Acute Allograft Rejection: Definition, Pathophysiology, And Management

The Challenge of Acute Allograft Rejection Following Renal Transplants

In medical practice, despite the induction of immunosuppression and the utilization of highly aggressive immunosuppressive regimens, incidences of acute allograft rejection following renal transplants are several. These incidences pose significant therapeutic and diagnostic challenges to health care providers and result in early mortalities and loss of graft. To add on, acute allograft rejections initiate chronic alloimmune responses and inflammation of the centered airway which predisposes patients to lung allograft dysfunctions that are chronic and bronchiolitis obliterans syndrome which is collectively major sources of mortalities and morbidities following a transplant.

This paper discusses Mrs. T who had received her first renal transplant in 6 weeks’ time and a recent test revealed that she had a creatinine level of 240mmol/L. Nurses have a role in assessing patients and instituting evidence-based interventions to improve health outcomes in clinically unsuspecting patients with acute allograft rejection that have recently undergone a renal transplant. This can be achieved by nurses having a proper understanding of the definition, pathophysiology, and management of acute allograft rejection. Only then can nurses convey the most appropriate health education and develop an effective plan of care for patients with acute allograft rejection.

Generally, there exist three forms of allograft rejection which are; acute, hyperacute and chronic. Acute rejection occurs within the initial 6-12 months following transplantation which is caused primarily by lymphocytes in the thymus (t-cells) (Benzimra, Calligaro & Glanville, 2017).  Unless the suppression of the immune system is achieved usually by the use of drugs, acute allograft rejection tends to occur in nearly all transplants apart from identical twins. Today, acute allograft rejection is still a prevalent issue in kidney transplantations. Generally, there are incidences of 38% within the first year following transplants. Despite the fact that when they occur by themselves they are rarely fatal, the indirect consequences have adverse effects on the outcomes of transplantation (Moreau et al., 2013). Tissues that are highly vascularized such as the liver, lungs, and kidneys host the earliest signs. In most cases, it is easy to identify acute rejection episodes and appropriate treatment offered promptly to prevent the failure of organs. However, when episodes recur, they lead to chronic allograft rejection/ nephropathy.

On the other hand, chronic allograft neuropathy defines the functional loss of transplanted tissues through fibrosis. It is a term used to explain long-term morbidities in recipients who have undergone transplantation and results from several factors including lymphocytes and antibodies (Fletcher, Nankivell & Alexander, 2013). Chronic allograft neuropathy also occurs from hypoperfusion, recurrent disease, and ischemia-reperfusion and infections. However, its diagnosis is often made using a biopsy of a suspected organ with the heart as the only organ that is exempted (Kloc & Ghobrial, 2014). In pediatric recipients of renal transplants, chronic allograft neuropathy is the leading cause of the loss of renal allograft. As outlined by Demetris et.al. (2014), chronic allograft neuropathy has great rates of survival with improvements in immunosuppression. However, opportunistic infections present challenges.

Acute allograft rejection is common during the first initial months following transplantation. However, it may also occur during an allograft’s life. It is mediated by the t-lymphocytes which are present in the circulation and may infiltrate an allograft via the endothelium of a vascular tissue. Following infiltration of a graft with lymphocytes, cytotoxic cells often start to target and kill the cells that function in an allograft (Ingulli, 2013).  Simultaneously, the release of lymphocytes locally tends to attract and stimulate the presence of macrophages to result in damage to tissues through a mechanism that is hypersensitive and delayed. These series of inflammatory and immunologic events results in nonspecific signs and symptoms such as lethargy, fever, pain and a tender graft site. Following kidney transplantation, acute allograft rejection is likely to affect up to 20% of patients in the initial 6 months (Benzimra, Calligaro & Glanville, 2017).  This may be evidenced by the abrupt increase in the concentration of serum creatinine to levels above 30 beyond the baseline.

The Role of Nurses in Assessing and Managing Acute Allograft Rejection

Any transplanted organ may be rejected through primary mediation and activation of alloreactive T cells and cells that present antigens such as dendritic, macrophages and lymphocytes. Primarily, it should be noted that the infiltration of T cells to allograft results in an acute allograft rejection that finally triggers cytotoxic and inflammatory effects (Benzimra, Calligaro & Glanville, 2017).  Should there be a failure to maintain immunosuppression; complex interactions may exist between B cells, T cells, and CD4 cells which may result in chronic allograft neuropathy and other complications.

The initial management of an acute allograft rejection aims at improving clinical outcomes and quality of life by addressing symptoms. Post-op, the overall health status of a patient should be assessed including fluid status and urine output to check for dehydration. Preferably, an input-output fluid chart can be used for this assessment with a urinary catheter in situ (Leblanc et al., 2018).  The patients wound should also be assessed daily to check for signs of poor wound healing and immediately intervene when necessary. The wound should be kept clean to avoid sepsis that would further result in more complications.

