PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2.

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs -1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH.

Human T-cell leukaemia virus type 1 and Adult T-cell leukaemia/lymphoma in Queensland, Australia: a retrospective cross-sectional study.

OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.

Creatinine index: a retrospective cohort study in an urban Australian dialysis context.

AIM: This study aimed to described the relationship between the CI and mortality in an Australian context. INTRODUCTION: Maintenance haemodialysis is a catabolic state associated with a significant decrease in lean body mass (LBM) and protein energy wasting. LBM can be derived or estimated from creatinine kinetic modelling, specifically the creatinine index (CI). This has been demonstrated in cohort studies to predict mortality. METHODS: One hundred seventy-nine patients undergoing haemodialysis in 2015 were included in this cohort. They were followed for 5 years with pertinent clinical data collected to calculate the CI as of December 2015. For analysis, patients were split into a high and low CI group based on the median (18.32 mg/kg/day). The primary outcome of interest was all-cause mortality, and secondary outcomes included myocardial infarction, stroke and transplantation. RESULTS: During follow-up, 69 (76.7%) patients in the low CI group and 28 (31.5%) patients in the high CI group died (P < 0.001). The relative risk (RR) of mortality within the low compared with the high CI group was 2.43 (95% confidence interval, 1.75-3.38). Fully adjusted Cox proportional hazards modelling demonstrated a hazard ratio (HR) of 0.498 (95% CI, 0.292-0.848) for survival in the high CI group. Lower CI was associated with increased risk of stroke (RR, 5.43 [95% CI, 1.24-23.84]), whereas transplant was more likely in the high CI group (RR, 6.4 [95% confidence interval, 1.96-20.88]). CONCLUSIONS: In a single-centre Australian haemodialysis cohort, the CI was strongly associated with mortality and stroke risk. The CI is an accurate and simple method to identify patients with low LBM at risk for significant morbidity and mortality.

Willingness to be tested for a secondary cause of hypertension: a survey of the Australian general community.

BACKGROUND: Primary aldosteronism (PA) represents the most common and potentially curable cause of secondary hypertension. However, PA is not commonly screened for, and up to 34% of patients who screen positive do not complete the full diagnostic process. This suggests that the diagnostic process may pose a barrier to patients and may contribute to the under-diagnosis of PA. AIMS: To evaluate the willingness of the Australian general public to undergo testing for secondary causes of hypertension and identify enablers or barriers to testing from the patients' perspective. METHODS: An online survey containing questions on knowledge and attitudes towards hypertension, willingness to be tested and enablers/barriers towards testing was distributed to the Australian community. RESULTS: Of 520 adult respondents (mean age 50.4 years, SD 27.3 years; 28.8% hypertensive; 56.0% female), the majority of non-hypertensive and hypertensive respondents (82.7% vs 70.0%; P = 0.03) were willing to undergo testing for a secondary cause of hypertension that involved blood and urine tests. Greater knowledge of hypertensive risk modification strategies and complications was predictive of willingness to be tested, whereas age, sex, education level, geographic location, socio-economic status and cardiovascular comorbidities were not. The top three barriers to testing included fear of a serious underlying condition, lack of belief in further testing and increased stress associated with further testing. CONCLUSION: A high proportion of patients are willing to engage in testing for a secondary cause of hypertension. Education about the risks associated with hypertension and the testing process may overcome several barriers to testing.

Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism.

BACKGROUND: Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system. METHODS: Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured. RESULTS: EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P < 0.01) correlations with DRC (r = 0.691) and PRA (r = 0.754) during FST. DRC and PRA were below their assays' functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P < 0.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P < 0.01) correlations with the ARR, whether renin was measured by DRC (r = 0.878) or PRA (r = 0.880). CONCLUSIONS: Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.

Haemodialysis withdrawal in Australia and New Zealand: a binational registry study.

