Sickle cell nephropathy
Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease, it causes renal complications as a result of sickling of red blood cells in the microvasculature. The hypertonic and relatively hypoxic environment of the renal medulla, coupled with the slow blood flow in the vasa recta, favors sickling of red blood cells, with resultant local infarction (papillary necrosis). Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.
Also the sickle cell disease in young patients is characterized by renal hyperperfusion, glomerular hypertrophy, and hyperfiltration. Many of these individuals eventually develop a glomerulopathy leading to glomerular proteinuria (present in as many as 30%) and, in some, the nephrotic syndrome. Co-inheritance of microdeletions in the -globin gene ( thalassemia) appear to protect against the development of nephropathy and are associated with lower mean arterial pressure and less proteinuria.
Mild azotemia and hyperuricemia can also develop. Advanced renal failure and uremia occur in 10% of cases. Pathologic examination reveals the typical lesion of "hyperfiltration nephropathy" namely, focal segmental glomerular sclerosis. This finding has led to the suggestion that anemia-induced hyperfiltration in childhood is the principal cause of the adult glomerulopathy. Nephron loss secondary to ischemic injury also contributes to the development of azotemia in these patients.
In addition to the glomerulopathy described above, renal complications of sickle cell disease include cortical infarcts leading to loss of function, persistent hematuria, and perinephric hematomas. Papillary infarcts, demonstrable radiographically in 50% of patients with sickle trait, lead to an increased risk of bacterial infection in the scarred renal tissues and functional tubule abnormalities. Painless gross hematuria occurs with a higher frequency in sickle trait than in sickle cell disease and likely results from infarctive episodes in the renal medulla. Functional tubule abnormalities such as nephrogenic diabetes insipidus result from marked reduction in vasa recta blood flow, combined with ischemic tubule injury. This concentrating defect places these patients at increased risk of dehydration and, hence, sickling crises. The concentrating defect also occurs in individuals with sickle trait. Other tubule defects involve potassium and hydrogen ion excretion, occasionally leading to hyperkalemic metabolic acidosis and a defect in uric acid excretion which, combined with increased purine synthesis in the bone marrow, results in hyperuricemia.
Management of sickle nephropathy is not separate from that of overall patient management. In addition, however, the use of ACE inhibitors has been associated with improvement of the hyperfiltration glomerulopathy. Three-year graft and patient survival in renal transplant recipients with sickle nephropathy is diminished as compared to those with other causes of end-stage renal disease.