Clinical features and diagnosis of heme pigment-induced acute kidney injury
- Mark A Perazella, MD, FACP
Mark A Perazella, MD, FACP
- Professor of Medicine
- Yale University School of Medicine
- Mitchell H Rosner, MD
Mitchell H Rosner, MD
- Professor of Medicine
- University of Virginia Health System
Acute kidney injury (AKI) can occur in patients who have rhabdomyolysis and, less commonly, in patients with hemolysis [1,2]. In both groups, AKI is caused by the nonprotein heme pigment that is released from either myoglobin or hemoglobin and is toxic to the kidney. Hypovolemia may contribute in patients with rhabdomyolysis due to crush injury.
The clinical features and diagnosis of heme pigment-induced AKI due to nontraumatic rhabdomyolysis and to hemolysis will be reviewed here. Prevention and treatment of heme pigment-induced AKI, AKI due to crush injury, and overviews of rhabdomyolysis and hemolysis are discussed separately. (See "Prevention and treatment of heme pigment-induced acute kidney injury" and "Crush-related acute kidney injury (acute renal failure)" and "Clinical manifestations and diagnosis of rhabdomyolysis" and "Diagnosis of hemolytic anemia in the adult".)
Heme pigment-containing proteins include myoglobin and hemoglobin. Myoglobin is released from muscle in patients with traumatic or nontraumatic rhabdomyolysis, whereas hemoglobin is released from hemolyzed red blood cells. Both myoglobin and hemoglobin are filtered by the glomerulus into the urinary space where they are degraded, thus releasing heme pigment.
Heme pigment may injure the kidney in three ways:
●Tubular obstruction, possibly in association with uric acid [1,3]
- Zager RA. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Int 1996; 49:314.
- Better OS, Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N Engl J Med 1990; 322:825.
- Heyman SN, Rosen S, Fuchs S, et al. Myoglobinuric acute renal failure in the rat: a role for medullary hypoperfusion, hypoxia, and tubular obstruction. J Am Soc Nephrol 1996; 7:1066.
- Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol 2000; 8:72.
- Zager RA, Burkhart KM, Conrad DS, Gmur DJ. Iron, heme oxygenase, and glutathione: effects on myohemoglobinuric proximal tubular injury. Kidney Int 1995; 48:1624.
- Olerud JE, Homer LD, Carroll HW. Incidence of acute exertional rhabdomyolysis. Serum myoglobin and enzyme levels as indicators of muscle injury. Arch Intern Med 1976; 136:692.
- Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore) 2005; 84:377.
- McMahon GM, Zeng X, Waikar SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med 2013; 173:1821.
- Wilhelm-Leen ER, Winkelmayer WC. Predicting the outcomes of rhabdomyolysis: a good starting point. JAMA Intern Med 2013; 173:1828.
- Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990; 30:583.
- Mishra SK, Das BS. Malaria and acute kidney injury. Semin Nephrol 2008; 28:395.
- Lau HK, Li CH, Lee AC. Acute massive haemolysis in children with glucose-6-phosphate dehydrogenase deficiency. Hong Kong Med J 2006; 12:149.
- Jha V, Chugh KS. Community-acquired acute kidney injury in Asia. Semin Nephrol 2008; 28:330.
- Anuradha S, Arora S, Mehrotra S, et al. Acute renal failure following para-phenylenediamine (PPD) poisoning: a case report and review. Ren Fail 2004; 26:329.
- Kanjanabuch T, Sitprija V. Snakebite nephrotoxicity in Asia. Semin Nephrol 2008; 28:363.
- Zhang L, Yang Y, Tang Y, et al. Recovery from AKI following multiple wasp stings: a case series. Clin J Am Soc Nephrol 2013; 8:1850.
- Viraraghavan R, Chakravarty AG, Soreth J. Cefotetan-induced haemolytic anaemia. A review of 85 cases. Adverse Drug React Toxicol Rev 2002; 21:101.
- Kapur G, Valentini RP, Mattoo TK, et al. Ceftriaxone induced hemolysis complicated by acute renal failure. Pediatr Blood Cancer 2008; 50:139.
- Nair RK, Khaira A, Sharma A, et al. Spectrum of renal involvement in paroxysmal nocturnal hemoglobinuria: report of three cases and a brief review of the literature. Int Urol Nephrol 2008; 40:471.
- Kirkizlar O, Kendir M, Karaali Z, et al. Acute renal failure in a patient with severe hemolysis. Int Urol Nephrol 2007; 39:651.
- Brem AS. Insights Into Glucocorticoid-Associated Hypertension. Am J Kidney Dis 2001; 37:1.
- Mate-Kole MO, Yeboah ED, Affram RK, Adu D. Blackwater fever and acute renal failure in expatriates in Africa. Ren Fail 1996; 18:525.
- Pinho FM, Yu L, Burdmann EA. Snakebite-induced acute kidney injury in Latin America. Semin Nephrol 2008; 28:354.
- Abdulkader RC, Barbaro KC, Barros EJ, Burdmann EA. Nephrotoxicity of insect and spider venoms in Latin America. Semin Nephrol 2008; 28:373.
- Prakash J, Gupta A, Kumar O, et al. Acute renal failure in falciparum malaria--increasing prevalence in some areas of India--a need for awareness. Nephrol Dial Transplant 1996; 11:2414.
- Vermeulen Windsant IC, Snoeijs MG, Hanssen SJ, et al. Hemolysis is associated with acute kidney injury during major aortic surgery. Kidney Int 2010; 77:913.
