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 630 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 30-300
Kidney mg/g (330 mg/mmol;
damage category
as defined by A2) generally
corresponds to microalbuminuria, now referred to as
structural abnormalities or
moderately increased
functional
Urine ACR >300 abnormalities
mg/g (>30 other
mg/mmol; category A3) generally
correspondsthan decreased GFR now termed severely
to macroalbuminuria,
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: 1962

Criteria for definition of CKD

Urinary sediment abnormalities as markers of kidney

damage
Kidney damage as defined by
Isolated non-visible (microscopic) hematuria with
structural abnormalities or
abnormal RBC morphology (anisocytosis) in GBM
functional abnormalities other
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: 1962

Criteria for definition of CKD

Renal tubular disorders

Renal tubular
Kidneyacidosis
damage as defined by
Nephrogenic diabetes
structural insipidus
abnormalities or
functional abnormalities other
Renal potassium wasting
than decreased GFR
Renal magnesium wasting
Fanconi syndrome
Non-albumin proteinuria
Cystinuria

Kidney Int Suppl. 2013, 3: 1962

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

Kidney Int Suppl. 2013, 3: 1962

Criteria for definition of CKD
History of kidney transplantation
Kidney biopsies in most kidney transplant
recipients have histopathologic
abnormalities even
Kidney if GFR
damage is >60by
as defined
ml/min/1.73m2 (GFR
structural categoriesorG1-G2) and
abnormalities
ACR is <30functional
mg/g (<3 abnormalities
mg/mmol)other
than decreased
Kidney transplant GFR
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: 1962

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
progression of the disease
High cost treatment
There is an accepted and
Low quality of life 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,doesnt 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 doesnt return to the bloodstream & isnt
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
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
Complications

Increased
Increased Kidney
Kidney CKD
CKD
Normal
Normal Damage
Damage GFR
GFR
risk
risk failure
failure death
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;13:730736

 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;64:369378

Thank
yOu