Kidney outcomes of malignant hypertension-associated thrombotic microangiopathy in patients with and without IgA nephropathy: a propensity score-matched analysis

Abstract

Background: IgA nephropathy (IgAN) can cause hypertension, and severe hypertension can exacerbate the progression of IgAN. However, the long-term kidney outcome of malignant hypertension (mHTN)-associated thrombotic microangiopathy (TMA) with IgAN is not well defined.

Methods: A total of 292 individuals with mHTN-associated TMA confirmed by kidney biopsy were included. Propensity score matching (PSM) analysis was performed to adjust for clinical characteristics in the comparison between cases with and without IgAN. Cox regression analysis was utilized to identify risk factors associated with long-term kidney outcome.

Results: A total of 86 mHTN-associated TMA with IgAN patients were compared with 206 mHTN-associated TMA with non-IgAN patients. After PSM, 61 pairs of patients with mHTN-associated TMA were matched. The mHTN-associated TMA with IgAN patients exhibited significantly lower serum albumin, higher 24-hour proteinuria, and a higher ratio of global sclerosis than those with non-IgAN. mHTN-associated TMA with IgAN was independently associated with impaired kidney function recovery [hazard ratio (HR), 0.48; 95% confidence interval (CI), 0.24-0.96, P = .038] compared with non-IgAN. This association remained significant after PSM (HR, 0.41; 95% CI, 0.17-0.99, P = .047). In addition, mHTN-associated TMA with IgAN was independently associated with kidney replacement therapy (KRT) compared with non-IgAN (HR, 2.31; 95% CI, 1.38-3.88; P = .002). This difference remained significant after PSM comparison (HR, 2.38; 95%CI, 1.14-4.99; P = .021). In addition, mHTN-associated TMA with IgAN patients had a higher incidence of receiving KRT and a lower incidence of kidney function recovery with a 25% reduction in creatinine levels than in non-IgAN patients, regardless of intensive blood pressure control.

Conclusions: The long-term kidney outcomes for mHTN-associated TMA patients with concomitant IgAN are significantly poorer than that of patients with non-IgAN. Monitoring kidney pathological characteristics will aid management and risk assessment at an early stage.

Keywords: IgA nephropathy; kidney biopsy; kidney replacement therapy; malignant hypertension; thrombotic microangiopathy.

Figure 1:

Representative light and electron microscopic findings of malignant hypertension-associated TMA (a) Periodic acid-Schiff (PAS) staining showing diffuse winkling of the capillary loop and capsular thickening (arrow), tubular atrophy and interstitial fibrosis (original magnification ×400). (b) PAS staining showing marked thickening of the medial layer in kidney arterioles (arrow) (original magnification ×400). (c) PAS staining showing vessel walls thickening with an onion-peel appearance and luminal narrowing and occlusion (arrow). Tubular atrophy and interstitial fibrosis are present (original magnification ×400). Scale bars 20 μm, in a–c. (d) Electronic micrograph showed diffuse winkling of the capillary loop (red arrow) and mild segmental subendothelial widening with flocculent material underneath (yellow arrow). Scale bar 2 μm.

Figure 2:

Cumulative incidence curve for a 50% decrease in creatinine, or a decrease in creatinine to normal, or kidney survival free from replacement therapy for 1 month, and free from dialysis for the patient. The log-rank test is used to compare the survival distributions between the groups, with the P value indicating the statistical significance of the observed differences in the rate of cumulative incidence: (a) overall comparison and (b) propensity score-matched comparison.

Figure 3:

Survival curve for KRT in mHTN-associated TMA. The log-rank test is used to compare the survival distributions between the groups, with the P value indicating the statistical significance of the observed differences in the rate of progression to KRT: (a) overall comparison and (b) propensity score-matched comparison.