Causes ,diagnosis and treatment of acute kidney disease

1. Acute kidney injury (AKI)
Professor
/
Mohammed
Bamashmos
(MD)

2. Definition of AKI
► A sudden, sustained, and usually reversible decrease in the glomerular
filtration rate (GFR) occurring over a period of hours to days.
> 30 definitions used in published studies

3. KDIGO Definition of AKI ( 2012 )
Defined by any of the following:
► Increase in SCr by ≥0.3 mg/dL within 48 hours
► Increase in Scr by ≥1.5 times baseline, which is known or presumed to
have
occurred within the prior seven days
► Urine volume <0.5 mL/kg/h for six hours

4. KDIGO Classification of AKI ( 2012 )
Stage Serum creatinine Urine output
1 1.5-1.9× baseline
OR
>0.3 mg/dL 🡹
<0.5 ml/kg/hr for 6-12 hrs
2 2-2.9× baseline
<0.5 ml/kg/hr > 12 hrs
3 3 times baseline
OR
increase in Cr to ≥4.0 mg/dL
OR
Initiation of RRT
<0.3 ml/kg/hr > 24 hrs
OR
Anuria > 12 hrs
KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012

5. RIFLE

6. AKIN
Stage 1 Increase of more than or equal to 0.3 mg/dl
or increase to more than or equal to
150% to 200% (1.5- to 2-fold) from baseline
Stage 2 Increased to more than 200% to 300%
(>2- to 3-fold) from baseline
Stage 3 Increased to more than 300% (43-fold)
from baseline, or more than or equal to 4.0
mg/dl
(X354 mmol/l) with an acute increase of at least
0.5 mg/dl (44 mmol/l) or on RRT

7. Conceptual model for AKI

8. Definitions of Terminology
► Azotemia - the accumulation of nitrogenous wastes (high BUN)
► Uremia – clinical manifestation (symptomatic renal failure)
► Oliguria – UOP < 400 mL/24 hours
► Anuria – UOP < 100 mL/24 hours

9. Epidemiology
► ≈ 5-10% in hospitalized pts
► ≈ 30 % in ICU pts.
► 5-6% ICU pts require RRT

10. Acute
Tubular
Necrosis
Acute
Interstitial
Nephritis
Acute
GN
Acute
Vascular
Syndromes
Intratubula
r
Obstructio
n
Classification of the Etiologies
of AKI
Prerenal AKI Postrenal AKI
Intrinsic AKI
Acute Renal Injury

13. Prerenal AKI
► Intravascular volume depletion:
► Bleeding, GI loss, Renal loss, Skin loss (burn), Third space
loss, poor oral intake (NPO, AMS, anorexia)
► Decreased effective circulating volume:
-congestive heart failure, cirrhosis, nephrotic syndrome, sepsis
► Decreased flow through renal artery:
-RAS or occlusion (compartment syndrome), hepatorenal
syndrome, hypercalcemia
-pharmacologic impairment (RAAS blocker, NSAIDs, CNI)
► Systemic vasodilation

14. Intrarenal mechanisms for autoregulation of the GFR

16. Renal / Intrinsic AKI
► Tubule : ATN (sepsis, ischemic, toxins)
► Interstitium : AIN (Drug, infection, neoplasm)
► Glomerulus : AGN (primary, post-infectious, rheumatologic, vasculitis,
HUS/TTP)
► Vasculature : Atheroembolic dz, renal artery thromboembolism, renal
artery dissection, renal vein thrombosis
► Intratubular Obstruction
► Myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis, drugs (bactrim, indinavir,
acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

18. Acute Tubular Necrosis (ATN)
► Sepsis (48%)
► Ischemia (32%)
►prolonged prerenal
azotemia
►Hypotension
►hypovolemic shock
►cardiopulmonary arrest
►cardiopulmonary bypass
► Direct toxic Injury (20%)
► Exogenous
► Radiocontrast
► Aminoglycosides
► Vancomycin
► Amphotericin B
► Cisplatin
► Acyclovir
► Calcineurin inhibitors
► HIV meds (tenofovir)
► Endogenous (pigment nephropathy)
► Rhabdomyolysis
► Hemolysis

19. Sites of tubular injury in (ATN).
• The S-3 segment of the
proximal tubule and the
medullary thick ascending
limb are particularly
vulnerable to ischemic
injury
• because of the
combination of
borderline oxygen
supply and high
metabolic demands.

