The incidence of dialysis-requiring acute kidney injury (AKI-D) has increased in the past decade in the United States. From 2000 to 2009, there were 1.09 million hospitalizations (95% confidence interval [CI], 1.04–1.15 million) with AKI-D in the United States. From 2007 to 2009, the population incidence of AKI-D increased by 11% per year (95% CI, 1.07–1.16; P < 0.001).1 Hospitalized patients with AKI-D were older than their counterparts who did not have AKI-D (63.4 vs 47.6 years), were more likely to be male (57.3% vs 41.1%), to be black (15.6% vs 10.2%), to have sepsis (27.7% vs 2.6%), to have heart failure (6.2% vs 2.7%), and to undergo cardiac catheterization (5.2% vs 4.4%) and mechanical ventilation (29.9% vs 2.4%).1 The temporal trend in the 6 diagnoses—septicemia, hypertension, respiratory failure, coagulation/hemorrhagic disorders, shock, and liver disease—sufficiently and fully accounted for the temporal trend in AKI-D.2 This chapter will discuss the diagnosis of acute kidney injury and types of renal replacement therapy.
DIAGNOSIS OF ACUTE KIDNEY INJURY
Acute kidney injury is considered when there is an abrupt decrease in urine output. Diagnostic criteria have gone through an evolution, from RIFLE (risk, injury, failure, loss of kidney function, and end-stage kidney disease) criteria, AKIN (Acute Kidney Injury Network) criteria, and now KDIGO (Kidney Disease: Improving Global Outcomes) criteria.3-5 This was deemed necessary for research, clinical, and prognostication purposes. See Tables 26-1 and 26-2.
|RIFLE Category||Serum Creatinine Criteria||Urine Output Criteria|
|A. The acute dialysis quality initiative (ADQI) criteria for the definition and classification of AKI (ie, RIFLE criteria)|
|Risk||Increase in serum creatinine ≥ 1.5 × baseline or decrease in GFR ≥ 25%||< 0.5 mL/kg/h for ≥ 6 h|
|Injury||Increase in serum creatinine ≥ 2.0 × baseline or decrease in GFR ≥ 50%||< 0.5 mL/kg/h for ≥ 12 h|
|Failure||Increase in serum creatinine ≥ 3.0 × baseline or decrease GFR ≥ 75% or an absolute serum creatinine ≥ 354 µmol/L with an acute rise of at least 44 µmol/L||< 0.3 mL/kg/h > 24 h or anuria ≥ 12 h|
|B. The acute kidney injury network (AKIN) criteria for the definition and classification of AKI|
|Stage 1||Increase in serum creatinine ≥ 26.2 µmol/L or increase to ≥ 150–199% (1.5- to 1.9-fold) from baseline||< 0.5 mL/kg/h for ≥ 6 h|
|Stage 2||Increase in serum creatinine to 200–299% (> 2- to 2.9-fold) from baseline < 0.5 mL/kg/h for ≥ 12 h||< 0.5 mL/kg/h for ≥ 12 h|
|Stage 3||Increase in serum creatinine to ≥ 300% (≥ 3-fold) from baseline or serum creatinine ≥ 354 µmol/L with an acute rise of at least 44 µmol/L or initiation of RRT||< 0.3 mL/kg/h ≥ 24 h or anuria ≥ 12 h|
|Stage||Serum Creatinine||Urine Output|
|1||1.5 to 1.9 × baseline or ≥ 0.3 mg/dL (≥ 26.5 µmol/L) increase||< 0.5 mL/kg/h for 6–12 h|
|2||2.0 to 2.9 × baseline||< 0.5 mL/kg/h for ≥ 12 h|
|3||3.0 × baseline or increase in serum creatinine to ≥ 4.0 mg/dL (≥ 353.6 µmol/L) or initiation of renal replacement therapy or in patients < 18 y, a decrease in eGFR to < 35 mL/min per 1.73 m2||< 0.3 mL/kg/h for ≥ 24 h or anuria for ≥ 12 h|
Investigation of the etiology of AKI begins with the characterization of the urinalysis with or without urine culture and serum and urine electrolytes. Fractional excretion of sodium (FENa) is represented by the following relationship: (Urine Sodium × Serum Creatinine)/(Serum Sodium × Urine Creatinine) × 100. An FENa less than 1 suggests prerenal and an FENa greater than 2 suggests acute tubular necrosis (ATN). Limitations to an FENa less than 1 is that it is also seen in chronic diseases such as liver cirrhosis, congestive heart failure, vasculitis, acute glomerulonephritis, nonoliguric ATN, and contrast-induced nephropathy. An alternative is fractional excretion of urea (FEurea), which represents the relationships among urine urea nitrogen, blood urea nitrogen (BUN), serum creatinine, and urine creatine and can help distinguish the 2 main causes of renal failure regardless of recent diuretic use. An FEurea greater than 0.4 indicates an intrinsic cause of renal failure, while an FEurea less than 0.3 indicates a prerenal cause.6 A BUN-to-creatinine ratio of 20:1 can suggest prerenal causes of AKI, although this might be erroneous in the setting of elevated BUN from gastrointestinal bleeding or corticosteroid use. Urine eosinophils can suggest acute interstitial nephritis but can also be seen in transplant rejection, pyelonephritis, atheroembolic disease, and rapidly progressive glomerulonephritis. Imaging studies such as renal ultrasound or CT scan are sometimes considered.
