Question: How is wound healing affected in the person with chronic kidney disease?

Answer:  The rise in the incidence and prevalence of patients with wounds can be attributed to the increase in patients needing acute care, long-term care, and home care, as well as those with uncontrolled diabetes and nutritional impairment. Approximately 5 million individuals in the United States have some type of chronic nonhealing wound often associated with inadequate blood flow (Hall & Schumann, 2001). While there are numerous wound care topical treatments, a thorough understanding of wound healing will guide decision making. This article will briefly review the wound healing process and the risk factors that the patient with chronic kidney disease (CKD) may have that can affect wound healing.

Wound healing is a process that involves a series of complex events that starts with the injury and ends with wound closure. To understand how wound healing is affected in the person with kidney disease, the phases of wound healing will be reviewed.

There are two types of wounds: those with loss of tissue and those without. Partial thickness wounds are shallow wounds involving loss of the epidermis (top layer) and possible partial loss of the dermis. These wounds heal by regeneration because the epidermis can regenerate. A clean surgical incision or an abrasion is an example of a wound with little tissue loss. The skin edges approximate and healing occurs quickly; the wound is resurfaced between day 4 and 7 (Waldrop & Doherty, 2000). In contrast, a wound involving loss of tissue heals by secondary intention. These full thickness wounds extend through the epidermis into the dermis and heal by scar tissue formation.

Partial Thickness Wound Repair
The phases of partial thickness wound repair include the inflammatory response, epithelial proliferation and migration, and re-establishment of the epidermal layers. The inflammatory response is triggered by tissue trauma, causing redness and swelling to the area with a moderate amount of serous exudate. This response is generally limited to 24 hours post-wounding. Epithelial cells begin to migrate across the wound bed soon after the wound occurs. The epithelial cells begin to proliferate, providing new cells to replace the lost cells. Epithelial proliferation and migration starts at both the wound edges and the epidermal cells lining the epidermal appendages allowing for quick resurfacing. New epithelium is only a few cells thick and must undergo re-establishment of the epidermal layers. The cells slowly re-establish normal thickness and appear as dry pink tissue.

Full Thickness Wound Repair
The three phases of full thickness repair include: inflammatory, proliferative, and remodeling. The inflammatory phase begins within minutes of the injury and lasts approximately 3 days. Hemostasis causes blood vessels to constrict and platelets to gather to stop bleeding. Clots form a fibrin matrix that will provide a framework for cellular repair. Damaged tissue and mast cells secrete histamine, resulting in vasodilatation of surrounding capillaries and exudation of serum and white blood cells into damaged tissues. This results in localized redness, edema, and warmth. Leukocytes reach the wound within a few hours. The primary acting white blood cell is the neutrophil, which begins to ingest bacteria and small debris. The second important leukocyte is the monocyte, which transforms into macrophages. The macrophages are the “garbage cells” that clean a wound of bacteria, dead cells, and debris. Macrophages continue the process of clearing the wound of debris and release growth factors that attract fibroblasts, the cells that synthesize collagen (connective tissue). Collagen can be found as early as the second day and is the main component of scar tissue. In a clean wound, the inflammatory phase accomplishes control of bleeding and the establishment of a clean wound bed. The inflammatory phase is prolonged if too little inflammation occurs, as in debilitating kidney disease or after administration of steroids. Too much inflammation also prolongs healing because arriving cells compete for available nutrients.

With the appearance of new blood vessels, the proliferative phase begins and lasts from 3 to 24 days. The main activities in this phase include the filling of the wound with granulation tissue, contraction, and re-surfacing of the wound by epithelialization. Fibroblasts are present in this phase and are the cells that synthesize collagen, providing the matrix for granulation. Collagen mixes with the granulation tissue, and this matrix will support the re-epithelialization and provide strength and structural integrity. During this period, the wound contracts to reduce the area that requires healing. Lastly, the epithelial cells migrate from the wound edges to resurface. In a clean wound, in  the proliferative phase, the vascular bed re-establishes (granulation tissue), the area is filled with replacement tissue (collagen, contraction, and granulation tissue), and the surface is repaired (epithelialization). Impairment of healing during this stage usually results from systemic factors such as age, anemia, hypoproteinemia, and zinc deficiency.

Remodeling, the final stage of healing, may take more than a year, depending on the depth and extent of the wound. The collagen scar continues to reorganize and gain strength for several months. However, a healed wound usually does not have the tensile strength of the tissue it replaces. Collagen fibers undergo remodeling or reorganization before assuming their normal appearance. Usually scar tissue contains fewer pigmented cells and has a lighter color than normal skin.

Wound Healing Risk Factors
 
Wound healing is vulnerable to a number of factors that may be present in the person with kidney disease. Diabetes mellitus is an important risk factor for both development of wounds as well as infection and failed healing. Elevated blood glucose levels are associated with significant reduction in phagocytic ability of the white blood cells and diminished wound strength (West & Gimbel, 2000). Wound repair in patients with diabetes is characterized by reduced collagen synthesis and deposition, decreased wound breaking strength, and impaired leukocyte function. Insulin therapy and exogenous growth factors have been shown to increase collagen deposition and improve tensile strength. Many of the adverse effects of diabetes are at least partially related to glycemic control, as well as measures to maximize tissue perfusion and reduce repetitive trauma (Waldrop & Doughty, 2000). Careful monitoring and control of blood glucose can facilitate wound healing.

Hypertension produces changes to blood vessel walls, which can contribute to peripheral arterial disease. Artherosclerotic disease can result in chronic reduction in blood flow to tissues and, in some cases, the development of ulcerations especially in the lower extremities. Wounds in the limbs of persons with artherosclerotic disease can be difficult to heal because of the poor perfusion.

An acute or chronic illness such as kidney disease can compromise cardiovascular function and precipitate hypoxia. Restricted tissue perfusion will delay the phases of wound healing making the patient with a wound susceptible to infection and other wound healing issues. Renal failure and edema increase tissue nutritional needs or diminished flow contributing to tissue hypoxia.

A patient with CKD has a disrupted defense response as manifested by depressed neutrophil function, leucopenia related to complement activation, diminished T and B lymphocyte function, and a reduction in natural killer cell activity (Headley & Wall, 2002). Thus, the inflammatory response to wounding will be altered making the patient with CKD more susceptible to infection.
 
Conclusion

Wound healing in the person with kidney disease can be compromised if the following risk factors are present: diabetes mellitus, hypertension, and artherosclerotic disease as well as restricted perfusion. Each renal patient with a wound should be evaluated for wound healing risk factors, and, if possible, those risk factors should be reduced or corrected. Decreasing or eliminating the risk factors will facilitate each phase of wound healing, decrease the risk of infection, and support the person with a wound to move onto healing.

References
Hall, P., & Schumann, L. (2001). Wound care: Meeting the challenge. Journal of the American Academy of Nurse Practitioners, 13, 258-266.

Headley, C., & Wall, B. (2002), ESRD-Associated cutaneous manifestations in a hemodialysis population. Nephrology Nursing Journal, 29, 525-539.

Waldrop, J.,& Doughty, D. (2000). Wound healing physiology. In R.A. Byrant (Ed.), Acute and chronic wounds: Nursing management (pp. 17-43). St. Louis: Mosby.

West, J.M., & Gimbel, M.L. (2000). Acute surgical and traumatic wound healing. In R.A. Byrant (Ed.), Acute and chronic wounds: Nursing management (pp.  197-203). St. Louis: Mosby.