In 2024 there were more than 44,900 people living in the UK with a kidney transplant. 2,868 renal transplants were performed in the UK in 2021/2022 with the projected estimate for renal transplants expected to rise to 12,000 by 2033. Evidence from the renal registry suggests that transplant recipients with poor graft function receive inferior care compared to patients with native kidney disease. Although dedicated outpatient transplant clinics have been established to combat this problem – having an overview understanding of common complications that occur in transplant recipients can help ensure proper initial care is provided to transplant patients who present to the hospital.
Causes of End Stage Renal Failure
Guidelines in the management of declining renal function recommend that preparations for Renal Replacement Therapy (RRT) should be completed by the time the eGFR has fallen to 10 -15ml/min/1.73m2 as long as there are no indications for delay. Renal Replacement Therapy is provided via Peritoneal dialysis, Haemodialysis and renal transplantation. Common causes for end stage renal failure that require RRT in the UK are:
Diabetes, Glomerulonephritis, Hypertension and Polycystic Kidney disease.
Renal Transplantation:
Immunological workup occurs as part of the medical evaluation in preparation for renal transplantation. This includes ABO blood type compatibility, Human Leukocyte Antigen (HLA) matching as well as extensive antibody panels to reduce the risk of antibody mediated rejection. HLA compatibility is done on 6 key antigens and the fewer the mismatches, the lower the risk of rejection. Â The first 6 months of management following a renal transplant occurs closely with the multi-disciplinary team of the transplanting centre, which allows for monitoring of both medical and surgical immediate or early complications. Management during this period includes induction immunosuppression (typically high dose steroids and Basiliximab or anti-thymocyte globulin), infection prophylaxis, close monitoring of graft function and initiation of maintenance immunosuppression. Maintenance immunosuppression often includes tapering of steroids, Calcineurin inhibitors such as tacrolimus and Anti-proliferative agents such as mycophenolate or cyclosporine. Renal transplant recipients are followed up regularly in nephrology transplant clinics as an outpatient which involves close monitoring for early and late complications and overall graft function.
Renal Transplant Complications
| Allograft Rejection | Immune mediated rejection of the allograft may occur if the recipient’s immune system recognises the ‘foreign’ antigens on the allograft. The immune process may be antibody or T-cell mediated rejection. Hyperacute rejection occurs within minutes of transplantation and is associated with pre-existing donor-specific antibodies such as in ABO incompatibility. Acute rejection can happen days to weeks after the transplant whereas chronic rejection typically occurs more than 3 months after transplantation. Both can be either antibody mediated or T-Cell mediated rejection. Typical features include pain and tenderness over the allograft, fever, decline in urine output and decline in renal function. Renal biopsy is the gold-standard for diagnosis and Immunosuppression is the mainstay of treatment, all of which will be guided by the renal team. |
| Infection | Immunosuppression plays an important role in preventing immune mediated rejection of the allograft, however it also increases the susceptibility to microbial and opportunistic infections Common virus’s that infect include Cytomegalovirus (CMV), Ebstein-barr virus (EBV) and Herpes Simplex Virus (HSV). Important differential: BK virus, also known as polyoma virus. Its prevalence has been reported to be as high as 10% in transplant recipients and is known to cause severe complications such as BK nephropathy and ureteric stenosis; with 15-20% resulting in loss of the allograft. The mainstay of treatment for viral infections includes anti-viral medication when indicated and reduction of immunosuppression to allow the persons immune system to control the infection. In certain cases agents such as leflunomide, an immunosuppressant that has antiviral properties, are used to treat viral infections. |
