EVALUATION OF THE PATIENT

WITH HEMATURIA AND/OR

PROTEINURIA

DR IFIORA
F.A
16/02/2010
 PMhx  Introduction
 Obstetric hx  Overview
 FSHx  Pathogenesis
 Review of systems  Pathology
 Examination  Epidemiology

 Investigations
 Definitions
 Hematuria
 Conclusion
 proteinuria
 history

OUTLINE
 INTRODUCTION 1
OVERVIEW 1

Patients with glomerular disease usually have hematuria with variable degrees
of proteinuria
Also extraglomerular diseases
UTI

Urolithiasis

Tubular disorders
Glomerular disease can be
Primary glomerular disease
Systemic dz with glomerular involvement
Hereditary diseases
 INTRODUCTION 2
OVERVIEW 2

The Glomerular Syndromes

[common to Glomerular diseases]
Acute nephritic • Hematuria, azotemia, variable proteinuria, oliguria, edema,
syndrome and hypertension
Rapidly progressive Acute nephritis, proteinuria, and acute renal failure
glomerulonephritis
Nephrotic syndrome Urine prot.>40mg/m²/hr, hypoalbuminemia, edema
± hyperlipidemia ± lipiduria
Chronic kidney Kidney injury[proteinuria] for > 3 months with
disease
progressive decline in GFR.
Asymptomatic
hematuria or Glomerular hematuria; subnephrotic proteinuria
proteinuria
RIFLE CRITERIA FOR ACUTE RENAL DYSFUNCTION
Non-Oliguric Oliguric
Abrupt (1-7 days)
Decreased UO relative to

Specificity
Risk decrease (> 25%) in GFR or
Scr x 1.5
the fluid input
Sustained (> 24 hrs) UO < 0.5/ml/kg/h x 6hr
Adjusted creat or GFR UO < 0.5/ml/kg/h
Injury decrease> 50% or x 12 hr ??
Scr x 2

Adjusted creat or GFR

decrease > 75% UO < .5/ml/kg/h ARF ~ earliest
Failure Scr x 3 or Scr > 4mg% x 24 hr time point for
When acute > 0.5mg% Anuria x 12 hrs provision of RRT

Loss Irreversible ARF or persistent

ARF > 4 wks
Loss of renal fxn.
ESRD [ie failure] for > 3 months
STAGES OF CKD
 INTRODUCTION 3
OVERVIEW 3

 Histologic pictures of glomerular diseases are common to

the glomerular syndromes
 One or more of 4 basic tissue reactions
 Extra glomerular diseases that manifest haematuria
and/or proteinuria include
 UTI
 Urolithiasis
 Toxic nephropathies
INTRODUCTION 4
PATHOGENESIS OF GLOMERULAR INJURY 1

 May be the result of

 Genetic disorder
 Immunologic disorder
 Coagulation disorder
12
INTRODUCTION 5
PATHOGENESIS OF GLOMERULAR INJURY 2:NORMAL KIDNEY/GLOMERULUS 1
NORMAL KIDNEY/GLOMERULUS 2
ARSIACA
NORMAL KIDNEY/GLOMERULUS 3
NORMAL KIDNEY/GLOMERULUS 6
NORMAL GLOMERULUS 7
NORMAL KIDNEY/GLOMERULUS 4
NORMAL KIDNEY/GLOMERULUS 5
Introduction 6
PATHOGENESIS OF GLOMERULAR INJURY
3
Normal glomerulus: light microscopy
INTRODUCTION 7
PATHOGENESIS OF GLOMERULAR INJURY 4
Electron micrograph of the normal glomerular capillary (Cap) wall
demonstrating the endothelium (En) with its fenestrations (f), the
glomerular basement membrane (B) with its central dense layer, the
lamina densa (LD), and adjoining lamina rara interna (LRI) and
externa (LRE) (long arrow) and the epithelial cell foot processes (fp)
with their thick cell coat (c
Introduction 8
PATHOGENESIS OF GLOMERULAR INJURY
Cellular
5 location of injury during glomerulonephritis
(From Chadban SJ, Atkins RC: Glomerulonephritis.
Lancet 2005;365:1797–1806.)
INTRODUCTION 9
PATHOGENESIS OF GLOMERULAR INJURY
6
Genetic disorders

 Mutations affecting protein components of glomerulus

 Exons of DNA
 Regulatory regions of above
 Abnormal post transcriptional modification
 Abnormal post translational modification
INTRODUCTION 10
PATHOGENESIS OF GLOMERULAR INJURY 7

