Syndromes in Nephrology

Acute nephritis
Glomerulopathies
Acute renal failure
Chronic kidney disease
Urinary tract infection
Polycystic kidney symptomatic
Urinary tract obstruction
Nephrolithiasis
Hypertension
Renal tubular defects

Cross-Section of the Kidney

Nephron
Renal Medulla
Papilla
Renal Cortex
Branch of the
Renal Vein
Branch of the
Renal Artery

R E NAL ANAE M I A

Renal Vein
Renal Artery
Renal Pelvis
Ureter

Manifold Tasks of the Kidney

Bone
BoneStructure
Structure

Metabolic
Metabolic
End
EndProducts
Products

Blood
BloodFormation
Formation
Calcium
Balance

Vitamin D
Activation
Erythropoietin
Synthesis

Removal of
Urea, Creatinine etc.

Functions

Water Balance

Potassium
Balance
Recovery of
Bicarbonate
Cardiac
CardiacActivity
Activity

R E NAL ANAE M I A

Sodium
Removal
Regulation
RegulationofofBlood
BloodpH
pH

Blood
BloodPressure
Pressure

GLOMERULONEPHATIES

dr Haerani Rasyid, MS, SpPD, K-GH

dr Hasyim Kasim , SpPD, K-GH
Prof Dr dr Syakib Bakri, SpPD, K-GH
Division of Nephrology
Department of Internal Medicine
Faculty of Medicine, Hasanuddin University

Glomerulopathies

Glomerulopathy : a group of diverse conditions including, but not lim

to, glomerulonephritis having in common the fact that the dis

process begins in the glomerulus or that the glomerulus is the m

importantly diseased part of the nephron.

Glomerulopathies are the most common causes of end-stage renal dis

Classification
Clinical

Presentation (5 Clinical manifestation).

Histopathological Classification: (percutaneus
biopsy and open biopsy).
Etiology and Pathogenesis Classification.
Immunological Classification.

Clinical Presentations of glomerular disease

Asymptomatic
Proteinuria 150mg to 3g/day
Hematuria > 2 red blood cells
Perhigh-power field (> 10x106 cells/L
In spun urine (red blood cells
Usually dysmorphic

Nephritic
syndrome
Oliguria
Hematuria : red cells casts
Proteinuria; usually < 3g/day
Hypertension
Oedema
Abrupt onset

Nephrotic
syndrome
Proteinuria; adult > 3,5 g/day
Child > 40 mg/h per m2
Edema
Hypercholesterolemia
Lipidemia

Rapidly progressive glomerulonephr

Renal failure over days/weeks
Chronic glomerulonephritis
Hypertension
Renal insufficiensy
Proteinuria > 3 g/day
Shrunken smooth kidneys

Proteinuria usually < 3 g/day

Hematuria; red cell casts
Blood pressure often normal
May have other features of vasculitis

Clinical syndrome

Manifestation

Major etiologies

Asymptomatic proteinuria

Urinary protein excretion < 2 g/d

Low-grade glomerular disease

( IgA nephropathy, MN or
MPGN)
Heriditary glomerular disease
(Alports syndrome)
Tubulointerstitial disease

Asymptomatic hematuria

Urinary RBCs > 2/ HPF (spun

sediment)

Low-grade glomerular disease

( IgA nephropathy, Thin
basement membran disease)

Nephrotic syndrome

Heavy proteinuria (>3,5 g/d),

edema, high serum cholesterol,
urine lipids

MCNS, FSGS, MN, MPGN

Diabetic nephropathy
Amyloid (myeloma, LCDD)
Fibrillary GN

RPGN

Presents as GN with ARF (oliguria,

rising serum creatinin)

Anti GBM nephritis

(Goodpastures)
Vasculitis Syndromes
(Wegeners polyangiitis, HSP,
mixed cryoglobulinemia)
Immune-complex associated
(IgAN, poststrep GN)

Nephritic syndrome

RBCs, RBC cast, proteinuria,

hypertension, renal disfunction.

Poststreptococcal AGN
Other post infectious GN
(abcess, endocarditis)
IgA nephropathy
LN (WHO class III/ IV)

GLOMERULONEPHRITIS
Glomerulonephritis (GN)
o

Initially coined by Klebs (1889).

A group of diseases occuring either as primary

renal disorders or a secondary manifestation of
a sistemic disease state.

Inflammation within the glomerulus.

Renal manifestation of hematuria, proteinuria

and impaired glomerular filtration

Unpredicteble disease course make clinical

management problematic

DEFINITION
Glomerulonephritis: (GN) injury with
evidence of inflammation such as
leukocyte infiltration, antibody deposition,
and complement activation.
GN primary: pathology is confined to the kidney.
GN secondary: when part of a multisystem
disorder.

Dwi-Lestari

EM : Normal glomerular c

Dwi-Lestari

NOMENCLATURE

Acute:

glomerular injury occurring over days or

weeks.
Sub

acute or rapidly progressive (RPGN): over

weeks or a few months.

Chronic:

over many months or years.

Injury Localization
1.

Overview of slides : assesses injury and

localizes to the specific anatomic compartment
(glomerular/ vascular/ tubulointerstitial).

2.

Assessment of type of injury, extent of injury in

each glomerulus.
Terminology : diffuse, focal, global and segmental.

Diffuse : at least 60% glomeruli involved.

Focal : some glomeruli < 60%.

Global : involved 1 glomerulus as a whole.

Segmental : part of 1 glomerulus.

 Proliferative

: glomerular cell number

(intracapillary and extracapillary)
A crescent: is a half-moon shaped. Cells in
Bowman`s space.
Membranous : expansion of the GBM by
immune deposits.
Sclerosis : non-fibrilar extracellular material
Fibrosis : Collagens type I and III

Mechanism of Injury in Glomerulonephritis

Immuno pathogenesis
Genetic
Influence

Inflammation

Resolution

Genetic
Influence
Scarring

Variable rate
of progression

Renal Failure

Immunologic Mechanism of Glomerular Injury

In situ antigen-antibody interaction (1)

Exogenous planted antigens (1)

Circulating immune complexes (2)
Intrinsic glomerular antigen (3)
Cell-mediated mechanism (?)

