SEMINAR ON ACUTE KIDENY INJURY

AND CHRONIC RENAL FAILURE

Presenter: Debella k(SR1)

Moderator: Dr Bedri (uro-surgeon)

 Outline
• Introduction- Physiological anatomy of the
kidneys & Glomerular Filtration
• Acute Kidney Injury
• Clinical approach to the DDx of AKI
• Chronic Kidney Disease

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 Introduction-Physiological anatomy of the kidneys

FUNCTIONS: TWO MAJOR REGIONS:

 Excretion pale outer cortex.

 Regulation inner medulla.
 Secretion
 metabolism

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 Renal Blood Flow
RBF is 20% of total cardiac output.
RBF is not evenly distributed to all
parts of the kidney.
Regulated by changes in the
vascular resistance of all the
arteries.
• interlobar arteries,
• arcuate arteries,
• interlobular arteries (also called
radial arteries)
• afferent arterioles,
• Glomerular capillaries
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The Nephron is the functional unit
of the kidney

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Glomerular filtration

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Determinants of Glomerular Filtration

GFR = LpS × (Δhydrostatic pressure − oncotic pressure)

Lp = glomerular permeability
S = glomerular surface area
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 Determinants of Glomerular Filtration

 Hydraulic and oncotic pressure differences

between the glomerular capillary and the
Bowman space.
 Permeability of the glomerular Membrane.
Glomerular surface area.
 Renal plasma flow

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 Regulation of GFR
• Under normal circumstances, GFR is tightly
maintained at a relatively constant level,
despite large fluctuations in systemic arterial
pressures and renal blood flow.
• accomplished through the processes of auto
regulation of IGP and tubuloglomerular
feedback.

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 Regulation of GFR
Autoregulation of IGP Tubuloglomerular feedback
• ?Myogenic stretch
receptors in the afferent
arteriole
• ↓MAP ↓afferent
arteriolar tone ↑flow
into the glomerulus thus
maintaining GFR.
• Effective to a MAP of about
70 mm Hg

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 Neurohormonal control
• Under abnormal conditions however, neurohumoral
responses become more important.
• Norepinephrine, Epinephrine, and Endothelin Constrict
Renal Blood Vessels and ↓ GFR
• Endothelial-Derived Nitric Oxide ↓ Renal Vascular
Resistance and ↑ GFR
• Angiotensin II Preferentially Constricts Efferent
Arterioles.
• So, arteriolar tone is a net balance of the
vasoconstrictive and vasodilatory forces crucial for
maintenance of RBF and GFR.
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 Clinical Assessment of Glomerular Filtration Rate

• Unfortunately, GFR cannot be measured directly. It can,

however, be estimated by a variety of methods.
1. Renal Clearance.
 The best estimate of GFR can be obtained by measuring
the rate of clearance of a given substance from the
plasma.
 In order to be accurate, It must:
- Be able to achieve a stable plasma concentration,
- Be freely filtered across the glomerulus, from the
plasma.

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 Clinical Assessment cont.……
- Not be secreted, reabsorbed, synthesized, or otherwise metabolized
by the renal tubules, and
- Not be impacted by any other means of removal.
 Inulin clearance
 Radiolabelled compounds
 24-hour creatinine clearance
2.Plasma Markers
 Plasma creatinine (PCr).
 Plasma urea
 Plasma cystatin C
3. Mathematical Correction. developed to improve the accuracy of the
PCr estimation of GFR.
 Cockcroft-Gault formula(Cr Cl).
 MDRD formulas: more complex but more accurate than the Cockcroft-
Gault.
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 ACUTE KIDNEY INJURY
Definition :
Rapid reduction in renal function characterized by
progressive azotemia occurring during the course of
hours to days. cardinal feature is a decline in GFR.
Kidney Disease: Improving Global Outcomes (KDIGO) AKI
• ↑serum creatinine ≥0.3 mg/dL within 48 hours
from baseline.
• ↑serum creatinine ≥1.5 times from baseline within
the previous 7 days.
• Urine volume less than 0.5 mL/kg/hr for 6 hours.
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 Epidemiology
• 2% to 5% acute care hospital
admissions
• >20% of to the intensive care
unit admissions
• Once AKI occurred, associated
with higher morbidity and
mortality.

