Medicine non-adherence in kidney transplantation

Background: The increasing prevalence of chronic kidney disease, the relative shortage of kidney donors and the economic- and health-related costs of kidney transplant rejection make the prevention of adverse outcomes following transplantation a healthcare imperative. Although strict adherence to immunosuppressant medicine regimens is key to preventing kidney rejection, evidence suggests that adherence is sub-optimal. Strategies need to be developed to help recipients of kidney transplants adhere to their prescribed medicines. Findings: This review has found that a number of factors contribute to poor adherence, for example, attitudes towards medicine taking and forgetfulness. Few investigations have been conducted, however, on strategies to enhance medicine adherence in kidney transplant recipients. Strategies that may improve adherence include pharmacist-led interventions (incorporating counselling, medicine reviews and nephrologist liaison) and nurse-led interventions (involving collaboratively working with recipients to understand their routines and offering solutions to improve adherence). Strategies that have shown to have limited effectiveness include supplying medicines free of charge and providing feedback on a participant's medicine adherence without any educational or behavioural interventions. Conclusion: Transplantation is the preferred treatment option for people with end-stage kidney disease. Medicine non-adherence in kidney transplantation increases the risk of rejection, kidney loss and costly treatments. Interventions are needed to help the transplant recipient take all their medicines as prescribed to improve general well-being, medicine safety and reduce healthcare costs. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Nephrologists' management of patient medications in kidney transplantation: results of an online survey

Rationale, aims and objectives: Medication adherence is essential in kidney transplant recipients to reduce the risk of rejection and subsequent allograft loss. The aim of this study was to delineate what 'usual care' entails, in relation to medication management, for adult kidney transplant recipients. Methods: An online survey was developed to explore how nephrologists promote and assess medication adherence, the management of prescriptions, the frequency of clinic appointments and the frequency of clinical screening tests. Nephrologists from all acute kidney transplant units in Victoria, Australia, were invited to participate. Data were collected between May and June 2014. Results: Of 60 nephrologists invited to participate, 22 completed the survey (response rate of 36.6%). Respondents had a mean age of 49.1±10.1 years, with a mean of 20.1±9.9 years working in nephrology and 14 were men. Descriptive analysis of responses showed that nephrologists performed frequent screening for kidney graft dysfunction that may indicate medication non-adherence, maintained regular transplant clinic visits with patients and emphasized the importance of medication education. However, time constraints during consultations impacted on extensive patient education and the long-term medication follow-up support was often delivered by the renal transplant nurse coordinator or pharmacist. Conclusions: This study highlighted that nephrologists took an active approach in the medication management of kidney transplant recipients, which may assist with facilitating long-term graft survival. Ultimately, promoting medication adherence needs to be patient centred, involving an interdisciplinary team of nephrologists, pharmacists and renal transplant nurse coordinators, working together with the patient to establish optimal adherence.

Renal transplantation in patients with primary immunoglobulin A nephropathy

Background. Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial.
Methods. We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984–2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed.
Results. Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 ± 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 ± 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001).
Conclusions. Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.

Examining the preparation and ongoing support of adults to take their medications as prescribed in kidney transplantation.

RATIONALE, AIMS AND OBJECTIVES: The shortage of kidney donors and benefits of kidney transplantation make graft success imperative. Medication adherence is critical to prevent the risk of graft rejection. This paper examines how adults are prepared and supported by renal transplant co-ordinators and pharmacists to take their medications as prescribed in kidney transplantation. METHODS: Renal transplant co-ordinators and pharmacists of all five hospitals offering adult kidney transplantation in Victoria, Australia, were interviewed between November 2013 and February 2014. All data underwent qualitative descriptive analysis. RESULTS: Nine renal transplant co-ordinators and six pharmacists were interviewed. Although there was no standardized approach to education or other evidence-based strategies to facilitate medication adherence, there were similarities between sites. These similarities included printed information, pre-transplant education sessions, the use of medication lists and medication administration aids, intensive education in hospital and ensuring an adequate supply of medications post-discharge. CONCLUSIONS: Renal transplant co-ordinators and pharmacists recognized the importance of early patient education concerning immunosuppressant medication. However, each site had developed their own way of preparing a patient for kidney transplantation and follow-up in the acute hospital setting based on experience and practice. Other non-educational strategies involving behavioural and emotional aspects were less common. Differences in usual care reinforce the necessity for evidence-based health care for best patient outcomes.

