Paroxysmal nocturnal hemoglobinuria manifesting as hemolytic anemia with acute kidney injury

Amol Bhawane; Manish Ramesh Balwani; Amit S Pasari; Priyanka R Tolani

doi:10.4103/jina.jina_12_18

CASE REPORT

Year : 2018 | Volume : 5 | Issue : 4 | Page : 140-142

Paroxysmal nocturnal hemoglobinuria manifesting as hemolytic anemia with acute kidney injury

Amol Bhawane¹, Manish Ramesh Balwani², Amit S Pasari², Priyanka R Tolani³
¹ Department of Medicine, Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
² Department of Nephrology, Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
³ Department of Medicine, Northern Railway Central Hospital, New Delhi, India

Date of Web Publication

27-May-2019

Correspondence Address:
Dr. Manish Ramesh Balwani
Department of Nephrology, Jawaharlal Nehru Medical College, Sawangi, Wardha - 440 003, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jina.jina_12_18

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized by low-grade, chronic hemolytic anemia accompanied by either thrombocytopenia or leukopenia with usually benign kidney involvement secondary to chronic tubular deposition of hemosiderin. Acute kidney injury (AKI) may be seen during hemolytic crisis. We report the case of a 45-year-old man with PNH who developed reversible AKI requiring temporary hemodialysis support following herpes zoster infection.

Keywords: Acute kidney injury thrombocytopenia, hemolytic anemia, paroxysmal nocturnal hemoglobinuria

How to cite this article:
Bhawane A, Balwani MR, Pasari AS, Tolani PR. Paroxysmal nocturnal hemoglobinuria manifesting as hemolytic anemia with acute kidney injury. J Integr Nephrol Androl 2018;5:140-2

How to cite this URL:
Bhawane A, Balwani MR, Pasari AS, Tolani PR. Paroxysmal nocturnal hemoglobinuria manifesting as hemolytic anemia with acute kidney injury. J Integr Nephrol Androl [serial online] 2018 [cited 2023 Oct 3];5:140-2. Available from: http://www.journal-ina.com/text.asp?2018/5/4/140/259159

Introduction

Acute kidney injury (AKI) due to hemolysis-induced tubular damage is a recognized complication of paroxysmal nocturnal hemoglobinuria (PNH). Acute tubular necrosis (ATN) and thus AKI due to PNH probably result from hemoglobin (Hb)-mediated toxicity on renal tubules due to hemolysis.^[1] Intravascular hemolysis in PNH can lead to two forms of renal disease: (1) a severe hemolytic episode of any cause with massive hemoglobinuria which can cause AKI probably from ATN and (2) chronic hemolysis resulting in iron deposition in the kidneys in almost all patients. Timely diagnosis and management of PNH will prevent progression of kidney disease and complications of PNH.^[2]

Case Report

A 45-year-old male was admitted to our center with history of fever, dyspnea on routine activities, and oliguria for 4 days with pedal edema for 3 days. He had developed reddish lesions over the right palm for the past 5 days with burning sensation in lesions. There was no history of abdominal pain, skin rashes, joint pains, loose stools, dysuria, burning urination, or recent intake of any medications. He gives a history of reddish urine on and off for 2 years. He gives a history of six units of packed red blood cell (RBC) transfusion for anemia in the past 2 years. Three months back, he was investigated for anemia. Bone marrow examination showed erythroid hyperplasia and direct Coombs test positivity. Three months back, his reports also showed anemia with indirect hyperbilirubinemia. He was provisionally diagnosed outside as probable autoimmune hemolytic anemia. Now on admission, he had pallor, edema feet, and high blood pressure with reddish elevated palpable zoster like lesions over the right palm. Rest of other systemic examinations were normal. Investigations revealed the following: Hb – 5.4 g/dL, total leukocyte count – 10,300/μL, platelet count – 113,000/μL, serum creatinine – 12.4 mg/dL, serum Na/K – 130/6.29 mEq/dL, serum total bilirubin – 2.17 mg/dL (indirect level; 1.29 mg/dL), and serum aspartate transaminase – 68 U/L, whereas alanine aminotransferase, alkaline phosphatase, and serum albumin were normal. Serum lactate dehydrogenase level was 3371 U/L. Sickle cell disease screening was negative. Peripheral smear showed predominantly normocytic normochromic anemia with few pencil cells. Urinalysis showed nil protein and no RBCs on microscopy. Chest X-ray and ultrasonography of abdomen were normal. Serum antinuclear antibody was negative and urine culture was sterile. The reticulocyte count was 2.6%. Hb electrophoresis and glucose-6-phosphate dehydrogenase levels were normal. Coombs test – both direct and indirect were negative. Hams test was negative. Urine for Hb came to be positive. Dermatologist opinion was taken for right palm lesions who confirmed it as herpes zoster and was started on valacyclovir.

