Rebecca P. Winsett

Effects of Theophylline on Erythropoietin Production in Normal Subjects and in Patients with Erythrocytosis after Renal Transplantation

BACKGROUND Erythrocytosis occurs in 10 to 15 percent of renal-transplant recipients, and there is in vitro evidence that the production of erythropoietin is modulated by adenosine. METHODS We prospectively evaluated the effects of theophylline, a nonselective adenosine antagonist, in eight patients with erythrocytosis after renal transplantation and in five normal controls. RESULTS After an eight-week course of theophylline treatment, the mean (+/- SEM) serum erythropoietin levels were significantly reduced in both the renal-transplant recipients (from 60 +/- 14 units per liter at base line to 9 +/- 7 units after treatment; P less than 0.05) and the normal subjects (from 6.9 +/- 0.8 units per liter at base line to 4.7 +/- 0.5 units per liter after treatment; P less than 0.05). Similarly, the hematocrits were reduced in both the transplant recipients (from 0.58 +/- 0.04 at base line to 0.46 +/- 0.03 after treatment; P less than 0.05) and the normal subjects (from 0.43 +/- 0.01 at base line to 0.39 +/- 0.01; P less than 0.05). In the renal-transplant recipients, red-cell mass was also reduced after eight weeks of theophylline (from 3197 +/- 82 ml at base line to 2273 +/- 69 ml after treatment; P less than 0.05). The previous requirement of weekly phlebotomy was eliminated in all recipients. Plasma and urinary cyclic AMP levels were not increased. These effects were reproducible when the subjects were rechallenged with theophylline after a recovery period. CONCLUSIONS Theophylline attenuates the production of erythropoietin in both normal subjects and patients with erythrocytosis after renal transplantation and may be useful in the treatment of the latter condition.

Kidney-pancreas transplantation: The effect of portal versus systemic venous drainage of the pancreas on the lipoprotein composition

We have previously shown that both kidney-alone and combined kidney-pancreas transplantation lower VLDL and IDL apoB while increasing LDL apoB, apoA-I, and HDL free cholesterol (FC). In this report, we analyze the lipoproteins of 31 patients who have undergone combined kidney-pancreas transplantation. Systemic venous drainage of the pancreas was utilized in 20 of these patients while 11 had portal venous drainage. Six lipoprotein subfractions (VLDL, IDL, LDL, HDL-L, HDL-M, HDL-D) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase HPLC) and lipid (by enzymatic assays) composition of each subfraction was determined. After three months, there were few group differences. However, the portal group had substantial reductions in VLDL apoB at both six (-50% vs. +1%) and twelve months (-57% vs. +149%, P = .042) while the systemic group had increases in VLDL apoB. Similar differences were seen in IDL apoB (six months: -38% vs. +13%; twelve months: -61% vs. +56%, P = .008). LDL apoB increased in both groups at six months (portal: +7%; systemic: +30%) but fell in the portal group at twelve months (-17% vs. +41%, P = .0007). IDL triglyceride, cholesterol ester, phospholipids, and free cholesterol also fell by 19% to 47% in the portal group while they rose by 8% to 44% in the systemic patients, six and twelve months after surgery (P < .05). In addition, the VLDL and LDL free cholesterol to phospholipid ratios (FC/PL) fell (improved) by 16% to 26% in the portal patients while they rose by 9% to 28% in the systemic subjects during this time (P < .04). Finally, there were substantial improvements in the LDL composition of the portal patients compared to the systemic patients at six (PL/apoB: +23% vs. -16%, P = .005; CE/apoB: +14% vs. -14%, P = .037) and twelve months (PL/apoB: +39% vs. -13%, P = .011; CE/apoB: +41% vs. -15%, P = .011). These data indicate that portal drainage of the transplanted pancreas reduced the number of VLDL, IDL, and LDL particles, reduced the total mass of IDL (by 35%), and normalized the VLDL and LDL particle composition. These improvements were not seen in the patients who received systemic drainage of their pancreas. HDL-M also improved in the portal patients (TG: -29% vs. +12%, P = .025) (PL: +22% vs. -5%, P = .014) (total mass: +16% vs. +0.2%, P = .044) but not in the systemic patients six months after surgery. These results suggest that portal venous drainage of the pancreas leads to greater improvements in the lipoprotein composition of IDDM patients than does systemic drainage.

