Posaconazole Serum Drug Levels Associated With Pseudohyperaldosteronism.

BACKGROUND: Posaconazole tablets are well tolerated and efficacious in the prophylaxis and treatment of aspergillosis, mucormycosis, and other invasive fungal infections. There have been case reports of posaconazole-induced pseudohyperaldosteronism (PIPH); however, its occurrence and association with serum posaconazole drug levels have not previously been investigated. METHODS: In this single-center, retrospective, observational study, we examined the occurrence of PIPH in outpatients newly starting posaconazole and evaluated differences in serum posaconazole concentrations and clinical characteristics between those with and without this syndrome. RESULTS: Sixty-nine patients receiving posaconazole were included, of whom 16 (23.2%) met the definition of PIPH. Patients with PIPH were significantly older (61.1 vs 44.7 years, P = .007) and more frequently had hypertension prior to starting posaconazole (68.8% vs 32.1%, P = .009). Patients with PIPH had a significantly higher median serum posaconazole level than those without PIPH (3.0 vs 1.2 µg/mL, P ≤ .0001). There was a positive correlation between serum posaconazole levels and changes in systolic blood pressure (r = .37, P = .01), a negative correlation between serum posaconazole levels and changes in serum potassium (r = -.39, P = .006), and a positive correlation between serum posaconazole levels and serum 11-deoxycortisol (r = .69, P < .0001). CONCLUSIONS: Posaconazole is associated with secondary hypertension and hypokalemia, consistent with pseudohyperaldosteronism, and development is associated with higher serum posaconazole concentrations, older age, and baseline hypertension.

Management of posaconazole-induced pseudohyperaldosteronism.

BACKGROUND: Posaconazole-induced pseudohyperaldosteronism (PIPH) has been associated with elevated posaconazole serum concentrations. Clinicians are faced with the difficult task of managing patients with PIPH while maintaining the efficacy of antifungal therapy. Commonly, modifications to posaconazole therapy are utilized in managing PIPH, including dosage reduction of posaconazole or switch to an alternative antifungal. OBJECTIVES: To characterize the management of patients diagnosed with PIPH and their response to various therapeutic interventions. METHODS: We retrospectively reviewed 20 consecutive adult patients diagnosed with PIPH. Patient data collected included blood pressure, electrolytes, endocrine laboratory values and posaconazole serum concentrations collected before and after therapeutic intervention. RESULTS: Of 20 patients included, 17 patients (85%) underwent therapeutic modification, with posaconazole dose reduction (n = 11) as the most common change. Other modifications included discontinuation (n = 3), switch to an alternative antifungal (n = 2) and addition of spironolactone (n = 1). Clinical improvement (decrease in systolic blood pressure and increase in serum potassium) was observed in 9 of 17 patients (52.9%). An average decrease in systolic blood pressure of 7.1 mmHg and increase in serum potassium of 0.22 mmol/L was observed following therapeutic modification. CONCLUSIONS: We report our experience with PIPH management, for which there is no universally effective strategy. We utilized a stepwise approach for management, starting with posaconazole dose reduction and repeat assessment of clinical and laboratory parameters. If resolution of PIPH is not achieved, an alternative triazole antifungal or the addition of an aldosterone antagonist are additional potential interventions. It is possible for PIPH to persist after therapeutic modification despite these interventions. Thus, early diagnosis and continuous monitoring is warranted.

Protected Time for Program Administration among Nephrology Program Leadership in the United States.

