CHRONIC KIDNEY DISEASE

I Gde Raka Widiana

Div of Nephrology and Hypertension

Department of Medicine School of Medicine University
Udayana/Sanglah General Hospital
Buku rujukan 1
Buku Rujukan 2
 Definition of CKD

Structural or functional abnormalities of the

kidneys for >3 months, as manifested by either:
1. Kidney damage, with or without decreased GFR, as
defined by
• pathologic abnormalities
• markers of kidney damage, including abnormalities in
the composition of the blood or urine or abnormalities in
imaging tests
2. GFR <60 ml/min/1.73 m2, with or without kidney
damage
 Epidemiology
• Chronic kidney disease (CKD) is a worldwide
problem, due to dialysis economic burden and
high mortality from cardiovascular disease.
• High blood pressure and diabetes mellitus are
major contributors.
• In Indonesia, CKD was reported in 12,5%
among patients with high blood pressure and
diabetes mellitus in the community.
 INDONESIAN
RENAL REGISTRY Etiology of ESRD
(2014)

Hypertension and DM are the top 2 causes of ESRD

Diagnosis of high blood pressure is still to be validated in ESRD patients
 Diabetes and hypertension are
leading causes of kidney failure

Incident ESRD rates, by primary diagnosis, adjusted for age, gender, & race.
USRDS ADR, 2007
1
Apparatus juxta glomerularis
 Pathophysiology
• Repeated injury to kidney
 Sign and symptoms
• Trias
1. Anemia
2. Edema,
3. Hypertension
• Hematuria, flank pain,
• Uremic syndrome lethargy and fatigue,
loss of appetite.
• Elevated SC or
• Abnormal urinalysis.
 Sign of risk factor of CKD

1)Modifiable
Diabetes,
Hypertension,
History of acute kidney injury,
Frequent NSAID and traditional/herbal medicine use
2) non-modifiable
Family history (kidney disease,
diabetes, hypertension)
Age 60 or older (GFR declines normally with age),
Race/ethnic status
 Stages in Progression of Chronic Kidney Disease and
Therapeutic Strategies

Complications

Increased Kidney CKD

Normal Damage  GFR
risk failure death

Screening CKD risk Diagnosis Estimate Replacement

for CKD reduction; & treatment; progression; by dialysis
risk factors Screening for Treat Treat & transplant
CKD comorbid complications;
conditions; Prepare for
Slow replacement
progression
 Clinical Practice Guidelines for the Detection,
Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased
Test for CKD Risk factor management
risk
Diagnosis
Kidney
Comorbid Specific therapy, based on diagnosis
damage with
1 >90 conditions Management of comorbid conditions
normal or 
CVD and CVD Treatment of CVD and CVD risk factors
GFR
risk factors
Kidney
Rate of
2 damage with 60-89 Slowing rate of loss of kidney function 1
progression
mild  GFR
Moderate 
3 30-59 Complications Prevention and treatment of complications
GFR
Preparation for kidney replacement therapy
4 Severe  GFR 15-29
Referral to Nephrologist
5 Kidney Failure <15 Kidney replacement therapy
1
Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot
urine total protein-to-creatinine ratio of greater than 200 mg/g.
Early treatment can make a
difference
100

No Treatment
Current Treatment
Early Treatment
GFR (mL/min/1.732)

10
Kidney Failure
0
4 7 9 11

Time (years)
Who Should be Involved in the
Patient Safety Approach to CKD?

Kidney Kidney
damage and damage and Moderate Severe Kidney
normal or  GFR mild   GFR  GFR failure
GFR

Stage 1 Stage 2 Stage 3 Stage 4 Stage 5

GFR 90 60 30 15

Primary Care Practitioner Nephrologist

Consult?

Patient safety
The Patient (always)
and other subspecialists (as needed)
Proteinuria is an important marker of
kidney damage and prognosis of
deterioration of kidney function.
Albuminuria as a Risk Factor for CVD in PREVEND

Hillege HL et al. Circulation 2002: 106: 1777-1782

 Importance of Proteinuria in CKD
Interpretation Explanation

Marker of kidney Spot urine albumin-to-creatinine ratio >30 mg/g or

damage spot urine total protein-to-creatinine ratio >200 mg/g
for >3 months defines CKD
Clue to the type Spot urine total protein-to-creatinine ratio >500-
(diagnosis) of CKD 1000 mg/g suggests diabetic kidney disease,
glomerular diseases, or transplant glomerulopathy.

Risk factor for adverse Higher proteinuria predicts faster progression of

outcomes kidney disease and increased risk of CVD.
Effect modifier for Strict blood pressure control and ACE inhibitors are
interventions more effective in slowing kidney disease
progression in patients with higher baseline
proteinuria.

