Possible beneficial association between renin-angiotensin-aldosterone-system blockade usage and graft prognosis in allograft IgA nephropathy: A retrospective cohort study [post]

2019 unpublished
Although immunoglobulin A nephropathy (IgAN) is associated with a high risk of renal allograft failure, evidences for its treatment, including renin-angiotensinaldosterone system blockade (RAASB) usage, remain limited. Methods In this bi-center retrospective cohort study, we included patients who were recently diagnosed with IgAN through allograft biopsies. We identified their 6-month antihypertensive medication prescriptions and investigated the association between the medication types,
more » ... ation types, albuminuria changes, and consequent 5-year death-censored-graft-failure (DCGF). The mixed effect model and cox regression analysis were used. Results A total of 464 allograft IgAN patients were included: 272, 38, 33, and 121 patients in the no antihypertensive medication, single agent RAASB, single agent beta blocker (BB)/calcium channel blocker (CCB), and combination therapy groups, respectively. High-degree albuminuria after 6 months of allograft IgAN diagnosis was an important prognostic parameter and a partial mediator for the association between the subgroups and 5-year DCGF. The usage of single RAASB was associated with decrement of albuminuria from allograft diagnosis (P for interaction = 0.03). The single BB/CCB group demonstrated significantly worse prognosis than the single RAASB group (adjusted hazard ratio, 2.76 1.09-6.98; P=0.03). Conclusions In conclusion, RAASB may be beneficial for graft prognosis in early allograft IgAN patients who require single antihypertensive medication therapy, by means of reducing albuminuria. Further investigation of treatment strategy in allograft IgAN is warranted. Background Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis during both the pre-and post-transplant eras [1-3], has demonstrated better posttransplant prognosis than other etiologies of end-stage renal disease (ESRD) in the short-4 term [4]. However, the development or recurrence of IgAN in allograft is associated with an increased risk of graft failure in the long-term [5, 6]. Although this accelerated graft dysfunction has been repetitively observed [4, 7, 8], evidence for treatment strategies of allograft IgAN remains limited. As allograft glomerulonephritis is one of the major obstacles in the improvement of long-term graft outcome in modern transplant medicine, the development of an adequate management strategy for allograft IgAN would be beneficial for prolonged graft use. Renin-angiotensin-aldosterone system blockade (RAASB), which includes angiotensin converting enzyme inhibitors and angiotensin receptor blockades, has been shown to effectively suppress the progression of native IgAN [9-12]. However, the benefits of RAASB during post-transplant periods are still debatable [13-16], although this is mainly related to a low prescription rate of the medications in the post-transplantation period [15]. In addition, whether RAASB usage is associated with better prognosis for primary glomerulonephritis in allograft, including IgAN [17, 18], is uncertain, even though a clinical guideline recommend its usage, with a low-grade recommendation level [19]. In this study, we aimed to provide supporting evidence for the potential benefits of RAASB in allograft IgAN. We reviewed our retrospective cohort of allograft IgAN patients and identified their prescribed hypertensive medication categories [8, 20]. We then compared their prognosis in terms of death-censored-graft-failure (DCGF) and changes in albuminuria levels. Methods Study design and study population This was a retrospective cohort study performed in two tertiary referral hospitals in Korea. We included transplant recipients who were diagnosed with pathologically confirmed allograft IgAN. The exclusion criteria were as follows: 1) patients who were 3. Abbas F, El Kossi M, Jin JK, Sharma A, Halawa A: Recurrence of primary glomerulonephritis: Review of the current evidence. World J Transplant 2017, 7(6):301-316. 4. Wyld ML, Chadban SJ: Recurrent IgA Nephropathy After Kidney Transplantation. Transplantation 2016, 100(9):1827-1832. 5. Briganti EM, Russ GR, McNeil JJ, Atkins RC, Chadban SJ: Risk of renal allograft loss from recurrent glomerulonephritis. N Engl J Med 2002, 347(2):103-109. 6. Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RDM, Clayton PA, Teixeira-Pinto A, Wong G: Recurrent glomerulonephritis after kidney transplantation: risk factors and allograft outcomes. Kidney Int 2017, 92(2):461-469. 7. Han SS, Huh W, Park SK, Ahn C, Han JS, Kim S, Kim YS: Impact of recurrent disease and chronic allograft nephropathy on the long-term allograft outcome in patients with IgA nephropathy. Transpl Int 2010, 23(2):169-175. Glomerular crescents are associated with worse graft outcome in allograft IgA nephropathy. Am J Transplant 2019, 19(1):145-155. 9. Coppo R, Peruzzi L, Amore A, Piccoli A, Cochat P, Stone R, Kirschstein M, Linne T: IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria.
doi:10.21203/rs.2.10961/v2 fatcat:enp3itvpenchve7hnchoyzdwhi