Sarah Moran

Renal transplantation in antineutrophil cytoplasmic antibody-associated vasculitis.

Purpose of reviewThis review aims to provide a state-of-the-art perspective on the role of kidney transplantation in cases of end-stage kidney disease due to antineutrophil cytoplasmic antibody (ANCA) vasculitis. We focus on patient and graft survival in recent years, timing of transplant, impact of ANCA status, and relapse of vasculitis in the allograft. Recent findingsGraft and patient outcome compare very favorably with other causes of kidney failure and several recent studies have indicated that these outcomes have improved further in recent years. Relapse of vasculitis posttransplant appears to be lower in the modern era of transplant induction. There may be an excess mortality in those transplanted less than 1 year after induction of vasculitis remission, so it is probably wise to wait for this period before proceeding with the graft. ANCA status at transplant does not appear to influence outcome. SummaryKidney transplantation is an excellent treatment for kidney failure due to vasculitis, although one must never lose sight of the cause of the original vasculitic kidney failure in the event of clinical deterioration of an allograft recipient, even if the diagnosis of ANCA vasculitis was many years previously.

Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non‐specific manifestations of renal injury

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal‐associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti‐neutrophil cytoplasm autoantibody (ANCA)‐associated vasculitis (AAV) patients. Thirty‐eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non‐specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy‐related.

Prolonged Duration of Renal Recovery Following ANCA-Associated Glomerulonephritis.

Background: As renal biopsies are not routinely repeated to monitor treatment response in anti-neutrophil cytoplasm antibody (ANCA)-associated glomerulonephritis, serum creatinine (SC) and proteinuria assessed by urine protein:creatinine ratio (UPCR) measurements are relied upon to provide a non-invasive estimate of disease activity within the kidney. However, sparse information exists about the time to achieve maximal improvement in these parameters, which has important implications for treatment decisions and disease-scoring systems. Methods: We analysed patients with ANCA-associated glomerulonephritis and renal impairment from cohorts in the United Kingdom and Ireland, with the primary objective of determining actuarial time to nadir SC and UPCR. Time to disappearance of haematuria was analysed as a secondary objective. Results: Ninety-four patients fulfilled our selection criteria, with 94 (100%) and 66 (70%) having reached their nadir SC and UPCR respectively during the follow-up period. Nadir SC was achieved after a median of 88 days (95% CI 74-102), UPCR at 346 days (95% CI 205-487). Those of Indo-Asian ethnic origin reached their nadir SC faster (34 days) than other ethnicities (p < 0.01). There were no significant differences in time to nadir SC or UPCR on the basis of gender, clinical diagnosis, ANCA positivity or renal biopsy findings. Conclusion: In this retrospective study, nadir creatinine and proteinuria occur later than other signs of clinical remission, suggesting that ongoing renal recovery continues for a significant time after diagnosis. It may benefit disease-scoring systems to take into account SC levels beyond the initial assessment.

The Irish Kidney Gene Project - Prevalence of Family History in Patients with Kidney Disease in Ireland

Background: The prevalence of kidney disease (KD) due to inherited genetic conditions in Ireland is unknown. The aim of this study was to characterise an adult kidney disease population in Ireland and to identify familial clusters of kidney disease within the population. Methods: This was a multicenter cross-sectional study of patients with kidney disease in the Republic of Ireland, from January 2014 to September 2014, recruiting from dialysis units and out-patient renal departments. A survey was performed by collecting data on etiology of kidney disease and whether a family history of kidney disease exists. Medical records were cross-referenced to confirm the etiology of kidney disease. Results: A total of 1,840 patients were recruited with a mean age of 55.9 years (range 17-94.5) and a male predominance (n = 1,095; 59.5%). A positive family history was reported by 629 participants (34.2%). Excluding polycystic kidney disease (n = 134, 7.3%), a positive family history was reported by 495 participants (26.9%). Kidney disease due to an unknown etiology was the commonest etiology in the non-polycystic kidney disease group with a positive family history (10.6%, n = 67). Kidney diseases that are not classically associated with familial inheritance including tubulo-interstitial kidney disease, congenital abnormalities of the kidney and urinary tract and glomerulonephritis demonstrated familial clustering. Conclusion: In an Irish non-polycystic kidney disease population, 26.9% reports a positive family history. The commonest etiology of kidney disease in the positive family history cohort, excluding autosomal dominant polycystic kidney disease, was kidney disease due to unknown etiology. Examining families with kidney disease provides an opportunity to better understand disease pathogenesis and potentially identify genetic predispositions to kidney disease.

Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: A cohort study

Background Early detection of renal involvement in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is of major clinical importance to allow prompt initiation of treatment and limit renal damage. Urinary soluble cluster of differentiation 163 (usCD163) has recently been identified as a potential biomarker for active renal vasculitis. However, a significant number of patients with active renal vasculitis test negative using usCD163. We therefore studied whether soluble CD25 (sCD25), a T cell activation marker, could improve the detection of renal flares in AAV. Methods sCD25 and sCD163 levels in serum and urine were measured by enzyme-linked immunosorbent assay in 72 patients with active renal AAV, 20 with active extrarenal disease, 62 patients in remission and 18 healthy controls. Urinary and blood CD4+ T and CD4+ T effector memory (TEM) cell counts were measured in 22 patients with active renal vasculitis. Receiver operating characteristics (ROC) curves were generated and recursive partitioning was used to calculate whether usCD25 and serum soluble CD25 (ssCD25) add utility to usCD163. Results usCD25, ssCD25 and usCD163 levels were significantly higher during active renal disease and significantly decreased after induction of remission. A combination of usCD25, usCD163 and ssCD25 outperformed all individual markers (sensitivity 84.7%, specificity 95.1%). Patients positive for sCD25 but negative for usCD163 (n = 10) had significantly higher C-reactive protein levels and significantly lower serum creatinine and proteinuria levels compared with the usCD163-positive patients. usCD25 correlated positively with urinary CD4+ T and CD4+ TEM cell numbers, whereas ssCD25 correlated negatively with circulating CD4+ T and CD4+ TEM cells. Conclusion Measurement of usCD25 and ssCD25 complements usCD163 in the detection of active renal vasculitis.

IgA Vasculitis in Adults

Purpose of reviewImmunoglobulin A vasculitis (IgAV) is a small vessel vasculitis with skin, joint, gastrointestinal and renal manifestations. Our understanding of the natural history of this disease is limited due to the overall low incidence of IgAV in adults and a lack of consensus regarding diagnostic criteria. In this review, we describe IgAV in the adult population, focusing on diagnostic and classification systems, and treatments strategies.Recent findingsRecent data from larger longitudinal adult cohorts demonstrate that IgAV is associated with significant morbidity and mortality. Treatment regimen remains controversial but emerging retrospective observational data support potential benefit of immunosuppression. As illustrated in trials of IgA nephropathy, immunosuppression carries significant risks of toxicity.SummaryTreatment regimen and selection of patients who will benefit from treatment remains challenging. Prospective treatment trials are needed to elucidate both the patient populations that will derive benefit and what treatment is most efficacious.