Chronic Kidney Disease

Haerani Rasyid
Nephrology & Hypertension Division, Internal Medicine Department,
Medical Faculty Hasanuddin University
2016
 Criteria for definition of CKD

Albuminuria as a marker of kidney damage [increased glomerular permeability], urine AER 6

≥30 mg/24 hours, approximately equivalent to urine ACR ≥ 30 mg/g (≥ 3 mg/mmol)*
• The normal urine ACR in young adults is <10 mg/g (<1 mg/mmol)
• Urine ACR 30-300Kidney damage
mg/g (3–30 as defined
mg/mmol; categoryby
A2)structural
generally corresponds to
‘‘microalbuminuria,’’ now referredor
abnormalities to functional
as ‘‘moderately increased’’
abnormalities other
• Urine ACR >300 mg/g (>30 mg/mmol; category A3) generally corresponds to
than decreased GFR
‘‘macroalbuminuria,’’ now termed ‘‘severely increased’’
• Urine ACR >2200 mg/g (220 mg/mmol) may be accompanied by signs and symptoms of
nephrotic syndrome (e.g., low serum albumin, edema, and high serum cholesterol)
• Threshold value corresponds approximately to urine reagent strip values of trace or +,
depending on urine concentration.
• High urine ACR can be confirmed by urine albumin excretion in a timed urine collection
expressed as AER

Kidney Int Suppl. 2013, 3: 19–62

 Criteria for definition of CKD

Urinary sediment abnormalities as markers of kidney damage

Kidney damage as defined by structural
• Isolated non-visible (microscopic) hematuria with abnormal RBC
abnormalities or functional abnormalities other
morphology (anisocytosis) in GBM disorders
than decreased GFR
• RBC casts in proliferative glomerulonephritis
• WBC casts in pyelonephritis or interstitial nephritis
• Oval fat bodies or fatty casts in diseases with proteinuria
• Granular casts and renal tubular epithelial cells in many parenchymal
diseases (non-specific)

Kidney Int Suppl. 2013, 3: 19–62

 Criteria for definition of CKD

Renal tubular disorders

• Renal tubular acidosis
• NephrogenicKidney damage as defined by structural
diabetes insipidus
abnormalities or functional abnormalities other
• Renal potassium wastingGFR
than decreased
• Renal magnesium wasting
• Fanconi syndrome
• Non-albumin proteinuria
• Cystinuria

Kidney Int Suppl. 2013, 3: 19–62

 Criteria for definition of CKD
Pathologic abnormalities detected by histology or inferred
(examples of causes)
• Glomerular diseases (diabetes,
Kidney damage autoimmune
as defined by structuraldiseases,
systemic infections, drugs,
abnormalities or neoplasia)
functional abnormalities other
than decreased
• Vascular diseases GFR
(atherosclerosis, hypertension, ischemia,
vasculitis, thrombotic microangiopathy)
• Tubulointerstitial diseases (urinary tract infections, stones,
obstruction, drug toxicity)
• Cystic and congenital diseases

Kidney Int Suppl. 2013, 3: 19–62

 Criteria for definition of CKD
History of kidney transplantation
• Kidney biopsies in most kidney transplant recipients have
histopathologic abnormalities even if GFR is >60
Kidney damage as defined by structural
ml/min/1.73m2 (GFR categories G1-G2) and ACR is <30 mg/g
abnormalities or functional abnormalities other
(<3 mg/mmol)than decreased GFR
• Kidney transplant recipients have an increased risk for
mortality and kidney failure compared to populations without
kidney disease
• Kidney transplant recipients routinely receive subspecialty
care

Kidney Int Suppl. 2013, 3: 19–62

 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 referred 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
Risk Factors Contributing to CKD

 Susceptibility Factors (increased susceptibility to

kidney damage)
Older age
Race
Low income or education
Obesity
Genetic Factors / Family History
Reduction in kidney mass

Levey AS. Ann Intern Med.2003;139:137-147

Risk Factors Contributing to CKD
 Initiation Factors (directly initiate kidney
damage)
Diabetes
Hypertension
Autoimmune Diseases
Systemic infection
Urinary infections and stones/obstruction
Drug toxicity

Levey AS. Ann Intern Med.2003;139:137-147

Risk Factors Contributing to CKD

 Progression Factors (cause worsening

kidney damage)
Higher level of proteinuria
Higher blood pressure
Poor glycemic control
Smoking