Activation
of
mediators
of
glomerular
injury

Activation
of
mediators

Mechanism of Immune Renal Injury

Etiologic Agent

Infections
Loss of tolerance

IR Genes

Immune Response
Antibody
IgG, IgA

T Cells

Deposit Formation
In situ, complex trapping

Mediation
Complement, Chemokines

Cytokines, Vasoactive

Effector Cells
PMNs, macrophages
Proliferation, PDGF

Glomerular cells (mesangial prolif)

Response

Sclerosis, TGF -

Complement activation

NEPHROTIC SYNDROME

Nephrotic syndrome

Clinical entity having miltiple causes and characterize

by increased glomerular permeability manifested
by massive proteinuria and lipiduria.
Massive proteinuria > 3.5 g/day/1.73m2 body surface
in the absence of a depressed GFR.

Nephrotic Syndrome

Clinical features of nephrotic syndrome

Proteinuria (>3.5g/24h)
Hypoalbuminaemia
Oedema
+/- Hypercholesterolaemia

Nephrotic Syndrome
Diagnostic triad
Proteinuria > 3.5g/dL
Serum Albumin < 30g/L
Oedema
Complications
Hypercholesterolemia

Pathophysiology
Disease of glomerular capillary wall
Urinary protein loss
Low plasma oncotic pressure
Salt and water retention by kidneys
Increased hepatic synthesis and reduced
metabolism of lipoproteins

Thrombosis

Venous obstruction caused by oedema

Increased hepatic synthesis of clotting factors
urinary loss of anti thrombotic protein
(prot C,prot S, ATIII)

Infections

Urinary loss of immunoglobulins and other defence

protein

Renal Failure

Intravascular volume depletion (acute)

Intrarenal oedema (acute)
Primary renal disease causing glomerular damage
Proteinuria causing interstitial inflamation

Malnutrition

Severe protein loss

Formation of nephrotic edema

Underfill

Overfill

Proteinuria

Tubular
Defect causing
Sodium retention

Hypoalbuminemia

Plasma colloid
Oncotic pressure

Normal/raised
Plasma volume

Reduced
plasma volume

Vasopresin

Atrial natriuretic
Peptide (ANP)
Normal/low

Water
retention

Renin angiotensin
System activated
Aldosteron

Sodium
retention
Edema

Vasopressin
normal

ANP

Aldosteron

Pathophysiology of the Nephrotic Syndrome

Lipid abnormalities in nephrotic

syndrome
Hepatic
synthesis

Hepatic
secretion

HDL

VLDL

IDL
LDL
HDL

VLDL deposition in
vascular tissues
Catabolism
Endhotelial
lipoprotein lipase

Oxidized
LDL
Atherogenicity

Urine clearance of

Lecithin
cholesterol
acyltransferas
e (LCAT)
activity

HDL3

smaller HDL3
Cholesterol removal from
tissue to liver impaired

HDL2
Lipoprot
ein (a)

Atherogenicity

Coagulation abnormalities in Nephrotic Syndrome

Hepatic
synthesis
Hyperlipidemia

Accelerated
atherogenesis

Coagulation
proteins
Raised: fibrinogen,
factors V, VII, von
Willebrand factor,
protein C 1
-macroglobulin
Unchanged/reduced:
Prothrombin factors
IX, X, XI, XII,
antithrombin III

Urine
clearance

Platelets aggregability

Volume concentration
Hemoconcentration

Immobility
Arterial thrombosis

Venous
thromboembolis
m

Clinical Features of The Nephrotic Syndrome

Manifestations of the nephrotic syndrome itself

Signs and symptoms determined by the underlying disease

involving the kidney

Clinical manifestation of nephrotic syndro

Oedema
Hypertension
Dyslipidemia
Hypercoagulable state
Hypoproteinemia / proteinuria
Progressive renal failure
Trace metal deficiencies
Endocrine disturbances
Infectious / immunodeficiency states

sification of the disease states associated with the development

nephrotic syndrome

I. Idiopathic nephrotic syndrome due to Primary Glomerular Disease

II.Nephrotic syndrome associated with spesific etiologic events or in w

glomerular disease arises as a complication of other disease
1.
2.
3.
4.
5.
6.
7.

Medications
Allergens
Infection ( bacterial, viral, protozoal, helminthic )
Neoplasmic ( solid tumors, leukemia and lymphoma )
Multisystem disease
Heredofamilial and metabolic disease
Miscellaneous

iagnostic approach in nephrotic syndrom

I. Clinical
II. Laboratory studies
III. Renal biopsy

I. Clinical
History
Preexisting disease
Previous infection
Drug ingestion
Arthritis, rash
Current pregnancy
Family history of renal disease
Physical examination
Severe obesity
Rash, arthritis
Diabetic retinopathy
Hypertension
Evidence of malignancy
Lipodystrophy
Lymphoadenopathy/hepatosplenomegaly

II. Laboratory Studies

Urinalysis
In all cases ( nondiagnstic )
Creatinine clearance
Serum protein electrophoresis
Serum tota;cholesterol, lipoprotein
Serum ionized calcium
Parathyroid hormone
In selected cases ( to establis the diagnosis )
Complement level
Antinuclear antibody assay
Cryoglobulins
Hepatitis and HIV serology
Serum and urine immunoelectrophoresis

III. Renal biopsy

Minimal change disease

Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative glomerulonephritis
Other glomerulonephritis

Suggested approach for initial treatment

( Minimal change disease )
Children

Prednisone 60 mg/m2/day until remission, then 40 mg/m2/48 h for

12 weeks, then reduce by 5-10 mg/m2/48 h every month.

Adults

Prednisone 1mg/kg/day until remission or for 6 weeks, then 1.6 mg/kg/

for 1 month, then reduce by 0.2-0.4 mg/kg/48 h.

Elderly

Prednisone 1 mg/kg/day until remission or for 4 weeks, then 0.8 mg/kg

for 2 weeks, then 1.6 mg/kg/48 h for 2 weeks. Then reduce by 0.4 mg/
every 2 weeks. If no remission continue with 1.2 mg/kg/48 h for anothe
4 weeks then reduce.

Contraindications to prednisone

Cyclophosphamide 2 mg/kg/day or chlorambucil 0.15mg/kg/day for 8-1

weeks

ACUTE KIDNEY INJURY

Acute Renal Failure (ARF)

Acute Kidney Injury (AKI)

Acute Kidney Injury (AKI)

digunakan oleh
Acute Dialysis Quantitative Initiative (ADQI), (2002),
menggantikan definisi
Acute Renal Failure (Gagal Ginjal Akut).
Di Indonesia, definisi AKI telah digunakan secara
resmi oleh PERNEFRI.
:

Gangguan Ginjal Akut

(GGA = GgGA)

Acute Kidney Injury

An

abrupt and sustained decrease (days to

weeks/within 48 hours) in renal function resulting in
retention of nitrogenous (urea and creatinine) and nonnitrogenous waste products.

