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Edit Comment Close Premium member Presentation Transcript Office Nephrology : Office Nephrology Chair: Paul RoyManagement Of Proteinuria : Management Of Proteinuria Amanda Walker Chair: Paul RoyOffice management of proteinuria in children: Office management of proteinuria in children Dr. Amanda M. Walker Paediatric Renal & Continence Service, Monash Medical Centre MelbourneWhat are the proteins in urine?: What are the proteins in urine? Plasma proteins Renal tissue enzymes antigens tubular secretionsProteinuria - plasma proteins (Albumin): Proteinuria - plasma proteins (Albumin)Mechanisms of Albuminuria: Mechanisms of Albuminuria Altered filtration Glom haemodynamics Incr intraglom blood flow or pressure Glom pathology Reduced filtration barrier (size & charge) Altered reabsorption Prox conv tubule pathol CombinationSelectivity index: Selectivity index Selectivity index = u IgG x s Tf s IgG u Tf Albumin 66,000 Transferrin 90,000 IgG 160,000 ≤0.10 highly selective ≥0.11 ≤0.20 mod selective ≥0.21 poorly selective May have prognostic signif with nephrotic syndrome response & progression to ESRF (Bazzi et al., Kidney Int, 2000, 58, 1732)Effect of proteinuria: Effect of proteinuria Tubular cell culture Proteinuria Stim inflamm mediators Endothelin-1 Monocyte chemottractive protein (MCP-1) Bazzi et al., Kidney Int, 2000, 58, 1732 www.renal.com.ar/cgi-bin/i/monografias/patologia/images/slide9.jpgProteinuria - tubular proteins: Proteinuria - tubular proteins LMW proteins - tubular pathology: Normal values (spot) Lysozyme (10 – 66mg/mol Cr) ß2 microglobulin (6 – 41 mg/molCr) RBP (<1 – 24 mg/mol Cr) LMW proteins - tubular pathology LMWP <40,000 Daltons Freely filtered by glom; 99.9% reabsorbed - prox tubule Catabolized by tubular lysosomes Sensitive marker for tubular pathology i.e. small dec prox tub fx ---- large incr LMWP (Pediatric Nephrology, 1994 ed Holliday, Barratt & Avner 403)Tubular proteinuria: Tubular proteinuria www.gen.umn.edu/faculty_staff/jensen/1135/webanatomy/wa_urinary/wa_wcb_nephron3.htmlSummary of proteins found in urine: Summary of proteins found in urine Alb /transferrin/ IgG glomerular filtration/ prox tubule Retinol Binding Protein/amino acids prox tubular dysfunction (reabsorption) 1 microglobulin / NAG prox tubular necrosis/damageDetection of proteinuria: Detection of proteinuria extremely sensitive albumin (as it contains the most amino groups), much less sensitive globulins insensitive Bence-Jones proteins. amino groups in proteins bind and alter the colour of pH indicator (tetra-bromophenol blue) even though the pH is unchanged.False negatives and positives on FWT: False negatives and positives on FWT Screening FWT +++/++++ >1gm/m2/day pos predictive value of 89% 0/trace <0.1g/m2/day neg predictive value 60% Improved with automated colour reading Abitbol, J Ped, 1990,116(2),243 false positive radiographic contrast media, low pH false negative high urinary conc of penicillin, sulphonamides high pH, moving urine, dilute urineQuantification of proteinuria: Quantification of proteinuria 24 hour protein excretion N <150 mg/day Timed urine collection Total protein Albumin Urinary Pr:Cr ratioProteinuria – normal values: 145 mg/ m2/day 110 mg/ m2/day 85 mg/ m2/day 150 mg/day Proteinuria – normal values 2 – 10 yrs Wingo & Clapp, 2000,AmJ Med Sci, 320, 188 www:news.bbc.com.uk;www:keepkidshealthy.comProteinuria – normal values: Proteinuria – normal values Relatively constant after 12 months of age < 4mg/m2/hr or <100 mg/ m2 /24 hr Nephrotic range proteinuria > 40mg/ m2 /hr overnight sample (ISKDC) 1.7g/24 hr for adults Suggested 3.5g/1.73 m2 /day (80mg/ m2 /hr) Glassock, 1988 in Cameron, JS Glassock RJ (ed) The Nephrotic syndrome, 219 Urinary Pr:Cr ratio: Urinary Pr:Cr ratio High correlation b’t timed urine collections & U Pr:Cr ratio UCr excretion stable Comparison 1st am sample & 24hr/overnight R= 0.81 - 0.99 (>11 studies - CARI draft guidelines) U Pr:Cr < 20 - 25mg/mmol <4mg/m2/hr <2 yr old N < 50mg/mmol Nephrotic range U Pr:Cr 200 - 250 mg/mmol Urinary Alb:Cr ratio: Urinary Alb:Cr ratio Good for detection of glomerular pathology, miss tubular proteinuria More expensive, N range less well defined for children MicroAlbUria U Alb:Cr >2.5 mg/mmol Proteinuria U Alb:Cr >30 mg/mmol UAlb:Cr Diabetics, known glomerular disease Slide20: Ringsrud & Linne, 1995 Urinalysis & body fluids, MosbyClassification of isolated proteinuria: Classification of isolated proteinuria Character (intermittent/ constant) Posture (orthostatic/ non – ortho) Quantity (non- nephrotic / nephrotic)Transient proteinuria: Transient proteinuria Common children, adolescents & adults Fever, exercise, extreme cold, Adrenaline admin, CCF, seizures Asymptomatic usu screening abn Normal urinary sediment Resolves spontaneously Repeat sample 2 -3 times before Ix Hogg et al., 2000, Pediatrics, 105, 1242Idiopathic intermittent proteinuria: Idiopathic intermittent proteinuria Proteinuria independent of body posture in most (>50%) but not all random urine samples Usu <30 yrs old , N renal function & N BP Renal Bx of 51 pts 40% normal/ min histological change 60% variety of lesions Glom hypercellularity and sclerosis No em studies done, no clinicopath correlations Benign prognosis if proteinuria resolves over a few yearsOrthostatic proteinuria: Orthostatic proteinuria Definition: absence of proteinuria during recumbency and its appearance during quiet upright ambulation or standing Transient (80%) not well studied Persistent (20%) Sinniah et al., 1977, Clin Nephrol, 7,1Orthostatic proteinuria: Orthostatic proteinuria 60% proteinuria in childhood 75% proteinuria in adolescents Rare >30 yrs old Rarely >1g/m2/day Dodge et al 1976, J Pediatr, 88, 327 Hogg et al., 2000, Pediatrics, 105, 1242 Orthostatic proteinuria: Orthostatic proteinuria ?normal variant Postural changes in protein excretion seen with N pop’n 20% of 120 N volunteers (<150 mg/day) incr protein excretion when upright Mahurkar et al, Br Med J, 1975,1, 712 116 adolescents Incr U Pr:Cr in upright position Houser et al., 1986, J Pediatr, 109, 556 Orthostatic proteinuria ?glomerular abnormality: Orthostatic proteinuria ?glomerular abnormality Bx - N or Mild focal and segmental mesangial hypercellularity Focal or diffuse capillary wall thickening Occ focal foot process fusion Mesangial & capillary deposits C3, IgG Sinnah et al, 1977, Clin Nephrol, 7,1-14 Orthostatic proteinuria ?haemodynamic abnormality: Orthostatic proteinuria ?haemodynamic abnormality Upright position Venous pooling in legs Renal vein congestion Decr renal blood flow (incr Ang II) Incr efferent arteriolar resistance Incr proteinuriaOrthostatic proteinuria ?Nutcracker phenomenom: Orthostatic proteinuria ?Nutcracker phenomenom Entrapment of L renal vein bt Aorta & sup mesenteric