BACKGROUND: Withdrawal from dialysis is an increasingly common cause of death in patients with end-stage kidney disease (ESKD). As most published reports of dialysis withdrawal have been outside the Oceania region, the aims of this study were to determine the frequency, temporal pattern and predictors of dialysis withdrawal in Australian and New Zealand patients receiving chronic haemodialysis. METHODS: This study included all people with ESKD in Australia and New Zealand who commenced chronic haemodialysis between 1 January 1997 and 31 December 2016, using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Competing risk regression models were used to identify predictors of dialysis withdrawal mortality, using non-withdrawal cause of death as the competing risk event. RESULTS: Among 40 447 people receiving chronic haemodialysis (median age 62 years, 61% male, 9% Indigenous), dialysis withdrawal mortality rates increased from 1.02 per 100 patient-years (11% of all deaths) during the period 1997-2000 to 2.20 per 100 patient-years (32% of all deaths) during 2013-16 (P < 0.001). Variables that were significantly associated with a higher likelihood of haemodialysis withdrawal were older age {≥70 years subdistribution hazard ratio [SHR] 1.77 [95% confidence interval (CI) 1.66-1.89]; reference 60-70 years}, female sex [SHR 1.14 (95% CI 1.09-1.21)], white race [Asian SHR 0.56 (95% CI 0.49-0.65), Aboriginal and Torres Strait Islander SHR 0.83 (95% CI 0.74-0.93), Pacific Islander SHR 0.47 (95% CI 0.39-0.68), reference white race], coronary artery disease [SHR 1.18 (95% CI 1.11-1.25)], cerebrovascular disease [SHR 1.15 (95% CI 1.08-1.23)], chronic lung disease [SHR 1.13 (95% CI 1.06-1.21)] and more recent era [2013-16 SHR 3.96 (95% CI 3.56-4.48); reference 1997-2000]. CONCLUSIONS: Death due to haemodialysis withdrawal has become increasingly common in Australia and New Zealand over time. Predictors of haemodialysis withdrawal include older age, female sex, white race and haemodialysis commencement in a more recent era.

Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.

PURPOSE OF REVIEW: The application of advanced genetic techniques has recently begun to unravel the genetic basis for familial primary aldosteronism type 2 (FH-II). RECENT FINDINGS: Whole-exome sequencing in a large family with FH-II revealed a shared rare damaging heterozygous variant in CLCN2 (chr.3: g.184075850C>T, p.Arg172Gln) in three severely affected members. The gene encodes a chloride channel, ClC-2. A cohort of 80 unrelated individuals diagnosed with early-onset primary aldosteronism was also examined for CLCN2 mutations finding three further occurrences of p.Arg172Gln mutations and four single cases of other potentially damaging heterozygous mutations for an overall prevalence of 9.9%. A concurrent report also found a different CLCN2 mutation (p.Gly24Asp) in a single severely affected patient from a cohort of 12 with early-onset PA for a prevalence of 8.3%. Cases of primary aldosteronism associated with CLCN2 mutations appear to be bilateral and respond well to medical treatment. In the adrenal, ClC-2 has been demonstrated to localize predominantly to the zona glomerulosa (ZG), and functional analysis suggests that mutations in ClC-2 predispose ZG cells to depolarization, thus leading to calcium influx via activation of voltage-gated calcium channels and increased aldosterone production. Germline CLCN2 mutations appear to account for a substantial proportion of early-onset primary aldosteronism cases, and genetic testing for mutations in this gene should be considered in appropriate cases.

Incremental and twice weekly haemodialysis in Australia and New Zealand.

BACKGROUND: Haemodialysis is usually started at a frequency of three times a week, with occasional patients starting twice weekly ('incremental dialysis'). Incremental haemodialysis (HD) may preserve residual kidney function and has been associated with reduced mortality. In the present study, we report prevalence and outcomes of incremental dialysis in Australia and New Zealand. METHODS: The cohort was all adults starting renal replacement therapy with HD in Australia and New Zealand 2004-2015. We used cox proportional hazards modelling with a primary exposure of dialysis frequency at first survey date (≥ or <3 times per week). The primary outcome was all-cause mortality (primary), cardiovascular and non-cardiovascular mortality (secondary). RESULTS: Eight-hundred fifty of 27 513 subjects were started on twice weekly HD (prevalence 3%). Compared to conventional patients, incremental dialysis patients were older (67 vs 62 years, P < 0.001), had a lower body mass index (26.1 vs 27.7 kg/m2 , P < 0.001), had a higher starting estimated glomerular filtration rate (7.59 vs 6.66 mL/min P < 0.001) and had less diabetes (39.2% vs 50.2%, P < 0.001). In a multivariate model, incremental start dialysis was not associated with all-cause mortality (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.92-1.16) or cardiovascular mortality (HR = 0.87, 95% CI = 0.71-1.07), but was associated with an increased risk of non-cardiovascular mortality (HR = 1.25, 95% CI = 1.11-1.42). CONCLUSION: Incremental dialysis was used infrequently, and there was evidence of patient level differences. All-cause mortality was similar, but there were differences in cause specific mortality. Incremental dialysis needs to be tested in prospective trials to define the safety and efficacy of this approach.

