AKI VS CKD

SPECTRUM OF KIDNEY INJURIES

Azreen Adnan, MD FASN

Associate Professor
Consultant Nephrologists And Physician
Chronic Kidney Disease Resource Center
School Of Medical Sciences
USM
ISSUES IN NEPHROLOGY
AKI – Acute Kidney Injury
Unstable kidney injury biomarkers
Renal excretory diminished at anuric state
Dialyzable vs Non-dialyzable drugs
Regular dialysis vs PRN dialysis
Acute on Chronic Kidney Disease
What is the potential insult?
When is the kidney recovering?
CKD Stage V (End Stage Renal Disease)
AKI: TRADITIONAL UNDERSTANDING

Pre renal • Renal hypoperfusion

• Glomerular
Intrinsic renal • Tubulo-interstitial
• Vascular (macro and micro)

• Intra renal obstruction

Post renal • Extra renal obstruction
DEFINITION OF
ACUTE KIDNEY INJURY

• Sudden onset (within 48 hrs) renal impairment characterized

by:
• absolute increase in serum creatinine of ≥ 26.4 μmol/L
• ≥ 50% increase in serum creatinine or
a reduction in urine output (documented oliguria of
< 0.5 mL/kg/hr for > 6hrs).

Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes in
Acute Kidney Injury. Critical Care 2007; 11: R31.
ETIOLOGY OF ACUTE KIDNEY INJURY
 USE OF PPI TO PREVENT
ADVERSE EFFECT OF NSAID IN
PREVENTION OF PEPTIC ULCER
DISEASE MAYBE HARMFUL !
AVOIDING NSAID IS A RECOGNIZED METHOD OF
PREVENTING PROGRESSION OF CKD (CHRONIC
KIDNEY DISEASE)
RIFLE CLASSIFICATION

ADQI 2005
AKIN CLASSIFICATION

• Modification of the RIFLE classification by Acute

Kidney Injury Network (AKIN).

• Recognizes that small changes in serum creatinine

(>26µmol/L) adversely impact clinical outcome.

• Uses serum creatinine, urinary output and time.

Coca S, Peixoto A, Garg A, et al.: The prognostic importance of a small acute decrement in kidney function in
hospitalized patients: a systematic review and meta-analysis. American Journal of Kidney Diseases 2007; 50:712-
720.
 AKIN CLASSIFICATION

AKIN Serum Creatinine Criteria Urine Output Time

stage Criteria
1  Cr ≥ 0.3 mg/dL or  ≥ < 0.5 mL/kg/hr > 6 hrs
150-200% from baseline
2  Cr to > 200-300% from < 0.5 mL/kg/hr > 12 hrs
baseline
3 Cr to > 300% from < 0.5 mL/kg/hr X 24 hrs
baseline or Cr ≥ 4mg/dL or anuria X 12 hrs
with an acute rise of at least
0.5 mg/dL

*Patients needing RRT are classified stage 3 despite the stage they were before starting RRT
Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes in
Acute Kidney Injury. Critical Care 2007; 11: R31.

AKIN 2007
PATHOPHYSIOLOGY OF ACUTE KIDNEY INJURY:
ROLES OF POTENTIAL INHIBITORS OF INFLAMMATION
SPECTRUM OF KIDNEY INJURIES

AKI

CKD
MAINTAINING HEMODYNAMICS
AKI INITIAL CLINICAL ASSESSMENT

• Is this Acute ? Acute on CKD ? Or CKD

• Is there any pre-renal issue?
• Is there any potential kidney insulting factor? (intrinsic)
• Has there been any major occlusion?
• Is there any GU tract obstruction
• Is there any evidence of parenchymal disease
 CLINICAL APPROACH IN AKI - SUMMARY

Hilton, R. BMJ 2006;333:786-790

 USING CREATININE: PROBLEMS.

• In an unsteady state,
Creatinine does not accurately
reflect the GFR

• By the time Creatinine is

abnormal, there is a 50%
decline in GFR.
 DIAGNOSIS OF RENAL INJURY
• Se.Creatinine:
Limitations:
Does not rise until 50% kidney function lost
Does not accurately depict kidney function until steady state
reached
• Conventional urinary Biomarkers: FeNa, casts
 BIOMARKERS IN AKI

Biomarker Source Cardiac surgery CIN Sepsis K.Tx Commercial

test

NGAL Plasma Early Early Early Early Biosite

Cystatin C Plasma Intermediate Intermediate Intermediate Intermediate Dade-Behring

