ACUTE RENAL FAILURE IN CRITICAL ILLNESS AND RENAL
REPLACEMENT THERAPY
ARF: Definition and Pathophysiology
- Definition.: sudden, sustained decline in glomerular filtration rate, usually
associated with azotemia and a fall in urine output (oliguria or anuria)
- Problems with definition
-- Incr BUN: seen with GI bleeding, severe catabolic states (infection),
drugs (corticosteroids)
-- Incr creatinine: seen in pts with large muscle mass
-- Decr UOP: in pts with decr intake of solute (sodium) or protein, less
urine will be requ’d for solute excretion so may have baseline decr UOP
- Pathophysiology: 4 Factors
-- Decreased glomerular capillary permeability (endoth cell swelling?)
-- Back-leak of glomerular filtrate
-- Tubular obstruction – debris in the tubules secondary to injured
epithelial cells form casts that obstruct, increase intratubular pressure
-- Hemodynamic abnormalities – particularly in hypoxic medulla
-- obstruction of medullary capillaries
-- intrarenal vasoconstriction (too much endothelin and TXA2,
too little NO, PGE2 and PGI2); kidney attempts to preserve BP
-- Acute Tubular Necrosis – (ATN) Condition characterized by tubular cell
necrosis that occurs sec to hemodynamic instability (hypoxia, hypotension, etc.)
Clinical Conditions Associated with ARF
- Sepsis – Mediator-related renal hypoperfusion
-- may be assoc with decreased systemic BP (however, RBF may not be
affected by systemic blood vasodilation)
-- elevated levels vasopressor, angiotensin II, norepi, etc
-- endotoxin directly decreases GFR and increases afferent arteriolar
resistance (which is different from other causes of ARF)
-- TNF induces WBC release of toxins, local mediators of vascular tone
-- Hepatorenal syndrome
-- Definintion: clinical condition that occurs in patients with chronic
liver disease and advanced hepatic failure characterized by impaired
renal function and marked abnormalities in the arterial circulation
and activity of the endogenous vasoactive systems.
-- In the kidney there is marked renal vasoconstriction that results
in low GFR. In the extrarenal circulation there is a predominance
of arteriolar vasodilation that results in the reduction of total
systemic vascular resistance and arterial hypotension
-- occurs secdondary to local and systemic mediators: PG (act as
impt renal vasodilators), R-A system, AVP, etc
-- Risk factors; classical parameters of liver fx not prognostic
-- clinical sx: Type I: rapid (days/weeks) incr in BUN, decr UOP,
hyponatremia, hyperkalemia, rarely acidotic, occurs spontaneously but can
be seen with SBP; survival in these patients < 2 weeks. Type II:less severe
-- Diagnosis: Decreased GFR in the absence of other causes of ARF in
patients with liver failure (Crs may be normal or low sec to low protein
intake or decr production, and BUN may be high if bleeding)
-- can determine GFR by finding resistive index by Doppler
-- Management: Avoid low volume states during paracentesis, give
prophylactic abx for pts at risk for spontaneous bacterial peritonitis,
dialysis may not be helpful.
-- Treat liver disease: peritoneovenous shunts, transjugular
intrahepatic portasystemic shunt (TIPS), transplant (though CsA
may hinder resolution of ARF)
-- Heart failure
Chronic Heart Failure
-- Because of neurohumoral elements (PG, R-A, etc.), pts with low
RBF still have preserved GFR and an increased filtration fraction
-- this occurs secondary to increased efferent arteriolar resistance
and glomerular hydrostatic pressures
-- there is also enhanced sodium reabsorption in the Loop of Henle
-- all of this ultimately leads to edema and cardiac dilatation
-- The kidney’s goal : preservation of CO, BP, and GFR; so
hypotension and things that alter the neurohumoral balance
(NSAIDS) can precipitate renal failure
Acute Heart Failure
-- the major determinants of renal well-being are CO, renal
perfusion pressure, and the adequacy of intravascular volume
resuscitation
-- labs typically abnormal 3 days after insult
-- Hemolytic Uremic Syndrome
-- Definition: Disease of non-immune hemolytic anemia,
thrombocytopenia, and renal failure due to platelet thrombi and fibrin
deposition in the microcirculation of the kidney
-- occurs in kids between 1-10 yo (in the summer, can be in
epidemics); usu presents with bloody diarrhea, fever, CNS
involvement, etc.