Immune mechanisms
 Commonest cause of glomerular injury
1. Anti body mediated injury
In-situ-immune complex deposition
 Fixed intrinsic tissue antigens eg Collagen type IV
 Planted antigens
 Exogenous[infectious agents, drugs]
 Endogenous[Immunoglobulins, immune complexes]
Circulating immune complex deposition
Leads to complement activation
 Endogenous antigens
 Exogenous antigens
 Cleared in acute infections eg PSGN cf SLE etc
 Cytotoxic antibodies
ANTIBODY-MEDIATED GLOMERULAR INJURY CAN RESULT EITHER FROM THE DEPOSITION OF CIRCULATING
IMMUNE COMPLEXES (A) , FROM IN SITU FORMATION OF COMPLEXES EXEMPLIFIED BY ANTI-GBM DISEASE (B)
OR HEYMANN NEPHRITIS (C). D AND E, TWO PATTERNS OF DEPOSITION OF IMMUNE COMPLEXES AS SEEN BY
IMMUNOFLUORESCENCE MICROSCOPY: GRANULAR, CHARACTERISTIC OF CIRCULATING AND IN SITU IMMUNE
COMPLEX NEPHRITIS (D) AND LINEAR, CHARACTERISTIC OF CLASSIC ANTI-GBM DISEASE (E).
INTRODUCTION 11
PATHOGENESIS OF GLOMERULAR INJURY 8

2. Cell mediated immune injury

 Sensitized Tcells implicated
INTRODUCTION 12
PATHOGENESIS OF GLOMERULAR INJURY 9

Coagulation disorders

 Activated directly after endothelial cell injury

 Indirectly after complement activation
 Fibrin deposits may occur within glomerular capillaries or within the
bowman space in crescent
INTRODUCTION 13
PATHOGENESIS OF GLOMERULAR INJURY
10
Progression of glomerular diseases

 Outcome of injury from above three depends on

 Initial severity of renal damage
 Nature and persistence of antigens
 Immune status, age , and genetic predisposition of the host.
 Once any insult decreases functioning nephrons, and ↓ GFR to 30-50%[ie 50-
80% ↓], progression to ESRD progresses at a relatively constant rate. The
secondary factors that leads to this have 2 histologic appearances
 FSGS
 Tubulointerstitial fibrosis
FSGS

Ssee next slide for mechanism

 INTRODUCTION 14
PATHOLOGY 1

 Glomerulus may be injured by several mechanisms,but has limited no:

of histopathologic responses
 Different dz states may have similar histologic appearance
INTRODUCTION 15
PATHOLOGY 2

1. HYPERCELLULARITY
increase in cell nos: in glomerular tufts xrised by one of
a. cellular proliferation of mesangial or endothelial
cells
b. crescent formation [accum. of cells composed
of proliferating parietal epith. Cells and infilterating
leucocytes] induced by presence of fibrin, in bowmans
space
c. leucocyte infilteration
ACUTE PROLIFERATIVE GLOMERULONEPHRITIS. A, NORMAL GLOMERULUS. B,
GLOMERULAR HYPERCELLULARITY IS DUE TO INTRACAPILLARY LEUKOCYTES AND
PROLIFERATION OF INTRINSIC GLOMERULAR CELLS. C, TYPICAL ELECTRON-DENSE
SUBEPITHELIAL "HUMP" AND A NEUTROPHIL IN THE LUMEN.  (COURTESY
OF DR. H. RENNKE, BRIGHAM AND WOMEN'S HOSPITAL, BOSTON, MA
INTRODUCTION 16
PATHOLOGY 3

2. BASEMENT MEMBRANE THICKENING

light microscopy: thickening of cap. Walls
electron microscopy: deposition of
immune complexes
subepithelial
subendothelial
within GBM
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS,
SHOWING MESANGIAL CELL PROLIFERATION, INCREASED
MESANGIAL MATRIX (STAINING BLACK WITH SILVER
STAIN), BASEMENT MEMBRANE THICKENING
ELECTRON MICROGRAPH OF A BIOPSY SPECIMEN FROM A CHILD WITH
ALPORT SYNDROME DEPICTING THICKENING, THINNING, SPLITTING,
AND LAYERING OF THE GLOMERULAR BASEMENT MEMBRANE
EFFACEMENT OF FOOT
PROCESS
 INTRODUCTION 17
PATHOLOGY 4

