Intravascular Hemolysis and Acute Renal Failure After Mitral and Aortic Valve Repair

Abstract

Intravascular hemolysis is a rare, but well known, complication of prosthetic cardiac valve replacement or repair.1Yeo T.C. Freeman W.K. Schaff H.V. Orszulak T.A. Mechanisms of hemolysis after mitral valve repair: Assessment by serial echocardiography.J Am Coll Cardiol. 1998; 32: 717-723Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 2Sayed H.M. Dacie J.V. Handley D.A. Lewis S.M. Cleland W.P. Haemolytic anaemia of mechanical origin after open heart surgery.Thorax. 1961; 16: 356-360Crossref PubMed Scopus (56) Google Scholar, 3Garcia M.J. Vandervoort P. Stewart W.J. et al.Mechanisms of hemolysis with mitral prosthetic regurgitation Study using transesophageal echocardiography and fluid dynamic simulation.J Am Coll Cardiol. 1996; 27: 399-406Abstract Full Text PDF PubMed Scopus (100) Google Scholar The development of acute renal failure from conditions that lead to severe intravascular hemolysis and hemoglobinuria is also well known and best described in patients with paroxysmal nocturnal hemoglobinuria.4Clark D.A. Butler S.A. Braren V. Hartmann R.C. Jenkins Jr, D.E. The kidneys in paroxysmal nocturnal hemoglobinuria.Blood. 1981; 57: 83-89PubMed Google Scholar, 5Rubin H. Paroxysmal nocturnal hemoglobinuria with renal failure.JAMA. 1971; 215: 433-436Crossref PubMed Scopus (35) Google Scholar, 6Chow K.M. Lai F.M. Wang A.Y. Chan Y.L. Tang N.L. Li P.K. Reversible renal failure in paroxysmal nocturnal hemoglobinuria.Am J Kidney Dis. 2001; 37: E17Abstract Full Text PDF PubMed Google Scholar, 7Hothi D.K. Bass P. Morgan M. Acharya J. Humphries S.E. Gilbert R.D. Acute renal failure in a patient with paroxysmal cold hemoglobinuria.Pediatr Nephrol. 2007; 22: 593-596Crossref PubMed Scopus (12) Google Scholar, 8Jose M.D. Lynn K.L. Acute renal failure in a patient with paroxysmal nocturnal hemoglobinuria.Clin Nephrol. 2001; 56: 172-174PubMed Google Scholar, 9Khajehdehi P. Reversible acute renal failure with prolonged oliguria and gross hematuria in a case of paroxysmal nocturnal hemoglobinuria.Scand J Urol Nephrol. 2000; 34: 284-286Crossref PubMed Scopus (8) Google Scholar, 10Kirkizlar O. Kendir M. Karaali Z. et al.Acute renal failure in a patient with severe hemolysis.Int Urol Nephrol. 2007; 39: 651-654Crossref PubMed Scopus (7) Google Scholar, 11Kondo H. Uga S. Kaihara A. Kawada M. Yamano T. Acute renal failure in a case of paroxysmal nocturnal hemoglobinuria—A review of literature in Japan.Nippon Jinzo Gakkai Shi. 1990; 32: 835-840PubMed Google Scholar, 12Kumpers P. Herrmann A. Lotz J. Mengel M. Schwarz A. A blue kidney—Chronic renal failure as a consequence of siderosis in paroxysmal nocturnal hemoglobinuria?.Clin Nephrol. 2006; 66: 210-213PubMed Google Scholar, 13Rother R.P. Bell L. Hillmen P. Gladwin M.T. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease.JAMA. 2005; 293: 1653-1662Crossref PubMed Scopus (1151) Google Scholar However, acute renal failure as a consequence of intravascular hemolysis after the placement of prosthetic cardiac valves has been reported only rarely.14Ackermann D. Vogt B. Gugger M. Marti H.P. Renal haemosiderosis: An unusual presentation of acute renal failure in a patient following heart valve prosthesis.Nephrol Dial Transplant. 2004; 19: 2682-2683Crossref PubMed Scopus (13) Google Scholar, 15Shingu Y. Aoki H. Ebuoka N. et al.A surgical case for severe hemolytic anemia after mitral valve repair.Ann Thorac Cardiovasc Surg. 2005; 11: 198-200PubMed Google Scholar The renal lesion most often shown with chronic hemolysis is acute tubular necrosis with widespread tubular hemosiderosis. It is unclear whether hemosiderosis is the direct cause of renal tubular damage or instead predisposes to tubular injury.6Chow K.M. Lai F.M. Wang A.Y. Chan Y.L. Tang N.L. Li P.K. Reversible renal failure in paroxysmal nocturnal hemoglobinuria.Am J Kidney Dis. 2001; 37: E17Abstract Full Text PDF PubMed Google Scholar, 16Pardo-Mindan F.J. Diez J. Esparza N. Robledo C. Renal siderosis in patients with heart-valve prostheses: Clinical implications.Nephrol Dial Transplant. 