Paroxysmal nocturnal haemoglobinuria

2. Paroxysmal nocturnal haemoglobinuria

Introduction

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by an increased sensitivity to complement-mediated erythrocyte lysis leading to cyclical haemoglobinuria. It is also known as Marchiafava-Micheli syndrome. Although commonly regarded as a type of haemolytic anaemia, PNH is in reality, a myelodysplastic, haematopoietic stem-cell disorder. It is most common in second decade of life with a male preponderance.

DIAGNOSTIC PEARLS AND PITFALLS

Age/Sex: Second decade/males.
Presentation: Symptoms due to intravascular haemolysis and thrombosis.
Imaging: Low signal intensity renal cortex on MRI.

Clinical features

Most common presentation includes haemolytic anaemia with symptoms of fatigue, jaundice, and red or black urine. Some patients can present with thrombosis due to hypercoagulable state induced by complement activation. Rarely patients can have pain abdomen, dysphagia or erectile dysfunction due to depletion of nitric oxide by the free haemoglobin in the circulation. Recurrent episodes of haemoglobinuria lead to renal insufficiency and pulmonary hypertension over time.

Aetiopathogenesis

PNH occurs due to somatic mutation in the gene on the X-chromosome which codes for a protein involved in the assembly of phosphatidylinositol glycan (PIG), which anchors many proteins to the surface of cell membranes. Due to lack of PIG, the two protective proteins which inactivate complement complexes, decay accelerating factor (DAF; CD55) and membrane inhibitor of reactive lysis (MIRL; CD59) are not present in PNH red cells, which then become sensitive to lysis by complement.

PNH can lead to chronic renal failure due to deposition of haemosiderin in the proximal convoluted tubules in the renal cortex or due to repeated microinfarctions secondary to microvascular thrombosis or direct nephrotoxic effect of iron.

Fig. 10.12.4.2.1 depicts the pathogenesis of PNH.

Fig. 10.12.4.2.1 Pathophysiology of paroxysmal nocturnal haemoglobinuria.

Diagnostic imaging

Ultrasound can only demonstrate morphological alterations in the kidneys due to secondary chronic renal failure but does not demonstrate iron deposits.

CT without intravenous contrast can show high attenuation of the renal parenchyma.

MRI shows low signal on both T1- and T2-weighted images with inversion of the signal intensity of the renal cortex (i.e. reversed renal cortex-medulla differentiation) due to ferric iron present in the haemosiderin which deposits in the renal cortex. T2-weighted imaging has higher magnetic susceptibility and shorter examination times and is hence superior to T2-weighted imaging in detection of renal cortical haemosiderosis.

In case of PNH, bone marrow signal on MRI is normal. Bone marrow intensity shows fatty degeneration with ageing.

Differential diagnosis

• Other causes of intravascular haemolysis – Haemolysis due to malfunctioning prosthetic cardiac valve.
• Sickle cell anaemia – Extravascular haemolysis.

The levels of iron deposits in the liver and spleen are usually normal in PNH which is in contrast to other haemolytic anaemias. Decrease in signal intensity of liver and spleen on MRI is seen in patients with PNH who have received multiple blood transfusions.

Low Signal Intensity Renal Parenchyma on MRI: Causes

Categories	Conditions	MRI Features
Haemolysis	Paroxysmal nocturnal haemoglobinuria	Low signal intensity in the renal cortex
	Mechanical haemolysis	Low signal intensity in the renal cortex
	Sickle cell disease	Low signal intensity in the renal cortex and spleen
Infection	Haemorrhagic fever with renal syndrome	Well-defined zone of low signal intensity in the outer medulla
Vascular disease	Acute renal vein thrombosis	Renal swelling, indistinct corticomedullary differentiation on T1-WI, low signal intensity of the renal cortex and medulla
	Renal cortical necrosis	Low signal intensity of the inner renal cortex. Swelling of both kidneys and loss of corticomedullary differentiation on T2-WI
	Arterial ischaemia and infarction	Infarcted area shows low signal intensity on both T1- and T2-WI. Signal intensity may be higher in haemorrhagic infarcts
	Rejection of a transplanted kidney	Loss of corticomedullary differentiation. Low signal intensity is seen if combined with diffuse haemorrhagic necrosis or cortical necrosis
	Acute nonmyoglobinuric renal failure	Initially high signal intensity on T1-WI and variable signal intensity on T2-WI. Low signal intensity on both T1- and T2-WI after the 7th day

