Acute Renal Failure aka Acute Kidney Injury

1
Acute Renal Failureaka Acute Kidney Injury
2
Definition of Acute Kidney Injury (AKI) based on
Acute Kidney Injury Network
Stage Increase in Serum Creatinine Urine Output
1 1.5-2 times baseline OR 0.3 mg/dl increase from baseline lt0.5 ml/kg/h for gt6 h
2 2-3 times baseline lt0.5 ml/kg/h for gt12 h
3 3 times baseline OR 0.5 mg/dl increase if baselinegt4mg/dl OR Any RRT given lt0.3 ml/kg/h for gt24 h OR Anuria for gt12 h
3
RIFLE criteria for diagnosis of AKI based on The
Acute Dialysis Quality Initiative
Increase in SCr Urine output
Risk of renal injury Injury to the kidney Failure of kidney function 0.3 mg/dl increase 2 X baseline 3 X baseline OR gt 0.5 mg/dl increase if SCr gt4 mg/dl lt 0.5 ml/kg/hr for gt 6 h lt 0.5 ml/kg/hr for gt12h Anuria for gt12 h
Loss of kidney function End-stage disease Persistent renal failure for gt 4 weeks Persistent renal failure for gt 3 months
Am J Kidney Dis. 2005 Dec46(6)1038-48
4
Increase in Creatinine without AKI

• Inhibition of tubular creatinine secretion
• Trimethoprim, Cimetidine, Probenecid
• Interference with creatinine assays in the lab
  (false elevation)
• glucose, acetoacetate, ascorbic acid, cefoxitin
• flucytosine

5
Increase in BUN without AKI

• Increased production
• GI Bleeding
• Catabolic states (Prolonged ICU stay)
• Corticosteroids
• Protein loads (TPN-Albumin infusion)

6
New Biomarkers in AKIAlternatives to Serum
Creatinine

• Urinary Neutrophil Gelatinase-Associated
  Lipocalin (NGAL)
• Ann Intern Med 2008148810-819
• Urinary Interleukin 18
• Am J Kidney Dis 200443405-414
• Urinary Kidney Injury Molecule 1 (KIM-1)
• J Am Soc Nephrol 200718904-912

7
AKI and Mortality(Brigham and Womens, 9210
adults)Multivariable Odds Ratio for Death
AKI (? in SCr gt0.5) Age (per 10 yr) CKD CV dis. Respiratory dis GI dis. Cancer Infection 6.5 1.7 2.5 1.5 3 2.4 2.9 7.5 lt0.0001 lt0.0001 lt0.0001 lt0.04 lt0.0001 lt0.001 lt0.0001 lt0.0001
8
Major Disease Categories Causing AKI
Disease Category Incidence
Prerenal azotemia caused by acute renal hypoperfusion 55-60
Intrinsic renal azotemia caused by acute diseases of renal parenchyma -Large renal vessels dis. -Small renal vessels and glomerular dis. -ATN (ischemic and toxic) -Tubulo-interestitial dis. -Intratubular obstruccttion 35-40 gt90
Postrenal azotemia caused by acute obstruction of the urinary tract lt5
9
Prerenal Azotemia

• Intravascular volume depletion
• bleeding, GI loss, Renal loss, Skin loss, Third
  space loss
• Decreased cardiac output
• CHF
• Renal vasoconstriction
• Liver Disease, Sepsis, Hypercalcemia
• Pharmacologic impairment of autoregulation and
  GFR in specific settings
• ACEi in bilateral RAS, NSAIDS in any renal
  hypoperfusion setting

10
Intrinsic Renal Azotemia

• Large Renal Vessel Disease
• Thrombo-embolic disease
• Renal Microvasculature and Glomerular Disease
• Inflammatory glomerulonephritis, allograft
  rejection
• Vasospastic malignant hypertension, scleroderma
  crisis, pre-eclampsia, contrast
• Hematologic HUS-TTP, DIC
• Acute Tubular Necrosis (ATN)
• Ischemic
• Toxic
• Tubulo-interestitial Disease
• Acute Interestitial Nephritis (AIN), Acute
  cellular allograft rejection, viral (HIV, BK
  virus), infiltration (sarcoid)
• Intratubular Obstruction
• myoglobin, hemoglobin, myeloma light chains,
  uric acid, tumor lysis, drugs (indinavir,
  acyclovir, foscarnet, oxalate in ethylene glycol
  toxicity)