1990; 5: 847-850Crossref PubMed Scopus (26) Google Scholar The pathogenesis of hemoglobinuria-associated acute tubular necrosis may involve complex mechanisms of tubular injury, and hemosiderosis could be only a marker of this injury process. We report the case of a man who developed severe intravascular hemolysis and acute renal failure shortly after mitral valve repair and aortic valve replacement. On the renal biopsy specimen, widespread acute tubular necrosis and marked hemosiderosis were shown. A 43-year-old Hispanic man who presented in December 2006 with a 1-month history of dyspnea on exertion was given a diagnosis of aortic stenosis and mitral regurgitation resulting in pulmonary hypertension and right-sided heart failure. Baseline serum creatinine level was 0.9 mg/dL (79.5 μmol/L), and hemoglobin level was 12.5 g/dL (125 g/L). He underwent aortic valve replacement with a St Jude Biocor bioprosthetic valve and mitral valve repair with a St Jude ring (St Jude Medical, Inc, St Paul, MN). At the time of discharge 10 days later, serum creatinine level was 1.1 mg/dL (97.2 μmol/L). Two weeks after the patient's surgery, he presented with “dark urine” and had a hemoglobin level of 6.8 g/dL (68 g/L) with moderate schistocytes on peripheral smear. Platelet count was normal at 202,000/μL, but lactate dehydrogenase level was 3,000 U/L and serum haptoglobin was undetectable. A workup for hemolytic anemia showed normal coagulation study results, glucose-6-phosphate dehydrogenase (G6PD) level, and expression of CD55 and CD59 (to assess for paroxysmal nocturnal hemoglobinuria). Coombs' test and evaluation for cryoglobulins showed negative results. Creatinine levels during this time ranged from 1.1 mg/dL (97.2 μmol/L) to 1.7 mg/dL (150.3 μmol/L). On reevaluation in March 2007, it was believed that the intravascular hemolysis was caused by the mitral or aortic valve prosthesis. Blood pressure was 156/100 mm Hg, and examination noted scleral icterus and a III/VI systolic murmur heard best over the apex on cardiac examination. He had no skin lesions or purpura, and the remainder of examination findings was normal. Laboratory evaluation showed a hemoglobin level of 7.8 g/dL (78 g/L) with schistocytes and tear cells, platelet count of 185,000/μL, lactate dehydrogenase level of 2,252 U/L, total bilirubin level of 5.8 mg/dL (99.2 μmol/L), and undetectable haptoglobin. Reticulocyte count was 15%. A transthoracic echocardiogram showed a normal-appearing bioprosthetic aortic valve with an increased valve gradient of 38 mm Hg. The mitral valve ring prosthesis had a normal transmitral gradient, but there was moderate mitral regurgitation. The patient's serum creatinine level was 1.8 mg/dL (159.1 μmol/L), blood urea nitrogen level was 40 mg/dL (14.3 mmol/L), and serum albumin level was 3.6 g/dL (36 g/L). Urinalysis showed specific gravity of 1.020, brown urine, pH of 5.5, 3+ protein, large blood, 18 red blood cells/high-power field, and 15 granular casts/high-power field. Protein-creatinine ratio was 0.8 g/g. Serological tests showed C3 level of 85 mg/dL (0.85 g/L; normal, 88 to 203 mg/dL [0.88 to 2.03 g/L]) and C4 level of 12 mg/dL (0.12 g/L; normal, 13 to 49 mg/dL [0.13 to 0.49 g/L) with normal or negative antinuclear antibody, anti–double-stranded DNA antibody, antineutrophil cytoplasmic antibody, hepatitis B surface antigen, and hepatitis C antibody. A renal ultrasound showed an atrophic right kidney and normal 12.5-cm left kidney with no hydronephrosis. The patient had greater than 2 L/d of urine output, but serum creatinine level peaked at 2.6 mg/dL (229.8 μmol/L) during 10 days. To further assess the cause of the acute renal failure associated with proteinuria, intravascular hemolysis, and