Diagnosis

Renal hemosiderosis

Findings

To exclude renal artery stenosis as a cause of her renal failure, both magnetic resonance imaging (MRI) and MR angiography (MRA) of the kidneys were performed (Philips Intera 1.5T, Philips Medical Systems, Andover, MA). The MRI revealed hypointensity of the renal cortex relative to the medulla bilaterally on both T1-weighted (T1W) (Figure 1) and T2-weighted (T2W) images (Figure 2). No hydronephrosis or focal masses were noted. The MRA revealed no renal artery stenosis or dissection.

Multidetector (16-slice) CT axial noncontrast images of the kidneys (Figure 3) had been acquired 6 months earlier when the patient presented with abdominal pain from a renal stone (Siemens SOMATOM, Siemens Medical Solutions, Erlangen, Germany). Other than the renal stone (not shown), no focal lesion or cortical calcification was identified.

The low T1 and T2 renal cortical signal seen on the MRI images is abnormal. Normally, on T1W imaging, the renal cortex is hyperintense relative to the medulla. Normal T2W images of the kidney have diffusely high signal and poor differentiation between the cortex and medulla (Figure 4).¹

Diagnostic considerations of the renal MRI findings include renal hemosiderosis and cortical nephrocalcinosis.²The patient's medical history and laboratory results were inconsistent with cortical nephrocalcinosis. Furthermore, renal cortical calcifications were absent on the CT scan. Given the imaging findings and intravascular hemolysis caused by a dysfunctional mitral valve, the most likely cause for the renal MRI findings was renal hemosiderosis.

Discussion

Severe intravascular hemolysis is the underlying etiology of renal hemosiderosis. Intravascular hemolysis is diagnosed with laboratory studies that show anemia, low haptoglobin, elevated lactate dehydrogenase, and blood smear schistocytes. Reported causes of intravascular hemolysis that result in renal hemosiderosis are mechanical hemolysis (ie, from a dysfunctional valve replacement), paroxysmal nocturnal hemoglobinuria, and sickle cell anemia.²

Other hemolytic anemias also can cause renal hemosiderosis.³ Mechanical hemolysis causes intravascular hemolysis by the shearing of normal red blood cells, which results in large amounts of circulating free hemoglobin.⁴ Paroxysmal nocturnal hemoglobinuria is a rare myelodysplastic, hematopoietic stem cell disorder. Lysis of red blood cells (RBCs) is caused by increased sensitivity to complement-mediated hemolysis. It is diagnosed via an acidified serumlysis test (Ham’s test).⁵ Sickle cell disease usually causes extravascular hemolysis, rather than intravascular hemolysis, as the abnormal sickle-shaped RBCs are hemolyzed in the spleen. In an acute crisis, however, up to one third of hemolytic activity is intravascular. Many patients with sickle cell disease, however, present without renal pathology or MR manifestations.²

Hemosiderin accumulates in the kidneys by the following pathway. When free hemoglobin from lysed RBCs circulates in the vasculature, haptoglobin and hemopexin bind to it and are depleted. The free hemoglobin is filtered by the kidney as opposed to hemoglobin which is bound to haptoglobin and hemopexin, which is cleared by the liver. In the kidney, the hemoglobin is either excreted by or reabsorbed in the proximal convoluted tubules (which are in the renal cortex) and stored as hemosiderin and ferritin.⁶

On MRI, hemosiderin has strong paramagnetic properties. At low concentrations, it shortens T1 relaxation times. At high concentrations, as seen with renal hemosiderosis, it shortens T2 relaxation times and this results in low signal. T1-weighted images are influenced by T2effects, which is why the renal cortex in hemosiderosis is dark on T1W images as well.²T2-weighted imaging has been noted to be more sensitive than T1W imaging in identifying hemosiderin deposition.²

Most cases of renal hemosiderosis are not associated with renal failure.⁶ Rare reports of renal failure linked to renal hemosiderosis have been reported in the literature.^3,7,8 Pathologic findings in a patient with acute renal failure and renal hemosiderosis have been reported as tubular damage, slight chronic tubulointerstitial inflammation and fibrosis. The pathophysiologic connection between the 2 entities has not been clarified, but it has been suggested that the iron may cause cytotoxic radicals to form or cause abnormalities in fatty acids and that these eventually lead to cell death.⁷

In this patient’s case, renal hemosiderosis may or may not have been an incidental finding. The patient’s hypertension and poor hemodynamic state most likely caused her renal failure, although the causes of her deteriorating renal function are still unclear. The patient later underwent a mitral valve replacement repair. The goal of the surgery was to improve the patient’s cardiovascular and anemic state, and, therefore, improve her quality of life. If the renal hemosiderosis contributed to her renal dysfunction, the decreased renal iron deposition could theoretically slow the deterioration of her kidney function, although a complete halt to her progressing renal disease would be unlikely.

Conclusion

Renal hemosiderosis is a diagnostic consideration when MRI of the kidneys exhibits abnormally low renal cortical signal in T1W and T2W sequences. Clinical history and laboratory studies compatible with intravascular hemolysis, including that caused by mechanical hemolysis from a dysfunctional cardiac valve replacement as in this case or paroxysmal nocturnal hemoglobinuria, aid with diagnosis.

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4. Roberts WC, Morrow AG. Renal hemosiderosis in patients with prosthetic aortic valves. Circulation. 1966;33:390-398.
5. Rimola J, Martin J, Puig J, et al. The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings. Br J Radiol. 2004;77: 953-956.
6. Siegelman ES, Mitchell DG, Semelka RC. Abdominal iron deposition: Metabolism, MR findings, and clinical importance. Radiology. 1996;199:13-22.
7. Ackerman D, Vogt B, Gugger M, Marti HP. Renal haemosiderosis: An unsual presentation of acute renal failure in a patient following renal valve prosthesis. Nephrol Dial Transplant.2004;19:2682-2683. Erratum in: Nephrol Dial Transplant. 2004;19:3210.
8. Chow K, Lai FM, Wang AY, et al. Reversible renal failure in paroxysmal nocturnal hemoglobinuria. Am J Kidney Dis. 2001;37(2):e17.

Products Used

• Philips Intera 1.5T MRI scanner (Philips Healthcare, Bothell, WA)
• SOMATOM 16-slice CT scanner (Siemens Medical Solutions, Malvern, PA)