Comparison of Efficacy and Safety of Albumin Versus Fresh Frozen Plasma in Managing Diuretic Resistant Edema in Children With Idiopathic Nephrotic Syndrome.

Edema is a major component of nephrotic syndrome (NS), defined by Kidney Disease Improving Global Outcomes (KDIGO) guidelines is, urine protein/creatinine ratio ≥ 2 mg/mg, and hypoalbuminemia ≤ 2.5 g/dl). Nephrotic syndrome is one of the most common pediatric renal diseases with an annual incidence of 1.2-16.9/100,000 children. It is characterized by edema, massive proteinuria (>40 mg/m2/h), and hypoalbuminemia (serum albumin <3 g/dL)(Kallash \& Mahan, 2021). Edema affects the quality of life of pediatric patients with NS, even when it is only mild to moderate in severity, and this is especially seen in patients with steroid resistant NS. Albumin infusions can be a highly effective method to treat edema in patients with NS. Edema can develop in nephrotic syndrome, chronic kidney disease (CKD), heart failure, and liver cirrhosis. Usually, the patients with edema respond to dietary sodium restriction in combination with a loop diuretic. However, some patients become resistant to diuretics. Diuretic resistance is defined as the failure to achieve the therapeutically desired reduction in edema even when a maximal dose of diuretic is employed (Hoorn \& Ellison, 2017).

The causes of diuretic resistance include poor adherence to drug therapy or diet, pharmacokinetic issues, and compensatory sodium reabsorption. Impaired tubular secretion of diuretics is a common cause of diuretic resistance. The cornerstone of managing diuretic resistance is breaking the pathophysiological cycle (Bell \& Mandalia, 2022). First-line management of edema involves sodium restriction and oral diuretics, most commonly loop diuretics like furosemide. However, a state of diuretic resistance often develops. This resistance is primarily due to two reasons reduced delivery: The hypoalbuminemia reduces the transport of furosemide to its site of action in the nephron, as the drug is highly protein-bound. Compensatory mechanisms are the intense activation of renin-angiotensin-aldosterone system and other neurohormonal pathways counteracts the natriuretic effect of diuretics, leading to rebound sodium retention (El-Halaby et al., 2022). Fresh Frozen Plasma (FFP) is a viable, cost-effective alternative to intravenous albumin for managing diuretic resistant edema in children with idiopathic nephrotic syndrome (INS) but it may require more infusions than albumin. FFP cost half than albumin and same duration required to reduce edema but with double number of infusion and it is safe in pediatric patients with NS presenting with moderate to severe edema. The cost-effectiveness may place FFP as a better choice especially in developing countries of the world (Al Mamun et al., 2015).

Due to availability of limited local data, the aim of this randomized control trial study is to evaluate the efficacy of albumin versus fresh frozen plasma in managing diuretic resistant edema in children with idiopathic nephrotic syndrome in children's hospital and institute of child health Multan Punjab Pakistan, so that the overall morbidity and mortality due to NS can be reduced