11
Postrenal azotemia

• Stones
• Blood clots
• Papillary necrotic tissue
• Urethral disease
• anatomic posterior valve
• functional anticholinergics, L-DOPA
• Prostate disease
• Bladder disease
• anatomic cancer, schistosomiasis
• functional neurogenic bladder

12
Initial diagnostic tools in AKI

• History and Physical exam
• Detailed review of the chart, drugs administered,
  procedures done, hemodynamics during the
  procedures.
• Urinalysis
• SG, PH, protein, blood, crystals, infection
• Urine microscopy
• casts, cells (eosinophils)
• Urine lytes
• Renal imaging
• US, Mag-3 scan, Retrograde Pyelogram
• Markers of CKD
• iPTH, sizelt9cm, anemia, high phosphate, low
  bicarb
• Renal biopsy

13
Likelihood ratio (LR) of ATN vs pre-renal
azotemia on the basis of the number of granular
casts in urinary sediment
Granular casts/hpf LR for ATN LR for pre-renal
0 0.23 4.35
1-5 2.97 0.34
6-10 9.68 0.1
Clin J Am Soc Nephrol 4691-693, 2009
14
RBC cast
Granular cast
Hyaline cast
Granular cast
Granular cast
WBC cast
Oval fat body and Hyaline cast
WBC cast
15
Treatment of AKI

• Treatment is largely supportive in nature!
• Pharmacologic treatments under study
• Dopamine no benefit
• Atrial Natriuretic Peptide (ANP) or ANP-analogue
  (Anaritide) promising
• Human Insulin like growth factor 1 no benefit
• Renal Replacement therapy remains the cornerstone
  of management of minority of patients with severe
  AKI

Nephron Clin Pract 2009112c222-c229
16
Is there a role for Dopamine in prevention or
treatment of AKI in ICU setting?

• Clinical Outcomes
• No effect on mortality
• No effect on the need for or incidence of Renal
  Replacement Therapy (RRT)
• Renal Physiologic Outcomes
• Diuretic effect and increased creatinine
  clearance on the first day which was not
  significant on the following days.
• Adverse effect
• on the immune, respiratory, and endocrine
  system.

Ann Intern Med. 2005142510-524 ANZICS Clinical
Trial Group. Lancet 20003562139-2143
17
Role of ANP analogues in AKI?

• 61 patients in 2 cardiothoracic ICU with post-op
  AKI assigned to receive recombinent ANP
  (50ng/kg/min) or placebo
• The need for RRT before day 21 after development
  of AKI was significantly lower in ANP group (21
  vs 47)
• The need for RRT or death after day 21 was
  significantly lower in ANP group (28 vs 57)

Crit Care Med. 2004 Jun32(6)1310-5
18
Is there a role for Fenoldepam in prevention or
treatment of AKI in ICU setting?

• Dopamine-1 receptor agonist, lack of Dopamine-2,
  and alpha-1 receptor effect, make it a
  potentially safer drug than Dopamine!
• Reduces in hospital mortality and the need for
  RRT in AKI
• Reverses renal hypoperfusion more effectively
  than renal dose Dopamine
• So far so good specially in cardiothoracic ICU
  patients, awaiting more powered trials in other
  groups!

J Cardiothorac Vasc Anesth. 2008 Feb22(1)23-6.
J Cardiothorac Vasc Anesth. 2007
Dec21(6)847-50 Am J Kidney Dis. 2007
Jan40(1)56-68 Crit Care Med. 2006
Mar34(3)707-14
19
Is there a role for diuretics in the treatment of
AKI in ICU setting?

• PICARD Study
• Cohort study of 552 pts in 4 UC hospitals
• Odds Ratio
• In-hospital Mortality 1.77
• Non-recovery of renal function 1.68
• Improved urine output and shorter duration of RRT
  (none has clinical relevance in ICU pts)
• But diuretics continue to be used for volume
  control in AKI in ICU setting!

