Heamaturia & protienuria Dr.Badi AlEnazi Consultant pediatric endocrinologest and diabetologist

Haematuria may occur as an isolated symptom or as part of a systemic disorder. It may be visible to the naked eye (frank or macroscopic haematuria) or be detected only on microscopic analysis of the urine.

The source of the blood may be anywhere from glomerulus to urethra most cases in childhood are due to UTI or primary glomerular disease.

DDx Urinary tract infection (UTI). Glomerulonephritis (post-streptococcal, Henoch-Schonlein purpura, ). IgA nephropathy. Acute haemorrhagic cystitis. Viral (adenovirus). drugs (cyclophosphamide). Calculus. Trauma. Exercise-induced. Usually after severe exercise and resolves within 48 hours. Tumours. Wilms’ tumour (uncommon presentation),

DDX Coagulopathies. Sickle cell disease. Renal vein thrombosis. Gross haematuria and palpable renal mass in a newborn infant. Factitious haematuria. As part of the Munchausen by proxy spectrum

Post strep Glomerulonephritis Strep pharyngitis, or strep skin infection, followed 10 to 14 days by microscopic hematuria, nephritis, or nephrosis Diagnosis: positive ASO low C3 which normalize in 8 weeks Management: supportive Prognosis: Excellellent

Pt came with abdominal pain and palpable rash and hematuria

This is a boy who presented with abdominal mass and hematuria

RBCs

RBCs Cast

WBCs Cast

This patient had history of loin pain and hematuria

This urine sample of patient presented with hamaturiamhypertension after 3 week of URTI

This is a peripheral smear for patent who presented with hematuria

Clinical Features The urine is usually pink or brown in colour because of the presence of the oxidized haem pigment..

Clinical Features If the urine is bright red with or without clots then a lower urinary tract source should be suspected. Haematuria may be an isolated finding or be associated with symptoms of a systemic disorder, e.g. Henoch-Schbnlein purpura (rash, joint pains).

Clinical Features Hypertension and oliguria are features of acute GMN. Frequency and dysuria suggest a UTI which may be accompanied by microscopic haematuria Loin pain or renal colic suggests the presence of a calculus.

Hematuria: Historicall Clues Recent vigorous exercise or trauma. History of new onset of incontinence, dysuria, frequency, or urgency. History of unilateral flank pain that may radiate to the groin. flank pain without radiation but with fever, dysuria, and frequency and/or urgency.

Hematuria: Historicall Clues The timing of hematuria during micturition, especially terminal hematuria. The color of urine may distinguish glomerular bleeding from extraglomerular bleeding.

Hematuria: Historicall Clues A history of predisposing clinical conditions such as sickle cell disease or trait or coagulopathy such as severe hemophilia. Children who have papillary necrosis usually have sickle cell disease, or trait, and the gross hematuria generally is associated with pain , typically abdominal or flank pain. Exposure to medications that can cause hemorrhagic cystitis.

Hematuria: Historicall Clues A history of pharyngitis or impetigo (two or three weeks prior to onset of hematuria). Nephritic syndromes, whether immune or non-immune, usually present with a classical triad of hypertension, azotemia, reduced urine output, edema,

Hematuria: Historicall Clues Patients who have lupus nephritis may develop either microscopic or gross hematuria but they often have associated symptoms (e.g, rashes, arthritis, anorexia )

This girl came with haematureia

Hematuria: Historicall Clues Patients who have immunoglobulin A nephropathy typically develop recurrent episodes of gross hematuria

Hematuria: Historicall Clues Patients who have hemorrhaagic cystitis typically have bright red blood in the urine (terminal gross hematuria) and dysuria, abdominal pain, frequency, urgency.

Hematuria: Historicall Clues Hx of skin or joint abnormalities Weight gain, swelling, recent URTI Hx of favabeen ingestion Family Hx: hematuria, deafness, CRF

Hematuria: Physical Findings Hypertension, growth impairment Chest: murmurs, . . Abdomen: masses, ascites, tenderness. . . Abnormal urinary stream Edema, skin rashes, joint swelling

symptomaticHematuria: Diagnostic Approach GLOMERULAR HEMATURIA 1-IMMUNE MEDIATED GN 2-NONIMMUNNE GN POST INFECTIOUS ALPORTS SYNDROME IgA NEPHROPATHY BENIGN FAMILIAL

symptomatic Hematuria: Diagnostic Approach-cont’d NON GLOMERULAR HEMATURIA: URINARY TRACT CYSTITIS, INFECTION UT CALCULI UT ANOMALIES HYPERCALCIURIA HYPERURICOSURIA SICKLE CELL TRAIT Unrecognized UT Anomalies, Infection , stones.

Urinary dipsticks are not very reliable. They are also positive for myoglobin and free haemoglobin

Urine microscopy should always be performed to confirm the presence of red cells The presence of red cell casts indicates an intrarenal cause (either glomerular or tubular) Glomerular casts indicate a glomerular cause. Pyuria and bacteriuria point to an infective cause which should be confirmed by culture.

Urine culture will confirm a bacterial infection. CBC and coagulation tests. To exclude coagulopathies and sickle cell disease.

Radiology. An abdominal US scan may identify a renal mass, evidence of obstruction or a renal tract calculus.

Proteinuria Protein is normally found in the urine of healthy children Since albumin has a relatively small molecular size, it tends to become the dominant constituent in proteinuria.

