Chronic kidney disease and fundamentals of kidney transplant

1. Chronic kidney disease

Chronic kidney disease is a major health problem because of its high prevalence, morbidity and mortality, and socioeconomic cost.

CKD should not be understood solely as an elevated creatinine value. It is defined by the persistent presence of abnormalities of kidney structure or function for more than three months with implications for health. It can manifest through markers of kidney damage —such as albuminuria, urinary sediment abnormalities, structural or histologic abnormalities— and/or through a persistent reduction in glomerular filtration rate.

Two elements are fundamental:

1. Estimated glomerular filtration rate. It allows assessment of kidney function and helps establish the stage of the disease.
2. Albuminuria. It is not only a marker of kidney injury but also an important prognostic indicator of kidney progression and cardiovascular risk.

2. Progression of CKD

As kidney function declines, the risk of the following increases:

• Fluid and electrolyte disturbances.
• Metabolic acidosis.
• Anemia.
• Mineral and bone disease.
• Volume overload.
• Cardiovascular disease.
• Uremic symptoms.
• Need for renal replacement therapy.

In advanced stages we must stop thinking only about "treating kidney disease" and begin planning which renal replacement strategy will be most appropriate for that patient.

3. Renal replacement therapy

When kidney function deteriorates to an advanced degree, there are three main alternatives:

The patient's blood circulates through an extracorporeal circuit and a dialyzer that removes toxins and excess fluid. It usually requires adequate vascular access and regular sessions.

It uses the peritoneum as an exchange membrane. It allows treatment to be carried out at home in appropriately selected and trained patients.

It consists of implanting a functioning kidney from a living or deceased donor. In the teaching material provided, transplant is presented as the renal replacement therapy alternative associated with greater long-term survival.

4. Why transplant?

The goal of kidney transplant is not only to get the patient off dialysis. A successful transplant seeks to:

• Restore adequate kidney function.
• Improve survival.
• Improve quality of life.
• Reduce the limitations associated with dialysis.
• Promote social and occupational rehabilitation.

But transplant does not mean a definitive cure of kidney disease. The recipient enters a new clinical situation that requires:

• Immunosuppression.
• Regular check-ups.
• Monitoring of graft function.
• Infection prevention.
• Cardiovascular and metabolic control.
• Oncologic surveillance.

5. Where can the kidney come from?

There are two main possibilities.

The organ comes from a deceased donor who meets the corresponding donation criteria. This requires an organized process of: donation → procurement → preservation → allocation → implantation. The recipient must be adequately evaluated and ready to receive the organ when a compatible donor appears.

A healthy person donates one of their kidneys to a recipient. Living-donor transplant has particular characteristics and may offer advantages related to planning of the procedure and ischemia times. The material provided also notes less delayed graft function and better graft survival compared with deceased-donor transplant.

But there is a principle that must accompany the entire process:

6. The concept of the waiting list

Deceased-donor transplant requires a system to allocate available organs among potential recipients. The patient must first complete an evaluation that determines their suitability for transplant.

Allocation takes into account different variables related to the recipient and the donor. The material provided mentions, among others:

• Time on dialysis.
• Sensitization.
• Blood group.
• Histocompatibility.
• Recipient characteristics.
• Compatibility with the donor.

The goal is not simply to find "a kidney of the same blood group," but to determine whether an appropriate donor-recipient combination exists.

7. Compatibility: concepts the urologist should know

Although the detailed immunologic evaluation falls to the specialized team, the transplant surgeon must understand some basic concepts.

Blood group compatibility is one of the factors considered in selecting the recipient.

Human leukocyte antigens take part in immune recognition and in the response against the graft.

A patient may have developed antibodies against certain antigens as a result of previous exposures. These can include:

• Previous transplants.
• Transfusions.
• Pregnancies.

Highly sensitized patients pose a particular challenge.

Before transplant, the recipient is assessed for a relevant immune response against the potential donor. In the material you provided, the crossmatch appears as one of the studies performed during the procurement process before the final allocation of the kidney.

8. The great immunologic challenge

The recipient's immune system recognizes the transplanted kidney as foreign tissue. Without immunosuppression, a response capable of damaging or destroying the graft can be triggered.

That is why kidney transplant needs to maintain a balance:

• Too little immunosuppression → increases the risk of rejection.
• Too much immunosuppression → increases the risk of infection, toxicity, and other complications.

This balance will accompany the patient for the entire life of the graft.

9. Immunosuppression: general concept

In this first lesson the resident does not need to memorize complete drug regimens. The resident should understand that there are conceptually two phases:

It is used around the time of transplant to achieve intense initial immunosuppression in selected patients according to immunologic risk and the protocol used.

It is given afterward to lower the long-term risk of rejection. Regimens may combine different drug classes.

Immunosuppression has a biological cost. It can promote:

• Infections.
• Metabolic abnormalities.
• Drug toxicity.
• Cardiovascular complications.
• Certain tumors.

That is why the goal is not simply to "immunosuppress heavily," but to find a balance between protecting the graft and keeping the recipient safe.

Complications change depending on the time elapsed since the procedure and the intensity of immunosuppression. During the first year, acute graft dysfunction and infections are especially important; later, chronic dysfunction and cardiovascular, metabolic, and oncological complications become more relevant.

For teaching purposes, they can be grouped as:

• Hyperacute rejection.
• Acute rejection.
• Chronic rejection.

• Arterial thrombosis.
• Venous thrombosis.
• Hemorrhage.
• Urinary fistula.
• Ureteral stricture.
• Obstruction.

Related to immunosuppression, surgery, the environment, and certain transmitted or reactivated infections.

• Cardiovascular.
• Metabolic.
• Drug toxicity.
• Neoplasms.

Surgical complications and graft management will be covered in depth in the corresponding lessons of the module.