artery L flank pain, macrohaem, peripelvic & ureteric varices Isolated orthostatic proteinuria Orthostatic proteinuria ?Nutcracker phenomenon: Orthostatic proteinuria ?Nutcracker phenomenon Cho et al, 2001, Nephrol Dial Transplant, 16,1620 1997 - 1999, Seoul 6 - 16 yrs 39 orthostatic proteinuria 22/39 (54%) +ve 28 control 0/28 +ve Renal venography (gold standard) Doppler U/s AP diameter L renal vein Peak LRV velocities Renal hilum As passes bt Ao & SMA Ratio >5 = highly suggestiveOrthostatic proteinuria prognosis: Orthostatic proteinuria prognosis 20 yrs 43 pts orthostatic proteinuria 85% no proteinuria No deterioration in renal function Springberg et al.,1982, Ann Intern Med., 97, 516 6 pts Dx orthostatic proteinuria 42 -50 yrs earlier Resolution of proteinuria, N renal fx Rytand,1981, N Eng J Med., 305, 618Persistent isolated proteinuria: Persistent isolated proteinuria X’s in upright & recumbent position Male predominance Structural disease Tendency to progressCauses of constant proteinuria: Causes of constant proteinuria Early glomerular disease FSGS (primary or secondary), IgA nephropathy Essential hypertension Early diabetic nephropathy Membranous GN Overflow proteinuria Low molecular weight proteins (myoglobin, Hb, a.a.) Tubular proteinuriaInvestigation of proteinuria: Investigation of proteinuria Personal & family Hx of renal disease Thorough examination include BP, growth Urine M & C (?haematuria) U Pr:Cr (Early morning and late evening) Timed urine collection Serum biochem, (include Alb, TPr, lipids) Imaging (Ultrasound ± Doppler, DMSA) Renal BxManagement of isolated proteinuria: Management of isolated proteinuria Transient Nil i.e. discharge Orthostatic (<1g/m2/day; N AM UPr:Cr) Intermittent review, early AM UPr:Cr Persistent Define disease Monitor for proteinuria, GFR, HPTProgression of persistent proteinuria: Progression of persistent proteinuriaPersistent proteinuria: Persistent proteinuria proteinuria, GFR, HPT Consideration for ACEI Reduce proteinuria Delays progression of CRF in adults with Chronic nephropathies & >2g/day proteinuria and/or HPT (REIN study; Ruggenenti et al, AmJKD,2000, 35, 1155) Office management of proteinuria: Office management of proteinuria Detect and define the pattern of isolated protein loss FWT will not detect all proteins Intermittent and low grade - good Px Persistent or mod grade - closer evaluation disease definition more guarded PxProteinuria in children: Proteinuria in children Positive (+) protein on first morning urine by dip-stick Preschool children (age 4.5 yrs) in South Aus 23/9355 children (0.25%) 7/23 children (+) on retesting Hogg et al., 1998, J Paediatr Child Health, 34, 420 School aged children 4 urine samples 1 of 4 (+) protein in 10.7% children, 0.1% 4/4 Vehaskari et al., 1982, J Pediatr, 101, 661 Prevalence of proteinuria: Prevalence of proteinuria Taiwan screening program 10,288,620 elementary & junior high school students 1992 - 1996 4 yr prevalence of (++) proteinuria Girls Lowest at 7 yrs 3.48 x 10-4 Peak at 12 yrs at 10.02 x 104 Boys Lowest at 7 yrs at 2.21 x 10-4 Peak at 13 yrs at 8.7 x 10-4 Lin et al.,2000, Pediatr Nephrol, 14, 953 You do not have the permission to view this presentation. 