Case Presentation
A 70-year-old female presented with high indirect bilirubin levels and mild renal dysfunction on a routine assessment. Relevant past medical history included mild chronic anemia and episodes of hematuria in the previous year, which were treated as low urinary tract infections.
Additional workup revealed increased LDH and reticulocyte count, hematuria and low haptoglobin levels, thus suggesting hemolytic anemia.
An abdominal MRI was also performed, revealing an abnormal bilateral renal cortex hypointensity, both on T1W and T2W, as well as cortical thinning (Fig.1 and Fig.2), with a relative signal increase on T1 out-of-phase compared to T1 in-phase (Fig.3). No other abdominal abnormalities were noticed, including in the renal medulla. Isolated renal hemosiderosis was therefore assumed.

Figure 1: Axial T2FSE. Abnormally diffuse hypointense renal cortex (arrows) and normal medulla signal (*).

Figure 2: Axial T1GRE (in-phase). Reversed T1 renal cortex-medulla differentiation with abnormal T1 hypointense renal cortex (arrows) and normal medullar intensity (*).

Figure 3: Axial T1GRE (out-of-phase). Diffuse cortical hypointensity (arrows) on T1 out-of-phase. Note that on T1 GRE out-of-phase the renal cortical intensity is relatively less dark than on T1 GRE in-phase (Fig.2).
Further analytical evaluation excluded autoimmune and microangiopathic hemolytic anemias. Finally, a screening confirmed the presence of the Paroxysmal Nocturnal Hemoglobinuria (PNH) clone.
Discussion
PNH is a rare acquired myelodysplastic disorder characterized by increased complement-mediated intravascular hemolysis.1 Clinical features of PNH include hemoglobinuria, iron deficiency anemia and venous thrombosis.1,2 Hemosiderin accumulation resulting from intravascular hemolysis occurs exclusively in the kidney and is frequent in PNH.1,3 Chronic renal insufficiency secondary to PNH is most likely due to microvascular thrombosis, rather than iron/hemosiderin-induced tubular damage.2
The intravascular hemolytic process releases free hemoglobin into the plasma that either attaches to haptoglobin or remains unbound. The unbound plasmatic hemoglobin is filtered in the glomerulus and reabsorbed at the renal cortical proximal tubules, leading to the deposit of heme iron as hemosiderin in the renal cortex. If the renal tubular absorptive capacity is exceeded, the filtered hemoglobin is excreted as hemoglobinuria.2
MRI is the most sensitive imaging method to detect hemosiderin deposits.
In normal kidneys, the cortex appears more intense than the medulla on T1W MRI images, and both the cortex and medulla have high signal intensity on T2W.3 (Fig. 4) In renal hemosiderosis, the renal cortex appears dark on T1W and T2W and the medulla retains its normal signal, resulting in T1 reversed cortex-medulla differentiation;1 on T1 GRE out-of-phase the renal cortical intensity is relatively higher than on T1 GRE in-phase.

Figure 4: Normal kidney signal at MRI (another patient from the hospital database). T1W image (a) displays normal cortex-medulla differentiation, with the cortex (arrows) appearing more intense than the medulla (*). T2W (b) depicts both medulla (*) and cortex (arrows) normal high signal.
Because of its superparamagnetic properties, high concentrations of hemosiderin dramatically reduce T2 relaxation time and decrease signal in both T1W and T2W.1 Gradient-echo imaging is also sensitive to T2 signal loss because it lacks the 180º refocusing pulse of the spin-echo sequences.2,3 On gradient-echo sequences, the longer the echo time the greater the T2 decay, which explains the differences between T1 in-phase and T1 out-phase.4
Although renal hemosiderosis is characteristic of PNH, it has also been reported in other hemolytic anemias.2,3 However, opposed to what occurs in most hemolytic anemias (e.g., sickle cell disease, autoimmune hemolytic anemia, hereditary spherocytosis), in PNH the reticuloendothelial system contributes little to the red cell destruction. Therefore, the signal intensity in the liver and the spleen is generally normal in PNH, unless transfusion siderosis or vascular thrombosis have occurred.2
Isolated renal hemosiderosis without reticuloendothelial iron overload is very suggestive of PNH and mechanical valvular hemolysis is a differential diagnosis to be considered.3
PNH is a chronic, progressive, and life-threatening disease. About 4 or 5 decades ago the 10-year survival after diagnosis was only 50 percent, with thrombosis as the leading cause of death.5 Presently the treatment options for PNH include supportive care (RBCs transfusion, immunosuppressive treatment, etc.), allogeneic stem cell transplantation or eculizumab (a complement blockade antibody). The advances in treatment in the last decades (i.e., eculizumab) have significantly improved long term survival in PNH.6