**3.1 Diabetic patients with chronic kidney disease and end-stage renal disease**

Chronic kidney disease (CKD) is clinically defined by the presence of persistent albuminuria (albumin-to-creatinine ratio ≥ 30 mg/g for at least 3 months) regardless of etiology [73, 74]. It is estimated that about 40% of patients with DKD are expected to develop CKD at a point in their life [75]. The progression of CKD to end-stage renal disease (ESRD; the final stage of CKD) is higher in diabetic patients compared to their nondiabetic counterpart, so as is the mortality rate of these patients with DFU [76]. Calciphylaxis, uremic pruritus and nephrogenic systemic fibrosis are skin disorders that increase the risk of DFU development in patients with DKD [77–79]. Calciphylaxis, for example, presents with painful skin lesions which progress into a necrotic nonhealing skin ulcer and occasionally, gangrene in ESRD patients. It is a rare and life-threatening complication in which calcium accumulates in small blood vessels of the skin, occurring in about 1% of ESRD patients annually [78, 80]. Although its exact pathophysiology remains unclear, some studies suggest that abnormal bone and mineral metabolism, hyperparathyroidism, and vitamin D therapy contribute to the development of this disorder [81, 82]. Given that the most common clinical presentation of calciphylaxis is nonhealing lower extremity ulcers, its timely identification by relevant healthcare professionals is critical [83, 84].