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OfficeNephrology Walker Mercede Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 578 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: February 28, 2008 This Presentation is Public Favorites: 2 Presentation Description No description available. Comments Posting comment... By: rabb (28 month(s) ago) I like your presentation on nephrology very much. you have brilliantly made the topic on proteonuria easy and simple.KINDLY ALLOW ME TO DOWNLOAD THIS PRESENTATION. Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Office Nephrology : Office Nephrology Chair: Paul RoyManagement Of Proteinuria : Management Of Proteinuria Amanda Walker Chair: Paul RoyOffice management of proteinuria in children: Office management of proteinuria in children Dr. Amanda M. Walker Paediatric Renal & Continence Service, Monash Medical Centre MelbourneWhat are the proteins in urine?: What are the proteins in urine? Plasma proteins Renal tissue enzymes antigens tubular secretionsProteinuria - plasma proteins (Albumin): Proteinuria - plasma proteins (Albumin)Mechanisms of Albuminuria: Mechanisms of Albuminuria Altered filtration Glom haemodynamics Incr intraglom blood flow or pressure Glom pathology Reduced filtration barrier (size & charge) Altered reabsorption Prox conv tubule pathol CombinationSelectivity index: Selectivity index Selectivity index = u IgG x s Tf s IgG u Tf Albumin 66,000 Transferrin 90,000 IgG 160,000 ≤0.10 highly selective ≥0.11 ≤0.20 mod selective ≥0.21 poorly selective May have prognostic signif with nephrotic syndrome response & progression to ESRF (Bazzi et al., Kidney Int, 2000, 58, 1732)Effect of proteinuria: Effect of proteinuria Tubular cell culture Proteinuria Stim inflamm mediators Endothelin-1 Monocyte chemottractive protein (MCP-1) Bazzi et al., Kidney Int, 2000, 58, 1732 www.renal.com.ar/cgi-bin/i/monografias/patologia/images/slide9.jpgProteinuria - tubular proteins: Proteinuria - tubular proteins LMW proteins - tubular pathology: Normal values (spot) Lysozyme (10 – 66mg/mol Cr) ß2 microglobulin (6 – 41 mg/molCr) RBP (<1 – 24 mg/mol Cr) LMW proteins - tubular pathology LMWP <40,000 Daltons Freely filtered by glom; 99.9% reabsorbed - prox tubule Catabolized by tubular lysosomes Sensitive marker for tubular pathology i.e. small dec prox tub fx ---- large incr LMWP (Pediatric Nephrology, 1994 ed Holliday, Barratt & Avner 403)Tubular proteinuria: Tubular proteinuria www.gen.umn.edu/faculty_staff/jensen/1135/webanatomy/wa_urinary/wa_wcb_nephron3.htmlSummary of proteins found in urine: Summary of proteins found in urine Alb /transferrin/ IgG glomerular filtration/ prox tubule Retinol Binding Protein/amino acids prox tubular dysfunction (reabsorption) 1 microglobulin / NAG prox tubular necrosis/damageDetection of proteinuria: Detection of proteinuria extremely sensitive albumin (as it contains the most amino groups), much less sensitive globulins insensitive Bence-Jones proteins. amino groups in proteins bind and alter the colour of pH indicator (tetra-bromophenol blue) even though the pH is unchanged.False negatives and positives on FWT: False negatives and positives on FWT Screening FWT +++/++++ >1gm/m2/day pos predictive value of 89% 0/trace <0.1g/m2/day neg predictive value 60% Improved with automated colour reading Abitbol, J Ped, 1990,116(2),243 false positive radiographic contrast media, low pH false negative high urinary conc of penicillin, sulphonamides high pH, moving urine, dilute urineQuantification of proteinuria: Quantification of proteinuria 24 hour protein excretion N <150 mg/day Timed