ACUTE RENAL FAILURE

1
ACUTE RENAL FAILURE
2
INTRODUCTION

• Functions of the kidneys
• maintain control of body fluid composition/volume
• level of water loss/conservation
• volume of blood, extracellular fluid
• control over electrolyte concentrations
• potassium, magnesium, phosphorous
• acid/base balance

3
INTRODUCTION

• Renal Anatomy
• Nephron
• basic functional unit of the kidney
• filtration, reabsorption, secretion, etc..
• Glomerulus
• tufts of capillaries
• site of filtration
• afferents, efferents, tuft
• Proximal tubule, Loop of Henle, distal tubule,
  collecting tubules

4
ESTIMATION OF RENAL FUNCTION

• Cockcroft and Gault Equation
• Estimates renal function when creatinine levels
  are at steady-state
• not usually the case in acute renal failure

CLCr(ml/min) (140-Age)x(Wt.)
72(Scr)
x .85 (female)
5
ACUTE RENAL FAILURE

• Definition
• abrupt decline in renal function characterized by
  the inability of the kidney to excrete waste
  products and maintain acid-base balance
• increase in Scr of 0.5mg/dL when baseline Scr is
  lt 3.0mg/dL
• or increase in Scr of 1.0mg/dL when baseline Scr
  is gt3.0mg/dL
• usually reversible
• occurs primarily in hospital setting

6
CLASSIFICATIONS

• Anuric lt 50ml/day urine output
• Oliguric 50-400ml/day urine output
• Non-oliguric gt400ml/day urine output

7
ETIOLOGY

• Pre-renal azotemia
• Most common cause of ARF
• Characterized by decreased renal perfusion
• Intrinsic renal azotemia
• Result of direct damage to interstitium/glomerulus
  
• Post-renal azotemia
• Caused by obstruction of urine flow from kidneys
  to bladder
• Least common

8
ETIOLOGY PRE-RENAL

• Causes of pre-renal azotemia
• Decreased cardiac output CHF, MI, PE,
  Beta-blockers
• Peripheral vasodilation bacterial sepsis,
  vasodilators (nitrates, hydralazine,etc.)
• Hypovolemia blood loss, dehydration, diarrhea,
  burns, third-spacing, diuresis
• Vascular Obstruction NSAIDS, ACE-I,
  vasopressors, renal artery occlusion

9
ETIOLOGY INTRINSIC

• Causes of intrinsic azotemia
• Glomerular disease bacterial endocarditis,
  drug-induced vasculitis, postinfectious
  glomerulonephritis, systemic lupus erythamatosus
• Vascular disease serum sickness
• Tubulointerstitial disease ATN, hypercalcemia

10
ETIOLOGY POST-RENAL

• Bladder obstruction
• infection
• tumor
• BPH
• anticholinergics (diphenydramine, meclizine,
  benztropine)
• ganglionic blockers (trimethaphan)

11
DRUG-INDUCED RENAL FAILURE
12
Diagnosis

• History and clinical presentation
• Laboratory data
• UA
• Diagnostic studies
• Radiologic studies
• Biopsy

13
DIAGNOSIS-URINALYSIS
14
CLINICAL COURSE

• Oliguric phase
• average duration of 7-10 days
• accumulation of BUN and Scr
• Diuretic Phase
• average duration of 2-3 days
• progressive increase in urine volume
• BUN and Scr begin to decline
• Recovery Phase
• most of the improvement begins in 2-4 weeks
• may take up to 12 months for recovery
• many patients recover full renal function

15
Sample Case

• What is BAs estimated CLcr?
• Signs/Symptoms of ARF?
• What are possible causes of BAs ARF?
• Dosage adjustments of meds?
• What is appropriate Tx of BAs ARF?

