Adult IgA Nephropathy Research Articles

Different pathological roles of toll-like receptor 9 on mucosal B cells and dendritic cells in murine IgA nephropathy.

Although pathogenesis of IgA nephropathy (IgAN) is still obscure, pathological contribution of mucosal immunity including production of nephritogenic IgA and IgA immune complex (IC) has been discussed. We have reported that mucosal toll-like receptor (TLR)-9 is involved in the pathogenesis of human and murine IgAN. However, cell-type expressing TLR9 in mucosa remains unclear. To address this, we nasally challenged cell-specific CpG DNA ((i): dendritic cell: (DC), (ii): B cell, (iii): both), known as ligand for TLR9, to IgAN prone mice and analyzed disease phenotype of each group. After 8 times of the weekly administration, every group showed deterioration of glomerular damage. However, CpG-A-group showed clear extension of mesangial proliferative lesions with increase of serum IgA-IgG2a IC and its glomerular depositions, while CpG-B-group showed extent of glomerular sclerotic lesions with increase of serum and glomerular IgA and M2 macrophage infiltration. Present results indicate that mucosal TLR9 on B cells and DC may differently contribute to the progression of this disease via induction of nephritogenic IgA or IgA-IgG IC, respectively. This picture is suggestive for the pathological difference between child and adult IgAN.

Hypertension, Chronic Kidney Disease, and Renal Pathology in a Child with Hermansky-Pudlak Syndrome

We report a child with Hermansky-Pudlak Syndrome (HPS) and chronic kidney disease (stage II) with histological diagnosis of focal segmental glomerulosclerosis (FSGS). A 15-year-old male of Puerto Rico ancestry with history of HPS, hypertension (HTN), asthma, obesity, and chronic kidney disease (CKD) stage II presented with new-onset proteinuria without edema. His blood pressure had been controlled, serum creatinine had been 0.9–1.4 mg/dL, and first morning urine protein/creatinine ratio (UPC) ranged from 0.2 to 0.38. Due to persistent nonorthostatic proteinuria with CKD, renal biopsy was performed and FSGS (not otherwise specified) with chronic diffuse tubulopathy (tubular cytoplasmic droplets) and acute tubular injury was reported. Ceroid-like material is known to infiltrate tissues (i.e., lungs, colon, and kidney) in HPS, but the reason for the renal insufficiency is unknown. Nonspecific kidney disease and in one adult case IgA nephropathy with ANCA-positive glomerulonephritis have previously been reported in patients with Hermansky-Pudlak syndrome. To our knowledge, we report the first pediatric renal pathology case of HPS associated with CKD. This paper discusses presentation and management of renal disease in HPS.

Efficacy and safety of lisinopril for mild childhood IgA nephropathy: a pilot study

Even in children with mild immunoglobulin (Ig)A nephropathy (IgA-N) showing minimal/focal mesangial proliferation, persistent proteinuria seems to be a risk factor for progression of the disease, indicating the need for an effective and safe treatment even in such cases. Studies carried out to date have indicated that angiotensin-converting enzyme inhibitors (ACEIs) reduce urinary protein excretion and preserve renal function in adult IgA-N. However, no prospective study of ACEI only for childhood IgA-N has yet been carried out. In this prospective single-arm pilot trial, we administered lisinopril (0.4 mg/kg per day) as therapeutic treatment to 40 children with mild IgA-N with proteinuria [morning urinary protein/creatinine ratio (uP/Cr) >or= 0.2 g/g]. Thirty-three patients reached the primary endpoint (uP/Cr < 0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method was 80.9%. Mean uP excretion was reduced from 0.40 to 0.18 g/m(2)/day (p < 0.0001). Of the 40 patients treated, five (12.5%) showed dizziness, and four of these five needed the lisinopril dose reduced. However, lisinopril therapy was continued in all patients during the 2-year treatment period. No other side effect, such as cough, was observed. We conclude that the efficacy and safety of lisinopril is seemingly acceptable for the treatment of children with mild IgA-N.

IgA Nephropathy in children and adults: comparison of histologic features and clinical outcomes

While some studies have reported that IgA nephropathy has a relatively benign clinical course in children, others have shown that renal outcomes of paediatric patients with IgA nephropathy followed into adulthood are similar to those of patients diagnosed as adults. Some of this variability may be related to differences in histologic severity of cohorts of patients diagnosed as children versus adults. We retrospectively examined correlations between renal biopsy findings, clinical features at presentation and renal survival in 99 children and adolescents (<or=17 years old) with IgA nephropathy and compared these findings to those of 125 adults with IgA nephropathy. Compared with adults, paediatric patients were more likely to have minimal histologic lesions (24% versus 14%) and less likely to have advanced chronic lesions (3% versus 17%). Similar fractions of paediatric and adult patients showed focal and diffuse glomerulonephritis (GN), respectively. Among these latter two groups, renal survival was significantly better in patients diagnosed as children than as adults by univariate and multivariate analyses. By multivariate analysis, other significant, independent predictors of renal survival were estimated percent interstitial fibrosis and histologic grade (diffuse versus focal GN). In patients with proliferative IgA nephropathy, the clinical course is more likely to be benign when the disease is diagnosed in childhood versus adulthood. This difference can be accounted for only in part by more advanced disease at the time of biopsy in adults.

