The management of diabetic neuropathy in CKD

Abstract

A 64-year-old male with a 15-year history of poorly controlled type 2 diabetes and a 10-year history of hypertension and hyperlipidemia had developed multiple diabetes-related complications within the last 5 years. He first developed albuminuria 5 years ago, and over the next several years experienced fairly rapid decline in kidney function, with eGFR of 55 mL/min/1.73m² noted 2 years ago. He was diagnosed with proliferative retinopathy 5 years ago and underwent laser photocoagulation. Four years ago, he noted symptoms of peripheral neuropathy manifested as shooting pain and numbness with loss of light touch, thermal and vibratory sensation in a stocking distribution. Last year he developed a non-healing ulcer on the plantar aspect of his left foot which was complicated with gangrene and resulted in a below-the-knee amputation of the left leg one year ago. He now reports a new onset of weakness, lightheadedness and dizziness on standing that affects his daily activities. He reports lancinating pain in his right lower extremity, worse in the evening. Medications include: neutral protamine Hagedorn insulin twice daily and regular insulin on a sliding scale, metoprolol 50 mg/d, lisinopril 40 mg/d, atorvastatin 80 mg/d, furosemide 40 mg/d and aspirin 81 mg/d. Blood pressure is 127/69 mm Hg with a pulse rate of 96 bpm while supine and 94/50 mmHg with a pulse rate of 102 bpm while standing. Strength is normal but with a complete loss of all sensory modalities to the knee in his remaining limb and up to the wrists in both upper extremities, and he is areflexic. Today's laboratory evaluations show a serum creatinine of 2.8 mg/dl, an estimated GFR (eGFR) of 24 ml/min/1.73m², a hemoglobin A₁c (HbA₁c) of 7.9 % and 2.1 g of urine protein per gram of creatinine. What would be the most appropriate management for this patient?

Figure 1

Proposed paradigm of the mechanisms inducing neurotoxicity in diabetic patients with CKD. Abbreviations: AGE, advanced glycation endproducts; CKD, chronic kidney disease; NF-κB: Nuclear factor kappa B; PARP: poly(ADP-ribose) polymerase; PKC: protein kinase C; PTH, parathyroid hormone; RNS: Reactive nitrogen species; ROS: Reactive oxygen species, GSH: glutathione; GSSG: oxidized glutathione; TCA, tetracylic antidepressant; VEGF: Vascular endothelial growth factor; NADP, nicotinamide adenine dinucleotide phosphate; NADPH, reduced NADP; SDH, sorbitol dehygrogenase; PAI 1, plasminogen activator inhibitor 1. Adapted and reproduced from Edwards et al with permission of Elsevier.