Levey AS. Ann Intern Med.2003;139:137-147

Detection of CKD: Who to screen?
 Family history of kidney disease
 Diabetics
 Hypertension
 Recurrent urinary tract infections
 Urinary obstruction
 Systemic illness that affect kidneys
 Patients over 60
 Individuals receiving potentially nephrotoxic drugs, herbs,
substances or taking indigenous medicine
 All patients of Cardiovascular disease
 Pts of obesity, metabolic syndrome, smokers
 Clinical Manifestation of
Chronic kidney disease

Neurologic Abnormalities
Central
Cognitive change
Lethargy Cardiovascular Abnormalities
Stupor Hypertension
Coma Pericarditis
Peripheral Accelerated atherosclerosis
Motor neuropathy Vascular calcifications
Sensory neuropathy
Myoclonus
Fasciculations
 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 Metabolic Abnormalities
deposition Glucose intolerance
Hyperparatiroidism
Vitamin D deficiency
Hyperlipidemia
Sexual dysfunction
Pleural-Pulmonary Abnormalities Malnutrition
Pleuritis and effusion
Parenchymal calcification
Edema
 Clinical Manifestation of
Chronic kidney disease)

Electrolytes
Bone Abnormalities
Hyperkalemia
Osteomalacia
Hyponatremia
Osteitis fibrosa
Hyperphosphatemia
Osteosclerosis
Hypocalcaemia
Aluminum associated
Hyperuricaemia
osteomalacia
Metabolic Acidosis
 What is the Benefit of
Early Detection of
Chronic Kidney Disease?
 CKD
 Asymptomatic in early
 CKD is easily detectable,
stage
preventable
 A progressive disease  There is an efficient
 High morbidity and screening test
mortality  Treatment can reduce
 High cost treatment progression of the disease
 Low quality of life  There is an accepted and
effective treatment for
delaying disease
progression
 How to screen CKD
• All subjects
– Measurement of blood pressure
– eGFR calculation using serum creatinine
– Microalbuminuria and proteinuria, Cystatin C
– Urine sediment dipstick for RBC, WBC
• Selected subjects
• USG, Serum electrolytes, Ca, Ph, PTH
• Urine osmolality, Na, Specific gravity
 Frequency of Screening
1. Diabetics should be tested at least once a yr.

2. Others at risk to be tested once in 2 years

Who should perform the screening?

• Doctors
• Nurses
• Trained health care profesionals
 Why eGFR ? Why not Creatinine ?

SCr eGFR CKD

Age Gender Race (mg/dL) (ml/min/1.73 m2) Stage
20 M B 1.3 91 1

20 M W 1.3 75 2

55 M W 1.3 61 2

20 F W 1.3 56 3

55 F B 1.3 55 3

85 F W 1.3 41 3
Estimated GFR is not valid in :
• Children
• Malnutrition
• Pregnancy
• Acute Kidney Injury
• Oedematous states
Cystatin-C as a new marker of
Glomerular Fitration Rate
 Cystatin C (CysC), as a marker of GFR

 CysC : A member of the family of cysteine proteinase

inhibitors.
 Produced at a constant rate.
 Freely filtered by the glomerulus. is not secreted, but is
reabsorbed by tubular epithelial cells & subsequently
catabolized,doesn’t return to the blood flow.
 The use of serum CysC to estimate GFR is based on the
same logic as the use of blood urea nitrogen & creatinine,
but because it doesn’t return to the bloodstream & isn’t
secreted by renal tubules, it has been suggested to be
closer to the “ideal” endogenous marker.
 Cystatin C (CysC), as a marker of GFR
Cystatin C Estimasi LFG Penilaian LFG N
(mg/L) (ml/menit) Mean + SD (ml/menit)
0,6 145 125 + 34 14
0,7 119 111 + 26 31
0,8 99 93 + 16 21
0,9 85 84 + 27 17
1,0 74 79 + 15 21 GFR (ml/min) = 99.43 x (cys C)-1.5837
1,1 65 68 + 12 15
1,2 58 61 + 16 9
1,3 52 55 + 13 15
1,4 47 55 + 14 12
1,5 - 1,6 41 40 + 19 12
1,7 - 1,8 35 42 + 10 9
1,9 - 2,0 30 32 + 7 7
2,1 - 2,3 26 34 + 6 7
2,4 - 2,6 22 28 + 11 5
2,7 - 3,0 18 24 + 7 5

Normal range CysC in normal adults : 0.51 - 0.98 mg/L

Grubb AO. Adv Clin Chem. 2000;35:70

Factors affecting conventional markers of kidney
function
 Microalbuminuria
( Albuminuria “Moderately Increased” )
Imp. of Albuminuria in CKD

