ProteinurProteinuriaia

ProteinurProteinuriaia

The primary care approachThe primary care approach

Presented byPresented by feras ghoshehferas ghosheh

66thth Y medical student Y medical studentAL-QUDS UNIVERSITYAL-QUDS UNIVERSITY

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ProteinuriaINTRODUCTIONDEFINITIONEPIDEMIOLOGY PATHOGENESIS DIFFERENTIAL DIAGNOSIS CLINICAL FEATURES Specific Entities INVESTIGATIONS MANAGEMENT

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INTRODUCTION

The protein is found in normal urine, and it’s divided into:

1-60% plasma proteins: albumin (major) IgG, IgA ,light chains ,heavy chains , transferrin ,haptoglobin ,lysozyme ,amylaze ,kallikrein.

2- 40% originating from the secretions of the urinary tract including: tamm-horstall ,urokinase and secertory IgA.

The reasonable upper limit of normal protien excretion in healthy children = 150 mg/24 hrs.

DEFINITIONDEFINITION

The excretion of an excessive The excretion of an excessive amount of protein (>150mg/day) in amount of protein (>150mg/day) in the urine as defined by qualitative, the urine as defined by qualitative, semi-quantitative, and quantitative semi-quantitative, and quantitative methods. methods.

EPIDEMIOLOGY incidence: 1 - 5% (depend upon age and number of

samples) prevalence: 5 - 11% (1+ proteinuria) only 10% of kids with proteinuria will have

abnormalities after 6-10 month of follow-up of those children with isolated proteinuria, <2%

will have significant underlying renal disease the incidence of proteinuria in patients with

underlying renal disease is remarkably high

PATHOGENESIS

There are three basic types of proteinuria:

1-glomerular2-tubular

3 -overflow

11 . .GlomerularGlomerular

mechanisms: mechanisms: . increased GFR . increased GFR . increased glomerular . increased glomerular

permeability permeability basement membrane basement membrane endothelial, epithelial cell injury endothelial, epithelial cell injury electrostatic charge barrier electrostatic charge barrier

proteins: larger proteins: larger macromolecules, albumin macromolecules, albumin

22 . .TubulointerstitialTubulointerstitial

impaired tubular reabsorption of impaired tubular reabsorption of filtered proteins filtered proteins

proteins: low MW proteins, proteins: low MW proteins, lysozyme, B2-microglobulinlysozyme, B2-microglobulin

Tamm-Horstall protein Tamm-Horstall protein

33 . .Overload ProteinuriaOverload Proteinuria

increased load overloads tubular increased load overloads tubular reabsorptive capacity reabsorptive capacity

proteins: low MW plasma proteins: low MW plasma proteins, Ig light chains, proteins, Ig light chains, myoglobulin, lysozyme, albumin myoglobulin, lysozyme, albumin

11 . .Benign ProteinuriaBenign Proteinuria

a. Benign Transient Proteinuriaa. Benign Transient Proteinuria

b. Orthostatic Proteinuriab. Orthostatic Proteinuria

c. Persistent Asymptomatic c. Persistent Asymptomatic ProteinuriaProteinuria

22 . .Pathologic ProteinuriaPathologic Proteinuria

A- GlomerularA- Glomerular

1. Hereditary 1. Hereditary

2. Non-Hereditary 2. Non-Hereditary

B-Tubulointerstitial B-Tubulointerstitial

1. Hereditary1. Hereditary

2. Non-Hereditary2. Non-Hereditary

A- Glomerular1. Hereditary Congenital Nephrotic

Syndrome Alport Syndrome

2. Non-hereditary

1. Acute (GN)

-Poststrep GN -H.U.Syndrome -H.S. Purpura

2. Chronic1 .Primary

Minimal Change Disease* FSGN Mesangioproliferative GN Membranous GN Membranoproliferative GN

2. Secondary Berger (IgA) Nephropathy Goodpastures Nephropathy SLE Nephropathy Wegeners Nephropathy Diabetic Nephropathy Renal Vein Thrombosis Sickle Cell Disease

B-Tubulointerstitial

1.Hereditary Cystinosis Galactosemia Lowe Syndrome Medullary Cystic Kidney Proximal RTA Wilson Disease

2. Non-Hereditary Acute Tubular Necrosis analgesic abuse antibiotics cystic diseases heavy metal poisoning homograft rejection hypokalemia interstitial nephritis penicillamine reflux

33 . .Overload ProteinuriaOverload Proteinuria

11 . .NeoplasticNeoplastic

AmyloidosisAmyloidosis Leukemia (monocytic, monomyelocytic) - Leukemia (monocytic, monomyelocytic) - lysozymurialysozymuria Multiple MyelomaMultiple Myeloma Waldenstrom's MacroglobinemiaWaldenstrom's Macroglobinemia

