Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.

Physician Prevention of Acute Kidney Injury.

BACKGROUND: The frequency of acute kidney injury has become substantially greater over the recent past. Acute kidney injury, moreover, is associated with increased mortality and morbidity over both the short and long term. Despite these facts, its therapy has not changed significantly for many decades. Currently, therefore, prevention is the only action that can reduce the frequency and consequences of acute kidney injury. METHODS: Charts of 492 patients were reviewed retrospectively for the presence of acute kidney injury based on creatinine elevation. One hundred seventy patients were found to have acute kidney injury defined as a sustained elevation of serum creatinine ≥ 0.3 mg/dL for 48 hours or more. An agent or event was determined to be responsible for renal injury if there was the defined increase in serum creatinine within 48 hours of exposure. Charts were reviewed to determine if the renal injury was preventable. RESULTS: Fifty-one cases were considered to be preventable. Of these, 16 had not received saline prophylaxis for intravenous contrast when appropriate, 15 were not treated appropriately for hemodynamic instability or for hypertension, 9 had inappropriate use of medications, and 11 received multiple nephrotoxic agents. CONCLUSIONS: In a retrospective analysis of 170 hospitalized patients who developed acute kidney injury during admission, 30% of episodes could have been avoided if physicians had taken appropriate preventive actions.

Efficacy and safety of canagliflozin in patients with type 2 diabetes and stage 3 nephropathy.

BACKGROUND/AIMS: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT2 inhibitor, was evaluated in patients with stage 3 chronic kidney disease (CKD; eGFR ≥30 to <60 ml/min/1.73 m(2)). METHODS: This analysis used integrated data from four randomized, placebo-controlled, phase 3 studies that enrolled patients with T2DM and stage 3 CKD. RESULTS are presented for the overall population as well as subgroups with stage 3a CKD (eGFR ≥45 and <60 ml/min/1.73 m(2)) and stage 3b CKD (eGFR ≥30 and <45 ml/min/1.73 m(2)). RESULTS: Among all subjects studied with stage 3 CKD, placebo-subtracted reductions in HbA1c (-0.38 and -0.47%; p < 0.001), body weight (-1.6 and -1.9%; p < 0.001), and systolic blood pressure (-2.8 and -4.4 mm Hg; p < 0.01) were seen with canagliflozin 100 and 300 mg, respectively. Decreases in HbA1c, body weight, and systolic blood pressure were examined in the stage 3a and 3b CKD subgroups, with greater decreases in HbA1c, -0.47% (-0.61, -0.32) and body weight in subjects in stage 3a CKD, -1.8% (-2.3, -1.2) with canagliflozin 100 mg. Initial declines in eGFR were seen early following treatment initiation with canagliflozin, but trended towards baseline over time. The most common adverse events with canagliflozin included genital mycotic infections and adverse events related to reduced intravascular volume likely secondary to osmotic diuresis. CONCLUSION: In subjects with T2DM and stage 3 CKD, canagliflozin reduced HbA1c, body weight, and blood pressure, and was generally well tolerated.

Blood pressure, hypertension, RAAS blockade, and drug therapy in diabetic kidney disease.

Type 2 diabetes is the most common cause of CKD and ESRD in the United States and the Western world. Hypertension is prevalent in this cohort, and control of blood pressure is perhaps the most important risk factor to reduce CKD progression. The most recent blood pressure target recommended by the Kidney Disease: Improving Global Outcomes and Kidney Disease Outcomes Quality Initiative guideline committees is less than 140/90 mmHg for all patients with CKD. There is some evidence for those with 1 g or more of albuminuria, albeit weak, to support a blood pressure target of less than 130/80 mmHg. Multiple studies demonstrate that renin-angiotensin-aldosterone system (RAAS) blockers are important in reducing cardiovascular risk and progression of CKD in those with advanced proteinuric nephropathy. However, there is no evidence that they prevent nephropathy or that reduction in microalbuminuria alone is associated with slowed nephropathy progression. The purpose of this article is to review the major studies that have evaluated cardiovascular and kidney endpoints in patients with diabetes and the role of RAAS blockers in the treatment of this disease.

Management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration.

PURPOSE: The management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration (CVVH) is reported. SUMMARY: A 46-year-old African-American woman with New York Heart Association class IV, American College of Cardiology- American Heart Association stage D heart failure arrived from an outside facility with complaints of dyspnea after minimal exertion, orthopnea, and lower-extremity edema. A transthoracic echocardiogram revealed an estimated left ventricular ejection fraction of 15%. The patient subsequently required left ventricular assist device placement on hospital day 5 as a potential bridge to transplantation. A total digoxin loading dose of 500 µg i.v. (8.2 µg/kg) was given in two divided doses six hours apart. The next morning, the serum digoxin concentration was 1.9 ng/mL, and the patient was started on a maintenance digoxin dosage of 125 µg i.v. daily. On postoperative day (POD) 20, the patient developed acute kidney injury, and CVVH was initiated. The sieving coefficient (Sc), transmembrane clearance (CLtm), digoxin concentration in ultrafiltration fluid (Cuf), and need for supplemental digoxin were determined to account for CVVH- associated digoxin loss. After 14 days of CVVH, the patient's clinical condition improved, and CVVH was transitioned to intermittent hemodialysis. On POD 66, the patient was discharged to an extended-care facility without adverse reactions related to digoxin therapy. CONCLUSION: Analysis of serum digoxin concentration and digoxin Cuf values suggested that digoxin was cleared by CVVH, allowed calculation of Sc and CLtm values, and facilitated determination of digoxin requirements in a critically ill patient requiring CVVH.