Gagal Ginjal Kronik

( Chronic Kidney Disease / CKD )

Dr. Bowo Widiasmoko SpPD

RS Bethesda / FK UKDW

Renal failure or kidney failure

Describes a medical condition in which the kidneys fail to
adequately filter toxins and waste products from the blood.
The two forms are
acute (acute kidney injury)
chronic (chronic kidney disease)
Described as a decrease in the glomerular filtration rate.
Biochemically, renal failure is typically detected by an
elevated serum creatinine level.

Kidney Functions

Clasification
Renal failure can be divided into two categories:
acute kidney injury
chronic kidney disease.
The type of renal failure is determined by the trend in the
serum creatinine.
Other factors which may help differentiate acute kidney injury
from chronic kidney disease include anemia and the kidney
size on ultrasound. Chronic kidney disease generally leads to
anemia and small kidney size.

Acute-on-chronic renal failure

Acute kidney injuries can be present on top of chronic kidney
disease, a condition called acute-on-chronic renal failure (AoCRF).
The acute part of AoCRF may be reversible, and the goal of
treatment, as with AKI, is to return the patient to baseline renal
function, typically measured by serum creatinine.
Like AKI, AoCRF can be difficult to distinguish from chronic
kidney disease if the patient has not been monitored by a physician
and no baseline (i.e., past) blood work is available for comparison.

Symptoms
Symptoms can vary from person to person.
Someone in early stage kidney disease may not feel sick or
notice symptoms as they occur.
When kidneys fail to filter properly, waste accumulates in the
blood and the body, a condition called azotemia.
If the disease progresses, symptoms become noticeable (if the
failure is of sufficient degree to cause symptoms).
Renal failure accompanied by noticeable symptoms is termed
uraemia

High levels of urea in the blood, which can result in:

Vomiting and/or diarrhea, which may lead to dehydration

Nausea
Weight loss
Nocturnal urination
Foamy urine
More frequent urination, or in greater amounts than usual,
with pale urine
Less frequent urination, or in smaller amounts than usual,
with dark coloured urine
Blood in the urine
Pressure, or difficulty urinating

Chronic Kidney Disease

also known as chronic renal disease, is a
progressive loss in renal function over a period of
months or years.
The symptoms of worsening kidney function are
unspecific, and might include feeling generally
unwell and experiencing a reduced appetite.
Often, chronic kidney disease is diagnosed as a
result of screening of people known to be at risk of
kidney problems, (high blood pressure or diabetes)
Chronic kidney disease may also be identified when
it leads to one of its recognized complications, such
as cardiovascular disease, anemia or pericarditis

Chronic Kidney Disease

Signs and symptom
CKD is initially without specific symptoms and can only be detected
as an increase in serum creatinine or protein in the urine.
As the kidney function decreases:

blood pressure is increased due to fluid overload and production

of vasoactive hormones

Urea accumulates, leading to azotemia and ultimately uremia

(symptoms ranging from lethargy to pericarditis and
encephalopathy).

Chronic Kidney Disease

Signs and symptom

Potassium accumulates in the blood (known as

hyperkalemia potentially fatal cardiac arrhythmias)
Erythropoietin synthesis is decreased (potentially leading
to anemia, which causes fatigue)
Fluid volume overload - symptoms may range from mild
edema to life-threatening pulmonary edema

Chronic Kidney Disease

Signs and symptom

Hyperphosphatemia - due to reduced phosphate excretion,

associated with hypocalcemia, secondary
hyperparathyroidism, renal osteodystrophy.
Metabolic acidosis, due to accumulation of sulfates,
phosphates, uric acid etc. This may cause altered enzyme
activity by excess acid acting on enzymes and also
increased excitability of cardiac and neuronal membranes
by the promotion of hyperkalemia due to excess acid.

Common presentation of
CKD
Asymptomatic urine abnormalities :

proteinuria/ haematuria
Nephritic/Nephrotic syndrome
Hypertension
Unexplained anaemia
Incidental finding of elevated serum
Creatinine
Uraemic emergencies

Screening Methods
Serum Creatinine
Estimated glomerular filtration rate
(GFR)
Urine testing :

Serum Creatinine
Sr creatinine is poor reflection of early renal
disease/failure
Damage < 60% sr creatinine still normal
Almost all early renal failure patients are
asymptomatic
SCREENING IS THEREFORE VERY IMPORTANT

Estimated Glomerular Filtration rate

Estimate of GFR by the Cockcroft and Gault equation

Man

1.23 x (140-Age) x BW
Sr Cr (umol/l)

