#4542 L-ARGININE-NITRIC OXIDE MOLECULAR PATHWAY IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
نویسندگان
چکیده
Abstract Background and Aims Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited, complex disease, cystogenesis phenotypic changes in this disorder being not yet fully understood. Recently, arginine, important for renal cells metabolism, was proved to play role ADPKD physiopathology (1). The inability of recycle or synthesize intracellular arginine through the urea cycle defined as auxotrophy. Arginine auxotrophy induces cell hyperproliferation, cysts formation (2). We aimed explore L-Arginine (Arg) - Nitric Oxide (NO) molecular pathway ADPKD, a multisystemic, auxotrophe disease. Method developed prospective, case control study, Carol Davila Clinical Hospital Nephrology, Bucharest, Romania. study included group 62 subjects with (mean age -54.3years old, men:women 34:28, 1A 1B Mayo risk classes) 37 healthy subjects, similar sex, mean age. diagnosis based on familial history, clinical exam CT MRI scan. excluded from that presented other organs except kidney, eGFR<60mL/min/1.73mp, history hematuria, infection, urinary tract lithiasis, unstable blood pressure hypertensive treatment less than 6 months; metabolic disorders (carbamoyl phosphate synthase 1 N-acetyl glutamate deficiencies, lack ornithine transcarbamilase, hyperargininemia, phenylketonuria). Laboratory tests: serum level enzymatic activity arginase 2 (ARG-2) nitric oxide inducible (NOS-2), levels stable metabolites (nitrate, direct nitrite, total nitrite), endogenous inhibitors synthesis (Asymmetric Dimethylarginine -ADMA, Symmetric SDMA). Results In patients, had statistically significant lower compared (Table 1). principal enzymes metabolizes – synthase, respectively were higher when ARG2/Arg, NOS2/Arg, Nitrite/Arg, Nitrate/Arg, ADMA/Arg SDMA/Arg ratios overexpressed group. Conclusion kidney auxotrophic arginine. phenotype low progression (1A Mayo) by alteration L-Arginine-NO pathway, reduction systemic moderately increased activities ARG2 NOS2, bioactivity NO. Exploring reprogramming related L-Arg-NO pathways disturbances could offer more information about physiopathology.
منابع مشابه
Autosomal dominant polycystic kidney disease.
The lack of reliable data on frequency, age of onset, survival, spontaneous mutation rate and prognosis in autosomal dominant polycystic kidney disease is a continual source of frustration to physicians involved in counselling patients and their relatives. The only major study to address all of these issues in a defined population was presented by Dalgaard as a 251-page doctoral thesis in 1957 ...
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ژورنال
عنوان ژورنال: Nephrology Dialysis Transplantation
سال: 2023
ISSN: ['1460-2385', '0931-0509']
DOI: https://doi.org/10.1093/ndt/gfad063c_4542