Haematuria A Challanging Medical Problem.mansfans.com

HAEMATURIA A Challenging Medical Problem By TAREK MEDHAT ABBAS, MD Lecturer of Nephrology Urology & Nephrology Center Mansoura University Egypt Urology & Nephrology Center, Mansoura University, Egypt

Haematuria Definitions: Normally the number of RBCs in urine should not be more than 5 RBCs/ high power field on microscopic examination of fresh centrifuged So, urine sample. haematuria is defined as a secretion of more than 5 RBCs/ HPF in urine. www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Dete ction & q uantification of hematur ia Screening test ( dipsticks ) - 0.02-0.03 mg/dL of Hb, myoglobin - ~5-20 RBC/mm³ Semiquantitative estimation - centrifugation of 10-15 ml of urine - resuspention of sediment in 1 ml of residual urine - high-power microscopy Counting chamber – the number of cells in 1 microliter of unspun urine Urology & Nephrology Center, Mansoura University, Egypt

Cl assi ficat ion of hematu ria Macroscopic - Microscopic Symptomatic - Symptomless Transient - Persistent www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Haematuria may be the only symptom or may be associated with other manifestations, according to the cause e.g. loin pain and fever with infection and renal colic with renal stones. Haematuria could be gross (causing redcoloured urine) or microscopic (urine appears normal but RBCs are seen on In gross microscopic examination). hematuria, urine looks red if alkaline, but brown or coca-cola like if urine is acidic due to denaturation of the hemoglobin. Urology & Nephrology Center, Mansoura University, Egypt

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Hematuria

Transient phenomenon of little significance

Sign of serious renal disease

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Cause s o f Hematuria Kidney disease Lesions along the urinary tract Conditions unrelated to kidney and urinary tract www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

First: PRE-RENAL Hemorrhagic blood disease Sickle cell anemia

Liver disease

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Use of anticoagulant

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Malignant hypertension

Urology & Nephrology Center, Mansoura University, Egypt

Haematuria of renal origin: 

Glomerular haematuria: Primary glomerular disease (e.g. IgA nephropathy, mesangial proliferative glomerulonephritis crescentic glomerulonephritis)

Secondary

or

glomerulonephritis

i.e. renal involvement is a part of systemic disease (e.g. post-strephococcal glomerulonephritis, HenochSchönlein purpura, SLE, polyarteritis nodosa).

Urology & Nephrology Center, Mansoura University, Egypt

Renal infection and tubulointerstitial diseases: Pyelonephritis, renal papillary necrosis, tuberculosis, and toxic nephropathies. Stone disease, idiopathic hypercalciuria Renal neplastic diseases: Renal cell carcinoma, transitional cell carcinoma of the renal pelvis and others. Hereditary renal diseases: Modularly, sponge kidney, polycystic kidney disease, Alport’s syndrome, and thin basement membrane disease. Urology & Nephrology Center, Mansoura University, Egypt

Loin-pain haematuria syndrome. Coagulation defect: use anticoagulant, liver disease thrombocytopaenia.

of and

Renal vascular disease: Renal infarction, renal vein thrombosis or malignant hypertension. Exertional haematuria. www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Haematuria of ureteral origin:  Nephrolithiasis. 

Malignancy.

 Ureteral inflammatory condition secondary to nearby inflammation e.g. diverticulitis, appendicitis or salpingitis.  Ureteral trauma e.g. during ureteroscopy.  Ureteral varices, aneurysms, or arteriovenous malformation. Urology & Nephrology Center, Mansoura University, Egypt

Haematuria of bladder origin:  Infection: schistosoma, bacterial cystitis.  Neoplasm.

viral

or

 Foreign body in the bladder e.g. stones.  Trauma: During instrumentation or accidental.  Drug: e.g. cyclophosphamide induced haemorrhagic cystitis.www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Hematuria of urethral (or associated structures) origin:  Urethritis: foreign body or local trauma to the urethra.  Prostate: Acute prostatitis, benign prostatic hypertrophy. www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Acute nephri ti c syndr ome Hematuria Proteinuria

Reduced renal function Edema Hypertension www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Idio path ic Hyp erc alciuria Definition: Calcium excretion > 4 mg/kg/day Urinary Ca/Creatinine > 0.2 Possible mechanism of hematuria: microcrystals damaging the tubular or mucosal epithelia. Resolution of hematuria with anticalciuric therapy Urology & Nephrology Center, Mansoura University, Egypt

Alport syndrome - her edi tary disorder of G BM

Autosomal dominant

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Autosomal recessive

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X-linked dominant

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Renal disea se Macro /Microhematuria Proteinuria Nephrotic syndrome Hypertension Renal failure- males Progressive or juvenile – 20 y Nonprogressive – 40 y Urology & Nephrology Center, Mansoura University, Egypt

Hearing defe cts Sensorineural bilateral Never congenital Boys- 85% . Girls – 18% < 15y Progression of hearing loss parallels renal impairment

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Diagnosi s of Alport sy ndrome

Hematuria with or without proteinuria Hypertension Renal failure Ocular defects – anterior lenticonus Familial hematuria Sensorineural hearing loss Progression to renal failure occurring in at least one affected subject Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