urine collection Total protein Albumin Urinary Pr:Cr ratioProteinuria – normal values: 145 mg/ m2/day 110 mg/ m2/day 85 mg/ m2/day 150 mg/day Proteinuria – normal values 2 – 10 yrs Wingo & Clapp, 2000,AmJ Med Sci, 320, 188 www:news.bbc.com.uk;www:keepkidshealthy.comProteinuria – normal values: Proteinuria – normal values Relatively constant after 12 months of age < 4mg/m2/hr or <100 mg/ m2 /24 hr Nephrotic range proteinuria > 40mg/ m2 /hr overnight sample (ISKDC) 1.7g/24 hr for adults Suggested 3.5g/1.73 m2 /day (80mg/ m2 /hr) Glassock, 1988 in Cameron, JS Glassock RJ (ed) The Nephrotic syndrome, 219 Urinary Pr:Cr ratio: Urinary Pr:Cr ratio High correlation b’t timed urine collections & U Pr:Cr ratio UCr excretion stable Comparison 1st am sample & 24hr/overnight R= 0.81 - 0.99 (>11 studies - CARI draft guidelines) U Pr:Cr < 20 - 25mg/mmol <4mg/m2/hr <2 yr old N < 50mg/mmol Nephrotic range U Pr:Cr 200 - 250 mg/mmol Urinary Alb:Cr ratio: Urinary Alb:Cr ratio Good for detection of glomerular pathology, miss tubular proteinuria More expensive, N range less well defined for children MicroAlbUria U Alb:Cr >2.5 mg/mmol Proteinuria U Alb:Cr >30 mg/mmol UAlb:Cr Diabetics, known glomerular disease Slide20: Ringsrud & Linne, 1995 Urinalysis & body fluids, MosbyClassification of isolated proteinuria: Classification of isolated proteinuria Character (intermittent/ constant) Posture (orthostatic/ non – ortho) Quantity (non- nephrotic / nephrotic)Transient proteinuria: Transient proteinuria Common children, adolescents & adults Fever, exercise, extreme cold, Adrenaline admin, CCF, seizures Asymptomatic usu screening abn Normal urinary sediment Resolves spontaneously Repeat sample 2 -3 times before Ix Hogg et al., 2000, Pediatrics, 105, 1242Idiopathic intermittent proteinuria: Idiopathic intermittent proteinuria Proteinuria independent of body posture in most (>50%) but not all random urine samples Usu <30 yrs old , N renal function & N BP Renal Bx of 51 pts 40% normal/ min histological change 60% variety of lesions Glom hypercellularity and sclerosis No em studies done, no clinicopath correlations Benign prognosis if proteinuria resolves over a few yearsOrthostatic proteinuria: Orthostatic proteinuria Definition: absence of proteinuria during recumbency and its appearance during quiet upright ambulation or standing Transient (80%) not well studied Persistent (20%) Sinniah et al., 1977, Clin Nephrol, 7,1Orthostatic proteinuria: Orthostatic proteinuria 60% proteinuria in childhood 75% proteinuria in adolescents Rare >30 yrs old Rarely >1g/m2/day Dodge et al 1976, J Pediatr, 88, 327 Hogg et al., 2000, Pediatrics, 105, 1242 Orthostatic proteinuria: Orthostatic proteinuria ?normal variant Postural changes in protein excretion seen with N pop’n 20% of 120 N volunteers (<150 mg/day) incr protein excretion when upright Mahurkar et al, Br Med J, 1975,1, 712 116 adolescents Incr U Pr:Cr in upright position Houser et al., 1986, J Pediatr, 109, 556 Orthostatic proteinuria ?glomerular abnormality: Orthostatic proteinuria ?glomerular abnormality Bx - N or Mild focal and segmental mesangial hypercellularity Focal or diffuse capillary wall thickening Occ focal foot process fusion Mesangial & capillary deposits C3, IgG Sinnah et al, 1977, Clin Nephrol, 7,1-14 Orthostatic proteinuria ?haemodynamic abnormality: Orthostatic proteinuria ?haemodynamic abnormality Upright position Venous pooling in