Hematuria For the boards... Gital Karamchandani-Patel, MD 4/11/2017 One of the most common reasons that kids are referred to a nephrologist by their pediatrician Gital Karamchandani-Patel, MD

Definition Macroscopic (gross) Hematuria Microscopic Hematuria 4/11/2017 Definition Macroscopic (gross) Hematuria any discolored urine visible to the human eye Microscopic Hematuria >5 RBC/hpf seen under microscope 50 RBC per microliter of unspun urine on a dipstick is also suggestive of hematuria RBC seen on dipstick must be confirmed with an U/A microscopic urine is done on fresh centrifuged urine sample

Hematuria What is your first step? 4/11/2017 Hematuria Patient comes to your office complaining that their urine is reddish in color... What is your first step? Good H+P Have to get a really good history What kinds of questions are you going to ask? ask about foods, drugs ask about recent illnesses ask about menstrual cycle ask about dysuria, fever ask about visual changes ask about family history Perform a good physical exam what to look for on PE: vitals (BP), edema, flank masses, bruising

Hematuria Is it really blood? Urine Dipstick Detects Hgb, myoglobin 4/11/2017 Hematuria Is it really blood? Urine Dipstick Detects Hgb, myoglobin Detects protein In your office, you will have dipsticks readily available to you Hemoglobin and myoglobin will produce the same color changes on the dipstick as intact RBCs via a peroxidase reaction myoglobinuria may occur secondary to rhabdomyolysis (viral disease, crush injury, DIC) false-positive test for blood can result from the presence of drugs such as ascorbic acid, sulfonamides, iron sorbitol, metronidazole, and nitrofurantoin Best thing is to send U/A to the lab for a urinalysis On your dipstick, you can also see if you have proteinuria. Isolated hematuria is something a PCP should be able to manage…when you have hematuria with proteinuria, you should refer to a nephrologist.

4/11/2017 Hematuria Urinalysis Definitive for the presence of RBC

Hematuria Upper urinary tract Lower urinary tract calyx glomerulus 4/11/2017 Hematuria Upper urinary tract glomerulus collecting tubules interstitium Lower urinary tract calyx pelvis ureter bladder urethra Once you have determined that it really is blood that you are dealing with, you need to try to figure out where it is coming from. Blood cells can come from anywhere in the urinary tract. The blood will look different depending on where it is coming from.

What PREP wants you to know... 4/11/2017 What PREP wants you to know... Know the differential diagnosis of a child with gross hematuria

4/11/2017 So to recap what our thinking process whenever we have someone present with gross hematuria to help us with our differential get a good history make sure it really is blood with a U/A if it really is blood, do you have protein in your urine as well? If there are no RBC, is there something in the history that could cause discolored urine? -Myoglobin? PREP wants you to know that myoglobin can yield false + results for hematuria on urinalysis -Hemoglobin? -Diet/Drugs? -Porphyria?

Glomerular Hematuria brown, tea colored urine proteinuria 4/11/2017 Glomerular Hematuria brown, tea colored urine proteinuria deformed urinary RBCs RBC casts Proteinuria RBC casts- RBC’s leak from the damaged glomerular walls Proteinuria occurs bc protein leaks thru glomerular basement membrane Deformed RBCs in the urine because they travel through the convoluted filtering system\ Urinary casts are cylindrical aggregations of particulate matter that form in the distal nephron, dislodge, and eventually pass into the urine. They form via precipitation of Tamm-Horsfall mucoprotein which is secreted by renal tubule cells, and sometimes also by albumin in conditions of proteinuria. Cast formation is pronounced in environments favoring protein denaturation and precipitation (low flow, concentrated salts, low pH).

Glomerular Hematuria RENAL MULTI-SYSTEM IgA nephropathy 4/11/2017 Glomerular Hematuria RENAL IgA nephropathy Alport syndrome Thin glomerular BM disease Post infectious MPGN MULTI-SYSTEM SLE nephritis HSP nephritis Wegener syndrome Goodpasture syndrome HUS Sickle cell Disease These will all be associated with proteinuria will have brown/tea colored urine

W/u for Glomerular Hematuria 4/11/2017 W/u for Glomerular Hematuria CBC C3, C4 antistreptolysin-O titer, streptozyme titer serum electrolytes, BUN, serum Cr, serum albumin test for lupus Hep B antinuclear cytoplasmic antibody titer Hep B because that can cause membranous nephropathy ANCA for Wegeners

Extraglomerular Hematuria 4/11/2017 Extraglomerular Hematuria Hematuria from lower urinary tract terminal hematuria blood clots nl urinary RBCs minimal proteinuria Terminal hematuria is when the onset of gross hematuria occurs at the end of the urine stream

Extraglomerular Hematuria 4/11/2017 Extraglomerular Hematuria UPPER URINARY TRACT pyelonephritis ATN papillary necrosis nephrocalcinosis thrombosis malformation SCD tumor PCKD LOWER URINARY TRACT cystitis urethritis urolithiasis trauma coagulopathy heavy excersise UPJ obstruction ureterocele Munchausen, MBP

W/u for Extraglomerular Hematuria 4/11/2017 W/u for Extraglomerular Hematuria serum creatinine urine culture sickle cell preparation in AA urinary Ca/Cr ratio C3,C4 U/S of kidneys/bladder to R/O polycystic kidney disease, tumor, ureteropelvic junction obstruction, and stones Based on your history and physical you will determine what tests you want to order

4/11/2017 Proteinuria For the boards...

