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British Journal of Radiology (2004) 77, 953-956
© 2004 British Institute of Radiology
doi: 10.1259/bjr/51760601
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Case report

The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings

J Rimola, MD J Martín, MD, PhD J Puig, MD A Darnell, MD and A Massuet, MD

Unitat de Diagnòstic per la Imatge d’Alta Tecnologia (UDIAT), Corporació Sanitària del Parc Taulí, 08208 Sabadell, Spain


   Abstract
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 Abstract
Case reports
 Case four
 Discussion
 References
 
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired stem-cell disorder characterized by defective haematopoiesis, which results in an increased sensitivity of the erythrocytes to complement-mediated intravascular haemolysis. Renal damage is infrequent but can produce chronic renal failure due cortical deposits of haemosiderin and microvascular thrombosis. MRI provides characteristic images of the kidneys that enable haemosiderin deposition to be diagnosed; in PNH, MRI typically shows reversed renal cortex-medulla differentiation on T1 weighted images and substantial loss of cortical signal intensity on both T1 and T2 weighted images. We describe the MRI findings of renal cortical haemosiderosis occurring in four patients with PNH.


   Case reports
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 Abstract
 Case reports
Case four
 Discussion
 References
 
Case one
A 38-year-old male was admitted to the emergency department with dark urine and anaemia. He had received multiple blood transfusions 2 years earlier for bone marrow aplasia during respiratory infection. Physical examination showed conjunctival jaundice, but the remainder of the examination was unremarkable. Laboratory findings included: creatinine 1.2 mg dl–1, lactic dehydrogenase (LDH) 5701 U l–1, total bilirubin 3.5 mg dl–1, direct bilirubin 0.2 mg dl–1, anaemia with haemoglobin 9.5 g dl–1, haematocrit 37%. Urine analysis was positive for protein and blood. Coomb's test was negative but the acidified serum-lysis test (Ham test) was positive. Paroxysmal nocturnal haemoglobinuria (PNH) was diagnosed. The patient responded well to treatment with steroids and fluid therapy.

The kidneys appeared normal on abdominal ultrasound. Abdominal MRI was performed, obtaining images in the axial and coronal planes using both T1 and T2 weighted images. The half-Fourier single-shot turbo spin-echo (HASTE) sequence was used for T2 weighted images, and in and out-of-phase gradient-echo sequences were used for T1 weighted images. Extremely low signal intensity was seen in the renal cortex on both T1 and T2 weighted images. Especially dark renal cortex was seen on in-phase gradient-echo sequences (Figure 1Go). These findings were consistent with cortical renal haemosiderosis.



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  		Figure 1. Case one. (a) Axial T1 weighted in-phase gradient-echo image of the kidneys showing notably low signal intensity of the renal cortex. Note the medullary area is not affected by the iron deposition. (b) Coronal T2 weighted half-Fourier single-shot turbo spin echo (HASTE) image. The renal cortex is of low signal intensity compared with the renal medullary zone.

 
Case two
A 38-year-old woman with a 7 year history of PNH was admitted to the hospital with low back pain, dark urine, jaundice and vomiting. The only clinically remarkable finding on physical examination was conjunctival jaundice.

The laboratory blood test revealed: creatinine 6.1 mg dl–1, total bilirubin 1.6 mg dl–1 and direct fraction 0.6 mg dl–1, elevated LDH, anaemia with haemoglobin 8.9 g dl–1, normal platelet and leukocyte counts. Coomb's test was negative. The Ham test was positive. Urinalysis at admission showed 4–5 erythrocytes and 18–20 leukocytes per high power field. Consistent with PNH, follow-up haemograms and renal function tests showed a return to normal after treatment.

Abdominal MR examination was performed to evaluate the iron deposition in solid organs, especially in the kidneys. In and out-of-phase T1 weighted gradient-echo and T2 weighted HASTE sequences were performed, finding a reversal of the normal ratio of cortical and medullary intensities on T1 weighted images and a very low cortical signal intensity on T2 weighted images of both kidneys. These findings are indicative of iron deposition in the renal cortex (Figure 2Go). Other solid abdominal organs were normal on MRI.



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  		Figure 2. Case two. (a) Axial T1 weighted in-phase gradient-echo slice showing a reversal of renal cortex-medulla differentiation with low signal intensity of the renal cortex. (b) Coronal half-Fourier single-shot turbo spin echo (HASTE) image of both kidneys shows the cortical zones with low signal intensity and the medullary area with normal signal intensity.