16
TREATMENT GOALS

• Determine exact diagnosis
• Remove offending agent/Treat causes
• Prevent complications (i.e. hyperkalemia)
• Reverse oliguria/Improve renal blood flow
• Correction of intravascular volume

17
VOLUME CONTROL

• Must know patients fluid status
• pre-renal azotemia fluids can improve condition
• ATN fluids can be harmful, causing
  fluid-overload
• Must monitor fluid balance (I/Os) carefully
• avoids fluid overload
• assess efficacy of diuretic therapy
• Maintain euvolemia, tissue perfusion, electrolyte
  balance

18
VOLUME CONTROL

• Crystalloids
• use in hypovolemia (shock, dehydration)
• 0.9 NaCl, 0.45NaCl/D5W\
• 500-1000 mL of normal saline (NS) over 30 minutes
• check BP, HR, UOP after administration
• Colloids
• use in hypovolemia due to hemorrhage
• blood, albumin

19
DIURETICS

• For use in patients with adequate intravascular
  volume
• maintain hydration, then start diuretic therapy
• Help kidneys to start working again
• increase tubular flow, preventing obstruction
• Loop diuretics increase renal blood flow
• Mannitol reduces cell swelling
• Main goal is to maintain UOP

20
DIURETICS

• Loop diuretics
• furosemide most commonly used
• initial dose 40-80mg IV bolus
• can double dose if no response in few hours
• max dose 2000mg/day
• continuous infusion
• start 40-80mg IV bolus, then start 10mg-20mg/hr
  and titrate up

21
DIURETICS

• Loop diuretics
• bumetanide 40x more potent than furosemide
• 1mg bumetanide 40mg furosemide
• ethacrynic acid in patients with sulfa allergies
• Side Effects
• ototoxicity, vertigo, cramping, rash, pruritis,
  electrolye abnormalities
• Monitoring Paramters (MP)
• UOP, renal function, electrolytes, glucose

22
DIURETICS

• Mannitol
• osmotic diuretic
• 20 solution
• give 12.5-25gm IV bolus over 3-5 minutes
• may repeat in one hour if no response
• D/C if no response after second dose
• Max dose 50gm/day

23
DIURETICS

• Mannitol
• may cause extracellular fluid expansion
• lead to CHF, pulm. edema, HTN
• Side Effects
• headache, n/v/d, HTN, CHF, pulmonary edema
• MP
• UOP, renal function, chest x-ray, cardiovascular
  status

24
DOPAMINE

• Low doses (0.5-2ug/kg/min) can selectively dilate
  renal blood vessels
• increase renal blood flow, increase GFR, increase
  UOP
• Side Effects
• vasoconstriction at higher doses, tachycardia,
  angina
• MP
• UOP, blood pressure, cardiac output

25
DIALYSIS

• Useful in tx of hyperkalemia, volume overload,
  acidosis, uremia
• Advantages rapid onset of action
• Disadvantages
• requires venous access, danger for
  hemodynamically unstable patients, infections,
  removal of drugs by dialysis

26
Electrolyte Imbalances

• Hyperkalemia
• Metabolic acidosis
• Hyperphosphotemia
• Hypermagnesemia
• Hypocalcemia

27
HYPERKALEMIA

• First
• Insulin/Dextrose
• Calcium gluconate
• Sodium Bicarbonate
• Second
• Sodium polystyrene sulfate (kayexalate)

28
COMPLICATIONS

• Infection
• Risk factors impaired immunity, invasive
  procedures
• Sites pulmonary, urinary common
• Preventive measures minimize catheters, RT
• Nausea/Vomiting e-lyte disturbances
• Stress ulcers
• Cardiovascular arrythmias, fluid overload
• Neurologic e-lyte disturbances

29
NUTRITION

• Fluid/Electrolytes
• restrict potassium intake to prevent hyperkalemia
• lt40 mEq/day
• restrict sodium intake (lt 3gm/day)
• Protein
• patients are highly catabolic in ARF
• proteins are necessary for () nitrogen balance
• can worsen uremia
• Monitor UOP, Wt, I/O, Chest exam, blood
  chemistries

30
CHRONIC RENAL FAILURE

• Definition
• Progressive decline in renal function, evidenced
  by a rise in BUN/SCr, decline in CrCl, and
  development of uremic symptoms
• irreversible damage
• Three stages
• Mild renal insufficiency (CrCl 30-60 mL/min)
• Moderate renal insufficiency (CrCl 15-30 mL/min)
• Severe renal insufficiency (CrCl lt15 mL/min)

