IgA glomerulonephritis (IgAGN) is one of the most common forms of primary glomerulonephritis worldwide, accounting for 25-50 % of all patients with primary glomerulopathy. The hallmark for diagnosis is the deposition of immunoglobulin A (IgA) in the glomerular mesangium, leading to histological damage of various degrees. A broad spectrum of clinical presentation and variable prognosis is typical for the disease and approximately 25-30 % of patients eventually develop end-stage renal disease (ESRD).
After the description of the disease in the late 1960s a considerable body of information has accumu-lated especially on the prognostic features and etiology of IgAGN. The classical risk factors for poorer prognosis comprise kidney insufficiency, urinary protein excretion above 1g/24 h, prevalence of hypertension and certain histopathological changes at the time of the biopsy. Novel risk factors include hyperuricemia, hypertriglyceridemia and several gene polymorphisms. The current understanding of the etiology relies on observed aberrant glycosylation in the IgA1 molecule, leading to subsequent accumulation in the mesangium.
Reports from population studies and kidney patients with varying degrees of renal insufficiency have shown insulin resistance and inflammatory parameters to be associated with renal function. Whether these cause kidney insufficiency or simply act as markers of reduced glomerular filtration rate (GFR) is not well established. Furthermore, some population studies have shown that moderate alcohol consumption can prevent kidney insufficiency. Previous studies with alcoholic patients have reported alcohol consumption to be linked with the development of secondary IgAGN, but no information is available on the impact of alcohol in established IgAGN.
The purpose of the present series was to further investigate the prognostic role of insulin resistance, inflammatory markers and alcohol consumption and to gather data on the use of the biomarkers available in evaluating alcohol consumption in patients with IgAGN.
The original study population consisted of 223 patients in whom IgAGN had been diagnosed. From this retrospective group a cohort were invited to attend physician’s appointment twice. The median time from the diagnostic renal biopsy was 11 years on the first visit and the second took place approximately 6 years thereafter. ESRD had developed in 7 % of the patients by the time of the second visit and IgAGN was classified as progressive in 19.5 % as assessed by cystatin-C and 30.8 % as assessed by GFR estimated by the MDRD equation eGFR(MDRD). Serum insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein (CRP), serum albumin and total leuco-cyte count (WBC) at the first visit showed significant associations with subsequent progression of IgAGN. The patients in the progressive group had higher insulin, HOMA-IR, CRP and WBC levels and lower serum albumin levels than stable subjects.
Detailed information on alcohol consumption was obtained at the first visit and biomarkers evaluating the use of alcohol were obtained simultaneously. ESRD patients were excluded from both alcohol stud-ies. Both cross-sectional and longitudinal data were analysed in the alcohol consumption study and only a cross-sectional approach was utilized in the biomarker study. Moderate drinkers were found to have the best kidney function regardless of mode of measurement. Light drinkers among women and moderate drinkers among men evinced the best kidney function. In multivariate analyses of the whole population, adjusted by hypertension and 24-h urinary protein excretion, moderate alcohol consumption was a significant factor in better kidney function when analysed both cross-sectionally and longitudinally.
Serum carbohydrate-deficient transferrin (CDT), gamma glutamyl transferase (GGT), alanine ami-notransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), a combination marker mathematically derived from GGT and CDT (gamma-CDT) and a novel alcohol consumption marker IgA antibody against acetaldehyde-modified hemoglobin (anti-adduct IgA) were used to evaluate the use of alcohol and liver function. Serum levels of anti-adduct IgA were higher in IgAGN pa-tients than in healthy controls and were elevated in 63 % of IgAGN patients. Moreover, the levels were not associated with alcohol consumption, as was the case in the male control population. CDT, MCV and gamma-CDT seemed to be the most useful consumption markers in the IgAGN population.
In conclusion, insulin resistance and inflammatory markers are associated with the progression of IgAGN and could be useful in establishing the prognosis. Whether they have an independent prognostic role remains to be elucidated in future prospective studies. Moderate alcohol consumption might be beneficial in protecting against kidney function decline and the protective level might vary according to gender. The most useful parameters for evaluating alcohol consumption in these patients seem to be markers other than anti-adduct IgA.