JAMA. 2002 Nov 27288(20)2547-53 Crit Care
Resusc. 2007 Mar9(1)60-8
20
Results of individual RCTs comparing CRRT to IHD
in AKI in ICU
Study n n Primary endpoint Mortality Mortality Persistent RRT requirement
CRRT IHD CRRT IHD CRRT IHD
Mehta et al KI 2001 84 82 ICU mortality 59.5 41.5 14 7
Augustine et al AJKD 2004 40 40 In-hospital mortality 67.5 70 61.5 66.7
Uehlinger et al NDT 2005 70 55 In-hospital mortality 47 51 2.7 3.7
Vinsonneau et al Lancet 2006 175 184 60-day mortality 67.4 68.5 1.8 0
Lins et al NDT 2009 172 144 In-hospital mortality 58.1 62.5 16.9 25.5
21
CRRT vs SLED (Sustained low efficiency dialysis)

• SLED became popular because of CRRT
  disadvantages
• Expensive, continuous pt immobilization, need for
  specialized machines and pre-mixed commercial
  solutions, and anticoagulation
• Only 2 small studies compared these 2 in
  hemodynamically unstable pts with AKI
• They did not see significant differences in
  hemodynamic parameters and solute clearance
• They did not look at any patient-relevant
  outcomes, so the jury is still out there

Am J Kidney Dis 200443342-349 J Artif Organs
2007301083-1089 Am J Kidney Dis 200851804-810
22
Results of RCTs comparing benefits of the
intensity of RRT (high vs low dose dialysis)
Study n Low dose modality High dose modality Endpoint Results for low dose Results for high dose P
Schiffl et al NEJM 2002 146 Thrice-weekly IHD Daily IHD 1-Mortality 2-Time to renal recovery 46 16 days 28 9 days Sig
Ronco et al Lancet 2000 425 CVVH dose of 20 ml/kg/h CVVHDF dose of 35 or 45 ml/kg/h 90-day survival 34 59 Sig
Palvesky et al NEJM 2008 1100 High dose CRRT 35 ml/kg/h or SLED X 6/wk or IHD X 6/wk Low dose CRRT 20 ml/kg/h or SLED X 3/wk or IHD X 3/wk 60-day mortality 51.8 53.6 NS
RENAL Clinical Trial (not published) 1500 CVVHDF 25 ml/kg/h CVVHDF 40 ml/kg/h 90-day Survival NS
Veterans Administration/National Institute of
Health Acute Renal Failure Trial Network Study
23
Overall conclusion on RRT modality benefit in AKI

• CRRT does not confer a survival advantage as
  compared to IHD
• SLED may replace CRRT although there is no
  outcome benefit study up to this date
• There is limited data regarding the ideal timing
  of RRT initiation and the preferred mode of
  solute clearance
• No evidence to support a more intensive strategy
  of RRT in the setting of AKI

24
Case 1

• 26 yo F is involved in a MVA, with multiple
  fractures, blunt chest and abdominal trauma. She
  was briefly hypotensive on arrival to ED,
  received 6L NS and normalized BP. Non contrast CT
  showed small retroperitoneal hematoma. On day2
  her SCr is 0.9 mg/dl, lipase is elevated and
  tense abdominal distension is noted. US showed
  massive ascites. UOP drops to lt20 cc/hr despite
  of 10 L total IV intake. On day3, SCr is
  2.1mg/dl, CVP is 17, UNa is 10 meq/L, with a
  bland sediment.
• What is the cause of her AKI?
• What bedside diagnostic test and therapeutic
  intervention is indicated?

25

• Bladder pressure was 29 mmHg
• UOP and SCr improved with emergent paracenthesis.
• Dx Abdominal Compartment Syndrome causing
  decreased renal perfusion from increased renal
  vein pressure.

26
Case 2

• 59 yo M, s/p liver transplant in 2001 and acute
  on chronic rejection, now decompensated ESLD, is
  admitted with worsening ascites, hepatic
  encephalopathy and GI bleed (which is now
  controlled). The only medications he has been
  receiving are Lactulose and prilosec. He has been
  hemodynamically stable with average BP100/70
  mmHg.He had a 3.5 L paracenthesis on day 2. His
  SCr has been slowly rising from 1.2 to 4.7 mg/dl
  within the 2nd to 4th day of admission and his
  UOP has dropped to 150 cc/day. His daily FeNa is
  lt1 despite of 2 L fluid challenge. His Urine
  sediment is blend. His renal US is normal.
• What is the cause of his AKI?

