The other contributor is glomerular hypoxia in that it releases local prostaglandins: a potent vasodilator, and nitric oxide synthase which increases renal blood flow and therefore GFR. Hemolysis also plays a role in hyperfiltration through the release of heme oxygenase-1 (HO-1) in response to kidney injury and this enzyme converts heme to biliverdin with the by-product being carbon monoxide. Biliverdin and carbon monoxide both act as antioxidants and carbon monoxide also acts as a vasorelaxant, and this causes an increase in GFR. A consistent increase in GFR can lead to proteinuria, glomerulosclerosis, and can eventually worsen progressive chronic kidney disease (CKD).Albuminuria is caused by microvascular damage in the kidneys, hemolysis and endothelial dysfunction. From the increased GFR and the ischemic injury caused by the polymerization of sickle cells, scar tissue develops in the glomeruli which reduces the ability of the glomerulus to properly filter proteins leading to proteinuria. The chronic hemolysis causes the release of iron and free hemoglobin in the kidneys. The iron builds up and leaves deposits in the kidneys, and this causes the overproduction of mesangial cells eventually leading to interstitial and glomerular fibrosis. The free plasma hemoglobin contains cytotoxic heme groups which damage renal tubular epithelial cells and the hemoglobin ends up in the filtrate causing hemoglobinuria. Though the hemoglobin can be reabsorbed in the proximal tubules through binding cubilin and megalin, in doing so it competes with albumin, so the build up of hemoglobin in the filtrate reduces albumin resorption which can worsen albuminuria.
IV iron therapy is recommended if not receiving the necessary iron from blood transfusions but the dosing is unclear.Diuretics are generally not used because of the decrease in blood volume which can cause a person with SCD to have a sickle cell crisis but it can help treat circulatory overload; a condition caused from blood transfusions where there is too much fluid in the circulatory system. Loop diuretics (furosemide) have also been used in treating severe hematuria by increasing urine flow. == References ==