31
Staging of CRF
32
ETIOLOGY

• Systemic Causes
• Diabetes Mellitus (40)
• Hypertension (30)
• Autoimmune disease (SLE)

33
ETIOLOGY

• Renal Causes
• glomerulonephritis (strep. Infection)
• glomerulosclerosis (glomerular hypertension)
• lead to proteinuria, eventual deterioration
• interstitial nephritis
• UTI (pyelonephritis)
• ischemic renal disease (renal artery stenosis)
• congenital abnormalities (polycystic kidney
  disease, medullary cystic disease)

34
ETIOLOGY

• Drug-Induced Causes
• Antibiotics (amphotericin b, aminoglycosides,
  sulfonamides)
• Analgesics (NSAIDs, Acetaminophen)
• Chemotherapy (cisplatin, methotrexate)
• Other (ACE-Is, cyclosporin, tacrolimus)

35
RISK FACTORS

• Reversible risk factors which further compromise
  Renal function
• low cardiac output (CHF)
• Dehydration/hypovolemia
• Hypertension
• Urinary obstruction/infection
• Drugs
• Identify and correct if found

36
RISK FACTORS

• Diabetics
• screen for microalbuminuria
• limit protein intake to 0.5-0.8 g/kg/day
• intensive blood glucose control
• strict blood pressure control
• Non-diabetics
• limit protein intake to 0.6 g/kg/day
• blood pressure control

37
COMPLICATIONS

• Anemia
• Hemostatic defects
• Renal osteodystrophy
• Hyperkalemia
• Hyperuricemia
• Carbohydrate abnormalities
• HTN
• GI disturbances
• Dermatologic problems

38
COMPLICATIONS

• Hematological
• anemia (normocytic, normochromic)
• decreased erythropoietin (EPO) production
• blood loss
• decreased RBC lifespan from uremic toxins
• can also have iron and folate deficiencies
• platelet dysfunction
• due to uremic toxins
• Avoid anti-platelet drugs (ASA, NSAIDs)

39
ANEMIA

• Recommended target Hct is 33-36
• Dialysis, anabolic steroids, transfusions are
  second-line
• Recombinant Human Erythropoietin
• stimulates RBC production in the bone marrow
• dosing
• start 50-100 units/kg three times/week
• titrate by increments of 25 units/kg
• reduce dose when target Hct is reached or Hct
  increases by gt 4 points in any two week period

40
ANEMIA

• Erythropoietin
• increase dose if Hct does not increase by 5-6
  points over 8 weeks and Hct is below target range
• doses gt300 units/kg generally do not give a
  greater response
• adverse reactions
• hypertension
• iron deficiency
• seizures
• flu-like syndrome

41
ANEMIA

• Monitoring Parameters
• prior to therapy evaluate
• iron stores (nl 50-160 u/dL)
• transferrin saturation (should be gt 20)
• serum ferritin (should be gt 100 ng/mL)
• Blood pressure
• hematocrit
• measure 2x/week until stabilized
• after dosage adjustment, measure at least 2x/week

42
ANEMIA

• Delayed response
• iron deficiency most patients require suppl.
  Iron
• underlying infections
• occult blood loss
• aluminum toxicity
• underlying hematologic disease
• vitamin deficiencies

43
Sample Case

• What is TRs estimated CLcr?
• Signs/Symptoms of CRF?
• Why has TRs anemia not responded to
  erythropoetin administration?
• How should the anemia be managed?

44
COMPLICATIONS

• Calcium and Phosphate Metabolism
• hypocalcemia/hyperphosphatemia
• phosphate retention inhibits renal activation of
  vitamin D, which decreases gut absorption of
  calcium
• low calcium increases pararthyroid hormone (PTH)
  secretion
• PTH increases phosphorus secretion, increases
  calcium breakdown from bone
• renal osteodystrophy

45
CALCIUM-PHOSPHOROUS

• Goal lower phosphorous levels and optimize
  calcium levels
• Phosphorous restriction 800-1000 mg/day
• Phosphate binders
• retard phosphorous absorption from the gut
• administered just before or with meals
• Goal PO4 levels of 4.5-6.0 mg/dL in patients with
  ESRD, normal PO4 levels in patients with
  moderate to severe renal insufficiency