ALPORT’S SYNDROME

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Fam il ial benign essenti al hematuri a Familial hematuria without proteinuria and without progression to renal failure or hearing defect Diffuse attenuation of the GBM is usually considered the hallmark of the condition It’s non pathognomonic of FBEH Urology & Nephrology Center, Mansoura University, Egypt

Contin ue Autosomal dominant trait Normal antigenicity of the GBM

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Thi n base ment membr an e nephropathy Hematuria Proteinuria Attenuation of the GBM In children may be Alport In adults m/p benign disorder www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

HERE DITA RY NEP HR OP ATHY Benign Familial Hematuria

Alport Syndrome

Overlap of histological findings The prognosis appears to be depend more on the degree of clinical expression in other members of the family and less on the histological findings

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

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Hematuri a not repr ese nt ing ki dney o r uri nar y tract d isorder Following exercise Febrile disorders Gastroenteritis with dehydration Contamination from external genitalia Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Transient microscopic haematuria is relatively common. Up to 39% of adults between ages of 18 and 33 may have microscopic haematuria at least once, and up to 16% may have it in two or more occasions. Therefore, an extensive workup is not warranted except in high-risk patients, > 50 years of age and those patients with other clinical or urinary abnormalities. Urology & Nephrology Center, Mansoura University, Egypt

Patterns Of Haematuria Initial is usually urethral. Terminal hematuria is usually prostatic or bladder origin. Total hematuria is either bladder ureteral or renal origin. www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Differential Diagnosis of Haematuria: A. First, haematuria should be differentiated from other causes of red or brownish urine: Dipsticks (Hemastix) will be positive with haematuria, hemoglobinuria (hemolysis) and with myoglobinuria (muscle damage) but negative with other causes e.g. prophyrins (in porphyria), bile (in jaundice), melanin (in melanoma), alkaptonuria, food dyes and drugs as PAS or phenylphthalein. Microscopy will show RBC’s only with haematuria. Urology & Nephrology Center, Mansoura University, Egypt

False positive test for haematuria:  Haemoglobinuria.  Myoglobinuria.  Ascorbic acid.

False negative test for hematuria:  Highly diluted urine. Urology & Nephrology Center, Mansoura University, Egypt

 Haematuria could be glomerular (because of glomerular disease, sometimes called medical); or non glomerular (sometimes called surgical). Glomerular haematuria could be differentiated from non glomerular haematuria by: 1. The shape of RBCs in urine are small and dysmorphic in cases with glomerular haematuria while it will be normal in case of non glomerular haematuria. Urology & Nephrology Center, Mansoura University, Egypt

1. Means corpuscular volume of RBCs in urine

of patient with glomerular haematuria is smaller (< 72 FL) than that in peripheral blood, but in non glomerular cases is equal. 2. Proteinuria is present in most cases of glomerular hematuria but not in cases of non glomerular hematuria. 3. Casts, especially red cell casts are seen in glomerular haematuria. 4. Blood clots indicate non-glomerular bleeding and can be associated with pain & colic. 5. Three-glass test. Urology & Nephrology Center, Mansoura University, Egypt

Glo merular v ers us extr aglo meru lar b leedin g Urinary finding

Glomerular

Extraglomerular

Red cell casts

May be present

Absent

Red cell morphology Proteinuria

Dysmorphic

Uniform

May be present

Absent

Clots

Absent

May be present

Color

May be red or May be red brown Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Isolated Hematuri a (mi croscopic) No other urinary abnormalities No renal insufficiency No evidence for systemic disease Incidence ( school-aged children ) 4-6% - single urine examination 0.5-1% - repeated testing over 6-12 months

Urology & Nephrology Center, Mansoura University, Egypt

Et iol ogi es o f isol ated Hem at uria

Glomerular

- Benign Recurrent or Persistent Hematuria 1.Sporadic 2.Familial - IgA Nephropathy - Alport syndrome - PSAGN

Non-glomerular - Idiopathic Hypercalciuria - Cystic Kidneys - Urinary Tract obstruction - Tumors - Trauma

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Urology & Nephrology Center, Mansoura University, Egypt

He ma turia wit h f amil ia l associatio n Glomerular - Benign Familial Hematuria - Alport syndrome Non-glomerular - Idiopathic Hypercalciuria - Polycystic Kidney Disease - Urolithiasis - Tumors Urology & Nephrology Center, Mansoura University, Egypt

Approach to a case of haematuria First exclude haemoglobinuria and myoglobinuria since both of them can also cause positive dipstick test for haematuria. This is done by microscopic examination of fresh urine sample. In case of haematuria, RBCs could be seen while in the other two conditions no RBC’s could be seen. Urology & Nephrology Center, Mansoura University, Egypt

In case of myoglobinuria, clinical examination may show manifestations of muscle disease and the examination of urine by immunoelectrophoresis may show myoglobin. In case of haemoglobinuria, manifestations of haemolysis may be evident Urology & Nephrology Center, Mansoura University, Egypt

Eval uation of Hematuri a History Detailed review of family history hematuria proteinuria renal insufficiency deafness stones