| Malignancy | Renal transplant recipients are at higher risk of developing certain forms of cancer. Post-transplant lymphoproliferative disorders (PTLD) arise due to lymphoid or plasmacytoid proliferation and account for approximately 21% of all cancers in solid organ transplant patients. This is typically managed with reduction in immunosuppression but also may require chemotherapy. The incidence of skin cancer is also much higher in renal transplant recipients in comparison to the general population |
| Post-transplant Diabetes Mellitus | The incidence of Post-Transplant Diabetes Mellitus (PTDM) is reportedly 5-20% in renal transplant recipients and is associated with an increased risk in cardiovascular disease. Risk factors: Standard T2DM risk factors plus the use of corticosteroids and Calcineurin inhibitors such as Tacrolimus. A formal diagnosis of PTDM can be made from six weeks post-transplantation using an oral glucose tolerance test (gold standard) or after twelve weeks using HbA1c >48mmol/L (>6.5%). |
| Hypertension | Hypertension following kidney transplantation is common and is associated with reduced graft function and patient survival. Hypertension can be a side effect to the immunosuppressive therapy but also may be a sign of poor graft function. Resistant hypertension (often defined in the general population as clinic BP >160/90 mmHg on 3 or more antihypertensive agents) is more common in renal transplant recipients and it is recommended that further work-up should be performed to exclude transplant renal artery stenosis, non-compliance or other causes of secondary hypertension. |
| Dyslipidaemia | The leading cause of death in patients with a kidney transplant is cardiovascular disease. Dyslipidaemia is common in patients with kidney transplants, partly due to the immunosuppressive therapy. Lipid lowering agents should be considered for all renal transplant recipients with diabetes. First line agents include statins and ezetimibe and target aim is to reduce total cholesterol to ≤4.0 mmol/L, non-HDL cholesterol to ≤2.5 mmol/L and LDL cholesterol to ≤2 mmol/L. |
| Anaemia | The reported prevalence of anaemia in renal transplant patients is suggested to be between 20-30% and may be associated with poor outcomes. There are multiple factors that contribute in the development of anaemia such as suboptimal graft function, impact of immunosuppressive drugs, certain infections (Parvovirus-B19, BK polyomavirus, Adenovirus and Epstein-Barr virus) and haematinic deficiencies such as: iron, folate, vitamin B12 and erythropoietin. Haemoglobin targets for renal transplant patients range between 110-120 g/dl with recommendations to avoid drops <105 g/dl. |
| Recurrent of Primary Disease | Renal Registry data from the UK indicates around 3.5% of kidney transplants fail due to recurrent disease. Certain conditions are known to recur quickly and severely in a kidney transplant and patients are often counselled about this prospect. These conditions are often Focal Segmental Glomerulo-Sclerosis (FSGS), Atypical Haemolytic Uraemic Syndrome (HUS) and other complement abnormalities (C3 Glomerulo Nephritis (C3GN) and Dense Deposit Disease). FSGS and C3GN typically recur in the early post-transplant period whereas the risk of recurrence of other forms of glomerulonephritis increases with time post-transplantation. |
Drug Toxicity
Immunosuppressive drugs have narrow therapeutic windows, with significant risk of under and over-immunosuppression. The balance of risks and benefits needs to be closely weighed up and therefore use of these medications is closely monitored by specialist nephrologists.
Common forms of maintenance immunosuppression include:
- Corticosteroids such as Prednisolone or Methylprednisolone which are often used for shorter periods of time.
Common side effects include hyperglycaemia, hypertension, weight gain and fluid retention, osteoporosis and cataracts or glaucoma.
- Calcineurin inhibitors such as Tacrolimus or Cyclosporin cause Inhibition of calcineurin which helps to prevent T-Cell activation.
Common side effects include hypertension, nephrotoxicity, neurotoxicity, hyperglycaemia, gingival hyperplasia and hirsutism.
- Antiproliferative agents such as Mycophenolate mofetil and Azathioprine work by interfering with nucleotide synthesis and this inhibiting lymphocyte proliferation.
Common side effects include gastrointestinal disturbance, bone marrow suppression and are teratogenic, therefore avoided in pregnancy.
- mTOR (mammalian target of rapamycin) inhibitors act to inhibit T-Cell proliferation and examples include Sirolimus and Everolimus.