46
CALCIUM-PHOSPHOROUS

• Phosphate binders
• aluminum antacids
• predisposes to aluminum toxicity
• no longer first line agent
• calcium antacids
• effective in reducing phosphorous and increasing
  calcium
• watch for Ca x P04 gt 70

47
CALCIUM-PHOSPHOROUS

• Phosphate binders
• calcium antacids
• calcium carbonate
• inexpensive, effective
• give before meals
• calcium acetate
• binds 2x phosphorous than carbonate
• more soluble, better absorbed
• causes more nausea and diarrhea

48
CALCIUM-PHOSPHOROUS

• Phosphate binders
• calcium antacids
• calcium chloride
• very astringent and unpalpable
• calcium citrate
• binds poorly to phosphorous
• magnesium antacids
• fairly effective
• watch for magnesium accumulation
• diarrhea

49
CALCIUM-PHOSPHOROUS

• Vitamin D supplements
• added when other therapies fail
• improve renal osteodystrophy
• supplement with active forms of vitamin D
• most forms of vitamin D require renal activation
• dihydrotachysterol (DHT) and 1,25-dihydroxyvitamin
  D3 (calcitriol) do not require renal activation

50
CALCIUM-PHOSPHOROUS

• Vitamin D therapy
• calcitriol (Rocaltrol) drug of choice
• inhibits PTH secretion directly
• stimulates gut absorption of calcium
• faster onset of action (1 week)
• faster resolution of symptoms
• IV 0.5-4 mcg three times weekly
• give with adequate intake of calcium
• Oral .25-2 mcg/day
• SE hypercalcemia, fatigue, anemia, n/v/d, bone
  pain

51
COMPLICATIONS

• Potassium Abnormalities
• hyper/hypokalemia
• hyperkalemia
• decreased excretion, increased intake, acidosis
• hypokalemia
• inadequate intake, increased losses
• anorexia, nausea, vomiting

52
HYPERKALEMIA

• Reduce likelihood of arrhythmias
• calcium gluconate 10 5-10 ml slow IVP
• Shift potassium from outside cell to inside
• sodium bicarbonate 7.5 50 ml IV over 5 min
• may repeat in 15 minutes
• regular insulin 5-10 units over 5 minutes
• give with glucose 50 50 ml
• Potassium restriction 40 mEq/day

53
HYPERKALEMIA

• Reduce total body potassium
• kayexelate (sodium polystyrene sulfonate)
• PO 15-30 gm, up to 5x/day
• PR 30-60 gm retention enema for 30-60 min up to
  QID
• diuretics
• dialysis

54
COMPLICATIONS

• Hyperuricemia
• due to decreased renal excretion
• gouty attacks, itchy skin, uric acid stones
• Tx
• allopurinol 100-300 mg QD
• active metabolite, start at lower dosing range
• fluids, alkalinize urine
• Carbohydrate abnormalities
• due to peripheral resistance to insulin
• elevated post-prandial glucose
• Tx insulin, oral hypoglycemics, diet

55
HYPERTENSION

• Fluid/sodium restriction
• target dry weight
• sodium restriction 2-3 gm NaCl/day
• Dialysis
• Diuretics
• furosemide
• metolazone added to enhance loop diuretics
• avoid
• thiazides less effective in CrCl lt 30 ml/min
• potassium-sparing diuretics increase K levels

56
HYPERTENSION

• ACE-Inhibitors
• effective in patients with renin/angiotensin
  abnormalities induced by end stage renal disease
• also effective in diabetics with microalbuminuria
• watch for K increases
• dosage adjustment in renal disease
• Calcium channel blockers
• dihydropyridines shown to be effective in
  lowering hypertension in ESRD

57
HYPERTENSION

• Beta-blockers
• interfere with renin release
• metoprolol, labetalol, esmolol
• no dosage adjustment in renal disease
• Vasodilators
• minoxidil, hydralazine
• Central agonists
• clonidine safe and effective
• Alpha blockers
• can cause reflex tachycardia, sodium retention

58
DERMATOLOGIC PROBLEMS

• Dermatologic Problems
• pruritis, uremic frost
• Treatment
• diphenhydramine 25-50 mg po bid
• protein restriction, dialysis