INDICATIONS FOR RENAL REPLACEMENT THERAPY
Acute kidney injury treated with renal replacement therapy (AKI-RRT) occurs in approximately 13% of ICU patients.7 Indications for renal replacement therapy include refractory hyperkalemia, metabolic acidosis, uremic pericarditis, encephalopathy, refractory volume overload, and drug intoxications (aspirin, lithium, metformin, ethylene glycol, methanol, and Amanita). Delays in initiating RRT can result in serious preventable complications and even death.8-10
LOGISTICS INVOLVED IN RENAL REPLACEMENT THERAPY
The right internal jugular vein is the preferred site for a temporary hemodialysis (HD) catheter, but the femoral vein is a viable alternative.5,11 Subclavian access is not preferred due to kinking and/or the risk of stenosis. A hemodialysis catheter may be needed in end-stage renal disease (ESRD) patients undergoing continuous low-flow modalities, as such low blood flow rates may result in clotting of a preexisting arteriovenous fistula (AVF) or arteriovenous graft (AVG).
Renal replacement machines have a blood pump with an adjustable speed that determines blood flow rates (BFR) and a filter. In case of intermittent hemodialysis (IHD) or sustained low-efficiency dialysis (SLED), the dialysate flows in a countercurrent direction to maintain the gradient for diffusion of particles across the semipermeable membrane of the filter. Composition of the dialysate can be adjusted for patient-specific needs (eg, calcium, bicarbonate, and potassium concentrations). Dialysate flow can be interrupted with blood flowing through the filter resulting in pure ultrafiltration using principle of convection; pure ultrafiltration (PUF) and slow continuous ultrafiltration (SCUF) differ in the blood-flow rates they use. Dialysis filters have various sizes and UF coefficients depending on the surface area and porosity (eg, high flux and low flux).
For continuous venovenous hemofiltration (CVVH), blood flows through a filter generating ultrafiltrate. This removes plasma water containing solutes. The replacement fluids (RF) are added either before (predilution/inflow) the blood flows through the filter or after (postdilution/outflow). Effluent flow is reported as mL/kg/h. The difference between the effluent flow and volume of RF determines the net fluid removal. Addition of RF and removal of plasma water via convection through the filter results in changes in blood composition requiring periodic monitoring of blood chemistry. Replacement fluids are adjusted based on results of blood chemistry.
INTENSITY OF RENAL REPLACEMENT THERAPY
A Cochrane review assessed the effects of different intensities (intensive and less intensive) of continuous RRT (CRRT) on mortality and on recovery of kidney function in critically ill AKI patients.12 It included all randomized controlled trials (RCTs) of patients with AKI in the ICU regardless of age, comparing intensive (usually a prescribed dose ≥35 mL/kg/h) versus less intensive CRRT (usually a prescribed dose < 35 mL/kg/h). More intensive CRRT did not demonstrate beneficial effects on mortality or recovery of kidney function in critically ill patients with AKI. There was an increased risk of hypophosphatemia with more intense CRRT. Intensive CRRT reduced the risk of mortality in patients with postsurgical AKI.
Two large multicenter randomized control trials investigated whether there is a correlation with intensity of RRT with improved patient outcomes: the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement (RENAL) trial, which compared postdilution effluent flow of 40 mL/kg/h to 25 mL/kg/h13; and the Acute Renal Failure Trial Network (ATN) studies,14 which compared IHD, SLED, or CVVH 35 mL/kg/h 6 times per week, representing the intensive renal support protocol, versus IHD, SLED, or CVVH 20 mL/kg/h 3 times per week, regarded as the less intensive renal support. These studies demonstrated that increased intensity of RRT was not associated with improved patient outcomes.
