Specifically variants in G1 and G2 of apolipoprotein L1 in the African American have shown increased risk of albuminuria, and hyperfiltration. Environmental
Risk factors for papillary necrosis include analgesics, concomitant cirrhosis, diabetes, pyelonephritis, systemic vasculitis, renal vein thrombosis, and urinary tract obstruction. Diagnosis
Diagnosis is done through the exclusion of other potential causes. These include acute tubular necrosis from chronic ischemia, membranoproliferative glomerulonephropathy from hepatitis C, nephrolithiasis causing obstructive nephropathy, and papillary necrosis which could be caused by pyelonephritis, diabetes mellitus, or from NSAIDs. The use of renal biopsy is not necessary unless there is a sudden onset of large protein excretions or signs of rapidly declining renal function. Urinalysis, microalbumin to creatinine ratio, quantification of urine protein and ultrasound (to exclude obstructive nephropathy and detect papillary necrosis) are methods used to determine renal function. Early signs include abnormally large and distended glomeruli causing hyperfiltration from as young as two years old. Albuminuria has been used for initial diagnosis in children from as young as four years old but significant damage may have already occurred by the time albuminuria has been detected. Creatinine measurements may not always be accurate because while the glomerulus completely filters creatinine, secondary secretion in the proximal tubules is maximally utilized in those with SCD so GFR may appear to be higher than what it actually is. If exhibiting hematuria, a CT scan should be done to exclude medullary carcinoma and due to multiple blood transfusions, serologies of the autoantibody and complement levels of HIV, hepatitis B and C should also be done.
Papillary infarcts, demonstrable radiographically in 50% of patients with sickle trait, lead to an increased risk of bacterial infection in the scarred kidney tissues and functional tubule abnormalities. Other complications include end stage renal disease (ESRD), medullary carcinoma, nephritic syndrome due to concurrent HPV B19 infection (this infection can cause benign self-limiting red cell aplasia). Risk Factors
Genetic
When looking at SCN, the main contributors leading to either a decrease or increase in CKD progression are the type of hemoglobin inheritance, myosin heavy chain 9, and apolipoprotein L1 genes. In those with the HbSS or HbSβ0 (no normal hemoglobin), they exhibit more severe forms of renal dysfunction at a high occurrence rate compared to those with HbSS or HbSβ+ (reduced number of normal hemoglobin). This ties in with the fetal hemoglobin levels (HbF) in that HbF levels are directly proportional to renal protection, and it has been found that in those with HbSS, a greater than 20% elevation in HbF led to no significant loss in renal function. Alpha-thalassemia has also been found to decrease HbS levels where the co-inheritance of alpha gene deletions reduce red blood cells and hemolysis. This inheritance has been shown to protect against hyposthenuria but the effect on other symptoms are unknown. Specifically in the African American population, the inheritance of an S trait and/or a C trait increases the risk of developing ESRD. For myosin heavy chain 9, and apolipoprotein L1, polymorphisms in these genes can contribute to worsening proteinuria but are not specific towards SCD.