Outcome Of IgA Nephropathy Research Articles

Association of C1q deposition with renal outcomes in IgA nephropathy

IgA nephropathy (IgAN) is characterized by a highly variable clinical course. It has been reported that histopathologic lesions are risk factors for the progression of IgAN. The aim of this study was to investigate the relationships between co-deposition of C1q, clinicopathological features, and renal outcomes in patients with IgAN. This retrospective cohort study included 221 patients with primary IgAN who underwent renal biopsy at the Kyung Hee University Medical Center from January 1996 to December 2008. Patients were divided in two groups: C1qpositive and C1q-negative. Using propensity scores to minimize confounding factors, we selected 36 matched C1q-negative patients from among the 203 unmatched C1q-negative patients and compared them with the 18 C1q-positive patients. We evaluated baseline characteristics and the severity of histologic lesions. We expressed the average rate of monthly renal function decline as the slope of eGFR (ΔGFR/M). 18 patients with IgAN showed mesangial deposition of C1q (8.1%). The C1q-positive patients had higher mean systolic blood pressure values and more impaired renal function than the unmatched C1q-negative patients. However, this association was not seen when the C1qpositive patients were compared with the matched C1q-negative patients. The slope of eGFR (ΔeGFR/M) declined steeply in the C1q-positive group. The incidence of severe cases of tubulointerstitial inflammation (TII) and fibrosis (TIF) was also greater in the C1q-positive group than the unmatched C1qnegative group, while only the incidence of severe TIF was significantly greater in the C1q-positive group than the matched C1qnegative group. Biopsies from C1q-positive patients showed more intense IgA staining as well as positive rates of IgG and IgM staining than those of unmatched C1q-negative patients. However, compared with the matched C1q-negative group, only the IgG positive rate was significantly higher in the C1q-positive patients. Multiple regression analysis of C1q-positive and matched C1q-negative patients revealed that C1q deposition was a critical determinant of a poorer renal prognosis. Mesangial C1q deposition in the glomerulus is associated with a poor renal outcome and severe pathologic features in patients with IgAN. The deposition of C1q in IgAN could therefore serve as an indicator of a poor renal prognosis.

KIM-1 expression predicts renal outcomes in IgA nephropathy

Kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubular injury. Recently, a few studies have shown that urinary KIM-1 has clinical implications in IgA nephropathy (IgAN). We performed this study to determine whether tissue KIM-1 has clinical implications for predicting long-term outcome and whether urinary KIM-1 is correlated with tissue KIM-1 and kidney injury in IgAN patients. We assessed the prognostic prediction capability of tissue KIM-1 expression in 69 adult patients with IgAN retrospectively. Renal biopsies from all patients were scored by a pathologist who was blinded to the clinical data for the pathologic variables. The primary outcome was the composite of a 50% reduction in eGFR or end-stage renal disease. Tissue KIM-1 expression was assessed semiquantitatively by counting the stained tubules per 100× power field; 0 tubule indicates grade 0; 1-5 tubules, grade 1; 6-10 tubules, grade 2; and more than 10 tubules, grade 3. Comparing urinary KIM-1 and tissue KIM-1 expression, 50 consecutive IgAN patients were prospectively enrolled to measure urinary KIM-1 levels and examine their biopsy specimens by KIM-1 immunohistochemistry. Univariate analysis showed that tissue KIM-1 expression was associated with the renal outcome in IgAN. Multivariate regression analysis, as the relationship of tissue KIM-1 with prognosis, was consistent. Proteinuria at biopsy and tissue KIM-1 grade 3 were shown to have a prognostic value. The concentration of urinary KIM-1/Cr in patients with IgAN was significantly higher than that in the normal controls. Tissue KIM-1 expression is an independent predictor of adverse renal outcomes in IgA nephropathy patients.

Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

OBJECTIVES:The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB.METHODS:We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB.RESULTS:The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course.CONCLUSION:An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.

Predictors of long term outcomes of IgA nephropathy

IgA Nephropathy (IgAN) was first described by Berger and Hinglais in 1968. The correlations between clinical as well as histopathological features on presentation and disease progression still remain unclear.