27

• Patient required HD.
• He had a second liver transplant and came off HD
  after the surgery with stable SCr of 1.4 mg/dl.
• Dx Hepatorenal Syndrome (HRS)

28
Hepatorenal Syndrome

• Major diagnostic criteria
• No improvement with at least 1.5 L fluid
  challenge
• SCr gt1.5 mg/dl or GFRlt 40 cc/min
• Absence of proteinuria (lt500 mg/d)
• Other causes are rouled out (obstruction, ATN,
  etc.)
• Minor diagnostic criteria
• Urine volume lt 400 cc/day
• UNa lt 10 meq/L
• SNa lt 130 meq/L
• Urine RBC lt 50/hpf

29
Case 3

• 52 yo F underwent matched allo-Hematopoietic Stem
  cell transplant (HSTC) for AML. Between days 3-7
  she gradually gained 8 Kg and edema developed.
  Since day7 her Bili rose daily and peaked at 8
  with jaundice, RUQ tenderness, and ascites. Liver
  US showed reversal of flow in the portal vein.
  Since day8 SCr rose slowly from baseline of 1.0
  to 3.5 mg/dl, with 400 cc/day UOP on day10. Her
  FeNa was 0.05 despite of 1.5L fluid challenge.
  Her urine sediment was blend.
• What is the most likely cause of her AKI?

30

• She required HD for volume control, and remained
  HD dependent.
• Dx Portal/Hepatic Veno-Occlusive Disease (VOD)
• VOD is responsible for 90 of hepatorenal
  syndromes in HSCT

31
Case 4

• 45 yo M with CHF and Bipolar Disorder on Lithium
  for 10 years, admitted for abdominal pain after a
  heavy meal, which turned out to be due to acute
  cholecyctitis. He was kept NPO on D5 1/2NS 50
  cc/hr. Next morning he felt well but thirsty and
  hungry, BP120/80, I/O1200/4500. His SCr rose
  from 1.2 to 1.9 mg/dl. SNa 149 meq/L. UNa 10
  meq/L. UOsm 190 mOsm/Kg.
• What is the cause of his AKI?

32

• Patients IVF was changed to ½ NS, replacing 80
  of UOP per hour. SCr and SNa improved to baseline
  in 2 days.
• Dx Prerenal azotemia secondary to renal free
  water loss in DI.

33
Case 5

• 68 yo F with CAD, DM, HTN, PVD, CKD with baseline
  SCr of 1.4 mg/dl underwent elective cardiac angio
  and stent placement. No new meds. She has been
  hemodynamically stable throughout the procedure
  and afterward. Since day2 post procedure, her
  SCr has been gradually rising to 2.5 mg/dl with
  500-600 cc/day UOP. UA showed SG 1.025, 1
  protein. Urine eosinophils (). Serology tests
  showed low complements. She was discharged and in
  her f/u visit in 3 weeks she had SCr of 2.7.
• What could be the cause of her AKI?

34

• She never required RRT, but her SCr continued to
  rise slowly to 3.1 mg/dl. She died 7 months
  later.
• Dx Cholesterol emboli

35
Case 6

• 18 yo F with no PMH admitted with projectile
  vomitting, fatigue, and low PO intake. Her
  BP200/110, normal UOP with dry mucosa, trace
  edema, and otherwise normal exam. BUN120 mg/dl,
  Creat10 mg/dl which continued to rise on the
  following days, Hct25 without schistocytes on
  PBS, UA 3 protein, 3 blood, gt50 RBC, many RBC
  casts. FeNa 1. US showed normal sized kidneys.
• What other tests do you order?
• What may be the cause of her AKI?

