IgA Nephropathy and Thrombotic Microangiopathy
Abstract
Introduction: Although the association between thrombotic microangiopathy (TMA) and IgA nephropathy (IgAN) is a known fact, its prevalence, pathogenesis and progression are not clear yet. Methods: A descriptive, retrospective study involving 12 patients with IgAN and TMA (IgAN-TMA) was carried out; patients were diagnosed by a renal biopsy performed in our hospital in order to analyze clinicopathologic features. All the biopsy samples were processed for light microscopy and immunofluorescence. Results: The prevalence of patients with IgAN-TMA was 4.4% (12/274). The mean age was 33 and 58.3% of the subjects were men, showing, during diagnosis, mean systolic and diastolic blood pressure values of 171.3±53 mmHg and 97.5±19.8 mmHg, respectively. The average amount of protein in urine was 5.3 ± 3.7g/24 h and 8 patients had nephrotic- range proteinuria. Impairment of renal function was found in 11 patients, with a mean serum creatinine level of 7.2±4.7 mg/dL. No clinical or laboratory findings suggested thrombotic microangiopathy in any of the patients. The renal biopsy showed acute TMA with arteriolar fibrin thrombi in 75% of the subjects and ‘onion-skin-like’ chronic lesions with concentric intimal hyperplasia in 83.3% of them, which were associated with a high percentage of global glomerulosclerosis (72%), moderate tubular atrophy (38.6%) and/or interstitial fibrosis (31.3%). In 91.7% of the cases, TMA was related to histological grade 5. Conclusions: The prevalence and significance of the relationship between IgAN and TMA pose the question of whether TMA is the cause or consequence of advanced stage IgAN. Several clinicopathologic studies have proved that TMA plays a major role in IgAN progression. The connection of TMA with creatinine serum and proteinuria levels seems to support this conclusion. While systemic TMA usually affects multiple organs, in these cases, the kidney was the only one compromised. Endothelial injury and the subsequent microvascular thrombosis lead to ischaemia and kidney failure. The TMA-IgAN finding in patients with normal blood pressure at the time of the biopsy suggests that neither hypertension nor advanced parenchymal lesions are a prerequisite for the development of TMA. The physiopathological mechanisms leading to endothelial injury are still unknown, but appear to be different from those of malignant nephrosclerosis.
References
Nasri H. Thrombotic Microangiopathy in IgA Nephropathy. Iran Red Crescent Med J. 2013;15(12):e10234.
El Karoui K, Hill GS, Karras A, Jacquot C, Moulonguet L, Kourilsky O, et al. A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy. J Am Soc Nephrol. 2012;23(1):137-48.
Chang A, Kowalewska J, Smith KD, Nicosia RF, Alpers CE. A clinicopathologic study of thrombotic microangiopathy in the setting of IgA nephropathy. Clin Nephrol. 2006;66(6):397-404.
Lee HS, Lee MS, Lee SM, Lee SY, Lee ES, Lee EY, et al. Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee’s glomerular grading system. Nephrol Dial Transplant. 2005;20(2):342-8.
Roberts IS. Oxford classification of immunoglobulin A nephropathy: an update. Curr Opin Nephrol Hypertens. 2013;22(3):281-6.
Radford MG Jr, Donadio JV Jr, Bergstralh EJ, Grande JP. Predicting renal outcome in IgA nephropathy. J Am Soc Nephrol. 1997;8(2):199-207.
Lai KN, Tang SC, Schena FP, Novak J, Tomino Y, Fogo AB, et al. IgA nephropathy. Nat Rev Dis Primers. 2016;2:16001.
Soleymanian T, Najafi I, Salimi BH, Broomand B. Prognostic factors and therapy assessment of IgA nephropathy: report from a single unit in Iran. Ren Fail. 2011;33(6):572-7.
D´Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. 2000;36(2):227-37.
Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997;29(6):829-42.
Feiner HD, Cabili S, Baldwin DS, Schacht RG, Gallo GR. Intrarrenal vascular sclerosis in IgA nephropathy. Clin Nephrol. 1982;18(4):183-92.
Wu J, Chen X, Xie Y, Yamanaka N, Shi S, Wu D, et al. Characteristics and risk factors of intrarenal arterial lesions in patients with IgA nephropathy. Nephrol Dial Transplant. 2005;20(4):719-27.
Cai GY, Chen XM. Immunoglobulin A nephropathy in China: progress and challenges. Am J Nephrol 2009;30(3):268-73.
De Rosa GE, von Stecher F, Falcón MF, Robaina J, Marini A, Alberton V. Prevalencia y correlación clínicopatológica de lesiones vasculares renales en la nefropatía por IgA. Rev Nefrol Argent. 2012;10(1):8-19.
Nasri H, Mortazavi M, Ghorbani A, Shahbazian H, Kheiri S, Baradaran A, et al. Oxford-MEST classification in IgA nephropathy patients: A report from Iran. J Nephropathol. 2012;1(1):31-42.
Nasri H, Mubarak M. Significance of vasculopathy in IgA nephropathy patients with regard to Oxford classification and immunostaining findings: a single center experience. J Renal Inj Prev. 2013;2(2):41-5.
Zhang JJ, Jiang L, Liu G, Wang SX, Zou WZ, Zhang H, et al. Elevation of serum von Willebrand factor and anti-endothelial cell antibodies in patients with immunoglobulin A nephropathy are associated with intrarenal arterial lesions. Nephrology (Carlton). 2008;13(8):712-20.
