GLUTARİK ASİDÜRİ TİP 1 HASTALARINDA BÖBREK İŞLEVLERİNİN İNCELENMESİ

Abstract

Glutaric aciduria type 1 (GA1) is an inherited metabolic disorder. It results from the deficiency of glutaryl-CoA dehydrogenase (GCDH) enzyme. The disease primarily affects the nervous system. In recent years, it has been demonstrated that renal damage may accompany GA1, and kidney functions can deteriorate with age. However, there is limited information on when this involvement begins, which kidney regions are affected, and which examinations should be performed when in order to assess kidney involvement in clinical practice. 16 children and adult patients diagnosed with GA1 and followed at Hacettepe University Ihsan Dogramaci Children's Hospital Department of Pediatric Metabolic Diseases were included in the study. Demographic and clinical data were collected from hospital records. In addition to routine examinations, the study included the evaluation of blood pressure, renal ultrasonography, Doppler ultrasonography, serum cystatin C levels, and urinary biomarkers including β2-microglobulin (B2MG), Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and Uromodulin (UMOD). A control group consisting of two healthy individuals matched for age and gender for each GA1 patient was also included. Serum creatinine and cystatin C levels both were measured in the patients to estimate the glomerular filtration rate (eGFR). The mean eGFR based on creatinine was 118.93±17.83 and the eGFR based on cystatin C values was 95.25±20.52 ml/min/1.73 m2. The patients' urine protein to creatinine ratios [0.16 (0.09-0.22) and 0.07 (0.05-0.10)] and B2MG to creatinine ratios [122.39 (67.40-200.05) and 52.12 (31.03-103.43)] were significantly higher compared to the control group (p≤0.001). When evaluated according to eGFR based on cystatin C, eight patients had eGFR above 90 ml/min/1,73 m², while seven patients had eGFR below 90 ml/min/1,73 m². Right and left renal vein flow velocities were lower in patients with eGFR<90, while weight for height, serum alkalene phosphatase, and phosphorus values were higher. Urinary protein biomarkers did not significantly differ between the two groups. Renal involvement can be observed in GA1, even at a young age. Cystatin C measurements are mandatory in renal surveillance because creatinine-based eGFR is misleading. Renal dysfunction is probably mainly tubular in origin. Urinary B2MG and renal vein flow velocities should be explored further as biomarkers.