hypocomplementemia in a patient with a solitary kidney, an open renal biopsy was performed. There were 58 glomeruli in histological sections, and 4 were ischemic or hyalinized. Glomeruli appeared normal (Fig 1) without capillary thrombi. There was widespread acute tubular injury with epithelial thinning, sloughing of cellular debris into the tubular lumens, loss of tubular brush border (Fig 2), and numerous tubular mitotic figures. Hemosiderin granules were seen in most tubular epithelial cells and lumens, highlighted by the Prussian blue stain (Fig 3). Similar hemosiderin-laden epithelial cells were seen in urine sediment (Fig 4). Arterioles and arteries were normal and did not contain thrombi. Interstitial fibrosis and tubular atrophy were present in 10% of the cortex. Immunofluorescence and electron microscopy studies of glomeruli were unremarkable.Figure 2Proximal tubules show widespread evidence of acute tubular necrosis, including thinning of the epithelium, loss of brush border, sloughing of cellular debris into the lumen, and mitotic figures. Note the granules of hemosiderin diffusely present in the tubular cytoplasm (periodic acid–Schiff stain; original magnification ×330).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Hemosiderin-laden tubular epithelium stained with Prussian blue stain (original magnification ×330).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Urine cytological examination shows degenerating tubular epithelial cells containing copious granules of hemosiderin (Papanicolaou stain; original magnification ×330).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Hemosiderosis and widespread acute tubular necrosis with regeneration. After the biopsy, the patient was aggressively hydrated with normal saline, and serum creatinine levels slowly improved to 1.5 mg/dL (132.6 μmol/L). Cardiovascular surgery was consulted for possible valve repair, but it was decided not to pursue this because of the surgical risk in the setting of severe pulmonary hypertension. It was instead decided to place the patient on flecainide therapy for its negative inotropic effect to improve cardiac hydrodynamics. This led to a decrease in aortic valve gradient to 16 mm Hg, but moderate mitral regurgitation persisted. Seven months after the renal biopsy, with continued evidence of hemolysis, his hemoglobin level is stable at 11 g/dL (110 g/L) with 3% reticulocytes, serum creatinine level is 1.8 mg/dL (159.1 μmol/L; estimated glomerular filtration rate is 44 mL/min [0.73 mL/s]), and urinalysis shows trace protein with 3+ blood and 0 to 3 red blood cells/high-power field. We report a patient with massive hemolysis and acute renal failure caused by acute tubular injury after combined prosthetic valvular repair and replacement. Intravascular hemolysis associated with cardiac valve disease was described first in 1961 by Sayed et al,2Sayed H.M. Dacie J.V. Handley D.A. Lewis S.M. Cleland W.P. Haemolytic anaemia of mechanical origin after open heart surgery.Thorax. 1961; 16: 356-360Crossref PubMed Scopus (56) Google Scholar who reported a patient with hemolysis caused by an ostium primum atrial septal defect and unrepaired mitral cleft. Since then, intravascular hemolysis has become a well-known complication of valve replacement or repair,16Pardo-Mindan F.J. Diez J. Esparza N. Robledo C. Renal siderosis in patients with heart-valve prostheses: Clinical implications.Nephrol Dial Transplant. 1990; 5: 847-850Crossref PubMed Scopus (26) Google Scholar, 17Duong T. Khurana R.N. Francoz R.A. Severe intravascular hemolysis following mitral valve repair.J Invasive Cardiol. 