DEFINITION 3 *Increased excretion of protein in urine. *Normal protein excretion : 80 – 150mg daily increased excretion of protein in urine raise the suspicion of renal disease. Proteinuria can be due to Primary renal disorders a.Renovascular b.Glomerular c.Tubulointerstitial Overflow of abnormal proteins - - multiple myeloma 3.Secondary to non renal disorders - - amyloidosis 4.Physiological conditions - - st r en u o D u e p s t o f e U x r o e l o r g c y , i G s R e H and KMC,
Urine protein composition 30% albumin 30% globulin 40% tissue proteins (Tamm horsfall protein) 3
PATHOPHYSIOLOGY 4 3 categories: Glomerular 2.Tubular Overflow GLOMERULAR PROTEINURIA: most common Increased capillary permeability to proteins specially albumin IgA nephropathy,glomerular diseases,DM. 24hrs urine protein: >1gm - - suspect glomerular cause >3gm – confirm glomerular cause
TUBULAR PROTEINURIA: failure to reabsorb normally filtered protein of low molecular weight such as immunoglobulin 24hrs urine protein < 2 - 3gm protein are of LMW proteins rather than albumin proximal tubular functional defect such as glucosuria,aminaciduria,phosphaturia,and uricosuria(fanconi’s syndrome) 5
OVERFLOW PROTEINURIA: *due to increased concentration of abnormal immunoglobulin and other LMW proteins * increased serum level | increased glomerular filtration | exceeds tubular absorptive capacity *common condition: in multiple myeloma - - Bence jones protein (immunoglobulin light chain) 6
DETECTION syndrome 7 I.Qualitative tests: 1.Dipstick 2.3%sulfosalicylic acid 3.protein electophoresis 4.immunoassay of specific protein II.Quantitative tests: 1.24hrs urine collection test – Most sensitive 2.protein creatinine ratio(PCR): - better than 24hrs urine protein - conc. of protein compared with creatinine in spot urine collection -PCR>45mg/mmol or alb:creatinine >30mg/mmol indicates proteinuria - PCR >100mg/mmol— high level of nephrotic
PROTEIN DIPSTICK DIPSTICK GRADING 8 GRADE CONCENTRATION DAILY trace 5- 20mg/dl -- - 1+ 30mg/dl <0.5gm/day 2+ 100mg/dl 0.5-1gm/day 3+ 300mg/dl 1- 2gm/day 4+ >2000mg/dl >2gm/day *dipstick impregnated with tetrabromophenol blue *colour changes in response to pH shift related protein content of urine mainly albumin *background of stick – yellow *Various shades of green will develop- darker the green greater the concentration of protein.
20- -30mg/dl is the minimal conc. detected False negative results: Alkaline urine Dilute urine Primary protein is not albumin 9
3%SULFASALICYLIC ACID TEST 10 *Precipitation of primary protein with3%SSA will detect proteins <15mg/dl *More sensitive in detecting other proteins as well as albumin *pts with dipstick - ve, SSA +ve then suspect Multiple myeloma— Bence jones protein
PROTEIN ELECTROPHORESIS: *Differential qualitative assesment *to differentiate albumin&globulin *distinguish glomerular from tubular proteinuria Glomerular- albumin - 70%of total protein excreted Tubular– immunoglobulin are major protein excreted ,albumin – 10- 20% 11
IMMUNOASSAY 12 *detecting specific protein such as -- Bence jones protein in multiple myeloma
EVALUATION 13 Proteinuria classified into 1.transient 2.intermittent 3.persistent 1. TRANSIENT: *commonly occurs in pediatric *resolve within few days *due to fever,exercise,emotional stress *older pts –congestive cardiac failure
INTERMITTENT: 14 *related to postural change *upright posture *normalises when the pts is recumbent *orthostatic proteinuria- secondary to -increased pressure on renal vein due to standing -resolve spontaneously
PERSISTENT PROTEINURIA 15 *Further evaluation *mostly glomerular etiology *quantitative & qualitative analysis *>2gm of protein/24hrs *mostly HMW proteins like albumin establishes the glomerular etiology *glomerular proteinuria is the most common cause for abnormal and persistent proteinuria