3. HYALINISATION AND 4 SCLEROSIS

• hyalinisation is a light microscopy finding of accumulation of
homogenous eosinophilic material
• electron microscopy shows these to be extracellular amorphous
substances consisting of plasma proteins exuded into glomerular
structures,obliterating capillary lumina: [sclerosis]
FOCAL SEGMENTAL GLOMERULOSCLEROSIS, PAS STAIN. A, LOW-
POWER VIEW SHOWING SEGMENTAL SCLEROSIS IN ONE OF THREE
GLOMERULI (AT 3 O'CLOCK). B, HIGH-POWER VIEW SHOWING
HYALINE INSUDATION AND LIPID (SMALL VACUOLES) IN SCLEROTIC
AREA.
STAGES OF GLOMERULOSCLEROSIS
DEVELPT. OF TUBULOINTERSTITIAL
FIBROSIS
INTRODUCTION 18
PATHOLOGY 5

 Above 4 histologic changes subdivided

 diffuse [involving all glomeruli]
 focal [only a proportion of glomeruli]
 global [involving the entire glomerulus]
 segmental [affecting a part of each glomerulus]
 INTRODUCTION 19:
EPIDEMIOLOGY 1

 Hematuria: 0.5% of school aged children

 Proteinuria: 10% of children aged 8-15 yrs
 All ages: UTI,urolithiasis,toxic nephropathy
 1st 3 months: congenital nephrotic syndrome
finnish type
2° to TORCHS,HIV
PSAGN in tropics
 <4yrs: HUS
INTRODUCTION 20:
EPIDEMIOLOGY 2

 2-6yrs: idiopathic nephrotic syndrome

M:F ratio-2:1
80%-90% :MCNS
 3-5yrs: PSAGN [in tropics]
cold weather:pharyngitis[12]
warm weather:pyoderma[49]
M:F ratio- 2:1
 5-12yrs: PSAGN[in UK]
 2nd decade: other 2° nephrotic syndrome[>8yrs]
membranous glomerulonephritis
membranoproliferative glomerulonephritis
Alport syndrome
3-15yrs: HSP[PATHOLOGY:LEUKOCYTOCLASTIC VASCULITIS ]
 b) Heme +ve
DEFINITIONS hemoglobinuria
-ve in urine
acute i. porphyria
1. HEMATURIA: 5RBC/Ul microscopy
myoglobinuria
Ensure per urethra hematuria
a) heme –ve [-ve dipstick] glomerular
drugs: coke coloured
chloroquine dysmorphic RBC’s
metronidazole RBC casts
rifampicin ±proteinuria
fe sorbitol lower urinary tract
salicylates total or terminal
urinary metabolites: red urine
homogentisic a. normal RBC morph.
metHb,porphyr three glass test
tyrosinosis,urate
 DEFINITIONS 2
 Asymptomatic hematuria
 Isolated microscopic hematuria, and no other hematuria
in at least 2 additional urine sedimentsover a 1-2 week period: NO FURTHER EVALUATION
REQUIRED
 Persistent asymptomatic isolated microscopic hematuria of longer than 2 week duration e.g. Thin
Glomerular Basement Memb. Dz.
 Urine culture for UTI: dipstick in UTI: pyuria[>10 WBC/ uL uncen.ur.]
leucocyte esterase

nitrites
CRITERIA FOR UTI
+VE URINALYSIS
SYMPTOMS
100 CFU/ml[10⁵ in asymptomatic patients]
 Ca and creatinine conc .in culture –ve patients
 Ca/cr >0.2 :idiopathic hypercalciuria[a cz. Of urolithiasis]
 24 hr. Urinary calcium >4mg/kg
 Hb electrophorescis
 Renal and bladder USS
 Tumors,cystic lesions,hydronephrosis,urolithiasis
 S/E/U/CR : helps define renal failure
 DEFINITIONS 3

 PROTEINURIA
 Differentiate- proteinuria of renal dz.
[symptomatic and/or significant perst]
transient proteinuria
[asymptomatic,not persist × 3/7]
orthostatic proteinuria
[asymptomatic,persist if not 1st morn]
 10% children,8-15 yrs have proteinuria
 1% of above have persistent proteinuria
 HENCE, COLLECT 1st MORNING VOIDED URINE for 3 consecutive days.
 DEFINITIONS 4

false positive
a) Urine dipstick[qualitative] gross hematuria
primarily albuminuria antiseptic agents
negative urinary pH>7
trace :10-20mg/dl highly conc. Urine
+1 :30mg/dl consider positive if
+2 :100mg/dl ≥+1 if S.G≤1.O15
+3 :300mg/dl ≥ +2 if SG >1.015
+4 :1000-2000 If pt. is symptomatic
false negative hematuria
dil. Urine S.G<1.OO5 hypertension Evaluate as
non alb. proteinuria renal function Glomerular
disease

