Chapter 49. Sickle Cell Nephropathy

The major clinical consequences of sickle cell disease (SCD) are crises from vascular obstruction by sickled cells and anemia because of red blood cell (RBC) destruction. The obstruction can cause hematuria and renal papillary necrosis (RPN) with a defect in tubular function, especially in urinary concentration. The chronic consequences include sickle cell glomerulopathy, more indirectly related to sickling, and a specific form of renal malignancy.

Essentials of Diagnosis

• Acute gross hematuria or persistent microscopic hematuria.
• Without RBC casts or dysmorphic (other than sickle) RBCs.
• Ultrasound or helical computed tomography (CT) shows distinctive medullary abnormalities.

General Considerations

Hematuria in SCD is a specialized form of the sickle crisis, the consequence of renal medullary sickling, vascular obstruction, and RBC extravasation. The low PaO2, high osmolality, and acidic environment of the renal medulla lead to sickling.

Pathogenesis

The renal pathology associated with isolated hematuria, shows relatively insignificant changes, primarily medullary congestion. The later RPN in SCD is a focal process, with some collecting ducts surviving within a diffuse area of fibrosis. The relevant medullary pathology in SCD is found in the region of the collecting ducts, the inner medulla, and the papilla. Within the medullary fibrosis the vasa rectae are destroyed, following initial dilation and engorgement. The RPN of SCD contrasts with the RPN observed in analgesic abuse, in which the vasa rectae typically are spared, and most lesions occur in peritubular capillaries. Because calyces are affected separately and sequentially in SCD, acute obstruction and renal failure are uncommon.

Clinical Findings

Symptoms and Signs

Gross and often painless hematuria is dramatic and is usually unilateral (L>R) due to increased left renal vein pressure. Hematuria occurs at any age and is more often seen with a (higher gene frequency) sickle trait (HbAS).

RPN is usually discovered by radiologic investigation of patients with painless gross hematuria. However, hematuria is not invariably present in RPN, with no difference in the incidence between symptomatic (65%) and asymptomatic (62%) patients. RPN can be found even in young children.

Acute renal failure is not uncommon in SCD; it is seen most often with infections and evidence of rhabdomyolysis, and in patients with lower hemoglobin (Hb) (˜6.4 versus 8.7 g/dL). Volume depletion is a common precipitating cause. It is likely that nonsteroidal anti-inflammatory agents are partly responsible for some episodes of acute renal failure, in view of the maintenance of the glomerular filtration rate (GFR) in SCD by prostaglandin mechanisms.

Rhabdomyolysis with acute renal failure and disseminated intravascular coagulation has been seen, albeit rarely, in those with sickle trait who undergo rigorous military training, and there is an apparently increased risk of sudden unexplained death in patients with sickle trait.

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