Hence, a provisional diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was made and was investigated for PNH clone. He was till then managed symptomatically along with dialysis support. He required three sessions of hemodialysis in which three packed red cell transfusions were given. Provisional diagnosis of AKI due to hemolytic anemia was made. The patient was not willing for renal biopsy due to financial constraints. Presentation of AKI with hemolytic anemia in such a short span after fever led us to perform flow cytometric analysis of peripheral blood granulocytes which revealed the presence of a PNH clone. The diagnosis of PNH as a cause of hemolytic anemia was confirmed. He was further managed conservatively with steroids and antibiotics, and his kidney functions recovered to normal in the next 3 weeks.

Discussion

PNH is one of the causes of intravascular hemolysis. PNH is a disease characterized by a defect in the glycosylphosphatidylinositol (GPI) anchor due to an abnormality in the PIGA gene. This leads to partial or complete absence of certain GPI-linked proteins, particularly CD59 and CD55 (decay accelerating factor).^[2] The triad of hemolytic anemia, thrombosis, and pancytopenia defines PNH as a distinct syndrome. Intravascular hemolysis in PNH can lead to two forms of renal dysfunction: a severe hemolytic episode with massive hemoglobinuria which can cause AKI probably from acute tubular necrosis^[3] and chronic hemolysis which results in iron deposition in the kidneys in almost all patients. Chronic renal failure secondary to hemosiderosis and interstitial scarring may occur in patients with long-standing PNH.^[4]

Acute hemolytic episodes are often precipitated by nonspecific factors, such as infections, exercise, transfusion, reactions to drugs, immunizations, gastroenteritis, and surgery.^[4],[5] In our patient, recent episode of hemolysis was set probably due to herpes zoster infection. The role of hemosiderin accumulation in renal tubules as a result of hemolysis and hemoglobinuria in acute renal toxicity is controversial.^[6] The mechanisms of chronic kidney disease (CKD) in PNH are manifold. Incorporated iron has been proposed to exert a permanent local nephrotoxic effect on proximal tubular epithelial cells, resulting in tubular atrophy and interstitial fibrosis.^[7],[8] In addition, it has been proposed that the CKD could be due to repeated incidences of microinfarctions as a result of repeated episodes of microvascular thrombosis.^[4],[9] Flow cytometric analysis of peripheral blood cells (granulocytes or RBCs) using antibodies directed against GPI-anchored proteins is the most sensitive and informative assay for the diagnosis of PNH.^[10] Our patient presented with markedly deranged renal functions with very high creatinine level and features suggestive of intravascular hemolytic anemia. Two-year history of on and off reddish urine along with dipstick positivity for heme and negative urinary RBC microscopic detection leads us to suspect hemoglobinuria. We performed Hams test initially which came to be negative. However, as suspicion was high, flow cytometry was performed which confirmed the presence of PNH clones. The diagnosis was confirmed with the presence of PNH clone on flow cytometry. General goals for preventive therapy in heme pigment-induced AKI are correcting volume depletion and preventing intratubular cast formation. Early recognition of AKI and its immediate management with fluid resuscitation is important as persistent kidney injury predisposes to long-term consequences.^[11] The only potentially curative treatment for PNH is allogeneic hematopoietic cell transplantation. Treatment comprises transfusion therapy in the acute phase and correction of concomitant iron deficiency. Corticosteroids were started after confirmation of diagnosis of PNH. Corticosteroids may have a role in attenuating acute hemolytic exacerbations. For selected transfusion-dependent patients or patients with disabling symptoms (e.g., fatigue, thromboses, frequent paroxysms of pain, and end-organ damage), treatment with eculizumab is suggested.^[12] Our patient was discharged on iron supplement and folic acid and steroids. It is essential to diagnose PNH early in the course of disease as PNH may be lifelong and it may cause recurrent AKI.

Conclusion

Any history of reddish urine with evidence of hemolytic anemia and AKI should be evaluated for PNH. It requires a high index of suspicion to diagnose PNH early in its disease course. We may not get the classic triad of PNH described as hemolytic anemia, thrombocytopenia, and thrombosis. In our case, the patient was diagnosed with PNH after 2 years of onset of intermittent hematuria when the patient was referred for AKI secondary to hemolytic anemia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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