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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 1998  |  Volume : 9  |  Issue : 2  |  Page : 147-151
Paroxysmal Nocturnal Hemoglobinuria and Renal Failure


1 Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 King Faisal General Hospital, Taif, Saudi Arabia

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   Abstract 

In this report we present two cases of acute renal failure in paroxysmal nocturnal hemoglobinuria (PNH) patients, who both eventually recovered their renal function. We also highlight some of the possible pathophysiological changes, which may contribute to renal failure in patients with PNH.

Keywords: Hemoglobinuria, Nephrotoxic, Paroxysmal, Renal failure.

How to cite this article:
Al-Harbi A, Alfurayh O, Sobh M, Akhtar M, Tashkandy MA, Shaaban A. Paroxysmal Nocturnal Hemoglobinuria and Renal Failure. Saudi J Kidney Dis Transpl 1998;9:147-51

How to cite this URL:
Al-Harbi A, Alfurayh O, Sobh M, Akhtar M, Tashkandy MA, Shaaban A. Paroxysmal Nocturnal Hemoglobinuria and Renal Failure. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2019 Jun 17];9:147-51. Available from: http://www.sjkdt.org/text.asp?1998/9/2/147/39288

   Introduction Top


Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition in which an acquired defective clone of the hemopoietic stem cell is manifested by an increased sensitivity of the red blood cells (RBCs), granulocytes and platelets to complement lysis [1] . Two major clinical features characterize PNH, chronic intravascular hemolysis with episodes of hemoglobinuria and diffuse venous thrombosis.

The clinical course of these patients cannot be predicted and may vary from severe hemolysis and thrombosis to quiescence. Factors known to precipitate hemolysis include infection, drugs, immunization and exercise, but frequently the etiology remains unknown [2] . PNH is rare although not difficult to diagnose and a positive acid hemolysis test (Ham's test) is considered specific, while a positive sucrose lysis test is a sensitive diagnostic tool. Both of these tests are required to confirm diagnosis of PNH [1],[3] .

Venous thrombosis, intra-abdominally or in the central nervous system, is a common problem and is considered to be the leading cause of death in most patients [4] . Renal failure has been reported in PNH but is usually attributed to a concomitant renal disease or transfusion reactions. Both acute and chronic renal failure have been described but the mechanism remains unknown [2],[5],[6] .

The incidence and prevalence of PNH among the Saudi population is unknown. Here we describe two cases that presented with acute renal failure in two different renal units in the Kingdom. In the first case, the diagnosis of PNH was made at presentation and in the second case the diagnosis of aplastic anemia and PNH was made previously. Both patients recovered their renal function after supportive therapy with hemodialysis. We reviewed the English literature on PNH and renal diseases and present some speculations on the possible pathogenesis of acute and chronic renal disease in PNH patients.


   Case Histories Top


The first patient was a 33-year-old fireman who presented in 1987 with fever, vomiting, fatigue and dizziness and decreased urine output for two weeks. The urine appeared to be dark in color. Since 1982 the patient had been complaining of fatigue, frequent attacks of abdominal pain with occasional dark urine mainly in the morning. In 1985 a diagnosis of autoimmune hemolytic anemia was made and he was treated with prednisolone and azathioprine with no improvement.

At presentation he was puffy, pale, jaundiced, and had bilateral crepitations in the chest, bilateral flank pain and tenderness.

His WBC was 5.9 x 109/L with normal differential, RB C count 1.8 x 103/L, hemoglobin 52 g/L, platelet count 210 x 109 /L, reticulocyte count 15%, serum urea 52 mmol/L, and serum creatinine 1,880 umol/L. The alanine aminotransferase (ALT) was 60 IU/L, aspartate aminotransferase (AST) 55 IU/L, and total bilirubin 37 umol/L, mainly conjugated. His urine was positive for hemosiderin, but negative for myoglobulin.

A chest x-ray revealed evidence of fluid overload and consolidation in the left lower lobe. Ultrasound of the kidney revealed no evidence of obstruction although both kidneys were enlarged in size. There was no ascites. Other laboratory work-up included very low haptoglobin (0.5), Coomb's test was negative, and bone marrow aspiration and biopsy showed erythroid hyperplasia. Hemoglobin electrophoresis was normal.

PNH was suspected in the presence of anemia, hemolysis, negative Coomb's test and bone marrow findings with positive hemosiderin in the urine. Ham's test and sucrose lysis tests were positive, both confirming the diagnosis of PNH.

