The use of culturally adapted and translated depression screening questionnaires with South Asian haemodialysis patients in England.

BACKGROUND: Depression is common amongst patients receiving haemodialysis (HD). Assessment and intervention when faced with language and cultural barriers is challenging. To support clinician decisions, we conducted a cross-sectional study to assess the use of culturally adapted and translated versions of commonly-used depression screening questionnaires with South Asian patients receiving HD in England. METHODS: Patients completed adapted versions of the Patient Health Questionnaire (PHQ-9), the Centre for Epidemiological Studies Depression Scale Revised (CESD-R), and the Beck Depression Inventory II (BDI-II). All questionnaires were available in Gujarati, Punjabi, Urdu, and Bengali. A comparative sample of white-Europeans completed the questionnaires in English. The research was based across 9 National Health Service (NHS) Trusts in England. Structural validity of translated questionnaires was assessed using confirmatory factor analysis. Diagnostic accuracy was explored in a subgroup of South Asians against ICD-10 categories using the Clinical Interview Schedule Revised (CIS-R) with receiver operating curve (ROC) analysis. RESULTS: 229 South Asian and 120 white-European HD patients participated. A single latent depression factor largely accounted for the correlations between items of the PHQ-9, CESD-R and BDI-II. Issues with measurement equivalence implied that scores on the translations may not be comparable with the English language versions. Against CIS-R based ICD-10 diagnosis of depression, sensitivity was modest across scales (50-66.7%). Specificity was higher (81.3-93.8%). Alternative screening cut-offs did not improve positive predictive values. CONCLUSIONS: Culturally adapted translations of depression screening questionnaires are useful to explore symptom endorsement amongst South Asian patients. However, data indicate that standard cut-off scores may not be appropriate to classify symptom severity. Use of the CIS-R algorithms for optimal case identification requires further exploration in this setting. Strategies to encourage recruitment of under-represented groups in renal research are also warranted, especially for in-depth discussions related to psychological care needs.

How do patients from South Asian backgrounds experience life on haemodialysis in the UK? A multicentre qualitative study.

OBJECTIVES: End-stage kidney disease disproportionately affects people of South Asian origin. This study aimed to uncover the lived experiences of this group of patients on centre-based haemodialysis (HD), the most prevalent dialysis modality. DESIGN: The study utilised a qualitative focus group methodology. Seven focus groups were conducted across four NHS Trusts in the UK including three in Gujarati and two each in Punjabi and Urdu. This provided an inclusive opportunity for South Asian patients to contribute in their language of origin. A total of 24 patients participated. Focus groups were facilitated by bilingual project workers and data were forward translated and analysed using thematic analysis. RESULTS: Four themes were identified. This included (1) 'treatment imposition', which comprised of the restrictive nature of HD, the effects of treatment and the feeling of being trapped in an endless process. (2) The 'patient-clinician relationship' centred around the impact of a perceived lack of staff time, and inadequacies in the quality of interactions. (3) 'Coping strategies' highlighted the role of cognitive reappraisal, living in the moment and family support networks in facilitating adjustment. (4) 'Pursuit of transplantation' included equating this form of treatment with restoring normality, alongside cultural factors limiting hopefulness for receiving an organ. CONCLUSIONS: In general, the experiences of South Asian patients receiving HD were not unique to this ethnic group. We did find distinct issues in relation to interactions with healthcare professionals, views on access to transplantation and the importance of family support networks. The study provides useful insights which may help enhance culturally tailored renal care.

Human factors testing of the Quanta SC+ hemodialysis system: An innovative system for home and clinic use.

