IMPACT OF CALORIC RESTRICTION IN PATIENTS WITH RAPIDLY PROGRESSIVE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A RANDOMIZED CLINICAL TRIAL

• Grant number: 16/20089-4
• Support Opportunities: Scholarships abroad - Research
• Start date: September 23, 2017
• End date: September 22, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Auxiliadora Martins
• Grantee: Maria Auxiliadora Martins
• Host Investigator: Eduardo Nunes Chini
• Host Institution: Fundação de Apoio ao Ensino, Pesquisa e Assistência (FAEPA). Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Institution abroad: Mayo Clinic, Minnesota, United States

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations to PKD1 or PKD2. It is the fourth most common cause of end-stage renal disease (ESRD) and accounts for 5%, 10% and 11% of patients on renal replacement therapy in the United States, European Union and Australia. It is characterized by relentless development of kidney cysts, hypertension, and eventually ESRD. Despite recent advances in understanding its pathogenesis, there is no approved specific therapy in the United States and treatment is largely supportive. Suppression of vasopressin by enhanced hydration is thought to be beneficial4 and high dietary salt has been associated with faster kidney growth and renal function decline. The Aim of this application is to conduct a controlled, unblinded RCT comparing mild CR to a control diet in patients with rapidly progressive ADPKD, under conditions of standardized hydration and sodium intake, to determine whether it slows the rate of growth of the kidneys (primary endpoint), is well tolerated and safe, lowers levels of IGF-1 in serum and the excretion of inflammation (MCP-1) and fibrosis (TGF-²) biomarkers in urine, improves kidney texture, slows the decline of GFR and the rate of growth of the liver, and improves the quality of life. This RCT is likely to provide novel and important information on a potentially safe, effective and inexpensive therapy for ADPKD.