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Chronic Kidney

Disease

Gatot Sugiharto, MD, Internist


Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

Excretion organ system

Field, Pollock, Harris, The Renal System, 2001

Fungsi Ginjal

Mengeluarkan sisa metabolisme :


ureum,kreatinin,uric acid,aliphatic
amine,2
microglobulin,PTH,myoglobulin,dll
Mengeluarkan kelebihan air dan
elektrolit (K,Na,Al,H,P)
Produksi erythropoietin, reninangiotensin,vitamin D3 aktif
Menjaga keseimbangan asam basa
Membuang toksin dan obat
Replaced partially by HD

AJKD 2002: 39(2)

Why Classify Severity as the


Level of GFR?

AJKD 2002: 39(2)

Stages of chronic kidney disease


Stage

Description

GFR (mL/min/1.73
m2)

Kidney damage with normal


or GFR

90

Kidney damage with mild


GFR

60-89

Moderate GFR

30-59

Severe GFR

15-29

Kidney failure

(or dialysis )15>

Chronic kidney disease is defined as either kidney damage or GFR <60 mL/min/1.73 m2
for 3 months. Kidney damage is defined as pathologic abnormalities or markers of
damage, including abnormalities in blood or urine tests or imaging studies.

Definition and Stages of


Chronic Kidney Disease

AJKD 2002: 39(2)

Stages in Progression of CKD


and Therapeutic Strategies

AJKD 2002: 39(2)

Pathophysiology(1)

Approximately 1 million nephrons per


kidney
each has its own single-nephron GFR

With lose of nephrons over time, remaining


nephrons increase single-nephron GFR
Over time, this increased glomerular pressure
causes hypertrophy results and eventually
nephron death

Glomerulosclerosis
prolonged increased glomerular capillary
pressure leads to continuous cycle of nephron
destruction

Pathophysiology(2)

Hypertension cause of CKD - increases single


nephron GFR.
If you have Both diabetes and hypertension
risk of ESRD increased 5 to 6 fold compared to
hypertension alone

Hypercholesterolemia as cause of CKD


accumulation of apolipoproteins in glomerular
mesangial cells -> cytokine production and
infiltration of macrophages, LDL causes oxidative
damage
Use of statin therapy may reduce proteinuria and
CKD progression

Evaluation of Kidney Function(1)

Ideal agent to determine kidney function


nontoxic substance that is freely filtered at
glomerulus and not secreted, reabsorbed, or
metabolized by the kidney.
e.g. Inulin and radioactive labeled substances,
However, not practical in clinical practice

Creatinine - endogenous substance


derived from breakdown of muscle
creatine phosphate.
Primarily excreted by glomerular filtration and
a little by tubular secretion

Evaluation of Kidney Function(2)

Creatinine As nephron function declines, tubular secretion


increases, so, as disease progresses, creatinine
clearance may overestimate glomerular
filtration

Creatinine alone - is an OK evaluation of


glomerular filtration rate (if its high, then
there is a problem)
However, patients age /gender need to be
considered
creatinine clearance CrCl calculations should
be performed

When identifying kidney disease, recall


the relationship between S Cr and GFR

Cockcroft-Gault
Formula
to estimating GFR

(140-age) * (Wt in kg) * (0.85 if


female) / (72 * Cr)

Estimation of GFR in children

MDRD estimating equation is not


applicable to children

Updated Schwartz formula provides


reasonable estimate in children with mildmoderate CKD

(GFR 15-75 mL/min/1.73 m2)


Updated
Updated Schwartz
Schwartz Formula
Formula
eGFR
eGFR =
= kk ** Ht/S
Ht/Scr
cr

Where
Where k=0.4,
k=0.4, Ht
Ht in
in cm
cm and
and SScrcr in
in mg/dL
mg/dL and
and
measured
measured by
by enzymatic
enzymatic methodology
methodology

Proteinuria

Protein is not normally filtered at


glomerulus and only trace amounts should
be in urine
Albumen in urine - may precede increase
in Scr
Microalbuminuria-20-200 mcg/min (30300mg/24hr)
Proteinuria/albuminuria - >200 mcg/min
(albumin is more specific for glomerular
disease than protein)
Consider : Ingestion of high-protein meal

Etiology

Chronic Kidney Disease (CKD)


loss of functioning nephrons d/t
primary kidney disease
systemic disease
secondary to acute event causing damage to
kidney

Leading cause of end stage renal disease


(ESRD)
diabetes (43%)
hypertension (26%)
chronic glomerulonephritis (8%)

Possible causes of chronic kidney diseae


Include:
glomerulonephritis - accounts for 25% of cases
multisystem disease: eg Diabetes
acute pyelonephritis / tubulointerstitial disease
hypertension and vascular causes
polycystic kidney disease - the most common
cause of familial chronic renal failure
idiopathic in 15% of cases
Rarely: drugs - toxic nephropathy e.g. analgesic
nephropathy

connective tissue disease e.g. polyarteritis


nodosa

Distribution of the etiology of chronic kidney disease (CKD)


in children based upon age

Drug Induced Kidney Disease

Analgesic nephropathy - habitual


ingestion/misuse of analgesics (and usually
caffeine/codeine)
renal papillary necrosis (primary lesion)
Interstitial nephritis (secondary lesion)

