Department of Nephrology, Hôpital Tenon, Sorbonne Université, Paris, France.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
J Am Soc Nephrol. 2024 Jan 1;35(1):103-116. doi: 10.1681/ASN.0000000000000242. Epub 2023 Sep 29.
The pivotal event in the pathophysiology of IgA nephropathy is the binding of circulating IgA-containing immune complexes to mesangial cells, with secondary glomerular and tubulointerstitial inflammation and fibrosis. The paramount difficulty in the management of IgA nephropathy is the heterogeneity in its clinical presentation and prognosis, requiring an individualized treatment approach. Goal-directed supportive care remains the bedrock of therapy for all patients, regardless of risk of progression. Sodium-glucose transporter 2 inhibitors and sparsentan should be integral to contemporary supportive care, particularly in patients with chronic kidney damage. Pending the development of reliable biomarkers, it remains a challenge to identify patients prone to progression due to active disease and most likely to derive a net benefit from immunosuppression. The use of clinical parameters, including the degree of proteinuria, the presence of persistent microscopic hematuria, and the rate of eGFR loss, combined with the mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents score, is currently the best approach. Systemic glucocorticoids are indicated in high-risk patients, but the beneficial effects wane after withdrawal and come at the price of substantial treatment-associated toxicity. Therapies with direct effect on disease pathogenesis are increasingly becoming available. While targeted-release budesonide has garnered the most attention, anti-B-cell strategies and selective complement inhibition will most likely prove their added value. We propose a comprehensive approach that tackles the different targets in the pathophysiology of IgA nephropathy according to their relevance in the individual patient.
IgA 肾病的病理生理学中的关键事件是循环 IgA 免疫复合物与系膜细胞结合，继发肾小球和小管间质炎症和纤维化。IgA 肾病管理中的最大难题是其临床表现和预后的异质性，需要个体化的治疗方法。无论进展风险如何，目标导向的支持性治疗仍然是所有患者治疗的基础。钠-葡萄糖协同转运蛋白 2 抑制剂和 sparsentan 应该是当代支持性治疗的重要组成部分，特别是在有慢性肾脏损害的患者中。在可靠的生物标志物开发之前，识别因疾病活动而易于进展且最有可能从免疫抑制中获得净获益的患者仍然是一个挑战。使用临床参数，包括蛋白尿程度、持续镜下血尿的存在以及 eGFR 丧失率，结合系膜细胞增生、内皮下细胞增生、节段性肾小球硬化、肾小管萎缩/间质纤维化、新月体评分，是目前最好的方法。高危患者需要使用全身性糖皮质激素，但停药后疗效减弱，且治疗相关毒性较大。对疾病发病机制有直接作用的治疗方法越来越多。虽然靶向释放布地奈德引起了最多的关注，但抗 B 细胞策略和选择性补体抑制很可能证明它们的附加价值。我们提出了一种综合方法，根据个体患者的相关性，针对 IgA 肾病的病理生理学中的不同靶点进行治疗。