Common side effects include hyperlipidaemia, mouth ulcers, pneumonitis, proteinuria and impaired wound healing.
Clinical History
Transplant History:
When did the transplant occur? What type (living or deceased donor)? Any previous rejection episodes?
Follow up:
Which transplant centre? Is the patient attending their regular clinic follow up?
Renal function:
Weight? Urine output? Fluid overload symptoms (orthopnoea, leg swelling, shortness of breath)? Uraemic symptoms (lethargy, itchiness, nausea)? Symptomatic anaemia? Last known eGFR?
Symptoms:
Fever? graft pain? Reduced urine output? Swelling? Breathlessness? GI upset?
Drug history:
Immunosuppression regime and compliance? Current doses? Suffering any side effects? Review any potential interactions
Infection Exposure:
Any sick contacts? Recent travel? Viral illness?
Clinical Assessment
If renal function is dropping then always consider: Rejection, Infection, Obstruction, or Drug Toxicity. Important features to consider with renal transplant patients include:
Vitals:
Blood Pressure (Watch for Hypertension), HR, Temperature, RR, SpO2
Fluid assessment:
Skin turgor, peripheral perfusion, Jugular Venous Pressure (JVP), Mucous membranes, Pulmonary oedema, peripheral oedema (don’t forget to check dependent areas such as the sacrum)
Surgical site:
Any colour changes? Any Temperature changes? Swelling? Tenderness
Immunosuppression complications:
Oral thrush, gingival hyperplasia, Lymphadenopathy, Skin lesions, bruising, tremor
Neurological:
Tremor (e.g Tacrolimus), Confusion (Metabolic/Infective causes)
Investigations
Investigations will be guided by clinical suspicion following clinical history and examination and may differ in the context of each presenting complaint. In the context of declining renal function, particularly in renal transplant patients, the following information would be helpful in distinguishing possible causes of decline in renal function whilst awaiting a renal review.
| Bedside | Observations, weight, Fluid input/output chart, Urine dip, Urine Protein/Creatinine Ratio, Urine MC&S |
| Bloods | Full Blood Count (FBC), C-Reactive protein (CRP), Liver Function Tests (LFTs), Renal function (Urea & Electrolytes, Creatinine, eGFR), Bone Profile (Ca, Phos, PTH, Vitamin D) Viral Serology if indicated (HIV, Hep B, Hep C, HSV1 HSV2, VZV, EBV, CMV, BK Virus) Autoimmune profile (ANA, ANCA, Anti-GBM), Myeloma screen (Protein electrophoresis, Immunoglobulins, Kappa/Lambda light chains), Haematinics (B12, Folate, Iron studies) Coagulation screen and consider Group and Save Drug levels (Tacrolimus, ciclosporin and sirolimus all measured trough levels) |
| Imaging | – Chest Xray ?Pulmonary oedema – Renal Ultrasound ?Graft size ?Hydronephrosis/Hydroureter |
Management
Renal transplant patients present with a variety of complications and their management needs to be led by the renal physicians, so early escalation to the renal team is a must!
As with any acutely unwell patient, an A-E approach will help identify and manage any key problems. If the patient is presenting with a decline in renal function, then manage the patient the same as with any AKI eg hold nephrotoxic agents (NSAIDs, ACE Inhibitors/ ARBs if acutely unwell) and aim for euvolaemia.
Start empirical antibiotics early if infection suspected (after cultures)
Beware of dangerous interaction of Tacrolimus with Macrolides (Increases Tacrolimus levels).
Do not withhold immunosuppression without specialist input and do not start steroids unless advised by nephrology.
When to Escalate Immediately to the Renal Team
- Rising creatinine >20% from baseline
- Graft pain or tenderness
- Oliguria/anuria
- Suspected rejection or drug toxicity
- Suspected BK virus, CMV, or opportunistic infection
- Any uncertainty in managing immunosuppression
Dr Marios Magriplis, Acute Medicine CT4 (Reviewed by Dr Anil Jain, Consultant)