Depending on severity and duration of the renal

dysfunction, this accumulation is accompanied by
metabolic dysturbance, such as metabolic acidosis and
hyperkalaemia, changes in body fluid balance, and
effects on many other organ systems.

Acute Kidney Injury

An

acute and sustained increase in serum creatinine

concentration of 0.5 mg% if the baseline is < 2.5 mg%,
or an increase in serum creatinine concentration of >
20% if the baseline is > 2.5 mg%/. An Increase %
more than or equal 50%/1.5 fold from base line

Reduction

in urine out put(documented oliguria of less

then 0.5 ml/kg perhour for more than six hours)

TABEL 2 : RIFLE criteria ADQI

Bellomo et al, Curr Opin Crit Care 2002;6:505-8

EPIDEMIOLOGY
1%

of hospitalized patients

20%

of patients treated in ICU

4-15%

of patients after cardiovascular surgery

Cause of mortality
1.

(75%) : Sepsis/multy organ dysfuntion

syndrome 2. Cardiopulomonal( 50%)

Acute Renal Failure

Dialysis Treatments
Creatinine
M/l
Urine
l/day

Zllner,
Innere Medizin,
modified

Time / days

1. Damage
Damage to
Renal Tissue
(minutes to days)

2. Oliguria / Anuria
Complete Loss of
Renal Function
(up to 6 weeks)

3. Polyuria
Uncontrolled
Urine Quantities
(1 - 2 weeks)

4. Recovery
slow Recovery of
Renal Function
(several months)

Prerenal

35 %

Renal

50 %

Postrenal

10 %

CLASSIFICATION
OF
ACUTE KIDNEY INJURY

ACUTE KIDNEY INJURY

PRERENAL

Absolute decrease in effective blood volume

Haemorrhage
Volume depletion
Relative decrease in blood volume (ineffective arterial volume)
Congestive heart failure
Decompensated liver cirrhosis
Arterial occlusion or stenosis of renal artery
Haemodynamic form
NSAIDs
ACE-inhibitors or angiotensin-II
receptor antagonists in renal-artery
stenosis or congestive heart failure

Hypovolemia

Baroreceptor activation

Reduced affective
circulation volume

Respons neurohormonal

Axis renin-angiotensin
aldosterone

Vasopressin

Sympathetic nervous system

Vasoconstriction
contraction of mesangial cells
Reabsorpsi natrium and water

Reduced renal blood flow and glomerular filtration rate

Acute renal failure pre-renal

ACUTE KIDNEY INJURY

INTRINSIC RENAL

Vascular
Vasculitis,
Malignant HT

Glomerulonephritis

Ischaemic (50%)

Exogenous
Antibiotics (gentamicin)
Radiocontrast agents
Cisplatin

Acute interstitial nephritis

Drugs
Allergy

Acute tubular
necrosis

Nephrotoxic (35%)

Endogenous
Intratubular pigments (haemoglobinuria,
myoglobinuria)
Intratubular proteins (myeloma)
Intratubular crystals (uric acid, oxalate)

ACUTE KIDNEY INJURY

POSTRENAL

Obstruction of collecting system or

extrarenal drainage
Bladder-outlet obstruction
Bilateral ureteral obstruction or
unilateral in one functioning kidney

Rapidly reversible decrease

In GFR caused by renal
Hypo perfusion.
Causes 50% of ARF
Acute Tubuler Necrosis
(ATN) is an abrupt
Decrease of GFR caused
By tubular damage from:
- renal hypo perfusion
- nephrotoxic injury
- Tubulo-interstitial nephritis

Dwi Lestari

Rapidly reversible decrease

In GFR caused by obstruction
In renal or Uretero Uretheral - vesico urinary
(OBSTRUCTIVE UROPATHY)

Assessment of a Patient with

Acute Renal Failure (1)
Procedure

Information Sought

Clinical history and

examination

Clues to the cause of acute renal failure

Indicators of severity of metabolis disturbance
Estimate of volume status (hydration)

Urinalysis and urine

microscopy

Markers of glomerular or tubulointerstitial

inflammation, urinary tract infection or crystal
uropathy

Plasma biochemistry

To assess extent of GFR reduction and

metabolic consequences

Urine biochemistry

To differentiate prerenal from established

renal failure

Full blood count

To determine presence of anemia,

leucocytosis, and platelet consumption

Findings that suggest prerenal causes

Volume depletion
Congestive heart failure
Severe liver disease or other edematous state
Findings that suggest postrenal causes
Palpable bladder or hydronephrotic kidneys
Enlarge prostat
Abnormal pelvic examination
Large residual bladder urine volume
History of renal calculi (perform USG to screen obstruction)
Findings that suggest intrinsic renal disease
Hypotension, exposure to nephrotoxic drugs
Recent radiographic procedure with contrast

Finding in the urine sediment

If no abnormalities: suspect prerenal or postrenal azotemia
If eosinophils: suspect acute interstitial nephritis
If red blood cell casts: suspect glomerulonephritis or vasculitis
If renal tubular ephitelial cells and muddy brown casts: suspect acute tubular
necrosis

Assessment of a Patient with

Acute Renal Failure (2)
Procedure
Renal ultrasound
Plus, where appropriate :
Abdominal CT-Scan

Radionuclide scan
Cystoscopy +/- retragrade
pyelograms
Renal biopsy

Information Sought
To determine kidney size, presence of
obstruction, abnormal renal parenchymal
texture
To define structural abnormalities of the
kidneys or
urinary tract
To assess abnormal renal perfusion
To evaluate / relieve urinary tract obstruction

To define pathology of renal parenchymal

disease

Dwi Lestari

ALGORITMA UNTUK MENEGAKKAN DIAGNOSIS GgGA

The potential interventions in sepsis related AKI

1. Effective prevention/protection strategies for the
kidney in patient at risk
2. Early recognition and attenuation of renal damaged
3. Pathophysiology driven pharmacology support
4. Efficient extracorporeal blood purification therapy
5. Strategies that promote recovery of renal function

Ronco . ASN
2008

Renal Protection
Renal protection, there is damage before any symptom

MAP> 65 mmHg

CVP 8-12 mmHg (no ventilator)

12-15 mmHg (ventilator)

Urine > 0,5ml/BW/hour

SaO2 >70%
Koloid ,albumin ?