2004; 16: 146-148PubMed Google Scholar, 18Lam B.K. Cosgrove D.M. Bhudia S.K. Gillinov A.M. Hemolysis after mitral valve repair: Mechanisms and treatment.Ann Thorac Surg. 2004; 77: 191-195Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 19Mecozzi G. Milano A.D. De C.M. et al.Intravascular hemolysis in patients with new-generation prosthetic heart valves: A prospective study.J Thorac Cardiovasc Surg. 2002; 123: 550-556Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 20Reddy S.B. Pater J.L. Pym J. Armstrong P.W. Hemolytic anemia following insertion of Ionescu-Shiley mitral valve bioprosthesis.CMAJ. 1984; 131: 1469-1470PubMed Google Scholar, 21Santinga J.T. Batsakis J.T. Flora J.D. Kirsh M.M. Hemolysis in the aortic prosthetic valve.Chest. 1976; 69: 56-61Crossref PubMed Scopus (13) Google Scholar although usually mild and not clinically significant. In a prospective study by Mecozzi et al,19Mecozzi G. Milano A.D. De C.M. et al.Intravascular hemolysis in patients with new-generation prosthetic heart valves: A prospective study.J Thorac Cardiovasc Surg. 2002; 123: 550-556Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar severe hemolytic anemia was not observed in 278 patients with normally functioning prosthetic heart valves, whereas mild subclinical hemolysis was identified in 18% of patients overall. The risk of hemolysis was significantly greater in patients with a mechanical prosthesis (26% versus 5% for bioprosthesis), mitral valve replacement (36% versus 16% for aortic valve replacement), and double valve replacements (46% versus 16% for single valve replacement). The presence of severe hemolysis is uncommon and usually indicates malfunction of the prosthetic valve. The development of hemolysis after valvular replacement or repair has most often been associated with residual valvular regurgitation or the development of a perivalvular leak and often presents within 3 months of the surgical procedure.17Duong T. Khurana R.N. Francoz R.A. Severe intravascular hemolysis following mitral valve repair.J Invasive Cardiol. 2004; 16: 146-148PubMed Google Scholar, 18Lam B.K. Cosgrove D.M. Bhudia S.K. Gillinov A.M. Hemolysis after mitral valve repair: Mechanisms and treatment.Ann Thorac Surg. 2004; 77: 191-195Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Although the occurrence of hemolysis is independent of the severity of valvular regurgitation, the hydrodynamic nature of the regurgitant flow creates the high shear stress that results in fragmentation of red blood cells and hemolysis.1Yeo T.C. Freeman W.K. Schaff H.V. Orszulak T.A. Mechanisms of hemolysis after mitral valve repair: Assessment by serial echocardiography.J Am Coll Cardiol. 1998; 32: 717-723Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 3Garcia M.J. Vandervoort P. Stewart W.J. et al.Mechanisms of hemolysis with mitral prosthetic regurgitation Study using transesophageal echocardiography and fluid dynamic simulation.J Am Coll Cardiol. 1996; 27: 399-406Abstract Full Text PDF PubMed Scopus (100) Google Scholar, 18Lam B.K. Cosgrove D.M. Bhudia S.K. Gillinov A.M. Hemolysis after mitral valve repair: Mechanisms and treatment.Ann Thorac Surg. 2004; 77: 191-195Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Thus, the presentation of intravascular hemolysis 2 weeks after valvular replacement and repair in our patient most likely resulted from the high shear forces created by the combination of the high-pressure gradient across the prosthetic aortic valve and regurgitant mitral flow. The development of acute renal failure as a complication of massive intravascular hemolysis and hemoglobinuria occurs in a number of conditions, but is described best in patients with paroxysmal nocturnal hemoglobinuria.4Clark D.A. Butler S.A. Braren V. Hartmann R.C. Jenkins Jr, D.E. The kidneys in paroxysmal nocturnal hemoglobinuria.Blood. 1981; 57: 83-89PubMed Google Scholar, 5Rubin H. Paroxysmal nocturnal hemoglobinuria with renal failure.JAMA. 1971; 215: 433-436Crossref PubMed Scopus (35) Google Scholar, 6Chow K.M. Lai F.M. Wang A.Y. Chan Y.L. Tang N.L. Li P.K. Reversible renal failure in paroxysmal nocturnal hemoglobinuria.Am J Kidney Dis. 2001; 37: E17Abstract Full Text PDF PubMed Google Scholar, 7Hothi D.K. Bass P. Morgan M. Acharya J. Humphries S.E. Gilbert R.D. Acute renal failure in a patient with paroxysmal cold hemoglobinuria.Pediatr Nephrol. 