The first report from the patient outcomes registry for transplant effects on life (PORTEL): differences in side-effects and quality of life by organ type, time since transplant and immunosuppressive regimens.

Abstract: Background:  Post‐transplant patient quality of life (QOL) is affected by a number of different factors. A nationwide patient registry has been established to evaluate QOL and determine the effects of transplant and immunosuppressive regimens on patient outcomes.

Medication Adherence in Older Renal Transplant Recipients

This project examined patterns, predictors, and outcomes of medication adherence in a convenience sample of 37 renal transplant recipients aged 55 years or older in a Mid-Southern U.S. facility using an exploratory, descriptive, longitudinal design. Electronic monitoring was conducted for 12 months using the Medication Event Monitoring System. An alarming 86% of the participants were nonadherent with medications. Four clusters of medication taking and timing patterns were identified with evening doses presenting particular challenges. Depression, self-efficacy, social support, and medication side effects did not predict medication adherence. There was no significant difference in medication adherence scores between those with and without infections. Medication adherence pattern data from electronic monitoring provides an opportunity for health care professionals to move away from blaming the patient by attempting to identify predictors for medication nonadherence. Medication dose taking and timing patterns could be explored with patients so that medication adherence interventions could target specific patient patterns.

Cost‐effectiveness of post‐transplantation quality of life intervention among kidney recipients

Background:  The purpose was to demonstrate the cost‐effectiveness of an experimental post‐transplant care program designed to improve kidney transplant recipients’ quality of life (QoL). The intervention program integrated a three‐pronged interdisciplinary approach emphasizing: (i) proactive, patient‐initiated care to prevent transplant‐related morbidities, (ii) employment/vocational counseling, and (iii) enhancement of social support.

Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal failure: Effect of kidney and pancreas transplantation

Chronic renal failure (CRF) in nondiabetics is associated with a number of lipoprotein abnormalities that place these patients at high risk for atherosclerosis. This study compared the lipoprotein composition of nondiabetic controls (n = 68) with that of patients with insulin-dependent diabetes mellitus ([IDDM] n = 13) and of patients with IDDM and CRF ([IDDM + CRF] n = 74). Six lipoprotein subfractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], high-density lipoprotein-light [HDL-L], HDL-medium [HDL-M], and HDL-dense [HDL-D]) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase high-performance liquid chromatography [HPLC]) and lipid (by enzymatic assays) composition of each subfraction was determined. The only abnormalities found in IDDM patients were increases in IDL and HDL-L triglyceride (TG) levels and an increase in the HDL-L free cholesterol (FC) level. The IDDM + CRF group had multiple abnormalities including (1) elevated TG, apolipoprotein (apo) C-II, and apo C-III levels in all lipid subfractions; (2) elevated VLDL and IDL apo B, TG, FC, cholesterol ester (CE), and phospholipid (PL) levels (with an increased CE/TG ratio in VLDL only); (3) decreased HDL-M apo A-I, apo A-II, CE, and PL levels, but an increased HDL-D apo A-I level; and (4) decreased lecithin:cholesterol acyltransferase (LCAT) activity. Twenty-five of the IDDM + CRF patients underwent combined pancreas and kidney (P + K) transplantation, and 12 patients received only a kidney transplant. Lipoprotein composition was determined at 3, 6, and 12 months posttransplant. Both types of transplantation resulted in similar alterations in lipoprotein composition, even though there was essential normalization of blood glucose levels in most of the patients who received a pancreas transplant (hemoglobin A1C [HbA1C], 9.1% +/- 1.1% v 5.7% +/- 0.3% at 12 months, P < .01). These posttransplant changes included (1) no improvement in the elevated TG level in any lipid subfraction even though there was some reduction in apo C-III levels in VLDL; (2) reductions in levels of VLDL and IDL apo B but increases in LDL apo B; (3) increases in HDL apo C-III and FC concentrations despite an increase in LCAT activity; and (4) increases in apo A-I levels in HDL-L and HDL-M. The addition of a pancreas to a kidney transplant had no obvious impact on the lipoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunosuppressant side effect profile does not differ between organ transplant types

