Objective To analyze the characteristics of patients with hypertension after renal transplantation and the utilization of antihypertensive drugs in 5 cities in China from 2015 to 2018,so as to provide reference for clinical rational use of drugs. Methods Based on the multi-center prescription data which were randomly selected from the Hospital Prescription Analysis Cooperation Project,the utilization of antihypertensive drugs was analyzed by the drug utilization analysis method recommended by WHO. Results The data of 33 398 patients with hypertension after renal transplantation were extracted from 40 grade III hospitals (excluding military hospitals) in 5 cities.The ratio of male to female was 2.56.The median age was 43 years old.Patients in the middle age (from 41 to 64 year old)group accounted for the highest proportion (50.93%).The patients mainly purchased drugs in the outpatient pharmacy (81.94%).There was no diagnostic record of hypertension in 75.71% of the patients after renal transplant when using antihypertensive drugs.Among all classes of antihypertensive drugs,the number of calcium channel blockers (CCB) [dihydropyridine CCB (dCCB) 31.15%,non-dihydropyridine CCB (ndCCB) 10.54%],angiotensin II receptor blockers (ARB, 24.86%) and β receptor blockers (βBs,21.16%) prescription were the top three.The PDD/ DDD values of these three kinds of drugs were more than 1.The most commonly used single-drug antihypertensive regimen was dCCB,and the most commonly used combination regimen is dCCB+ARB and dCCB+βB. Conclusion The utilization of antihypertensive drugs in these 5 cities is basically reasonable.But it is still necessary to standardize the diagnostic records and adjustment of drug dosage.During the treatment,the patients' ages,complications,medication compliance and economic status should be considered comprehensively,and the individualized treatment principles should be followed.
Key words:
Drug utilization analysis
;
Kidney transplantation
;
Hypertension
MANGRAYM,VELLA JP.Hypertension after kidney transplant[J].Am J Kidney Dis,2011,57(2):331-341.
Hypertension in kidney transplant recipients is a major "traditional" risk factor for atherosclerotic cardiovascular disease. Importantly, atherosclerotic cardiovascular disease is the leading cause of premature death and a major factor in death-censored graft failure in transplant recipients. The blood pressure achieved after transplant is related inversely to postoperative glomerular filtration rate (GFR), with many patients experiencing a significant improvement in blood pressure control with fewer medications within months of surgery. However, the benefits of improved GFR and fluid status may be affected by the immunosuppression regimen. Immunosuppressive agents affect hypertension through a variety of mechanisms, including catechol- and endothelin-induced vasoconstriction, abrogation of nitric oxide-induced vasodilatation, and sodium retention. Most notable is the role of calcineurin inhibitors in promoting hypertension, cyclosporine more so than tacrolimus. Additionally, the combination of calcineurin-and mammalian target of rapamycin (mTOR)-inhibitor therapy is synergistically nephrotoxic and promotes hypertension, whereas steroid withdrawal and minimization strategies seem to have little or no impact on hypertension. Other important causes of hypertension after transplant, beyond a progressive decrease in GFR, include transplant renal artery stenosis and sequelae of antibody-mediated rejection. Calcium channel blockers may be the most useful medication for mitigating calcineurin inhibitor-induced vasoconstriction, and use of such agents may be associated with improvements in GFR. Use of inhibitors of the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, remains an attractive strategy for many transplant recipients, although some recipients may have significant adverse effects associated with these medications, including decreased GFR, hyperkalemia, and anemia. In conclusion, hypertension control affects both patient and long-term transplant survival, and its best management requires careful analysis of causes and close monitoring of therapies. Am J Kidney Dis. 57(2):331-341. (C) 2011 by the National Kidney Foundation, Inc.
CARPENTER MA,JOHNA,WEIR MR,et al.BP,cardiovascular disease,and death in the folic acid for vascular outcome reduction in transplantation trial[J].J Amer Society Nephrol,2014,25(7):1554-1562.
