RESUMEN
Primary hyperoxaluria type 1 (PH1) is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT. Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian, especially in Chinese. To update the genotypes of PH1 in the Chinese population, we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center, five of whom had delayed diagnosis and failed in kidney transplantation. Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT. Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations. Furthermore, a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees. To the best of our knowledge, 2 novel variants of AGXT, p.Gly41Trp and p.Leu33Met, were first reported. Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT) at a protein level. The systematic review revealed significant population heterogeneity in PH1. In conclusion, new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore, a genotype-phenotype correlation is found in PH1.
Asunto(s)
Pruebas Genéticas , Hiperoxaluria Primaria/genética , Transaminasas/genética , Pueblo Asiatico/genética , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Hiperoxaluria Primaria/sangre , Hiperoxaluria Primaria/patología , Masculino , Mutación , Linaje , Polimorfismo de Nucleótido Simple/genética , Transaminasas/sangre , Población Blanca/genéticaRESUMEN
BACKGROUND: A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage. METHODS: Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices. RESULTS: Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that. CONCLUSIONS: The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.
