Sickle cell nephropathy

Epidemiology

SCD affects anywhere from 70,000 to 100,000 people in the United States. It is seen most commonly in African Americans (1 out of 500 births), but can be found in a myriad of ethnicities including South American, Caribbean, Mediterranean, Indian, and Saudi Arabian. The sickle cell trait is even more common, being found in over 2 million Americans and 1 out of 12 African Americans.³ The protective nature of the disease leads to its higher prevalence in areas where malaria is endemic.

Renal

Pathophysiology

The inner medulla of the kidney provides an acidic environment with low oxygen tension and high osmolality. This seems to be ideal to promote polymerization of deoxygenated hemoglobin S and sickling of the erythrocytes.⁵ The chronic sickling leads to ischemic injury and microinfarcts that result in microvascular damage and extravasation of blood in the medulla. Severe occlusions result in renal infarcts and papillary necrosis.¹¹

Glomerular hypoxia stimulates prostaglandin release and

Manifestations

There is a wide-ranging set of renal manifestations seen in SCD patients, from painless hematuria to progressive renal failure. The majority of these symptoms are seen more commonly in SCD patients rather than in those with sickle cell trait. The interesting exception is renal medullary carcinoma, which is more prominent in sickle cell trait.¹ This deadly cancer is often metastatic at presentation, is found in patients younger than 20, and has a male predominance in childhood. It carries a

Diagnosis and early detection

Diagnosis of renal disease secondary to SCD is largely based on observed clinical manifestations. It is primarily a diagnosis of exclusion. Renal biopsy is not typically needed unless there is acute onset of massive proteinuria or unexplained rapidly progressive renal failure. When suspecting SCN, diagnostic workup should begin with urinalysis and quantification of total urinary protein. The overall renal function needs to be assessed.¹¹ This is usually done by creatinine-based GFR

Differential diagnosis

It must be stressed that renal disease seen in a sickle cell patient should not be assumed to be SCN until more common causes have been ruled out. A comprehensive clinical, family, and social history should be obtained in order to formulate a full differential diagnosis. Some of the more common non-SCN causes of renal disease in sickle cell patients include acute tubular necrosis due to chronic ischemia and toxins, membranoproliferative glomerulonephritis due to hepatitis C, obstructive

Treatment

Hematuria is a common complication of SCN and often self-limited in nature. Conservative measures such as bed rest, to prevent dislodging of blood clots, and oral hydration are the preferred treatments. Severe cases have been treated with urine alkalinization, loop diuretics to increase urine flow, and blood transfusion to reduce the hemoglobin S concentration.11, 16 Refractory severe hematuria can be difficult to treat, and though many approaches have been attempted, none has been well

Prognosis

Survival is significantly decreased in sickle cell patients who develop renal failure. A study showed that sickle cell patients diagnosed with ESRD had an average survival rate of about 4 years after starting hemodialysis.⁵ Median survival rates of sickle cell patients with and without renal failure differ drastically at 29 and 51 years, respectively. The mortality risk that renal failure adds to a sickle cell patient is similar to the risk seen in patients who have had a stroke.¹¹ There is

Summary

Among the many systemic complications associated with SCD, the renal system remains one of the most susceptible to a variety of sickle-induced insults. Microthrombotic infarctions of the vasa recta capillaries and extravasation of blood in the medulla are the precipitating factors for a myriad of renal manifestations ranging from simple hematuria to nephrotic range proteinuria and renal failure. Physicians should always be vigilant for signs of any renal complications. Once a suspicion of renal