Hematuria

Tbilisi referral hospital, Tbilisi, Georgia

Nephrologist
Nino Maglakelidze
Definition of Hematuria

•Visible by naked eye (macrohematuria/gross hematuria)

•Detectable only on examination (microhematuria);

•Urine sediment is gold standard for the detection of microscopic

hematuria (3 RBC or more per high – power field);

•Dipstick is more sensitive and detects 1 to 2 RBCs per high power

field;
Dipstick false positive tests:

•Semen, which is present in the urine after ejaculation may cause a

positive heme reaction on the dipstick

•An alkaline urine with a pH greater then 9

•The presence of myoglobinuria or hemoglobinuria;

Classification of hematuria

• Non glomerular hematuria;

•Glomerular hematuria;
Glomerular hematuria:

•Isomorphic RBCs

•Dysmorphic RBCs more than 40%;

•Acantocytes 5%

•>1 erythrocytic casts;

Non glomerular hematuria:

•Isomorphic erythrocytes

•Dysmorphic erythrocytes less than 40%;

Glomerular diseases and hematuria

•Immunoglobulin A nephropathy (IgA)

•Thin glomerular basement membrane

•Membranoprolipherative glomerulonephritis

•Alport ‘s syndrome
Transient hematuria

• Postinfective glomerulonephritis

•Exercise
 IgA nephropathy

Epidemiology
IgA nephropathy is accounts 45% of renal biopsies in East Asian and
Caucasian people;

Diagnosis:
Kidney biopsy is gold standard;
Morphology of IgA nephropathy:

Light microscope: Mesangial expansion, mesangial and

endocapillary proliferation and hypercellularity;
Morphology of IgA nephropathy:

Immunohistology:
Dominant mesangial deposits of IgA alone or with IgM or IgG;
Subendothelial capillary wall IgA deposts may also occur;
Morphology of IgA nephropathy:

Electron microscope:
Mesangial electrone dense-deposit are seen on electrone
microscope;
Clinical Features:

•40-50% of patients present with one or recurrent hematuria, often

accompanying upper respiratory infection, ,, synpharyngitic
hematuria”

•30-40% microscopic hematuria with mild proteinuria;

•Less than 10% nephritic syndrome or an acute rapidly progressive

glomerulonephritis characterized by arterial hypertension, edema
and renal insufficiency;
Treatment:

Long term treatment with ACE or ARB when proteinuria <1g;

If proteinuria >1g treatment with corticosteroids during 6 month

Cyclophsphamide 2.5mg/kg in combination with steroids during 3

months;
Then followed with Azathioprine 1.5 mg/kg;

Treatment with fish oil in case if proteinuria >1 g;

Mycophenolat mophetile - MMF?

Cyclosporine 3-5 mg/kg ?

 Alport’s Syndrome

Hereditary X-link disease

Mutation of genes which encodes alpha – 3; alpha-4 and alpha 5

chains of IV collagen;

IV collagen alpha chains are located in glomerular basement

membrane, eye and ear;

Alport syndrome can be autosomal recessive

COL4A3 or COL4A4 genes and accounts around 15%.

It can be also autosomal dominant , which arise from heterozygous

mutations ofCOL4A3 or COL4A4 genes and accounts 20- 30%;
 Alport’s Syndrome

Epidemiology

Alport ‘s syndrome account 3% in children with ESRD

and 0.2% in adults with ESRD
 Alport’s Syndrome

Clinical signs:

Renal manifestation:

•Asymptomatic persistent hematuria

•Recurrent episodes of gross hematuria

•Over time patient develops proteinuria,

•arterial hypertension and

•renal insufficiency;
 Alport’s Syndrome

Extra renal manifestation:

Ear

•Hearing loss occur in 85% of affected boys and 15% in females;

Ocular manifestation:

•Lens – regular conical protrusion

•Retinal changes, white and yellow granulation;
•Corneal changes, corneal erosion cause corneal pain;

Arterial disease:

•Aneurisms of the aortic or abdominal aorta;

 Alport’s Syndrome

Diagnosis:

•Renal or skin biopsy

•Molecular genetic test

•Positive family history of persistent hematuria

•Presentation with chronic kidney disease and sensor neural defense

and or characteristic ocular findings regardless of family history;
Morphology of Alport syndrome

Light microscopy : Podocyte hypertrophy specimen. Segmental

glomerular sclerosis. Irregular thickening of the glomerular
basement membrane.
Morphology of Alport syndrome
Immunofluorescence: Distribution of the α5(IV) chain in the kidney
and the skin basement membranes
 Morphology of Alport syndrome

Electron microscope:
Longitudinal splitting of the lamina densa of the glomerular
basement membrane;
 Alport’s syndrom

Treatment:

•Annual monitoring of microalbuminuria and proteinuria as soon as

the diagnosis of Alport syndrome is diagnosed;

•ARB is initiated when patient develop overt proteinuria;

•Over time patient will develop End Stage Renal Disease;

•Renal transplantation is preferred for the patients who develops

ESRD;

•Insignificant risk of developing anti-GBM disease after kidney

transplantation; (<3%);
 Thin basement membrane

Epidemiology:
Thin basement membrane accounts around 1 % in the
population;

Clinical signs:

•Microhematuria

•Gross hematuria and flank pain;

•Blood pressure and urinary protein excretion are typically

normal;
Pathogenesis of thin basement membrane

It has been suspected that the genetic defect in thin basement

membrane nephropathy (TBMN) would be similar to that in
hereditary nephritis (Alport syndrome).

