Introduction:
Renal transplantation following kidney failure or due to any genetic condition is associated with a high risk of acute injuries to the kidneys. This can happen to the person donating the kidneys (donor) and the person receiving the kidneys (recipient). This may be caused due to a number of features in the donor as well as the recipient's body, especially the activity of the immune system plays a major role. Acute kidney injury in renal transplantation patients can occur immediately after transplantation or after initial recovery of kidney function, or even post-transplantation. This could result in poor short-term or long-term outcomes in patients with grafted kidneys resulting in further life-threatening complications.
What Are the Normal Functions of the Kidney?
Kidneys are the two bean-shaped organs located in the retroperitoneal or the loin region. Each kidney measures about five inches or 10 to 12 cm. The main function of the kidney is to filter the waste products from the blood to maintain the acid-base balance and the fluid-electrolyte balance in the body.
What Is Renal Transplantation?
When the kidneys lose their function due to genetic or acquired causes, waste products start accumulating in the blood, acid-base balance is altered, fluid-electrolyte balance is disturbed, and the total homeostatic balance is affected, leading to serious life-threatening illnesses. In those cases, the damaged kidneys can be replaced by a normally functioning kidney from the donor as it helps the patient feel better and live longer, compared with lifetime dialysis.
What Are the Limitations of Renal Transplantation?
Although renal replacement is a better option as compared to lifetime dialysis, in certain cases, there is an increase in the risk of mortality. The scenarios with the risk of mortality include:
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Old age.
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Severe cardiac conditions.
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Heavy alcohol consumption.
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Drug users.
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Patients with an active or recently treated cancer.
What Is Acute Kidney Injury?
Acute kidney injury, also called acute renal failure, is characterized by the sudden loss of renal function within a few hours or a few days due to any underlying cause. Acute kidney injury can cause the kidneys to lose their normal function, thereby accumulating waste products in the blood, affecting the acid-base and the fluid-electrolyte balance. It can also affect other organs in the body, such as the heart, brain, lungs, etc.
What Is Delayed Allograft Function?
A delayed graft function is a form of acute kidney injury that occurs in the first week of renal transplantation. It literally means that the replaced or transplanted kidneys are not functioning for sometime immediately after the transplant. In such cases, dialysis is initiated till the underlying cause or the damage is resolved. Delayed allograft function can occur as a result of factors such as,
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Transplanted organ quality or the functioning state.
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Recipient's medical condition.
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Due to any surgical insult.
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Graft injury due to the dialysis treatment.
What Is the Epidemiology of Acute Kidney Injury in Renal Transplantation Patients?
Studies report that the incidence of acute kidney injury in renal transplantation patients is about 30 % when the kidneys are obtained from deceased donors and 50 % if the donors die after cardiac arrest.
What Are the Risk Factors For Acute Kidney Injury in Renal Transplantation Patients?
The risk factors can be categorized into three types for ease of understanding, and they are as follows:
Donor-Related Risk Factors:
The donor-related risk factors include:
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Hemodynamic instability in patients in the intensive care unit.
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A prolonged period of perfusion of the donor's kidney with a cold preservation fluid (cold ischemia time).
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The donor's kidney is received from an old-aged person.
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Donors with a history of chronic kidney disease.
Recipient-Related Risk Factors:
The recipient-related risk factors include:
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Vascular complications.
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History of major surgeries.
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Patients with high immunological risk.
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Increased body mass index.
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Pre-transplantation reduced urine output (oliguria).
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Pre-transplantation hemodialysis session.
Preoperative Risk Factors:
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History of hypotension (reduced blood pressure).
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History of hypovolemia (reduced fluid volume).
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High calcineurin inhibitor levels.
What Is the Pathogenesis of Acute Kidney Injury in Renal Transplantation Patients?
The pathogenesis behind acute kidney injury in patients with renal transplantation is the activity of the immune system.
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It has been proposed that the activation of the innate immune system following the transplantation of the kidneys. This, in turn, would activate the complement system resulting in the adhesion of those molecules to the endothelium of the transplanted kidney. The activated complements release a series of molecular patterns, these molecular pathways cross-talk with the adaptive immune system, thereby damaging the grafted kidneys and resulting in acute kidney injury.
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Another possible cause is the activation of apoptotic or cell death pathways. Following ischemia or the reperfusion injury caused due to a surgical mistake or an immune attack, the activated apoptotic pathways would mediate acute kidney injury.
What Are the Therapeutic Approaches to Treating Acute Kidney Injury in Renal Transplantation Patients?
The steps in treatment are as follows:
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The donor and the recipient targeted therapies in the preoperative period.
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Organ-targeted therapy.
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Therapies to treat early acute kidney injury in transplant recipients.
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Therapies to treat long-term acute kidney injury in transplant recipients.
1) The Donor and the Recipient Targeted Therapies in the Preoperative Period:
Studies report that the incidence of acute kidney injury can be reduced by using therapeutic strategies in the donor before harvesting the kidneys or in the recipient during the perioperative period.
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Low-dose of dopamine can be given to the donor prior to transplantation.
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Isotonic saline solutions can be used to prevent graft ischemia (reduced blood supply to the graft).
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Preoperative dialysis should be avoided as it would result in volume depletion.
2) Organ-Targeted Therapy:
In order to prevent acute kidney injury due to organ-related factors, organ storage and transplantation should be carried out in a safe manner. The steps include:
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Hypothermic perfusion machines are used, where they maintain the low temperature at a range of four to ten degrees centigrade, deliver a pulsatile flow and deliver oxygen if needed. This would help in preserving the vitality of the cells by restoring the cellular metabolism and reviving the organs, which would help the kidneys to resume their function.
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Multipotent adult progenitor cells can be administered to the organ through a machine to prevent kidney injury and fibrosis of the organ.
3) Therapies to Treat Early Acute Kidney Injury in Transplant Recipients:
The early acute injury following renal transplantation may occur due to acute tubular necrosis or surgical complications, which can be identified using computed tomography scans, and the respective treatment should be initiated.
4) Therapies to Treat Long-Term Acute Kidney Injury in Transplant Recipients:
Long-term acute kidney injury is the main cause of graft failure in many patients with renal transplants. It is mainly caused due to viral infection by the Polyomavirus and drug toxicity (commonly associated with the use of nonsteroidal anti-inflammatory drugs). These patients are at increased risk of graft failure and death due to further complications. Hence, regular follow-up and monitoring are indicated in high-risk patients, and the respective treatments should be started at the earliest.
Conclusion:
Acute kidney injury is one of the common complications seen in relation to the donor as well as the recipient. Research is in progress to identify the biomarkers that predict the highest risk for graft failure in the donor's kidney and to improve the prognosis of patients receiving renal transplants. E-alert systems are also under trial to identify the development of acute kidney injury during long-term follow-up. More studies with longer follow-ups are needed to identify the exact role of COVID-19 in causing acute kidney injury.