A histologic classification of IgA nephropathy for predicting long-term prognosis: emphasis on end-stage renal disease

A multicenter case-control study on IgA nephropathy (IgAN) was conducted to develop an evidence-based clinicopathologic classification of IgAN for predicting long-term renal outcome. Two hundred and eighty-seven patients including those with isolated hematuria or very mild proteinuria were enrolled. During a median follow-up of 9.3 years after biopsy, 49 patients (17%) progressed to end stage renal disease (ESRD). The associations between pathological variables and the need for chronic dialysis was examined by multivariate logistic regression analysis separately in patients who required dialysis earlier than 5 years (Early Progressors) and those who required dialysis within 5 to 10 years (Late Progressors) after biopsy. Independent pathological variables predicting progression to ESRD were global sclerosis, segmental sclerosis and fibrous crescents for Early Progressors, and global sclerosis and cellular/fibrocellular crescents for Late Progressors. Four histological grades, HG 1, HG 2, HG 3 and HG 4, were established corresponding to <25%, 25-49%, 50-74% and =75% of glomeruli exhibiting cellular or fibrocellular crescents, global sclerosis, segmental sclerosis or fibrous crescents. Eleven (7%) patients in HG 1, 12 (16%) in HG 2, 13 (31%) in HG 3 and 13 (68%) in HG 4 progressed to ESRD. Multivariate logistic analysis revealed that the risk of progression to ESRD was significantly higher in HG 2, 3 and 4 than in HG 1 (odds ratio, 2.4, 5.7 and 27.6 vs. 1.0). Our evidence-based histologic classification can identify the magnitude of the risk of progression to ESRD and is useful for predicting long-term renal outcome in IgAN.

Clinical Features and Outcomes of IgA Nephropathy with Nephrotic Syndrome

Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored. A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration. Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up. This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.

Globally sclerotic glomeruli in IgA nephropathy patients.

Implication for health policy/practice/research/medical education:Oxford classification system was based on actual clinical data, international collaboration, and validation of the reproducibility of defining pathologic lesions. The strongest pathologic predictor of clinical outcome in IgA nephropathy is the extent of tubular atrophy and interstitial fibrosis.

Histopathologic Features Aid in Predicting Risk for Progression of IgA Nephropathy

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Accurately identifying patients who are at risk for progressive disease is challenging. The extent to which histopathologic features improves prognostication is uncertain. We studied a retrospective cohort with biopsy-proven IgAN in Calgary, Canada. Renal biopsies were reviewed by a nephropathologist with histopathologic data abstracted using a standardized form. The primary outcome was the composite of doubling of serum creatinine, ESRD, or death. Spline models defined significant levels of interstitial fibrosis, glomerulosclerosis, hypertension, proteinuria, and creatinine. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models. Data from 146 cases were available for analysis with a median follow-up of 5.8 years. Greater than 25% interstitial fibrosis, >40% glomerular sclerosis, and a systolic BP >150 mmHg were risk thresholds. In univariable analyses, baseline creatinine, proteinuria, systolic BP, glomerular sclerosis, interstitial fibrosis, and crescentic disease were predictors of the primary outcome. In multivariable models adjusted for clinical characteristics, interstitial fibrosis (hazard ratio [HR]2.7; 95% confidence interval [CI] 1.2 to 6.0), glomerular sclerosis (HR 2.6; 95% CI 1.2 to 4.5), and crescents (HR 2.4; 95% CI 1.2 to 5.1) remained independent predictors of the primary outcome and significantly improved model fit compared with clinical characteristics alone. Baseline histopathologic parameters are independent predictors of adverse outcomes in IgAN even after taking into consideration clinical characteristics. Relatively small degrees of interstitial fibrosis confer an increased risk for progressive IgAN.

