Acute Kidney Injury: Complications associated with Acute Kidney Injury

Does this patient have complications associated with acute kidney injury?

Introduction

Acute kidney injury (AKI) is often associated with systemic complications including volume overload; electrolyte and acid-base disturbances, particularly hyponatremia, hyperkalemia and metabolic acidosis; nutritional and gastrointestinal disturbances; anemia and bleeding diatheses, and increased risk of infection. It is often difficult, however, to differentiate complications related to the AKI per se from those related to the underlying cause of AKI.

What tests to perform?

See reviews of specific conditions below for appropriate tests, if any.

How should patients with complications associated with AKI be managed?

Volume Overload

Disturbances of volume homeostasis are extremely common in the setting of AKI. Although effective intravascular volume depletion is a common contributing factor in the development of AKI it is an uncommon complication of AKI. Volume depletion as a result of renal salt and water wasting occasionally develops in patients with non-oliguric AKI; more commonly it may develop during recovery from acute tubular necrosis (ATN), when patients may become polyuric, or following relief of urinary obstruction, when a post-obstructive diuresis may occur.

In contrast to volume depletion, volume overload is a common complication of AKI, particularly in patients with oliguric or anuric AKI. Volume overload may develop as a consequence of volume resuscitation in patients with hypotension or may be related to underlying cardiac or hepatic disease. Volume overload often develops as a consequence of obligate intravenous infusions (eg, antibiotics, vasopressors or other medications) required for supportive care or associated with nutritional support in the setting of decreased urine output; volume overload is often exacerbated by the administration of excessive volumes of “maintenance” intravenous fluids.

Recent data have suggested that volume overload is a significant risk factor for mortality in patients with AKI. In one study, patients who had positive fluid balance at time of initiation of renal replacement therapy of >10% of body weight had an approximately 2-fold increase in mortality risk as compared to patients with less than 10% fluid gain.

In non-dialyzed patients, the odds of death associated with >10% fluid gain was 1.36. In pediatric patients, fluid gain of > 20% of body weight at the time of initiation of continuous renal replacement therapy was associated with a mortality rate of 65.6% as compared to 29.4% in patients with <10% fluid overload.

Diagnosis

Volume overload is a clinical diagnosis.Clinical findings may include:

• peripheral edema

• pulmonary vascular congestion / pulmonary edema

• ascites

• pleural effusion

• elevated central venous pressure or pulmonary artery occlusion (wedge) pressure

Treatment

Volume overload may be treated by limiting volume administration in combination with either diuretics or ultrafiltration during renal replacement therapy. Loop-acting diuretics such as furosemide can be used alone or in combination with metolazone or a thiazide diuretic.

Prognosis

Although observational studies have suggested that diuretic administration in acute kidney injury is associated with an increased mortality risk, this risk was seen predominantly in patients who were unresponsive to diuretic therapy.

In a post hoc analysis of data from the Fluid and Catheter Treatment Trial (FACTT) diuretic therapy was associated with improved survival in patients with acute kidney injury in the setting of acute lung injury. This benefit appeared to be mediated by attainment of negative fluid balance

We recommend a trial of diuretics to facilitate fluid management in volume replete or volume overloaded patients with oliguric acute kidney injury. If the patient fails to respond to high-dose diuretic therapy, further diuretic therapy should be withheld. Initiation of renal replacement therapy should be considered in patients who are diuretic-unresponsive or who develop progressive volume overload despite diuretic therapy

Disturbances of Potassium

Hyperkalemia is a common complication of acute kidney injury, particulary in oliguric AKI.

Serum potassium typically increases by 0.5 mmol/L per day in oliguric patients as the result of obligate potassium intake in the setting of impaired renal potassium excretion

Hyperkalemia may be worsened by efflux of potassium out of the intracellular compartment as the result of;

• coexistant metabolic acidosis

• hyperglycemia or other hyperosmolar state

Severe hyperkalemia may result from cell lysis when acute kidney injury develops in the setting of

• rhabdomyolysis

• intravascular hemolysis

• tumor lysis syndrome

• severe burn injury

Diagnosis

Mild hyperkalemia (<6 mmol/L) is usually asymptomatic. The most serious manifestation of more severe degrees of hyperkalemia is cardiac toxicity, with the risk of life-threating arrythmias including bradycardia, heart block ventricular tachycardia, ventricular fibrillation and asystole; and decreased myocardial contractility. Electrocardiographic manifestations of hyperkalemia include:

• peaked T-waves

• prolongation of the PR-interval

• P-wave flattening

• widening of the QRS complex

• sine wave pattern from blending of the QRS complex into the T-wave

Treatment

The treatment of hyperkalemia is briefly summarized here; for a more complete description, please see the chapter on hyperkalemia. The initial management of hyperkalemia should be based on the severity of hyperkalemia and the presence of electrocardiographic abnormalities.