Proteinuria Occurs in 10% of kids 8-15 yrs differentiate between 4/11/2017 Proteinuria Occurs in 10% of kids 8-15 yrs differentiate between renal disease transient benign

Proteinuria Dipstick detects mostly ALBUMIN negative (0 mg/dL) 4/11/2017 Proteinuria Dipstick detects mostly ALBUMIN negative (0 mg/dL) trace (10-20 mg/dL) 1+ (30 mg/dL) 2+ (100 mg/dL) 3+ (300 mg/dL) 4+ (1000-2000 mg/dL) False negatives may also occur if the protein in the urine is composed mainly globulins or Bence-Jones Proteins because the reagent on the test strips, Bromphenol blue, is highly specific for albumin

4/11/2017 Orthostatic proteinuria Transient proteinuria caused be temp >101oF excersise dehydration cold exposure CHF seizure stress Glomerular proteinuria is usually due to loss of albumin tubular proteinuria is usually due to loss of other proteins

Proteinuria What is your next step? 4/11/2017 Proteinuria A child comes into your office for a routine visit Screening urine dipstick reveals 1+ protein What is your next step?

Proteinuria R/O benign conditions sg >1.020 pH >7.5 mucoproteins 4/11/2017 Proteinuria R/O benign conditions sg >1.020 pH >7.5 mucoproteins acute illness Acute illnesses, excersise Once you have determined that none of these are what caused the + dipstick, you can move on to further evaluation.

Proteinuria Next step is to determine if this is transient or fixed 4/11/2017 Proteinuria Next step is to determine if this is transient or fixed R/O orthostatic proteinuria first am U/A W/u for persistent fixed proteinuria alb, C3, 24 hr urine protein Pr/Cr ratio W/u for glomerular hematuria if + RBCs

Let’s see who has been paying attention... 4/11/2017 Quiz Time Let’s see who has been paying attention...

4/11/2017 Quiz time #1 10 yr old boy coming in for school physical. Found to have 30 RBC/hpf on microscopic analysis. Fam Hx reveals uncle used to have “blood in his urine” What is your diagnosis? What is the diagnosis. You have something familial going on… Lets think about our differential for familial causes of hematuria

Quiz time #1 Familial Causes of Hematuria Polycystic kidney disease 4/11/2017 Quiz time #1 Familial Causes of Hematuria Polycystic kidney disease Thin basement membrane disease Alport syndrome (hereditary nephritis with deafness) Hypercalciuria with family history of nephrolithiasis Sickle Cell A family history of autosomal dominant polycystic kidney disease demands that this disease be ruled out by renal U/S. A family history of hematuria without renal failure may be seen with thin basement membrane disease. A family history of hematuria, chronic renal failure, dialysis, or renal transplantation with bilateral deafness at an early age and ocular abnormalities strongly suggests Alport syndrome. An audiogram is indicated for children suspected of having Alport syndrome because high-tone hearing loss may not be apparent on the initial examination. A family history of nephrolithiasis raises the diagnostic possibility of nephrolithiasis or hypercalciuria. Sickle cell disease or sickle cell trait in the patient's family may suggest this diagnosis a screening urinalysis in available first-degree relatives is an important test

Quiz time #2 Gross hematuria following a URI C3 is wnl 4/11/2017 Quiz time #2 Gross hematuria following a URI C3 is wnl What is your diagnosis? What two things could it be? Post strep IgA nephropathy how can you tell the difference?

IgA Nephropathy (Berger’s Disease) 4/11/2017 IgA Nephropathy (Berger’s Disease) IgA deposits seen on renal biopsy nl C3 elevated IgA in 15% often hypertensive need long-term f/u Assoc with viral URI or AGE 20-30% of children who have this will have progressive disease 15-20 years down the road

4/11/2017 Quiz time #3 This kid was in your office 2 weeks ago. Mom is calling and saying his urine looks like coca-cola. What is your diagnosis? This boy came into your office two weeks ago. His mom is calling the office saying is urine is tea colored. What is this boy’s diagnosis? impetigo What is it caused by? nephritogenic strain of GAS How do you diagnose it? Streptozyme (for skin), (ASO for throat) could this have been prevented with appropriate abx? NO What do you treat it with? What would you expect his C3 levels to be? LOW what happens to C3 level after 2 months? Returns to nl