2007; 22: 593-596Crossref PubMed Scopus (12) Google Scholar, 8Jose M.D. Lynn K.L. Acute renal failure in a patient with paroxysmal nocturnal hemoglobinuria.Clin Nephrol. 2001; 56: 172-174PubMed Google Scholar, 9Khajehdehi P. Reversible acute renal failure with prolonged oliguria and gross hematuria in a case of paroxysmal nocturnal hemoglobinuria.Scand J Urol Nephrol. 2000; 34: 284-286Crossref PubMed Scopus (8) Google Scholar, 10Kirkizlar O. Kendir M. Karaali Z. et al.Acute renal failure in a patient with severe hemolysis.Int Urol Nephrol. 2007; 39: 651-654Crossref PubMed Scopus (7) Google Scholar, 11Kondo H. Uga S. Kaihara A. Kawada M. Yamano T. Acute renal failure in a case of paroxysmal nocturnal hemoglobinuria—A review of literature in Japan.Nippon Jinzo Gakkai Shi. 1990; 32: 835-840PubMed Google Scholar, 12Kumpers P. Herrmann A. Lotz J. Mengel M. Schwarz A. A blue kidney—Chronic renal failure as a consequence of siderosis in paroxysmal nocturnal hemoglobinuria?.Clin Nephrol. 2006; 66: 210-213PubMed Google Scholar, 13Rother R.P. Bell L. Hillmen P. Gladwin M.T. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease.JAMA. 2005; 293: 1653-1662Crossref PubMed Scopus (1151) Google Scholar In all reported cases of paroxysmal nocturnal hemoglobinuria–associated acute renal failure, hemolysis was acute and severe, with renal biopsy showing acute tubular necrosis associated with marked hemosiderosis.6Chow K.M. Lai F.M. Wang A.Y. Chan Y.L. Tang N.L. Li P.K. Reversible renal failure in paroxysmal nocturnal hemoglobinuria.Am J Kidney Dis. 2001; 37: E17Abstract Full Text PDF PubMed Google Scholar, 8Jose M.D. Lynn K.L. Acute renal failure in a patient with paroxysmal nocturnal hemoglobinuria.Clin Nephrol. 2001; 56: 172-174PubMed Google Scholar, 10Kirkizlar O. Kendir M. Karaali Z. et al.Acute renal failure in a patient with severe hemolysis.Int Urol Nephrol. 2007; 39: 651-654Crossref PubMed Scopus (7) Google Scholar, 11Kondo H. Uga S. Kaihara A. Kawada M. Yamano T. Acute renal failure in a case of paroxysmal nocturnal hemoglobinuria—A review of literature in Japan.Nippon Jinzo Gakkai Shi. 1990; 32: 835-840PubMed Google Scholar Although intravascular hemolysis is common after placement of a prosthetic valve or valve repair, there have been only 2 reported cases of acute renal failure.14Ackermann D. Vogt B. Gugger M. Marti H.P. Renal haemosiderosis: An unusual presentation of acute renal failure in a patient following heart valve prosthesis.Nephrol Dial Transplant. 2004; 19: 2682-2683Crossref PubMed Scopus (13) Google Scholar, 15Shingu Y. Aoki H. Ebuoka N. et al.A surgical case for severe hemolytic anemia after mitral valve repair.Ann Thorac Cardiovasc Surg. 2005; 11: 198-200PubMed Google Scholar In both cases, hemolytic anemia was severe and developed shortly after surgery (within 2 weeks). In the first case, serum creatinine level increased to 3.6 mg/dL (318.2 μmol/L).15Shingu Y. Aoki H. Ebuoka N. et al.A surgical case for severe hemolytic anemia after mitral valve repair.Ann Thorac Cardiovasc Surg. 2005; 11: 198-200PubMed Google Scholar The second patient's creatine level increased to 8.2 mg/dL (724.9 μmol/L) before dialysis therapy was initiated.14Ackermann D. Vogt B. Gugger M. Marti H.P. Renal haemosiderosis: An unusual presentation of acute renal failure in a patient following heart valve prosthesis.Nephrol Dial Transplant. 2004; 19: 2682-2683Crossref PubMed Scopus (13) Google Scholar A renal biopsy performed in this patient showed acute tubular injury and widespread tubular hemosiderosis, similar to that seen in our patient.14Ackermann D. Vogt B. Gugger M. Marti H.P. Renal haemosiderosis: An unusual presentation of acute renal failure in a patient following heart valve prosthesis.Nephrol Dial Transplant. 