Outcomes and practice patterns with hemodiafiltration in Shanghai: a longitudinal cohort study.

BACKGROUND: Globally, there is increased clinical interest and uptake of hemodiafiltration (HDF) for increased removal of uremic toxins. To date, there has been no epidemiological analysis of HDF in China. We present HDF practice patterns and associated mortality risk in Shanghai. METHODS: This is an observational, prospectively collected, retrospective analysis of 9351 Chinese patients initiating hemodialysis in Shanghai from 2007 to 2014. The primary exposure was hemodialysis sub-modality at inception, classified into hemodiafiltration (HDF) and hemodialysis (HD), with adjustment for concommitant hemoperfusion. The primary outcome was patient mortality. We used Cox proportional hazards regression and Fine and Gray's proportional subhazards regression, with multiple imputation of missing co-variates by the chained equation method, adjusting for demographic and clinical variables. RESULTS: Overall, patients in the cohort were younger, with a more males, and with a lower body mass index when compared to corresponding non-Asian cohorts. Mortality rate was low although it doubled over the period of observation. HDF utilization increased from 7% of patients in 2007 to 42% of patients in 2014. The majority of patients received HDF once a week. The adjusted hazard ratio of death (95% confidence intervals) for HDF versus HD was 0.85 (0.71-1.03), and corresponding sub-hazard ratio 0.86 (0.71-1.03). There was strong effect modification by age. In those aged 40-60 years, the hazard ratio (95% confidence intervals) was 0.65 (0.45-0.94), and sub-hazard ratio also 0.65 (0.45-0.95). CONCLUSIONS: Our study has certain limitations resulting from the limited number of co-variates available for modelling, missing data for some co-variates, and the lack of verification of data against source documentation. Notwithstanding, there is evidence of clinical benefit from HDF in China, and potential to improve patient outcomes through the greater removal of middle and larger uremic solutes.

Large uremic toxins: an unsolved problem in end-stage kidney disease.

Patients with end-stage kidney disease (ESKD) on maintenance hemodialysis are subject to a high burden of inflammation and cardiovascular disease, driven at least in part by retention of uremic solutes. Existing dialysis technologies using high-flux membranes offer limited clearance of solutes >15 kDa. New approaches to improve the removal of large uremic toxins include the novel medium cut-off dialysis membranes with pores larger than those in high-flux membranes. These new membranes provide the potential to improve the clearance of large middle molecules up to 50 kDa. In this review, we discuss 18 uremic toxins with molecular weights between 15 and 60 kDa that are retained in ESKD, for which there is evidence of a link to inflammation and/or cardiovascular disease. These include inflammatory proteins, cytokines, adipokines and other signaling proteins. Improved clearance of this group of difficult to remove molecules has the potential to lead to improved outcomes in dialysis patients by reducing the burden of cardiovascular disease, which now needs to be assessed in robust clinical trials.

In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance.

Distal tubular sodium retention is a potent driver of hypertension, and the thiazide-sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1-related, proline alanine-rich kinase (SPAK) in human urinary exosomes. We isolated exosomes from daily urine samples in 25 patients undergoing fludrocortisone suppression testing (100 µg every 6 hours for 4 days) to diagnose or exclude primary aldosteronism. Over the course of the test, NCC levels increased 3.68-fold (P<0.01) and pNCC levels increased 2.73-fold (P<0.01) relative to baseline. The ratio of pNCC/NCC dropped by 48% (P<0.01). The abundance of WNK4 increased 3.23-fold (P<0.01), but SPAK abundance did not change significantly (P=0.14). Plasma potassium concentration strongly and negatively correlated with pNCC, NCC, and WNK4 abundance (P<0.001 for all). This study shows that, in humans, mineralocorticoid administration is associated with a rapid increase in abundance of NCC and pNCC, possibly via the WNK pathway. These effects may be driven by changes in plasma potassium.