1. Marker of CKD •Spot ACR > 30 mg/g for more than 3 months

2. Clue to Dx. •Spot ACR > 500 mg/g indicates DKD, Glomer,
Transplant GP
CKD
3. Prognostic •Higher proteinuria - severe CKD and higher CV risk
indicator
Index
4. Modified by •B.P control, use of ACEi / ARBs slow CKD predict
improvement
Rx.
5. Surrogate •Validated as the marker for CKD and is the goal of
therapy
Goal
Microalbuminuria
( Albuminuria “Moderately Increased” )

An abnormally elevated urinary albumin excretion (UAE)

in the absence of clinical proteinuria as measured by
standard laboratory methods

Ruilope LM and Rodicio JL. Blood pressure 1996;5(Suppl 4):48-52

 Pathophysiological processed associated
with ( Albuminuria “Moderately Increased” )

Local Process
1. Increased intraglomerular capillary pressure
2. Increased shunting of albumin through glomerular membrane pores

Systemic Process
1. Activation of inflammatory mediators
2. Increased transcapillary escape of albumin
3. Vascular endothelial dysfunction

Garg JP, Bakris GL. Vasc Med 2002;7:35.

( Albuminuria “Moderately Increased” )
Mostly in :

 1. Diabetic patients : - Type 1 DM (5-50 %)

- Type 2 DM (10-80 %)

 2. Hypertension (5-40 %)

 3. Elderly subjects (Non-HT, Non-DM; 5-12 %)

 4. General population (2-5 %) :

- Genetic background

- Intrauterine growth retardation

- Obese subjects

- Low nephron number

 Common causes of reversible
( Albuminuria “Moderately Increased” )

Systemic Factors:
• Fever
• Exercise
• Poor glycemic control
• Congestive heart failure
Local Factors:
• Urinary tract infection
• Hematuria

Stigant CE, Can J Diag,2006;96-99

 Interventions to slow
progression of CKD

To be avoided to prevent
acute reduction in GFR
 Important Guidelines

Interventions to slow To be avoided to prevent

progression of CKD 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
GP and Nephrologist in CKD

Internist
What can primary care providers do?

• Recognize and test at-risk patients

• Educate patients about CKD and treatment

• Focus on good glycemic control in people with diabetes

• For those with CKD:

– Blood pressure below 130/80
– Use an ACE inhibitor or ARB
– More than one drug is usually required
– A diuretic should be part of the regimen
What can primary care providers do?
(Continued)

• Monitor eGFR and UACR

• Treat cardiovascular risk, especially with smokers and

hypercholesterolemia
• Screen for anemia (Hgb), malnutrition (albumin), metabolic
bone disease (Ca, Phos, PTH)
• Refer to dietitian for nutritional guidance
• Consult or team with a nephrologist
Indications for referral of CKD patients to a
nephrologist
 GFR <30 mL/min/1.73 m2 (stage 4 or 5 CKD)
 Rapidly declining kidney function (>15% ↓ in GFR over 3
months)
 Significant proteinuria >1 g/24 hours
 Glomerular haematuria
 Kidney impairment plus hypertension that proves difficult to
control
 Diabetes with kidney impairment or proteinuria/albuminuria
 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 Rx. comorbid Rx. complications; & transplant
CKD conditions; Prepare for
↓ progression replacement
Rate of annual eGFR change

Annual rate of estimated

glomerular filtration rate
(eGFR) decline in each
patient and the
epresentative line of eGFR
change for all patients before
and after nephrology
referral.

Chen, et al. Nephrology. 2008;13:730–736

 TAKE HOME MESSAGE
Important to screening CKD (eGFR (creatinine, Cystatin C), albuminuria

Intervention Therapeutic goal

Specific renoprotective therapy
• ACE inhibitor or ARB treatment (consider Proteinuria <0.5 g/day
combination therapy if goals are not achieved GFR decline <2 mL/min/year
with monotherapy)
Adjunctive cardiorenal protective therapy
• Additional antihypertensive therapy (if <130/80 mmHg
needed)
• Dietary protein restriction 0.6-0.8 g/Kg/day
• Dietary salt restriction 3-5 g/day
• Tight glycemic control in diabetes HbA1c <6.5%
• Reduce elevated calcium-phosphorus product Normal values
• Lipid lowering therapy
• Anti-platelet therapy LDL-C <100 mg/dL
• Consider correction of anemia Thrombosis prophylaxis
• Smoking cessation Hb>12 g/dL
• Weight control Abstinence
Ideal body weight
Abbrevations are: ACE, angiotensin-converting-enzyme; ARB angiotensin receptor blockers; GFR, glomerular filtration rate;
HbA1c, Hemoglobin A1c; LDL-C, low-density-lipoprotein cholesterol; Hb, hemoglobin

Brenner BM. Kidney Int.2003;64:369–378

Thank
yOu