The patient was supported by hemodialysis and transfused with packed RBCs. The respiratory infection responded to erythromycin therapy. Gradually, his renal function started to improve and he regained normal renal function after two weeks. He was seen two years later with normal renal function, he was on iron tablets and folic acid only.

The second patient was a 30-year-old Saudi male electrical technician diagnosed in December 1984 as having aplastic anemia. In 1988 the diagnosis was revised as aplastic anemia and PNH. He was managed with immunoglobulin and danazole and was doing well until September 1993, when he presented with nausea, vomiting, fatigue and lower abdominal pain. For two weeks prior to his admission, his urine was dark in color and the output decreased.

At presentation he was pale, jaundiced and both flanks were tender, and he was anuric. His serum creatinine was 1,778 umol/L, urea 34 mmol/L, hemoglobin 77 g/L, platelets 108x109/L. ALT and AST were elevated to 70 and 114 IU/L, respectively, lactic dehydrogenase was more than 5,000 U/L, total bilirubin was 40 mmol/L, mainly conjugated. Haptoglobulin was decreased at 0.3 and urinary sodium was 116 mmol/L.

Ultrasound of the kidney revealed enlargement of both kidneys. Doppler study of the renal vessels revealed normal patency. His urine analysis was positive for hemosiderin and poteinuria.

The patient remained anuric for another two weeks and was supported by hemodialysis. During this period he complained of severe headache and a CT scan of the brain excluded sagittal sinus thrombosis.

A renal biopsy was performed [Figure - 1] which showed focal tubular loss and mild interstitial fibrosis. The glomeruli were normal. Renal tissue staining with Prussian blue showed intense and extensive deposition of hemosiderin mainly at the proximal tubules. The picture was also of resolving acute tubular necrosis.

In normal circumstances many glycoproteins are attached to the RBCs surface, each with a different function. PNH cells have a deficiency in many of these glycoproteins. One of the first to be identified is decay accelerating factor (DAF), which when present in normal quantities, effectively prevents RBC hemolysis by preventing the amplification of the steps of the complement cascade [7] . Other reports suggest that PNH cells are unable to place or maintain such protein linked on the cell surface [8] .

After four weeks he started to pass increasing amounts of urine, his renal function gradually improved and became normal after six weeks.


   Discussion Top


PNH is a complex hematological disorder characterized by various presentations in different patients. The common presentations are hemolytic anemia, venous thrombosis and deficient hematopoiesis. All blood elements including RBCs, platelets and granulocytes can be affected which suggests that PNH is a stem cell disorder [1].

According to the quantity of the glycoproteins present on their surface, PNH cells are classified as Class I, II and III. The most sensitive cells to complement lysis are those more deficient in glycoproteins (Class III) [7] . Accordingly the severity of hemolysis depends on both the proportion of normal and abnormal cells, and the degree of abnormality on the cell membrane [8] .

Recurrent abdominal pain in PNH patients is quite common, the mechanism of which is not fully known. However, when a patient presents with abdominal pain venous thrombosis should be suspected. Thrombosis in these patients is possibly due to some platelet aggregation defects, yet again the exact mechanisms are not fully known. The commonest site for venous thrombosis include the inferior vena cava and the hepatic vein ( Budd-Chiari syndrome More Details), and one of the devastating complications is sagittal sinus thrombosis [4] .

Acute and chronic renal failure have been described in PNH patients in several reports, and the old concept that PNH patients with renal impairment had an underlying renal disorder other than PNH is probably not correct [2],[5],[6]

Hemosiderin in the urine, a valuable marker of intravascular hemolysis, as well as pathological specimens showing heavy deposits of hemosiderin which may contribute to the renal damage, were seen in almost all patients with PNH [2],[5],[6],[9] . In other conditions in which intravascular hemolysis is known to occur such as prosthetic valves, renal hemosiderosis has been observed and kidney tissue showed severe tubular atrophy and interstitial fibrosis [10] .

The usual cause for acute renal failure in PNH is acute tubular necrosis [5] . However, when chronic renal failure occurs, chronic tubulo-interstitial changes with intense hemosiderin deposits in the proximal tubules, and arterial nephrosclerosis or hemosiderin deposition have been observed [2] . In such patients, a defective concentrating ability may be an early sign of chronic renal failure and GFR progressively declines [2] . Analysis of 17 patients with PNH revealed a high incidence of functional and anatomical abnormalities [11] , Recurrent microvascular thrombosis is considered to be one of the most significant pathological findings, which may cause some cortical necrosis and subsequent loss of concentrating ability.