Step 1: Acute treatment of hyperkalemic cardiac toxicity

Intravenous calcium is given to directly antagonize the cardiac toxicity of hyperkalemia. The onset of action is within minutes with a duration of action of 5 to 15 minutes. Calcium administration does not directly affect the serum potassium concentration. Intravenous calcium should be reserved for patients manifesting evidence of hyperkalemic cardiac toxicity

Step 2: Translocation of potassium from the extracellular compartment into the intracellular compartment

Intravenous insulin

Onset of action is usually within 5 to 15 minutes with a maximal effect within 30 to 60 minutes and a duration of action of 4 to 6 hours. Intravenous glucose should be administered concomitantly in patients who are not hyperglycemic in order to prevent hypoglycemia.

Catecholamines

inhaled albuterol

• onset of action within 5 minutes with a peak effect within 90 minutes

• intravenous beta-agonists are not available in the United States

Intravenous terbutaline

Intravenous epinephrine

Step 3: Enhanced potassium excretion

Increased renal potassium excretion

-intravenous loop diuretics

• only effective in non-oliguric patients

Increased gastrointestinal potassium excretion

-Sodium polystyrene sulfonate as a potassium-binding resin

• Must be given in combination with a cathartic agent

• Cannot be given orally in patients with bowel obstruction or ileus

• Must be used with caution in patients with underlying bowel or vascular disease due to risk of bowel ischemia/infarction

Hemodialysis

-Although potassium removal may be achieved over time with slower forms of renal replacement therapy, such as continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD), these modalities do not provide the rapid lowering of serum potassium that may be necessary in a patient with severe acute hyperkalemia

Hypokalemia is less common than hyperkalemia in patients with acute kidney injury. Hyperkalemia may complicate nonoliguric acute tubular necrosis (ATN), especially nephrotoxic ATN caused by aminoglycosides, amphotericin B or cisplatin, all of which are associated with tubular potassium wasting. Hypokalemia may also develop as a result of gastrointestinal potassium losses in patients with diarrhea or a high-output enterocutaneous fistula

Hyponatremia and Hypernatremia

Mild hyponatremia is a common complication associated with acute kidney injury. In the setting of reduced glomerular filtration rate, the ability of the kidney to excrete electrolyte free water is diminished. To the extent that water intake exceeds this decreased maximal free water excretion, hyponatremia will ensure.

Treatment

Hyponatremia in acute kidney injury is usually mild, with the serum sodium concentration remaining greater than 125 mmol/L. Treatment of hyponatremia is generally free-water restriction. In patients with severe AKI and more profound hyponatremia, renal replacement therapy may be necessary.

In patients with severe hyponatremia dialysis may need to be performed, using a dialysate solution with a reduced sodium concentration in order to minimize the rate of correction of the serum sodium concentration. Excessively rapid correction of hyponatremia can be associated with the development of central pontine myelinolysis. For this reason, the use of slower modalities of renal replacement therapy, such as continuous renal replacement therapy (CRRT) or sustained low efficiency dialysis (SLED), may be preferred over conventional intermittent hemodialysis.

Hypernatremia is a less common complication of acute kidney injury, but may develop during the diuretic phase of recovering acute tubular necrosis (ATN) or in the setting of a post-obstructive diuresis, if water intake is inadequate to match free-water losses.

Acid-Base Disturbances

Metabolic acidosis is the most common acid-base disturbance associated with acute kidney injury, developing as the result of impaired excretion of the daily load of metabolic fixed acid. Although initially a hyperchloremic metabolic acidosis develops, widening of the anion gap is often seen as the result of accumulation of phosphate, sulfate and small organic anions.Typically, the fall in plasma bicarbonate does not exceed 2 mmol/L per day unless another mechanism is superimposed.

Severe metabolic acidosis, often with marked elevation in the anion-gap may develop, as a result of underlying systemic disease, such as lactic acidosis due to tissue hypoperfusion, sepsis or advanced liver disease, diabetic ketoacidosis or toxic ingestions such as ethylene glycol.

Metabolic alkalosis is an infrequent finding in acute kidney injury, but may complicate overly aggressive treatment of acidemia with intravenous bicarbonate or loss of gastric acid due to vomiting or nasogastric drainage.

Complications of Mineral and Uric Acid Homeostasis

Hyperphosphatemia is a common complication of acute kidney injury, developing as a direct consequence of decreased renal excretion. Although usually mild to moderate in severity, severe hyperphosphatemia (10 mg/dL) may develop in highly catabolic patients or when AKI is associated with cell lysis, as occurs in rhabdomyolysis, tumor lysis syndrome and severe burn injuries.

Hyperphosphatemia can usually be treated using oral phosphate binders; in severe hyperphosphatemia, dialysis may be necessary, however there is no specific threshold serum phosphate level as an indication for dialysis.