 
Case three
A 43-year-old woman with no prior history presented at the emergency department with sudden asthenia and nausea, which resolved in 24 h without treatment, and conjunctival pigmentation. Laboratory results found anaemia with haemoglobin level of 9.0 mg dl–1, mild thrombocytopenia with a platelet count of 117 000 dl–1 and a white cell count of 3500 dl–1, creatinine 1 mg dl–1, elevated LDH, total bilirubin 3.5 mg dl–1 (direct bilirubin 0.7 mg dl–1). Protein analysis revealed IgG-{lambda} monoclonal gammopathy. Coomb's test was negative. The Ham test was positive. Abdominal ultrasound, radiological bone study and chest X-ray were normal. Bone marrow study was negative for lymphoproliferative processes; iron deposits were low, and flow cytometry studies were compatible with PNH. Treatment with corticosteroids and oral iron supplements brought about a slight improvement in the pancytopenia.

Abdominal MRI showed the typical kidney findings of bilateral low signal renal cortex both in T1 and T2 weighted MR images (Figure 3Go). No other intra-abdominal organs were affected.



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  		Figure 3. Case three. (a) T1 weighted axial gradient-echo image shows the cortical area of the kidneys with low signal intensity compared with the medullary zone, which maintains the intermediate signal intensity of a normal kidney. (b) The T2 weighted image shows the kidneys with a dark cortex due to iron deposition.

 

   Case four
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 Abstract
 Case reports
 Case four
Discussion
 References
 
A 78-year-old man with chronic myelomonocytic leukaemia was admitted to the emergency department for weakness and dark urine over 2 weeks. Physical examination showed conjunctival jaundice. Blood cell count showed anaemia and thrombocytopenia. Direct and indirect bilirubin were abnormal. Direct and indirect Coomb's test were negative. The Ham test was positive. Defects in glycoproteins CD 55 and CD 59 on the membrane of leukocytes, erythrocytes, and platelets were also observed. PNH was diagnosed. The patient has since received multiple blood transfusions.

Abdominal MRI done to study the iron deposition revealed low signal of the renal cortex on T1 and T2 weighted images, compatible with renal cortex haemosiderosis (Figure 4Go).



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  		Figure 4. Case four. A very dark renal cortical zone compared with the medullary area is seen in the T1 weighted image.

 

   Discussion
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 Abstract
 Case reports
 Case four
 Discussion
References
 
PNH is a rare, acquired myelodysplastic stem-cell disorder. This condition affects all three haematopoietic lines. It is characterized by acute and chronic intravascular haemolysis with or without gross haemoglobinuria, which is caused by increased sensitivity to complement-mediated haemolysis. Factors reported as precipitating haemolysis include infections, drugs, exercise, transfusions, surgery, but the cause often remains unknown. The clinical course of PNH is very variable. Moreover, these patients can exhibit a wide range of manifestations including bone marrow hypoplasia, venous thrombosis and increased sensitivity to infections. PNH can produce chronic renal failure caused by haemosiderin deposition in the proximal convoluted tubules in the renal cortex and repeated microinfarctions occur due to microvascular thrombosis or a direct nephrotoxic effect of iron [1, 2].

Free haemoglobin forms a complex molecule with haptoglobin and haemopexin. However, when plasma haptoglobin becomes saturated with haemoglobin, free haemoglobin is filtered by the glomeruli and is partially reabsorbed in the proximal tubules, where part of the iron will be incorporated into haemosiderin deposits and the rest will be excreted. The typical histological finding in the kidney is deposition of haemosiderin in epithelial cells of the proximal convoluted tubules in the renal cortex. Haemoglobinuric crises can precipitate acute renal failure, which is usually reversible. The pathogenesis of acute renal failure in PNH is unclear and multiple factors, such as haemolysis, infections, or thrombosis, are hypothetically involved [2, 3].

MRI of the kidneys using both T1 and T2 weighted pulse sequences is the best imaging technique to demonstrate haemosiderin deposition in the renal cortex in PNH.

On MRI, normal kidneys show low or medium signal intensity on T1 weighted images, the renal cortex being slightly hyperintense with respect to the medulla. Consequently, there is relatively good differentiation between cortex and medulla on images obtained with T1 weighted pulse sequences [4]. When haemosiderin deposition occurs in the renal cortex, it becomes darker than renal medulla and a typically reversed renal cortex-medulla differentiation is seen (Figures 1–4GoGoGoGo). All of our four cases showed this typical reversal of cortical-to-medullary intensity ratio on T1 weighted images (Figures 1–4GoGoGoGo).

The iron deposition is better demonstrated using T1 weighted gradient-echo pulse sequences because this pulse sequence is more sensitive to the magnetic susceptibility effect than spin-echo sequences.