Transplantation has enhanced the quality of life of all transplant recipients, but concern remains regarding the side effects of immunosuppressant drugs. In order to respond to these concerns, a survey to ascertain the side effect profile of transplant recipients was undertaken to identify the impact of chronic immunosuppression on quality of life. A nationwide survey of solid organ transplant recipients was carried out using a newly developed immunosuppressant side effect survey. Kidney, kidney–pancreas, liver and heart recipients responded to the survey (n=505) and reflect the national distribution based on the UNOS data for organ type, recipient race and gender. The survey had four subscales: emotional burden, life/role responsibilities, mobility and GI distress. A fifth subscale included miscellaneous side effects that are more prevalent during the first 2 years post‐transplant. Frequency and severity of each side effect were coded on a scale of 0–4 from ‘no problem’ to ‘always’ a problem. The entire range of possible scores (0–160) was reported, reflecting adequate variability in the responses. The sample consisted of 51% males, 77% Caucasians, 15% African Americans, with the remaining 8% other races. There were 225 (44.5%) kidney, 147 (29.1%) liver, 101 (20%) heart and 32 (6.4%) pancreas included. Age ranged from 18–71 years with time since transplant 1–21 years. Overall frequency (12.1±6.08), severity (10.5±6.96) and weighted scores (25.4±19.9) were low suggesting that, as a whole, immunosuppressant side effects, while present, were not severe or troublesome for most patients. Side effect profiles appeared similar among organ types. Differences were detected in the GI distress subscale with the heart recipients reporting significantly less GI distress than liver recipients (13.8 vs. 19.2; P<0.05). Side effect impact on mobility tended to increase between time eras; however, no statistical significance was detected. Side effects are a concern among health‐care professionals; however, based on the results of this study, immunosuppressant‐related side effects are not detrimental to quality of life and show no differences between types of organ transplanted.

Time‐in‐a‐bottle (TIAB): a longitudinal, correlational study of patterns, potential predictors, and outcomes of immunosuppressive medication adherence in adult kidney transplant recipients

This study examined patterns, potential predictors, and outcomes of immunosuppressive medication adherence in a convenience sample of 121 kidney transplant recipients aged 21 yr or older from three kidney transplant centers using a theory‐based, descriptive, correlational, longitudinal design. Electronic monitoring was conducted for 12 months using electronic monitoring. Participants were persistent in taking their immunosuppressive medications, but execution, which includes both taking and timing, was poor. Older age was the only demographic variable associated with medication adherence (r = 0.25; p = 0.005). Of the potential predictors examined, only medication self‐efficacy was associated with medication non‐adherence, explaining about 9% of the variance (r = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly associated with medication non‐adherence, although the small number of poor outcomes may have limited our ability to detect a link. Future research should test fully powered, theory‐based, experimental interventions that include a medication self‐efficacy component.

Contribution of Post-Transplant Social Support to the Quality of Life of Transplant Recipients

Abstract With advances in medicine and pharmacology, post-transplant quality of life (QoL) has become a major concern of researchers. In social work transplant practice, provision of social support towards QoL warrants attention. The purposes of this study were (1) to describe the social support networks of kidney, liver, and pancreas transplant recipients during the post-transplant phase of their recovery, and (2) to examine the correlations between the types and nature of social support networks and the QoL of these transplant recipients. We conducted an exploratory-descriptive study in a US universitys transplant clinic. Instruments were the Social Network Map, Adult Self-image Scale, Sickness Impact Profile, and Quality of Life Index. Descriptive statistics, and correlation analyses were used with a significance level of .05. We observed correlations between concrete and emotional support, and direction, closeness and duration of support, and QoL. Based on our findings, we discussed implications for research and practice.

Assessment of Depressive Symptoms During Post-Transplant Follow-Up Care Performed via Telehealth

Telehealth provides a successful medium for the treatment of depression and other mental health illnesses. Often, inadequate treatment for this condition is found in patients with chronic co-morbid conditions such as those presented by the transplant recipient, a population at risk for depression. One concern of healthcare providers is the inability to adequately screen for symptoms of depression. This secondary analysis describes depression screening of 138 transplant recipients receiving follow-up care via telehealth (TH) and standard care (SC) as part of a larger National Institute of Nursing Research-funded randomized clinical trial. Of subjects who consented, 70 (51%) were randomized to the TH portion of the study. Depressive symptoms were measured by the Center for Epidemiologic Studies-Depression (CES-D) survey at study entry and at 6 and 12 months postconsent into the study. Univariate and subgroup analyses using SAS found no differences between the TH (n = 70) and SC (n = 68) group for demographic and social characteristics. No differences in CES-D scores were found between TH and SC groups. The concern in adding distance in the care of this medically fragile population was not substantiated in this study.