INTRODUCTION: Uptake rates of home hemodialysis are the lowest among all modality types, despite providing patients with clinical and quality of life benefits at a lower cost to providers. Currently, there is a need to develop dialysis systems that are appealing to patients while also being suitable for use across the continuum of care. The SC+ hemodialysis system was developed by Quanta Dialysis Technologies Ltd. to provide patients with a dialysis system that is small, simple to use, and powerful enough to deliver acceptable dialysis adequacy. METHODS: As part of the SC+ design validation, human factors testing was performed with 17 Healthcare Professionals (nephrology nurses and healthcare assistants) and 15 Home Users (patients and caregivers). To assess usability and safety, the human factors testing involved between 4.5 and 6 hours of training and, after a period of training decay, a subsequent test session in which participants independently performed tasks on SC+. FINDINGS: Between the two user groups, there were only 29 errors observed out of 1216 opportunities for errors, despite minimal training. Errors that did occur were minor and attributed to an initial lack of familiarity with the device; none were safety related. DISCUSSION: Among prevalent dialysis patients and healthcare professionals, the SC+ hemodialysis system was easy to use, even with minimal training and a learning decay period, and had a high level of use safety. By taking into account human factors to optimize the user experience, SC+ has the potential to address systemic and patient barriers, allowing for wider self-care and home hemodialysis adoption.

Comparison of characteristics of centers practicing incremental vs. conventional approaches to hemodialysis delivery - postdialysis recovery time and patient survival.

INTRODUCTION: Conventional haemodialysis (HD) involves treatment times of around 4 hours thrice weekly, taking no account of residual kidney function (RKF). In incremental HD the frequency and duration of dialysis sessions are individualized according to RKF. There are no studies comparing these approaches. We utilized data from a recent multicenter study to compare patient characteristics and outcomes between a center practicing incremental HD and others using a conventional approach. METHODS: Seven hundred and nine patients attending for routine outpatient HD in five UK centers were studied. One center practiced incremental dialysis (n = 254) and four conventional HD (n = 455). Data collected included demographics, comorbidity, dialysis parameters, routine biochemistry and hematology, recovery time postdialysis, and Beck Depression Inventory-II score (BDI-II). Patients were followed for a minimum of 12 months. FINDINGS: Pre- and postdialysis BP, serum calcium and phosphate were higher in the incremental center, whilst sessional Kt/Vurea was lower (all P < 0.001), as was the proportion of patients with a mean postdialysis BP <100 mmHg (P = 0.011). Patients recovered from their HD session more quickly in the incremental center, with significantly more patients reporting recovery within 1 and 4 hours Short-term survival was significantly better in the incremental center both unadjusted and adjusted for age, gender, ethnicity, dialysis vintage, anuria, history of cancer, heart disease, diabetes mellitus, body mass index, serum albumin, BDI-II score, and sessional Kt/V. DISCUSSION: The association between incremental dialysis, shorter postdialysis recovery times and improved short-term survival may be related to reduced haemodynamic stress as a consequence of less intensive ultrafiltration and reduced length of dialysis sessions. Prospective studies are required to test this hypothesis.

Humoral immunity in late-onset Pre-eclampsia and linkage with angiogenic and inflammatory markers.

PROBLEM: Pre-eclampsia (PE) is a leading cause of maternal and foetal morbidity worldwide. Given the implication of immune mechanisms, we compared markers of humoral immunity in PE and their relationship to circulating markers of inflammation, angiogenic factors, and renal function. METHOD OF STUDY: Serum samples from 88 previously healthy women admitted to hospital with PE and 107 healthy pregnant controls at term were analysed for serum immunoglobulins (Ig), including IgG subclasses and free light chain (sFLC) levels, beta-2 microglobulin (B2-M), high-sensitivity C-reactive protein (HS-CRP), albumin, complement proteins (C3 & C4), creatinine, cystatin-C and the ratio of soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF). RESULTS: Compared to the controls, women with PE had significantly reduced renal function, serum IgG (subclass 1 & 3), albumin, and C4 levels, whilst concentrations of total sFLC, HS-CRP, B2-M, and sFLT-1:PlGF were raised. On multivariable analysis, sFLT-1:PlGF ratio (P < 0.001), sFLC (P < 0.001) and IgG1 (P < 0.024) were found to be independently associated with PE, after accounting for renal function, patient age, BMI, ethnicity, and parity. B2-M and sFLT-1:PlGF had comparable diagnostic association with PE (P = 0.184), and correlated strongly with each other (ρ = 0.588, P < 0.001) as well as with renal function and adverse clinical outcome. CONCLUSION: We describe for the first time that PE is independently associated with activation of the humoral immune system independent of deranged kidney function and angiogenic markers. The role of B2-M as a potential predictive marker of PE remains to be determined.

