Aine Burns

Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study.

BACKGROUND Renal involvement is frequently present in antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis and is an important cause of end-stage renal failure (ESRF). METHODS This retrospective, multicenter, sequential cohort study reports presenting features and outcome of 246 new patients diagnosed in London, UK, between 1995 and 2000. RESULTS Diagnostic subgroups were microscopic polyangiitis, 120 patients (49%); Wegeners granulomatosis (WG), 82 patients (33%); renal-limited vasculitis, 33 patients (13.5%); and Churg-Strauss angiitis, 11 patients (4.5%). Median age was 66 years, 57% were men, and median creatinine level at presentation was 3.87 mg/dL (342 micromol/L). ANCA was present in 92%. Cumulative patient survival at 1 and 5 years was 82% and 76%, respectively. Mortality was associated with age older than 60 years (P < 0.001), development of ESRF (P < 0.001), initial creatinine level greater than 2.26 mg/dL (200 micromol/L; P = 0.01), and sepsis (P < 0.048). ESRF occurred in 68 patients (28%), of whom 47% died. Fifty-six patients who presented with a creatinine level greater than 5.65 mg/dL (500 micromol/L) survived, and 31 patients (55%) achieved dialysis independence. Relapse occurred in 34% after a median of 13 months and was more common in patients with WG (P = 0.048) and proteinase 3-ANCA (P = 0.034). Leukopenia occurred in 41% and was associated with sepsis (P < 0.001). CONCLUSION Mortality and morbidity of ANCA-associated systemic vasculitis are improving compared with previous series, but remain high. Renal vasculitis often affects older patients, who have a particularly poor outcome. Early diagnosis improves outcome. Leukopenia, caused by immunosuppressive therapy, should be avoided because of the close association with sepsis and death.

Maximum conservative management for patients with chronic kidney disease stage 5

Following the expansion of dialysis services for patients with chronic kidney disease, an increasing number of elderly patients with varying degrees of frailty and additional comorbidities have been offered treatment. Life expectancy is somewhat limited in this group of patients, and initiation of dialysis may not necessarily improve quality of life. As such, an increasing number of centers are offering conservative care for patients who have made an informed decision not to have dialysis. As conservative care includes active treatment of anemia, volume overload, blood pressure control, and management of uremic symptoms, including pruritus, we term this approach as maximal conservative management of chronic kidney disease. We describe our experience of maximum conservative management, which although may not prolong life, can maintain the quality of life and functional ability until the final illness in the majority of patients. Although these patients do not go to the hospital on a regular basis, coordinated support from the hospital, the community, and the care giver/relative is required for successful care of the patient. Appropriate end of life planning can then be made according to the wishes of the patient.

Subarachnoid Hemorrhages in Vasculitis

Subarachnoid hemorrhage (SAH) is common in clinical practice. SAH associated with vasculitis is rare. We present an unusually interesting case of SAH from a vertebral artery aneurysm in a young woman found to have advanced renal impairment.

Induction treatment of ANCA-associated vasculitis with a single dose of rituximab

OBJECTIVES Rituximab is effective in inducing remission in ANCA-associated vasculitis (AAV), with randomized evidence to support its use as four infusions of 375 mg/m(2) (the conventional lymphoma dosing schedule). As B cell depletion (BCD) appears to occur very rapidly after the first dose, we questioned the need for repeat dosing and adopted a standard single-dose protocol of 375 mg/m(2) to treat active AAV. METHODS All consecutive cases with newly diagnosed or relapsing AAV for whom conventional immunosuppression was contraindicated or ineffective were enrolled. All were rituximab naive. Circulating CD19(+) B cells and clinical and serological markers of disease activity were recorded at regular intervals. Complete remission (CR) was defined as the absence of clinical features of AAV with a prednisolone dose <10 mg/day. RESULTS Nineteen patients were included, 17 (89%) with generalized disease and 2 (11%) with severe disease (creatinine level >500 μM). Eight (42%) were on additional immunosuppression at the time of rituximab treatment. Satisfactory BCD (<0.005 cells/μl) was achieved in 89% of patients after a median of 13 days. Three-month BCD probability was 89%. Median time to CR following a single dose of rituximab was 38 days and the 3-month probability of CR was 80%. Median time to B cell repopulation was 9.2 months and to disease relapse/redose was 27 months. Use of this single-dose protocol saved an estimated £4533/patient (US

Successful outcome of pregnancy in patients with anti-neutrophil cytoplasm antibody-associated small vessel vasculitis

7103; €5276) compared with a 4 × 375 mg/m(2) dosing schedule. CONCLUSION Our single-centre experience suggests that a single dose of rituximab of 375 mg/m(2) is a reasonable and more cost-effective therapy for inducing remission in patients with AAV.

