Prevention and treatment of heme pigment-induced acute kidney injury - UpToDate

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Prevention and treatment of heme pigment-induced acute kidney injury - UpToDate

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Prevention and treatment of heme pigment-induced acute kidney injury Authors: Mark A Perazella, MD, FACP, Mitchell H Rosner, MD Section Editor: Paul M Palevsky, MD Deputy Editor: Shveta Motwani, MD, MMSc, FASN All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Feb 2019. | This topic last updated: Aug 04, 2017.

INTRODUCTION Acute kidney injury (AKI) can occur in patients who have rhabdomyolysis and, less commonly, in patients with hemolysis [1,2]. In both groups of patients, AKI is caused by the nonprotein heme pigment that is released from either myoglobin or hemoglobin and is toxic to the kidney. The prevention and treatment of heme pigment-induced AKI due to nontraumatic rhabdomyolysis or hemolysis will be reviewed here. The clinical features and diagnosis of this disorder, AKI due to traumatic muscle injury, overviews of rhabdomyolysis and hemolysis, and the general management of oliguric AKI and its complications are discussed elsewhere. (See "Clinical features and diagnosis of heme pigment-induced acute kidney injury" and "Crush-related acute kidney injury" and "Clinical manifestations and diagnosis of rhabdomyolysis" and "Diagnosis of hemolytic anemia in the adult" and "Dialysis-related factors that may influence recovery of renal function in acute kidney injury (acute renal failure)".)

PREVENTION In addition to treating the underlying rhabdomyolysis or hemolysis, the general goals for prevention of AKI in all patients at risk for heme pigment-induced AKI are twofold: ●

Correction of volume depletion if present

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Prevention of intratubular cast formation

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The underlying conditions and factors that have led to rhabdomyolysis or hemolysis must also be addressed to avoid continued heme pigment release. These issues are reviewed here. The prevention of AKI in patients who have suffered trauma and are entrapped at the site of trauma are discussed separately. (See "Crush-related acute kidney injury", section on 'Prevention'.) The general approaches to the treatment of the factor(s) causing rhabdomyolysis (including an acute compartment syndrome) or hemolysis are discussed in detail elsewhere. (See "Clinical manifestations and diagnosis of rhabdomyolysis" and "Acute compartment syndrome of the extremities" and "Hemolytic anemia due to drugs and toxins".) Volume administration — The prevention of AKI requires early and aggressive fluid resuscitation. The goals of volume repletion are to maintain or enhance renal perfusion, thereby minimizing ischemic injury, and to increase the urine flow rate, which will limit intratubular cast formation by diluting the concentration of heme pigment within the tubular fluid, wash out partially obstructing intratubular casts, and increase urinary potassium excretion. Intravenous isotonic saline should be administered as soon as possible after the onset of injury (even while the patient is being rescued) or detection of hemolysis and continued until the muscle injury or hemolysis has resolved. The evidence to support this strategy is largely based upon studies of traumatic crush injuries that have resulted from large-scale natural or manmade disasters. Although these studies are predominantly retrospective and underpowered, they are believed to be broadly applicable to AKI that is due to nontraumatic rhabdomyolysis and to hemolysis as well, given their common underlying pathogeneses. These studies are discussed elsewhere. (See "Crush-related acute kidney injury".) The optimal fluid and rate of repletion are unclear. No studies have directly compared the efficacy and safety of different types and rates of fluid administration in this setting. In particular, no studies have directly compared the use of chloride-restricted (bicarbonate, lactate, or acetate as the accompanying anion) versus chloride-liberal fluid resuscitation strategies in the prevention of heme pigment-induced AKI due either to rhabdomyolysis or hemolysis. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Buffered crystalloid'.) In addition, the total amount and rate of volume repletion will vary depending on the underlying cause of rhabdomyolysis and hemolysis. As an example, attempted aggressive volume resuscitation in the setting of massive hemolysis may result in volume overload and pulmonary edema, especially in patients with compromised cardiac function. In contrast, volume overload is less likely to occur in patients with rhabdomyolysis, at least https://www-uptodate-com.ezproxy.javeriana.edu.co/contents/prevention-and-treatment-of-heme-pigment-induced-acute-kidney-injury/print?search=r…