Self-reported depression symptoms in haemodialysis patients: Bi-factor structures of two common measures and their association with clinical factors.

OBJECTIVE: To validate the factor structure of two common self-report depression tools in a large sample of haemodialysis (HD) patients and to examine their demographic and clinical correlates, including urine output, history of depression and transplantation. METHODS: Factor structures of the Beck Depression Inventory (BDI-II) and Patient Health Questionnaire (PHQ-9) were evaluated using confirmatory factor analysis (CFA). Data was utilised from the screening phase (n = 709) of a placebo-controlled feasibility randomised control trial (RCT) of sertraline in HD patients with mild to moderate Major Depressive Disorder. Alternative factor models including bi-factor models for the BDI-II and PHQ-9 were evaluated. Coefficient omega and omega-hierarchical were calculated. RESULTS: For both measures, bi-factor measurement models had the overall best fit to the data, with dominant general depression factors. Omega-hierarchical for the general BDI-II and PHQ-9 factors was 0.94 and 0.88 respectively. Both general factors had high reliability (coefficient omega = 0.97 and 0.94 respectively) and explained over 85% of the explained common variance within their respective models. BDI-II and PHQ-9 general depression factors were negatively associated with age and urine output and positively with a history of depression, antidepressant use within the last 3 months and a history of failed transplantation. In adjusted regression models, age, urine output and a history of depression remained significant. CONCLUSIONS: These data suggest that both the BDI-II and PHQ-9 are sufficiently unidimensional to warrant the use of a total score. Younger age, lower urine output and a history of depression appear consistent correlates of depression severity among HD patients.

Postdialysis recovery time is extended in patients with greater self-reported depression screening questionnaire scores.

INTRODUCTION: Most patients take time to recover after a hemodialysis (HD) session. It has been suggested that recovery time is associated with intradialytic hypotension and rapid solute clearances. Other studies have reported a linkage to depression. We investigated the association between recovery time and intradialytic hypotension and depression. METHODS: In five UK HD units, we screened for depressive symptoms using the Beck depression inventory-II, Patient Health Questionnaire, and recorded sessional blood pressures and Kt/Vurea. FINDINGS: Seven hundred and one HD patients were studied; 63.6% male, mean age 64.1 ± 16.6 years, 33.5% diabetic. About 24.1% recovered in <1 hour, 27% 1-4 hours, 15.4% 4-8 hours, 10.7% 8-12 hours, and 22.8% after 12 hours. Systolic blood pressure fell by ≥20 mmHg in 30.9% postdialysis, and to <100 mmHg in 7.6%. In multivariate analysis, patients with recovery times >1 hour were more likely to be female, have high self-reported Beck depression inventory-II scores, a past medical history of depression, and be living without a partner. Longer recovery times were also associated with very low postdialysis systolic blood pressures (<100 mmHg), and higher body weight. However, the model predicted only 18% of the variation in recovery times. We found no association between recovery times and short-term mortality risk. DISCUSSION: Prolonged postdialysis recovery times are associated with higher self-reported depression scores, and very low postdialysis blood pressure. Future studies investigating changes in dialysis practice and recovery times will need to target strategies to prevent intradialytic hypotension and adjust for patient psychological status.