Treatment

In acute attack, the use of steroids is still debatable. Transfusion therapy helps in correcting anaemia and suppresses the production of PNH cells by the bone marrow, thereby reducing the severity of haemolysis. Anticoagulation with warfarin decreases the risk of thrombosis. Monoclonal antibody that targets complement protein C5, Eculizumab, is FDA approved for the treatment of PNH. It significantly reduces haemolysis and leads to improvement in anaemia.

Conclusion

MR is the best imaging method to demonstrate iron overload in the renal cortex in patients with PNH.

Bone marrow signal on MRI is normal in PNH.

10.12.5

RENAL DISORDERS OF MIGRATION AND RENAL ANOMALIES

Priscilla Joshi, Anand Mukund Rahalkar, Nagesh Seth, Mangal Mahajan, M.D. Rahalkar, Vandana Jahanvi, Aparna Katdare, Palak Bhavesh Popat, Nilesh P. Sable, Ganesh Bakshi

Introduction

Renal anomalies encompass a spectrum which ranges from lethal renal agenesis to incidentally detected renal anomalies secondary to aberrant embryonic migration. Imaging helps in the early diagnosis, detection of complications, surgical planning and follow-up of these patients.

On an embryological basis, anomalies of the kidney and urinary tract can be divided into:

1. Abnormalities in renal parenchymal development.
2. Aberrant embryonic migration.
3. Abnormalities of the collecting system.

Imaging modalities

Imaging modalities used for evaluation include:

1. Plain radiographs of the abdomen for the KUB region.
2. Ultrasound.
3. Intravenous urography.
4. Computed Tomography (CT) with CT urography.
5. Magnetic Resonance Imaging (MR) with MR urography.

A number of anomalies can be detected antenatally on ultrasound. An anomaly scan includes evaluation of the kidneys – number, size, appearance, dilatation of the collecting system and presence of a distended urinary bladder. An over distended urinary bladder with bilateral hydronephrosis and hydroureter would indicate presence of a bladder outlet obstruction. Abnormalities if any, can be confirmed with a foetal MRI so that appropriate timely management can be instituted. These foetuses merit postnatal evaluation after birth and 4–6 weeks later.

Plain radiographs may be done in calculus disease and give a clue as to the presence of an anomaly.

1. On a radiograph of the abdomen covering the kidney ureter bladder and urethral area the following checklist should be followed (Table 10.12.5.1.1) check for presence of renal outlines, the axis of the kidneys, any opacities in the region of the urinary system. Evaluation of the psoas muscle outlines; other soft tissues and visualized bones completes the study.
2. Ultrasound is the modality used for screening the KUB area and is very often the only modality used.
3. CT being more widely available is useful in case a kidney is nonvisualized in its normal location or in the pelvis on ultrasound. It, however, has the inherent drawback of radiation. Detection of calculi is an advantage CT has over MRI.
4. MRI with MR urography is the new kid on the block and has the advantage of having no associated radiation and excellent soft-tissue contrast. It also helps in evaluation of complex anomalies since there is excellent delineation of the collecting system even without contrast administration. Injection of a diuretic helps better delineation of the collecting system and ureters, more so when evaluating for an ectopic ureteric opening. Excretory MR urography performed after administration of Intravenous gadolinium compound, with or without a diuretic helps assess renal function and delineates the renal outlines, the renal parenchyma in the nephrogram phase and the collecting system and ureters.