LANGKAH 1
Mengenal kondisi klinis yang dihadapi
- Menentukan diagnosis GgGA secara dini dan benar .
- Menentukan etiologi GGA
- Mengetahui komplikasi yang menyertai GgGA
(komplikasi penyakit dasar maupun komplikasi GgGA)

LANGKAH 2
Pada tahap mana GgGA yang dihadapi ? Risk Injury- Failure
Pemilihan jenis pengobatan yang tepat waktu, sangat tergantung pada tahap
mana GgGA yang kita hadapi

LANGKAH 3
Memilih jenis pengobatan yang tepat
Secara garis besar ada 2 jenis pengobatan untuk GgGA, yaitu terapi
konservatif dan terapi pengganti ginjal.

Dwi Lestari

Komplikasi yang menyertai GgGA

1.
2.
3.
4.
5.
6.

Gangguan keseimbangan cairan tubuh dan elektrolit

(retensi Natrium, edema)
Gangguan keseimbangan elektrolit (terutama
hiperkalemia)
Asidosis metabolik
Gagal Jantung
Gagal Nafas
Azotemia

Tujuan terapi konservatif adalah :

Mencegah memburuknya faal ginjal secara progresif
Meringankan keluhan-keluhan akibat akumulasi toksin azotemia
Mempertahankan dan memperbaiki metabolisme secara optimal
Memelihara keseimbangan cairan dan elektrolit

Beberapa prinsip terapi konservatif :

Hati-hati pemberian obat yang bersifat nefrotoksik
Hindari keadaan yang menyababkan deplesi volume cairan ekstraseluler dan
hipotensi
Hindari gangguan keseimbangan elektrolit dan asidosis metabolik
Hindari instrumentasi (kateterisasi dan sistoskopi) tanpa indikasi medis yang kuat
Hindari pemeriksaan radiologi dengan media kontras tanpa indikasi medis yang
kuat
Kendalikan hipertensi sistemik dan tekanan intraglomerular
Kendalikan keadaan hiperglikemia dan infeksi saluran kemih (ISK)
Diet protein yang proporsional

Dwi Lestari

Best cure is to prevent

Have

a high index of suspicion for

reversible factors - volume depletion,
decreasing cardiac function, sepsis,
urinary tract obstruction
Be sure patient is well-hydrated when
exposing patient to nephrotoxic drugs
Dwi Lestari

Management priorities in patients

with acute kidney injury

Search for and correct prerenal and postrenal factors.

Review medications and stop administration of nephrotoxins.

Optimise cardiac output and renal blood flow.

Monitor fluid intake and output; measure bodyweight daily.

Search for and treat acute complications (hyperkalaemia, hyponatraemia,

acidosis, hyperphospataemia, pulmonary oedema).

Provide early nutritional support.

Search for and aggressively treat infections.

Expert nursing care (management catheter care and skin in general;

physicological support).

Initiate dialysis before uraemic complication emerge.

Give drugs in doses appropriate for their clearance.

Indications for dialysis in acute kidney injury

Indications

Characteristics

Uremia

Asterixis, seizures, nausea & vomiting,

pericarditis

Hyperkalemia

K+ >6.5 mmol/L; K+ 5.5-6.5 mmol/L if ECG

changes
Fluid
overload

Metabolic
acidosis

Fluid overload resistant to diuretics,

especially pulmonary edema
pH < 7.2 despite sodium bicarbonate
therapy; sodium bicarbonate not tolerated
because of fluid overload

Proposed criteria for the initiation of renal replacement therapy in adult critically ill
patients

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

Oliguria (urine output < 200 ml/12 hr)

Anuria/extreme oliguria (urine output < 50 ml/12 hr)
Hyperkalemia ([K+] > 6.5 mmol/liter)
Severe acidemia (pH < 7.1)
Azotemia ([urea] > 30 mmol/liter)
Clinically significant organ (especially lung) edema
Uremic enchepalopathy
Uremic pericarditis
Uremic neuropathy/myopathy
Severe dysnatremia ([Na] > 160 or < 15 mmol/liter)
Hyperthermia/Hypothermia
Drug overdose with dialysable toxin

WHEN ?

The presence of :
- one of the above criteria is sufficient to initiate renal replacement therapy in a critically ill patients
- two of these criteria makes renal replacement urgent and mandatory.
- combined derangements suggest initiation of renal replacement therapy even before the above
mentioned limits have been reached.

CAVHD
CVVHD
CAVHF
CVVHF
CAVHDF
CVVHDF

CAVH

Willem KOLF 1943-1944

Dialysis in 15 pts
HD
(1 survived)l
Renal
Replacement

KRAMER
1977

HYBRID
DIALYSIS

Belding SCRIBNER 1960,

1960
begin chronic dialysis

George Haas 1914-1915

Dialysis in Animal

IHD
EDD
CAPD

SLED

Fred BOEN
1961

PD

SELLIGMENT & FINE

1945

APD

Dialysis modalities for acute kidney injury

Intermittent therapies
(up to 12 hours)
Hemodialysis
intermittent
daily
Hemodiafiltration
Slow Continous Ultra-Filtration
Extended Daily Dialysis
Sustained Low Efficient Dialysis

Continuous therapies
(24 hours)
Peritoneal dialysis
Ultrafiltration (SCUF)
Hemofiltration (CAVH, CVVH)
Hemodialysis (CAVHD, CVVHD)
Hemodiafiltration (CAVHDF, CVVHDF)

Adapted from Mehta RL. Supportive therapies; intermittent hemodialysis, continuous renal replacement therapies and peritoneal dialysis. In : Schrier RW, editor.
Atlas of diseases of the kidney, Current Medicine, Philadelphia: Blackwell Science; 1998: with permission.

WHICH ?