BACKGROUND: In 2022, the Accreditation Council for Graduate Medical Education reduced minimum program director protected time for program administration from 10 to 8 h/wk, with no core faculty requirement. We surveyed program leaders regarding the effect of these changes. METHODS: This is an anonymous, online survey of all US adult nephrology program directors (March 2023), who forwarded core faculty/associate program director (APD) surveys. The questions included protected time in 2022-2023 and 2021-2022, whether it was sufficient, estimated time needed, and two validated single-item burnout measures (emotional exhaustion and depersonalization). The analysis was descriptive. RESULTS: Program directors: Their response was 62% (92/149), with geographic distribution/approved fellow positions similar to those nationally. Overall, protected time slightly increased from 2021 to 2022, largely in >6-fellow programs, but 42% (13/31) of these were still not meeting minimum requirements. Only 37% (30/81) agreed that they had sufficient protected time. Those with ≤6 fellows estimated needing 11±4 h/wk (15±4 h/wk with >6 fellows). Twenty-five percent (20/81) reported high levels of emotional exhaustion. Core faculty: 57 of 149 program directors (38%) forwarded the link to 454 faculty. Ninety-four percent of APDs (49/52) responded, reported 3±3 h/wk protected time (42% had none), and estimated needing 6±3 h/wk, regardless of program size. Sixty-seven of 402 core faculty (17%) responded, reported 2±3 h/wk (50% had none), and estimated needing 5±3 h/wk, regardless of program size. ≥85% of APDs and core faculty precepted clinical rotations, gave lectures, evaluated fellows, mentored scholarly work, and participated in recruitment. The majority assisted in fellow remediation. Thirty-four percent (15/44) of APDs and 21% (13/61) of core faculty reported high levels of emotional exhaustion. CONCLUSIONS: Program leaders estimated minimum necessary program administration times (on the basis of program size) that exceeded the Accreditation Council for Graduate Medical Education requirements. APDs/core faculty contributed substantially to nonclinical training. Thirty-four percent of APDs and 25% of program directors had a high likelihood of burnout.

Nephrology Program Director Protected Time for Program Administration in the United States.

BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) required that program directors receive 10-20 h/wk of protected time for program administration (including didactic teaching). In July 2022, this was reduced for all internal medicine subspecialties on the basis of program size, with 8 h/wk required for programs with fewer than seven fellows, the majority of nephrology programs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We surveyed all 151 US adult nephrology program directors (ACGME Public List of Programs 2021-2022) to determine how much protected time they receive, how much they think is necessary, and the division of their professional time. The anonymous 20-question online survey was administered from March 31 to April 30, 2022. The analysis was descriptive. RESULTS: Response rate was 66% (99 of 151). Geographic distribution and approved fellow positions were similar to programs nationally; 59% had fewer than seven approved positions. Median protected time was 10 h/wk (interquartile range, 5-10), with 8 h/wk (interquartile range, 5-10) for those with fewer than seven positions. Program directors estimated needing 12 h/wk (interquartile range, 10-16) to effectively administer programs, including those with fewer than seven positions, a median 5 h/wk (interquartile range, 0-7) more than received. Of program directors reporting <10 h/wk for program administration, 62% provided >20 hours of direct patient care. Thirty-nine percent had no protected time for core faculty. Fellow recruitment (68%) was the most time-consuming task, and didactic teaching (80%) was the most professionally rewarding. CONCLUSIONS: Approximately half of the nephrology programs surveyed were not in compliance with the ACGME-stipulated 10-h/wk minimum protected time for the 2021-2022 training year. Program directors estimated a median of 12 h/wk are needed to effectively manage programs.

Living donor kidney versus simultaneous pancreas-kidney transplant in type I diabetics: an analysis of the OPTN/UNOS database.

BACKGROUND AND OBJECTIVES: Transplant options for type I diabetics with end-stage renal disease include simultaneous pancreas-kidney (SPKT), living donor kidney (LDKT), and deceased donor kidney transplant (DDKT). It is unclear whether SPKT offers a survival benefit over LDKT in the current era of transplantation. The authors compared outcomes of kidney transplant recipients with type I diabetes using data from the Organ Procurement and Transplant Network/United Network for Organ Sharing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Adult (age 20 to 59) type I diabetics who received a solitary first-time kidney transplant between 2000 and 2007 were studied. Outcomes included overall kidney graft and patient survival. Multivariate analysis was performed using a stepwise Cox proportional hazards model. RESULTS: Kidney graft survival was better for recipients of LDKT compared with SPKT (P = 0.008), although patient survival was similar (P = 0.346). On multivariate analysis, LDKT was associated with lower adjusted risks over 72 mo follow-up of kidney graft failure (HR 0.71; 95% CI 0.61 to 0.83) and patient death (HR 0.78; 95% CI 0.65 to 0.94) versus SPKT. Compared with DDKT, SPKT had superior unadjusted kidney graft and patient survival, partly due to favorable SPKT donor and recipient factors. CONCLUSIONS: Despite more transplants from older donors and among older recipients, LDKT was associated with superior outcomes compared with SPKT and was coupled with the least wait time and dialysis exposure. LDKT utilization should be considered in all type I diabetics with an available living donor, particularly given the challenges of ongoing organ shortage.