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 Etiology and Pathophysiology
Three broad categories:
 Prerenal azotemia,
 Intrinsic renal, and
 Postrenal azotemia

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 Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.
Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.
Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

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 Prerenal Azotemia
• Transient renal hypo perfusion
• Hallmark is
–reversibility and
–lack of structural damage to the kidney

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Prerenal Causes of Acute Kidney Injury

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Pathophysiology

• vasoconstriction
• sodium avidity
• Renal hypo Causes • water
perfusion reabsorption
• sympathetic Urine charx
nervous system
• RAAS -Low volume,
stimulates • ADH -Decreased
concentratio
n of urinary
Na, -High
urine
osmolality
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 Intrinsic Renal Disease
• Includes AGN, AIN, and ATN

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ACUTE TUBULAR NECROSIS

Incidence and Etiology

 The majority of all hospital-
acquired AKI is secondary to
ATN
▪ ischemic-
severe/prolonged
ischemia with injury to
parenchyma, following
prerenal hypo perfusion
▪ toxic
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 ATN-cont’d
 Nephrotoxins

 Endogenous:
 Pigment Nephropathy
 Exogenous:
-Myoglobin  Medications.
-Haemoglobin 
 Intrarenal Crystal Deposition
Heavy metals and
-Uric acid poisons.
-Calcium  Analgesics.
-Oxalate
 Tumor-Specific Syndromes
 Iv Contrast agents.
Tumor lysis syndrome  Chemotherapeutic
Plasma cell dyscrasia agents.
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ATN- pathophysiology

 Medulla receives 20% of total

renal blood flow
 O2 supply/demand balance is
delicate
 Nephron structures located in
outer medulla are most
sensitive to ischemic injury.
-S3 segment of proximal
tubules.
-Medullary thick ascending
segment of LH.
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Pathophysiology-contd

 A variety of biochemical changes occur during

ischemia and reperfusion, and these changes are
responsible for the cell dysfunction observed in
ATN.
 The sentinel biochemical event in renal ischemia
is the depletion of adenosine triphosphate(ATP).
 During prolonged oxygen deprivation, AMP is
further metabolized to the nucleosides
adenosine, inosine, and hypoxanthine.
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Pathophysiology-contd

 ATP depletion results in impaired function of

the plasma membrane and intracellular
ATPase.
-cytosolic concentrations of Na+ and K+ are
altered and cell swelling results.
- -high intracellular levels of
Ca2+,associated with multiple aspects of renal
cell injury; activate a calmodulin dependent
protease and disruption of the cytoskeleton.
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Pathophysiology-contd
 injury to tubular cells leads to aberrations in the
cytoskeletal organization of the tubule cells. This is
manifested as:
1.a loss in the cell polarity from redistribution of the
basolateral Na+/K+-ATPase resulting in impaired solute
and water transport.
2.Brush border loss and Impaired cell-cell and
cell-matrix adhesion resulting in Intratubule cast
formation and obstruction.
3. Loss of continuity of renal epithelium and Increased
intratubular pressure results in Back-leakage of filtrate.
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Pathophysiology-contd

 Hemodynamic abnormalities in ATN:

-Intrarenal vasoconstriction- endothelial
damage, ET production.
-Direct proximal tubular toxicity.
- -mechanical obstruction of tubules
from necrotic debris.
-back leak of filtrate across damaged and
denuded tubular epithelium.
-
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 ATN- Natural History
1.Oliguric phase-
usually begins less than 24 hours after the inciting incident.
may last for 1 to 3 weeks.
Urine volume averages 150 to 300 mL/day.
be alert for the expected complications.
2.Diuretic phase
 progressive increase in urine volume, a harbinger of renal recovery.
 SCr may continue to rise for another 24 to 48 hours.
 up to 25% of deaths with AKI.
3.Recovery phase
 Renal function returns to near baseline.
 abnormalities of urinary concentration and dilution may persist for
weeks or months.
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classic sediment of ATN includes
 Pigmented (muddy brown) granular casts and
renal tubular epithelial cells
 Increased concentration of urinary
Na+,FENa+>1%,urinary osmolality<400m

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 Postrenal Azotemia
 obstruction must
involve the outflow
tract of both kidneys,

 preexisting renal
dysfunction is present

 Lesion from renal pelvis

to the tip of urethra.
 Represent a potentially
reversible cause of AKI.

