PROTEINURIA DR.Mohammed almansour MD,SBFM,ABFM Assisstant professor Family medicine College of medicine,almajmaah university

outlines Case scenario Definition Pathophysiology Causes Clinical presentation Workup Management conclusion

case fatimah is 8 Years old Female presented to ER with:  Fever, sore throat x 4 days  Puffiness around eyes and swelling of feet x 2 days  Reduced urine output x 2 days How to approach this case? History: ◦ H/o similar symptoms at 8 months of age and treated with Prednisolone. ◦ H/o multiple relapses – responding to steroids

Problems list Acute:??URTI Acute on top of chronic: ◦ Puffiness,swelling(edema),low urine output ??? RENAL DISEASE What could be wrong with her kidneys?

Examination What do you expect to find? HR = 97 RR = 28 BP = 98/62 Temp = 37 Periorbital and pedal edema HEENT : normal No other significant findings

Clinical presentation

Work up Is there some thing to do at bedside? Urine dipstick For her was 3+ negative <15 mg/dl, trace mg/dl, mg/dl, mg/dl, mg/dl, 4+ >1000 mg/dl

Na = 132 K = 4.2 Cl = 100 HCO3=23 BUN = 38 Creat = 0.7 Protein = 5.3(6-8)Albumin = 1.6 (3.6–5) HB = 13 WBC = 18.6 Plt = 450 UA = Protein-500mg/dl SG-1.015, Urine protein/creat = 14.4 (<0.1) Cholesterol = 206 Blood Cultures = Negative

SO !!!!!!!!!!!!!!!! what is the abnormality in her urine? PROTEINURIA what is it? LET US SEE

Definition Normal urine protein excretion is up to 150 mg/d (4 mg/m 2 /hr). Therefore, the detection of abnormal quantities or types of protein in the urine is considered an early sign of significant renal or systemic disease

Significant proteinuria can be defined: ◦ Qualitative: 1+ on dipstick examination of 2 out of 3 random urine specimens collected one week apart if urine sp 1015 ◦ Semiquantitative: urine Pr/Cr ratio > 0.2 on early morning specimen ( r = 0.97 with 24 hs collection) in older children, >0.5 in infants. > 3 at any age is suspicious of nephrotic range. ◦ Quantitative: Normal: 40 mg/meter/hour

pathophysiology

pathophysiology The presence of abnormal amounts or types of protein in the urine reflects the following: Overproduction of plasma proteins that are capable of passing through the normal glomerular basement membrane (GBM), as they enter the tubular fluid in amounts that exceed the capacity of the normal proximal tubule to reabsorb them A defective glomerular barrier that allows abnormal amounts of proteins of intermediate molecular weight to enter the Bowman space. Systemic diseases that result in an inability of the kidneys to normally reabsorb the proteins through the renal tubules

causes Is it due to a pre-renal, renal or post- renal cause? Pre-renal: protein loss in urine without renal disease a. Tubular overload proteinuria i. Occurs when elevated levels of small MW proteins (< 68K daltons) pass through the normal glomerulus and appear in urine. Excessive amounts of the same protein are found in blood and urine. ii.e.g: hemoglobinemia (from intravascular hemolysis),

b. Functional proteinuria: transient alteration in glomerular function. Sometimes transient proteinuria (usually albumin) is noted in association with hypertension, strenuous exercise, extremes of heat or cold, venous congestion, fever, or seizures. c. Determining if proteinuria is pre-renal: evaluate for hyperproteinemia.

2. Renal proteinuria: protein loss in urine due to renal disease a. Glomerular disease Glomerular proteinuria results from a damaged glomerulus that allows for leakage of plasma proteins through the glomerulus. This form of proteinuria is usually profound and consists predominantly of albumin.e.g. nephrotic syndrome, nephritis,HUS,HS purpura……etc

b. Tubular disease Tubular proteinuria may occur due to tubular dysfunction (tubules fail to reabsorb filtered protein) or parenchymal inflammation.e.g acute tubular nephrosis, interstitial nephritis, drugs This form of proteinuria is usually mild. c. Determining if proteinuria is renal: significant proteinuria in association with an inactive urine sediment is likely due to a renal cause.

3. Post-renal proteinuria: protein added to urine after it has been formed. a. Lower urinary tract or genital disease This may occur when inflammatory exudates or blood proteins from the lower urinary or genital tract mix with urine (usually due to infection, hemorrhage, neoplasia, etc). b. Determining if proteinuria is post-renal Proteinuria in association with an active urine sediment (pyuria, hematuria, bacteriuria, crystalluria, etc.)

*Q: Is it possible to have both a renal and post-renal cause of proteinuria? *A: Yes - in these cases, you may note an active urine sediment, proteinuria, hypoalbuminemia, and hypercholesterolemia.

Back to our case Is it pre- renal,renal or post renal cause?

history In most patients, proteinuria is asymptomatic. So think of the pre-renal/renal /post renal approach Are symptoms present that suggest nephrotic syndrome or significant glomerular disease? Have changes occurred in urine appearance (eg, red/smoky, frothy)? Did this occur in relation to an upper respiratory tract infection? Is edema (eg, ankle, periorbital, labial, scrotal) present? Has the patient ever been told his or her blood pressure is elevated? Has the patient ever been told his or her cholesterol is elevated? Is there family hx of renal diseases? Drugs?

examination General looking(e.g.obese child) looking for edema (eg, ankle, leg, scrotal, labial, pulmonary, periorbital), ascites, and pleural effusions. Examine for signs of systemic disease (eg, retinopathy, rash, joint swelling or deformity, stigmata of chronic liver disease, organomegaly, lymphadenopathy, cardiac murmurs). Examine for such complications as venous thrombosis or peritonitis.

Back to our case What does fatimah have in hx and exam ?

Work up Initial investigations: Urine: ◦ Urine microscopy ◦ Urine collection (24 h) for quantification of albumin (or protein) excretion and creatinine clearance. ◦ Protein/creatinine ratio serum ◦ BUN, creatinine, total protein,albumin, cholesterol,TG,ca, and blood glucose.

Advance investigation: ◦ Depend on the cause you want to rule in or out ASO titer, C3 complement, ANA, hepatitis B serology Renal US, VCUG, renal scan Renal biopsy

management Medical care can be considered as having 2 components : ◦ Nonspecific treatment that is applicable irrespective of the underlying cause, assuming the patient has no contraindications to the therapy  Control BP(<125/75)  ACEI  Treat edema(cautious use of diuertic)  Diet: salt restriction ◦ Specific treatment that depends on the underlying renal or nonrenal cause

Close the case Do we reach diagnosis of fatimah’s disease? Does she need hospitalization?

NEPHROTIC SYNDROME The nephrotic syndrome is a clinical complex characterized by: proteinuria of >3.5 g per 1.73 m2 per 24 h (in practice, >3.0 to 3.5 g per 24 h), hypoalbuminemia, edema, hyperlipidemia, lipiduria, and Hypercoagulability In children the most common variety is MCNS with a characteristic response to corticosteroid therapy

conclusion Definition :>150 mg/d (4 mg/m 2 /hr) protein in urine proteinuria. Causes: ◦ pre-renal(overload/functional) protein in blood. ◦ Renal(Glomerular disease/ Tubular disease). INactive urine sediment(INside the kidney) ◦ Post-renal(infection/haemorrhage/cancer) active urine sediment

Most of time asymptomatic but don’t forget nephrotic syndrome presentation: ◦ Edema ◦ Cholesterol ◦ S.albumin Work up urine and blood Management:treat the cause

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