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Skin problems in chronic kidney disease

Abstract

Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a κ-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking.

Key Points

  • The treatment of uremic pruritus in patients with chronic kidney disease (CKD) is a difficult process of trial and error. Skin emollients, topical capsaicin and ultraviolet B phototherapy remain the first-line therapies, and systemic therapies such as gabapentin, activated charcoal and nalfurafine are reserved for therapy-resistant forms of uremic pruritus

  • The appearance—on the abdomen or other regions containing large amounts of subcutaneous fat—of livedo-reticularis-like skin lesions that turn into painful subcutaneous plaques or nodules, should raise clinical suspicion of calcific uremic arteriolopathy in a patient with CKD, particularly in the presence of additional risk factors such as obesity, diabetes, female sex and coumarin anticoagulation

  • The optimal treatment of calcific uremic arteriolopathy includes prompt and simultaneous initiation of aggressive wound care, antibiotics, optimization of dialysis therapy and rapid control of calcium and phosphate balance and secondary hyperparathyroidism; sodium thiosulfate and bisphosphonates can be administered concurrently in severe cases

  • Nephrogenic systemic fibrosis is highly suspected in a patient with CKD who has been exposed to gadolinium-based contrast agents and complains of painful tightening and swelling of the skin of the lower or upper extremities and has red or hyperpigmented skin plaques or nodules that become increasingly indurated

  • For patients with stages 4 and 5 CKD who require contrast-enhanced imaging, low-osmolar or iso-osmolar iodine-based contrast agents should be considered as an alternative to gadolinium-based contrast; if administration of gadolinium is absolutely necessary, use of low volumes of the more stable macrocyclic, ionic types of gadolinium-based contrast agent is advised

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Figure 1: Step-up therapeutic approach for uremic pruritus in a patient with chronic kidney disease.
Figure 2: Calcific uremic arteriolopathy in a 48-year-old female patient on hemodialysis with painful abdominal subcutaneous purpuric plaques and nodules and the start of necrotic ulcerations.
Figure 3: Histological skin lesions of calcific uremic arteriolopathy.
Figure 4: Calcific uremic arteriolopathy of the abdomen in a 44-year old male patient on hemodialysis.
Figure 5: Nephrogenic systemic fibrosis in a 56-year-old patient.
Figure 6: Typical histology of skin lesions associated with nephrogenic systemic fibrosis.
Figure 7: Porphyria cutanea tarda in a 50-year-old male patient on hemodialysis.

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Acknowledgements

The author would like to thank Professor Dr Evelyne Lerut for providing the histology microphotographs and Dr Kathleen Claes for her assistance in illustrating the clinical cases. Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Kuypers, D. Skin problems in chronic kidney disease. Nat Rev Nephrol 5, 157–170 (2009). https://doi.org/10.1038/ncpneph1040

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