36

• ANA (-), normal complements, cryo (-), serology
  for hepatitis B, and C (-), P-ANCA (), C-ANCA
  (-), anti-GBM (-), ASO (-), UPEP and SPEP without
  M spike, ESR 80.
• Her renal Bx showed crescentic glomerulonephritis,
  minimal non-specific immune complex deposits,
  without chronic changes.
• She remained dialysis dependent despite of
  steroid, cytoxan, and 10 plasmapheresis
  treatments.
• Dx Pauci-immune Crescentic Glomerulonephritis
  due to Wegners granulomatosis

37
Case 7

• 54 yo F with CAD, on statin, started a new
  exercise program with intense weight training.
  She was brought to ED with neck pain, and LE
  weakness. VS stable, normal UOP, with dry mucosa.
  LE muscle strength 2/5 bilaterally. BUN 40 mg/dl,
  creatinine8 mg/dl. FeNa 1.5. Renal US normal.
  UA 1.010, 3 blood, few RBCs, few granular
  casts.
• What would be the next test to order?
• What may be the cause of her AKI?

38

• Her CPK57,700
• She was treated with IV NaHCO3 gtt to alkalinize
  urine to PHgt6.5 .
• Her UOP remained normal but she required HD for
  uremia.
• Dx ATN due to Rhabdomyolysis

39
Case 8

• 47 yo M with CAD, and CHF, admitted with LE
  cellulitis, started on Zosyn. On day4 of
  admission BP90/60, HR68, normal UOP. LE
  edema(), few pruritic purpuric rash on the
  shins. SCr rose from 1.1 to 3.5 mg/dl. BUN96
  mg/dl. UA trace protein, small blood, few RBCs,
  moderate WBC, with few WBC casts. FeNagt1, Urine
  eosinophil (). Renal US showed 13 cm kidneys.
• What may be the cause of his AKI?
• What would be your next step?

40

• Zosyn was stopped.
• Patient required two HD treatment for uremia.
• Renal biopsy showed Acute Interestitial
  Nephritis.
• Subsequently he was started on Prednisone for one
  month and remained HD independent with stable SCr
  of 1.8-2 mg/dl.
• Dx AIN secondary to Zosyn

41
Case 9

• 72 yo M with DM, and prostate cancer metastatic
  to the bone, s/p XRT, on hormonal therapy. He is
  admitted with weakness, progressive weight loss,
  and persistent nausea. His med list also includes
  Diclofenac sodium daily for hip pain. BP150/90,
  350cc of urine collection immediately after foley
  placement, and normal exam. BUN107 mg/dl,
  creatinine9.8 mg/dl (2.0 almost 6 months PTA),
  which remained unchanged with hydration. Uric
  acid8.2 mg/dl. UA 1.010, 1 protein, 1 blood,
  few RBCs, no cast, no WBC. US showed 10-11 cm
  kidneys, no hydronephrosis.
• What seems to be the cause for his AKI?

42

• Patient was initiated on HD for uremia and
  remained HD dependent for his symptomatic uremia.
• Patient and his family were concerned about his
  renal recovery (outcome), so a renal Bx was done
  showing severe chronic interstitial nephritis,
  with fibrosis and glomerulosclerosis.
• Dx ESRD due to chronic tubulo-interstitial
  disease secondary to NSAIDs

43
Case 10

• 32 yo M s/p Cadaveric Renal Transplant (CRT) in
  2006 for adult PCKD, on prograf, prednisone, and
  cellcept, and history of BK viruria is admitted
  for increased Creatinine1.9 mg/dl, Hct27, WBC
  2,500, Plt 90,000. He seems well hydrated, with
  stable VS, and normal exam. UA 1.015, no
  protein, no blood, few granular casts. FeNa 1.
  (-) BK virus PCR in the blood.
• What would be your next step?
• What seems to be the cause for his allograft
  failure?

44

• Renal Bx showed acute cellular rejection BANFF
  IIb. No BK viral inclusions were identified.
• He received IV Solumedrol and Thymoglobulin and
  his creatinine dropped to a stable level of
  1.3-1.4 mg/dl.
• Dx Acute cellular rejection

45
Case 11

• 59 yo F with prolonged HTN, s/p OLT in 2000, on
  norvasc, prograf and prednisone was brought in
  for AMS. T39, BP95/60, HR104, UOP20 cc/hr,
  intubated for airway protection, otherwise normal
  exam. BUN80 mg/dl, creatinine6 mg/dl (normal
  baseline), K6.5 meq/L, Hct20, Plt20000, FeNa
  1, urine eosinophil (-), UA 2 blood, no
  protein, RBC gt 50/hpf, no WBC, no cast.
• What would be your next step?
• What could be the reason for her AKI?