Non Persistent Proteinuria Fever Strenuous exercise Cold exposure Epinephrine infusion Orthostatic

Proteinuria Glomerular Tubualr absorption Protein overload ATN Congenital: -Finish- type - TORCH infection Nephritis: - postinfectious GN - lupus - Wegner - HUS - Goodpasture Nephrotic: - Minimal change - FSGS - MPGN Drugs: captopril Neoplasia Renal vein throbosis ATN Fanconi Syndrome Cystic/dysplastic Interstial nephritis Pyelonephritis Hemolysis Rhabdomyolysis

This patient came with high liver enzyme, and protinuriea

MECHANISMS OF PROTEIN HANDLING BY KIDNEY Normal protein excretion affected by interplay of glomerular and tubular mechanisms Glomerular injury: abnormal losses of intermediate MW proteins like albumin Tubular damage: increased losses of low MW proteins

ABNORMAL PROTEIN EXCRETION Urinary protein excretion in excess of 100 mg/m2 per day or 4 mg/m2 per hour Nephrotic range proteinuria (heavy proteinuria) is defined as ≥ 1000 mg/m2 per day or 40 mg/m2 per hour.

ABNORMAL PROTEIN EXCRETION Glomerular proteinuria Due to increased filtration of macromolecules May result from glomerular disease (most often minimal change disease) or from nonpathologic conditions such as fever, intensive exercise, and orthostatic (or postural) proteinuria

ABNORMAL PROTEIN EXCRETION Tubular proteinuria Results from increased excretion of low molecular weight proteins such as beta-2-microglobulin, Tubulointerstitial diseases, can lead to increased excretion of these smaller proteins

ABNORMAL PROTEIN EXCRETION Overflow Proteinuria Results from increased excretion of low molecular weight proteins due to marked overproduction of a particular protein to a level that exceeds tubular reabsorptive capacity

ASYMPTOMATIC PROTEINURIA Levels of protein excretion above the upper limits of normal for age No clinical manifestations such as edema, hematuria, oliguria, and hypertension

MEASUREMENT OF URINARY PROTEIN Use of a urine dipstick to detect proteinuria   Dipstick proteinuria reflects primarily albuminuria.  False-positive dipstick tests are seen with gross hematuria, concentrated urine, alkaline urine (pH >8), or contamination with chlorhexidine or certain medications (e.g., phenazopyridine therapy).

MEASUREMENT OF URINARY PROTEIN Urine dipstick Measures albumin concentration Negative Trace — between 15 and 30 mg/dL 1+ — between 30 and 100 mg/dL 2+ — between 100 and 300 mg/dL 3+ — between 300 and 1000 mg/dL 4+ — >1000 mg/dL

MEASUREMENT OF URINARY PROTEIN Sulfosalicylic acid test Detects all proteins in the urine including the low molecular weight proteins that are not detected by the dipstick

ORTHOSTATIC PROTEINURIA Increase in protein excretion in the erect position compared with levels measured during recumbency Mechanism postulated to involve an increased permeability of the glomerular capillary wall and a decrease in renal plasma flow Long-term studies have documented the benign nature of this condition, with recorded normal renal function up to 50 years later

PERSISTENT PROTEINURIA Present for long periods after initial detection Absence of both orthostatic proteinuria and clinical evidence of renal disease Clinical course may be benign May be secondary to parenchymal disease

DIFFERENTIAL DIAGNOSES OF PERSISTENT PROTEINURIA Benign proteinuria Acute Glomerulonephritis Chronic Glomerular Disease that can lead to nephrotic syndrome Chronic nonspecific glomerulonephritis Chronic interstitial nephritis Congenital and acquired structural abnormalities of urinary tract

HISTORY Recent infection Weight changes Presence of edema Symptoms of hypertension Gross hematuria Changes in urine output Dysuria Skin lesions

HISTORY Swollen joints Abdominal pain Previous abnormal urinalysis Growth history Medications Family history Renal disease, hypertension, deafness, visual disorders

PHYSICAL EXAMINATION Vital signs Inspect for presence of edema, pallor, skin lesions, skeletal deformities Screening for hearing and visual abnormalities Abdominal exam Lung exam Cardiac exam

TRANSIENT PROTEINURIA Follow-up routinely Patient should have a repeat urinalysis on a first morning void in one year

ORTHOSTATIC PROTEINURIA Perform Orthostatic Test CBC BUN Creatinine Electrolytes 24-hr urine excretion < 1.5g/day  repeat UA and blood work in 1 year > 1.5g/day  refer to Pediatric Nephrologist

FURTHER EVALUATION OF PERSISTENT PROTEINURIA Examination or urine sediment CBC Renal function tests (blood urea nitrogen and creatinine) Serum electrolytes Cholesterol Albumin and total protein

OTHER TESTS Renal ultrasound Serum complement levels (C3 and C4) ANA Streptozyme testing, Hepatitis B and C serology HIV testing

PERSISTENT PROTEINURIA If further work-up normal, urine dipstick should be repeated on at least two additional specimens. If these subsequent tests are negative for protein, the diagnosis is transient proteinuria. If the proteinuria persists or if any of the studies are abnormal, the patient should be evaluated more extensively

Nephrotic Syndrome Nephrotic syndrome is a clinical state characterized by: Massive proteinuria (>40 mg/m2/hr) Hypoalbuminemia (albumin <2.5 g/dL) Edema Hypercholesterolemia .

Nephrotic Syndrome Minimal change disease Focal segmental glomerulosclerosis Membranoproliferative Membranous GN Infection: HIV, hepatits, syphilis Lupus, Ig A, HSP, post strep

Initial therapy Supportive: albumin 25% and lasix prn Salt restriction Fluid restriction while nephrotic Prednisone 60 mg/m2/day for 6 weeks followed by 40 mg/m2/day for 6 weeks then wean..

This is infant with protinuria since age of 2 month

Please remember : Edema Nephrotic range proteinuria Low albumin Nephritis Nephrosis Hematuria Hypertension Oliguria Increased Cr Edema Nephrotic range proteinuria Low albumin Hypercholestrolemia

Thank you