Modalities differ by utilizing either diffusion (dialysis) or convection (filtration) or a combination (diafiltration). Pump speed determines the blood flow across the machine, which is 350 mL/min in the conventional mode of hemodialysis and can be lowered in hemodynamically unstable patients to 200 mL/min. The lowering of blood flow results in a longer duration of treatment to achieve clearance and/or ultrafiltration and uses modalities such as SLED, CVVH, or continuous venovenous hemodiafiltration (CVVHDF) (see Fig. 26-1). These forms of hemodialysis use low blood-flow rates to avoid abrupt changes in hemodynamics and body milieu. Additionally, removal of solutes by conventional IHD can result in rapid changes in serum osmolality. Low blood-flow rates allow for more gradual shifts in osmolality, which is preferred in patients with central nervous system (CNS) injury (eg, stroke or traumatic brain injury) to avoid sudden changes in intracranial pressure. Peritoneal dialysis uses the patient’s peritoneal membrane to achieve clearance (both convection and diffusion) and ultrafiltration.
Modalities of continuous renal replacement therapies (CRRT). Techniques available today for renal replacement in the intensive care unit. CAVH = continuous arteriovenous hemofiltration; CHP = continuous hemoperfusion; CPFA = plasma filtration coupled with adsorption; CPF-PE = continuous plasma filtration–plasma exchange; CVVH = continuous venovenous hemofiltration; CVVHD = continuous venovenous hemodialysis; CVVHDF = continuous venovenous hemodiafiltration; CVVHDF = continuous high-flux dialysis; D = dialysate; HVHF = high-volume hemofiltration; K = clearance; Pf = plasma filtrate flow; Qb = blood flow; Qd = dialysate flow; Qf = ultrafiltration rate; R = replacement; SCUF = slow continuous ultrafiltration; SLED = sustained low-efficiency daily dialysis; UFC = ultrafiltration control system. UF = ultrafiltration; V = vein (Reprinted with permission from Cerda J, Ronco C. Modalities of continuous renal replacement therapy: technical and clinical considerations. Semin Dial. 2009;22(2):114-122.)
ANTICOAGULATION FOR RENAL REPLACEMENT THERAPY
Except for peritoneal dialysis, all modalities of RRT result in blood flowing through the circuit with resultant activation of the clotting cascade, which inevitably causes clotting of the circuit, resultant blood loss, and interruption of RRT. Clotted circuits can be flushed with IV fluids to minimize blood loss with an undesirable increase in the patient’s intravascular volume. An IV bolus of heparin (30 IU/kg) can be given at the beginning of IHD for ESRD patients to prevent clotting of the circuit in dialysis units. Continuous RRT requires hourly administration of heparin (5–10 IU/kg/h) depending on the duration of the treatment session, with a target partial thromboplastin time (PTT) 1.5 times the control. Frequent circuit clotting despite heparin should raise the possibility of heparin induced thrombocytopenia (HIT) and heparin induced thrombocytopenia with thrombosis (HITT). When HITT is suspected or confirmed, all heparin products must be stopped and replaced by an alternative. Patients with AKI requiring RRT in the ICU may have contraindications for heparin (bleeding risk, CNS injury, HIT). Low-molecular-weight heparins (LMWHs) have several advantages over unfractionated heparin (UFH), including a lower incidence of HIT, less affinity for antithrombin, less platelet (and polymorphonuclear cell) activation, less inactivation by platelet factor-4, greater and more consistent bioavailability, and no metabolic side effects.15 However, LMWHs are eliminated by CRRT. Although some studies have used fixed doses of LMWH, continuous intravenous administration of LMWH adjusted to achieve systemic anti-factor Xa levels of 0.25 to 0.35 U/mL may be the safer option, resulting in improved filter survival as compared with UFH.16
Another option is the use of citrate with CVVH. Regional citrate is more efficacious in prolonging circuit lifespan and reducing the risk of bleeding and should be recommended as the priority anticoagulant for critically ill patients who require CRRT.17 In adult patients with AKI, there is no difference in mortality between the groups treated with regional citrate and those treated with heparin.18 Citrate is infused before the blood enters the circuit to chelate calcium. The ratio of total calcium to ionized calcium (iCa) guides the infusion rate, as citrate accumulation may occur in liver failure, altering the ratio to greater than 2.5. Calcium citrate complexes are metabolized into bicarbonate in the muscles, liver, and kidney; thus, citrate toxicity causes both a metabolic alkalosis and a severe hypocalcemia.