Chronic

Kidney
Disease
objective
Patofisiologi chronic kidney disease
Diagnosis dan klasifikasi
Komplikasi
Treatment
CKD
five stages of
kidney disease
the early stages
(stages 1 and 2) as
well as kidney
failure (stage 5).

Stages 1 and 2 no symptoms
stages 3 and 4 clinical and lab
Stage 5 marked disturbance,
uremic syndrome.


Stage
GFR, mL/min per 1.73 m2

0 >90 risk factors
1 >90 demonstrated kidney damage
2 6089
3 3059
4 1529
5 <15
Source: Modified from National Kidney Foundation.
K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease:
Evaluation, classification and stratification. Am J Kidney Dis 39:suppl 1,
2002.
Definition and keywords
Chronic Renal Failure
End Stage Renal Disease
Uremia
Patofisologi
1. mechanisms specific to the underlying etiology
2. a set of progressive mechanisms (hyperfiltration
and hypertrophy of the remaining viable
nephrons), that are a common consequence
following long-term reduction of renal mass,
irrespective of underlying etiology
reduction in renal mass from an isolated insult may
lead to a progressive decline in renal function
over many years.
Progression of chronic renal injury

Risk Factors
( even normal GFR)
Clinical factors
Diabetes
Hypertension
Autoimmune diseases
Systemic infections
Urinary tract infections
Urinary stones
Lower urinary tract
obstruction
Neoplasia
Family history of chronic
kidney diseases
Recovery from acute
kidney failure
Reduction in kidney mass
Exposure to certain drugs
Low birth weight
Sociodemographic Factors
Older age
US ethnic minority status:
AfricanAmerican, American
Indian, Hispanic, Asian or
Pacific Islander
Exposure to chemical and
environmental conditions
Low income/education
stage CKD estimate the GFR

1. Equation from the
Modification of Diet in
Renal Disease study

2. Cockcroft-Gault
equation

Estimated GFR (mL/min per
1.73 m2) =
1.86 x (PCr)1.154 x (age)0.203


Estimated creatinine clearence
(mL/min) =
(140-age x body weight,kg)
72 x PCr (mg/dL)
Multiply by 0.742 for women
Multiply by 1.21 for African
Americans
Multiply by 0.85 for women

Adapted from AS Levey et al: Am J Kidney Dis 39 (Suppl 1): S1, 2002
~1 mL/min per year per 1.73 m2 decline in GFR :
120-130 mL/min/1.73 m 2
Albuminuria Persistence
24-h urine collection : "gold standard"
albumin-to-creatinine ratio in a spot first-morning
urine

>17 mg albumin/gr creatinine adult males
>25 mg albumin/gr creatinine adult females
signifies chronic renal damage

Microalbuminuria : screening early detection &
marker microvascular disease in general

Etiology and Epidemiology
6% : stages 1 and 2
4.5% : stages 3 and 4

diabetic nephropathy ( type 2 DM )
Hypertensive nephropathy ( elderly )

early stages of renal disease (vascular origin)
cardiovascular and cerebrovascular most advanced
stages of CKD .
variability (genetic loci) in the rate of progression to CKD
women of reproductive age are relatively protected
against progression of many renal diseases, and sex-
specific responses to angiotensin II and its blockade.
Pathophysiology and Biochemistry
of Uremia (1)
Hundreds of toxins that accumulate in
renal failure have been implicated in the
uremic syndrome.
monitoring the levels of urea and
creatinine in the patient with impaired
kidney function represents a vast
oversimplification of the uremic state.
Pathophysiology and Biochemistry
of Uremia (2)
more than renal excretory failure.
metabolic and endocrine functions ( normally
undertaken by the kidneys ) anemia, malnutrition, and
abnormal metabolism of carbohydrates, fats, and
proteins
decreased degradation, or abnormal regulation of
hormones (urinary retention), including PTH, insulin,
glucagon, sex hormones, and prolactin,
worsening systemic inflammation.
C-reactive protein + acute-phase reactants,
negative acute-phase reactants (albumin and fetuin)
malnutrition-inflammation-atherosclerosis/calcification
syndrome, which contributes in turn to the acceleration
of vascular disease and comorbidity
Pathophysiology and Biochemistry
of Uremia (3)
Manifestations in three spheres of dysfunction:
(1) accumulation of toxins normally undergoing
renal excretion, including products of protein
metabolism;
(2) loss of other renal functions, such as fluid and
electrolyte homeostasis and hormone regulation;
and
(3) progressive systemic inflammation and its
vascular and nutritional consequences.
Clinical Abnormalities in Uremia
Fluid and electrolyte disturbances
Volume expansion (I)
Hyponatremia (I)
Hyperkalemia (I)
Hyperphosphatemia (I)