# Proses difusi
( Perpindahan molekul melalui membran semi permeable
Dengan cara difusi)
# Dipengaruhi oleh :
- berat molekul
- perbedaan konsentrasi
- Resistensi/ jenis membran
# Proses Filtrasi
(Perpindahan cairan dengan cara convective)
# Dipengaruhi oleh :
- Perbedaan tekanan (transmembrane)
- Koefisien ultrafiltrasi

Proses difusi dan ultrafiltrasi

Dengan dialisis darah dibersihkan dengan proses difusi dan filtrasi

Melalui membran semi-permeable dalam Ginjal Buatan
Darah
Darah kotor
dialisat
bersih
masuk
Proses
difusi

Proses yang terjadi

dialisat
masuk

Proses
Filtrasi
ultrafiltrat
keluar
UltraFiltrat
Darah bersih
keluar
GINJAL BUATAN

Darah

Membran semi-permeable
Didalam ginjal buatan

a. Modifikasi proses dialysis, dengan

- Qb = 150 cc/menit
- Qd = 300 cc/menit
- tD = 6 12 jam / hari
b. Dimulai Juli, 1998 di University of Arkansas, Amerika
c. Indikasi untuk ARF dengen hemodinamik tidak stabil
d. Merupakan alternatif terapi dari CAVHD atau CVVHD
e. Biasanya menggunakan Mesin Fresenius 4008, dengan
ginjal BUKAN Cellulosa Acetate

Chronic Kidney Diseases

CKD
Haerani Rasyid
Nephrology and Hypertension Division,
Department of Internal Medicine
Medical Faculty Hasanuddin University

The Nephron

Filtration, Reabsorption and Secretion

Normal GFR 120 ml/min/1.73m2

In a day 210 L of water is filtered

Only 20% nephrons work at a time

2 L /day of urine is excreted

Factors Influencing Renal Function

H
AD

NPs

Na excretion
Water retention

Na reabsorbtion
Aldo
stero
n

Ca reabsorption,
PO4 excretion
Vit D synthesis
PTH

Vasoconstriction

Renin

EPO

Sodium
Reabsorbti
on
Calcium and
Phosphate
Reabsorbtio
n

Bone
marro

Red blood cells

Angiotensin
II

Aldosteron

Vitamin D

Calcium
absorbtion
Phosphate
absorbtion
Ca release
PO4 release

CKD
A Scary Challenge for Us All !!

CKD A Silent Killer

CKD at a glance

CKD Increased Death

CKD A Global Pandemic

CKD 1-2 are asymptomatic
10 million people of CKD
Term CRF no longer used
Dialysis death rate 100 x
Small in Creatinin - in
CV

Estimated Prevalence of CKD

(Stages 3-5) in the World

World Population is 6.65 Billion

CKD (Stages 3-5): 200 - 333 million

Prevalence of CKD

Do we care about CKD ?

1.

Doctors do not realize that CKD is hidden in their

patients of DM, HT and in elderly people

2.

Most doctors screen less than 10% of their clinic

patients for CKD in its early stages

3.

Patients are refered very late to nephrologists especially

after the CKD is irreversible

4.

Only < 1/4 of people with identified CKD get an ACE

Inhibitor

All are true - all over the globe

Now we know
why the titanic sank !!
< 0.5 %

5- 10%

LET US LEARN ABOUT

CKD

Some useful Definitions

1. Azotemia - Elevated blood urea nitrogen - Biochemical

(BUN >28 mg/dl) and creatinine (Cr >1.5mg/dl)2. Uremia is Azotemia + symptoms or signs of renal failure
3. End Stage Renal Disease (ESRD) - Uremia requiring

transplantation or dialysis (Renal replacement therapy)

4. Chronic Renal Failure (CRF) - Irreversible kidney

dysfunction with azotemia >3 months now not used

5. Creatinine Clearance (CCr) - The rate of filtration of

creatinine by the kidney (a marker of GFR)

6. Glomerular Filtration Rate (GFR) - The total rate of

filtration of fluid from blood by the kidney

Definition of CKD
1.

Either GFR < 60 ml/min/1.73m2 for 3 mon or

2.

Kidney damage for 3 mon as manifested by

a. Persistent microalbuminuria / macroproteinuria
b. Biochemical abnormalities in RFT
c. Persistent non-urological hematuria
d. Structural renal abnormalities by USG
e. Biopsy proven Glomerulonephritis (rarely needed)

(Any one of the above evidences)

CKD Definition
Damage

for three or more months, as defined by

structural or functional abnormalities of the
kidney, with or without decreased GFR,
manifested by pathologic abnormalities or
markers of kidney damage, including
abnormalities in the composition of the blood or
urine or abnormalities in imaging tests

GFR

< 60 mL per minute per 1.73 m2 for three

months or more, with or without kidney damage
Am J Kidney Dis 2002;39(2 suppl 1):S18.

Etiologi CKD
Etiologi

1989 *

1996

Glomerulonephritis
Obstruction
Diabetic nephropaty
Lupus nephritis
Polycystic KD
Hypertension
Unknown

40,12%
36,7%
6,13%
4,17%
2,12%
2,09%
9,32%

46,19%
12,85%
18,65%
0,16%
1,41%
8,46%
15,2%

2000
39,64%
13,44%
17,54%
0,23%
2,51%
15,72%
10,93%

Nephrology Centre in Indonesia

Sidabutar RP ( 1989 ) *

Methods of Glomerular Filtration

Rate (GFR) Measurement
Inulin Clearance
Alternative Filtration Markers
125

I-Iothalamate, 51Cr-EDTA, 99mTc-DTPA and

non-radioactive iohexol
Plasma Creatinine
Creatinine Clearance
Predictive Creatinine Clearance (the Cockroft-Gault Formula)

Creatinine Clearance

Ccr =

Ucr x V
Pcr

Pcr = Plasma concentration of creatinine

Ucr = Urine concentration of creatinine
V = Urine flow rate

Note (V) :

24 hr collection
Over night collection
Time collection

Estimated creatinine clearence (Ccr) with

respect age, gender and body weight
Cockcroft Gault Formula

Men
Ccr =

1.23 (140-age)(weight)

(140-age)(weight)
or
72 Pcr (mg/dl)

Ccr =

Pcr (mol/L)

Women
Ccr =

1.04 (140-age)(weight)

(140-age)(weight)
or
85 Pcr (mg/dl)

Ccr =
Pcr (mol/L)

Age years
Weight Kg
Pcr plasma creatinine
The formula estimates Ccr in obese patients and those on a low protein diet

STAGES OF CKD
NORMAL INCREASED RISK DAMAGE

COMPLICATIONS

CKD
DEATH

LOW GFR

RENAL FAILURE

CKD
Stage

eGFR
(mL/1.73
cm2)

Other Features

Suggested Management

90+

60-89

Mildly reduced renal

function plus
urine/structural
abnormalities or
diagnosis of genetic
kidney disease

Observation, control of BP.