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during its initial stages, due to the sequestration of significant amounts of fluid within damaged muscle. For patients who are at risk for heme-associated AKI due to rhabdomyolysis from any cause, we suggest initial fluid resuscitation with isotonic saline at a rate of 1 to 2 L/hour. The plasma creatine kinase (CK) concentration correlates with the severity of muscle injury, and concentrations >5000 unit/L identify patients who are at risk for the development of AKI. However, it may be difficult to identify patients who are at high risk for AKI based upon the initial plasma CK value since the CK level may still be rising from ongoing muscle injury. Thus, sequential CK measurements are critical in tailoring therapeutic interventions. All patients should be initially treated with vigorous fluid repletion until it is clear from sequential laboratory values that the plasma CK level is stable and not increasing. Patients who have a stable plasma CK level 5000 unit/L, 154 (40 percent) were treated with bicarbonate and mannitol [14]. There was no statistically significant difference in the incidence of renal failure (defined as serum creatinine >2.0 mg/dL [177 micromol/L]; 22 versus 18 percent), dialysis (7 versus 6 percent), or death (15 versus 18 percent) in patients who were or were not treated with bicarbonate and mannitol, respectively. However, there was a trend toward improved outcomes in patients with extremely high serum CK levels (greater than 30,000 unit/L) treated with bicarbonate and mannitol. Unless the patient is carefully monitored and losses replaced when appropriate, mannitol can lead to both volume depletion and, since free water is lost with mannitol, hypernatremia [9]. Mannitol administered in very high doses, or to patients with reduced renal excretion due to renal insufficiency, can cause hyperosmolality, volume expansion, and hyperosmolar hyponatremia. The increase in plasma osmolality can also cause passive movement of potassium out of cells and raise the plasma potassium concentration. AKI may occur if patients are treated with more than 200 g of mannitol per day. (See "Complications of mannitol therapy".) The use of mannitol administration may be of benefit in patients with marked elevations in CK (>30,000 unit/L); however, even in these patients with severe rhabdomyolysis, the true benefit

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associated with mannitol administration remains undefined. (See "Crush-related acute kidney injury", section on 'Use of mannitol'.) If mannitol is given, adding 50 mL of 20 percent mannitol (1 to 2 g/kg per day [total, 120 g], given at a rate of 5 g per hour) to each liter of fluid is suggested. Mannitol is contraindicated in patients with oligoanuria, and patients should have adequate urine outputs (>20 mL/hour). If mannitol is given, the plasma osmolal gap should be measured and mannitol discontinued if the osmolal gap rises above 55 mosmol/kg (calculator 1 and calculator 2). Mannitol should be discontinued if the desired diuresis of approximately 200 to 300 mL/hour cannot be achieved since there is a risk of hyperosmolality, volume overload, and hyperkalemia with continued mannitol administration under these conditions. (See "Complications of mannitol therapy".) Loop diuretics — We do not give loop diuretics unless volume overload is present. Loop diuretics have no impact on outcome in AKI [15,16]. In the context of rhabdomyolysis, loop diuretics may worsen the already existing trend for hypocalcemia since they induce calciuria and may increase the risk of cast formation [17,18]. (See "Possible prevention and therapy of ischemic acute tubular necrosis".) Despite these concerns, however, judicious use of loop diuretics may be justified in patients with rhabdomyolysis or hemolysis if there is evidence of volume overload. Patients who remain oliguric or anuric despite aggressive volume resuscitation should be considered to have established AKI. Among such patients, the rate of fluid administration should be decreased to a rate sufficient to maintain circulatory support. Such patients should be closely followed for indications to initiate dialysis. (See 'Treatment of established AKI' below.) Dialysis — The use of dialysis to remove myoglobin, hemoglobin, or uric acid in order to prevent the development of renal injury has not been demonstrated [3,19].

TREATMENT Treatment of metabolic abnormalities — Patients should be closely followed for the development of metabolic abnormalities including hyperkalemia, hypocalcemia, hyperphosphatemia, and hyperuricemia. (See "Clinical features and diagnosis of heme pigment-induced acute kidney injury", section on 'Clinical manifestations'.) To minimize the late occurrence of hypercalcemia as well as the risk of calcium-phosphate precipitation, calcium supplementation for hypocalcemia should be avoided unless significant signs

