When it comes to endothelial dysfunction, there is a correlation between soluble FMS-like tyrosine kinase-1 (sFLT-1) and worsening albuminuria. This is because sFLT-1 prevents the binding of vascular endothelial growth factor (VEGF) to a splice variant of its receptor (VEGFR-1) which induces endothelial dysfunction. This as well as other factors that reduce endothelial function such as stress, hypoxia, inflammation, leads to a production of endothelin-1 and this reduces the bioavailability of nitric oxide and releases reactive oxygen species. This induces widening of inter-podocyte radii and lowers the number of podocytes which increases the amount of albumin that is filtered in the glomerulus and worsens albuminuria. The use of endothelin receptor antagonism could have the potential effect to be renally protective. Presentation
Signs and Symptoms
Microalbuminuria is an early sign of SCN that has a 30-60% of developing in those with sickle cell disease (SCD).Hematuria can appear in a range of severities from painless and minute to excessive and painful. The presence of visible blood in the urine without pain occurs with a higher frequency in sickle trait than in sickle cell disease and likely results from infarctive episodes in the renal medulla. Despite this condition typically being self-limiting, investigation is recommended because of alternate causes such as renal stones, or medullary carcinoma, especially if bleeding is excessive and if also experiencing flank pain.Hyposthenuria is the inability for the kidneys to concentrate urine.
When predicting CKD progression, old age can be a contributor since there is an increase in renal injury and a  decrease in GFR in those over 30 years old. Also albuminuria, GFR, and lactic hydrogenase are used in determining CKD progression. The use of cystatin C may not be clear since while it increases when GFR declines, it has been shown that some people with SCN have similar levels to a healthy individual. Treatment
Lifestyle
Management of sickle nephropathy is not separate from that of overall patient management. Three-year graft and patient survival in kidney transplant recipients with sickle nephropathy is lower when compared to those with other causes of end-stage kidney disease.Certain medications should be avoided because of potential damage to the kidneys or can precipitate secondary complications. Nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen) should be avoided because of the decrease in renal blood flow causing a decrease in GFR as well as causing hemodynamic injury from glomerular hypertension.For hematuria, if mild then bed rest and hydration is sufficient to prevent the breakage of clots and to maintain a healthy blood volume, and possibly antibiotics or analgesics if necessary. If severe, then it is recommended to do an ultrasound to see if there is a complication such as renal infarcts or papillary necrosis.