Trials and tribulations with electronic medication adherence monitoring in kidney transplantation

Medication adherence in kidney transplantation is critical to prevent graft rejection. Testing interventions designed to support patients to take their prescribed medications following a kidney transplant require an accurate measure of medication adherence. In research, the available methods for measuring medication adherence include self-report, pill counts, prescription refill records, surrogate measures of medication adherence and medication bottles with a microchip-embedded cap to record bottle openings. Medication bottles with a microchip-embedded cap are currently regarded as the gold standard measure. This commentary outlines the challenges in measuring medication adherence using electronic medication monitoring of kidney transplant patients recruited from five sites. The challenges included obtaining unanimous stakeholder support for using this method, agreement on an index medication to measure, adequate preparation of the patient and training of pharmacy staff, and how to analyze data when periods of time were not recorded using the electronic adherence measure. Provision of this information will enable hospital and community pharmacists to implement approaches that promote the effective use of this adherence measure for optimal patient outcomes.

The transplant team's support of kidney transplant recipients to take their prescribed medications: a collective responsibility.

AIMS AND OBJECTIVES: To obtain an understanding of how health professionals support the kidney transplant patient to take their medications as prescribed long term. BACKGROUND: Kidney transplantation requires stringent adherence to complex medication regimens to prevent graft rejection and to maintain general well-being. Medication nonadherence is common in kidney transplantation, emerging in the first few months post-transplantation, leading to poor patient outcomes. DESIGN: Exploratory qualitative design. METHODS: Five focus groups were conducted with a total of seven renal nurse transplant coordinators, two renal transplant nurse unit managers, seven nephrologists, seven pharmacists, four social workers, and one consumer representative representing all five hospitals offering adult kidney transplantation in Victoria, Australia in 2014. The views of two general practitioners who were unable to attend the focus groups were incorporated into the data set. All data underwent thematic analysis. RESULTS: Analysis revealed that adherence was a collective responsibility involving the whole of the transplant team and the patient via education blitz in hospital, identifying and managing nonadherence, promotion of self-advocacy, and the partnership between the patient and health professional. Patients were directed how to take their complex medications to be self-empowered, yet the partnership between the patient and health professional limited the patient's voice. CONCLUSION: Although medication adherence was a collective responsibility, communication was often one-way chiefly as a result of staffing and time constraints, hindering effective partnerships necessary for medication adherence. Expert skills in communication and adherence counselling are necessary to identify barriers affecting medication adherence. Patients need to be systematically screened, prepared and supported long-term within an accommodating healthcare system for the reality of caring for their transplanted kidney. RELEVANCE TO CLINICAL PRACTICE: Kidney transplant recipients require systematic preparation and quality long-term follow-up to adhere to their prescribed medications.

Stressors and coping resources of Australian kidney transplant recipients related to medication taking: a qualitative study

AIM: To understand the stressors related to life post-kidney transplantation, with a focus on medication adherence, and the coping resources people use to deal with these stressors. BACKGROUND: Although kidney transplantation offers enhanced quality and years of life for patients, the management of a kidney transplant post-surgery is a complex process. DESIGN: A descriptive exploratory study. METHOD: Participants were recruited from five kidney transplant units in Victoria, Australia. From March to May 2014, patients who had either maintained their kidney transplant for ≥ 8 months or had experienced a kidney graft loss due to medication non-adherence were interviewed. All audio-recordings of interviews were transcribed verbatim and underwent Ritchie and Spencer's framework analysis. RESULTS: Participants consisted of fifteen men and ten women aged 26 - 72 years old. All identified themes were categorised into: 1) Causes of distress and 2) Coping resources. Post-kidney transplantation, causes of distress included the regimented routine necessary for graft maintenance, and the everlasting fear of potential graft rejection, contracting infections and developing cancer. Coping resources utilised to manage the stressors were firstly, a shift in perspective about how easy it was to manage a kidney transplant than to be dialysis-dependent and secondly, receiving external help from fellow patients, family members and healthcare professionals in addition to utilising electronic reminders. CONCLUSION: An individual well-equipped with coping resources is able to deal with stressors better. It is recommended that changes, such as providing regular reminders about the lifestyle benefits of kidney transplantation, creating opportunities for patients to share their experiences and promoting the utilisation of a reminder alarm to take medications, will reduce the stress of managing a kidney transplant.