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and symptoms of hypocalcemia develop or calcium administration is required for the management of hyperkalemia. Hyperkalemia should be anticipated and may occur even in the absence of severe AKI. Hyperkalemia should be aggressively treated with standard medical management. Dialysis may be required to treat severe hyperkalemia. (See "Treatment and prevention of hyperkalemia in adults".) Patients who develop hyperuricemia should be treated with allopurinol. Allopurinol should be given orally at 300 mg if uric acid levels are >8 mg/dL (476 micromol/L) or if there is a 25 percent increase from baseline. Allopurinol is not indicated in the treatment of hemolysis in the absence of hyperuricemia. We do not give rasburicase (recombinant xanthine oxidase) to hyperuricemic patients with rhabdomyolysis or hemolysis, as it has not been sufficiently studied in these circumstances. However, rasburicase is effective to rapidly lower serum uric acid concentrations in tumor lysis syndrome and was effective in two children with hyperuricemia and AKI from rhabdomyolysis [20]. Treatment of established AKI — Other than maintenance of fluid and electrolyte balance and tissue perfusion, there is no specific therapy once the patient has developed AKI. The initiation of dialysis may be necessary for control of volume overload, hyperkalemia, severe acidemia, and uremia. A detailed discussion of the indications for dialysis is presented elsewhere. (See "Renal replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".) Peritoneal dialysis may not be sufficient to achieve adequate metabolic control in patients with severe rhabdomyolysis, which may necessitate frequent hemodialysis or the use of high-dose continuous renal replacement therapy (RRT) [2,19].

PROGNOSIS The overall prognosis for patients with heme-induced AKI is favorable as most survivors recover sufficient kidney function to be dialysis independent, and many will recover to normal or near-normal kidney function [21].

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)

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INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) ●

Basics topic (see "Patient education: Rhabdomyolysis (The Basics)")

SUMMARY AND RECOMMENDATIONS ●

Patients with rhabdomyolysis are at risk for heme-induced acute kidney injury (AKI). Early and aggressive fluid resuscitation is the major preventive therapy. We recommend that all patients with rhabdomyolysis who have plasma creatine kinase (CK) values >5000 unit/L and those who have CK values that are increasing regardless of baseline value be administered intravenous fluid (Grade 1B). (See 'Volume administration' above.)

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The optimal fluid for the prevention of heme-induced AKI is not known. For patients with rhabdomyolysis who are to receive intravenous fluid, we suggest initial volume repletion with isotonic saline rather than other fluids (Grade 2C). (See 'Volume administration' above.)

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The optimal rate of repletion for the prevention of heme-induced AKI is not known. For patients with rhabdomyolysis who are to receive intravenous fluid, we suggest initial volume repletion at a rate of 1 to 2 L/hour rather than lower or higher rates (Grade 2C). The rate is adjusted to maintain the desired diuresis of approximately 200 to 300 mL/hour. (See 'Volume administration' above.)

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Heme-induced AKI from hemolysis may also be prevented by volume repletion. The volume requirements for patients with hemolysis are generally less than the volume requirements of patients with rhabdomyolysis. For patients at risk for heme-induced AKI from hemolysis, we suggest initial volume repletion with isotonic saline at a rate of 100 to 200 mL/hour rather than lower or higher rates (Grade 2C). (See 'Volume administration' above.)

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Prevention and treatment of heme pigment-induced acute kidney injury - UpToDate

Limited data suggest that alkalinization of urine may benefit patients with severe rhabdomyolysis. The administration of bicarbonate may cause severe alkalosis among anuric patients. For patients with rhabdomyolysis in whom a diuresis is established with volume repletion, we suggest the administration of an alkaline solution rather than isotonic saline, providing the patient is not hypocalcemic and has an arterial pH less than 7.5 and a serum bicarbonate less than 30 mEq/L (Grade 2C). (See 'Bicarbonate' above and "Crush-related acute kidney injury", section on 'Use of bicarbonate'.) The alkaline solution should be discontinued if the urine pH does not rise above 6.5 after three to four hours of the alkaline solution, if the arterial pH increases to 7.5, if the serum bicarbonate exceeds 30 mEq/L, or if symptomatic hypocalcemia develops. If the bicarbonate solution is discontinued, volume repletion should be continued with isotonic saline. (See 'Bicarbonate' above.)

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Loop diuretics have not been shown to be effective in preventing heme pigment-induced AKI but may be given to patients who develop volume overload as a result of aggressive volume administration. (See 'Mannitol' above.)

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Plasma potassium and calcium should be monitored several times daily until stable. Hyperkalemia should be treated as discussed elsewhere. (See "Treatment and prevention of hyperkalemia in adults".)

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Calcium supplementation should be given only for symptomatic hypocalcemia or severe hyperkalemia. (See "Treatment of hypocalcemia" and "Treatment and prevention of hyperkalemia in adults".)

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Dialysis may be necessary for control of hyperkalemia and correction of acidosis or for the treatment of volume overload. (See 'Treatment of established AKI' above.)

ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Joseph A Eustace, MB, MHS, MRCPI, who contributed to an earlier version of this topic review. We are saddened by the death of Sinead Kinsella, MD, MBS, MRCPI, who passed away in July 2016. UpToDate wishes to acknowledge Dr. Kinsella's past work as an author for this topic.

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