Management of cardiovascular risk
factors. Consider investigation for
cause of renal impairment

30-59

Moderately reduced renal

function

Observation, control of BP.

Management of cardiovascular risk
factors. Measure Ca2+, PO4, PTH, Hb
and cholesterol. The patient may need
treatment for anaemia or
secondary/tertiary
hyperparathyroidism.

Normal renal function but Observation, control of BP. Consider

urine dipstick
investigation for cause of urine
abnormalities or known
dipstick abnormalities
structural abnormality if
renal tract or diagnosis
of genetic kidney disease

15-29

Severely reduced renal

function

Regular observation, control of

BP and CVS risk factors. Measure
Ca2+, PO4, PTH, Hb and
cholesterol. Management as for
stage 3. Preparation for ESRF
with an early decision on the
preferred mode of RRT.

<15

End-stage renal failure

Can be managed conservatively

but RRT should be considered
for most patients (i.e. provision
of dialysis or transplantation

BP: blood pressure; CVS: cardiovascular system; Hb: hemoglobin;

PTH: parathyroid hormone; RRT: renal replacement therapy

Chronic Kidney Disease - Stages

CKD Prevalence

Who are at Risk for CKD

Diabetes
Hypertension
Age

, Family H/o Kidney Disease

Systemic Infections
Recurrent UTI
Urinary Stone Disease
Loss of Renal mass
Neoplasia of any part
Nephrotoxic Drugs (NSAIDs)

Risk of CKD is not uniform

Racial differences in CKD
Caucasians (Whites)

1.0 X

Asians (Indians)

1.3 X

Hispanics (Spanish)

1.5 X

Native Americans

2.0 X

Africans (Blacks) 3.8 X

Chronic kidney diseases ( CKD )

* Renal injury destruksi nefron yang bersifat
chronic progressive , irreversible
* Penurunan jumlah massa nefron menyebabkan
perubahan struktur dan hiper fungsi dari sisa nefron
* Respon mekanisme predisposisi sklerosis nefron
CKD
* uremia sindrom klinik yang mengenai seluruh
organ / sistim

Chronic kidney disease

Pathophysiology
Nitrogen and Lipid Metabolism

Pts are often hypercatabolic and have a

decrease capacity to eliminate nitrogenous
end products of protein catabolism.
Hypertriglyceridemia and, decreased HDL
are common in pts with CRF.
High incidence of premature
atherosclerosis

Clinical Manifestation of
Chronic kidney disease
Neurologic Abnormalities
Central
Cognitive change
Lethargy
Stupor
Coma
Peripheral
Motor neuropathy
Sensory neuropathy
Myoclonus
Fasciculations

Cardiovascular Abnormalities
Hypertension
Pericarditis
Accelerated atherosclerosis
Vascular calcifications

Clinical Manifestation of
Chronic kidney disease
Hematologic Abnormalities
Anemia
Leukocyte & lymphocyte dysfunction
Platelet defect
Gastrointestinal Abnormalities
Anorexia, nausea, vomiting
Gastroparesis
Hypomotility of bowel
Mucosal bleeding
Dermatologic Abnormalities
Pruritis
Calcium-phosphate
deposition

Clinical Manifestation of
Chronic kidney disease
Rheumatologic Abnormalities
Myopathy
Calcific bursitis
Avascular necrosis
Carpal tunnel syndrome
Articular amyloid deposition

Pleural-Pulmonary Abnormalities
Pleuritis and effusion
Parenchymal calcification
Edema

Metabolic Abnormalities
Glucose intolerance
Hyperparatiroidism
Vitamin D deficiency
Hyperlipidemia
Sexual dysfunction
Malnutrition

Clinical Manifestation of
Chronic kidney disease)

Electrolytes
Hyperkalemia
Hyponatremia
Hyperphosphatemia
Hypocalcaemia
Hyperuricaemia
Metabolic Acidosis

Bone Abnormalities
Osteomalacia
Osteitis fibrosa
Osteosclerosis
Aluminum associated
osteomalacia

Investigating CKD

K/DOQI CKD Staging

THE MECHANISM OF PROGRESSION OF

CHRONIC KIDNEY DISEASE
1. HYPERTENSION
2. PROTEINURIA
3. ANGIOTENSIN-II
4. HYPERGLYCEMIA.
5. PROTEIN INTAKE
6. SODIUM INTAKE
7. WATER INTAKE
8. HYPERLIPIDEMIA
9. SMOKING
10. NSAID
11. ANEMIA

12. HYPERINSULINEMIA
13. HOMOCYSTEINEMIA
14.
HYPERPHOSPHATEMI
A
15. POTASSIUM
DEPLETION
= LEVEL 1
16. HYPERCOAGULATION
= LEVEL 2
17. GENDER
= LEVEL 3

Hebert LA, et al : Kidney Int 2001; 59

Important Guidelines
Interventions to slow
progression of CKD

To be avoided to prevent
acute reduction in GFR

1.

Glycemic control in DM

1.

Volume depletion

2.

BP control ACEI / ARB

2.

Radiographic contrast

3.

Protein restriction

3.

Antibiotics / NSAIDS

4.

Lipid lowering therapy

4.

Cyclosporine / tacrolimus

5.

Weight reduction

5.

ACEI / ARB if Cr > 3.5mg

6.

Anemia Rx, Smoking

6.

Obstructive uropathy

RENAL BEGINNINGS
FLOW CHART
SERUM CREATININE

DEMOGRAPHIC DATA

GFR
STAGE 5
GFR < 15

STAGE 3
GFR 30 - 59

STAGE 4
GFR 15 - 29

EVALUATION
1.
2.
3.
4.
5.
6.

Diagnosis
Co morbid conditions
Severity
Complications related to GFR
Risk for further loss of GFR
Risk for cardiovascular disease

TREATMENT
1.
2.
3.
4.
5.
6.
7.

