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

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).

Proteomics of human glomerulonephritis by laser microdissection and liquid chromatography-tandem mass spectrometry.

AIM: Laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) enable clinicians to analyse proteins from tissue sections. In nephrology, these methods are used to diagnose diseases of abnormal protein deposition, such as amyloidosis, but they are seldom applied to the diagnosis and pathophysiological understanding of human glomerular diseases. METHODS: Renal biopsy specimens were obtained from five patients with IgA nephropathy (IgAN), five patients with membranous nephropathy (MN) and five kidney transplant donors (as controls). From 10-µm-thick sections of formalin-fixed, paraffin-embedded specimens, 0.3-mm2 samples of glomerular tissue were subjected to LMD. The samples were analysed by LC-MS/MS and investigated clinically and histologically. RESULTS: From the control glomeruli, we identified more than 300 types of proteins. In patients with IgAN, we detected significant increases not only in IgA1 and in C3, but also in the factors related to oxidative stress and cell proliferation in comparison to the controls. In patients with MN, levels of IgG1, IgG4, C3, C4a and phospholipase-A2-receptor were significantly elevated in comparison to the controls, as were the aforementioned factors related to oxidative stress and cell proliferations detected in IgAN. CONCLUSION: Application of LMD and LC-MS/MS to renal biopsy specimens enabled us to identify not only pathognomonic proteins for the diagnosis, but also several factors possibly involved in the pathogenesis of human glomerular diseases.

Granulomatosis with polyangiitis in a patient with a thoracic vertebral lesion: a case report.

Granulomatosis with polyangiitis is a systemic, small vessel vasculitis associated with the anti-neutrophil cytoplasmic antibody. We herein report a case of granulomatosis with polyangiitis with paravertebral lesions. A 69-year-old man presented to our hospital with fever, back pain, and myalgia. A computed tomography scan showed multiple lung nodules, while magnetic resonance imaging revealed soft tissue shadows around a thoracic vertebral lesion. A laboratory examination revealed positive myeloperoxidase anti-neutrophil cytoplasmic antibody. He was diagnosed with granulomatosis with polyangiitis. He was treated with oral glucocorticoid and intravenous cyclophosphamide, and the shadows resolved. Physicians should consider granulomatosis with polyangiitis in cases with paravertebral lesions.