Depression Symptoms in Haemodialysis Patients Predict All-Cause Mortality but Not Kidney Transplantation: A Cause-Specific Outcome Analysis.

Background: Depression is common in haemodialysis (HD) patients and associated with poor outcomes. Purpose: To evaluate whether depression symptoms predict survival and transplantation in a large sample of haemodialysis patients using cause-specific survival models. Methods: Survival data was collected between April 2013 and November 2015, as part of the screening phase of a multicentre randomised placebo-controlled trial of sertraline in HD patients. Depression was measured using the Beck Depression Inventory-II (BDI-II) and the Patient Health Questionnaire-9 (PHQ-9). Demographic and clinical data were collected via a self-report questionnaire and medical records. Competing risk survival analysis involved cause-specific and subdistribution hazard survival models. All models were adjusted for appropriate covariates including co-morbidity and C-reactive protein (CRP) in a subanalysis. Results: Of 707 cases available for analysis, there were 148 deaths. The mean survival time was 787.5 days. Cumulative survival at 12 months was 88.5%. During the study follow-up period, there were 92 transplants. The cumulative transplant event rate at 12 months was 7.8%. In separate adjusted models, depression symptoms predicted mortality (BDI-II HR = 1.03 95% CI 1.01, 1.04; PHQ-9 HR = 1.04 95% CI 1.01, 1.06). With respect to screening cut-off scores, a PHQ-9 ≥ 10 was associated with mortality (HR = 1.51 95% CI 1.01, 2.19) but not a BDI-II ≥ 16. Depression symptoms were not associated with time to transplantation in either cause-specific or subdistribution model. Conclusions: Consistent with past findings in HD patients, depression symptoms predicted survival but were not associated with kidney transplantation. Suitable treatments for depression need further evaluation, and their impact upon quality of life and clinical outcomes determined. Trial Registration Number: (ISRCTN06146268).

Measuring Fatigue Using the Multidimensional Fatigue Inventory-20: A Questionable Factor Structure in Haemodialysis Patients.

BACKGROUND/AIMS: Fatigue is recognised as a common and burdensome symptom among dialysis patients. A growing body of research is devoted to understanding fatigue in advanced kidney disease, yet its measurement is challenging within this context. Our aim was to evaluate the factor structure underlying the multidimensional fatigue inventory (MFI-20) and to examine its associations with clinical factors and mood. METHODS: Data was evaluated for confirmatory factor analysis (CFA) from the screening phase of a multicentre randomised placebo-controlled trial of sertraline in haemodialysis (HD) patients. Four hundred seventy patients completed the MFI-20, which purports to measure 5 components of fatigue (general fatigue, mental fatigue, physical fatigue, reduced motivation and reduced activity). CFA models were evaluated in MPlus 7.3 using the robust maximum likelihood (MLR) estimation. RESULTS: The evaluation of the original 5 factors revealed low internal reliability for the general factor and reduced activity, and high intercorrelations between all sum scores. CFA revealed poor model fit for the original 5-factor MFI-20 model (confirmatory fit index = 0.738; Tucker-Lewis index = 0.689; root mean squared error of approximation = 0.101). Alternative models, including 1, 3 and bi-factor models all demonstrated poor fit to the data. No reliable factor model was confirmed prohibiting the examination of factors associated with fatigue. CONCLUSIONS: We were not able to confirm the factor structure of the MFI-20 in a large sample of HD patients. Certain items may lack suitable face validity in this context.

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial.

BACKGROUND AND OBJECTIVES: Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. RESULTS: In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. CONCLUSIONS: Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants.

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

BACKGROUND: The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. METHODS/DESIGN: The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. DISCUSSION: There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. TRIAL REGISTRATION: ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

Patients with Wegener's granulomatosis demonstrate a relative deficiency and functional impairment of T-regulatory cells.