Specific therapy based on diagnosis

E & M of co morbid conditions
Slowing the loss of kidney function
Prevention and tx of CV disease
Prevention and tx of complications of low GFR
Preparation for RRT
Dialysis / Transplant

Interventions to slow the progression of

chronic kidney disease should be considered
in all patients with CKD
Interventions that have been proven to be effective
include :

(1) Strict glucose control in diabetes

(2) Stric blood pressure control
(3) Angiotensin-converting enzyme inhibitor or angiotensin-2
receptor blockade

Interventions that have been studied, but the

results of which are inconclusive, include :
(1) Dietary protein restriction
(2) Lipid-lowering therapy
(3) Partial correction of anemia

Am J Kidney Dis 2002 ; 39 (supp

Uremia
: diit protein 0,8 0,6 gr / kg bb / hari
Hiperkalemia
: diit rendah kalium ; 60 80 meq/hari
Asidosis metabolik : diit rendah protein / fosfat; HCO3
Stop rokok
Kontrol lipid ( preparat statin )
HbA1C < 7 %
Hipertensi
Anemia
Osteodistrofi renal
Komplikasi kardiovaskuler

hypertension
K/DOQI, 2004 / ADA, 2003 / JNC 7, 2003 : Target BP 130/80 mmHg
Lifestyle modification : DASH diet, exercise, etc
Agent is ARB, ACE-inh (initial) : Hypertension Diabetic Kidney Disease and Nondiabetic
Kidney Disease

Hypertension and Antihypertensive Agents in Diabetic Kidney Disease

(K/DOQI)
Clinical
Assessment

BP >130/80 mmHg

BP <130/80 mmHg
BP < 125 / 75 mmHg

Target BP

<130/80 mmHg

Preffered Agents for

CKD

ACE inhibitor or ARB

ACE inhibitor or ARB

( ekskresi protein > 1 gr / hari )

Other Agents to Reduce

CVD Risk and Reach
Target BP
Diuretic preffered, then
beta blocker or calcium
chanel blocker dh la

Anemia
Target hematocrit pre-dialysis , hemodialysis
Relieve symptom,

low risk side effect :

Hb 9,5 g% / Ht 29 - Hb 11g% / Ht 33% ( Pernefri/NKF-DOQI)

- erithropoetin
- preparat - iron ( bila kadar serum iron kurang )
Defisiensi Eritropoetin pada GGK

improvements in the quality of life, cardiacfunction,

physical work capacity, cognitive function, and sexual
function have been reported at a hematocrit
of 36% to39%.

Renoprotective Strategies Recommendation

1.
2.

3.
4.

5.
6.
7.
8.
9.

Control blood pressure

ACE inhibitor therapy
Angiotensin receptor blocker (ARB) if ACE
inhibitor
intolerant
Control blood glucose in diabetes
Dietary interventions
Protein intake, NaCl intake
Fluid intake
Control blood lipids
No cigarette smoking
Avoid regular use of NSAIDs
Correct anemia
Control hyperphosphatemia Hebert LA, et al : Kidney Int 2001; 59 :
1215

URINARY TRACT INFECTION

Syakib Bakri, Hasyim Kasim, Haerani Rasyid

*Division of Nephrology, Department of

Internal Medicine
Faculty of Medicine, Hasanuddin University

Urinary Tract Infections (UTI)

Frequent clinical problem
Any site in the urinary tract may be involved : the urethra, prostate,
bladder, ureter, kidney and perinephric space.
Bacterial infection is most common, but fungi, chlamydia, viruses
and parasites may be responsible in some patients
Women >>> Men

Terminology of Urinary Tract Infections (1)

Bacteriuria : Presence of bacteria in the urine.
Asymptomatic bacteriuria : 105 CFU/ml urine with or without pyuria, in a patient
without symptoms of UTI.
Cystitis : inflammation of the bladder
Bacterial cystitis
Abacterial cystitis (urethral syndrome)
Acute pyelonephritis: acute bacterial infection of the kidney characterized by
chills and fever (often high) and flank pain (usually unilateral), as well as
tenderness.
Chronic pyelonephritis : Radiological diagnosis where there is evidence of focal
scarring of the kidneys with associated calyceal abnormality indicating renal
damage due to a combination of reccurent infection with obstruction of the
pelviocalyceal system (chronic obstructive nephropathy) or vesicoureteral
reflux (reflux nephropathy).

Ribeiro RM, et al. Int Urogynecol 2002;13:19

Terminology of Urinary Tract Infections (2)

Reinfection : An infection with a different strain of microorganism or a different
serological type after (end of therapy) eradication of previous infection.
Most likely represent infections of the bladder, occur weeks to months after
treatment of the previous infection, response well to therapy,
usually associated with a normal urinary tract

Relapse : A consecutive urinary infection caused by the same strain or serotype of

bacteria, usually represent infection of the kidney or prostat, often recur
within 1 6 weeks after antimicrobials have been discontinued, some cases
represent persistent infection, anatomic abnormalities or renal insuficiency
are more common with relapsing or persistent infection, a long course of
antimicrobials or surgery may be required if the urine is to be permanently
sterilized

Ribeiro RM, et al. Int Urogynecol J 2002;13:

Terminology of Urinary Tract Infections (3)

Persistence : the continued presence of the microorganisms isolated at the beginning
of the treatment, owing to resistance to antimicrobial therapy, inadequate
drug dosage, or a urological abnormality. These unresolved infections may
be also in consequence of the patients non-compliance in taking medication,
mixed infections with two different bacterial strains with mutually exclusive
susceptibilities, or renal insufficiency (leading to an inadequate drug
concentration in the urine).

Recurrent UTI: patients with at least two infections within 6 months or three or
more during a single year, in which the initial episode is resolved and
is followed by another infection.

Ribeiro RM, et al. Int Urogynecol J 2002;13:

Diagnosis Urinary Tract Infection

1. Symptoms :
Lower UTI :
Frequency, dysuria, suprapubic pain
Upper UTI :
Fever, flank pain, and chills as well as symptoms similar to
bladder infection
2. Urinalysis

The presence of 10 WBC / mm3 fresh un-spun midstream urine

The presence of 10 WBC / high-power field sediment midstream
urine

3. Culture
4. Radiological evaluation

Ultrosound
Plain abdominal radiography
Intravenous urography
CT scanning

Criteria for diagnosis of significant bacteriuria

Symptomatic women :
102 coliform organisms/ml urine plus pyuria, or
105 of any pathogenic organism/ml urine, or
Any growth of a pathogenic organism from urine obtained by

suprapubic aspiration
Symptomatic men :
103 pathogenic organism/ml urine
Asymptomatic patients :
105 pathogenic organism/ml urine in two
consecutive samples

Classification of Urinary Tract Infection (1)

I. Lower urinary tract infection ( Cystitis )

Frequency, dysuria, suprapubic pain
II. Upper urinary tract infection ( Pyelonephritis )
Fever, flank pain, and chills as well as symptoms
similar to bladder infection

Classification of Urinary Tract Infection (2)

I. Uncomplicated urinary tract infection
Occurs in individuals with structurally and functionally normal genitourinary
tracts
Most common bacterial infection that occurs in women, but is uncommon in
men
May involve the bladder or the kidneys and may be symptomatic or
asymptomatic

II. Complicated urinary tract infection

As acute or chronic parenchymal infection associated with a functional or
structural urinary tract abnormality
e.g. : Neurogenic bladder, urinary tract obstruction, immunocompromized
patients, diabetes mellitus, polycystic kidney disease, renal transplant
recipient.

