IgA vasculitis tied to increased hypertension, CKD risk
Individuals with immunoglobulin A vasculitis (IgAV, otherwise known as Henoch-Schönlein purpura) – a type of small vessel vasculitis more common in children – have an increased risk of hypertension and chronic kidney disease (CKD), according to a retrospective analysis.
Researchers sought to evaluate cardiovascular (CV), venous thromboembolic, and renal outcomes in both adult-onset (≥16 years, mean age at study entry 43.0 years, 48.4 male; n=2,828) and childhood-onset IgAV (<16 years, mean age at study entry 17.6 years, 53.0 male; n= 10,405) using the large UK THIN* database. Participants were compared against age- and sex-matched controls at a 2:1 ratio. [Ann Rheum Dis 2019;78:261-269]
In the adult-onset cohort, more IgAV patients were diagnosed with hypertension (6.93 percent vs 5.57 percent, adjusted hazard ratio [adjHR], 1.42, 95 percent confidence interval [CI], 1.19–1.70; p<0.001) and CKD (5.11 percent vs 3.42 percent, adjHR, 1.54, 95 percent CI, 1.23–1.93; p<0.001) vs controls. All-cause mortality rate was also higher in the IgAV arm vs the control arm (8.42 percent vs 6.15 percent, adjHR, 1.27, 95 percent CI, 1.07–1.50; p=0.006), which achieved nonsignificance on sensitivity analysis (adjHR, 1.09, 95 percent CI, 0.83–1.42).
The increased CKD risk could be attributed to the higher burden of comorbidity and renal impairment at baseline, explained the researchers. For all-cause mortality, the lack of statistical significance on sensitivity analysis could be due to the reduced length of follow-up when only incident cases were considered, they added.
For childhood-onset IgAV, compared with controls, the IgAV arm also had a higher incidence of hypertension (1.34 percent vs 0.93 percent, adjHR 1.52, 95 percent CI, 1.22–1.89; p<0.001) and CKD (0.31 percent vs 0.16 percent; adjHR, 1.89, 95 percent CI, 1.16–3.07; p=0.010).
“The similar [hypertension] risk for children and adults … could be explained by renal manifestations of IgAV or by use of medications such as non-steroidal anti-inflammatory drugs and corticosteroids,” said the researchers. “The association remained significant [on] sensitivity analysis … suggesting that it is not solely an acute feature of the disease.”
There was no evidence of association between IgAV and other primary endpoints ie, ischaemic heart disease (IHD, adjHR, 1.08; p=0.637), stroke/transient ischaemic attack (adjHR, 0.95; p=0.758), or venous thromboembolism (VTE, adjHR, 1.21; p=0.424) despite evidence suggesting increased risk of these outcomes with IgAV. [G Ital Cardiol 2013;14:622-625; Clin Pediatr 2014;53:1396-1398; Indian J Dermatol 2013;58:409] According to the researchers, the results on VTE should be interpreted with caution as this could be an isolated acute event.
Although the database broadly represents the population in terms of chronic disease prevalence, mortality rates, and ethnicity, [Inform Prim Care 2011;19:251-255] the researchers underscored several confounding factors.
It was not certain whether the diagnoses were clinically- or biopsy-based, the researchers noted. “We are unable to identify patients with renal involvement at diagnosis and recognize [potentially] stronger associations with the outcomes if the cohort is restricted to patients with biopsy-proven IgAV, as previously shown in patients with biopsy-proven Henoch-Schönlein nephritis.” [J Am Soc Nephrol 2002;13:1271-1278]
Moreover, the lack of histological investigation may have misdiagnosed other vasculitides as IgAV, said the researchers. “[The] inclusion of such patients could increase the incidence of complications such as CKD … [W]e have no data on antineutrophil cytoplasm antibody testing and cannot exclude that this diagnosis may have been missed in some cases.”
Overall, the results underline the importance of blood pressure and renal function monitoring in patients with IgAV, noted the researchers. “Our data also suggest that IgAV should not be considered a ‘single hit’ disease – clinicians should monitor for long-term sequelae … Appropriate surveillance and risk factor modification could improve long-term outcomes in these patients.”
Further research is warranted to establish the origin of hypertension and evaluate unrecognized long-term sequelae in this setting, they said. The young age of most patients and the short follow-up may also require longer studies to address IHD risk, they added.