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proteinuria by dr khalid shawkey ramadan

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  1. 1. Proteinuria A common problem by Dr/ khalid s ramadan Internist Zagazig University Hospitals , Egypt Mouwasat Hospital Dammam, KSA
  3. 3. Definition Proteinuria is defined as excess serum protein excreted in the urine. Normal protein excretion < 150 mg total protein/d and ~30 mg albumin/d Microalbuminuria 30–300 mg albumin/d Also defined as 30–300 μg albumin/mg creatinine It is not detectable by dipstick analysis. Albuminuria and moderate proteinuria 300–3500 mg albumin/d Nephrotic-range proteinuria >3500 mg albumin/d Isolated proteinuria Proteinuria in the presence of an otherwise normal urinary sediment, a radiologically normal urinary tract, and absence of known renal disease
  4. 4. Physiology/Pathophysiol ogy • Protein flow through renal arteries = 121,000 g/day • Protein filtered through glomerulus = 1-2 g/day (< 0.001%) • Protein excreted in urine < 150 mg/day (<1% of filtered) • Composition of normal urine: Tamm- Horsfall protein 60-80%, albumin 10-20%.
  5. 5. Magnitude of proteinuria and protein composition depends on the mechanism of renal injury Glomerular proteinuria results from glomerular disorders, which typically involve increased glomerular permeability; this permeability allows increased amounts of plasma proteins (sometimes very large amounts) to pass into the filtrate. EXAMPLES Primary glomerular disorders (eg, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis) Secondary glomerular disorders (eg, diabetic nephropathy, preeclampsia, postinfectious glomerulonephritis, lupus nephritis, amyloidosis)
  6. 6. Tubular proteinuria results from renal tubulointerstitial disorders that impair reabsorption of protein by the proximal tubule, causing proteinuria (mostly from smaller proteins such as immunoglobulin light chains rather than albumin). Causative disorders are often accompanied by other defects of tubular function (eg, HCO3 wasting, glycosuria, aminoaciduria) and sometimes by glomerular pathology (which also contributes to the proteinuria). EXAMPLES Fanconi syndrome Acute tubular necrosis Tubulointerstitial nephritis Polycystic kidney disease
  7. 7. Overflow proteinuria occurs when excessive amounts of small plasma proteins (eg, immunoglobulin light chains produced in multiple myeloma) exceed the reabsorptive capacity of the proximal tubules. EXAMPLES Acute monocytic leukemia with lysozymuria Monoclonal gammopathy Multiple myeloma Myelodysplastic syndromes
  8. 8. Functional proteinuria occurs when increased renal blood flow (eg, due to exercise, fever, high-output heart failure) delivers increased amounts of protein to the nephron, resulting in increased protein in the urine (usually < 1 g/day). Functional proteinuria reverses when renal blood flow returns to normal. EXAMPLES Fever Heart failure Intense exercise or activity sizures
  9. 9. • Orthostatic proteinuria is a benign condition that most commonly occurs in children and adolescents in which proteinuria occurs mainly when the patient is upright. Thus, urine typically contains more protein during waking hours (when people are more often upright) than during sleep. It has a very good prognosis and requires no special intervention
  10. 10. Subnephrotic Proteinuria • Transient or orthostatic proteinuria • Hypertensive nephrosclerosis • Ischemic renal disease/renal artery stenosis • Interstitial nephritis • All causes of nephrotic-range proteinuria
  11. 11. Nephrotic Syndrome • Def: nephrotic-range proteinuria, lipiduria, edema, hypoalbuminemia, hyperlipidemia. • Implies glomerular origin of proteinuria. • Clinical manifestations: edema, hypercoagulability, immunosuppression, malnutrition, +/- hypertension, +/- renal failure.
  12. 12. Nephrotic Syndrome (cont.) • 75% have primary glomerular disease • 25% have secondary glomerular disease • Medications: NSAIDs, heavy metals, “street” heroin, lithium, penicillamine, a-INF • Infections: post-strep, HIV, hepatitis B/C, malaria, schistosomiasis • Neoplasms: solid tumors, leukemias, lymphomas, multiple myeloma • Systemic diseases: diabetes mellitus, SLE, amyloidosis
  13. 13. Diabetic Nephropathy • #1 cause of ESRD in the U.S. (~35% of all ESRD). • ~ 40% of all diabetics (type I and II) will develop nephropathy. • Microalbuminuria (> 30 mg/day) develops after ~ 5 years. Proteinuria after 11-20 years. Progression to ESRD ~15-30 years.
