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

Official title

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

Overview

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). 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. 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. The main purpose of the study is to compare the albumin versus fresh frozen plasma in managing diuretic resistant edema in children with idiopathic nephrotic syndrome The duration of study is six months after approval of synopsis. The study will be conducted in indoor Department of pediatric nephrology department, The Children's Hospital \& the Institute of Child Health, Multan. A sample size of 56 patients will be included in the study. Informed consent will be taken from included patients. The Group-A study population will be with intravenous albumin, 1 gm/kg/day in single daily dose over 4 hours followed by intravenous furosemide 1 mg/kg/day. Salt poor 20% human albumin will be administered which will be osmotically equivalent to 200ml of plasma. The Group-B study population will be with intravenous FFP 15ml/kg/day over 2 hours followed by intravenous furosemide 1 mg/kg. Primary outcomes will be response to treatment in form of resolution of clinical signs within 72 hours of treatment. Secondary outcomes will be duration of hospital stay, mortality, complication of treatment, complications of disease and hearing assessment. Data will be analyzed through SPSS v23. For quantitative variables, the mean standard deviation will be calculated and for qualitative variables, frequency and percentage will be calculated. This study will provide a better opportunity to study Albumin versus fresh frozen plasma in managing diuretic resistant edema in children with idiopathic nephrotic syndrome in The Children's Hospital \& the Institute of Child Health, Multan

Detailed description

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

Interventions

• Biological Human Albumin 20%
  The Group-A study population will be given intravenous albumin, 1 gm/kg/day over 4 hours in single daily dose followed by intravenous furosemide 1 mg/kg/day. Salt poor 20% human albumin will be administered which will be osmotically equivalent to 200ml of plasma. The Group-B study population will be given intravenous FFP 15ml/kg/day over 2 hours followed by intravenous furosemide 1 mg/kg
• Biological Fresh Frozen Plasma
  The Group-A study population will be given intravenous albumin, 1 gm/kg/day over 4 hours in single daily dose followed by intravenous furosemide 1 mg/kg/day. Salt poor 20% human albumin will be administered which will be osmotically equivalent to 200ml of plasma. The Group-B study population will be given intravenous FFP 15ml/kg/day over 2 hours followed by intravenous furosemide 1 mg/kg

Primary outcome measures

• time to resolution of edema [Time frame: baselines to 72 hours post intervention]
• Primary outcomes will be response to treatment in form of resolution of clinical signs within 24 to 48 hours of treatment [Time frame: 24 to 48 hours]

Secondary outcome measures (1)

• change in serum albumin level [Time frame: baselines to 72 hours post intervention]

Eligibility criteria

Inclusion criteria

• Children diagnosed with an idiopathic nephrotic syndrome and diuretic resistant as per the definition • Children of either gender. • Children of 2-12 years of age

Exclusion criteria

• • Patients with secondary nephrotic syndrome/heart failure/hepatic dysfunction/severe renal impairment • Children with severe sepsis/hemodynamically unstable. • Children who had recent exchange transfusion • Parents refused to follow up

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Kallash, M., & Maha

Identifiers

NCT: NCT07685093 · CHCMultan

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