Woman

1.04 x (140-Age) x BW
Sr Cr (umol/l)

Estimated Glomerular Filtration rate

MDRD
eGFR (mL/min/1.73m2)= 186 x
[SerumCreatinine(umol/L) x 0.0113]-1.154 x
Age(years)-0.203 (x 0.742 if female)

Continued.
The formula is named after the Modification of
Diet in Renal Disease study in the USA.
The results are expressed relative to a
standard body surface area of 1.73 m 2 to
allow for different body sizes.
The equation is only valid in persons over 17
years of age.
Results >60 mL/min/1.73m 2 are likely to
deviate from the true value and should not be
relied upon.
The use of the eGFR in patients on dialysis is
inappropriate and will give misleading results.

Urine Testing
Urine for protein
Dipstick
24 hour urinary protein

Urine microscopic examination

For RBC / Pus Cell / Cast

Urine for microalbuminuria

On morning urine sample
using strip for microalbumin

Targets for Screening

Hypertensive patients
Diabetic patients
Cardiovascular
disease
Proteinuria
Hematuria
Those on regular
NSAID/Herbs

Renal calculi
Anemia of unknown
aetiology
First and second
degree relatives of
ESRD
Autoimmune disease
(SLE/RA)
Reduction of kidney
mass(Nephrectomy

Risk factors for progression of CKD

Hypertension
Hyperglycemia
Proteinuria
Coffee
Smoking
Salt

Chronic Kidney Disease

Causes
The most common causes of CKD are diabetes mellitus,
hypertension, and glomerulonephritis.Together, these cause
approximately 75% of all adult cases.
Certain geographic areas have a high incidence of HIV
nephropathy.

Chronic Kidney Disease

Causes
kidney disease classified according to the part of the renal anatomy
that is involved (Vascular, Glomerular, Tubulointerstitial,
Obstructive):

Vascular, includes large vessel disease such as bilateral renal

artery stenosis and small vessel disease such as ischemic
nephropathy, hemolytic-uremic syndrome and vasculitis

Glomerular subclassified into

o

Primary Glomerular disease such as focal segmental

glomerulosclerosis and IgA nephritis

Secondary Glomerular disease such as diabetic nephropathy and lupus

nephritis

Chronic Kidney Disease

Causes

Tubulointerstitial including polycystic kidney disease,

drug and toxin-induced chronic tubulointerstitial nephritis
and reflux nephropathy
Obstructive such as with bilateral kidney stones and
diseases of the prostate
On rare cases, pin worms infecting the kidney can also
cause idiopathic nephropathy.

Classification of CKD by Diagnosis

Diabetic Kidney Disease
Glomerular diseases (autoimmune diseases, systemic
infections, drugs, neoplasia)

Vascular diseases (renal artery disease, hypertension,

microangiopathy)

Tubulointerstitial diseases (urinary tract infection,

stones, obstruction, drug toxicity)

Cystic diseases (polycystic kidney disease)

Diseases in the transplant (Allograft nephropathy,
drug toxicity, recurrent diseases, transplant glomerulopathy)

Stages
All individuals with a Glomerular filtration rate (GFR) <60
mL/min/1.73 m2 for 3 months are classified as having chronic
kidney disease, irrespective of the presence or absence of
kidney damage.
The rationale for including these individuals is that reduction
in kidney function to this level or lower represents loss of half
or more of the adult level of normal kidney function, which
may be associated with a number of complications.

Stage 1
Slightly diminished function. Kidney damage with normal or
relatively high GFR (90 mL/min/1.73 m2). Kidney damage is
defined as pathologic abnormalities or markers of damage, including
abnormalities in blood or urine test or imaging studies.
Stage 2
Mild reduction in GFR (60-89 mL/min/1.73 m2) with kidney
damage. Kidney damage is defined as pathologic abnormalities or
markers of damage, including abnormalities in blood or urine test or
imaging studies.

Stage 3
Moderate reduction in GFR (30-59 mL/min/1.73 m2).
Stage 4
Severe reduction in GFR (15-29 mL/min/1.73 m2)
Preparation for renal replacement therapy
Stage 5
Established kidney failure (GFR <15 mL/min/1.73 m2) or
permanent renal replacement therapy (RRT)

KIDNEY FAILURE
ACUTE KIDNEY INJURY

RECURRENT

CHRONIC KIDNEY DISEASE

CKD Stage 1

NORMAL

CKD Stage 2
CKD Stage 3
CKD Stage 4

HEMODYALISIS
PERITONEAL DYALISIS

CKD Stage 5
DYALISIS

TRANSPLANTATION

Treatment
The goal of therapy is to slow down or halt the otherwise
relentless progression of CKD to stage 5.
Control of blood pressure and treatment of the original
disease, whenever feasible, are the broad principles of
management. Generally, ACEIs or ARBs are used, as they
have been found to slow the progression of CKD to stage 5.

