Chapter 48: Sickle Cell Nephropathy

INTRODUCTION

Sickle cell disease (SCD) is an autosomal recessive hemoglobin disorder arising from the substitution of glutamate for valine at the sixth amino acid of the β-globin chain. The mutation results in poorly soluble hemoglobin S (HbS) tetramers that aggregate during cellular or tissue hypoxia, dehydration, or oxidative stress. Such aggregation can lead to red blood cell sickling deformity, premature destruction of erythrocytes, and widespread vaso-occlusive episodes, potentially leading to multiorgan damage. Various kidney complications including hematuria, renal papillary necrosis, renal tubular disorders, acute and chronic kidney injury, sickle cell glomerulopathy, and renal medullary carcinoma are reviewed in the current chapter.

HEMATURIA & RENAL PAPILLARY NECROSIS

General Considerations

Hematuria commonly occurs as a consequence of red blood cell sickling in the renal medulla leading to vascular obstruction and RBC extravasation into the collecting system. Hematuria may also indicate the presence of papillary necrosis, and in rare cases, renal medullary carcinoma.

Pathogenesis

The low oxygen tension or relatively hypoxic, hypertonic, and acidotic environment of the inner medulla predisposes red blood cells in the vasa recta to sickle, and causes increased blood viscosity, microthrombi formation, and ischemic necrosis. Such pathologic events can cause structural changes leading to RBC extravasation into the collecting system, renal infarction, and papillary necrosis. The left kidney is affected four times more than the right due to the increased venous pressure within the longer left vein that is compressed between the aorta and the superior mesenteric artery, a “nutcracker phenomenon.” The increased venous pressure leads to increased relative hypoxia in the renal medulla, hence sickling.

The renal papillary necrosis of SCD contrasts with that of the papillary necrosis observed in analgesic nephropathy, in which the vasa rectae are typically spared, and most lesions occur in peritubular capillaries.

Clinical Findings

A. Symptoms and Signs

Both microscopic and macroscopic painless hematuria may be observed. Bleeding typically remits spontaneously within a few days. Hematuria is usually unilateral and originates more frequently from the left than the right due to the nutcracker phenomenon. Bilateral hematuria occurs in approximately 10% of cases. Although renal papillary necrosis typically presents with painless gross hematuria, it may be complicated by obstructive uropathy and urinary tract infections. Current data suggest that hematuria and papillary necrosis do not portend greater risk for renal failure. Acute segmental or total renal infarction may present with flank or abdominal pain, nausea, vomiting, fevers, and presumably renin-mediated hypertension.

Renal papillary necrosis (RPN) is usually discovered by radiologic investigation of patients with ...