A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10-year prospective cohort study

Background. Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis, and a substantial number of patients succumb to end-stage renal disease (ESRD). However, prediction of the renal outcome in individual patients remains difficult. We have already published a scoring system using the data in a prospective cohort of IgAN patients followed up from 1995 to 2002.Methods. The cohort was further followed up until 2005 in 97 clinical units in Japan. The data from 2283 patients were analysed by Cox regression to determine the predictors of ESRD in IgAN, and their β-coefficients were converted into scores to estimate ESRD risk within 10 years.Results. During the follow-up (median, 87 months), 252 patients developed ESRD. Male sex, age less than 30 years, family histories of chronic renal failure and chronic glomerulonephritis, hypertension, proteinuria, mild haematuria, hypoalbuminaemia, low glomerular filtration rate and a high histological grade at initial renal biopsy were associated with the risk of ESRD in the multivariable analysis. A scoring system was framed to estimate the 10-year ESRD risk using eight variables significant in both univariable and multivariable models. This prognostic score accurately classified patients by risk: patients with estimates of 0–4.9, 5.0–19.9, 20.0–49.9 and 50.0–100% had an observed incidence of 1.7, 8.3, 36.7 and 85.5%, respectively. The corresponding area under the receiver-operating characteristic curve was 0.942 (95% confidence interval, 0.925–0.958).Conclusion. This validated scoring system to quantitatively estimate ESRD risk during the 10-year follow-up of IgAN patients will serve as a useful prognostic tool in clinical practice.

Validation of the Toronto Formula to Predict Progression in IgA Nephropathy

Background/Aim: Predicting outcome in IgA nephropathy (IgAN) is difficult. The Toronto formula uses average mean arterial blood pressure and proteinuria during the first 2 years of follow-up (MAP_0–2, UP_0–2) to predict the subsequent slope of estimated creatinine clearance (eCrCl). We aimed to validate the Toronto formula in a Scottish cohort and test the hypothesis that adding the slope eCrCl over the first 2 years of follow-up (eCrCl_0–2) would improve the predictive utility of a similar multivariate model. Methods: Adultsfrom our centre with biopsy-proven IgAN (n = 169) and at least 2 years of follow-up (median 129.4 months) were included. Clinical data were used to calculate MAP_0–2,UP_0–2,slope eCrCl_0–2and predicted slope eCrCl (using the Toronto formula). Results: There was a significant correlation between predicted slope eCrCl using the Toronto formula and actual slope eCrCl (R^{2 =} 0.21; p < 0.001). The formula predicted the actual rate of progression to within 4 ml/min/year in 75% of subjects, predicting patients with the most rapid deterioration with the greatest accuracy. The multivariate linear regression model created in our cohort using the same independent variables as the Toronto formula to predict the overall slope eCrCl had an R² of 0.22 (p < 0.001) and adding the slope CrCl_0–2 only increased this to 0.25. Conclusions: The Toronto formula is valid in a European population and useful for identifying patients at high risk of future deterioration in renal function. Adding slope eCrCl_0–2 to a predictive model containing MAP_0–2, andUP_0–2does not appear to improve prediction of the overall slope of eCrCl.

The effect of angiotensin type 1 receptor blockade on adhesion molecules in patients with IgA nephropathy.