Endocrine-metabolic disturbances
Secondary hyperparathyroidism (I or P)
Adynamic bone (D)
Vitamin Ddeficient osteomalacia (I)
Carbohydrate resistance (I)
Hyperuricemia (I or P)
Hypertriglyceridemia (I or P)
Increased Lp(a) level (P)
Decreased high-density lipoprotein level (P)
Protein-energy malnutrition (I or P)
Impaired growth and development (P)
Infertility and sexual dysfunction (P)
Amenorrhea (I/P)
2-Microglobulin associated amyloidosis (P or D)
Neuromuscular disturbances
Fatigue (I)b
Sleep disorders (P)
Headache (P)
Impaired mentation (I)b
Lethargy (I)b
Asterixis (I)
Muscular irritability
Peripheral neuropathy (I or P)
Restless legs syndrome (I or P)
Myoclonus (I)
Seizures (I or P)
Coma (I)
Muscle cramps (P or D)
Dialysis disequilibrium syndrome (D)
Myopathy (P or D)

Cardiovascular and pulmonary disturbances
Arterial hypertension (I or P)
Congestive heart failure or pulmonary edema (I)
Pericarditis (I)
Hypertrophic or dilated cardiomyopathy (I, P, or D)
Uremic lung (I)
Accelerated atherosclerosis (P or D)
Hypotension and arrhythmias (D)
Vascular calcification (P or D)
Dermatologic disturbances
Pallor (I)b
Hyperpigmentation (I, P, or D)
Pruritus (P)
Ecchymoses (I)
Nephrogenic fibrosing dermopathy (D)
Uremic frost (I)

Gastrointestinal disturbances
Anorexia (I)
Nausea and vomiting (I)
Gastroenteritis (I)
Peptic ulcer (I or P)
Gastrointestinal bleeding (I, P, or D)
Idiopathic ascites (D)
Peritonitis (D)

Hematologic and immunologic disturbances
Anemia (I)b
Lymphocytopenia (P)
Bleeding diathesis (I or D)b
Increased susceptibility to infection (I or P)
Leukopenia (D)
Thrombocytopenia (D)
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
B Improves with dialysis and erythropoietin therapy.
Fluid, Electrolyte and Acid-Base
Disorders
Sodium and Water Homeostasis
Potassium Homeostasis
Metabolic Acidosis

Treatment
dietary intake of salt (ECFV depletionGFR)
loop diuretics (metolazone)
Water restriction (only hyponatremia)
Restriction potassium/Potassium-binding resins
alkali supplementation

Disorders of Calcium and
Phosphate Metabolism (1)
Disorders of Calcium and
Phosphate Metabolism (2)
Bone Manifestations of CKD
Calcium, Phosphorus, and the Cardiovascular
System
Other Complications of Abnormal Mineral
Metabolism

Treatment:
prevention
low-phosphate diet
phosphate-binding agents (calcium acetate and calcium
carbonate total-body calcium >, hypercalcemia)
Calcitriol (hypercalcemia and/or hyperphosphatemia)
calcimimetic agents
target PTH level between 150 and 300 pg/mL


Cardiovascular Abnormalities
leading cause of morbidity and mortality every stage

Ischemic Vascular Disease
Heart Failure
Hypertension and Left Ventricular
Hypertrophy
-slow the progression of the kidney disease itself
-prevent the extrarenal complications of high blood
pressure 125/75, such as cardiovascular disease
and stroke->Salt restriction+diuretics
Lifestyle changes.
Hyperhomocysteinemia vitamin (oral folate).
Hyperlipidemia statins
Pericardial Disease
Uremic pericarditisabsolute indication dialysis
pericardial drainagerecurrent pericardial effusion.
Nonuremic causes of pericarditis and effusion : viral,
malignant, tuberculous, and autoimmune etiologies.
It may also be seen after myocardial infarction and
as a complication of treatment with minoxidil.