Familial IgA Nephropathy: A Study of HLA Class II Allogenotypes in a Chinese Kindred

Pregnancy in patients with anti-neutrophil cytoplasm antibody-associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case review of all women who became pregnant following diagnosis. We report 15 pregnancies in 13 women resulting in 15 live births including one twin pregnancy and 13 singleton pregnancies. One patient had an unplanned pregnancy and a first trimester miscarriage while taking methotrexate. All other pregnancies were planned following a minimum of 6 months clinical remission. Eleven successful pregnancies were delivered vaginally at full term, whereas three were delivered by cesarean section. All infants were healthy with no neonatal complications on their initial health check within the first 24 h of delivery and no evidence of neonatal vasculitis. One relapse occurred during pregnancy and was successfully treated with an increased dose of azathioprine and corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. One patient developed tracheal crusting and subglottic stenosis of infective etiology in the third trimester requiring tracheal debridement post delivery. No patient had a relapse in the first 12 months postpartum. Thus, successful pregnancy outcomes can occur following planned pregnancy in women in sustained remission on non-teratogenic therapies.

Do glomerular atherosclerosis and lipid-mediated tubulo-interstitial disease cause progressive renal failure in man ?

We have studied the restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II DQ, DR pattern of a Chinese family with IgA nephropathy (IgAN). The three affected and one apparently unaffected sibling shared the same DR and DQ pattern. The subjects were homozygous for DRw12, DQw7, DQ alpha 1b. The DQw7 allele was further confirmed by polymerase chain reaction (PCR) and allele-specific oligonucleotide (ASO) probing. This study confirms that IgAN can run in a family and is consistent with the possible immunopathogenetic effects of MHC class II antigens on IgAN.

Is dialysis a viable option for the older patient? Outcomes for patients starting dialysis aged 80 years or older.

The nephrotic syndrome presents the kidney with a new environment in which blood vessels, glomerular structures and tubules are exposed over substantial periods of time to lipoproteins. LDL has charge affinity with glomerular basement membrane glycosaminoglycans, so potentially increases or maintains albumin loss. This in turn stimulates LDL synthesis. HDL is small enough to be passed by the glomerular filter in substantial amounts and has been found to stimulate endothelin-1 production by human proximal tubular cells in culture. LDL also inhibits nitric oxide vasodilatory responses, an action which when added to that of endothelin-1 may result in decreased renal tissue oxygenation. Taken together, these aspects of the nephrotic syndrome broaden conventional definitions of atherosclerosis and offer a number of targets for therapy in progressive renal disease.

Clinician views of patient decisional conflict when deciding between dialysis and conservative management: Qualitative findings from the PAlliative Care in chronic Kidney diSease (PACKS) study

Background: Maximum conservative management (MCM) has been proposed as an alternative care pathway for the increasing number of elderly patients with progressive chronic kidney disease. Methods: Retrospective analysis of patients aged ≥80 years of age, starting dialysis between 2000 and 2009 in a centre with an established MCM programme. Demographic data, baseline biochemical markers and survival were collected. Results: 93 consecutive patients were studied; median age 83 years (IQR 81–86). 67 male, 32% diabetic. Median survival 46.5 months (range 0–107), with 1- and 5-year survival 78.5 and 38.3%, respectively. Factors predicting poorer survival were Caucasoid ethnicity (p = 0.04) and serum albumin ≤30 g/l (p = 0.01) at dialysis initiation. Duration of nephrology care prior to dialysis initiation did not effect survival. Conclusion: The very elderly electing dialysis were found to have good survival. Further patient characterisation is required to improve decision-making between dialysis and MCM for elderly patients with progressive chronic kidney disease.

The educational value of ward rounds for junior trainees

Background: Only a paucity of studies have addressed clinician perspectives on patient decisional conflict, in making complex decisions between dialysis and conservative management (renal supportive and palliative care). Aim: To explore clinician views on decisional conflict in patients with end-stage kidney disease. Design: Interpretive, qualitative study. Setting and participants: As part of the wider National Institute for Health Research, PAlliative Care in chronic Kidney diSease study, semi-structured interviews were conducted with clinicians (nephrologists n = 12; 7 female and clinical nurse specialists n = 15; 15 female) across 10 renal centres in the United Kingdom. Interviews took place between April 2015 and October 2016 and a thematic analysis of the interview data was undertaken. Results: Three major themes with associated subthemes were identified. The first, ‘Frequent changing of mind regarding treatment options’, revealed how patients frequently altered their treatment decisions, some refusing to make a decision until deterioration occurred. The second theme, ‘Obligatory beneficence’, included clinicians helping patients to make informed decisions where outcomes were uncertain. In weighing up risks and benefits, and the impact on patients, clinicians sometimes withheld information they thought might cause concern. Finally, ‘Intricacy of the decision’ uncovered clinicians’ views on the momentous and brave decision to be made. They also acknowledged the risks associated with this complex decision in giving prognostic information which might be inaccurate. Limitations: Relies on interpretative description which uncovers constructed truths and does not include interviews with patients. Conclusion: Findings identify decisional conflict in patient decision-making and a tension between the prerequisite for shared decision-making and current clinical practice. Clinicians also face conflict when discussing treatment options due to uncertainty in equipoise between treatments and how much information should be shared. The findings are likely to resonate across countries outside the United Kingdom.