An increased proportion of CD4(+) CD25(+) T cells has been reported in Wegener's granulomatosis (WG) and may represent an accumulation of regulatory T cells (Treg). CD25 is also expressed on recently activated effector T cells. We have determined the relative proportion of these subsets in a large patient cohort. The fraction of Treg in peripheral blood mononuclear cells from patients and healthy controls was determined by assessment of Foxp3 expression on CD4(+) CD25(+) T cells. The functional activity of Treg was determined by their ability to suppress proliferation and cytokine production in response to proteinase-3. Although WG patients demonstrated an increased fraction of CD4(+) CD25(+) T cells, the percentage of Foxp3-positive cells was decreased. In addition, the percentage of Treg was inversely related to the rate of disease relapse. CD4(+) CD25(hi) T cells were able to suppress T-cell proliferation to proteinase-3 in healthy controls and anti-neutrophil cytoplasm antibody (ANCA)- negative patients (at time of sampling) but not in ANCA-positive patients. In patients with active disease, an increased proportion of CD4(+) Foxp3(+) cells was associated with a more rapid disease remission. Patients with WG demonstrate abnormalities in the number and function of Treg and this is most pronounced in those with most active disease. This information is of value in understanding the pathogenesis and potential treatment of this disease.

Prediction of ESRD in pauci-immune necrotizing glomerulonephritis: quantitative histomorphometric assessment and serum creatinine.

BACKGROUND: Clinical and pathologic features that predict outcome have important potential application in patients with pauci-immune necrotizing glomerulonephritis (usually antineutrophil cytoplasmic antibody-associated vasculitis). This study examines the predictive value of simple quantitative renal histologic measurements in a large cohort with extended follow-up. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 390 consecutive patients with pauci-immune necrotizing glomerulonephritis at a single hospital (1983-2002); 90 patients underwent repeated kidney biopsy during follow-up. PREDICTORS: Age and serum creatinine concentration at biopsy, antineutrophil cytoplasmic antibody specificity, percentage of normal glomeruli, percentage of glomeruli with active lesions, and index of chronic damage (quantitative measurement of established cortical damage) in the initial kidney biopsy for all patients. The same factors were assessed in both biopsy specimens for patients undergoing an additional biopsy. OUTCOMES & MEASUREMENTS: End-stage renal disease and patient survival. RESULTS: Mortality at 1 and 5 years was 23% and 40%, respectively: standardized mortality ratio, 4.74 (95% CI, 3.62-6.32). End-stage renal disease was reached by 14% and 18% at 1 and 5 years, respectively. In multivariable analysis, serum creatinine level at biopsy and percentage of normal glomeruli in the initial biopsy specimen were the best predictors of kidney survival. C Statistics were 0.80 for creatinine level alone and 0.83 for creatinine level with normal glomeruli. In patients undergoing an additional biopsy, rapid progression in the index of chronic damage and serum creatinine level at the second biopsy were associated with kidney survival in multivariable analysis. LIMITATIONS: Retrospective analysis. External validity of the index of chronic damage requires further assessment. Selection bias may influence repeated biopsy analyses. CONCLUSIONS: Serum creatinine level at biopsy best predicts kidney survival in patients with pauci-immune necrotizing glomerulonephritis overall.

The role of renal biopsy in women with kidney disease identified in pregnancy.