2004; 19: 2682-2683Crossref PubMed Scopus (13) Google Scholar The pathophysiological process of hemolysis-associated acute tubular necrosis is multifaceted. With massive intravascular hemolysis, a large amount of free hemoglobin is released into the circulation. The free hemoglobin is rapidly bound by haptoglobin. Once haptoglobin has been saturated, excess free hemoglobin is filtered freely by the glomerulus and actively reabsorbed by proximal tubular cells. In the proximal tubules, hemoglobin is catabolized, resulting in the release of iron in the form of hemosiderin.13Rother R.P. Bell L. Hillmen P. Gladwin M.T. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease.JAMA. 2005; 293: 1653-1662Crossref PubMed Scopus (1151) Google Scholar Accumulation of hemosiderin may increase the susceptibility of the proximal tubule to injury through oxidative stress by free radical formation and lipid peroxidation.22Paller M.S. Hemoglobin- and myoglobin-induced acute renal failure in rats: Role of iron in nephrotoxicity.Am J Physiol. 1988; 255: F539-F544PubMed Google Scholar This can lead to membrane dysfunction and injury and ultimately results in proximal tubular cell death.23Sponsel H.T. Alfrey A.C. Hammond W.S. Durr J.A. Ray C. Anderson R.J. Effect of iron on renal tubular epithelial cells.Kidney Int. 1996; 50: 436-444Crossref PubMed Scopus (64) Google Scholar, 24Zhou X.J. Laszik Z. Wang X.Q. Silva F.G. Vaziri N.D. Association of renal injury with increased oxygen free radical activity and altered nitric oxide metabolism in chronic experimental hemosiderosis.Lab Invest. 2000; 80: 1905-1914Crossref PubMed Scopus (126) Google Scholar Consistent with this theory is the postmortem observation in 33 patients with prosthetic valves that episodes of acute renal failure were more frequent in patients with kidneys that had pronounced iron deposits.16Pardo-Mindan F.J. Diez J. Esparza N. Robledo C. Renal siderosis in patients with heart-valve prostheses: Clinical implications.Nephrol Dial Transplant. 1990; 5: 847-850Crossref PubMed Scopus (26) Google Scholar Additionally, free hemoglobin reacts with nitric oxide to form methemoglobin and nitrate. Depletion of nitric oxide leads to endothelial dysfunction, intrarenal vasoconstriction, ischemia, and direct cytotoxicity.24Zhou X.J. Laszik Z. Wang X.Q. Silva F.G. Vaziri N.D. Association of renal injury with increased oxygen free radical activity and altered nitric oxide metabolism in chronic experimental hemosiderosis.Lab Invest. 2000; 80: 1905-1914Crossref PubMed Scopus (126) Google Scholar Finally, in the presence of volume depletion, the increased urine concentration and acidic conditions in the distal tubule enhance the formation of intratubular methemoglobin casts. This results in intrarenal obstruction and also may promote increased uptake of toxic heme (and iron) by the proximal tubule, further worsening tubular damage.25Zager R.A. Gamelin L.M. Pathogenetic mechanisms in experimental hemoglobinuric acute renal failure.Am J Physiol. 1989; 256: F446-F455PubMed Google Scholar When hemolysis is self-limited or responsive to treatment, the acute tubular necrosis resolves and renal function normalizes.6Chow K.M. Lai F.M. Wang A.Y. Chan Y.L. Tang N.L. Li P.K. Reversible renal failure in paroxysmal nocturnal hemoglobinuria.Am J Kidney Dis. 2001; 37: E17Abstract Full Text PDF PubMed Google Scholar However, chronic or repeated episodes of severe hemolysis may lead to recurrent tubular injury and increased deposition of hemosiderin with such irreversible changes as tubular atrophy and interstitial fibrosis leading.4Clark D.A. Butler S.A. Braren V. Hartmann R.C. Jenkins Jr, D.E. The kidneys in paroxysmal nocturnal hemoglobinuria.Blood. 1981; 57: 83-89PubMed Google Scholar, 16Pardo-Mindan F.J. Diez J. Esparza N. Robledo C. Renal siderosis in patients with heart-valve prostheses: Clinical implications.Nephrol Dial Transplant. 