20. Major risk factors for AKI
Patient Factors
►Older age (>75 years) Diabetes
►Hepatic failure CKD
►Atherosclerosis Renal artery stenosis
►Hypertension Hypotension
►Hypercalcemia Sepsis
►Perioperative cardiac dysfunction
Rhabdomyolysis
►Tumor lysis syndrome

25. Medications and drugs
► Non-steroidal anti-inflammatory drugs
► Cyclooxygenase-2 inhibitors
► Cyclosporine or tacrolimus
► Angiotensin-converting enzyme inhibitors
► Angiotensin receptor blockers
► Iodinated contrast agents
► Aminoglycosides
► Amphotericin

26. Procedures
► Cardiopulmonary bypass procedures
► Surgery involving aortic clamp
► Increased intra-abdominal pressure
► Large arterial catheter placement with risk for athero-embolization
► Liver transplantation
► Kidney transplantation

27. Conceptual model for AKI

28. Evaluation and diagnosis of AKI
► The distinction between AKI and CKD is important for proper diagnosis and
treatment.
► The distinction is straightforward when a recent baseline SCr concentration is available, but
more difficult in the many instances in which the baseline is unknown
► Features suggestive of CKD are:
► radiologic studies (e.g., small, shrunken kidneys with cortical thinning on renal ultrasound
► evidence of renal osteodystrophy or
► laboratory tests such as normocytic anemia in the absence of blood loss
► secondary hyperparathyroidism with hyperphosphatemia and
► hypocalcemia

29. Overview of AKI, CKD, and AKD
AKI is a subset of AKD. Both AKI and AKD without AKI can be
superimposed upon CKD

30. Laboratory Findings in Acute Kidney Injury
Index Prerenal
Azotemia
Oliguric AKI (ATN)
BUN/PCr Ratio >20:1 10-15:1
Urine sodium (UNa), meq/L <20 >40
Urine osmolality, mosmol/L
H2O
>500 <400
Fractional excretion of
sodium
FEUrea
<1%
<35%
>2%
>35%
Response to volume Cr improves with IVF Cr won’t improve much
Urinary Sediment Bland, Hyaline Muddy brown granular casts,
cellular debris, tubular epithelial
cells

31. Fractional excretion of Na and
urine Na concentration
► In the absence of a sodium-wasting state, the urine-sodium concentration in
hypovolemic states should be < 20 mEq/L.
► The FENa, which includes the urine-sodium concentration, is the better test in
patients with AKI since it only measures sodium handling (the fraction of the
filtered sodium load that is excreted). It is not affected by changes in urine
output.
U Na x SCr
FENa = ——————— x 100
%
S Na x U Cr

33. Bio-markers of AKI
► Neutrophil Gelatinase-associated Lipocalin (NGAL)
► Secreted by renal tubules in renal tubular injuries
► Interleukin-18
► IL-18 is formed in the proximal tubules and can be detected in the urine
► biomarker for renal parenchymal injury
► Kidney Injury Molecule 1
► type 1 transmembrane protein
► Apart from its potential as a biomarker for ATN, may have a role in
determining risk for the development of AKI.
► Cystatin C
► Liver-type Fatty Acid–Binding Protein

34. Management of AKI

35. Primary preventive measures of AKI
► Optimizing volume status and hemodynamic status
► Fluid challenge should be continued as long as there is hemodynamic improvement.
► isotonic crystalloids should be used instead of synthetic
► Vasopressors should be initiated to maintain MAP above 65 mm Hg, and
norepinephrine is the first-choice vasopressor.
► Inotropic agents such as dobutamine should be administered if myocardial
dysfunction or ongoing signs of hypoperfusion are present.

36. Prevention of Drug and Nephrotoxin
Induced AKI
► Patient-related factors are
► age >60 years,
► preexisting CKD,
► volume depletion,
► diabetes,
► heart failure, and
► sepsis.
► Principles of prevention
► Correctly estimating the GFR before initiation of therapy,
► adjusting the dosage, and
► monitoring renal function during therapy.

37. ► Amphotericin
► AKI can occur in 1/3rd of treated pts
► Lipid formulations cause less nephrotoxicity
► Alternative antifungal agents such as itraconazole, voriconazole, and
caspofungin can be used

38. ACEi/ARBs & NSAIDs
► Cause vasodilation of the efferent glomerular arteriole, further reducing intra-glomerular
pressure already compromised by the BP-lowering effect of these agents.
► In patients with an increase in serum creatinine >30% after the initiation of ACE inhibitor
and ARB treatment following conditions should be suspected
► bilateral renal artery stenosis,
► stenosis of the renal artery in a solitary kidney,
► diffuse intrarenal small-vessel disease, or
► generalized volume depletion
► NSAIDs should be avoided in CKD and intravascular volume depletion because they
inhibit cyclooxygenase, which blocks prostaglandin-induced vasodilation of the afferent
arteriole, potentially reducing GFR and renal blood flow