Sir, Various studies have linked inflammation and endothelial dysfunction in patients with chronic renal disease [1]. Plasma levels of adhesion molecules [soluble intracellular adhesion molecule-1 (sICAM) and soluble vascular adhesion molecule-1 (sVCAM)] are markers of endothelial dysfunction and also risk factors for cardiovascular disease in patients with IgA nephropathy (IgAN) [2]. It is known that vascular lesion begins long before its clinical manifestation and its pathogenesis involves endothelial dysfunction and low-grade inflammation. Numerous studies provide evidence that ACE inhibitors or angiotensin II receptor antagonists (ARBs) are more effective than other antihypertensive drugs in slowing the progressive decline in glomerular filtration rate in IgAN [3]. Our aim was to test whether blocking the renin–angiotensin system (RAS) with irbesartan decreases levels of adhesion molecules in patients with biopsy-proven IgAN. We included in our study 36 patients (M/F 26/10, 51 ± 12.5 years). The inclusion criteria were biopsy-proven IgAN (defined by standard morphologic and immunohistochemical criteria), serum creatinine ≤1.5 mg/dl and urinary protein excretion ≥500 mg/day in at least three consecutive determinations during the previous 6-month period. Exclusion criteria were diabetes mellitus, coronary artery disease, peripheral vascular disease, stroke, acute infection or the inflammatory process on course and marked hypercholesterolaemia. Blood samples were collected from all patients before (T0) and after 16 weeks (T1) of treatment with 300 mg of irbesartan given once daily in the morning. A thorough blood chemistry control was performed in all patients. Creatinine clearance was determined by using venous blood for serum levels of creatinine and a 24-h urine collection. Serum and urinary creatinine concentration was measured using the Jaffe method. Serum intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were measured by immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 13.0 (SPSS, Chicago, IL, USA). Systolic (SBP) and diastolic blood pressure (DBP) was significantly lower after irbesartan was given (from SBP T0: 144 ± 19 mmHg DBP T0: 93 ± 9 mmHg to SBP T1: 129 ± 9 mmHg DBP T1: 88 ± 8 mmHg, P < 0.01). Proteinuria levels were also significantly lower after treatment: from 1.6 ± 0.7 g/24 h − T0 to 1.1 ± 0.9 g/24 h − T1 (P < 0.001). We observed a significant decrease of sICAM and sVCAM plasma levels in patients after treatment with irbesartan (sICAM T0: 628 ± 163 ng/ml to sICAM T1: 369 ± 112 ng/ml, P < 0.001; sVCAM T0: 1028 ± 649 ng/ml to sVCAM T1: 688 ± 248 ng/ml, P < 0.001) (Table ​(Table11). Table 1 Summary of before (T0) and (T1) the treatment in each parameter (BP, sICAM and sVCAM) Studies [2,4] have proven the important role of inflammation in the outcome of IgAN. Angiotensin type 1 (AT1) receptor antagonist significantly decreases proteinuria and slows renal deterioration in patients with IgAN. Our data suggest that treatment with irbesartan in patients with IgAN has a beneficial effect on inflammatory markers. The interfering with the inflammatory markers of AT1 antagonist could, at least partially, explain the effect of AT1 receptor blockade on renal survival in patients with IgAN. It is obvious that additional studies are needed to verify this hypothesis, especially in order to rule out the direct effect of lowering blood pressure on the inflammatory markers taken into consideration. Conflict of interest statement. None declared.

Predicting outcome of IgA nephropathy by use of urinary epidermal growth factor: monocyte chemotactic peptide 1 ratio

Predicting outcome of IgA nephropathy by use of urinary epidermal growth factor: monocyte chemotactic peptide 1 ratio

Presentation, prognosis and outcome of IgA nephropathy in Indian adults

IgA nephropathy (IgAN) is not well characterized in India. This retrospective study of 478 patients with IgAN was performed to clarify the presenting features, prognostic factors and the renal survival rates of the disease. Three hundred and forty-seven patients who had been followed on average for 27 months after diagnosis were divided into two groups based on renal function at diagnosis. In group 1 (229 patients), the creatinine clearance estimated by the Modification of Diet in Renal Disease formula was <85 mL/min and in group 2 (118 patients) it was >/=85 mL/min. The predominant modes of presentation were nephrotic syndrome, hypertension and renal failure. Twenty-nine percent of patients had more than a 20% decline in renal function at the last follow up. Multivariate analyses with stepwise logistic regression identified hypertension (odds ratio (OR) 3.5), nephrotic range proteinuria (OR 3.4) and sclerosed glomeruli on biopsy (OR 4.1) to be independently associated with progression in group 1 and hypertension (OR 2.3) in group 2. Seventeen percent of patients progressed to end-stage renal disease (ESRD). Using multivariate analysis by the Cox model, four risk factors for developing ESRD were identified: hypertension (hazard ratio (HR) 3.1); nephrotic proteinuria (HR 1.9); interstitial fibrosis (HR 2.5); and sclerosed glomeruli (HR 1.8). The renal survival rates at 1, 5 and 10 years were 84, 55 and 33%, respectively, with a median renal survival of 61 months from the time of biopsy. The relatively rapid rate of progression of IgAN in India is suggestive towards a 'malignant' nature of the disease in this country.