Natriuretic peptide guanylyl cyclase receptors in the kidney of the Japanese eel, Anguilla japonica

Natriuretic peptides are linked to osmoregulation, cardiovascular and volume regulation in fishes. The peptides bind to two guanylyl-cyclase-linked receptors, natriuretic peptide receptor-A (NPR-A) and NPR-B, to elicit their effects. Atrial natriuretic peptide (ANP) binds principally to NPR-A, whereas C-type natriuretic peptide (CNP) binds to NPR-B. The teleost kidney has an important role in the maintenance of fluid and electrolyte balance; therefore, the location of NPR-A and NPR-B in the kidney could provide insights into the functions of natriuretic peptides. This study used homologous, affinity purified, polyclonal antibodies to NPR-A and NPR-B to determine their location in the kidney of the Japanese eel, Anguilla japonica. Kidneys from freshwater and seawater acclimated animals were fixed overnight in 4% paraformaldehyde before being paraffin-embedded and immunostained. NPR-A immunoreactivity was found on the apical membrane of proximal tubule 1 and the vascular endothelium including the glomerular capillaries. In contrast, NPR-B immunoreactivity was located on the smooth muscle of blood vessels including the glomerular afferent and efferent arterioles, and on smooth muscle tissue surrounding the collecting ducts. No difference in the distribution of NPR-A and NPR-B was observed between freshwater and seawater kidneys. Immunoreactivity was not observed in any tissue in which the antibodies had been preabsorbed. In addition, there was no difference in NPR-A and NPR-B mRNA expression between freshwater-acclimated and seawater-acclimated eels. These results suggest that, although utilizing the same second messenger system, ANP and CNP act on different targets within the kidney and presumably elicit different effects.

Universal nonuniform random vector generator based on acceptance-rejection

The acceptance/rejection approach is widely used in universal nonuniform random number generators. Its key part is an accurate approximation of a given probability density from above by a hat function. This article uses a piecewise constant hat function, whose values are overestimates of the density on the elements of the partition of the domain. It uses a sawtooth overestimate of Lipschitz continuous densities, and then examines all local maximizers of such an overestimate. The method is applicable to multivariate multimodal distributions. It exhibits relatively short preprocessing time and fast generation of random variates from a very large class of distributions

Peripheral insulin resistance develops in transgenic rats overexpressing phosphoenolpyruvate carboxykinase in the kidney

Aims/hypothesis: To study the secondary consequences of impaired suppression of endogenous glucose production (EGP) we have created a transgenic rat overexpressing the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) in the kidney. The aim of this study was to determine whether peripheral insulin resistance develops in these transgenic rats.
Methods: Whole body rate of glucose disappearance (Rd) and endogenous glucose production were measured basally and during a euglycaemic/hyperinsulinaemic clamp in phosphoenolpyruvate carboxykinase transgenic and control rats using [6-3H]-glucose. Glucose uptake into individual tissues was measured in vivo using 2-[1-14C]-deoxyglucose.
Results: Phosphoenolpyruvate carboxykinase transgenic rats were heavier and had increased gonadal and infrarenal fat pad weights. Under basal conditions, endogenous glucose production was similar in phosphoenolpyruvate carboxykinase transgenic and control rats (37.4±1.1 vs 34.6±2.6 µmol/kg/min). Moderate hyperinsulinaemia (810 pmol/l) completely suppressed EGP in control rats (–0.6±5.5 µmol/kg/min, p<0.05) while there was no suppression in phosphoenolpyruvate carboxykinase rats (45.2±7.9 µmol/kg/min). Basal Rd was comparable between PEPCK transgenic and control rats (37.4±1.1 vs 34.6±2.6 µmol/kg/min) but under insulin-stimulated conditions the increase in Rd was greater in control compared to phosphoenolpyruvate carboxykinase transgenic rats indicative of insulin resistance (73.4±11.2 vs 112.0±8.0 µmol/kg/min, p<0.05). Basal glucose uptake was reduced in white and brown adipose tissue, heart and soleus while insulin-stimulated transport was reduced in white and brown adipose tissue, white quadriceps, white gastrocnemius and soleus in phosphoenolpyruvate carboxykinase transgenic compared to control rats. The impairment in both white and brown adipose tissue glucose uptake in phosphoenolpyruvate carboxykinase transgenic rats was associated with a decrease in GLUT4 protein content. In contrast, muscle GLUT4 protein, triglyceride and long-chain acylCoA levels were comparable between PEPCK transgenic and control rats.
Conclusions/interpretation: A primary defect in suppression of EGP caused adipose tissue and muscle insulin resistance.

The effect of water deprivation on the tonicity responsive enhancer binding protein (TonEBP) and TonEBP-regulated genes in the kidney of the spinifex hopping mouse, Notomys alexis