Acute rejection is managed by immunosuppressive therapy where a high dose of corticosteroids can be applied in the short term and repeated severally. While focusing on a triple therapy, an anti-proliferative agent and calcineurin inhibitor can be added. Some of the well-known immunosuppressive high-dose corticosteroids include hydrocortisone and prednisolone. Examples of calcineurin include; ciclosporin and tacrolimus (Leblanc et al., 2018). In patients who the use of steroids and calcineurin inhibitors is contraindicated, mTOR inhibitors may be prescribed. They include; everolimus and sirolimus among others. In most common practice, health care providers initiate treatment with intravenous solumedrol for 3 days.

To restore kidney function and prevent the loss of grafts, anti-T cell antibodies may be used and added to the immunosuppressive therapy. Although some are used to prevent rejection, they are still recommended for the initial treatment of acute allograft rejections. Perfect examples of specific antibody-based treatments which may be used include; polyclonal anti-T-cell antibodies and monoclonal anti-CD20 antibodies (Leblanc et al., 2018).  In other instances, similar cases of acute allograft rejection may be managed with blood transfer through photo immune therapy or photopheresis for the purposes of removing molecules in antibodies which are specific to a tissue that was transplanted.

Patients who are about to undergo an organ transplant or have already undergone organ transplant need to be adequately informed of the likelihood of rejection, possible consequences, and available alternatives. Information of rejection often results in a mixture of complex feelings such as guilt, depression, failure, and disappointment. With prior information, the intensity of these feelings may be reduced (Ghadami et. al., 2012). Patients need to also be informed that in case of rejection, a dialysis is still an option in treating kidney failure which results in lives that are more happy and productive. Alternatively, patients can be informed that the chances of re-transplantation are available.

Patients need to be educated on the importance of maintaining a healthy balanced diet and to maintain contact with social and family support systems to prevent chances of developing depression following an allograft rejection (Wang et al., 2017).  It is also mandatory that the patient is informed to look for any danger signs such as; reduced urination, fevers, swelling, flu-like symptoms, weight gain and pain over the site of transplantation and advised to return immediately to the healthcare provider.  Healthcare providers should emphasize on the importance of keeping to the list of medications that were prescribed upon discharge to prevent new drug-drug interactions that may prevent the desired health outcomes (García et al., 2016).  To promote a patient’s understanding, this information has to be delivered in simple language that takes note of cultural competency and aims at attaining effective clinical outcomes. Demonstrations and brochures may be used to ensure that the patient retains and understands essential information.

Area of Practice: Transplantation	Setting: In-patient immediate post-operatively
Patient Assessment	Intervention/Patient Management	Rationale
Overall Health Status -take Blood Pressure -take Respiratory rate -Measure Temperature -Measure pulse rate  -assess for the patient’s GCS score -measure oxygen saturation	-high blood pressures should cautiously be managed with anti-hypertensives such as diuretics, beta blockers or calcium channel blockers.	-following a renal transplant, hypertension is a common complication that may result from fluid overload, renal artery stenosis or rejection(Reyna-Sepúlveda et al., 2017). It may also be as a side effect of anesthesia medications used during surgery.
-High temperatures should be relieved with antipyretics	-Early complications of rejection in renal transplant patients presents with warning temperatures of above 380c (Benzimra, Calligaro & Glanville, 2017).  It may also be a sign of wound infection.
-oxygen administration through face and mask. -administration of diuretics and morphine -nurse initiated breathing techniques.	-Pulmonary edema is a common complication in patients who have just undergone kidney transplant that leads to shortness of breath and tachypnea (Whittier & Korbet, 2016).
Fluid Status -check for signs of fluid overload (swollen ankles, swollen feet, swollen face and probable weight gain).	-the patient should cautiously be given IV crystalloid fluids for the first 24 hours post-operatively. -A fluid input-output chart should be started to assess for renal function by measuring the amount of fluids given in comparison to that which is eliminated. -The patient should be inserted with a urinary catheter to help in this assessment.	-fluid retention is a major complication in patients who have just undergone renal transplant and it leads to a decrease in urine production and urine and frothy colored urine due to excess proteins(Benzimra, Calligaro & Glanville, 2017).
Wound -ask the patient about pain over the surgical site -ask for any discharge(bleeding or pus)	-In case of severe pain, strong pain medication such as IM morphine should be administered. -Wound of the surgical site should be kept clean daily by cleaning using saline solution. -In case of any bleeding, a surgical assessment should be done to establish the cause of bleeding. -the patient should be advised not to take a bath until the wound is fully healed.	– the immune system of renal transplant patients is suppressed thus  highly susceptible to bacterial fungal or viral infections(Reyna-Sepúlveda et al., 2017). Proper wound care helps to prevent sepsis which may further result to complications such as septic shock with a deteriorating health status (Reyna-Sepúlveda et al., 2017)

Overview of Acute Allograft Rejection

The care of a patient post renal allograft biopsy involves specialized monitoring and follows up. Once all the tissue is obtained by the physician for the biopsy, the needle is removed. Pressure is then applied to the site of the biopsy. This helps to tamponade any potential of loss of blood. The next step involves bandaging the site of the biopsy. During this time, the patient is actively involved. The patient is to lie supine in bed for between six and eight hours preceding the procedure (Whittier & Korbet, 2016). The patient is expected to stay in the hospital for at least half a day. In some cases, the physician may advise the patient to spend the night after the procedure in the hospital. During this brief period immediately after the procedure, the patient is put under pain medication. Regular checks are done for blood count and vital signs are monitored for the entire time that the patient is held in the hospital.