Acute Post-Infectious Glomerulonephritis 4/11/2017 Acute Post-Infectious Glomerulonephritis Caused by nephritogenic GAS infections of the pharynx or skin Most children recover complete renal function C3 levels LOW initially, then return to NL after 6-8 wks may have BP, proteinuria, hematuria for up to 3 mos after initial presentation

Quiz time #4 3 yr old F with diarrhea 4/11/2017 Quiz time #4 3 yr old F with diarrhea 6 days later develops a rash, abdominal pain on PE, you note pallor and purpura

Quiz time #4 What is your diagnosis? 4/11/2017 You get a CBC and peripheral smear reveals fragmented RBCs

Hemolytic-Uremic Syndrome 4/11/2017 Hemolytic-Uremic Syndrome MCC of ARF in children Caused by shiga toxin producing E.coli O157:H7 HUS is most common in kids less than 4yrs preceded by AGE with fever, vomiting, bloody diarrhea E.coli transmitted by undercooked meat, unpasteurized milk this organism has a verotoxin which is absorbed by the intestine and initiate endothelial cell injury microangiopathic hemolytic anemia

Quiz time #5 Infant comes in with hematuria h/o constipation 4/11/2017 Quiz time #5 Infant comes in with hematuria h/o constipation h/o TEF repair What is your diagnosis? What is your diagnosis? VATER association V vertebral anomalies A anal atresia TE TEF R radial limb anomalies What is your next study? Chromosomes for genetic syndrome should be ruled out

VATER association V vertebral anomalies A anal atresia T E 4/11/2017 VATER association V vertebral anomalies A anal atresia T E R radial limb anomalies TEF

4/11/2017 Quiz time #6 14yo female with hematuria More “tired” lately

Quiz time #6 What is your diagnosis? What labs will you order? 4/11/2017 Quiz time #6 What is your diagnosis? What labs will you order?

SLE nephritis C3 and C4 will be LOW 4/11/2017 SLE nephritis C3 and C4 will be LOW Sometimes will only manifest as kidney disease WHO staging of nephritis Class IV is the most common and most severe form of nephritis

Quiz time #7 11 yr old boy with gross hematuria, edema. 4/11/2017 Quiz time #7 11 yr old boy with gross hematuria, edema. Initial labs reveal LOW C3 and C4 What is your diagnosis? How do you make definitive dx? You know it is something glomerular because of hematuria and proteinuria. Lab work helps you.

Membranoproliferative Glomerulonephritis 4/11/2017 Membranoproliferative Glomerulonephritis MPGN is the MCC of chronic glomerulonephritis in children renal biopsy confirms dx

Confused about complement? What three conditions cause hypocomplementemia? P post infectious GN M membrano proliferative GN S SLE

4/11/2017 Quiz time #8 last one! It is 10pm. You are the intern on call for purple. A 5th floor nurse pages you to tell you that ortho has just consulted you on one of their patients for hematuria.

Quiz time #8 You look through the chart and the all you can decipher is that she was in a car crash 2 weeks ago. You go to examine her and note she is in a full body cast, o/w NAD and afebrile. What is the one test you will order before you go back to your call room?

Quiz time #8 Answer: Urine Ca/Cr ratio!! urinary calcium:urinary creatinine ratio of > 0.21 24-hour urinary calcium excretion of >4 mg/kg

Hypercalciuria Idiopathic 30% Immobilization Hyperparathyroidism 4/11/2017 Hypercalciuria Idiopathic 30% 15% go on to have renal stones Immobilization Hyperparathyroidism Furosemide Vit D intoxication Renal ultrasonography and plain abdominal radiography are helpful in ruling out the presence of nephrocalcinosis or nephrolithiasis. The finding of hypercalciuria in a child who has hematuria should not exclude consideration of other etiologies of hematuria

Thank you for your attention!

4/11/2017 PREP specs Plan the evaluation of hematuria in a child with sickle cell disease.

4/11/2017 PREP 2005 #70 A previously healthy 10 yr old AA boy reports a 2 day history of back pain and gross hematuria. There is no history of trauma or passed kidney stones. His vital signs are normal, and PE reveals R CVA tenderness. His older brother has several similar episodes when he was younger, as did his mother when she was a child.

4/11/2017 PREP 2005 #70 You suspect that this boy has sickle cell trait and papillary necrosis. Of the following, the BEST test to confirm the diagnosis is: A. abdominal xray B. CT C. intravenous pyelography D. renal scintigraphy E. renal U/S Ab x-ray will not help you look for papillary necrosis CT may show papillary necrosis IVP renal scintigraphy is done when obstruction is present, show tracer uptake of functioning kidney renal U/S will show vague changes in the medulla but not specific for papillary necrosis

PREP 2005 #70 Correct Answer: C 4/11/2017 Hematuria results from microthrombosis secondary to sickling they want you to know that IVP is the best test to look for papillary necrosis the difference is hematuria and PAIN