This hypothesis was confirmed in families in which TBMN was

associated with heterozygous defects in COL4A3 or COL4A4, the
genes that encode the alpha-3 and alpha-4 chains of type IV
collagen.

Patients with TBMN can be considered "carriers" of autosomal

recessive Alport syndrome.
Morphology of thin basement membrane:

Light microscopy of thin basement membrane syndrome showing

minor abnormalities
Very rare it has been seen sclerotic changes of glomeruli
Morphology of thin basement mambrane
Results from immunofluorescence microscopy are negative for IgG,
IgA, IgM, Clq, C3 and fibrinogen.

Electron microscopy: irregular thinning of glomerular basement

membrane;
 Thin basement membrane

Treatment:

•No randomized controlled studies have evaluated the efficacy of

therapy in patients with thin basement membrane;

•In case of proteinuria ARB is beneficial for patients with thin

basement membrane

Prognosis:

•Excellent long-term prognosis ;

•Or slowly progressive renal insufficiency can occur
 Nutcracker syndrome:

Compression of the renal vein between aorta and proximal superior

mesenteric artery;

Clinical signs:

•Microhematuria

•Gross hematuria

•Microhematuria may be associated with pain in left flank.

 Polycystic Kidney disease

•Autosomal recessive polycystic kidney disease (ARPKD) is a recessively

inherited disease characterized by cystic dilations of the renal collecting
ducts and developmental defects of hepatobiliary ductal plate
remodeling, which result in varying degrees of congenital hepatic
fibrosis;

•Autosomal dominant polycystic kidney disease (ADPKD) is a dominantly

inherited characterized by cystic dilations in all part of the nephron;
•Cyst in liver, pancreas and other organs is also common;
 Polycystic Kidney disease

Genetics:

ARPKD is caused by mutations in the PKDH1 gene located on

chromosome 6P21;

ADPKD is caused by mutation in the PKD1 gene which is located on

chromosome 16 and PKD2 gene which is located on chromosome 4;
 Polycystic Kidney disease

Diagnosis:

•Family history of ADPKD

•Multiple cysts on ultrasonography or CT scanning

•Cysts may also be seen in the liver or pancreas

•Genetic testing for PKD1 and PKD2

Diagnosis

Ultrasound of polycystic kidney disease

Diagnosis

CT scan of polycystic kidney disease

 Autosomal dominant polycystic disease

Clinical signs :

•Hematuria (rupture of cyst in collecting duct)

•Mild proteinuria
•Urinary tract infection
•Concentrating defect (increased thirst, polyuria, nocturia and
urinary frequency);
•Arterial hypertension
•Progressive renal insufficiency
•Nephrolithiasis (Uric acid stones, rare calciumoxalate)
•Flank and abdomen pain
•Renal cancer – renal cell carcinoma;
Treatment:
•Sodium restriction
•Increased fluid intake
•ACE or ARB blockers
•Statins

Vasopressin receptor antagonist – TENPO trial – Tolvaptan

1157 patients
Annual decline of kidney function was better in Tolvaptan group
(2.61 vs3.81mg/ml);
Adverse events 0.5 in Tolvaptan group
Liver enzymes elevation, chest pain, headache;

mTOR inhibitor
SIRENA trial
Rapamycin stabilize cyst growth
No deference in decrease eGFR
 Autosomal recessive polycystic kidney disease

Diagnosis:

Ultrasound of kidney and liver

•Kidney of ARPKD on ultrasound are characterized by bilateral large
echogenic kidneys with poor corticomedullary differentiation;

•Liver – hepatomegaly , increased echogenicity and dilation of

peripheral intrahepatic ducts and main bile ducts;

CT scan or MRI of kidney and liver;

Molecular genetic tests of PKDH1 gene mutation;

 Autosomal recessive polycystic kidney disease
Clinical manifestation

Disease presentation:
•One third before 1 year
•Two third between 1 to 20 year
•One third after 20 year

Renal manifestation:
•Arterial hypertension
•Polyuria and polydipsia due to reduced concentration ability
•Recurrent episodes of urinary tract infection
•Urinary abnormality, proteinuria, glucosuria, hyperphsphaturia
•Metabolic acidosis due to decreased urinary acidification capacity
•Progressive renal impairment
 Autosomal recessive polycystic kidney disease

Liver:

•Portal hypertension due to congenital fibrosis

•Ascites
•Splenomegaly
•Esophageal variceal hemorrhage

Other findings:

•Feeding difficulties
•Thrombocytopenia
•Growth impairment
•Hyponatremia
 Autosomal recessive polycystic kidney disease

Management and treatment of patients of ARPKD

•Hypertension – ACE or ARB

•Hyponatremia – fluid restriction
•Supplemental nasogastric feeding to obtain adequate caloric
intake

Renal management – ESRD renal replacement therapy

•Hemodialysis
•Peritoneal dialysis
 Autosomal recessive polycystic kidney disease

Hepatic complications:

•Bacterial cholangitis – empiric antibacterial treatment

•Progressive portal hypertension