Microangiopathy associated with poor outcome of immunoglobulin A nephropathy: a cohort study and meta-analysis

Abstract

Background Microangiopathy (MA) lesions are not rare in immunoglobulin A nephropathy (IgAN) and have been suggested a potential role of increasing risk in renal function decline. However, this suggestion has not been universally accepted. We aimed to investigate its role in our cohort and in multiple studies through a systematical meta-analysis. Methods This cohort study included 450 IgAN patients, confirmed by renal biopsy at Tongji Hospital, China, from January 2012 to December 2016. Clinical data were collected and analyzed. We systematically searched PubMed and Web of Science for studies investigating the association between MA lesions and IgAN. Results In our cohort, IgAN patients with MA were significantly older, and had higher blood pressure, more proteinuria, worse kidney function, and increased uric acid level compared to patients without MA. When comparing pathological features with the non-MA group, the MA group exhibited more global glomerulosclerosis and interstitial fibrosis/tubular atrophy. MA lesions were independently associated with a composite kidney outcome in IgAN patients [adjusted hazard ratio: 2.115; 95% CI: 1.035–4.320; P = 0.040]. Furthermore, this relationship was validated in a meta-analysis involving 2098 individuals from 5 independent cohorts. The combined data showed a 187% adjusted risk of poor renal outcome in IgAN patients with MA compared to patients without MA (adjusted risk ratio: 2.87; 95% CI: 2.05–4.02; I2 = 53%). Conclusion MA lesions could serve as a valuable predictor for disease progression in patients with IgAN, extending beyond the widely recognized Oxford MEST-C score.

Thrombotic microangiopathy in IgA nephropathy: pathophysiology, histopathology, and treatment perspectives

“…TMA predominantly manifests in arterial and arteriolar locations, with a notable absence of glomerular involvement (43,44). Histologically, TMA in IgAN is characterized by fresh fibrinous vascular thrombi, distinguished by the presence of bright reddish staining fibrinous material and marked dilation with smoothing of the internal elastic lamina (45,46). Chronic lesions exhibit organized thrombi with recanalized vascular channels, often displaying an "onion-skin" appearance (47,48).…”

“…Several studies have linked TMA in IgAN with poor prognosis (6,46). Recent studies showed that individuals with combined IgAN and TMA including frequent severe hypertension, acute kidney injury, nephrotic syndrome, lower GFR, and severe tubular atrophy/interstitial fibrosis at the time of biopsy (13,15).…”