MANGE KC,CIZMANB,JOFFEM,et al.Arterial hypertension and renal allograft survival[J].JAMA,2000,283(5):633-638.
CONTEXT: Several observational studies have investigated the significance of hypertension in renal allograft failure; however, these studies have been complicated by the lack of adjustment for baseline renal function, leaving the role of elevated blood pressure in allograft failure unclear. OBJECTIVE: To examine the relationship between blood pressure adjusted for renal function and survival after cadaveric allograft transplantation. DESIGN: Nonconcurrent historical cohort study conducted from 1985 through 1997. SETTING: University teaching hospital. PARTICIPANTS: A total of 277 patients aged 18 years or older who underwent cadaveric renal transplantation without another simultaneous organ transplantation and whose allograft was functioning for a minimum of 1 year. Follow-up continued through 1997 (mean follow-up, 5.7 years). MAIN OUTCOME MEASURE: Time to allograft failure (defined as death, return to dialysis, or retransplantation) by systolic, diastolic, and mean arterial blood pressure measurements at 1 year after transplantation. RESULTS: Multivariate Cox proportional hazards modeling demonstrated that nonwhite ethnicity, history of acute rejection, and nondiabetic kidney disease were significant predictors of failure (P = .01 for all). In addition, the calculated creatinine clearance at 1 year had an adjusted rate ratio (RR) for allograft failure per 10 mL/min (0.17 mL/s) of 0.74 (95% confidence interval [CI], 0.62-0.88). The RR per 10-mm Hg increase in blood pressure measured at 1 year after transplantation, after adjustment for creatinine clearance, was 1.15 (95% CI, 1.02-1.30) for systolic pressure, 1.27 (95% CI, 1.01-1.60) for diastolic pressure, and 1.30 (95% CI, 1.05-1.61) for mean arterial pressure. Supplemental analyses that did not include death as a failure event or reduce the minimum allograft survival time for study subjects to 6 months yielded results consistent with the primary analysis. There was no evidence of modification of the blood pressure-allograft failure relationship by ethnicity or diabetes mellitus. CONCLUSIONS: Systolic, diastolic, and mean arterial blood pressures at 1 year posttransplantation strongly predict allograft survival adjusted for baseline renal function. More aggressive control of blood pressure may prolong cadaveric allograft survival.
PISANOA,BOLIGNANOD,MALLAMACIF,et al.Comparative effectiveness of different antihypertensive agents in kidney transplantation:a systematic review and meta-analysis[J].Nephrol Dial Transplant,2020,35(5):878-887.
BACKGROUND: We conducted a systematic review and meta-analysis to compare benefits and harms of different antihypertensive drug classes in kidney transplant recipients, as post-transplant hypertension (HTN) associates with increased cardiovascular (CV) morbidity and mortality. METHODS: The Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing all main antihypertensive agents versus placebo/no treatment, routine treatment. RESULTS: The search identified 71 RCTs. Calcium channel blockers (CCBs) (26 trials) reduced the risk for graft loss {risk ratio [RR] 0.58 [95% confidence interval (CI) 0.38-0.89]}, increased glomerular filtration rate (GFR) [mean difference (MD) 3.08 mL/min (95% CI 0.38-5.78)] and reduced blood pressure (BP). Angiotensin-converting enzyme inhibitors (ACEIs) (13 trials) reduced the risk for graft loss [RR 0.62 (95% CI 0.40-0.96)] but decreased renal function and increased the risk for hyperkalaemia. Angiotensin receptor blockers (ARBs) (10 trials) did not modify the risk of death, graft loss and non-fatal CV events and increased the risk for hyperkalaemia. When pooling ACEI and ARB data, the risk for graft failure was lower in renin-angiotensin system (RAS) blockade as compared with control treatments. In direct comparison with ACEIs or ARBs (11 trials), CCBs increased GFR [MD 11.07 mL/min (95% CI 6.04-16.09)] and reduced potassium levels but were not more effective in reducing BP. There are few available data on mortality, graft loss and rejection. Very few studies performed comparisons with other active drugs. CONCLUSIONS: CCBs could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss. No definite patient or graft survival benefits were associated with RAS inhibitor use over conventional treatment.