  15. 15. Clinical Evaluation History • Diabetic history if applicable, esp. h/o retinopathy/neuropathy • Known renal disorders • recent serious illness (particularly with fever) • intense physical activity . • pregnancy
  16. 16. Clinical Evaluation History (cont.) • sickle cell disease • cancer (particularly myeloma and related disorders). • Medications and toxins • SLE • red or brown urine (glomerulonephritis) • bone pain (myeloma).
  17. 17. Clinical Evaluation Physical Examination • BP and weight • Fundoscopic exam • Cardiopulmonary exam • Rashes • Edema
  18. 18. Clinical Evaluation Urine dipstick • Urine dipstick primarily detects albumin • positive urine dipstick test usually suggests overt proteinuria. • Dipstick testing is also unlikely to detect excretion of smaller proteins characteristic of tubular and overflow proteinuria • Persistent proteinuria is a sign of a glomerular disorder and requires further testing
  19. 19. Clinical Evaluation Sulfosalicylic Acid (SSA) Assay • Turbidimetric assay based on precipitation of proteins. • Measures all proteins.
  20. 20. Test sample
  21. 21. Clinical Evaluation Urine Sediment • Red cell casts or dysmorphic RBCs suggest glomerulonephritis. • WBCs suggest interstitial nephritis or infection. • Lipid bodies suggest hyperlipidemia and possible nephrotic syndrome.
  22. 22. Clinical Evaluation Quantitation of Proteinuria • 24-hr urine is gold standard, however is often not easily obtained. • Spot urine protein/creatinine ratio is easier to get, nearly as accurate. • ALWAYS GET A CREATININE WITH ANY QUANTITATIVE MEASURE OF URINE!
  23. 23. Clinical Evaluation other tests • ultrasonography or CT to detect size of kidneys. • lipid profile . • complement levels . • cryoglobulins • hepatitis B and C serology • antinuclear antibody testing • urine and serum protein electrophoresis • renal biopsy
  24. 24. Clinical Evaluation Who To Biopsy • Non-diabetic nephrotic syndrome • SLE for classification • Planned use of immunosuppressive agents in primary GNs (renal insufficiency, severe edema, hypertension) • Diagnosis of plasma cell dyscrasias • < 2 gms proteinuria without other signs: conservative therapy (biopsy resulted in management change in only 3/24 patients in prospective trial)
  25. 25. E v a l u a t i o n o f P r o t e i n u r i a D i p s t i c k p o s i t i v e S S A n e g a t i v e T r a n s i e n t : P e r i o d i c r e a s s e s s m e n t O r t h o s t a t i c R e a s s u r a n c e , P e r i o d i c R e a s s e s s m e n t S S A p o s i t i v e b u t d i p s t i c k n e g a t i v e o r d i s p r o p o r t i o n a t e l y F i x e d s m a l l F u r t h e r e v a l u a t i o n ( R e n a l u l t r a s o u n d , N e p r h o l o g y R e f e r r a l ) P e r s i s t e n t T r a n s i e n t o r p e r s i s t e n t ? ( C o n f i r m o n 2 4 h r u r i n e o r s p o t r a t i o O v e r f l o w p r o t e i n u r i a ( L i g h t c h a i n s , l y s o z y m u r i a , e t c A s s e s s m e n t o f P r o t e i n u r i a
  27. 27. Management broad lines • Blood pressure control • Diabetic control • ACEI ,, calcium channel blockers • Lipid control • Dietary protein restriction
  28. 28. Management ACE Inhibitors • Have benefit over and above blood pressure control. • Type I Diabetes: Captopril use associated with slower progression, less proteinuria with or without co-existing HTN (Lewis et al, 1993, Viberti et al, 1994) • Type II Diabetes: Enalapril use associated with slower progression, less proteinuria. (Ravid et al, 1993, 1996).
  29. 29. Management ACE Inhibitors • Nondiabetic disease: use of benazepril vs. placebo reduced by 38% the 3-yr progression of renal failure in various diseases. Reduction greater with higher proteinuria (Maschio et al, 1996). • Similar data emerging for angiotensin II receptor antagonists.
  30. 30. Screening of proteinuria in diabetic patient
  31. 31. Prognosis • Diabetic nephropathy: progression to ESRD over 10-20 years after onset of proteinuria. • Isolated non-nephrotic proteinuria: 20-yr follow-up shows incidence ~40% renal insufficiency, ~50% HTN. • Nephrotic syndrome: variable but poorer overall prognosis.
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