In desert rodents, the production of concentrated urine is essential for survival in xeric environments in order to conserve water. Reabsorption of water in the kidney is dependent on large osmotic gradients in the renal medulla. This causes the renal cells to be bathed in a hypertonic extracellular fluid that can compromise cellular function. In response to hypertonicity, kidney cells accumulate compatible, non-ionic osmolytes that lower the ionic strength within the cells to isotonic levels by replacing intracellular ionic electrolytes. The tonicity-responsive enhancer binding protein (TonEBP) is a transcription factor that regulates the expression of genes that encode proteins that catalyse the accumulation of compatible osmolytes. We investigated the expression of TonEBP mRNA and protein and compatible osmolyte genes in the Spinifex hopping mouse, Notomys alexis, an Australian desert rodent that produces a highly concentrated urine. TonEBP mRNA expression was unchanged after 3 days of water deprivation but was significantly increased after 7 and 14 days of water deprivation. Immunohistochemistry showed that during water deprivation TonEBP had translocated from the cytoplasm into the nucleus of cells in the renal medulla and papilla. In addition, 3, 7 and 14 days of water deprivation caused a significant increase in aldose reductase (AR), myo-inositol (SMIT), betaine/GABA (BGT-1) and taurine (TauT) transporter mRNA expression, which is indicative of an increase in TonEBP activity. In desert rodents, TonEBP regulation of gene transcription is probably an important mechanism to protect renal cells in the face of the large corticomedullary gradient that is required to concentrate urine and conserve water.

Expression of natriuretic peptide receptor mRNA and functional response to atrial natriuretic peptide and C-type natriuretic peptide in rainbow trout (Oncorhynchus mykiss) head kidney leucocytes

The stimulatory effect of vasomodulatory natriuretic peptide hormones on macrophages and peripheral blood leucocytes in mammals is well-established. However, the relationship in lower vertebrates has not been characterised. Expression of atrial natriuretic peptide, ventricular natriuretic peptide and C-type natriuretic peptide-1, and the guanylyl cyclase-linked (GC) natriuretic peptide receptor-A and -B-type receptors (NPR-A and NPR-B, respectively) was determined by PCR from the mRNA of rainbow trout head kidney leucocytes yielding gene fragments with 100% homology to the same respective natriuretic peptide and NPR-A and -B sequences obtained from other rainbow trout tissues. A mixed population of isolated rainbow trout head kidney leucocytes was stimulated in vitro with trout atrial natriuretic peptide (specific NPR-A agonist) and trout C-type natriuretic peptide (NPR-A and -B agonist) as well as the cGMP agonist 8-bromo-cGMP or the GC inhibitor 8-bromo-phenyl-eutheno-cGMP. Respiratory burst was stimulated by trout atrial natriuretic peptide, trout C-type natriuretic peptide-1 and 8-bromo-cGMP in a dose dependant manner with the highest activity as a result of stimulation with trout C-type natriuretic peptide-1 in excess of that achieved by phorbol myristate acetate (PMA). Equimolar concentrations of the inhibitor, inhibited the respiratory burst caused by the natriuretic peptides and 8-bromo-cGMP. The natriuretic peptide receptors on rainbow trout head kidney leucocytes appear to have a stimulatory function with regard to respiratory burst that is activated through a cGMP second messenger pathway and the natriuretic peptides expressed in the head kidney leucocytes may well act in a paracrine/autocrine manner.

Prevalence of kidney damage in Australian adults - the AusDiab Kidney Study

The incidence of ESRD is increasing dramatically. Progression to end-stage may be halted or slowed when kidney damage is detected at an early stage. Kidney damage is frequently asymptomatic but is indicated by the presence of proteinuria, hematuria, or reduced GFR. Population-based studies relating to the prevalence of kidney damage in the community are limited, particularly outside of the United States. Therefore, the prevalence of proteinuria, hematuria, and reduced GFR in the Australian adult population was determined using a cross-sectional study of 11,247 noninstitutionalized Australians aged 25 yr or over, randomly selected using a stratified, cluster method. Subjects were interviewed and tested for proteinuria—spot urine protein to creatinine ratio (abnormal: >=0.20 mg/mg); hematuria—spot urine dipstick (abnormal: 1+ or greater) confirmed by urine microscopy (abnormal: >10,000 red blood cells per milliliter) or dipstick (abnormal: 1+ or greater) on midstream urine sample; and reduced GFR—Cockcroft-Gault estimated GFR (abnormal: <60 ml/min per 1.73 m2). The associations between age, gender, diabetes mellitus, and hypertension, and indicators of kidney damage were examined. Proteinuria was detected in 2.4% of cases (95% CI: 1.6%, 3.1%), hematuria in 4.6% (95% CI: 3.8%, 5.4%), and reduced GFR in 11.2% (95% CI: 8.6%, 13.8%). Approximately 16% had at least one indicator of kidney damage. Age, diabetes mellitus, and hypertension were independently associated with proteinuria; age, gender, and hypertension with hematuria; and age, gender, and hypertension with reduced GFR. Approximately 16% of the Australian adult population has either proteinuria, hematuria, and/or reduced GFR, indicating the presence of kidney damage. Identifying and targeting this section of the population may provide a means to reduce the burden of ESRD.