Can Screening and Confirmatory Testing in the Management of Patients with Primary Aldosteronism be Improved?

Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy. In addition to verapamil slow release, hydralazine and prazosin, moxonidine has minimal effects on the ARR and can be used to control hypertension during work-up. Fludrocortisone suppression testing, while probably the most reliable means of definitively confirming or excluding PA, is time consuming and expensive, requiring a five day inpatient stay. A novel approach, upright (seated) saline infusion suppression testing (SST), has shown excellent reliability with much greater sensitivity than conventional recumbent SST in a recent pilot study, and requires only a day visit. Accurate measurement of aldosterone is essential for each step of PA workup: introduction of new, highly reliable high-throughput mass spectrometric methods into clinical practice has represented a major advance. In response to concerns raised about accuracy of renin assays, new mass spectrometric methods for measuring angiotensin II are currently being assessed in the clinical setting.

Does ACTH improve the diagnostic performance of adrenal vein sampling for subtyping primary aldosteronism?

OBJECTIVE: Adrenal vein sampling (AVS) is used for determining treatment options for primary aldosteronism (PA), but is a difficult procedure. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve AVS success rates by increasing cortisol secretion, but effects on lateralization are controversial. We therefore assessed the effects of ACTH in regard to AVS success and lateralization in our unit, after a change in protocol to ACTH-stimulated AVS. SETTING: AVS was performed after overnight recumbency in patients with PA confirmed by fludrocortisone suppression testing. Bilateral sequential sampling was performed before and after an intravenous bolus of 250 mcg of ACTH. Lateralization was defined as an aldosterone/cortisol ratio in one adrenal vein at least twice peripheral, combined with a contralateral adrenal ratio no higher than peripheral (contralateral suppression). RESULTS: In 47 AVS procedures, the median adrenal/peripheral cortisol gradient increased on the left (11·6 vs 18·2 µg/100 ml, P < 0·001) and right (15·6 vs 31·5 µg/100 ml, P < 0·001) after ACTH. A total of 34 of 47 studies were diagnostic pre-ACTH (six failing because of low aldosterone levels bilaterally and seven failing to cannulate one or both sides) vs 44 of 47 (P = 0·011) studies diagnostic post-ACTH (failure to cannulate one or both sides in 3). Concordance between diagnostic studies pre- and post-ACTH was 91%, but two bilateral cases became unilateral after ACTH and one unilateral case before ACTH was bilateral afterwards. CONCLUSIONS: ACTH improved cortisol gradients and aldosterone secretion, resulting in a reduction in the proportion of nondiagnostic studies. There was a low proportion of discordance between pre- and post-ACTH diagnoses, the significance of which is unclear.

Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison.

Treatment-resistant hypertension is an increasingly recognised problem and is markedly over-represented in patients with chronic kidney disease (CKD). Recent evidence has clarified the heightened risk for both adverse renal and cardiovascular outcomes associated with resistant hypertension, even when blood pressure control is attained. The diagnosis of resistant hypertension in CKD is reliant on accurate blood pressure measurement, and out of office measurements are important due to the high prevalence of masked hypertension in these patients. Treatment strategies include careful dietary measures to restrict sodium intake, and a focus on improving adherence to antihypertensive medications. Medication choices should focus on a sensible foundation and then diuretic titration to combat the salt and volume retention inherent in CKD. In this review, we discuss the epidemiology, pathogenesis and consequences of resistant hypertension in CKD, and then review the optimal diagnostic and management strategies.

Does concomitant autonomous adrenal cortisol overproduction have the potential to confound the interpretation of adrenal venous sampling in primary aldosteronism?