- Schechter MA, Daneshmand MA, Patel CB, et al. Outcomes after implantable left ventricular assist device replacement procedures. ASAIO J 2014; 60:44.
- Ravichandran AK, Parker J, Novak E, et al. Hemolysis in left ventricular assist device: a retrospective analysis of outcomes. J Heart Lung Transplant 2014; 33:44.
- Sauret JM, Marinides G, Wang GK. Rhabdomyolysis. Am Fam Physician 2002; 65:907.
- Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore) 1982; 61:141.
- Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med 1988; 148:1553.
- Sharp LS, Rozycki GS, Feliciano DV. Rhabdomyolysis and secondary renal failure in critically ill surgical patients. Am J Surg 2004; 188:801.
- Knapik JJ. Extreme Conditioning Programs: Potential Benefits and Potential Risks. J Spec Oper Med 2015; 15:108.
- Centers for Disease Control and Prevention (CDC). Hemolysis associated with 25% human albumin diluted with sterile water--United States, 1994-1998. MMWR Morb Mortal Wkly Rep 1999; 48:157.
- Fabris, A, Pellanda, et al. Rhabdomyolysis. In: Critical Care Nephrology, Ronco, C, Bellomo, R (Eds), Kluwer Academic Publishers, Amsterdam 1998. p.739.
- Grossman RA, Hamilton RW, Morse BM, et al. Nontraumatic rhabdomyolysis and acute renal failure. N Engl J Med 1974; 291:807.
- Marchand A, Galen RS, Van Lente F. The predictive value of serum haptoglobin in hemolytic disease. JAMA 1980; 243:1909.
- Grover DS, Atta MG, Eustace JA, et al. Lack of clinical utility of urine myoglobin detection by microconcentrator ultrafiltration in the diagnosis of rhabdomyolysis. Nephrol Dial Transplant 2004; 19:2634.
- Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care 2005; 9:158.
- Tesser Poloni JA, Perazella MA. A rarely recognized cause of acute kidney injury in rhabdomyolysis. Am J Med Sci 2017; In press.
- Corwin HL, Schreiber MJ, Fang LS. Low fractional excretion of sodium. Occurrence with hemoglobinuric- and myoglobinuric-induced acute renal failure. Arch Intern Med 1984; 144:981.
- Poels PJ, Gabreëls FJ. Rhabdomyolysis: a review of the literature. Clin Neurol Neurosurg 1993; 95:175.
- Mikkelsen TS, Toft P. Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis. Acta Anaesthesiol Scand 2005; 49:859.
- de Meijer AR, Fikkers BG, de Keijzer MH, et al. Serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey. Intensive Care Med 2003; 29:1121.
- Hatamizadeh P, Najafi I, Vanholder R, et al. Epidemiologic aspects of the Bam earthquake in Iran: the nephrologic perspective. Am J Kidney Dis 2006; 47:428.
- Veenstra J, Smit WM, Krediet RT, Arisz L. Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis. Nephrol Dial Transplant 1994; 9:637.
- Li SF, Zapata J, Tillem E. The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis. Am J Emerg Med 2005; 23:860.
- Saenz AJ, Lee-Lewandrowski E, Wood MJ, et al. Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston marathon. Am J Clin Pathol 2006; 126:185.
- Lappalainen H, Tiula E, Uotila L, Mänttäri M. Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for follow-up. Crit Care Med 2002; 30:2212.
- Lordon RE, Burton JR. Post-traumatic renal failure in military personnel in Southeast Asia. Experience at Clark USAF hospital, Republic of the Philippines. Am J Med 1972; 53:137.
- STRAUSS MB. Acute renal insufficiency due to lower-nephron nephrosis. N Engl J Med 1948; 239:693.
- Llach F, Felsenfeld AJ, Haussler MR. The pathophysiology of altered calcium metabolism in rhabdomyolysis-induced acute renal failure. Interactions of parathyroid hormone, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol. N Engl J Med 1981; 305:117.
- Akmal M, Bishop JE, Telfer N, et al. Hypocalcemia and hypercalcemia in patients with rhabdomyolysis with and without acute renal failure. J Clin Endocrinol Metab 1986; 63:137.
- Lane JT, Boudreau RJ, Kinlaw WB. Disappearance of muscular calcium deposits during resolution of prolonged rhabdomyolysis-induced hypercalcemia. Am J Med 1990; 89:523.
- Chao YW, Yang AH, Ng YY, Yang WC. Acute interstitial nephritis and pigmented tubulopathy in a patient after wasp stings. Am J Kidney Dis 2004; 43:e15.
- Knochel JP. Hypophosphatemia and rhabdomyolysis. Am J Med 1992; 92:455.
- Lee S, Kim W, Park SK, et al. A case of acute renal failure, rhabdomyolysis and disseminated intravascular coagulation associated with severe exercise-induced hypernatremic dehydration. Clin Nephrol 2004; 62:401.
- Bagley WH, Yang H, Shah KH. Rhabdomyolysis. Intern Emerg Med 2007; 2:210.
- Gunst JJ, Langlois MR, Delanghe JR, et al. Serum creatine kinase activity is not a reliable marker for muscle damage in conditions associated with low extracellular glutathione concentration. Clin Chem 1998; 44:939.
- Causes of rhabdomyolysis
- - Risk prediction score for severe acute kidney injury or death
- Causes of hemolysis
- CLINICAL MANIFESTATIONS
- Other laboratory findings
- - Creatine kinase
- - Potassium
- - Calcium
- - Phosphate
- - Transaminases
- - Other
- SOCIETY GUIDELINE LINKS