Hypothesized If validated, then lowering proteinuria would be a

surrogate outcomes goal of therapy.
and target for
interventions
 High blood pressure
• Important comorbidity has to be controlled
• It contributes to rapid deterioration of kidney
function.
• Particular antihypertensive drugs may result in
delaying reduced rate of kidney function
decline in CKD (compelling drugs)
 Clinical Practice Guidelines for Management of
Hypertension in CKD
Type of Kidney Disease Blood Pressure Preferred Agents Other Agents
Target for CKD, with or to Reduce CVD Risk
(mm Hg) without and Reach Blood
Hypertension Pressure Target
Diabetic Kidney Disease

ACE inhibitor Diuretic preferred,

Nondiabetic Kidney
or ARB then BB or CCB
Disease with Urine Total
Protein-to-Creatinine
Ratio 200 mg/g <130/80
Nondiabetic Kidney Diuretic preferred,
Disease with Spot Urine then ACE inhibitor,
Total Protein-to-Creatinine ARB, BB or CCB
ratio <200 mg/g None preferred
Kidney Disease in Kidney CCB, diuretic, BB,
Transplant Recipient ACE inhibitor, ARB
 Screening of CKD
Estimat GFR (eGFR) using
• CKD-EPI (2009)
• MDRD and
• Cockroft Gault.
GFR calculators are available online at www.kidney.org/GFR.
Albuminuria calculated by
1. albumin-creatinine ratio (ACR) whereas albumin concentration
in milligrams divided by creatinine concentration in grams
(using spot first morning urine sample)
2. 24hr urine test rarely necessary.
 Treatment in CKD
Aiming to slow decline in kidney function, bay mean of:
Blood pressure control:
– targeting blood pressure ≤140/90 mm Hg If ACR normal
(<30 mg/g);
– ≤130/80 mm Hg if ACR 30-300 mg/g:
– ≤130/80 mm Hg if ACR >300 mg/g,
– Individualize targets and agents according to age,
coexistent CVD, and other comorbidities.

Compelling antihypertensive agents are ACE or ARB

 ACEi or ARB
• Slowing CKD progression using ACEi or ARB has to be
considered: risk/benefit of these
• Carefully assessed in the elderly and medically fragile.
• Check labs afterm initiation of treatment;
– if less than 25% SCr increase, continue and monitor and
– if more than 25% SCr increase, stop ACEi and evaluate for
RAS acting drugs.
• Avoid volume depletion
• Avoid ACEi and ARB in combination.
• Monitor risk of adverse events (impaired kidney
function, hyperkalemia).
 Glucose Control
• Targeting HbA1c ~7.0% and can be extended
above 7.0% with comorbidities or limited life
expectancy, and risk of hypoglycemia.
• Attention should be paid  Risk of
hypoglycemia increases as kidney function
becomes impaired and declining kidney
function  non-renally-cleared drugs.
Modification of Other CVD Risk Factors
1. Smoking cessation,
2. exercise,
3. weight reduction to optimal targets,
4. lipid-lowering therapy.
– In adults >50 years,
• when eGFR ≥ 60 → statin is indicated
• when eGFR < 60 statin or statin/ezetimibe combination
– in adults < 50 yrs, statin is indicated if history of known
CAD, MI, DM, stroke.
• Aspirin is indicated for secondary but not primary
prevention.
 Anemia
• Initiate iron therapy if
– TSAT ≤ 20% and
– ferritin ≤ 200 ng/mL for non dialysis
– ferritin ≤ 300 ng/mL for dialysis
– IV iron for dialysis,
– Oral for non-dialysis CKD
• Individualize erythropoiesis-stimulating agent (ESA) therapy:
– Start ESA if Hb <10 g/dL, and
– Maintain Hb 11-12 g/dL.
– No more than 13 g/dL
• Ensure adequate Fe stores.
• Appropriate iron supplementation is needed for ESA to be
effective
 CKD-Mineral and Bone Disorder
(CKD-MBD)

• Risk for uremic osteodystrophy and soft tissue

calcification (coronary arterial disease)
• Treat with D3 as indicated to achieve normal
serum levels
• Calcium suplementation
• Limit phosphorus in the diet (CKD stage 4/5),
• Refer to renal RD
• May need phosphate binders
 Metabolic acidosis

• Usually occurs later in CKD

• Natrium bicarbonate therapy
• Maintain serum bicarb >22mEq/L
• Correction of metabolic acidosis may slow CKD
progression and improve patients functional
status
 Hyperkalemia

• Reduce dietary potassium

• Correct acidosis
• Insulin+beta agonist combined therapy
• Stop NSAIDs, COX-2 inhibitors, potassium-
sparing diuretics (Aldactone)
• Stop or reduce beta blockers, ACEi/ARBs
• Avoid salt substitutes that contain potassium
 Renal Replacement Therapy
Indication: CKD stage 5
Dialysis:
– a.Hemodialysis
– b. CAPD (Continuous ambulatory peritoneal
dialysis)

Kidney transplantation
• Thanks