The chemokine receptor 5 Δ32 mutation is associated with increased renal survival in patients with IgA nephropathy

Chemokine receptor 5 (CCR5) plays an important role in the recruitment of monocytes and T cells in inflammation and experimental studies suggest that CCR5 might be involved in the pathogenesis of IgA nephropathy. A mutation in the CCR5 gene (CCR5 Delta32), leading to a nonfunctional receptor, was recently described. We therefore evaluated the potential role of this mutation on renal survival in patients with IgA nephropathy. The distribution of the CCR5 Delta32 genotype was determined by polymerase chain reaction (PCR) analysis in 228 patients with biopsy-proven IgA nephropathy. In 190 patients with available demographic and clinical follow-up data, the effect of the mutation on the clinical outcome was analyzed using the Log-rank test and the Cox proportional hazard model. In vitro, the influence of the CCR5 Delta32 genotype on the chemotactic response of monocytes was assessed. Of the 190 patients, 158 (83.2%) had a CCR5 wild-type genotype, 29 (15.3%) were heterozygous, and three patients had a homozygous CCR5 Delta32 genotype (1.6%). Renal survival was significantly longer in patients with the CCR5 Delta32 genotype than in the wild-type group (Log-rank P < 0.001). Using the multivariate Cox proportional hazard model, the CCR5 Delta32 genotype was identified as an independent factor associated with a lower risk to develop end-stage renal disease (ESRD) [hazard ratio (HR) 0.23, 95% CI 0.09 to 0.57, P= 0.002]. In vitro analysis of monocytes from CCR5 Delta32 carriers showed a reduced chemotactic response to CCR5 ligands in vitro. Our study demonstrates an independent role of the CCR5 Delta32 genotype for the clinical outcome in IgA nephropathy. In vitro experiments revealed a reduced chemotactic response of monocytes from CCR5 Delta32 carriers, thus pointing out a possible pathophysiologic explanation for the beneficial effect of the CCR5 Delta32 genotype.

Cohort Study of Advanced IgA Nephropathy: Efficacy and Limitations of Corticosteroids with Tonsillectomy

Background: Elevated serum creatinine is associated with poor outcome in IgA nephropathy (IgAN). The efficacy and limitations of corticosteroids in advanced IgAN (Cr ≧1.5 mg/dl), however, remains controversial. Methods: We retrospectively investigated 70 patients with advanced IgAN (Cr ≧1.5 mg/dl) classified into three groups according to their treatment regimens, that is, steroid pulse with tonsillectomy, conventional steroid, and supportive therapy. We evaluated the three groups to elucidate predictors for the endpoints ESRF and doubled serum creatinine from baseline. Results: Steroid pulse with tonsillectomy, conventional steroid and supportive therapy were performed in 30, 25 and 15 patients, respectively. During the mean follow-up period of 70.3 (12–137) months, 41.4% of patients reached ESRF (13.3 vs. 56.0 vs. 73.3%, p < 0.001) and 45.7% doubled serum creatinine from baseline (16.7 vs. 64.0 vs. 73.3%, p < 0.001). The incidence of ESRF in the patients treated by steroid pulse with tonsillectomy was significantly lower than the incidences in the patients treated by conventional steroid and supportive therapy at a baseline creatinine level of 1.5–2 mg/dl, but no statistical difference was observed at a level of >2 mg/dl. The Kaplan-Meier estimated probability of renal survival without ESRF was 89.2, 74.1 and 72.2% at 5 years and 82.8, 51.0 and 45.1% at 8 years, respectively (p = 0.017). The predictors for ESRF, identified in a Cox proportional hazards model, were baseline serum creatinine (p < 0.001) and interstitial infiltrate (p = 0.003). Steroid pulse with tonsillectomy also had a protective effect on the risk of reaching ESRF (p = 0.013). By target cross-stratification, the patients with baseline creatinine of 1.5–2 mg/dl who underwent steroid pulse with tonsillectomy showed a better renal survival rate than the others (p < 0.001). Conclusion: Steroid pulse therapy combined with tonsillectomy may be more effective than conventional steroid therapy in patients with a baseline creatinine level of ≤2 mg/dl.

