
    • Fibrillary glomerulonephritis. IgA MPGN Ivanyi B , Degrell P Nephrol. Dial. Transplant. 2004;19:2166-2170Nephrol Dial Transplant Vol. 19 No. 9 © ERA-EDTA 2004; all rights reserved
    • Antibody mediated glomerulopathy Immunofleurescence Linear glomerular Paucity of Glomerular immune complex glomerular IF IgG IF staining localization with granular IF Immunoglobulin Serology Anti-GBM Serology : anti DNA, low staining complement, anti HCV, anti HBV, Serology: ANCA cryoglobulinemia, ASOT, IgA +Lunge -Lunge vasculitis Esinophilia hge hge Anti GBM No vasculitis No asthema +asthema Good GN ANCA GN Wegner GN Churg Pasture S Strauss IgA Fibillary IgA SLE MPGN Sub-epNo vasculitis ASOT GN + vasculitis Lupus I, II deposite IgA PSGN 20 nm fibrill HSP Nephritis MGNnephropathy
    • Finally To assess the presence of proteinuria (dip stick) Quantitative protein. In mild 0.2-2gm--- we need to think in transient proteinuria, orthostatic proteinuria, isolated proteinuria. In moderate proteinuria 2-4gm differ acc to  Presence or absence of active sediment.  GFR. Nephrological consultation with renal biopsy and laboratory investigation is indicated in:  Non nephrotic rang proteinuria if the cause is unknown  Nephrotic range proteinuria with normal GFR or with low GFR  Patient with active urinary sediment
    • Approach to patient with glomerular diseases  Investigation to recognize the glomerular syndrome1s  History taking and examination.  Urinalysis : RBCs, RBCs cast, proteinuria.t  Quantitative urinary protein. Nephrotic range proteinuria (>3.5 gm/24h), subnephrotic range.  Renal function tests: blood urea, creatinine, estimated GFR, creatinine clearance.  Renal imaging ( to differentaite between acute and chronic and to exclude obstructive uropathy) •Investigation to recognize histopathological diagnosis2nd •Renal biopsy • Investigation to recognize the underlying causes: • ANA (antinuclear antidoy) Anti-ds DNA positive in systemic lupus erythromatosis (SLE). • C3, C4 (complement) may be comsumed.3r • ASOT (anti-streptolysin O titre) positive in post streptococcal GN.d • ANCA (antineutrophilic antibody) positive in Wagner granulomatosis. • Antiglomerular basement membrane (AGBM) positive in Goodpasuture syndrome.