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A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction
Published on: August 27, 2019
mTOR inhibitors: do they help preserve renal function?
J Moro1, L Almenar, L Martínez-Dolz
1Cardiac Failure and Transplant Unit, Cardiology Service, Valencia, Spain. moro@uv.es
Background:
Renal function deterioration is one of the main problems facing heart transplant recipients. The mammalian target of rapamycin (mTOR) inhibitors, in combination with or replacing calcineurin inhibitors, may help preserve renal function. The aim of this study was to evaluate the progression of renal function after switching the immunosuppressive regimen.
Patients And Methods:
We studied 23 heart transplant recipients (5.5 +/- 4.5 years since transplantation). An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Patient clinical characteristics and renal function were studied after switching. The statistical analysis used Student t test for paired data.
Results:
The reason for the transplantation was ischemic cardiopathy (52%), dilated myocardiopathy (39%), or other causes (9%). Mean age at time of transplantation was 52 +/- 9 years. Comorbidities were as follows hypertension (43%), insulin-dependent diabetes (22%), hypercholesterolemia (39%), and ex-smokers (70%). The reason for the switch was increased creatinine (65%), appearance of tumors (26%), or others (8%). Previous creatinine level was 1.89 +/- 0.6 mg/dL with clearance of 61.7 +/- 23 mL/min and at the end of follow-up (mean follow-up, 11 +/- 6 months) creatinine level was 2.0 +/- 1.45 mg/dL with clearance of 68.3 +/- 35 mL/min, namely, no significant difference (P = .49 and P = .57, respectively). In the subgroup of patients who switched treatment due to renal dysfunction, initial creatinine level was 2.38 +/- 0.4 mg/dL with clearance of 42.3 +/- 10 mL/min and at the end of follow-up it was 2.28 +/- 0.2 mg/dL and 43.6 +/- 11 mL/min, respectively (P = .68 for creatinine and clearance).
Conclusions:
The introduction of mTOR inhibitors to the immunosuppressant regimen may be useful to delay renal functional deterioration caused by calcineurin inhibitors.
Insights
Switching to mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients did not significantly alter renal function. This immunosuppressive regimen change may help delay calcineurin inhibitor-induced kidney damage.
Area of Science:
- Nephrology
- Cardiology
- Immunology
Background:
- Renal function decline is a major complication in heart transplant recipients.
- Mammalian target of rapamycin (mTOR) inhibitors are explored as alternatives to calcineurin inhibitors to preserve kidney function.
- This study evaluates renal function changes after switching immunosuppressive strategies.
Purpose of the Study:
- To assess the impact of switching from calcineurin inhibitors to mTOR inhibitors on renal function in heart transplant patients.
- To determine if mTOR inhibitors can mitigate or reverse renal function deterioration post-transplant.
Main Methods:
- A cohort of 23 heart transplant recipients with a mean follow-up of 11 months was studied.
- Cyclosporine was replaced with an mTOR inhibitor (everolimus or sirolimus).
- Renal function (creatinine levels and creatinine clearance) was monitored before and after the switch, with statistical analysis using the Student t test.
Main Results:
- No significant difference was observed in mean creatinine levels (1.89 vs. 2.0 mg/dL) or creatinine clearance (61.7 vs. 68.3 mL/min) post-switch.
- In patients switched due to renal dysfunction, renal function parameters also showed no significant change (creatinine 2.38 vs. 2.28 mg/dL, clearance 42.3 vs. 43.6 mL/min).
- The primary reasons for switching were increased creatinine (65%) and tumor development (26%).
Conclusions:
- Introducing mTOR inhibitors into the immunosuppressive regimen did not lead to significant changes in renal function in this cohort.
- The findings suggest that mTOR inhibitors may not improve, but do not worsen, renal function compared to calcineurin inhibitors in the short term.
- Further research is needed to confirm the long-term effects and potential benefits of mTOR inhibitors in delaying renal functional deterioration in heart transplant recipients.
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