DEFINITIONS 5
b) For persistent asymptomatic p. ,
assess significant proteinuria with
quantitative tests
 Urine prot./Cr. Ratio
 <2yrs: ≥0.5 significant
 >2yrs: ≥0.2 significant
>1 nephritic range
>3 nephrotic range
 Timed[24hr]urine protein
 More precise,cumbersome
 Normal: ≤4mg/m²/hr
 Abn.:4-40 mg/m²/hr
 Neph.range: >40 √
Asymptomatic patients with low
c)
grade iso. prot.:
[urinary prot./Cr. - 0.2-1]
 Ren. biopsy not indicated
 Transient or resolving
 Pathology of an evolving CKD,may
not yet show
 Hence, re-evaluate every 4-6 months:
 Physical exam.[+Bld. Pr.]
 Urinalysis
 Serum creatinine
 Urine prot./Cr. ratio
 Indication for ren. Biopsy
 Urine Prot/Cr. Ratio >1
 Hematuria
 Hypertension
 Reduced renal function
 EVALUATING THE PATIENT
1. HISTORY
a. Coke-coloured urine-glomerular hematuria
b. Red urine
c. Edema
i. Nephritic /Nephrotic syndrome
i. Post infectious glomerulonephritis
ii. IgA nephropathy
iii. Membranoproliferative glomerulonephritis
iv. HSP nephritis
v. HUS
vi. SLE nephritis
vii. Wegener granulomatosis
viii. Microscopic polyarteritis nodosa
ii. ARF
iii. CKD
d. Frequency,dysuria,unexplained fevers: UTI
e. Unexplained bruising: child abuse
f. Hemoptysis: Goodpasture S/Goodpasture dz.
g. Bleeding diathesis: Hemorrhagic disorders
h. Headache,epistaxis,visual changes,easy fatiguability:Htn/Ht. Failure
 EVALUATING THE PATIENT 2
2. PAST MEDICAL HISTORY
a) Age at onset:
i. Aetiology
ii. prognostication
b) Recent URTI
i. AGN: 1-2 weeks
ii. HSP nephritis
iii. IgA nephropathy 1-2 days
iv. Alport syndrome
c) Recent skin infection
i. AGN 3-6 weeks
d) Recent GIT infection
i. HUS
ii. IgA nephropathy
e) Hand foot syndrome/blood transfusions
i. SCD
 EVALUATING THE PATIENT 3

3. DRUG HISTORY
a. Nephrotic syndrome d interstitial nephritis
i. ACE inhibitors cephalosporins
ii. NSAIDS cimetidine
iii. Penicillamine mannitol
b. Renal vasculitis neomycin
i. Hydrallazine NSAIDS
ii. Isoniazid methicillin
iii. Sulphonamides radiocontrast agents
c. Nephrolithiasis rifampicin
i. Furosemide salicylates
ii. Vitamin D streptomycin
iii. Allopurinol cotrimoxazole
 EVALUATING THE PATIENT 4

Calculation
Of GFR

4. OBSTETRIC HISTORY
a. Birth weight
b. G.A at delivery
 EVALUATING THE PATIENT 5

5. FAMILY MEDICAL AND SOCIAL HISTORY

a. Sickle cell dz/trait

b. some genetic diseases predispose to Urolithiasis.

i. Cystinuria
ii. 1º hyperoxaluria
iii. Type 1 RTA
iv. Cystic fibrosis
c. IgA nephropathy:Ch 6q22-23
d. Alport syndrome:X-linked;AD;AR
e. Thin GBM disease
f. Benign familial hematuria
g. Polycystic kidney disease
h. SLE
EVALUATING THE PATIENT 6

6. EXAMINATION
a. General examination
 Signs of heart failure: Nephritic syndrome
 Rash: SLE nephritis, HSP nephritis
 Edema,weight gain
b. Digestive/urinogenital system
 Unilateral or bilateral flank mass
 Renal vein thrombosis
 ARPKD
 ADPKD
 Tumors

