*2.2.10. Sickle cell nephropathy and acute kidney injury*

The prevalence of acute kidney injury (AKI) in children with SCD presenting to the hospital emergency room may be as high as 17% [89], AKI is underreported in pediatric SCD patients. In adults, AKI is reported in 4–10% of patients, and in up to 14% of adults with acute chest syndrome. AKI in SCD may also reflect the frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) to treat painful crises in this patient population [52]. A recent retrospective analysis reported 8% of AKI in 149 pediatric patients admitted for acute chest syndrome using the Kidney Disease Improving Global Outcomes (KDIGO) and higher with increased hospital length of stay [90]. The true incidence of AKI in pediatric SCD patients may be underestimated in retrospective studies [89, 90]. In addition, serum creatinine may be an inaccurate marker of renal function in SCD due to the relatively high proximal tubular secretion of creatinine found in this population [91]. Interestingly, a recent adult study showed that even in patients with a normal creatinine level during a pain crisis, acute tubular injury likely occurs, as evidenced by a more than twofold rise in urinary neutrophil gelatinase-associated lipoprotein excretion [92]. NSAID use is common in children with SCD [93], without evidence to support its benefit compared to other less nephrotoxic options. Similarly, the use of non-steroid anti-inflammatory agents (NSAIDS) in children with SCD hospitalized for various indications, including dehydration due to gastroenteritis, was associated with a significant increase in the incidence of AKI [94, 95]. Therefore hemodynamic changes may increase the risk of AKI secondary to NSAIDs, Another contributing factor includes potential toxic tubular effects of free hemoglobin during a sickle crisis. Some SCD patients with CYP2C9 allele variants that alter NSAID metabolism may be at increased risk of toxicity. During vaso-occlusive pain crises and acute chest syndrome, the risk of AKI is increased by the drop in hemoglobin leading to hypoxic-ischemic events, hemolysis or inflammation. In murine SCD models, brief episodes of hypoxic-ischemic events produce profound acute renal injury [36, 96]. The murine model of SCD has shown that an increase in hemolysis or exposure to excess cell-free hemoglobin can also lead to renal injury [97].
