Are GLP-1 Receptor Analogues Safe in Patients with CKD?

Introduction: We present three cases where CKD patients received GLP-1 analogues. All three are females but have varying manifestations of renal disease i.e. transplant, CKD and ongoing RRT. All patients took Tirzepatide, which is a long-acting GIP (glucose-dependent insulinotropic polypeptide) & GLP-1 receptor agonist. Case Description: 1. 48F with CKD-5, secondary to T2DM and Alport’s disease, on peritoneal dialysis, started GLP-1 analogues for better glycaemic control and weight loss. Baseline Creatinine was 572 prior to treatment and was noted to rise to 1100. The medication dosage was decreased and then discontinued however, her renal clearance has not improved and she has been switched to Haemodialysis. 2. 65F with CKD-4, secondary to diabetes, started GLP-1 analogues as part of her diabetes management. Remained on the medication for 10 weeks with up titration. Renal function declined from a baseline eGFR of 20 to an eGFR of 16. This improved to 21 after four weeks of discontinuing the medication. 3. 52F with T2DM, obesity and a well-functioning renal transplant (eGFR 46) used a single dose of GLP-1 analogues. Renal function started to decline leading to further investigations due to concerns of rejection. She was started on high dose steroids and Mycophenolate however; transplant kidney biopsy revealed no signs of rejection. eGFR declined to 16 and has not recovered. She has been restarted on haemodialysis. Discussion: GLP-1 analogues have shown benefits in the management of diabetes & obesity. Overall, they can lead to improved kidney health in the long-term through improved glycaemic control & obesity, however, there is limited evidence of using GLP-1 analogues or dual GIP & GLP-1 receptor agonists with pre-existing CKD. In these cases, the kidney function declined significantly around the same time the medication was started and in one case the renal function improved following discontinuation. This leads us to question the safety of these medications in CKD. Renal Functions as noted before, during and after Tirzepatide - Baseline Peak Cr/eGFR drop Renal function post cessation of medication Case 1 Cr 572, eGFR 7 Cr 1223, eGFR 3 Cr 1184, eGFR 3 Case 2 Cr 219, eGFR 20 eGFR 16 eGFR 21 Case 3 Cr 118, eGFR 46 Cr 564, eGFR 7 Cr 617, eGFR 6