P0010INCREASED SERUM URIC ACID LEVELS ARE ASSOCIATED TO RENAL ARTERIOLOPATHY AND PREDICT POOR OUTCOME IN IGA NEPHROPATHY

Abstract

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of End Stage Renal Disease (ESRD). In addition to the classical progression factors, including hypertension, proteinuria, and decreased renal function, other atherosclerosis-related factors, such as hypertriglyceridemia, have been reported to the renal progression of IgAN. Above all, many studies have indicated an association between hyperuricemia and progression of IgAN. Increased serum uric acid (SUA) levels are also well known to be associated with hypertension, endothelial dysfunction and development of cardiovascular and kidney diseases both in general population and high-risk patients. Previous studies suggested that uric acid induces proliferation of vascular smooth muscle cells, activates the renin–angiotensin–aldosterone system (RAAS) and also reduces the synthesis of nitric oxide. Furthermore, there is evidence that uric acid can promote the oxygenation of low-density lipoproteins (LDL) and increase the production of free oxygen radicals, increasing inflammation and oxidative stress. In consequence of these processes, SUA might specifically promote atherosclerosis and arteriolar damage, possibly playing a major role in pathogenesis and progression of IgAN. The aim of the present study was to explore the correlation between SUA levels, renal damage and its implication for renal outcome and all cause death in IgAN patients. Method The data for clinical features, laboratory and renal pathological examination were collected from 145 renal biopsy-proven IgAN patients and were retrospectively analyzed to determine the correlation between SUA levels, renal damage and overall outcome. Hyperuricemia (HU) was defined as the highest SUA gender-specific tertile. Biopsy-proven arteriolar damage was defined by the presence of arteriolar hyalinosis or intimal thickening. The primary outcome was death or ESRD. Results The mean baseline serum uric acid levels of the 42 female and 103 male patients at the time of kidney biopsy were 5.4 ±1.7 and 7.2 ±1.8 mg/dL, respectively. HU was >7.7 mg/dl for males and > 6.2 mg/dl for females. Patients were stratified on the basis of baseline gender-specific SUA level tertiles. Clinical and histologic characteristics are described in table 1. The higher the gender-specific SUA tertile, the greater the prevalence of arteriolar damage (p=0.02). No other histologic feature was significantly correlated with uric acid levels, therefore we analyzed laboratory and clinical characteristics on the basis of the presence/absence of biopsy-proven arteriolar damage (Table 2). At logistic regression analyses SUA was associated with arteriolar damage at univariate (OR 1.45 CI [1.12-1.87], p=0.004) and multivariate analyses (OR 1.75 CI [1.10-2.93], p=0.03), recorded in Table 3. Receiver Operating Curve (ROC) was performed and the sensitivity and specificity of SUA for predicting arteriolar damage were showed in Figure 1. The area under the ROC curve was 0.67 (IC95% 0.61 to 0.73) indicating that SUA is a fair test for detecting arteriolar damage. Patients with arteriolar damage had a worst outcome compared to patients without it (Kaplan Maier survival analysis, log rank test p=0.002, Figure 2a). HU and arteriolar damage had a synergic impact on progression of IgAN. Patients having both arteriolar damage and HU, showed a reduced survival free from the primary outcome as compared to those having only one risk factor or neither (log rank test p=0.003, Figure 2b). Conclusion SUA levels are directly associated with arteriolar damage and poor prognosis in patients with IgAN. Our study suggests the presence of higher SUA levels in IgAN patients identifies a sub-population at increased risk of progressing to ESRD or death, for whom a particular surveillance is warranted, possibly because of the pathogenetic role of SUA on arteriolar damage.