WHELTON PK,CAREY RM,ARONOW WS,et al.2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention,Detection,Evaluation,and Management of High Blood Pressure in Adults:A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines[J].Circulation,2018,138(17):e484-e594.
JENNINGS DL,TABER DJ.Use of renin-angiotensin-aldosterone system inhibitors within the first eight to twelve weeks after renal transplantation[J].Ann Pharmacother,2008,42(1):116-120.
JONES TE,MORRIS RG.Pharmacokinetic interaction between tacrolimus and diltiazem:dose-response relationship in kidney and liver transplant recipients[J].Clin Pharmacokinet,2002,41(5):381-388.
OBJECTIVE: To study the dose-response relationship of the pharmacokinetic interaction between diltiazem and tacrolimus in kidney and liver transplant recipients. DESIGN: Nonrandomised seven-period stepwise pharmacokinetic study. PATIENTS: Stable kidney (n = 2) and liver (n = 2) transplant recipients maintained on oral tacrolimus twice daily but not taking diltiazem. METHODS: Patients were treated with seven incremental dosages of diltiazem (0 to 180 mg/day) at > or = 2-weekly intervals. At the end of each interval, 13 blood samples were taken over a 24-hour period to allow determination of morning (AUC(12)), evening (AUC(12-24)) and 24-hour (AUC(24)) areas under the concentration-time curve for tacrolimus, as well as AUC(24) for diltiazem and three of its metabolites. RESULTS: There was considerable interpatient variability in tacrolimus-sparing effect. In the two kidney transplant recipients, an increase in tacrolimus AUC(24) occurred following the 20 mg/day dosage of diltiazem (26 and 67%). The maximum increase in tacrolimus AUC(24) occurred at the maximum diltiazem dosage used (180 mg/day), when the increase was 48 and 177%. In the two liver transplant recipients, an increase in tacrolimus AUC(24) did not occur until a higher diltiazem dosage (60 to 120 mg/day) was given. The increase at the maximum diltiazem dosages used (120 mg/day in one and 180 mg/day in the other) was also lower (18 and 22%) than that exhibited by the kidney transplant recipients. The increase in tacrolimus AUC(12) was similar to the increase in AUC(12-24) when diltiazem was given in the morning only (dosages < or = 60 mg/day). Hence, diltiazem affects blood tacrolimus concentrations for longer than would be predicted from the half-life of diltiazem in plasma. CONCLUSIONS: The mean tacrolimus-sparing effect of diltiazem was similar in magnitude to the cyclosporin-sparing effect previously reported. Whether the lesser tacrolimus-sparing effect with diltiazem seen in the liver transplant recipients was due to functional differences in the transplanted liver is not known, but it was not due to lower plasma diltiazem concentrations. Diltiazem makes a logical tacrolimus-sparing agent because of the potential financial savings and therapeutic benefits. Because of interpatient variability, the sparing effect should be demonstrated in each patient and not merely assumed.
FRIED LF,EMANUELEN,ZHANG JH,et al.Combined angiotensin inhibition for the treatment of diabetic nephropathy[J].N Engl J Med,2013,369(20):1892-1903.
BACKGROUND: Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of >/= 30 ml per minute per 1.73 m(2) if the initial estimated GFR was >/= 60 ml per minute per 1.73 m(2) or a decline of >/= 50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217.).
MANN JF,SCHMIEDER RE,MCQUEENM,et al.Renal outcomes with telmisartan,ramipril,or both,in people at high vascular risk (the ONTARGET study):a multicentre,randomised,double-blind,controlled trial[J].Lancet,2008,372(9638):547-553.
BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS: The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION: In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention,Detection,Evaluation,and Management of High Blood Pressure in Adults:A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Renal outcomes with telmisartan,ramipril,or both,in people at high vascular risk (the ONTARGET study):a multicentre,randomised,double-blind,controlled trial
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