Improved 24-hour blood pressure control with sirolimus versus calcineurin inhibitor based immunosuppression in renal transplant recipients.
BACKGROUND
Calcineurin inhibitors (CNI) have brought dramatic improvements in early renal allograft survival. However, CNI are associated with posttransplant hypertension (PTHTN), a risk factor for mortality from cardiovascular disease and graft failure. Sirolimus (SRL) is emerging as an alternative to CNI. SRL effects on blood pressure (BP) in humans are unclear. We compared the prevalence of PTHTN among patients receiving SRL as maintenance immunosuppression with a group receiving CNI by using 24-hour ambulatory BP (AMBP). AMBP has been shown to predict cardiovascular events and progression of kidney disease better than casual office BP measurements in chronic kidney disease (CKD) patients.


METHODS
Renal transplant recipients with office hypertension (defined as BP > 130/80 or on antihypertensive medications), receiving stable immunosuppression and displaying consistent serum creatinine values for > or =6 months were eligible. We enrolled the first 40 patients to consent. Office BP was measured twice using a BP-Tru machine. AMBP was then analyzed for systolic BP (SBP), diastolic BP (DBP), and nocturnal blood pressure fall (NF; "dipping"). Patients were placed in the SRL group (n = 18) and the CNI group (n = 20) based on their maintenance immunosuppressive protocol. Two patients were excluded because of incomplete data. All patients received mycophenolate mofetil, and 14/38, maintenance steroids. We collected, demographics as well as type and date of renal allograft, medications, comorbidities, CKD stage, proteinuria, and plasma creatinine at the time of study enrollment.


RESULTS
Patients in the SRL group displayed lower 24-hour SBP than the CNI group (128.0 +/- 10.8 vs 137.7 +/- 14; P = .029). Nightime MAP, nightime SBP, and nighttime DBP were all lower in the SRL group. NF did not reach significance between the SRL and CNI groups (44% vs 15%; P = .074). Patient demographics and number of antihypertensive medications did not differ.


CONCLUSIONS
The lower 24-hour SBP seen in the SRL group by AMBP may lead to improved cardiovascular and renal outcomes over time. Long-term patient follow-up will be needed to clarify the effect of the lower 24-hour SBP.
Steigerwalt
S P
SP
Department of Nephrology, St. John Hospital and Medical Center, 18000 E Warren, Detroit MI 48224, USA.
Brar
N
N
Dhungel
A
A
Butcher
D
D
Steigerwalt
S
S
El-Ghouroury
M
M
Provenzano
R
R
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology*; D015992:Body Mass Index; D002102:Cadaver; D019703:Calcineurin / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D003928:Diabetic Nephropathies / Q000601:surgery; D005260:Female; D006801:Humans; D006973:Hypertension / Q000401:mortality / Q000517:prevention & control / Q000601:surgery; D007165:Immunosuppression Therapy / Q000379:methods*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D018670:Monitoring, Ambulatory / Q000379:methods; D011183:Postoperative Complications / Q000401:mortality / Q000517:prevention & control; D011184:Postoperative Period; D020123:Sirolimus / Q000627:therapeutic use*; D014019:Tissue Donors / Q000706:statistics & numerical data
D000959:Antihypertensive Agents; D019703:Calcineurin; D020123:Sirolimus