Analgesic Syndrome - includes above +


anemia, peptic ulcer disease, urinary tract
infection, atherosclerosis

NSAIDs- may induce ischemic state within


renal medulla by decreasing prostaglandin
mediated vasodilatation

AJKD 2002: 39(2)

Risk factors for CKD


Non-modifiable risk
factor
Older age

Modifiable risk factor

Male gender

Proteinuria

Black Race

Dyslipidemia

Genotype

Hyperuricemia

Hypertension

Smoking

Diabetes and hypertension are


leading causes of kidney failure

.Incident ESRD rates, by primary diagnosis, adjusted for age, gender, & race
USRDS ADR, 2007

CLINICAL PRESENTATION

Early stages of CKD asymptomatic.

Direct kidney injury or disease.

Incidental findings of an elevation in the serum


creatinine concentration and/or abnormalities on
urinalysis.

Detection of congenital or structural anomalies by


imaging studies.

Poor growth.

Symptoms and/or signs of severe renal impairment.

Systemic symptoms and findings due to a


concurrent systemic disease

Clinical features
Symptoms

Fatigue
Dyspnoea
Pleuritic pain
Ankle Swelling
Restless legs
Nausea, anorexiavomiting
Diarrhoea
Pruritus
Reduced concentration
Bone pain
Impotence/ infertility
Menorrhagia

Signs

Pallor

^ BP

Cardiomegaly

Pleural effussion

Pericarditis

Pulm / peripheral oedema

Retinopathy

Prox myopathy

Periph neuropathy

Late: Aryythmias,
encephalopathy, seizures,
coma

Uremic state

anorexia
nausea,
vomiting
growth retardation
platelate dysfunction
pericardial disease
peripheral neuropathy
central nervous system
abnormalities ranging from loss of
concentration and lethargy to
seizures, coma and death.

COMPLICATIONS OF CKD

Disorders of fluid, electrolytes & acid based

Renal Osteodystrophy

Anemia

Hypertension

Dyslipidemia

Endocrine abnormalities

Growth impairment

Decreased clearance of renally excreted


substances from the body (uremia).

Fluid and electrolyte abnormalities

Sodium and water balance


Usually is maintained untill GFR <10-15
CKD 2-3 are less able to respond to rapid
infusions of sodium & are prone to fluid
overload

Hyperkalemia : Reduced GFR


inadequate potassium excretion &
decreased delivery of sodium to DT.

Metabolic acidosis
CKD 3 :
Ammonium excretion begins to fall.
Reduction in titratable acid excretion
(primarily as phosphate).
Decreased bicarbonate reabsorption.
Body utilizes bone to buffer the excess
hydrogen ions.

Renal Osteodystrophy:

Decreased renal clearance of phosphorus


resulting in retention of phosphate and
elevation of serum parathyroid hormone
(PTH)
Decreased production of Calcitriol.
CKD2 reduced calcitriol level &
elevated PTH
CKD3 Subtle signs of bone.
bone pain, difficulty in walking, and/or
skeletal deformities with more advanced
disease.

Anemia

Normochromic, normocytic. Due to


reduced renal erythropoietin production
Microcytosis may reflect iron deficiency
or aluminum excess
Macrocytosis may be associated with
vitamin B12 or folate deficiency.
Occurs at a GFR of 30-58ml/min/1.73m.

Consequences of Anemia in
CKD
Reduced oxygen delivery to tissues
Decrease in Hgb compensated by increased
cardiac output
Progressive cardiac damage and progressive renal
damage1
Increased mortality risk2
Reduced quality of life (QOL)3
Fatigue
Diminished exercise capacity
Reduced cognitive function
Left ventricular hypertrophy (LVH)4

Silverberg et al. Blood Purif. 2003;21:124-130. 2. Collins et al. Semin Nephrol. 2000;20:345-. 1
349; 3. The US Recombinant Human Erythropoietin Study Group. Am J Kidney Dis. 1991;18:50.59; 4. Levin. Semin Dial. 2003;16:101-105
The Johns Hopkins University School of 2005

Hypertension

Volume expansion
Activation of the renin-angiotensin
system.
May be due to medications used to treat
the underlying renal disease.
can be present in the earliest stages of
CKD and its prevalence increases with
progressive declines in GFR..

Dyslipidemia and atherosclerosis

Young adults (25 to 34 years) with CKD have at


least a 100-fold higher risk for CVD related mortality
compared to the general population.
40 to 50 % of patients with CKD have triglyceride
levels greater than 200 mg/dL (2.26 mmol/L).
20 to 30% have total cholesterol levels greater than
240 mg/dL (6.2 mmol/L), 10 to 45 % have LDL
cholesterol levels greater than 130 mg/dL (3.4
mmol/L).
lipoprotein lipase activity is reduced in advanced
renal failure; the increase in parathyroid hormone
secretion may play a contributory role.
A circulating lipase inhibitor also may be retained in
renal failure.

