Beneficial outcomes of glucagon like peptide-1 agonist therapy in a patient with Bardet Biedl syndrome and kidney transplant

Abstract

Abstract Introduction Bardet Biedl syndrome (BBS) is a rare hereditary disorder characterized by early-onset obesity, metabolic syndrome, type 2 diabetes, hypogonadism, polydactyly and renal failure. There is lack of data on the use of glucagon-like peptide-1 receptor agonist (GLP-1RA) for management of patients with BBS and kidney transplant. Herein, we report our findings on body weight, graft kidney function and metabolic parameters in a patient with BBS and kidney transplant. Clinical Case A 35-year-old man with BBS was referred to our clinic for morbid obesity, diabetes and dyslipidemia. He also had retinitis pigmentosa, acanthosis nigricans, hypertension and hypogonadotropic hypogonadism, but no polydactyly. Due to polycystic kidney disease, the patient underwent cadaveric kidney transplantation ten years ago. He quickly gained weight after starting glucocorticoids following the kidney transplant. Current medical treatment consisted of metformin 1000 mg BID, testosterone 250 mg injection every three weeks, amlodipine 5 mg daily, mycophenolate mofetil 500 mg BID, and cyclosporin 25 mg BID. His body mass index (BMI) was 45 kg/m2, body fat percentage was 41%, waist and hip circumferences were 120 and 125 cm, respectively. On laboratory examination, his fasting plasma glucose and glycated hemoglobin (HbA1c) levels were 140 mg/dL and 7.8%, respectively. A low-density lipoprotein level of 178 mg/dL, a high-density lipoprotein level of 45 mg/dL, and a triglyceride level of 200 mg/dL were found in the lipid profile. His serum creatinine and estimated glomerular filtration rate (eGFR) were 1.9 mg/dL and 66.3 mL/min/1.73 m2, respectively. The initial treatment strategy was lifestyle changes and dietary management which did not result in significant weight loss after 6 months. Following a thorough discussion on medical treatment options with the patient, exenatide was started considering obesity, diabetes and patient preference for affordability. Initial dose of 5 mcg BID was gradually titrated up to 10 mcg BID, with frequent monitoring of his kidney function tests. Over a 6-month period, exenatide treatment resulted in significant weight loss, with a reduction in BMI to 40 kg/m2, body fat percentage to 35%, waist and hip circumferences to 114 and 120 cm, respectively. HbA1c decreased from 7.8% to 6.2%, and eGFR increased from 66.3% to 84.2%. His hypertension, dyslipidemia, and urinary protein: creatinine ratio also significantly improved. He has maintained his weight and glycemic control during further follow up of 10 months. Conclusion Weight management in BBS could be challenging, and kidney transplantation may make it even more difficult. Here we show that GLP-1RA use results in significant weight loss along with improvements in glycemic control, metabolic parameters, and renal function in a patient with BBS and kidney transplant. More data are needed to confirm long term efficacy and safety of GLP-1RA in these patients.