*4.1.6. Interleukin-18*

Interleukin-18 (IL-18) represents a proinflammatory cytokine that might worsen the degree of AKI. Animal studies have shown that IL-18 is induced in the proximal tubule and detectable in the urine following ischemic AKI. Numerous pediatric studies have proved that urine IL-18 obtained 6- to 12-h post-CPB moderately predicts AKI [128–131]. Cerqueira et al. [131] performed a cross-sectional study composed of 45 SCA patients. They founded that IL-18 levels were correlated closely with markers of hemolysis, endothelial dysfunction and others cytokines levels. These findings suggest probable influences of IL-18 in the pathophysiology of vascular occlusion in SCA. In a recent article published by Duarte et al. [132], the author demonstrated that IL18 is associated with diastolic function in SCD patients, and may be involved in the pathogenesis of the disease. Genetic polymorphisms within the IL-18 gene regions are also associated with diastolic function in SCD, likely by affecting expression levels of the genes [132].

*4.2.2. Urinary excretion of uromodulin*

**5. Current treatment**

**5.1. Treatment of hematuria**

**5.2. Treatment of proteinuria**

for the early determination of renal damage in SCD patients.

be necessary in order to reduce HbS level and sickling [146].

caproic acid (EACA) to promote clotting [147].

mia, the latter condition often present in SCD patients.

Urinary excretion of uromodulin (UMOD), also known as Tamm-Horsfall Protein (THP), is the most abundant protein excreted in urine. It is a glycoprotein that is expressed in the thick ascending limb (TAL) of the loop of Henle [140–143]. It has also several roles in salt transport in the tubules, in the innate immunity and in the protection against kidney stones [144]. Recently, UMOD has been studied as a marker of acute renal injury both in mouse models of ischemia-reperfusion injury and in studies conducted in adult and pediatric patients prior to CPB [140, 143, 145]. These encouraging results suggest the possibility of studying UMOD also

Sickle Cell Nephropathy: Current Understanding of the Presentation, Diagnostic and…

http://dx.doi.org/10.5772/intechopen.76588

169

The treatment of renal complication in SCD patients should include an adequate fluid intake in order to avoid dehydration due to hyposthenuria. The chronic use of drugs toxic to the kidneys, such as non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided due to the potential for adverse hemodynamic-related renal function deterioration, precipitation of papillary necrosis, and the development of NSAID-associated interstitial nephritis and glomerulonephropathies.

Hematuria in SCD is typically self-limited. Patients with hematuria should be advised to maintain a high urine output by oral hydration and remain at rest. However, in cases of massive hematuria, a high urine output should be maintained with combination of isotonic fluids and loop diuretics, and adopt measures to alkalinize urine, with sodium bicarbonate or acetazolamide. These measures modify the acid and hypertonic environment of the medullar region, which favors erythrocyte dehydration, HbS concentration and its polymerization [80]. Patients are advised to maintain a urinary volume of 2–4 L/day. Also blood transfusion may

In cases of refractory hematuria, high doses of oral urea may be required to achieve blood urea nitrogen levels greater than 100 mg/dL, or treatment with vasopressin or epsilon-amino-

The benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARB) in slowing kidney disease progression in many situations are well-known. Improving nocturia has been reported to be an additional beneficial effect of ACE, presumably as a result of reduction in GFR [148]. A recent Cochrane database review, in 2015, reported the potential for reduction in albuminuria and proteinuria with the use of captopril in patients with SCD compared with those without the disease [148]. However, the administration of ACE and ARB should be carried out carefully due to the risk of hypotension and hyperkale-

The use of hydroxyurea (HU) has been suggested to reduce proteinuria and hyperfiltration as suggested in one prospective study consisting of 26 patients with SCD. However, no