NGAL Urine Early Early Early Early Abbott

IL 18 Urine Intermediate Absent Intermediate Intermediate None

KIM 1 Urine Intermediate Not tested Not tested Not tested none

NGAL: Neutrophil Gelatinase Associated Lipocalin

TEMPORAL PATTERN OF BIOMARKERS IN AKI
KIM 1
IL 18
NAG
Cystatin C Se Cr
NGAL

2 12 1-3
hrs hrs days
Time
Insult
 AKI Management

Conservative Treat Primary Condition RRT

Fluid Balance Electrolytes Diet

Acute Intermittent Continuous
• CAPD
• CCPD
• SCUF
• APD • Intermittent PD
• AHD • Intermittent HD • CVVH
• Intermittent HF
• SLED • CVVHD
• EDD
• CVVHDF
MODALITY OF TREATMENT IN AKI

1. CRRT
CVVH, CVVHD, CVVHDF

2. SLEDD-f
3. SLEDD

4
POTENTIAL DRUGS TO AVOID DURING AKI
• NSAIDs
• ACEi, ARB
• Aminoglycosides
CONCLUSION

• AKI carries high mortality

• AKI is reversible if prevented and identified early
• Dialysis modality and early initiation improves outcome
 CHRONIC KIDNEY DISEASE:
OVERVIEW AND MANAGEMENT
DEFINITION
 CKD CLINICAL STAGES

Stage Description GFR

(ml/min/1.73 m2)

1 Kidney damage with normal or ↑ GFR  90

2 Kidney damage with mild  GFR 60-89

3 Kidney damage with moderate  GFR 30-59

4 Severe  GFR 15-29

5 Kidney Failure (ESRD) < 15 (or dialysis)

Electronic Clinical Management System For CKD Patients (Predialysis and General
Nephrology)
 ETIOLOGY OF CKD

1. Diabetes - most common cause ESRD (risk 13 x )

2. Over 30% cases ESRD are primarily due to diabetes
3. CKD associated HTN causes @ 23% ESRD cases
4. Glomerulonephritis accounts for ~10% cases
5. Polycystic Kidney Disease - about 5% of cases
6. Rapidly progressive glomerulonephritis (vasculitis) - about 2%
of cases; Drug induced Tubulo-interstitial
7. Renal Vascular Disease - renal artery stenosis
 ENDOGENOUS FILTRATION MARKERS
CREATININE & CYSTATIN C6,7
Creatinine Cystatin C
Small Amino Acid derived from muscle mass Relatively small molecule derived from all nucleated cells

Both filtered by the glomerulus and secreted (10-15%) by the Filtered but not secreted by the kidney
proximal tubule

Dependant on age, sex, race and muscle mass Only determinants are age and sex, therefore more uniform
across populations

Can be affected by alterations in muscle mass and drugs that Not affected by muscle mass. May be influenced by thyroid
inhibit tubular secretion (cimetidine, trimethoprim) function and corticosteroid use

Inexpensive and easy to use Expensive, therefore will be reserved for confirmatory testing of
renal function

Used in estimation of CrCl and eGFR Incorporated into equations (CKD-EPI) estimating eGFR

Am J Kidney Dis. 2014; 63(5): 820-834

Curr Opin Nephol Hypertens 2014; 23: 258-266
DRUG CLEARANCE AND DIALYSIS

Type of dialysis
HD and frequency, PD, CVVH

Drugs properties
Molecular weight, charge, water solubility, volume of distribution, dialyzer
membrane binding, non renal excretion pathway

Dialysis properties
Type of dialyser (pore size, surface area), flow rate/blood flow, dialysate
composition, volume of dialysate (PD), temperature, pH

Patient properties
Residual renal function, blood pressure, Kt/v
 SUMMARY
• AKI and CKD management is a complex and dynamic clinical
management
• A reliable and stable biomarker should be considered for the
management especially in AKI setting
• Individualized treatment is required to ensure the accuracy and
safety clinical care to these patients
• AKI and CKD should not be seen as separate entity but as a
spectrum of a dynamic disease condition
• Dialysis modalities and concomitant drugs used should be reviewed
regularly
• Interaction between nephrologists and renal pharmacists is very
important to ensure the success of the management of these patients
 SUMMARY
• AKI and CKD management is a complex and dynamic
clinical management
• Individualized treatment is required to ensure the accuracy
and safety clinical care to these patients
• AKI and CKD should not be seen as separate entity but as a
spectrum of a dynamic disease condition
• Dialysis modalities and concomitant drugs used should be
reviewed regularly
• Interaction between nephrologists and renal pharmacists is
very important to ensure the success of the management of
these patients