Dados do Trabalho

Título

ACE activity and its expression as a hypertension biomarker in the urine of pediatric renal transplant recipients.

Introdução

Pediatric hypertension is a risk factor for hypertension in adults with prevalence ~3,5%.Renin Angiotensin System controls cardiovascular and renal functions. Angiotensin Converting Enzyme (ACE) has isoforms: somatic N- and C- domain (130-190 kDa) and testicular C-domain (90-110 kDa). Casarini et al. described the N-domain isoform of 90kDa in urine of hypertensive humans as a possible hypertension biomarker.

Objetivo

Analyze expression and activity of ACE isoforms in urine of pediatric renal transplant recipients before and after transplantation and urine of donor, to verify the 90 kDa isoform transmission and correlating with hypertension.

Método

30 pediatric renal transplant recipients with living donors; ACE activity was performed before, 1, 3, 6 months post transplantation using ZPhe-HL and HHL as substrates and its ratio. Western blotting analysis to evaluate ACE isoforms (190,90 and 65kDa).

Resultados e Conclusões

69% had pre-transplant hypertension, 85.7% family history. After 6 months 25% remained hypertensive. From the pre-transplant until the sixth month after, ACE activity was reduced. In the linear regression model with random effects between ACE activity and various variables, including pre-transplantation for ZPhe-HL remained significant time, and uropathy with higher activity of ACE (0.023 mU/mg creatinine more); with HHL, time, uropathy and for weight, reduction of ACE activity (0.00038 mU/mg creatinine at 1 kg increase). At post-transplant time and weight remained significant with ZPhe-HL. For HHL, uropathy, proteinuria (0.010 mU/mg creatinine more) and weight. Recipients before transplantation had higher urinary ACE activity when compared to controls. Western blotting showed that all recipients without ACE 90KDa when received a kidney from the donor that had this isoform, started to express it. Increased ACE activity in uropathies may be associated with renal injury or intra-renal production. Proteinuria, a marker of renal injury, can be associated with increase on ACE activity. With nutritional recovery and a healthy kidney, recipients can reverse the degree of renal damage and decrease ACE production. Western blotting analysis demonstrated that 100% of the recipients without the pre-transplantation isoform of 90 kDa, whose donors had this isoform, started to express it after transplantation, suggesting a transmission of the biological profile to the recipient.

Palavras Chave

Angiotensin converting enzyme, hypertension, chronic kidney disease, pediatric kidney transplantation

Área

ÁREA CLÍNICA