Background: Rising numbers of patients reaching end-stage kidney disease intensify the demand for expansion of the living–kidney-donor pool. On the basis of low risk in white donors with essential hypertension, our transplant center undertook a structured program of accepting hypertensive donors if kidney function and urine protein were normal. This study reports outcomes of hypertensive donors 1 year after kidney donation. Methods: We studied detailed measurements of blood pressure (oscillometric, hypertensive therapy nurse [RN], and ambulatory blood pressure monitoring [ABPM]), clinical, and renal characteristics (iothalamate glomerular filtration rate [GFR], urine protein, and microalbumin) in 148 living kidney donors before and 6 to 12 months after nephrectomy. Twenty-four were hypertensive (awake ABPM>135/85 mm Hg and clinic/RN BP>140/90 mm Hg) before donation. Results: After 282 days, normotensive donors had no change in awake ABPM pressure (pre 121±1/75±2 vs. post 120±1/ 5±1 mm Hg), whereas BP in hypertensive donors fell with both nonpharmacologic and drug therapy (pre 142±3/85±2 to post 132±2/80±1 mm Hg, P<.01). Hypertensive donors were older (53.4 vs. 41.4 years, P<.001) and had lower GFR after kidney donation (61±2 vs. 68±1 mL/min/1.73m2, P<.01). After correction for age, no independent BP effect was evident for predicting GFR either before or after nephrectomy. Urine protein and microalbumin did not change in either group after donor nephrectomy. Conclusions: Our results indicate that white subjects with moderate, essential hypertension and normal kidney function have no adverse effects regarding blood pressure, GFR, or urinary protein excretion during the first year after living kidney donation. Although further studies are essential to confirm long-term safety, these data suggest that selected hypertensive patients may be accepted for living kidney donation.
7092 Background: We are conducting a pilot, exploratory study of the potential value of alemtuzumab(alem) in maintenance therapy of previously treated chronic lymphocytic leukemia (CLL) patients(pts) after they have achieved stable disease or partial remission with chemo or chemo-immunotherapy. We present the results of serially monitored CD19+ (B)lymphocytes and CD4+ (T) lymphocytes on eight evaluable patients. Methods: 30mg doses of alem were administered SC to all patients at the following schedule: wkly for 8 doses (8 wks), followed by q2 wks for 8 doses(16 wks), followed by q3 wks for 8 doses (24 wks). This schedule provides a total of 48 wks of maintenance treatment with alem. Patients received standard prophylaxis with sulfamethoxizole and acyclovir with regular CMV monitoring by quantitative PCR. Results: In the table we present data on the pattern of decrease in blood CD19+(B) cells and CD4+ (T) cells on eight evaluable pts at different time points after starting alem maintenance. Because flow cytometry was not done on all pts at each time point, the number of pts contributing to the calculation of mean counts at each given time point is variable. CD19+(B) cells were markedly reduced to 37% of baseline consistently, from 8 wks onward. CD4+(T) cells, on the other hand, were consistently higher than 50% of the baseline after 8 wks. No opportunistic infections were seen in any pt and treatment was well tolerated. Conclusion: These results from a single institution based pilot study demonstrate that alem used in maintenance schedule is effective in keeping the blood levels of CD19+(B) cells extremely low without concordant suppression of CD4+(T) lymphocytes. No significant financial relationships to disclose. [Table: see text]
We appreciate the issues raised by Dr. Herman and colleagues regarding follow-up of living kidney donors with treated hypertension. They underscore dilemmas faced by all transplant programs. At some point, each must identify criteria consistent with its population and its interpretation of best medical practices. Most criteria are subject to varied opinions and can be controversial when data are sparse. Several questions addressed measurement of blood pressure (BP), which we discuss elsewhere (1). Our data support the observations of Odzemir that classification of BP differs between ambulatory monitoring (ABPM) and “office” readings. Small differences result in large classification errors when patients are near a specific “cutoff” level. This is most common in older