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Published on: January 2, 2017
Effect of rapamycin on spleen size in longstanding renal transplant recipients
N C Araújo1, S B Sampaio Gonçalves de Lucena2, S da Silveira Rioja1
1Division of Nephrology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Background:
Based on evidence available in the literature, rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, but not calcineurin inhibitors (CNIs), has been shown to decrease spleen size. Small spleen, in some instances, is associated with hyposplenism, a condition recently reported in patients with longstanding renal transplant. Accordingly, the effect of immunosuppressive drugs on spleen size was evaluated.
Methods:
Renal transplant recipients (35 taking mTOR and 68 CNI) were included, in whom a standardized investigation of the kidney allograft and spleen with the use of color Doppler ultrasound was performed and a peripheral smear were reviewed for the presence of Howell-Jolly bodies (HJBs).
Results:
We enrolled 103 patients (64 men; 66 from a deceased donor). The mean age was 47.7 years (range, 23.0-74.0 y). Mean transplant duration was 1,899 days (range, 181-6,883 d). According to the presence of HJBs, the prevalence of hyposplenism was 47.6% for the entire cohort. The differences between the mTOR and CNI groups regarding sex and the presence of HJBs were not statistically significant (P > .05). Age, creatinine, hemoglobin, leukocytes, platelets, and Doppler parameters in spleen and kidney were similar in both groups (P > .05). mTOR patients had a decreased spleen length size (90.09 ± 13.02 mm vs 111.95 ± 18.66 mm; P < .001), a longer transplant duration (3,576 ± 1,594 d vs 1,036 ± 1,369 d; P < .001) and higher serum cholesterol (227.50 ± 38.75 mg/dL vs 182.67 ± 37.74 mg/dL; P < .001) and triglycerides (194.23 ± 79.88 mg/dL vs 148.70 ± 55.54 mg/dL; P = .003) levels compared with the CNI group. A multivariate analysis showed mTOR inhibitor to be the most important predictor of spleen size. In both the mTOR and CNI groups, the comparison between the subgroups of present and absent HJBs did not show any difference.
Conclusions:
The findings of this study suggest that small spleens in transplant recipients may be linked to treatment with an mTOR inhibitor, although this apparently does not compromise splenic function.
Insights
Mammalian target of rapamycin (mTOR) inhibitors, unlike calcineurin inhibitors (CNIs), are linked to smaller spleen size in renal transplant patients. This reduction in spleen size does not appear to impair splenic function.
Area of Science:
- Transplantation immunology
- Pharmacology
- Medical imaging
Background:
- Mammalian target of rapamycin (mTOR) inhibitors, but not calcineurin inhibitors (CNIs), are associated with decreased spleen size in literature.
- Small spleen size is increasingly reported in renal transplant recipients, potentially indicating hyposplenism.
- The impact of different immunosuppressive drug classes on spleen size in renal transplant recipients warrants investigation.
Purpose of the Study:
- To evaluate the effect of mTOR inhibitors versus CNIs on spleen size in renal transplant recipients.
- To determine if spleen size reduction correlates with hyposplenism, indicated by Howell-Jolly bodies (HJBs).
Main Methods:
- A cohort of 103 renal transplant recipients was studied (35 on mTOR inhibitors, 68 on CNIs).
- Kidney allograft and spleen size were assessed using color Doppler ultrasound.
- Peripheral blood smears were analyzed for the presence of Howell-Jolly bodies (HJBs) to assess splenic function.
Main Results:
- Patients on mTOR inhibitors exhibited significantly smaller spleen length compared to those on CNIs (90.09 mm vs 111.95 mm).
- The prevalence of hyposplenism (indicated by HJBs) was 47.6% across the cohort, with no significant difference between the mTOR and CNI groups.
- Multivariate analysis identified mTOR inhibitor use as the primary predictor of reduced spleen size.
Conclusions:
- Treatment with mTOR inhibitors is associated with decreased spleen size in renal transplant recipients.
- Despite the reduction in spleen size, splenic function, as assessed by HJBs, does not appear to be compromised by mTOR inhibitor therapy.
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