Endocrine Dysfunction:

Growth hormone metabolism


changes in the plasma concentration of GH, its release, and its
end-organ responsiveness due to insulin growth factor binding
proteins.
Thyroid function
alterations in the production, distribution, and excretion of
thyroid hormones.
Sick euthyroid syndrome: low T4 and T3, a normal TSH level,
normal or decreased TBG levels or TRH stimulation test results

Gonadal hormones
Delayed puberty ( average delay 2.5 years)
In males, reduced levels of free testosterone,
dihydrotestosterone, adrenal androgens, and increases LH & FSH
Postpubertal females low estrogen, elevated LH and FSH, and
loss of the LH pulsatile pattern. These disturbances result in
anovulation

Neurodevelopment

Neurologic findings range from seizures


and severe mental retardation to subtle
deficits resulting in poor school
performance.
Uremia, malnutrition & Aluminum.

Treatment of CKD

Patients in stage 1 to 4
Reduce risk factors for progression
(hypertension, diabetes)
Provide interventions that delay progression

Management of secondary complications


fluid and electrolyte abnormalities, anemia,
hyperphosphatemia, hyperparathyroidism,
metabolic acidosis, malnutrition

Renal replacement - hemodialysis,


peritoneal dialysis

GENERAL PRINCIPALS of Management

Treat reversible renal dysfunction


Prevent or slow the progression of renal
disease
Treat the complications of CKD
Identify and adequately prepare the
child/family in whom renal replacement
therapy will be required

Slowing CKD progression

progression of CKD is greatest during the


two periods of rapid growth: infancy and
puberty.
strict blood pressure control
Proteinuria reduction
Dietary protein restriction, lipid lowering
therapy, and correction of anemia.
Avoiding Nephrotoxic drugs

Management CKD Complications(1)

Sodium & water retention:


dietary sodium restriction (1.2 1.5 g/day)
and diuretic therapy (furosemide, thiazide
diuretics)
Fluid & sodium supplementation

Hyperkalemia:

Low potassium diet.


Administration of a loop diuretics.
Correct acidosis.
formula can be mixed with kayexalate
Renal replacement therapy must be
considered if conservative management fails

Management CKD Complications(1)

Metabolic acidosis:
guidelines by the K/DOQI working group are to maintain the serum
bicarbonate level at or above 22 mEq/L
Sodium bicarbonate is started at 1-2 meq/kg/d

Renal osteodystrophy :
Low phosphate diet.
Administration of phosphate binders.
Vitamine D replacement therapy

Hypertension:
The K/DOQI guidelines recommend a target blood pressure of less
than 90th percentile for age, gender, and height, or less than
120/80 mmHg, whichever is lower.
Non pharmacologic therapy
Pharmacological therapy: diuretics, ACE inhibirors, ARBs

Management Anemia

Screening and evaluation of anemia


Annual testing regardless of stage or cause of CKD
Dx is made when Hgb level is below the 5th % of normal adjusted
for age & sex.
Red blood cell indices, Reticulocyte count, Iron parameters (serum
iron, total iron binding capacity, percent transferrin saturation
[TSAT] and serum ferritin)
Test for occult blood in stool

Treatment of anemia
K/DOQI guidelines recommend a target Hb between 11 and 12
g/dL, FDA recommend a Hb of 10-12
Iron therapy: targeted to maintain a TSAT 20 percent and serum
ferritin 100 ng/dL
Iron status should be monitored every 1-3 mon.
Erythropoiesis stimulating agent
initial EPO dose in older children not receiving dialysis is 80 to 120
u/kg per week

Treatment for analgesic


nephropathy

abstinence from NSAIDs and combination


analgesics
high fluid intake to prevent obstruction of
the tubules with necrotic debris
If still need analgesics - consider
propoxyphene, aspirin, APAP alone
Patients requiring chronic analgesics
should use lowest dose to control pain,
avoid combination products, and maintain
hydration status

RENAL REPLACEMENT
THERAPY

CKD - RRT

Indications (Absolute):

Uncontrolled hyperkalemia and acidosis


Uncontrollable hypervolemia (pulmonary edema)
Pericarditis
AMS and somnolence (advanced encephalopathy)
Bleeding diathesis

Indications (Relative):

Nausea, vomiting and poor nutrition


Metabolic acidosis
Lethargy and Malaise
Worsening kidney function <10 ml or <15 ml in
diabetics

CKD - RRT

Transplantation:
Preemptive transplant carries both patient and
graft survival advantage.
Graft survival better with living donor kidneys.
Immunosuppresion is almost always a must.

Hemodialysis System

.Copyright 2010, 2007, 2004, 2000, Mosby, Inc., an affiliate of Elsevier Inc. All Rights Reserved

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