donors. No initial pressure in our study was absolutely excluded. However, we aimed to achieve “normal” levels (defined as <140/90 mmHg by an RN) using a “simple regimen,” defined as lifestyle measures and an angiotensin receptor blocker with or without a thiazide. Subjects requiring more therapy (three or more drugs) and/or having other disqualifiers (glucose intolerance, low GFR, abnormal structure, or microalbuminuria) were among those not accepted. No systematic evaluation of the retina or LVH was undertaken. ABPM measurements were obtained overnight for 18 hr as we have described (2) to obtain awake and nocturnal readings without interfering with daytime tests. These include CT angiography and others that affect BP. These intervals achieve more than 90% concordance with the entire awake period of a 24 hr monitor, as others have established (3,4). A small time-of-day effect (2–4 mm Hg higher) in the afternoon was considered acceptable. For BP classification, the awake period (normal <135/85 mm Hg) is an accepted standard. Nocturnal pressures and day–night variation are presented separately in our report. If we had averaged all pressures recorded, lower overall pressures would have been observed due to the nocturnal decline. These points, of course, are tangential to the broader issue: how and what criteria should be applied for selection of living kidney donors? Some “historical” criteria may no longer apply. These authors note that previous studies suggest that subsequent “hypertension” was more common with higher predonation BP (i.e. 160/95 mmHg). Newer population-based studies demonstrate that pressure rises with age in the U.S. More than 75% of those above age 65 now have “hypertension,” the threshold of which has been lowered to 140/90 mmHg. The Joint National Commission (JNC 7) emphasizes that the lifetime risk of hypertension exceeds 90% for someone reaching age 55 with normal pressures (5). Hence, nearly everyone will become “hypertensive,” regardless of whether they undergo donor nephrectomy. Early identification and treatment of hypertensive donors initiates care that might be delayed otherwise. Fortunately, we are not truly breaking new ground. Pressures acceptable in 1987 (160/95 mm Hg) were higher than those in our “hypertensive donors.” Experience with more than 47,000 donors since 1987 is reassuring in that neither adverse mortality nor renal disease risk has been identified, despite numerous studies. We agree that changes in demographics and life expectancy limit applying previous experience to current kidney donors. It is essential to improve follow-up care and data collection. Blood pressure is but one of the criteria undergoing careful review. We believe it is paramount for active transplant centers to develop practice parameters and monitor their results closely, as we are doing. Stephen C. Textor Sandra J. Taler Nancy Driscoll Timothy S. Larson James Gloor Matthew Griffin Fernando Cosio Thomas Schwab Mikel Prieto Scott Nyberg Michael Ishitani Mark Stegall Department of Medicine Division of Nephrology and Hypertension Department of Transplant Surgery and Transplant Center Mayo Clinic Rochester, MN
Idelalisib is a first-in-class oral selective inhibitor of phosphatidylinositol 3-kinase delta, which is selectively expressed in hematopoietic cells, where it is critical to B-cell receptor signaling and B-cell development and function.Idelalisib is approved in the United States for the treatment of relapsed chronic lymphocytic leukemia (CLL; in combination with rituximab), relapsed follicular lymphoma (FL), and small lymphocytic lymphoma (SLL) and in the European Union for the treatment of CLL (in combination with rituximab).Approval was based on clinical activity in a phase II trial in indolent non-Hodgkin lymphoma and a phase III trial in CLL.Because idelalisib is a relatively new treatment option for patients with relapsed CLL, SLL, and FL, with a safety profile distinct from other agents, it is important for advanced practitioners (APs) to familiarize themselves with the adverse event (AE) profile and educate their patients as well.As active members of the oncology care team, APs can play a vital role in optimizing outcomes in patients receiving idelalisib therapy.This review will familiarize APs with the AE profile of idelalisib and provide practical information about the identification and management of AEs associated with idelalisib therapy.