Once the patient is discharged from the hospital, continuous monitoring is done to prevent complications. Renal biopsy patients are likely to develop bleeding and pain at the biopsy site. For bleeding, three distinct parts within the kidney are monitored. These are under the renal capsule, the collecting system, and below the renal capsule. Care is taken to prevent kidney profusion from being compromised (Patel, Young, Kriegshauser, & Dahiya, 2018). This way, chances of subcapsular hematomas developing is minimized. Additionally, monitoring also focuses on the patient’s hypertension and page kidney effect. Perinephric bleeding is prevented so that hemodynamic instability does not occur. The other complication to be prevented during post renal allography is an arteriovenous fistula. While the condition may be asymptomatic in most cases, it may exhibit itself as hypertension, hematuria, or renal insufficiency. These conditions are monitored and checked progressively.

Conclusion

Acute allograft rejection is a critical and life-threatening complication that arises from organ transplantation that affects thousands of patients who opt for an organ transplant. Nurses have the role of performing clinical assessments and instituting evidence-based interventions in clinically unsuspecting patients with acute allograft rejection. However, a proper understanding of the definition, pathophysiology and initial management of acute allograft rejection can support the ability of nurses to provide prioritized clinical care, patient health education and follow-up care in health settings. Following the diagnosis of an acute allograft rejection, nurses should assess a patient’s overall health status, fluid status, urine output, and the wound. Health education should be provided in simple English language and should include information on nutrition and diet, medications, physical exercise, wound care, the social support system, danger signs, and currently available alternatives.  

References

Benzimra, M., Calligaro, G. L., & Glanville, A. R. (2017). Acute rejection. Journal of Thoracic Disease, 9(12), 5440–5457.

Demetris, A. J., Murase, N., Starzl, T. ., & Fung, J. J. (2014). Pathology of Chronic Rejection: An Overview of Common Findings and Observations About Pathogenic Mechanisms and Possible Prevention. Graft (Georgetown, Tex.), 1(2), 52–59.

Fletcher, J. T., Nankivell, B. J., & Alexander, S. I. (2013). Chronic allograft neuropathy. Pediatric Nephrology (Berlin, Germany), 24(8), 1465–1471.

García, P., Huerfano, M., Rodríguez, M., Caicedo, A., Berrío, F., & Gonzalez, C. (2016). Acute Rejection in Renal Transplant Patients of a Hospital in Bogota, Colombia. International Journal of Organ Transplantation Medicine, 7(3), 161–166.

Ghadami, A., Memarian, R., Mohamadi, E., & Abdoli, S. (2012). Patients’ experiences from Their received education about the process of kidney transplant: A qualitative study. Iranian Journal of Nursing and Midwifery Research, 17(2 Suppl1), S157–S164.

Ingulli, E. (2013). Mechanism of cellular rejection in transplantation. Pediatric Nephrology (Berlin, Germany), 25(1), 61–74.

Kloc, M., & Ghobrial, R. M. (2014). Chronic allograft rejection: A significant hurdle to transplant success. Burns & Trauma, 2(1), 3–10.

Leblanc, J., Subrt, P., Paré, M., Hartell, D., Sénécal, L., Blydt-Hansen, T., & Cardinal, H. (2018).Practice Patterns in the Treatment and Monitoring of Acute T Cell-Mediated Kidney Graft Rejection in Canada. Canadian Journal of Kidney Health and Disease, 5.

Moreau, A., Varey, E., Anegon, I., & Cuturi, M.-C. (2013). Effector Mechanisms of Rejection. Cold Spring Harbor Perspectives in Medicine, 3(11), a015461.

Patel, M. D., Young, S. W., Kriegshauser, J. S., & Dahiya, N. (2018). Ultrasound-guided renal transplant biopsy: practical and pragmatic considerations. Abdominal Radiology, 1-7.

Reyna-Sepúlveda, F., Ponce-Escobedo, A., Guevara-Charles, A., Escobedo-Villarreal, M., Pérez- Rodríguez, E., Muñoz-Maldonado, G., & Hernández-Guedea, M. (2017). Outcomes and Surgical Complications in Kidney Transplantation. International Journal of Organ Transplantation Medicine, 8(2), 78–84.

Wang, W., van Lint, C. L., Brinkman, W.-P., Rövekamp, T. J. M., van Dijk, S., van der Boog, P. M., & Neerincx, M. A. (2017). Renal transplant patient acceptance of a self-management support system. BMC Medical Informatics and Decision Making, 17, 58.

Whittier, W. L., & Korbet, S. M. (2016). Indications for and complications of renal biopsy. UpToDate, Waltham, MA.