Hypocalcemia in AKI develops as a consequence of skeletal resistance to parathyroid hormone and reduced renal conversion of 25-hydroxyvitamin D to the active 1,25-dihydroxyvitamin D by the kidney. In rhabdomyolysis, calcium sequestration in injured muscle may result in more profound degrees of hypocalcemia. The hypocalcemia associated with AKI is usually asymptomatic and does not require specific treatment.

Symptomatic hypocalcemia requires treatment with intravenous calcium, however the aggressiveness of therapy may need to be tempered in the setting of concomitant severe hyperphosphatemia, as calcium infusion may result in metastatic calcium phosphate deposition.

It is unusual for hypercalcemia to develop as a consequence of AKI. More commonly, when hypercalcemia is present in the setting of AKI, both are a consequence of an underlying disease, such as multiple myeloma, or the AKI is mediated in part by the hypercalcemia. Hypercalcemia may develop during the recovery from myoglobinuric AKI in rhabdomyolysis as calcium deposited in injured muscle is mobilized.

Mild asymptomatic hypermagnesemia is common in oliguric AKI as the result of impaired excretion of ingested magnesium. More severe hypermagnesemia is usually iatrogenic, as the result of parenteral administration, as in the management of AKI associated with pre-eclampsia. Hypomagnesemia may complicate non-oliguric nephrotoxic AKI associated with aminoglycosides, cisplatin and amphotericin B. Renal magnesium wasting may persist even after renal function has recovered.

Mild hyperuricemia, as a result of decreased renal uric acid excretion, is common in AKI. More severe elevations in serum uric acid develop when AKI develops in the setting of hypercatabolism or cell lysis. In the setting of tumor lysis syndrome, acute urate nephropathy underlies the development of AKI. In this setting, uric acid levels are often in excess of 20 mg/dL. Measurement of the urinary uric acid:creatinine ratio may help differentiate between hyperuricemia due to renal insufficiency and renal failure due to tumor lysis syndrome; in the former the ratio is usually less than 0.75, while in the latter the ratio is typically greater than 1.0.

Gastrointestinal and Nutritional Complications

The major gastrointestinal complications associated with acute kidney injury include anorexia, nausea and vomiting and upper gastrointestinal bleeding, primarily due to stress ulcers and gastritis.

Acute kidney injury is recognized as a hypercatabolic state, however the precise mechanism for the hypercatabolic state is not known. A variety of factors including the hypercatabolic nature of underlying disorders (eg, sepsis, rhabdomyolysis, trauma); hormonal disturbances including elevated levels of glucagon, catecholamines, growth hormone and cortisol and insulin resistance; and acute uremia per se, which has been associated with accumulation of proteases in the blood.

As a result of these factors, protein catabolic rate may exceed 1.5 to 1.7 g/kg/day. AKI may also be associated with impaired carbohydrate metabolism with hyperglycemia as a result of insulin resistance and accelerated hepatic gluconeogenesis and impaired lipid metabolism.

Adequate nutrition support should provide a caloric intake of at least 25 to 30 kcal/kg per day with a protein/amino acid intake of 1.2 to 15 g/kg per day. Enteral feeding is preferred; however, if adequate nutritional intake cannot be provided via the enteral route, parenteral nutrition should be provided.

Hematologic Complications

Anemia develops rapidly in AKI and is usually multifactorial in origin. Contributing factors include:

• decreased erythropoesis

• bleeding

• hemodilution

• reduced red blood cell survival time

• phlebotomy for blood tests

In patients with vasculitis or microangiopathic hemolytic anemia, hemolysis may also be a significant contributing factor.

Although a brisk reticulocytosis may be seen following administration of exogenous erythropoesis stimulating agents (ESAs), benefit with regard to survival or other clinical outcomes has not been demonstrated. Routine administration of ESAs to patients with anemia associated with AKI is not recommended.

Bleeding diatheses with prolongation of the bleeding time is common. Contributing factors include both thrombocytopenia and platelet dysfunction. Severe coagulopathy and thrombocytopenia may be associated with disseminated intravascular coagulation in patients with sepsis or malignancy.

Infectious Complications

Infectious complications are common in AKI, occurring in 50 to 90% of cases of severe AKI and accounting for up to 75% of deaths. Contributing factors include both defects in the host immune response, both due to AKI per se and to underlying morbidity, and as a result of the multiple breaches of muccocutaneous barriers (eg, intravascular catheters including dialysis catheters, bladder catheters, endotracheal intubation for mechanical ventilation) required for therapeutic management of the seriously ill patient.

What happens to patients with complications associated with AKI?

See discussions of specific complications.

How to utilize team care?

N/A

Are there clinical practice guidelines to inform decision making?

Indicated where applicable. See also chapters on specific complications.