Bacterial etiology of urinary tract infection

E. coli : 70-95% (uncomplicated UTI), 21-54% (complicated)
S. Saprophyticus : 5-20% (uncomplicated), 1-4% (complicated)
Enterococci : 1-2% (uncomplicated), 1-23% (complicated)
Proteus mirabilis : 1-2% (uncomplicated ), 1-10% (complicated)
Klebsiella spp : 1-2% (uncomplicated), 2-17% (complicated)
Pseudomonas aeruginosa : <1% (uncomplicated), 2-19%
(complicated)

Clinical Classification of Urinary Tract Infection

1.Acute uncomplicated cystitis in women

2. Acute uncomplicated pyelonephritis in women
3. Complicated UTI in both sexes
4. Recurrent infections in women
5. Asymptomatic bacteriuria
McBryde C, Redington. Primary Care Case Rev 2001 ;

Acute uncomplicated cystitis in women

Single dose or 3-day course of treatment
(trimethoprim sulfamethoxasole, quinolone, amoxycillin)

Follow-up urine culture 7-14 days later

Cured
(sterile urine)

No investigation

Failure or relapse
(identical pathogens)

Reinfection
(new pathogen)

Ultrasonography urinary tract

KUB radiograph
Treatment for 2 weeks

Catel WR. Clin Drug Invest 1995 ; 9 (suppl 1) :

Clinical Classification of Urinary Tract Infection

1. Acute uncomplicated cystitis in women

2.Acute uncomplicated pyelonephritis in wome

3. Complicated UTI in both sexes
4. Recurrent infections in women
5. Asymptomatic bacteriuria
McBryde C, Redington. Primary Care Case Rev 2001 ;

Acute uncomplicated pyelonephritis in women

Severe illness

Moderate severity
Outpatients and oral
therapy possible
(trimethoprim
sulfamethoxasole,
quinolone, amoxycillin)

Hospitalization with initial

parenteral therapy
(trimethoprimsulfametaxazol,
ceftriaxone, quinolone,
gentamicin
with/without ampicilin
Urologic evaluation

No resolution
in 5 days

Resolution
in 5 days

No resolution
in 5 days
Radiologic evaluation

Treatment 14 days

Oral treatment 14 days or

longer as required

Clinical Classification of Urinary Tract Infection

1. Acute uncomplicated cystitis in women

2. Acute uncomplicated pyelonephritis in women
3.Complicated UTI in both sexes
4. Recurrent infections in women
5. Asymptomatic bacteriuria
McBryde C, Redington. Primary Care Case Rev 2001 ;

Complicated UTI in both sexes

Hospitalize, urine culture, blood culture
Empiric therapy with parenteral regimen
Significant clinical improvement

Yes
5 Days
Switch to or continue
oral regimen
For total 2 weeks

No

Review antimicrobial susceptibility pattern

Radiologic & urologic evaluation
Correct reversible risk factors

Review treatment plan as appropriate,

treat for total 2 weeks or longers if necessary

Follow-up urine culture after treatment

Clinical Classification of Urinary Tract Infection

1. Acute uncomplicated cystitis in women

2. Acute uncomplicated pyelonephritis in women
3. Complicated UTI in both sexes
4.Recurrent infections in women
5. Asymptomatic bacteriuria
McBryde C, Redington. Primary Care Case Rev 2001 ;

Recurrent infections in women

Reccurent UTI in women
Relapse

Conventional antibiotic
therapy 2-6 weeks

Sexually active

Antibiotic therapy :
On demand or
Postcoital or
Longterm prophylaxis

Diagnosis

Reinfection

3 year

2 year

Conventional antibiotic
therapy 3-7 days

Postmenopausal

Estrogen substitution
(oral & topical)
Antibiotic therapy :
On demand or
Longterm prophylaxis
Madersbacher S, et al. Curr Opin Urol 2000 ; 10

Drug regimens for long-term, low-dose prophylaxis of

recurrent urinary tract infection
Drug

Dose*

Nitrofurantoin

50 mg

Trimethoprim

100 mg

Co-trimoxazole

0.24 g

Norfloxacin

200 mg

Ciprofloxacin

125 mg

Cephalexin

125 mg
( useful if renal insufficiency)

Hexamine hippurate

1g

* Treatment is effective if taken each night, alternate nights, three times a week,
or just after intercourse

Clinical Classification of Urinary Tract Infection

1. Acute uncomplicated cystitis in women

2. Acute uncomplicated pyelonephritis in women
3. Complicated UTI in both sexes
4. Recurrent infections in women
5. Asymptomatic bacteriuria
McBryde C, Redington. Primary Care Case Rev 2001 ;

Indication for the treatment of patients with

asymptomatic bacteriuria
Definitive

Possible

Not indicated

Pregnancy

Diabetes mellitus

Elderly

Before an invasive
genitourinary
procedure

Short-term
indwelling
catheterization

School girls and

premanopausal women

Intermittent
catheterization

Children with reflux

Long-term
indwelling catheter

Patients with abnormal

urinary tract

Renal transplant

Raz R. Nephrol Dial Transplant 2001 ; 16 (suppl 6

Indication for imaging studies in

patients with Urinary Tract Infections

Infections in a newborn

Reccurent infection occuring in childhood

Two or more infections in adult females

One infection in adult males

Elevated creatinine level

History of urinary calculi

Neurologic bladder dysfunction

Persistent hematuria

Previous genitourinary surgery

Prolonged fever after initiation of antibiotic therapy

Relapsing infection

Urea-splitting organisms

Unusual causative organism

THANK YOU