Children with sickle cell anemia, and often those with sickle cell trait, may present with a wide spectrum of significant urinary tract disorders, including hyposthenuria, acidosis, hematuria, proteinuria, nephrotic syndrome, chronic renal failure, and urinary tract infection (Box 330.1).

Hyposthenuria (inability to concentrate the urine maximally) is a common finding resulting from chronic damage to the renal medulla. Medullary environment, which is hyperosmolar, acidotic, and hypoxic, predisposes to sickling of red blood cells. Deformed sickled cells may obstruct blood flow in medullary vessels, thus leading to disruption of the normal concentrating mechanism. Hyposthenuria first appears in young children and is reversible by administration of multiple blood transfusions. However, hyposthenuria is irreversible in adolescents, and maximal urine concentration is approximately 450 mOsm/L. Clinically, children with hyposthenuria present with polyuria and often with enuresis; they are at greater risk for dehydration. Patients with sickle cell anemia also may have a mild defect in maximal urinary acidification (inability to decrease urine pH to less than 5.3) and potassium excretion by the distal tubule; however, clinically significant hyperchloremic metabolic acidosis and hyperkalemia are rare findings, even during sickle cell crises.

Microscopic or gross hematuria is a common finding, and episodes can last from days to months. The onset of hematuria usually is sudden and unprovoked, although some cases are associated with trauma, exercise, upper respiratory tract infection, or sickle cell crisis. Bleeding usually is painless, unless it is accompanied by papillary necrosis. The hematuria usually is unilateral, with the left kidney involved four times more frequently than the right. Most of the episodes are self-limited in children. However, massive, life-threatening, and prolonged periods of gross hematuria, which rarely occur in children, may be seen in men. The occlusion of blood flow in vasa recta may lead to papillary necrosis, a frequent complication of sickle cell nephropathy. Papillary necrosis presents usually as painless gross hematuria, although it may present in rare instances as renal colic secondary to the passage of blood clots or sloughed papillae. Intravenous pyelography is the method of choice for the radiographic demonstration of renal papillary necrosis. Membranoproliferative glomerulonephritis, renal artery thrombosis, and renal vein thrombosis are other complications of sickle hemoglobinopathy that can lead to hematuria.