Hematologic Abnormalities
(1)
Anemia
normocytic normochromic
decreased tissue oxygen delivery
and utilization, increased cardiac
output, ventricular dilatation, and
ventricular hypertrophy.
Treatment : 11 to 12 g/dL.
human EPO and modified EPO
products
oral iron supplementation
Blood transfusions


Causes of Anemia in CKD

Relative deficiency of
erythropoietin
Diminished red blood cell survival
Bleeding diathesis
Iron deficiency
Hyperparathyroidism/bone marrow
fibrosis
"Chronic inflammation"
Folate or vitamin B
12
deficiency

Hemoglobinopathy
Comorbid conditions:
hypo/hyperthyroidism, pregnancy,
HIV-associated disease,
autoimmune disease,
immunosuppressive drugs
Hematologic Abnormalities
(2)
Abnormal Hemostasis
Patients with later stages
prolonged bleeding time,
decreased activity of platelet factor III,
abnormal platelet aggregation and adhesiveness,
and impaired prothrombin consumption
Treatment :
reversed temporarily with desmopressin (DDAVP),
cryoprecipitate, IV conjugated estrogens, blood
transfusions, and EPO therapyOptimal dialysis
correct a prolonged bleeding time
No anticoagulationconventional high-molecular-
weight heparin


Neuromuscular Abnormalities
Central nervous system (CNS)
peripheral
autonomic neuropathy
abnormalities in muscle structure and function
Patofisiologi : Retained nitrogenous metabolites & middle molecules
(PTH)
Early CNS : memory, concentration, and sleep
Subtle uremic neuromuscular disease stage 3
Neuromusc irritability: hiccups, cramps, and
fasciculations/twitching later
Peripheral neuropathy stage 4 (electrophysiologic and histologic
earlier) renal replacement therapy.
advanced untreated asterixis, myoclonus, seizures, and coma
sensory nerves > motor (dialysis)
lower extremities > upper
distal parts of the extremities > proximal
The "restless leg syndrome
Gastrointestinal and Nutritional
Abnormalities
Uremic fetor
Gastritis, peptic disease, and mucosal ulcerations abdominal
pain, nausea, vomiting, and GI bleeding uremic toxins
Constipation
Protein restriction nausea and vomiting risk for malnutrition
Protein-energy malnutrition stage 3 renal replacement th/.
diminished intake resistant anabolic actions insulin and other
hormones and growth factors.
Metabolic acidosis and the activation of inflammatory cytokines
protein catabolism.
edema-free body weight; serum albumin concentration; and
measurement of urinary protein nitrogen appearance,
Dual-energy x-ray absorptiometry
clinical signs
additional laboratory tests (serum pre-albumin and cholesterol levels)

Endocrine-Metabolic Disturbances
Impaired glucose metabolism slowing decline
fasting blood glucoseusually normal / only slightly
elevated, mild glucose intolerance no specific therapy.
insulin slightly to moderately elevated uremic patients
Metformin contraindicated when the GFR < normal.
women estrogen menstrual abnormalities and
inability to carry pregnancies to term
GFR ~40 mL/min high spontaneous abortion (~20% live)
pregnancy hasten progression of the kidney disease itself.
Men plasma testosterone and sexual dysfunction
and oligospermia may supervene.
Sexual maturation delayed or impaired, even with
dialysis.
Many of these abnormalities improve or reverse with
intensive dialysis or successful renal transplantation.

Dermatologic Abnormalities
Anemic pale
defective hemostasis multiple ecchymoses
Pruritus is quite common & tenacious
advanced CKD, even on dialysis : more pigmented
deposition of retained urochromes.
management
rule out unrelated skin disorders (scabies),
control phosphate concentration.
EPO improve uremic pruritus,
Local moisturizers, mild topical glucocorticoids, oral antihistamines,&
UV radiation.
nephrogenic fibrosing dermopathy induration,arms
and legs.~scleromyxedema, common on dialysis. exposure
to the magnetic resonance contrast agent, gadolinium :
precipitate