OBJECTIVE: Demonstration of unilateral aldosterone production by adrenal venous sampling (AVS) is required to select appropriate candidates for adrenalectomy in patients with primary aldosteronism (PA). During AVS, aldosterone and cortisol levels are measured to assess successful cannulation and lateralization. In patients with aldosterone-producing adenoma (APA), concurrent autonomous cortisol secretion might confound AVS results. DESIGN AND PATIENTS: We retrospectively examined results in eight patients with cortisol-producing adenoma (CPA), but without PA, who underwent AVS. RESULTS: In all eight, cortisol was higher on the CPA side than contralateral (CL) (median 6·7-fold [range 2·4-27·2]; P = 0·012]). By cortisol criteria, CL catheter placement would have been labelled inadequate in six despite adrenal venous aldosterone levels markedly higher than peripheral (41·6-fold [7·2-510·5]; P < 0·001), suggesting successful cannulation. In all eight, adrenal venous aldosterone/cortisol (A/C) ratios on the CL side were indicative of increased aldosterone production (≥2 times peripheral), but in only three patients on the CPA side (difference CL side 44·5-fold [6·0-109·0] vs CPA side 1·65-fold [1·0-23·0]; P = 0·017). A/C ratios were higher on the CL vs the CPA side in seven (20·0-fold [4·7-76·0]). CONCLUSION: These results in patients with CPA suggest that in patients with APA, concurrent autonomous unilateral cortisol hypersecretion could confound AVS accuracy by increasing cortisol levels (reducing A/C ratio) on the CPA side, while reducing levels (increasing A/C ratio and suggesting failed cannulation) on the CL side. Misclassification of PA subtype or repeat AVS could result, underscoring the importance of adequately assessing cortisol production prior to AVS and the need to consider alternatives.

Should aldosterone suppression tests be conducted during a particular phase of the menstrual cycle, and, if so, which phase? Results of a preliminary study.

BACKGROUND: As renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin, aldosterone and female sex steroids during fludrocortisone suppression testing (FST). METHODS: In 22 women undergoing FST who experienced regular menstrual cycles, renin (measured as both plasma renin activity and direct renin concentration), aldosterone (mass spectrometry) and cortisol, progesterone, oestradiol, LH and FSH (immunoassay) levels were compared, relative to phase of cycle. Aldosterone levels were compared to those in age-matched males undergoing FST. RESULTS: Progesterone (P < 0·0001) and aldosterone (P = 0·006) levels were higher in nine women (after one of 10 was excluded with anovulatory cycle) studied during the luteal phase than in the 12 studied during the follicular phase. All studied during the luteal phase had positive FST, and all three with negative FST were studied during the follicular phase. There were no significant differences in other parameters measured except FSH, which was higher (P = 0·02) during the follicular phase. Aldosterone was higher (P = 0·01) in women studied in the luteal (but not follicular) phase compared to men. CONCLUSION: The menstrual cycle may affect the outcome of FST and other suppression testing used to diagnose primary aldosteronism. Larger patient numbers and preferably restudy of the same patient in both phases should clarify this and determine the optimum time in the cycle for testing.

Natural disasters and dialysis care in the Asia-Pacific.

The impact of natural disasters on the provision of dialysis services has received increased attention in the last decade following Hurricane Katrina devastating New Orleans in 2005. The Asia-Pacific is particularly vulnerable to earthquakes, tsunami, typhoons (also known as cyclones and hurricanes) or storms and flooding. These events can seriously interrupt provision of haemodialysis with adverse effects for patients including missed dialysis, increased hospitalization and post-traumatic stress disorder. Furthermore, haemodialysis patients may need to relocate and experience prolonged periods of displacement from family and social supports. In contrast to haemodialysis, most literature suggests peritoneal dialysis in a disaster situation is more easily managed and supported. It has become apparent that dialysis units and patients should be prepared for a disaster event and that appropriate planning will result in reduced confusion and adverse outcomes should a disaster occur. Numerous resources are now available to guide dialysis units, patients and staff in preparation for a possible disaster. This article will examine the disaster experiences of dialysis units in the Asia-Pacific, the impact on patients and staff, methods employed to manage during the disaster and suggested plans for reducing the impact of future disasters.

Feasibility study of colestipol as an oral phosphate binder in hemodialysis patients.