Other pathological and radiological findings include papillary necrosis, kidney infarction as a result of renal artery thrombosis, cortical thinning, and enlarged kidney possibly due to congestion [2],[11] . Both of our patients had enlarged kidneys by ultrasound, and the second patient had evidence of acute tubular necrosis.

The pathogenesis of acute renal failure in PNH patients is complex and factors involved include nephrotoxic and ischemic effects of hemoglobin and iron, especially in the presence of acidemia at night, which may lead to complement activation and hemolysis [12],[13] . Free hemoglobin, which results from hemolysis is converted by the renal tubules into hemosiderin. This in turn leads to tubular damage and acute renal failure.

On the other hand, chronic renal failure in PNH is probably the result of progressive micro infarction and hemosiderin deposition in tissues, which correlate with the frequency of intravascular hemolysis [2],[6],[11] .

Both of our patients had full recovery and the pathological findings in the second patient confirmed the presence of hemosiderin deposits and changes suggestive of acute tubular necrosis and there were no chronic changes.

In summary, acute renal failure in patients with paroxysmal nocturnal hemoglobmuria (PNH) is not unusual, while chronic renal failure rarely occurs. Such patients need to be supported by hemodialysis until they recover their renal function.

 
   References Top

1.Forman K, Sokol RJ, Hewitt S, Stamps BK. Paroxysmal nocturnal haemoglobinuira. A clinic op athological study of 26 cases. Acta Hacmatoll984;71:217-26.  Back to cited text no. 1    
2.Claris DA, Butler SA, Braren V, Hartmann RC, lenkins DE Jr. The kidneys in paroxysmal nocturnal hemoglobinuria. Blood 1981;57(1):83-9.  Back to cited text no. 2    
3.Hartmann RC, Jenkins DE Jr, Arnold AB. Diagnostic specificify of sucrose hemolysis test for paroxysmal nucturnal hemoglobmuria. Blood 1970;35(4):462-75.  Back to cited text no. 3    
4.Al Hakim M: Katiriji B, Osorio L Weisman R. Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria: report of two cases. Neurology 1993;43:742-6.  Back to cited text no. 4    
5.Rubin H. Paroxysmal nocturnal hemoglobinuria with renal failure. JAMA 1971;215 (3):433-6.  Back to cited text no. 5    
6.Zachee P, Henckens M, Van Damme B, Boogaerts MA, Rigauts R Verberckmoes RK. Chronic renal failure due to renal hemosiderosis in a patient with paroxysmal nocturnal hemoglobinuna. Clin Nephrol 1993;39(1):28-31.  Back to cited text no. 6    
7.Kmoshita T, Medof ME, Silber R. Nussensweig V. Distribution of decayaccelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Medl985;162;75-92.  Back to cited text no. 7    
8.Rosse WF. Paroxysmal nocturnal hemoglobinuria and decay-accelerating factor. Ann Rev Med 1990:41:431-6.  Back to cited text no. 8    
9.Jackson GH. Noble RS, Maung ZT, Mam J, Smith SR, Reid MM. Severe hemolysis and renal failure in a patient with paroxysmal nocturnal haemoglobinuria. J Clin Pathol 1992;45:176-7.  Back to cited text no. 9    
10.Pardo-Mindan FJ, Diez J, sparza N, Robledo C. Renal siderosis in patients with heart-valve prostheses: clinical implications. Nephrol Dial Transplant 1990:5:847-50.  Back to cited text no. 10    
11.Braren V, Butler SA, Hartmann RC, Jenkins DE Jr. rologic manifestations of paroxysmal nocturnal hemoglobinuria. J Urol 1975:114:430-4.  Back to cited text no. 11    
12.Halpern SE, Leonard JE, Whitcomb WR Bottomlcy SS. Urinary iron excretion studies in paroxysmal nocturnal hemoglobinuria. Arch Intern Med 1971;127: 1028-32.  Back to cited text no. 12    
13.Paller MS, Hedlund BE. Role of iron in postischemic renal injury in the rat. Kidney Int 1988;34:474-80.  Back to cited text no. 13  [PUBMED]  

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Correspondence Address:
Ali Al-Harbi
Department of Internel Medicine, North West Armed Forces Hospital, P.O. Box 100, Tabuk
Saudi Arabia
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PMID: 18408291

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    Abstract
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