The Case | Acute kidney injury and hemolysis in a 58-year-old woman.

A 58-year-old woman was transferred from a primary care hospital to our tertiary referral hospital because of acute kidney injury (AKI). Her past medical history was unremarkable, except for recurring episodes of herpes zoster. She had not been on any medications before admission. The patient was admitted to the primary care hospital because of severe gastroenteritis 1 week before the transfer. During hospitalization, the patient developed AKI. The physical examination was unremarkable, except for bilateral costovertebral tenderness. At the time of transfer, the patient presented with oliguria, a plasma creatinine of 8.84 mg/dl, plasma urea of 180 mg/dl, and a mild normocytic, normochromic anemia with a hemoglobin of 9.9 g/dl, mild thrombocytopenia of 128 G/L, normal leukocytes, and markedly elevated lactate dehydrogenase of 1626 IU/L. There were no schistocytes on a peripheral blood smear; however, haptoglobin was not detectable. A Coombs test was not available. There was proteinuria with an albumin-to-creatinine ratio of 4 g/g, and the urinary sediment showed evidence of tubular damage but was not nephritic. Testing for antinuclear antibody, antineutrophil cytoplasmic antibody, antiglomerular basement membrane antibody was negative, and complement levels were within normal limits. A renal ultrasound showed bilaterally normal kidney size without evidence of urinary outflow obstruction or arterial or venous thrombosis. During the week after transfer the patient developed anuria, and hemodialysis was initiated. A kidney biopsy was performed (Figure 1). What is the clinical diagnosis? The kidney biopsy showed unremarkable glomeruli (Figure 1a); however, there was extensive tubular damage with pronounced dilatation of the tubular lumina, with widespread damage of the tubular epithelium and focally denuded tubular basement membranes. There were also detached intraluminal tubular cells (Figure 1b). The striking finding was brownish intracellular pigment deposits in a large proportion of the tubular cross sections (Figure 1b), which very likely represented tubular hemosiderin deposits. In Perls’ Prussian blue–stained sections, these pigments clearly stained positive, indicating the presence of iron and strongly suggesting acute tubular necrosis due to recurring episodes of hemoglobinuria/hemolysis (Figure 1c, d). Therefore, flow cytometry for CD55 and CD59 confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). When asked, the patient recalled at least one episode of brownish urine during the last few years. PNH is caused by an acquired loss of functional phosphatidylinositol glycan anchors in hematopoietic stem cells due to X-linked somatic mutations, which results in increased susceptibility to complement-mediated cytolysis.1Rosse W.F. Paroxysmal nocturnal hemoglobinuria as a molecular disease.Medicine (Baltimore). 1997; 76: 63-93Crossref PubMed Scopus (142) Google Scholar Clinically, PNH presents with intravascular hemolysis, gross hemoglobinuria, and thrombosis, and may result in bone marrow failure and pancytopenia. Despite gross hemoglobinuria, PNH frequently lacks clinically evident kidney involvement. AKI in PNH patients has been reported, whereas CKD is relatively uncommon.2Ballarín J. Arce Y. Torra Balcells R. et al.Acute renal failure associated to paroxysmal nocturnal haemoglobinuria leads to intratubular haemosiderin accumulation and CD163 expression.Nephrol Dial Transplant. 2011; 26: 3408-3411Crossref PubMed Scopus (48) Google Scholar Nevertheless, AKI stage 3 as in our case is very rare. Hemolysis and intravascular volume depletion, for example due to gastroenteritis, as was the case in our patient, seems to be a common trigger of AKI in PNH patients. This is thought to result from increased intratubular hemoglobin concentration and slower tubular flow rates and is conservatively treated with volume repletion and urine alkalization.3Chow K.M. Lai F.M. Wang A.Y. et al.Reversible renal failure in paroxysmal nocturnal hemoglobinuria.Am J Kidney Dis. 2001; 37: E17Abstract Full Text PDF PubMed Google Scholar Since the introduction of eculizumab, a monoclonal anti-C5 antibody, targeted treatment has become available, which has been shown to reduce hemolysis and thrombotic events, and has been tolerated well in patients with renal impairment.2Ballarín J. Arce Y. Torra Balcells R. et al.Acute renal failure associated to paroxysmal nocturnal haemoglobinuria leads to intratubular haemosiderin accumulation and CD163 expression.Nephrol Dial Transplant. 2011; 26: 3408-3411Crossref PubMed Scopus (48) Google Scholar In our case, diuresis returned spontaneously; dialysis treatment was discontinued; and finally renal function recovered to normal levels. The patient was transferred to hematology for further treatment.