Renal Disease in Inborn Errors of Immunity: a Case Series

Abstract

Renal disease is an underappreciated complication of inborn errors of immunity (IEIs). Chronic kidney disease (CKD) is associated with significant morbidity and mortality in the general population; however, clinical experience with CKD in IEIs is limited. We examined the age of onset, progression, and outcomes of CKD in 4 adult IEI patients seen at our centre. Immunologic diagnoses for all patients were made clinically and with the support of genetic testing. Renal biopsy pathology reports, age at symptom onset and diagnosis of IEI, age at diagnosis of CKD, serum creatinine levels, and measures of proteinuria were assessed.We reviewed the charts of four patients with IEIs and CKD. The IEI diagnoses were: 1) STAT3 loss-of-function (Job syndrome), 2) common variable immunodeficiency (CVID) with compound heterozygous TNFRSF13B (TACI) variants, 3) CVID with negative whole exome sequencing (WES), and 4) combined immunodeficiency with negative WES. All patients received renal biopsy-confirmed diagnoses of CKD. Biopsies were performed between adolescence and adulthood (mean age 27.25 years, range 18–35), on average 18.5 years after their initial symptoms of an underlying IEI (range 13–24 years). The histopathological diagnoses respectively were 1) immune complex-mediated mesangial proliferative and membranous glomerulonephritis, 2) interstitial nephritis with glomerulosclerosis and interstitial fibrosis with lymphocytic infiltration likely from lymphoma, 3) granulomatous infiltration from underlying CVID, and 4) lupus nephritis predominantly with proteinuria. In all cases, despite treatment, renal disease was non-reversible. One patient required renal transplantation, and one patient became dialysis dependent. For two patients, renal function stabilized but did not revert to pre-disease levels. Renal disease is a potentially serious comorbidity that can develop in IEIs, predisposing to further infections and impairing quality of life. Practitioners caring for people with IEIs should be aware that CKD can affect young adults and may present several years from IEI symptom onset. Monitoring for renal disease and prompt referral to a nephrologist for potential treatment should be pursued, as recognizing CKD in its early stages may help prevent or slow progression.