-- assoc with E. Coli 0157:H7- (verotoxin may be found in the
stool)
-- 5-10% mortality in the acute phase (nonrenal)
-- Acute Renal Failure
-- Decr UOP appears 2-14 days into illness, 60% of pts with HUS
have ARF with oliguria
-- Management: minimize fluid and Na and K intake, watch
nutrition (pts usu catabolic), consider PD when anuric or severely
oliguric, antihypertensives
-- Abx don’t work; chromosorb in trials (binds to enteric toxins)
-- Steroids, anticoagulants don’t work; may do plasma exchange if
neurologically affected
-- Prognosis: of pts requiring dialysis > 8 days, 60% recovered
renal fx: pts requiring dialysis > 28 days, never recover.
Associated abnormalities with acute renal failure
-- Coagulopathy-- impaired platelet-vessel wall dysfx may be corrected with
hemodialysis so uremia-related toxin may be impt
-- Nutrition
-- ICU pts with higher EE in the absence of ARF than in the presence
(may be sec to metabolic demands of a healthier kidney)
-- pts will have incr glycemia and insulin resistance
-- pts have decr lipolytic activity (incr TG and cholesterol) but are a major
source of fuel in pts with ARF
-- pts have high protein turnover associated with a hypercatabolic state.
-- pts have low vit D levels and low levels of antioxidants like vit E
Diagnosis of acute renal failure
-- Decrease or increase (change) in UOP, incr BUN/Cr in pts without other
reasons
-- Source of ARF
-- FENa = UNa/SNa
prerenal < 1 CANNOT BE ON DIURETICS
UCr/SCr
postrenal > 1
-- Prerenal failure: urine Na < 20, urine osmolarity > 500
Intrinsic/Postrenal failure: urine Na > 50, urine osmolarity < 300
-- Imaging techniques
-- Ultrasound - kidneys usually normal size with prerenal failure and may
be increased in size in pts with ATN and acute glomeular nephritis
-- Doppler ultrasound – look at Resistive Index (RI) which provides
functional information
-- Prerenal – Normal RI
-- ATN – increased RI
-- Hepatorenal syndrome – may have elevated RI
-- HUS – elevated RI, hyperechogenic cortex
Management of acute renal failure
-- Basic Management
-- Normal hemodynamics, fluid status (insensibles + UOP), O2 delivery,
good nutrition, etc
-- maintain nl elytes (watch K+, acid/base, iCa, phosphorous, UA, etc)
-- Fluid Management
-- Must maintain adequate preload (intravascular volume)
-- Diuretics
-- Loop Diuretics: more effective and less toxic with continuous
infusion vs bolus dosing; works better with combination tx
(thiazides); decr tubular cell metabolic demand so is
cytoprotective; consider giving albumin if level low.
-- Mannitol: antioxidant, osmolar agent
-- Inotropes: maintain BP; supplemental Dopamine may work in a pt but as a
whole, it does not improve UOP
Renal Replacement Therapy
-- Indications
-- anuric/oliguric failure
-- need for more “vascular space” (HA, blood products)
-- metabolic abnormalities
-- intoxication
-- experimental – SIRS, liver failure
-- Relative Contraindications
-- Active bleeding
-- Recent cerebral hemorrhage
-- Lack of access
-- Hemodynamic instability
-- Medical futility
-- Physiology
-- Diffusion: transmembrane solute movement in response to
concentration gradient
-- Convection: transmembrane solute movement in association with
ultrafiltered plasma water (“solvent drag”); mass transfer rate determined
by ultrafiltration rate (pressure gradient) and membrane sieving properties
-- Hemodialysis
-- Occurs using diffusion
-- Hemofiltration
-- Occurs using convection
-- Allow transfer of small solutes (urea, creatinine, UA, K+, etc); no
protein-bound substances are permeable
-- Modalities
-- SCUF = slow continuous ultrafiltration
-- No replacement soln; no dialysate
-- CVVH = continuous venovenous hemofiltration
-- (+) replacement soln; no dialysate
-- replacement fluid is added to prevent sludging post-filtration
which can occure with filtration rate > 25% (see figure)
-- CVVHD = continuous venovenous hemodialysis
-- (+) dialysate; (-) replacement soln
-- CVVHDF = cont. venovenous hemodiafiltration
-- (+) dialysate and replacement soln
-- Solute Clearance – determined by blood flow rate, dialysate/replacement fluid
flow rate, and membrane properties
-- Fluid Balance
-- UFnet = pt removal set on machine – (total fluid in – UOP)
-- Total fluid in excludes replacement fluid (which is accounted for in
machine settings)
-- Anticoagulation
-- Adjust heparin to keep ACT (postfilter) 160-200 sec
-- If pt coagulopathic, may not need heparin
-- Complications
-- Hypotension
-- Bleeding/clotting
-- Hemolysis
-- Arrhythmia
-- Infection
-- Access/technical problems
-- Anaphylaxis