 Replacement of erythropoietin and calcitriol, two hormones

processed by the kidney, is often necessary in patients with
advanced CKD.
Phosphate binders are also used to control the serum
phosphate levels, which are usually elevated in advanced
chronic kidney disease.
When one reaches stage 5 CKD, renal replacement therapy is
required, in the form of either dialysis or a transplant

Prognosis
The prognosis of patients with chronic kidney disease is guarded as
epidemiological data has shown that all cause mortality (the overall
death rate) increases as kidney function decreases.
The leading cause of death in patients with chronic kidney disease is
cardiovascular disease
While renal replacement therapies can maintain patients indefinitely
and prolong life, the quality of life is severely affected.

Prognosis
Renal transplantation increases the survival of patients with
stage 5 CKD significantly when compared to other therapeutic
options
High intensity home hemodialysis appears to be associated
with improved survival and a greater quality of life, when
compared to the conventional three times a week hemodialysis
and peritoneal dialysis.

Glomerulonephritis
Renal disease characterized by inflammation of the
glomeruli, or small blood vessels in the kidneys.
It may present with isolated hematuria and/or proteinuria
(blood resp. protein in the urine); or as a nephrotic
syndrome, a nephritic syndrome, acute renal failure, or
chronic renal failure.
They are categorised into several different pathological
patterns, which are broadly grouped into nonproliferative or proliferative types.
Diagnosing the pattern of GN is important because the
outcome and treatment differs in different types.
Primary causes are ones which are intrinsic to the
kidney, whilst secondary causes are associated with
certain infections (bacterial, viral or parasitic pathogens),
drugs, systemic disorders (SLE, vasculitis) or diabetes.

Non Proliferative
This is characterised by the numbers of cells (lack of hypercellularity) in the glomeruli.
They usually cause nephrotic syndrome. This includes the following types:

1.
2.
3.

Minimal change GN
Focal Segmental Glomerulosclerosis (FSGS)
Membranous glomerulonephritis

Proliferative
This type is characterised by increased number of cells in the glomerulus (hypercellular).
Usually present as a nephritic syndrome and usually progress to end-stage renal failure
(ESRF) over weeks to years (depending on type).

1.
2.
3.
4.

IgA nephropathy (Berger's disease)

Post-infectious
Membranoproliferative/mesangiocapillary GN
Rapidly progressive glomerulonephritis

Minimal change GN
This form of GN causes 80% of nephrotic syndrome
in children, but only 20% in adults.
no changes visible on simple light microscopy, but
on electron microscopy there is fusion of podocytes
(supportive cells in the glomerulus).
Immunohistochemistry staining is negative.
Treatment consists of steroids to halt the disease
process (typically Prednisone 1mg/kg).
Over 90% of children respond well to steroids, being
essentially cured after 3 months of treatment.
Adults have a lower response rate (80%). Failure to
respond to steroids ('steroid resistant') or return of
the disease when steroids are stopped ('steroid
dependent') may require cytotoxic therapy (such as
ciclosporin) which is associated with many sideeffects.

IgA nephropathy (Berger's disease)

IgA nephropathy is the most common type of
glomerulonephritis in adults worldwide.
It usually presents as macroscopic haematuria
(visibly bloody urine).
It occasionally presents as a nephrotic syndrome.
It often affects young males within days (24-48hrs)
after an upper respiratory tract or gastrointestinal
infection.
Microscopic examination of biopsy specimens
shows increased number of mesangial cells with
increased matrix (the 'cement' which holds
everything together).
Immuno-staining is positive for immunoglobulin A
deposits within the matrix.
Prognosis is variable, 20% progress to ESRF.

Rapidly progressive glomerulonephritis

Crescentic glomerulonephritis induced by
infective endocarditis on PAS staining and
immunofluorescence.
PAS staining demonstrated circumferential and
cellular crescent formation with interstitial
nephritis. Immunofluorescence demonstrated C3
positive staining in mesangial area
Photomicrograph of renal biopsy showing crescent
formation and tuft narrowing. Periodic acid silver
methenamine stain.
Rapidly progressive glomerulonephritis
(Crescentic GN) has a poor prognosis, with rapid
progression to kidney failure over weeks.
Steroid therapy is sometimes used.