22 . .OthersOthers

IDDM (microalbuminuria)IDDM (microalbuminuria) repeated albumin or blood transfusionsrepeated albumin or blood transfusions RhabdomyolysisRhabdomyolysis most common causes of proteinuria in childhoodmost common causes of proteinuria in childhood

CLINICAL FEATURES:1 .History of Presenting Illness

at the end of the history, one should be able to discern: 1 .benign vs pathologic proteinuria (if pathologic then)

2 .glomerular vs tubulointerstitial proteinuria (if glomerular then) 3 .hereditary vs non-hereditary (if non-hereditary then)

4 .acute GN vs chronic GN (if chronic then) 5 .primary GN vs secondary GN

6 .nephrotic vs non-nephrotic proteinuria 7 .proteinuria with or without hematuriauria

onset when began with conditions identified around the initial presentation, i.e., drug ingestion record of previous urinalyses precipitation/palliation identification of triggering agents infectious, drugs, foods, chemicals, vaccinations helps to identify acquired forms of tubulointerstitial proteinuria

quality quality associated with hematuria associated with hematuria severity severity more likely to be pathologic proteinuria if associated with more likely to be pathologic proteinuria if associated with

hematuria or Nephrotic Syndrome (edema, hematuria or Nephrotic Syndrome (edema, hypoalbuminemia, hypercholesterolemia) hypoalbuminemia, hypercholesterolemia)

if Nephrotic Syndrome present: if Nephrotic Syndrome present: likely to be a primary GN likely to be a primary GN unlikely to be benign etiology or secondary GN unlikely to be benign etiology or secondary GN

timingtiming acute vs acute-on-chronic acute vs acute-on-chronic intermittent vs persistent intermittent vs persistent duration of proteinuria duration of proteinuria associated symptomsassociated symptoms past medical history past medical history functional inquiry functional inquiry

helps to differentiate acute GN from chronic GN helps to differentiate acute GN from chronic GN

helps to identify overload proteinuria causeshelps to identify overload proteinuria causes

Family History helps to differentiate hereditary from non-hereditary forms of both glomerular and tubulointerstitial forms

of proteinuria :

1 .Proteinuriafamily members must have had previous urinalysis to ascertain this

2 .Renal DiseasePolycystic Kidney Disease

Nephrotic Syndrome, Fanconi Disease

renal dialysis

kidney transplantation

3 .Others

hearing/ocular impairment (Alport Syndrome)

Specific Entities

1 .Benign Transient Proteinuria benign proteinuria associated with precipitating

factors - fever, exercise, stress, cold weather, dehydration, high blood pressure, seizures, etc

Orthostatic Proteinuria2 . diagnosis based upon the Postural Test has a benign clinical course

33 . .Persistent Asymptomatic ProteinuriaPersistent Asymptomatic Proteinuria proteinuria that persists for 3-6 months proteinuria that persists for 3-6 months renal biopsy after 6 months of persistent renal biopsy after 6 months of persistent

proteinuria and if FSGS then at risk for chronic proteinuria and if FSGS then at risk for chronic renal failure renal failure

44 . .Congenital Nephrotic SyndromeCongenital Nephrotic Syndrome onset at birth with Nephrotic Syndrome onset at birth with Nephrotic Syndrome

(massive proteinuria, hypoalbuminemia, edema, (massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia) and hyperlipidemia)

very difficult to treat with poor prognosis very difficult to treat with poor prognosis

55 . .Poststreptococcal GNPoststreptococcal GN proteinuria + hematuria proteinuria + hematuria

associated symptomsassociated symptoms prodrome of pharyngitis, URTI, impetigo prodrome of pharyngitis, URTI, impetigo

Nephrotic and/or Nephritic SyndromeNephrotic and/or Nephritic Syndrome

6. Hemolytic Uremic Syndrome6. Hemolytic Uremic Syndrome proteinuria + hematuria proteinuria + hematuria associated symptoms associated symptoms

prodrome of bloody diarrhea prodrome of bloody diarrhea anemia and thrombocytopenia (petechiae) anemia and thrombocytopenia (petechiae) Nephrotic and/or Nephritic Syndrome Nephrotic and/or Nephritic Syndrome

7. Henoch-Schoenlein Purpura7. Henoch-Schoenlein Purpura proteinuria + hematuria proteinuria + hematuria associated symptoms associated symptoms

purpuric rash, arthritis, abdominal pain purpuric rash, arthritis, abdominal pain Nephrotic and/or Nephritic Syndrome Nephrotic and/or Nephritic Syndrome