Other considerations

N/A

What is the evidence?

Prowle, JR, Echeverri, JE, Ligabo, EV, Ronco, C, Bellomo, R. “Fluid balance and acute kidney injury”. Nat Rev Nephrol. vol. 6. 2010. pp. 107-115. (A concise review summarizing the relationship between fluid balance and outcomes in patients with acute kidney injury.)

Bouchard, J, Soroko, SB, Chertow, GM, Himmelfarb, J, Ikizler, TA, Paganini, EP, Mehta, RL. “Fluid accumulation, survival and recovery of kidney injury in critically ill patients with acute kidney injury”. Kidney Int. vol. 76. 2009. pp. 422-427. (A post hoc analysis of data from the observational PICARD study demonstrating an increased mortality in patietnts with greater than 10% volume overload as compared to patients without this degree of volume overload.)

Sutherland, SM, Zappitelli, M, Alexander, SR, Chua, AN, Brophy, PD, Bunchman, TE, Hackbarth, R, Somers, MJ, Baum, M, Symons, JM, Flores, FX, Benifield, M, Askenazi, D, Chand, D, Fortenberry, JD, Mahan, JD, McBryde, K, Blowey, D, Goldstein, SL. “Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediaric continuous renal replacement registry”. Am J Kidney Dis. vol. 55. 2010. pp. 316-325. (A retrospective analysis of pediatric data demonstrating increased mortality associated with increasing severity of volume overload in critically ill chrildren with AKI.)

Mehta, RL, Pascual, MT, Soroko, S, Chertow, GM. “PICARD Study Group: Diuretics, mortality, and nonrecovery of renal function in acute renal failure”. JAMA. vol. 288. 2002. pp. 2547-2553. (A retrospective post hoc analysis demonstrating an increased mortality risk after propensity score adjustment in patients with AKI treated with diuretics. The increased mortality risk, however, appeared to be predominantly in patients unresponsive to diuretic administration.)

Grams, ME, Estrella, MM, Coresh, J, Brower, RG, Liu, KD. “Fluid balance, diuretic use and mortality in acute kidney injury”. Clin J Am Soc Nephrol. vol. 6. 2011. pp. 966-973. (A post hoc analysis of data from the ARDS Network FACTT study demonstrating improved survival in patients with acute lung injury and AKI associated with both negative fluid balance and with diuretic use, with the benefit of diuretics mediated through the effect on volume balance.)

Evans, KJ, Greenberg, A. ” Hyperkalemia: A review”. J Intensive Care Med. vol. 20. 2005. pp. 272-290. (A review of the etiologies and management of hyperkalemia.)

Lameire, N, Van Biesen, W, Vanholder, R. “Electrolyte disturbances and acute kidney injury in patients with cancer”. Semin Nephrol. vol. 30. 2010. pp. 534-547. (A review of electrolyte disturbances associated with acute kidney injury in patients with malignancy-associated AKI.)

Abu-Alfa, AK, Younes, A. “Tumor lysis syndrome and acute kidney injury: evaluation, prevention, and management”. Am J Kidney Dis. vol. 55. 2010. pp. S1-S13. (A review of the current diagnositic criteria and management strategies for prevention and treatment of tumor lysis syndrome.)

Tungsanga, K, Boonwichit, D, Lekhakula, Sitprija, V. “Urine uric acid and creatinine ratio in acute renal failure”. Arch Int Med. vol. 144. 1984. pp. 934-937. (A description of the use of the urine uric acid to creatinine ratio to differentiate between hyperurecemia due to acute kidney injury and AKI due to acute urate nephropathy.)

Fiaccadori, E, Maggiore, U, Clima, B, Melfa, L, Rotelli, Borghetti, A. “Incidence, risk factors and prognosis of gastrointestinal hemorrhage complicating acute renal failure”. Kidney Int. vol. 59. 2001. pp. 1510-1519. (A description of gastrointenstinal hemorrhage in patients with AKI.)

Druml, W. “Nutritional management of acute renal failure”. J Ren Nutr. vol. 15. 2005. pp. 63-70. (A review of nutritional management in patients with AKI.)

Park, J, Gage, BF, Vijayan, A. “Use of EPO in critically ill patients with acute renal failure requiring renal replacement therapy”. Am J Kidney Dis. vol. 46. 2005. pp. 791-798. (A review of the use of ESA therapy in patients with AKI requiring renal replacement therapy.)

Brivet, FG, Kleinknecht, DJ, Loriat, P, Landis, PJ. “Acute renal failure in intensive care units – causes, outcome, and prognostic factors of hospital mortality: a prospective, multicenter study. French Study Group on Acute Renal Failure”. Crit Care Med. vol. 24. 1996. pp. 192-198. (A review of causes and outcomes of AKI in critically ill patients with data on the infectious complications seen in this population.)

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