 Ascites(nephrotic syndrome)
 Tender hepatomegaly [heart failure]

EVALUATING THE PATIENT 7

EXAMINATION 2
c. Central Nervous System
 Uraemic encephalopathy [renal failure]
 Seizures: Alport syndrome
 Sensoryneural hearing loss: Alport syndrome

EVALUATING THE PATIENT 8

EXAMINATION 3
d. Respiratory system
 Signs of pleural effussion: heart failure

EVALUATING THE PATIENT 9

EXAMINATION 4
e. Cardiovascular system
 Hypertension: nephritic syndrome
 Signs of heart failure: nephritic syndrome

EVALUATING THE PATIENT 10

EXAMINATION 5
 OTHER INVESTIGATIONS
[1-6:GLOMERULAR PROTEINURIA/HEMATURIA]

1. FULL BLOOD COUNT

a. Anemia
i. SLE [coombs +ve hemolytic;a. Of chronic disease]
ii. RVT [microangiopathic hemolytic]
iii. HUS [microangiopathic hemolytic+ARF]
iv. ARF
v. CRF
b. Leukopenia
i. SLE
c. Thrombocytopenia
i. SLE
ii. RVT
iii. HUS
OTHER INVESTIGATIONS 2
2 SERUM ALBUMIN:
 <2.5g/dl in nephrotic syndrome
3 SERUM CHOLESTEROL
 Reduced in nephrotic syndrome
4 CXRAY
 Cardiomegaly and pulm. Congestion in Ht. failure
5 ASO titre
 PSAGN following pharyngeal infections
 MPGN
6 SERUM C3
 Low in :PSAGN[differentiates from IgA nephropathy]
MPGN [diff. from PSAGN by chronicity, >2months]
SLE
7 Ophthalmoscopy:anterior lenticonus ALPORT
8 Audiogram:sensorineural hearing loss SYNDROME
 OTHER INVESTIGATIONS 3

9. Plain abdominal X-ray

10. Abdominal USS
11. IVU
12. MCU
In suspected:UTI esp in males
urolithiasis
obstructive uropathies
 RENAL BIOPSY
INDICATIONS

 Non nephrotic proteinuria: urine p/Cr >1

 Nephrotic syndrome
 Steroid resistant
 Steroid dependent b/4 commencing cyclophosphamide
 ARF with unclear diagnosis
 Unexplained CKD
 Renal transplant dysfunction
 Persistent microscopic or recurrent gross hematuria, associated
with any of:
 Decreased renal function
 proteinuria
 Hypertension
 Uncooperative patient  Multiple cysts

 Uremia  Solitary kidney

 Uncontrolled Htn.  Perinephric abscess

 Unc. Bleeding diasthesis  Renal neoplasm

RENAL BIOPSY 3
CONTRA-INDICATIONS
 FBC
 Coagulation profile
 SE/U/Cr
 Urinalysis
 Urine MCS
RENAL BIOPSY 4
PRE-BIOPSY INVESTIGATIONS
RENAL BIOPSY 5
BIOPSY NEEDLES TRUCUT NEEDLE
MANUALLY OPERATED, SHEATHED NEEDLE
MEDITECH NEEDLE
SPRING LOADED, SHEATHED NEEDLE
MONOPTY NEEDLE
SPRING LOADED, SHEATHED NEEDLE
PERCUTANEOUS RENAL BIOPSY
PROCEDURE
 caudal pole of the left kidney should be used .
 The patient should be positioned prone with a firm
pillow under the abdomen.
 Two percent lignocaine should be infiltrated from the
skin down to the kidney and a 5-mm incision made.
 Biopsy is done.
 The patient is then asked to breathe normally and
then to take frequent liberal fluid thereafter. Local
pressure on the biopsy site should be exerted with a
pillow.
 Vital signs are recorded every 15 minutes for about
four hours and thereafter every half-hour. The
appearance of the urine passed hourly is observed
during this period in a urine rack kept for that
purpose. Hemoglobin level estimation is checked at
approximately four-to-six hours after the procedure.
 COMPLICATIONS OF
PERCUTANEOUS RENAL BIOPSY
 Pain.
 Haemorrhage such as persistent haematuria and
perirenal haematoma.
 Arteriovenous fistula.
 Biopsy of other organs e.g. liver and spleen.
 Death. A mortality of 0.2% reported in the 1970s but
none was described in 3 large series from 1990s.
CONCLUSION
Thank you