BACKGROUND: Renal disease may present for the first time in pregnancy, either as symptomatic disease or as a consequence of antenatal screening. The role of antenatal and post-partum percutaneous renal biopsy in the management of such patients is discussed. METHODS: We describe two series of women; the first is a series of 20 women presenting with renal disease of a severity to warrant renal biopsy during pregnancy whilst the second, comprises 75 women who had an initial presentation of renal disease in pregnancy and underwent post-partum renal biopsy. RESULTS: Biopsy during pregnancy revealed a glomerular disorder in 19/20 (95%) with immediate change of management in 9/20 (40%). In 17/20 (85%) there was delivery of a live infant at median gestation of 36 weeks (range 25-40). Follow-up of women [median 103.3 months (2.5-256)] showed 9/20 (45%) had a GFR of <60 ml/min/1.73 m(2) [six at end-stage renal failure (ESRF)] and 3/20 were dead. The majority (62/75; 82.6%) of women undergoing post-partum renal biopsy presented with significant proteinuria (40% pre-eclampsia) during pregnancy not resolving post-partum. A glomerular abnormality was found in 64%. At last follow-up of 47 women [median 51.5 months (range 1-212)], 14 patients (29.7%) had significant proteinuria and 20 (42.6%) had a GFR<60 ml/min/1.73 m(2). Six women (12.7%) had ESRF. CONCLUSIONS: Diagnosis and follow-up of renal disease diagnosed in pregnancy is important as progressive disease occurs in this group. Routine antenatal screening provides a useful diagnostic opportunity to detect asymptomatic renal disease. In a selected sub-group, renal biopsy during pregnancy can be helpful in initiation of correct treatment and allowing progression of pregnancy to fetal viability.

Recurrences and infections during continuous immunosuppressive therapy after beginning dialysis in ANCA-associated vasculitis.

BACKGROUND: Approximately 20% of patients with antineutrophil cytoplasm antibody-associated systemic vasculitis (AASV) develop end-stage renal failure (ESRF). It is not clear whether continuation of immunosuppression, with its associated risks, is beneficial because relapse rates after the development of ESRF are reported to be low. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single tertiary-care referral center. 46 patients with AASV who developed ESRF from 1971 to 2004. OUTCOMES & MEASUREMENTS: Treatment, relapse rates before and after dialysis therapy, patient outcome after dialysis therapy, and infection (defined as admission to hospital or intravenous antibiotics) were recorded. RESULTS: Patients with AASV on dialysis therapy had 1- and 5-year survival rates of 82% and 55%, equivalent to current 1- and 5-year survival rates of dialysis patients reported by the UK renal registry, respectively. Infection rates in patients with ESRF were high in those with AASV on dialysis therapy; 106 events in 35 patients (dialysis patients with AASV, 0.89 infections/patient-year; confidence interval [CI], 0.74 to 1.08). Eight of 9 patients who died of infection were receiving immunosuppressive therapy. No patient died of active disease. Relapse rates after dialysis commencement were less than those predialysis (6 relapses in 4 patients; 0.05 relapses/patient-year postdialysis; CI, 0.02 to 0.1 compared with 18 relapses in 11 patients; 0.13 relapses/patient-year predialysis; CI, 0.07 to 0.19). LIMITATIONS: This is a retrospective study spread over 3 decades with no control group. CONCLUSIONS: Patients with AASV and ESRF are less likely to experience relapse than before dialysis therapy. Patients with AASV on dialysis therapy have a high rate of infection. These results may not be applicable to patients with pulmonary involvement.

Cholestasis in pregnancy associated with ciclosporin therapy in renal transplant recipients.

Obstetric cholestasis (OC) presents with pruritus in the second half of pregnancy and is associated with increased risk of foetal distress, intra-uterine death and premature delivery. From a tertiary referral, renal-obstetric clinic, we report the occurrence of OC in 5/23 pregnancies of women with renal transplants maintained on ciclosporin treatment (European incidence 0.1-1.5% of pregnancies). All required premature delivery for foetal reasons at 33-37/40 (median 34/40). Ciclosporin, at therapeutic concentrations, inhibits bile salt excretion pump (BSEP) function in rats and humans. We propose that OC developed in our patients because the mild inhibition of the canalicular pumps by ciclosporin was only revealed in pregnancy when increases in progesterone metabolites overwhelmed pump function. We suggest that all pregnant women receiving ciclosporin should be closely monitored from the second trimester for the development of OC. If detected, enhanced foetal and maternal monitoring to optimize time of delivery and pregnancy outcome is required.