Is tumor necrosis factor genotype (TNFA2/TNFA2)a genetic prognostic factor of an unfavorable outcome in IgA nephropathy?

The purpose of this study was to examine whether there are the associations between TNF alpha and TNF beta gene polymorphisms and the development and progression of Ig A nephropathy (IgAN). A cross-sectional study on TNF alpha and TNF betagene polymorphisms by polymerase chain reaction with restriction fragment length poly-morphisms was performed on 76 patients with primary IgAN confirmed by renal biopsy and 100 healthy controls. The allele with G-->A substitution was designated as TNFA2 for the TNF alpha gene and TNFB2 for the TNF betagene. A patient in whom dialysis treatment was started or whose serum creatinine became double or over during the follow-up duration was designated as a "progressor". The TNFA2/ TNFA2 genotype was more prevalent in the progressor than in the non-pregressor group (20.0 vs 3.3%, p<0.05). Clinical factors such as serum creatinine, systolic and diastolic blood pressure (p<0.001, respectively) were higher and pathologic factor such as Grade IV or V renal lesions was more prevalent (p<0.01) in the progressor than in the non-progressor group. Therefore, TNFA2/TNFA2 genotype may be a risk factor for the progression of IgAN.

Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy.

The prognosis of IgA nephropathy (IgAN) is variable and about 10-20% of patients progress to end-stage renal disease (ESRD) in 10 years. Hypertension, proteinuria and renal insufficiency at the time of diagnosis are risk factors associated with poor prognosis. Lipid abnormalities may have a role in the progression of glomerulonephritides, and glomerulosclerosis and atherosclerosis may have similar pathophysiological mechanisms. We therefore evaluated factors associated with cardiovascular diseases, especially hypercholesterolaemia, hypertriglyceridaemia, and hyperuricaemia, as predictors of the progression of IgAN. A total of 223 patients with IgAN (141 men, 82 women; median age 41 years, range 8-78 years) were studied. The following parameters were recorded at the time of renal biopsy: presence of hypertension or diabetes, smoking habits, body mass index (BMI), serum creatinine, total and HDL-cholesterol, triglycerides, and urate and 24-h urinary protein excretion. The patients were followed up for 0.2-17 years (median 10 years) with respect to progression of renal disease defined as elevation of serum creatinine above 125 micromol/l in men or 105 micromol/l in women, and over 20% elevation from baseline. Forty-one patients (18%) showed progression. Hypertriglyceridaemia and hyperuricaemia were significantly more common at the time of renal biopsy in patients with progressive than in those with stable disease. In patients with normal renal function at the time of diagnosis initial hypertriglyceridaemia, hyperuricaemia, hypertension and proteinuria were independent risk factors for progression of IgAN in the Cox regression hazard model. Our results show that hypertriglyceridaemia and hyperuricaemia at the time of diagnosis are important, previously underestimated predictors of poor outcome in IgAN, although causality between these factors and progression cannot be inferred from the present study.

IgA nephropathy with myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO ANCA): a discrepancy between the histological activity and MPO ANCA

Anti-neutrophil cytoplasmic antibodies (ANCA) of the immunoglobulin (Ig)G type are associated with rapidly progressive glomerulonephritis. Such antibodies have been detected only rarely in patients with Henoch-Schonlein purpura (HSP) or IgA nephropathy (IgAN). We report a patient with biopsy-proven IgAN with fibrous crescents in whom high titers of IgG ANCA occurred and were confirmed to be anti-myeloperoxidase antibodies (MPO ANCA) by solid-phase enzyme-linked immunosorbent assay (ELISA) and inhibition studies. During a 1-year follow-up period, high titers of MPO ANCA persisted but creatinine clearance remained over 50 ml/min per 1.48 m.2 This case suggests the lack of a reliable association between fulminant outcome of IgAN with crescents and high titers of IgG MPO ANCA, and indicates the involvement of subsets of IgG MPO ANCA which recognize important or unimportant epitopes of MPO in the pathogenesis.

Do proteinuria and hypertension at biopsy influence long‐term outcome of IgA nephropathy?

Do proteinuria and hypertension at biopsy influence long‐term outcome of IgA nephropathy?