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 Pathophysiology
• The impact of the obstruction is influenced by:
-the extent or degree of obstruction.
- its chronicity.
- the baseline condition of the kidneys, the potential for recovery.
-the presence of other mitigating factors.
• A number of vasoactive substances are thought to play a role in
the changes in RBF and GFR occurring with both unilateral and
bilateral ureteral obstruction.
• The varying hemodynamic patterns :
- vasoactive hormones synthesized and released at different
rates.
- physical damage to glomerular and tubular units, and
-extra renal compensatory mechanisms.
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 Pathophysiology
Bilateral Ureteral Occlusion
Unilateral Ureteral Occlusion
• RBF and ureteral pressure change occur
in Triphasic pattern.
1.First phase: 1-2hrs
high tubular and collecting system
pressure.
increased RBF due to afferent arteriolar
vasodilation
2.Second phase:3-4hrs
-Tp remains elevated
-RBF and GFR begins to decline.
3.Third phase:5-24hrs
-further decline in RBF and GFR.
-parallel decline in tubular pressure.
-a shift in regional blood flow from
outer cortex to juxtamedullary region.
• RBF and ureteral pressure change occur
in Biphasic pattern.
• Modest increase in RBF lasting about
90min.
• Prolonged and profound decrease in
RBF:
-renal nerve stimulation
- endothelin
- angiotensin ll and TXA2.
• A shift in regional blood flow from
medulla to outer cortex.
• Tubular and collecting system pressure
remain elevated>24hrs due to prolonged
post glomerular vasoconstriction.
• Post obstructive diuresis is much greater.
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 CLINICAL APPROACH TO THE DIFFERENTIAL
DIAGNOSIS OF AKI

 Differentiating among pre renal/renal/post renal cause of AKI:

o Thorough History & P/E

- Assessing volume and hemodynamic status.
-Potential nephrotoxic insult.
- Presence of systemic disease.
-Presence of risk factors for AKI.
-Assessment of urine volume.
o Blood and urine indices
o Imaging studies
-Abdominal ultrasonography.
-Plain abdominal radiography.
-Radio nucleid renal scan.
-Radio contrast studies (IVP, CT, angiography) are of limited value.
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Patterns of Urinary Indices in Acute Kidney
Injury

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Complications
Complications ofof AKI Kidney Injury
Acute

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 Management of AKI
 Optimizing volume status with isotonic fluids
 Treating the underlying disease states (i.e.,
heart failure, cirrhosis).
 Discontinuation of Nephrotoxic drugs.
 Obstruction needs appropriate drainage.
 Rx of fluid & electrolyte abnormality.

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 RRT
Indications
 Refractory severe
 volume overload,
 hyperkalemia,
 metabolic acidosis
 Uremic symptomatology

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Prognosis of Acute Tubular Necrosis

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 AKI in Hospitalized Patients
• Development of AKI anytime after 48hrs hospital admission in a
patient admitted with normal renal function.
• A common complication in hospitalized patients.
• Associated with significant morbidity and mortality.
• RISK FACTORS:
- Advanced age
-Comorbid conditions:
-DM,HTN,CLD
-Prior Renal Disease
-Cardiac Illness
-polytrauma
-Emergency surgery
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Etiology:
ATN(45%)
Pre-renal(21%)
Post-renal(10%)
Diagnosis
high index of suspicion.
Through Hx and PE.
Serial monitoring of UOP and serum creatinine.
Prevention
adequate hydration with isotonic fluids.
use of potentially nephrotoxic drugs cautiously.
keep use of radiologic contrast agents to minimum.
use of non-ionic contrast agents.
early detection and treatment of infections.

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CHRONIC KIDNEY DISEASE

Definition:
 Sustained kidney injury longer than 3
months resulting in a GFR of less than 60
mL/min/1.73 m2.
 Implies a persistent abnormality in
glomerular filtration rate (GFR) with a wide
spectrum of causes.

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RISK FACTORS AND STAGING OF CKD
 Risk factors:
-Small for gestation age(SGA)
- Childhood obesity,
- Hypertension,
-Diabetes mellitus,
-Autoimmune disease,
-Advanced age,
-African ancestry,
-Family history of kidney disease,
- Previous episode of acute kidney injury, and
-The presence of proteinuria, abnormal urinary sediment,
or structural abnormalities of the urinary tract.
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Etiologies for Chronic Kidney Disease

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Pathophysiology

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Clinical manifestation

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Clinical Assessment of CKD Patients.
 Aims:
Diagnosis and staging of CKD.
Predicting progression of disease.
Approach to treatment of CKD.
1.Renal function assessment.
 Serum markers of RF
 Renal clearance
 Mathematical equations.
2.Proteinuria.
3.Radiographic assessmen.t
4.Urine analysis and renal biopsy.
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Management
Aim:
 Delay progression.
 Prevent uremic complications.
 Modify comorbidities.
 Prepare patients for RRT.

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Delay progression

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Reference

INTERNET

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Thank you!!!

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