BACKGROUND: Currently available calcium- and aluminium-based phosphate binders are dose limited because of potential toxicity, and newer proprietary phosphate binders are expensive. We examined phosphate-binding effects of the bile acid sequestrant colestipol, a non-proprietary drug that is in the same class as sevelamer. METHODS: The trial was an 8 week prospective feasibility study in stable hemodialysis patients using colestipol as the only phosphate binder, preceded and followed by a washout phase of all other phosphate binders. The primary study endpoint was weekly measurements of serum phosphate. Secondary endpoints were serum calcium, lipids and coagulation status. Analyses used random effects mixed models. RESULTS: Thirty patients were screened for participation of which 26 met criteria for treatment. At a mean dose of 8.8 g/24 h of colestipol by study end, serum phosphate dropped from 2.24 to 1.96 mmol/L (P < 0.001). Three patients required calcium supplementation. LDL cholesterol dropped from 1.75 to 1.2 mmol/L (P < 0.001). Three patients dropped out because of side effects or intolerance of the required dose. CONCLUSION: The results support the feasibility of a larger trial to determine the efficacy of colestipol as a phosphate binder and that other non-proprietary anion-exchange resins may also warrant investigation.

Understanding barriers to optimal medication management for those requiring long-term dialysis: rationale and design for an observational study, and a quantitative description of study variables and data.

BACKGROUND: Rates of medication non-adherence in dialysis patients are high, and improving adherence is likely to improve outcomes. Few data are available regarding factors associated with medication adherence in dialysis patients, and these data are needed to inform effective intervention strategies. METHODS/DESIGN: This is an observational cross-sectional study of a multi-ethnic dialysis cohort from New Zealand, with the main data collection tool being an interviewer-assisted survey. A total of 100 participants were randomly sampled from a single centre, with selection stratified by ethnicity and dialysis modality (facility versus home). The main outcome measure is self-reported medication adherence using the Morisky 8-Item Medication Adherence Scale (MMAS-8). Study data include demographic, clinical, social and psychometric characteristics, the latter being constructs of health literacy, medication knowledge, beliefs about medications, and illness perceptions. Psychometric constructs were assessed through the following survey instruments; health literacy screening questions, the Medication Knowledge Evaluation Tool (Okuyan et al.), the Beliefs about Medication Questionnaire (Horne et al.), the Brief Illness Perception Questionnaire (Broadbent et al.). Using the study data, reliability analysis for internal consistency is satisfactory for the scales evaluating health literacy, medication knowledge, and beliefs about medications, with Chronbach's α > 0.7 for all. Reliability analysis indicated poor internal consistency for scales relating to illness perceptions. MMAS-8 and all psychometric scores are normally distributed in the study data. DISCUSSION: This study will provide important information on the factors involved in medication non-adherence in New Zealand dialysis patients. The resulting knowledge will inform long-term initiatives to reduce medication non-adherence in dialysis patients, and help ensure that they are addressing appropriate and evidence based targets for intervention.

Reninoma: the importance of renal vein renin ratios for lateralisation and diagnosis.

BACKGROUND/AIM: Reninomas are rare juxtaglomerular tumours which can cause severe hypertension and hypokalaemia. Diagnosis can be problematic and these tumours can be difficult to locate on imaging. In this report we aim to demonstrate the value of carefully performed renal vein renin ratios (RVRRs) to assist in locating these tumours. METHOD/RESULTS: We report on 3 patients diagnosed with reninoma in our unit. The patients were all female, young (17, 16 and 30 years), severely hypertensive and hypokalaemic (2.5, 2.5 and 3.1 mmol/l). Plasma renin activity (PRA) was elevated (31.9, 274 and 175 ng/ml/h), and aldosterone was high-normal (19.9 ng/dl) or elevated (207 and 109.3 ng/dl). Renal artery stenosis was excluded by renal artery Doppler, DTPA scan and angiography. Renal CT detected the lesion in 2 patients, with one lesion visible on pre- and post-contrast CT and the other on post-contrast CT only. RVRRs were performed several weeks after withdrawing interfering medications, maintaining a <40 mmol/day low-sodium diet and maintaining recumbency overnight the night before and during the procedure. Ratios before and after captopril or enalaprilat administration were obtained and lateralised the tumours in all 3 cases (dominant/non-dominant ratios of 2.3, 4.3 and 3.8). All of the patients underwent nephrectomy yielding a typical juxtaglomerular tumour and resulting in cure of hypertension and hypokalaemia. CONCLUSIONS: Reninoma should be suspected in young hypertensives (especially females) with significant hypokalaemia and high PRA or direct renin concentration after renovascular hypertension has been excluded. CT imaging and carefully performed RVRRs provide the highest likelihood of locating these tumours.