Precipitating factors infection exercise

Abdominal pain HSP hydronephrosis pyelonephritis urolithiasis

Urology & Nephrology Center, Mansoura University, Egypt

History Taking Past history （ previous episodes, recent 　 food and drug ingestion, exercise, 　 instrumentation, menstruation… ） Dysuria ? Associated bladder irritability or flank pain ? Time of hematuria  initial: urethritis, stricture, meatal stenosis  total: bladder, ureter, kidney  terminal: bladder neck or prostatic urethra Urology & Nephrology Center, Mansoura University, Egypt

History Taking (2) Associated symptoms Fever, chills, other bleeding point, dyspnea, recent URI, Painful hematuria: stone, inflammation, cancer bladder, cancer prostate, SEP, trauma Painless gross hematuria  consider tumor Urology & Nephrology Center, Mansoura University, Egypt

Evaluat ion of Hemat uria Phys ical Ex amin ation I- GENERAL EXAMINATION: Growth failure Hypertension Pallor Edema Rash Examination of the skin for hemorrhagic spots Abdomen: search for a mass or tenderness General manifestations of the cause Urology & Nephrology Center, Mansoura University, Egypt

LOCAL EXAMINATION • External genitalia: bleeding

infection trauma PR examination: prostate or bladder cause Suprapubic tenderness or mass Tender loin Palpable renal mass www.MansFans.com Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

INVESTIGATIONS

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Study of hemorrhagic profile Blood picture: Sickle cell anemia Lymphoma leukemia

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Urine analysis Volume: low in nephritic syndrome Colour: red in macroscopic hematuria, smokey in nephritic syndrome Bilharzial ova Crystals Malignant cells Urology & Nephrology Center, Mansoura University, Egypt

Examination of urine for:  Proteinuria.  Casts.(RBC in nephritic syndrome, PUS cells in UTI, WBC in pyelonephritis)  Pus.  Bacteria (specific and non specific)  Culture (Ordinary and special)  PCR (TB-DNA)

Urology & Nephrology Center, Mansoura University, Egypt

Radiological investigations Ultasound, plain X-ray, I.V.P. (if serum creatinine is normal), CT, MRI and possibly angiography, for the diagnosis of surgical diseases e.g. stone, malignancy, infection, or malformations. Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

Urology & Nephrology Center, Mansoura University, Egypt

OTHER INVESTIGATIONS RBCs in urine could be examined for its shape to differentiate glomerular (small, distorted) from non glomerular causes (by phase contrast microscopy). Kidney function tests. Specific investigations for diagnosis of systemic disease causing haematuria e.g. SLE. Endoscopic study: to diagnose neoplastic disease , UB ulcers Kidney biopsy: for glomerular haematuria. Urology & Nephrology Center, Mansoura University, Egypt

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Dipstick+

Yes

Transient cause? • Sexual intercourse • Menstruation • Vigorous exercise • Infection • GU instrumentation

Biopsy Cystic disease Nephrology referral

Yes

RBCs present NO

Repeat UA when condition resolved

Nephrology referral

Uriinalysis (UA) with microscopy

Persistent hematuria

Yes

Glomerular etiology? • Proteinuria > 500 mg/24 hr • UA shows RBC casts +/- dysmorphic RBCs • Renal insufficiency

Appropriate work up and therapy

NO Imaging: • Ultrasound

• Hemoglobinuria • Myoglobinuria

• Spiral CT

• Mass • Hydronephrosis • Stricture

• Age > 50 • Aromatic amine exposure • smoker

Urology referral • Cysto+/• Cytology

Evaluation of haematuria

Age < 50 Surveillance

Work-u p o f a chil d wi th Hematuri a Phase I: Urinalysis ( sediment examination ) RBC’s morphology Urine culture BUN, Creatinine, Proteins, Electrolytes Antibodies against strept. & other antigens Complement, ANF, Immunoglobulins Renal US Urinalysis of 1st degree relatives 24h urine collection: Ca, Creat.,Protein, UA

Phase II:

Hearing test Cystoscopy Renal biopsy

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Iso la ted h ematuria The child needs to be monitored for the appearance of new clinical signs: hypertension proteinuria changes in the pattern or severity of hematuria If there is no change in the first year,observation at yearly intervals is adequate Urology & Nephrology Center, Mansoura University, Egypt

Is ola te d h ematu ria Possible outc ome

Disappearance of hematuria Hematuria will persist follow-up should be continued The hematuria will no longer be “isolated” - further investigation Urology & Nephrology Center, Mansoura University, Egypt

Most common causes of hematuria by age and sex Age/sex 0-20

Common causes AGN, UTI, congenital urinary tract anomalies with obstruction 20-40 male UTI, stones, bladder tumor 40-60 female bladder tumor, stone, UTI >60 male BPH, bladder tumor, UTI >60 woman Bladder tumor, UTI

Urology & Nephrology Center, Mansoura University, Egypt

Treatment Of Haematuria Treatment of the cause. Haemostatic e.g.:  Cyclokapron.  Vitamin K  DDAVP  Frish frozen plasma.

 Haematenics and blood transfusion. Urology & Nephrology Center, Mansoura University, Egypt