1990; 5: 847-850Crossref PubMed Scopus (26) Google Scholar In a study of patients with long-standing paroxysmal nocturnal hemoglobinuria, 47% of patients (9 of 19 patients) had a creatinine clearance of 60 mL/min or less (≤1.00 mL/s).4Clark D.A. Butler S.A. Braren V. Hartmann R.C. Jenkins Jr, D.E. The kidneys in paroxysmal nocturnal hemoglobinuria.Blood. 1981; 57: 83-89PubMed Google Scholar Autopsy studies performed in 7 patients with chronic kidney disease showed moderate to heavy deposits of hemosiderin in the proximal tubules in all patients, and this was associated with marked tubulointerstitial fibrosis or cortical thinning in 6 patients. Thus, the goal is to treat the underlying cause of the hemolysis to minimize the potential for recurring damage and the potential for chronic injury. The primary treatment of patients with severe hemolysis associated with a malfunctioning prosthetic valve is repair or replacement of the prosthetic valve. Surgical revision successfully resolves the problem in essentially all patients.18Lam B.K. Cosgrove D.M. Bhudia S.K. Gillinov A.M. Hemolysis after mitral valve repair: Mechanisms and treatment.Ann Thorac Surg. 2004; 77: 191-195Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Pharmacological approaches with the use of antioxidants or agents directed at increasing red blood cell flexibility or decreasing hydrodynamic shear forces also have been tried. Use of the antioxidant N-acetylcysteine led to resolution of hemolysis and acute renal failure in a patient with hemolysis caused by a paravalvular leak of a prosthetic aortic valve.14Ackermann D. Vogt B. Gugger M. Marti H.P. Renal haemosiderosis: An unusual presentation of acute renal failure in a patient following heart valve prosthesis.Nephrol Dial Transplant. 2004; 19: 2682-2683Crossref PubMed Scopus (13) Google Scholar, 18Lam B.K. Cosgrove D.M. Bhudia S.K. Gillinov A.M. Hemolysis after mitral valve repair: Mechanisms and treatment.Ann Thorac Surg. 2004; 77: 191-195Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Pentoxifylline also has been effective in a small number of patients.26Geller S. Gelber R. Pentoxifylline treatment for microangiopathic hemolytic anemia caused by mechanical heart valves.Md Med J. 1999; 48: 173PubMed Google Scholar, 27Golbasi I. Turkay C. Timuragaoglu A. et al.The effect of pentoxifylline on haemolysis in patients with double cardiac prosthetic valves.Acta Cardiol. 2003; 58: 379-383Crossref PubMed Scopus (11) Google Scholar Finally, propranolol decreased the severity of hemolysis in 5 patients with severe hemolytic anemia from prosthetic aortic valves.28Santinga J.T. Flora J.D. Rush J.B. Penner J.A. Willis P.W. The effect of propranolol on hemolysis in patients with an aortic prosthetic valve.Am Heart J. 1977; 93: 197-201Abstract Full Text PDF PubMed Scopus (8) Google Scholar In our patient, use of aggressive hydration and flecainide, an agent directed at decreasing cardiac shear forces to minimize ongoing hemolysis, led to improvement and stabilization of hemoglobin levels and renal function. However, the failure of creatinine levels to normalize is explained best by the chronic irreversible damage from hemolysis, indicated by chronic changes noted on the renal biopsy specimen (ie, hemosiderosis, interstitial fibrosis, and tubular atrophy). In summary, we present a patient who developed severe hemolysis and acute renal failure shortly after placement of prosthetic cardiac valves. The cause of the hemolysis appeared to be from shear forces on red blood cells, most likely resulting from a combination of a high transvalvular pressure gradient and mitral regurgitation. On renal biopsy, acute tubular necrosis and extensive deposition of hemosiderin were found. Acute renal failure from hemolysis after placement of prosthetic cardiac valves is a rare, but serious, complication that should be recognized because chronic kidney disease may ensue. Support: None. Financial Disclosure: None.