Positive renal familial history in IgA nephropathy is associated with worse renal outcomes: a single-center longitudinal study

Abstract

Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although most IgAN cases are sporadic, few show a familial aggregation. However, the prevalence and prognosis of IgAN individuals with positive familial history (FH) of renal disorders remains uncertain. To address these issues, we conducted a longitudinal observational study on a single-institution cohort of patients with biopsy-proven IgAN. Methods A total of 467 IgAN patients who underwent renal biopsy during 1994 to 2019 were ascertained to have positive- or negative-FH by history taking and were followed for an average of 8.9 years. We compared the clinical and pathological features of the two subgroups. The primary outcome, a composite of a hard endpoint (end-stage renal disease [ESRD]) and surrogate endpoint (a 50% or more reduction in the estimated glomerular filtration rate [eGFR] from baseline), was evaluated. To estimate the risk for progression to ESRD, a Cox proportional hazards analysis was performed for a subset of patients who underwent follow-up for > 2 years and had an eGFR > 30 mL/min/1.73 m2 at baseline (n = 389; observation, 8.7 years). Results Positive-FH subtype accounted for 11.6% (n = 54) of all IgAN patients. At baseline, there were no significant differences between the positive- and negative-FH subgroups regarding age, sex, comorbid disease, MEST-C score, observation period, and therapeutic interventions. However, the eGFR value at baselines was significantly lower in the positive-FH subgroup than in the negative-FH subgroup (P < 0.01). On multivariate analysis, positive-FH emerged an independent determinant of poorer renal outcomes (odds ratio, 2.31; 95% confidence interval, 1.10–4.85; P = 0.03), after adjusting for confounding factors. eGFR at follow-up was significantly lower in the positive-FH subgroup than in the negative-FH subgroup after adjustment for age and observation period. Conclusions Positive-FH was found in 11.6% of all IgAN patients, consistent with the incidence seen in previous literature. A significantly lower eGFR at baseline and last follow-up and unfavorable renal outcomes in the positive-FH subgroup suggest that certain genetic risk factors predisposing to renal failure may exist in a fraction of our IgAN cohort. (331 words).

Out of sight: chronic kidney diseases among diabetic patients attending care and follow up. Findings from pastoralist health facilities of Southern Ethiopia

“…Another justification for this might be CKD more affects immediate and near relatives who shared more genes through mutation that the risk of getting kidney problem either to immediate child or family. This statement goes with the studies conducted in Korea and Japan (35,36).…”

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“…The exact mechanisms through which the gut microbiota may induce IgA nephropathy are not fully understood, and research in this area is still ongoing. Some hypotheses and associations have been proposed, such as the following: (a) dysbiosis—gut permeability: a compromised gut barrier allows bacterial components, such as lipopolysaccharides, to translocate from the gut into the bloodstream leading to endotoxemia, further triggering an immune response; this immune activation may lead to the production of IgA antibodies against these bacterial components and may contribute to the formation of immune complexes [ 40 , 57 ]; (b) IgA production—immune activation: the gut-associated lymphoid tissue (GALT) is rich in IgA-producing B cells; gut dysbiosis can influence the activation and proliferation of these B cells, leading to the production of more IgA antibodies; some of these IgA antibodies may be directed against gut-derived antigens or bacterial products, and in some instances, these antibodies can cross-react with antigens in the kidneys, contributing to the formation of immune complexes in the glomeruli [ 58 ]; (c) genetic factors: genetic predisposition is believed to play a role in the development of IgA nephropathy; certain genetic variations may affect the immune response to gut bacteria and their products, making some individuals more susceptible to the production of autoantibodies and the subsequent development of IgA nephropathy [ 59 ]. In IgA nephropathy, it was noticed that gut dysbiosis is induced by an increased presence of bacteria species belonging to Streptococcus ssp., Escherichia - Shigella ssp., and Eubacterium ssp., and low contents of Bifidobacterium ssp., Enterococcus ssp., Clostridium ssp., Leuconostoc ssp., Prevotella ssp., and Lactobacillus ssp.…”

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“…Although IgAN occurs sporadically, about 5–8% of patients have relatives with biopsy-proven IgA or abnormality in urine. Patients with familial history of IgAN often have a worse prognosis [ 90 ]. However, the clinical presentations of IgA are inconsistent.…”