Evaluation and Management of
Patients with CKD
Initial Approach
History and Physical Examination
hypertension, DM, urinalyses, preeclampsia or early loss. Drugs
(NSAID,gold,penisilamin,AM,ARV,PPI,litium). Uremic.
BP-target organ damage. Funcuscopy+precordial. Edema-polineuropati.
Asterixis-PericardialFrictRub.
Laboratory Investigation
SLE-vasculitis, elektroforesis, HepB&C HIV, Ca-Phosphor-PTH, Hb-Fe-B12-
Folat, 24urine
Imaging Studies
renal ultrasound : DM, amyloidosis, and HIV. Polycystic kidney. A
discrepancy >1 cm .
Renovascular: Doppler sonography, nuclear medicine studies, or CT or MRI
studies. voiding cystogram .
Renal Biopsy
Establishing the Diagnosis and Etiology of CKD
Creatinine. ECFV depletion. hyperphosphatemia, hypocalcemia, and elevated
PTH and BAP chronicity. Normochromic normocytic anemia. Bilaterally
reduced kidney size (<8.5 cm) Biopsy:etiology in early-stage

Treatment
Stage Description GFR, mL/min
per 1.73 m2
Action a
1 Kidney damage
with normal or
GFR
>90 Diagnosis and treatment, treatment of
comorbid conditions, slowing
progression, CVD risk reduction

2 Kidney damage
with mild GFR
6089 Estimating progression
3 Moderate
GFR
3059 Evaluating and treating complications
4 Severe GFR 1529 Preparation for kidney replacement
therapy
5 Kidney failure <15
(or dialysis)
Kidney replacement (if uremia present)
a : Includes actions from preceding stages.
Note: CVD, cardiovascular disease.
Source: National Kidney Foundation: Am J Kidney Dis 39(2 Suppl 1):S1, 2002.a
Slowing the Progression of CKD
Protein Restriction (35 kcal/kg)
0.60-0.75 g/kg/day 50% high biologic value. stage 5:0.90
Reducing Intraglomerular Hypertension and
Proteinuria 125/75 mmHg ACE inhibitors and ARBs
Slowing Progression of Diabetic Renal
Disease Control of Blood Glucose (90130 mg/Dl, <7%)
& Control of Blood Pressure and Proteinuria
Managing Other Complications of Chronic
Kidney Disease

Preparation for Renal
Replacement Therapy

protein restriction temporary relief of symptoms
and signs of impending uremiaprotein-energy
malnutrition long-term management.
dialysis and kidney transplantation :
extended the lives of hundreds of thousands of
patients with CKD worldwide.
Clear indications renal replacement :
pericarditis, encephalopathy, intractable muscle
cramping, anorexia, and nausea not attributable to
reversible causes such as peptic ulcer disease,
evidence of malnutrition, and fluid and electrolyte
abnormalities, principally hyperkalemia, that are
refractory to other measures.

Patient Education

Social, psychological, and physical preparation
renal replacement therapy +choice about :
hemodialysis, peritoneal dialysis, and kidney
transplantation.
Kidney transplantation best potential for
complete rehabilitation, because dialysis
replaces only a small fraction of the kidneys'
filtration function and none of the other renal
functions, including endocrine and anti-
inflammatory effects.

Absolute indications for dialysis
severe volume
overload
refractory to
diuretic agents,
severe
hyperkalemia
and/or acidosis,
encephalopathy
not otherwise
explained, and
pericarditis or
other serositis.

Additional indications for
dialysis
symptomatic uremia (e.g., intractable
fatigue, anorexia, nausea, vomiting,
pruritus, difficulty maintaining attention and
concentration)
and protein-energy malnutrition/failure to
thrive without other overt cause.
Contraindications to Renal
Transplantation

ABSOLUTE CONTRAINDICATIONS
Active glomerulonephritis
Active bacterial or other infection
Active or very recent malignancy
HIV infection
Hepatitis B surface antigenemia
Severe degrees of comorbidity
(e.g., advanced atherosclerotic
vascular dsease)
RELATIVE CONTRAINDICATIONS
Age 70 years
Severe psychiatric disease
Moderately severe degrees of
comorbidity
Hepatitis C infection with chronic
hepatitis or cirrhosis
Noncompliance with dialysis or
other medical therapy
Primary renal diseases
Primary focal sclerosis with prior
recurrence in transplant
Multiple myeloma
Amyloid
Oxalosis