[Genotype-phenotype correlation in ADPKD: a possible role for NGAL?]

Area of Science:

• Nephrology
• Genetics
• Biomarkers

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is a leading genetic cause of chronic kidney disease (CKD).
• Inter- and intra-familial variability in ADPKD suggests influence from genetic heterogeneity and modifier genes.
• Neutrophil gelatinase-associated lipocalin (NGAL) is a potential biomarker in CKD.

Purpose of the Study:

• To investigate plasma NGAL levels in ADPKD patients.
• To explore the correlation between NGAL and genotype-phenotype characteristics in ADPKD.
• To assess NGAL as a biomarker in relation to kidney function and disease progression.

Main Methods:

• Plasma NGAL, creatinine, urea, and cystatin C (CysC) were measured in ADPKD patients on dialysis (PKD1_TRS), affected relatives (PKD1_AMB), wild-type (WT) relatives (PKD1_WT), and healthy controls (CTR).
• Patients with PKD2 mutations and CKD stage II-III were also included.
• Estimated glomerular filtration rate (eGFR) was calculated using the MDRD formula.

Main Results:

• Plasma NGAL levels were significantly higher in PKD1_TRS patients compared to all other groups.
• NGAL levels increased progressively from PKD1_WT to PKD1_AMB to PKD1_TRS.
• NGAL showed strong positive correlations with CysC, creatinine, and urea, and a strong inverse correlation with eGFR.

Conclusions:

• This study is the first to evaluate plasma NGAL in the context of ADPKD genotype-phenotype correlation.
• Elevated NGAL levels in ADPKD patients, especially those on renal replacement therapy, suggest its role as a marker of disease severity.
• NGAL closely correlates with renal function markers like CysC and eGFR, supporting its utility in monitoring ADPKD progression.