46

• Her PBS showed many schistocytes and fragmented
  RBCs.
• Her Prograf was replaced with Sirolimus
• She underwent plasmapheresis, and required HD for
  anuria, and persistent hyperkalemia. She came off
  HD after 2.5 months with stable creatinine1.2
  mg/dl.
• Dx TTP secondary to Prograf

47
Case 12

• 72 yo F with depression and hypothyroidism, was
  found by neighbors on the floor, unconscious, in
  respiratory distress. Intubated for airway
  protection. VS stable, anuric, Lungs CTA. BUN 50
  mg/dl, Creatinine4 mg/dl, with high anion gap
  metabolic acidosis, and an osmolar gap of gt 10.
  Lactic acid1.8, FeNa 1, urine eosinophil (-),
  UA 1.020, 1 blood, no protein, few RBCs, many
  oxalate crystals, few granular casts. US showed
  normal sized kidneys with no hydronephrosis.
• What is your next step?
• What seems to be the cause for her AKI?

48

• Her ethylene Glycol level came back after 2 days
  to be 40 mg/dl.
• Pt was given Fomepizole and initiated on HD for
  persistent acidemia. She remained HD dependent,
  eventually extubated, started therapy for
  depression and discharged to NH.
• Dx Ethylene Glycol toxicity

49
Case 13

• 38 yo M with post ERCP pancreatitis, is admitted
  to ICU, intubated for hypoxic respiratory
  distress, is anuric, febrile, and hypotensive,
  requiring massive volume resuscitation, on two
  vasopressors. He has received 11 L of NS and
  other IV meds within the last 8 hours and
  currently his CVP12, has coarse crackles, and 2
  edema. His Creatinine rose from 1.2 to 3.5 the
  morning after the above event, FeNa gt 1, UNa 45
  meq/L, UA 1.010, no protein, no blood, moderate
  epithelial cells, many muddy brown granular cell
  casts, moderate epithelial cell casts. US showed
  normal sized kidneys with no hydronephrosis.
• What is the cause of his AKI?

50

• He was started on CVVH for volume control. Has
  had a long hospital stay complicated with
  polymicrobial bacteremia and VAP.
• Dx ATN secondary to renal ischemia and sepsis

51
Natural Clinical Course of ATN

• Initiation Phase (hours to days)
• Continuous ischemic or toxic insult
• Evolving renal injury
• ATN is potentially preventable at this time
• Maintenance Phase (typically 1-2 wks)
• Maybe prolonged to 1-12 months
• Established renal injury
• GFR lt 10 cc/min, The lowest UOP
• Recovery Phase
• Gradual increase in UOP toward post-ATN diuresis
• Gradual fall in SCr (may lag behind the onset of
  diuresis by several days)

52
When to do renal biopsy in AKI ?

• Any evidence of glomerular disease
• -nephrotic range proteinuria
• -sub-nephrotic range proteinuria with hematuria
• -RBC cast
• AKI in renal allograft
• Determine the prognosis and chance of recovery of
  renal function in dialysis dependent AKI.
• Whenever potential Bx result can change the
  management or prognosis.

53
When to initiate RRT in a patient with AKI ?

• 1) Renal Replacement Therapy
• Electrolytes imbalances
• Acid-base disturbances
• Uremic complications
• -Encephalopathy
• -Pericarditis
• -Persistant nausea, and food intolerance

54

• 2) Renal/Multiorgan Support Therapy
• -Protects other organs by improving overall
  body milieu (balance of inflammatory
  mediators)
• -Allowing therapies for other organs that pt
  could not otherwise tolerate
• -volume resuscitation
• -aggressive nutrition

55

• 3) Removal of toxic agents in overdose
• -Ethylene Glycol
• -Methanol
• -Salicylates
• -Lithium
• -Theophylline
• -Isopropanol

56
Thank you!