legs Renal vein congestion Decr renal blood flow (incr Ang II) Incr efferent arteriolar resistance Incr proteinuriaOrthostatic proteinuria ?Nutcracker phenomenom: Orthostatic proteinuria ?Nutcracker phenomenom Entrapment of L renal vein bt Aorta & sup mesenteric artery L flank pain, macrohaem, peripelvic & ureteric varices Isolated orthostatic proteinuria Orthostatic proteinuria ?Nutcracker phenomenon: Orthostatic proteinuria ?Nutcracker phenomenon Cho et al, 2001, Nephrol Dial Transplant, 16,1620 1997 - 1999, Seoul 6 - 16 yrs 39 orthostatic proteinuria 22/39 (54%) +ve 28 control 0/28 +ve Renal venography (gold standard) Doppler U/s AP diameter L renal vein Peak LRV velocities Renal hilum As passes bt Ao & SMA Ratio >5 = highly suggestiveOrthostatic proteinuria prognosis: Orthostatic proteinuria prognosis 20 yrs 43 pts orthostatic proteinuria 85% no proteinuria No deterioration in renal function Springberg et al.,1982, Ann Intern Med., 97, 516 6 pts Dx orthostatic proteinuria 42 -50 yrs earlier Resolution of proteinuria, N renal fx Rytand,1981, N Eng J Med., 305, 618Persistent isolated proteinuria: Persistent isolated proteinuria X’s in upright & recumbent position Male predominance Structural disease Tendency to progressCauses of constant proteinuria: Causes of constant proteinuria Early glomerular disease FSGS (primary or secondary), IgA nephropathy Essential hypertension Early diabetic nephropathy Membranous GN Overflow proteinuria Low molecular weight proteins (myoglobin, Hb, a.a.) Tubular proteinuriaInvestigation of proteinuria: Investigation of proteinuria Personal & family Hx of renal disease Thorough examination include BP, growth Urine M & C (?haematuria) U Pr:Cr (Early morning and late evening) Timed urine collection Serum biochem, (include Alb, TPr, lipids) Imaging (Ultrasound ± Doppler, DMSA) Renal BxManagement of isolated proteinuria: Management of isolated proteinuria Transient Nil i.e. discharge Orthostatic (<1g/m2/day; N AM UPr:Cr) Intermittent review, early AM UPr:Cr Persistent Define disease Monitor for proteinuria, GFR, HPTProgression of persistent proteinuria: Progression of persistent proteinuriaPersistent proteinuria: Persistent proteinuria proteinuria, GFR, HPT Consideration for ACEI Reduce proteinuria Delays progression of CRF in adults with Chronic nephropathies & >2g/day proteinuria and/or HPT (REIN study; Ruggenenti et al, AmJKD,2000, 35, 1155) Office management of proteinuria: Office management of proteinuria Detect and define the pattern of isolated protein loss FWT will not detect all proteins Intermittent and low grade - good Px Persistent or mod grade - closer evaluation disease definition more guarded PxProteinuria in children: Proteinuria in children Positive (+) protein on first morning urine by dip-stick Preschool children (age 4.5 yrs) in South Aus 23/9355 children (0.25%) 7/23 children (+) on retesting Hogg et al., 1998, J Paediatr Child Health, 34, 420 School aged children 4 urine samples 1 of 4 (+) protein in 10.7% children, 0.1% 4/4 Vehaskari et al., 1982, J Pediatr, 101, 661 Prevalence of proteinuria: Prevalence of proteinuria Taiwan screening program 10,288,620 elementary & junior high school students 1992 - 1996 4 yr prevalence of (++) proteinuria Girls Lowest at 7 yrs 3.48 x 10-4 Peak at 12 yrs at 10.02 x 104 Boys Lowest at 7 yrs at 2.21 x 10-4 Peak at 13 yrs at 8.7 x 10-4 Lin et al.,2000, Pediatr Nephrol, 14, 953