Increased Risk of End-Stage Renal Disease in Familial IgA Nephropathy

Abstract

ABSTRACT. Primary IgA nephropathy (IgAN) is characterized by recurrent episodes of macroscopic hematuria accompanied by upper respiratory tract infections or persistent asymptomatic microscopic hematuria with or without proteinuria. IgAN may involve one or more members of a family. Three generations of a cohort of 110 patients with biopsy-proven IgAN, living in Southern Italy, were checked for urinalysis, and the relative risk (RR) of developing the disease was evaluated. A total of 19 unrelated familial, 37 suspected, and 54 sporadic cases of IgAN were identified. Renal survival was estimated by the Kaplan-Meier method for censored data and compared by use of the log-rank test. More than 50% of the patients with IgAN clustered in kindred with more than two probably affected relatives. In 19 unrelated IgAN families, 8 had single-generation (SG) and 11 multigenerational (MG) involvement showing a prevalent vertical transmission of the trait. The RR was 16 times higher in first-degree relatives (odds ratio [OR], 16.4; 95% confidence interval [CI], 5.7 to 47.8; P < 0.0001) and >2 times higher, even if NS, in second-degree relatives (OR, 2.4; 95 % CI, 0.7 to 7.9; P = 0.145). The clinical and histologic picture of familial and sporadic IgAN appeared to be similar. The 20-yr renal survival rate from the apparent onset of the disease was significantly poorer in patients with familial (41%) than in patients with sporadic (94%) IgAN (P = 0.003). Furthermore, 15-yr renal survival from the time of renal biopsy was significantly worse in familial IgAN (P = 0.02); end-stage renal disease was present in 64% of familial and only in 8% of patients with sporadic IgAN. Finally, renal survival was significantly worse in patients belonging to families with SG rather than with MG involvement (P = 0.03). These data show, for the first time, that familial IgAN may be considered a nonbenign disease that occurs frequently in first-degree relatives. Familial IgAN has a poorer outcome than sporadic IgAN. Therefore, an accurate family history and urinalysis in all family members is urgently recommended in clinical practice. This procedure might avoid late referral of subjects with persistent and underestimated urinary abnormalities and late diagnosis of the disease.

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

“…Our observation indicates that the prevalence of positive-FH was 11.6% among histologically proven, primary IgAN cases. The incidence of family clustering is almost comparable to that in previous studies: 6.7% in China [ 8 ] and 17.2–34% in Italy [ 5 ] (Additional file 2 ). Other studies with Caucasians showed a lower frequency of familial aggregation in total sporadic cases: 1.8% in Ireland [ 6 ] and 1.4% in the US [ 15 ].…”

“…Of note, we could not find any difference in the age of onset and MEST-C score at initial biopsy. However, familial cases were diagnosed younger and showed histologically milder disease at an earlier stage, pointing to the importance of earlier diagnosis [ 5 , 8 , 15 ]. More attention for familial clustering and active screening of family members for eGFR and urinalysis are recommended in clinical practice.…”

“…We defined a subset of positive-FH by subclassifying IgAN patients under the categories of either ‘familial’ or ‘suspected-familial’ renal history, employing the definitions that fit with those of previous literature [ 3 – 5 ]: specifically, “familial” renal history is ascertained when at least two first-degree family members have a biopsy-proven IgAN; and “suspected-familial,” is assigned, if one first-degree family member has a biopsy-proven IgAN and other relatives have persistent microscopic hematuria and/or renal failure with chronic kidney disease of unknown cause. The family history was updated based on the latest medical record.…”

“…There are some controversial results regarding renal outcomes among familial IgAN patients. Studies on IgAN patients in China and Italy showed that the positive-FH subtype accounts for up to 7 and 17% of all IgAN patients, respectively, and positive-FH was consistently associated with a worse renal prognosis [ 5 , 8 ]. Studies on Irish patients with IgAN reported that the positive-FH subgroup accounts for 1.8% of the total IgAN prevalence and had unfavorable outcomes [ 4 ].…”

Association between geriatric nutritional risk index and pathological phenotypes of IgA nephropathy

“…IgAN mainly manifests as the deposition of IgA in the glomeruli, a disease that is mediated by immune complexes ( Rodrigues, Haas & Reich, 2017 ). IgA deposition in the mesangial region of the glomerulus causes inflammation that promotes mesangial proliferation and interstitial damage, which progresses to end-stage renal disease (ESRD) in nearly 40% of patients, although some patients maintain stable renal function for many years ( Schena et al, 2002 ). Patients with IgAN have many different clinical manifestations, ranging from asymptomatic hematuria and proteinuria to massive proteinuria to acute renal failure ( D’Amico, 2004 ).…”