A 35-year-old type 1 diabetic presented eight months following a renal transplant with fever, night sweats and malaise. He had experienced two episodes of transplant rejection, which were successfully reversed with corticosteroids. He was currently maintained on prednisolone and ciclosporin. On examination he had a temperature of 39°C (102.2°F). The heart rate was 120 beats/min and blood pressure was 140/60 mmHg. The respiratory rate was 40/min. Precordial examination revealed an early diastolic murmur at the left lower sternal edge. The chest was clear. The abdomen including the graft was non-tender. Investigations are shown.
Hb 10 g/dl WCC 10 109/l Neutrophils 7 109/l Lymphocytes 2.5 109/l Eosinophils 0.04 109/l Basophils 0.1 109/l Monocytes 0.4 109/l Platelets 300 109/l ESR 100 Sodium 130 mmol/l Potassium 5.5 mmol/l Chloride 87 mmol/l Bicarbonate 22 mmol/l Urea 9 mmol/l Creatinine 130 mol/l Glucose 6 mmol/l Urine output 45 ml/hr Urinary microscopy Red blood cells and no white cell casts ECG Sinus tachycardia
What is the most likely diagnosis?
a. Acute renal transplant rejection.
b. CMV infection.
c. Infective endocarditis.
d. Gram-negative sepsis.
e. Ciclosporin nephrotoxicity.
Answer:
Infection is the commonest life-threatening complication of long-term immunosuppressive therapy (Table). More than 6 months post-transplant most patients have stable allografts and are maintained on minimal immunosuppressive therapy. Infection in the majority of these patients is usually similar to that seen in the general population. The patient in question has a murmur of aortic regurgitation and a high fever, raising the possibility of infective endocarditis. The overall incidence of bacterial endocarditis is much greater in renal transplant recipients than in the general population. Independent risk factors for bacterial endocarditis include a history of hospitalization for valvular heart disease, graft loss and increased duration of dialysis before transplantation. The mean time from transplantation to diagnosis of endocarditis is estimated to be three and a half years (range two months to 15 years), with an overall mortality of 50%. The increased susceptibility of renal transplant recipients to infective endocarditis can probably be explained by a combination of necessary invasive procedures (e.g. intravascular line placement) during the immediate post-transplant period as well as immunosuppression for prevention of organ rejection. Pre-existing valvular abnormality in renal transplant patients may also be conducive to endocarditis similar to that in non-transplant patients. Immunosuppression plays an important role in the development of fungal endocarditis, but may also be important in the clearance
of streptococci from the blood in this patient population. In contrast to the frequent pre-existing valve abnormality associated with bacterial endocarditis, the great majority of solid organ transplant recipients with Aspergillus endocarditis have no pre-existing valvular abnormalities. Myocardial abscesses have been commonly reported with Aspergillus endocarditis. The most common causes of endocarditis among renal transplant recipients are fungi (particularly Aspergillus species) and S. aureus. Less common causes include Corynebacterium species, viridans streptococci, vancomycin-resistant Enterococcus species, Brucella species, Clostridium species, Nocardia species and Erysipelothrix species. Skin manifestations of endocarditis and/or splenomegaly seem to be uncommon in transplant patients, while septic emboli and mycotic aneurysms are more frequent. The most common clinical signs and symptoms at the time of presentation are fever and embolic phenomena. The mitral valve is thought to be the most frequently involved cardiac valve, followed by the intramural cardiac surface and the aortic valve. Even in the absence of immunosuppression the leucocyte count is elevated in only 20–30% of cases and may be normal. Most episodes of acute rejection occur in the first six months after surgery. However, the absence of a rise in serum creatinine, fall in urine output and graft pain/tenderness make rejection unlikely. Ciclosporin nephrotoxicty is a recognized compli cation in transplant patients and is characterized by a falling glomerular filtration rate, hyperkalaemia, hyperuricaemia and a hyperchloraemic acidosis.