8. Primary Glomerulonephritis8. Primary Glomerulonephritis isolated proteinuria +/- Nephrotic Syndrome isolated proteinuria +/- Nephrotic Syndrome associated symptoms associated symptoms

edema, hypoalbuminemia, hyperlipidemia edema, hypoalbuminemia, hyperlipidemia

99 . .Secondary GlomerulonephritisSecondary Glomerulonephritis proteinuria +/- hematuria associated with a proteinuria +/- hematuria associated with a

disease entity, i.e., SLE, Goodpastures disease entity, i.e., SLE, Goodpastures Disease, Wegeners Disease, Diabetes MellitusDisease, Wegeners Disease, Diabetes Mellitus

1010 . .Hereditary Tubulointerstitial ProteinuriasHereditary Tubulointerstitial Proteinurias tubular proteinuria tubular proteinuria associated symptoms associated symptoms episodes of vomiting, dehydration, weakness, fever, episodes of vomiting, dehydration, weakness, fever, anorexia, constipation, failure to thrive, polydipsia, anorexia, constipation, failure to thrive, polydipsia, polyuriapolyuria

INVESTIGATIONS 1 .Proteinuria (Diagnosis)

1 .Qualitative - Dipstick measures a range of protein concentrations depth of colour increases in a semiquantitative manner with

increasing urinary protein concentration to rule out false positives must have:

3 samples with proteinuria first voided early morning samples pH < 6.0 with known specific gravity

1+ (72-240 mg/24 hrs) or greater is considered abnormal dependent on specific gravity of urine sample FP: gross hematuria, highly alkaline urine, UTI

2 .Semi-quantitative - Protein/Creatinine Ratio in Urine

random early morning single voided specimen children < 2 years : < 0.5 children > 2 years : < 0.2 nephrotic : > 3.5

correlates with the 24 hour protein excretion data

33 . .Quantitative - 24 hr. urine Quantitative - 24 hr. urine collectioncollection

gold standard gold standard if dipstick is 1+ or more than obliged to do a if dipstick is 1+ or more than obliged to do a

24 hour urine collection 24 hour urine collection 24 hr. urine collection 24 hr. urine collection

Protein (mg)/m2/hr Protein (mg)/m2/hr < 4 mg/m2/hourr (normal) < 4 mg/m2/hourr (normal) 4-40mg/m2/hour (proteinuria) 4-40mg/m2/hour (proteinuria) 40 mg/m2/hour (nephrotic) 40 mg/m2/hour (nephrotic)

Protein (mg)/24 hr Protein (mg)/24 hr 2 to 12 months : > 155 mg/24 hr 2 to 12 months : > 155 mg/24 hr 3 to 4 years : > 140 mg/24 hr 3 to 4 years : > 140 mg/24 hr 4 to 10 years : > 190 mg/24 hr 4 to 10 years : > 190 mg/24 hr 10 to 16 years : > 250 mg/24 hr 10 to 16 years : > 250 mg/24 hr

FP: radiographic contrast media, FP: radiographic contrast media, cephalosporins, pencillin analogues, cephalosporins, pencillin analogues, sulfonamide metabolites sulfonamide metabolites

2 .Indications for Further Investigation

Non-orthostatic Proteinuria Persistent Proteinuria Symptomatic (edema, elevated BP, abdominal

pain, hematuria)

33 . .First Line First Line InvestigationsInvestigations

11 . .UrinalysisUrinalysisR&M, C&S, R&M, C&S, microscopymicroscopy orthostatic testorthostatic test

2424 hour collectionhour collection total proteintotal protein creatinine clearancecreatinine clearance

22 . .SerumSerumelectrolytes, BUN, electrolytes, BUN, creatinine, albumin, creatinine, albumin, cholesterol, cholesterol, triglyceride, triglyceride, calcium, protein, calcium, protein, CBCCBC orthostatic testorthostatic test

4. Second Line 4. Second Line InvestigationsInvestigations

1. Urine1. Urineprotein electrophoresis can be protein electrophoresis can be

used to differentiate used to differentiate glomerular (albumin) from glomerular (albumin) from tubular (Tamm-Horstall) tubular (Tamm-Horstall) proteinuria proteinuria

2. Serum2. SerumIgA, PTH, ANA, protein IgA, PTH, ANA, protein

electrophoresis, ASOT, anti-electrophoresis, ASOT, anti-GBM antibodies, uric acid, C3, GBM antibodies, uric acid, C3, C4 C4

3. Imaging Studies3. Imaging Studiesrenal ultrasound to rule out renal renal ultrasound to rule out renal

vein thrombosis vein thrombosis

4. Renal Biopsy4. Renal Biopsyindicated for: indicated for:

progressive proteinuria with progressive proteinuria with hematuria hematuria

all forms of Nephrotic Syndrome all forms of Nephrotic Syndrome except that caused by steroid-except that caused by steroid-responsive Minimal Change responsive Minimal Change DiseaseDisease

MANAGEMENT

treat underlying disorder treat complications

Thank youThank you

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