Page 1355 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

928 PART 8: Renal and Metabolic Disorders

Terlipressin increases resistance in the splanchnic circulation allowing PREvENTION OF ACUTE RENAL FAILURE
redistribution of blood to extra-splanchnic organs including the kidney,
thereby switching off the RAS. Randomized controlled trials have shown Frequently, AKI develops in hospitalized patients in whom it is predict-
114
that use of terlipressin with and without albumin improved GFR in patients able and can be prevented or ameliorated. To intervene effectively, it is
with HRS. 117,118 This may be of particular benefit as a supportive therapy in important to identify the patients at risk (Table 97-9). There is an addi-
patients awaiting liver transplantation. Randomized trials have not shown tive interaction among the risk factors. Unfortunately, most attempts
any superiority of terlipressin over other systemic vasoconstrictors, such as to modify the course of AKI are probably too late if tubular damage
vasopressin, norepinephrine or octreotide and midodrine in combination. has already begun. 10
The ADQI group produced a consensus document regarding management Although AKI may be prevented or ameliorated by judicious use and
of HRS. Terlipressin and albumin was the recommended regimen for first monitoring of nephrotoxic drugs, and perhaps evolving cytoprotective
line management, with the recommendation that treatment should be and anti-inflammatory therapies, the major focus in AKI prophylaxis and
discontinued after 4 days in nonresponders. 116 therapy remains optimization of renal perfusion. The primary causes
An alternative therapy for HRS is transjugular intrahepatic portosys- of renal hypoperfusion differ between the major types of shock, and
temic shunt (TIPS). TIPS has been shown to improve refractory ascites therapies vary accordingly. The role of hemodynamic monitoring
in patients with type 2 HRS. In patients with type 1 HRS, TIPS may and support with fluids and vasoactive drugs in the prevention of
119
improve survival but data are limited. 120,121 It is not recommended as a AKI in the ICU is important, but there is little high-grade evidence to
first line treatment for HRS. TIPS is contraindicated in patients with guide these therapeutic choices. As discussed above, renal perfusion
116
serum bilirubin levels >85.5 mmol/L (5 mg/dL), severe encephalopathy is optimized by using fluids and vasoactive drugs to seek an adequate
or history of recurrent encephalopathy, severe bacterial infection, seri- perfusion pressure and cardiac output.
ous cardiac or pulmonary dysfunction, or a Child–Pugh score >11. It appears that colloids are not superior to crystalloids for prevention
Renal replacement therapy (RRT) can be used in HRS as a supportive of AKI in critically ill patients. A large randomized, controlled prospec-
therapy in patients awaiting liver transplantation. CRRT may be pre- tive trial of albumin versus saline in almost 7000 critically ill patients
ferred in patients with hemodynamic instability, but there are no large found no demonstrable effect of one over the other on mortality, renal
122
trials comparing methods of RRT in HRS. 116 function, or the frequency of renal replacement therapy. Of note,
■ ACUTE RENAL FAILURE IN RENAL TRANSPLANTATION patients with cirrhosis were excluded from this trial, and limited data
suggest that albumin is useful to prevent AKI in cirrhotic patients
123
The approach to the transplant patient with AKI is no different from with spontaneous bacterial peritonitis, or those undergoing large-
that in any other patient, with the exception that several unique entities volume paracentesis. Another comment regarding this study relates to
must be considered. It is simplest to consider these in relation to the time the volume of fluids used; few patients in the study received very large
since transplantation occurred. Within the first few hours or days after volume fluid resuscitation (>5 L), and consequently the results may
surgery, technical problems are the first consideration. In addition to not be applicable to all patients. The patients in the albumin group also
hypovolemia and ATN, these include vascular thrombosis, ureteral ste- received less fluid compared with the saline group.
nosis, urinary leaks, and obstructive fluid collections such as hematomas Hydroxyethyl starch (HES) is a widely used alternative to human
or lymphoceles. Hyperacute rejection, though often apparent at the time albumin. A variety of HES preparations are available which differ in
of surgery, may not be recognized for several hours or days. Thorough molecular weight, concentration, molar substitution, and substitution of
diagnostic evaluation is mandatory, including renal ultrasound, confir- hydroxyethyl for hydroxyl groups. The molar substitution refers to the
matory tissue typing (particularly the direct cross-match), and occa- number of hydroxyethyl groups per glucose molecule: 0.4 (tetrastarch),
sionally angiography or transplant biopsy. Surgical intervention is often 0.5 (pentastarch), 0.6 (hexastarch), and 0.7 (hetastarch). The colloid
required in addition to the usual supportive measures. osmotic pressure is dependent on the concentration of colloid in solu-
During the period beginning approximately a week after surgery and tion; a 10% solution is hyperoncotic. There has been concern that these
continuing for the next several months, drug effects, acute rejection, products may increase the risk of AKI, particularly hyperoncotic HES
124
and infectious processes are of particular concern. It is during this time solutions with molar substitutions greater than 0.5. In the efficacy of
that antirejection drug dosages are at their highest levels, and as a result volume substitution and insulin therapy in severe sepsis (VISEP) study,
complications related to these drugs are most frequent. The immunosup- patients were randomized to receive a hypertonic solution (10%) of low
pressive drugs cyclosporine and tacrolimus are frequent causes of dose- molecular weight HES (200/0.5) or an isotonic modified Ringer’s lactate
dependent acute nephrotoxicity, and levels should be monitored closely; solution. The trial was stopped prematurely due to safety concerns fol-
thrombotic microangiopathy is a rarer adverse effect of these calcineurin lowing the first interim analysis. The HES group had a higher rate of
inhibitors. The clinical diagnosis of acute rejection is often difficult to make, AKI (35.9% vs 22.8%) and a trend toward greater mortality at 90 days. 124
frequently requiring histologic confirmation or empirical antirejection Colloid-induced AKI is associated with morphological abnormali-
therapy. Although an acute rejection episode occurs in the majority of renal ties of the proximal tubular cells, called osmotic nephrosis. The tubu-
transplant recipients within the first year following engraftment, it is increas- lar pathology observed occurs as a consequence of accumulation of
ingly uncommon thereafter. Thus a diagnosis of acute rejection several years proximal tubular lysosomes due to pinocytosis of exogenous osmotic
after transplantation is less likely as long as the patient adheres to therapy.
One of the most frequent and severe infections compromising renal
function in transplant recipients is cytomegalovirus (CMV), which can TABLE 97-9 Risk Factors for the Development of Acute Renal Failure
cause dysfunction in many organ systems, including the central nervous Preexisting chronic renal failure
system, lungs, liver, and kidneys. CMV is often suspected clinically on
the basis of fever, multisystem organ involvement (including AKI), and Volume depletion
progressive leukopenia. It is more common in patients who have received Diabetes mellitus
intensive immunosuppression for severe or recurrent rejection episodes. Elderly patients
Late causes of AKI in transplant recipients include recurrence of
the patient’s original renal disease, de novo transplant glomerulopa- Postoperative patients
thy, infections, transplant artery stenosis, and urologic problems such Congestive heart failure
as stricture or rejection of the ureter. In addition to renal ultrasound, Urinary tract infection
transplant biopsy is often useful in defining the cause of AKI late in the
course of a kidney transplant. Prior history of acute renal failure

section08.indd 928 1/14/2015 8:27:56 AM