39. Aminoglycosides
► AKI usually occurs 5 to 10 days after initiation of the treatment;
► This type of AKI is typically non-oliguric and associated with
decreased urine
► Because of nephrotoxicity, ototoxicity, and vestibular toxicity, the
AKI KDIGO guidelines have recommended avoiding the use of
aminoglycosides in patients with AKI and those at risk unless no other
alternative is available.
► Once-daily administration can decrease tubular cell toxicity by
reducing drug taken up by proximal tubular cells

40. Tumor Lysis Syndrome
► caused by uric acid and calcium phosphate precipitation in the tubules
► Aggressive hydration with isotonic saline is initiated 2 days before the chemotherapy to
maintain a high urinary output, allowing the elimination of uric acid and phosphate
► If urinary output decreases despite adequate fluid intake, a loop diuretic should be
added, but RRT will be required if oliguria persists
► The use of urine alkalinization to promote elimination of urates is not recommended
because it can induce calcium phosphate deposition and therefore aggravate TLS

41. Rhabdomyolysis
► Crush injury
► Adequate hydration
► The urine output should be maintained
► around 300 ml/h, which may require an infusion of up to 12
► liters of fluid per day
► Sodium bicarbonate
► A solution with 2.7% sodium bicarbonate (50 mmol/l) should be given
every second or third liter to maintain urinary pH above 6.5 and to
prevent intratubular deposition of myoglobin and uric acid.

42. Contrast induced nephropathy
► Adequate hydration
► N-Acetylcysteine
► NAC at a dose of 600 mg orally twice daily the day before and the day
of the procedure prevent AKI after radiocontrast dye administration

43. Prevention of
CIN

44. Loop diuretics
► Diuretics have been shown to be ineffective in the prevention of AKI
or for improving outcomes once AKI occurs.

45. Treatment of AKI
► General measures
► Initial management of established AKI includes careful assessment of
the cause of renal dysfunction and the patient’s volume status.
► maintenance of adequate hemodynamic status
► nephrotoxic agents should be avoided, including intravascular radiocontrast
dye. Gadolinium-based contrast agents should be avoided because of the
risk of development of nephrogenic systemic fibrosis (NSF).

46. Treatment of AKI complications
►Fluid overload
► all intakes should be minimized
► loop diuretic therapy can be initiated in conjunction with measures to optimize systemic and
renal perfusion.
► Morphine and nitrates can be used to alleviate the respiratory symptoms in urgent situations.
Morphine reduces the patient’s anxiety and decreases the work of breathing
► If no response to medical treatment- might require dialysis

47. Hyperkalemia
► IV calcium is urgently needed- 10 ml of 10% calcium gluconate over 10 mins.
► Sources of oral or i.v. potassium should be identified and removed
► β-adrenergic antagonists,
► Potassium sparing diuretics,
► ACE inhibitors,
► ARBs
► Shifting of K+ from EC to IC space:
► Glucose and insulin infusion- effect starts in 20- 30 mins and last 2-6 hrs
► Sodium bicarbonate infusion- starts at 15 min and last for 2-3 hrs
► Salbutamol nebulization
► Potassium excretion should be increased by the administration of
► saline,
► loop diuretics, and
► cation exchange resins- keyxalate
► If hyperkalemia is unresponsive to conservative measures, emergency HD is the treatment of
choice

48. Sodium Disorders
► Hyponatremia is more common in AKI associated with heart failure,
liver failure, or diuretics.
► In these settings, water restriction to below the level of output is
mandatory

49. Calcium, Phosphorus, and Magnesium
Disorders
► Hyperphosphatemia and hypocalcemia are common in AKI.
► Hyperphosphatemia is usually caused by reduced excretion by the
kidneys
► Hypocalcemia occurs due to
► Hyperphosphatemia
► skeletal resistance to parathyroid hormone (PTH) and
► low calcitriol production from the dysfunctional kidney.
► Hypocalcemia can also occur during rhabdomyolysis and pancreatitis

50. Acid base disorders
► Metabolic acidosis is the most common acid-base abnormality
► caused by reduced regeneration of bicarbonate and failure to excrete
ammonium ions
► When metabolic acidosis is simply a complication of AKI,
► sodium bicarbonate can be administered if [HCO3] fall below 15 to 18
mmol/l.

51. Nutrition
► increased risk of protein-energy malnutrition because of
► poor nutrient intake and
► high catabolic rate
► Recommended nutritional requirement in AKI
► Calorie: 20 to 30 kcal/kg/day
► Protein intake: 0.8 to 1.0 g of protein/kg/day & in patients on RRT, 1.0 to
1.5 g per kilogram per day.

52. Indication of RRT
► Absolute indications:
► Uremic encephalopathy
► Uremic pericarditis
► Relative indications:
► Volume overload not responding to medical treatment
► Hyperkalemia not responding to medical therapy
► Metabolic acidosis not responding to medical treatment

53. Thank you