On T2 weighted images, the cortex and medulla both have a very similar, moderately high signal intensity in normal kidneys and no distinction between cortex and medulla can be made [4]. Haemosiderin contains ferric iron and deposits of haemosiderin explain the low signal intensity of the renal cortex depicted in T2 weighted images in patients with PNH [5–8]. All four patients showed low signal intensity of the renal cortex in images obtained with T2 weighted pulse sequences (Figures 1–4GoGoGoGo).

The renal medulla is not affected in PNH and has a normal intensity on MRI, and reversal of renal cortex-medulla differentiation is not seen as occurs on T1 weighted images.

The low signal intensity of the renal cortex on MRI is characteristic but not pathognomonic. This finding has been reported in other diseases such as sickle-cell disease and haemolysis due to malfunctioning prosthetic cardiac valve [9–11].

In contrast to other haemolytic anaemias, levels of iron deposits in the liver and spleen are usually normal in PNH. However, if a patient with PNH has received multiple blood transfusions, these iron levels may increase, resulting in decreased signal intensity of liver and spleen on MRI [5]. None of our cases shows abnormal signal intensity in other abdominal organs. Case 3 received some blood transfusions but only for a short period of time and his liver and spleen signal on MRI were normal.

CT without intravenous contrast can show spontaneously high attenuation of the renal parenchyma. Ultrasound can only demonstrate morphological alterations in the kidneys due secondary chronic renal failure, but does not demonstrate iron deposits. MR is the best imaging method to demonstrate iron overload in the renal cortex in patients with PNH [6, 7].

Although PNH is a stem-cell disorder which can produce ineffective haematopoiesis with intramedullary haemolysis, bone marrow signal on MRI is also normal. Bone marrow intensity changes can be observed with ageing due to fatty degeneration [8].

Tanaka et al propose three patterns (type A, B and C) of haemosiderin deposition in PNH. Type A affects the cortex and pyramids; Type B only affects the periphery of the kidney; and Type-C signal intensity of the renal cortex is normal. In all our patients the MR images were obtained a short time after the last haemolysis and these four cases present the type-B pattern described by Tanaka. These findings lend support to Tanaka's hypothesis, which speculates that the extent of the low signal intensity on T2 weighted MRI is directly related to the time elapsed from the last haemolytic attack [8]. Follow-up MR images are not available in our patients since no further studies were deemed necessary. To date all patients have shown a good clinical response to treatment.

In conclusion, renal involvement in PNH due to haemosiderosis in the renal cortex can be clearly demonstrated by MRI, where the signal intensity of the renal cortex on both T1 and T2 weighted sequences is markedly decreased and normal renal cortex-medulla differentiation is inverted on the T1 weighted sequence. The liver and spleen have normal signal intensity except when multiple blood transfusions are administered.

Received for publication May 30, 2003. Revision received December 11, 2003. Accepted for publication February 3, 2004.


   References
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 Abstract
 Case reports
 Case four
 Discussion
 References
 

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  4. Hricak H, Crooks L, Sheldon P, et al. Nuclear magnetic resonance imaging of the kidney. Radiology 1983;146:425–32.[Abstract/Free Full Text]
  5. Roubidoux MA. MR of kidney, liver and spleen in paroxysmal nocturnal hemoglobinuria. Abdominal Imaging 1994;19:168–73.[CrossRef][Medline]
  6. Kim SH, Han MC, Lee JS, et al. Paroxysmal nocturnal hemoglobinuria. Case report of MR and CT findings. Acta Radiol 1991;32:315–6.
  7. Mulopulos GP, Turner DA, Schwarts MM, et al. MRI of kidneys in paroxysmal nocturnal hemoglobinuria. AJR Am J Roentgenol 1986;146:51–2.[Free Full Text]
  8. Tanaka YO, Anno I, Yuji I, et al. Paroxysmal nocturnal hemoglobinuria: MR findings. J Comput Assist Tomogr 1993;17:749–53.[Medline]
  9. Jeong JY, Kim SH, Lee HJ, et al. Atypical low-signal-intensity renal parenchyma: causes and patterns. RadioGraphics 2002;22:833–46.[Abstract/Free Full Text]
  10. Lande IM, Glaze GM, Sarnaik S, et al. Sickle-cell nephropathy: MR imaging. Radiology 1986;158:379–83.[Abstract/Free Full Text]
  11. Lee JW, Kim SH, Yoon CJ. Hemosiderin deposition on the renal cortex by mechanical hemolysis due to malfunctioning prosthetic cardiac valve. Report of MR findings in two cases. J Comput Assist Tomogr 1999;23:445–7.[CrossRef][Medline]



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M. Bessler and J. Hiken
The Pathophysiology of Disease in Patients with Paroxysmal Nocturnal Hemoglobinuria
Hematology, January 1, 2008; 2008(1): 104 - 110.
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