What is the appropriate workup for a patient with a one-month history of fever and cough, who underwent a kidney transplant 10 years ago and has stable Chronic Kidney Disease (CKD), currently maintained on cyclosporine (Cyclosporin) and prednisone for immunosuppression?

From the Guidelines

For a patient with fever and cough for one month who has a history of kidney transplant on cyclosporine and prednisone, I recommend a comprehensive workup focusing on both common and opportunistic infections. Start with chest imaging (X-ray or CT scan), complete blood count, comprehensive metabolic panel including renal function tests, blood cultures, sputum cultures, and urinalysis. Consider bronchoscopy with bronchoalveolar lavage if initial tests are inconclusive. Specific testing should include PCR for respiratory viruses, testing for Pneumocystis jirovecii pneumonia (PCP) as recommended by the KDIGO clinical practice guideline for the care of kidney transplant recipients 1, tuberculosis screening, fungal studies (including Aspergillus, Cryptococcus), and CMV viral load. Monitor cyclosporine levels as infections may alter drug metabolism. Empiric antibiotic therapy may be warranted depending on severity, typically with a respiratory fluoroquinolone or beta-lactam plus macrolide while awaiting culture results. The prolonged duration of symptoms (one month) in an immunocompromised host raises concern for opportunistic infections that wouldn't typically affect immunocompetent individuals. The patient's chronic immunosuppression with cyclosporine and prednisone increases susceptibility to bacterial, viral, and fungal pathogens, while their CKD may affect drug clearance and dosing. Given the patient's history of kidney transplant, it is essential to consider the guidelines for the care of kidney transplant recipients, which emphasize the importance of preventing and treating complications that occur after kidney transplantation 1. Additionally, the clinical practice guideline for the management of asymptomatic bacteriuria highlights the risk of urinary tract infections in renal transplant patients and the potential for these infections to lead to more severe complications such as graft loss or acute graft rejection 1. Maintain close follow-up as the clinical picture evolves and be prepared to adjust therapy based on diagnostic findings. Key considerations in the management of this patient include:

• The potential for opportunistic infections due to chronic immunosuppression
• The need for comprehensive testing to identify the underlying cause of the patient's symptoms
• The importance of monitoring cyclosporine levels and adjusting therapy as needed
• The potential for drug interactions and the need to consider the patient's CKD when selecting antimicrobial therapy.

From the Research

Patient Presentation

• The patient presents with fever and cough for one month, with a history of kidney transplant 10 years ago and stable chronic kidney disease (CKD).
• The patient is currently using cyclosporine and prednisone for maintenance immune suppression.

Immunosuppression Management

• According to 2, developing expertise in the management of immunosuppressive drugs is key to the success of kidney transplantation.
• The study 3 suggests that in kidney transplant recipients with COVID-19 pneumonia, calcineurin inhibitors and antimetabolites were held, while prednisone was continued.
• However, 4 found that discontinuing calcineurin inhibitors was associated with higher peak high-sensitivity C-reactive protein (hs-CRP) and worse outcomes.

Infection and Rejection

• 5 found that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection.
• The study 4 also found that kidney transplant recipients with COVID-19 have high rates of intensive care unit (ICU) admissions, acute kidney injury (AKI), and death, and that those with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 are at highest risk.

Current Immunosuppression Protocols

• According to 6, mycophenolate and calcineurin inhibitors, with or without prednisone, continue to constitute the backbone of modern maintenance immunosuppression.
• However, alternatives to calcineurin inhibitors such as belatacept and mammalian targets of rapamycin inhibitors exist, and their wider-scale adoption is being considered.