Histological differences in new-onset IgA nephropathy between children and adults

It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.

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.

Applicability of steroid therapy in 275 adult patients with IgA nephropathy determined using a histological scoring system and degree of proteinuria.

The purpose of this study was to propose clinical and pathologic criteria for the indication for steroid therapy (ST) in adult IgA nephropathy (IgAN). We analyzed 275 adult IgAN patients retrospectively, using a histological scoring system. The histological score was expressed by evaluating, semiquantitatively, the extent of glomerular and tubulointerstitial lesions in terms of the activity index (AI) and chronicity index (CI). To determine the applicability of ST, three groups were categorized by evaluating the statistical significance of the correlation between the AI and CI, together with the daily amount of urinary protein (UP) and the outcome. In group A, which had a CI > or = 5 alone, 33 out of 43 patients showed a decline in renal function. There was no statistically significant difference between the subgroup with ST and that without ST. In group B, which had CI < 5, AI < 5, and UP < 1.0 g/day, 169 out of 174 patients had normal renal function irrespective of whether or not they received ST. Thus, ST had no beneficial effects in group A and B patients. In group C, which had CI < 5 and AI > or = 5 or UP > or = 1.0 g/day, patients with ST had a significantly higher incidence of an outcome with normal renal function (22 out of 24 patients) than that in patients without ST (19 out of 34 patients) (P < 0.01). Thus, ST had beneficial effects in group C patients. . We propose that a histological criterion be used in combination with the degree of proteinuria as an indication for ST in adult IgAN patients.

A-20C angiotensinogen gene polymorphism and proteinuria in childhood IgA nephropathy.

We have previously reported that the TT genotype of the angiotensinogen gene and the ID/DD genotype of the angiotensin-converting enzyme gene are associated with increased severity of proteinuria in IgA nephropathy in Japanese children. Recently it was reported that polymorphism at -20 from adenine to cytosine in the angiotensinogen gene, increasing the level of this transcript, was associated with the progression of renal dysfunction in adult IgA nephropathy. We therefore investigated whether this polymorphism is involved in IgA nephropathy in Japanese children. We identified this polymorphism in 105 children with IgA nephropathy and 119 healthy adults using polymerase chain reaction/restriction fragment length polymorphism analysis. At the time of biopsy, all patients had normal blood pressure and renal function. There were no differences in the genotypes and allele frequencies of this polymorphism between patients with IgA nephropathy and controls. The number of patients with the AC/CC genotype showing heavy proteinuria (>or=1.0 g/day per m(2) body surface area) at biopsy was significantly higher than that with the AA genotype ( P=0.039, chi-squared test). The AC/CC genotype of this polymorphism may be associated with an increased severity of proteinuria, suggesting that this polymorphism may play a significant role in the progression of IgA nephropathy in Japanese children.

Histological lesions as predictors for the effectiveness of steroid therapy in adult IgA nephropathy: Uni‐ and multivariate analysis

Histological lesions as predictors for the effectiveness of steroid therapy in adult IgA nephropathy: Uni‐ and multivariate analysis

The effect of continuance of proteinuria on the decline of renal function in adult IgA nephropathy: A middle‐term study on 625 patients

NephrologyVolume 7, Issue s4 p. A104-A107 The effect of continuance of proteinuria on the decline of renal function in adult IgA nephropathy: A middle-term study on 625 patients M HAGIWARA, M HAGIWARA Sakura National Hospital, Chiba, JapanSearch for more papers by this authorS SUZUKI, S SUZUKI Sakura National Hospital, Chiba, JapanSearch for more papers by this authorK JOH, K JOH Sakura National Hospital, Chiba, JapanSearch for more papers by this author M HAGIWARA, M HAGIWARA Sakura National Hospital, Chiba, JapanSearch for more papers by this authorS SUZUKI, S SUZUKI Sakura National Hospital, Chiba, JapanSearch for more papers by this authorK JOH, K JOH Sakura National Hospital, Chiba, JapanSearch for more papers by this author First published: 22 October 2002 https://doi.org/10.1046/j.1440-1797.7.s.33.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume7, Issues4October 2002Pages A104-A107 RelatedInformation

The effect of continuance of proteinuria on the decline of renal function in adult IgA nephropathy: A middle‐term study on 625 patients

NephrologyVolume 7, Issue s3 p. A104-A104 The effect of continuance of proteinuria on the decline of renal function in adult IgA nephropathy: A middle-term study on 625 patients M HAGIWARA, M HAGIWARA Sakura National Hospital, Chiba, JapanSearch for more papers by this authorS SUZUKI, S SUZUKI Sakura National Hospital, Chiba, JapanSearch for more papers by this authorK JOH, K JOH Sakura National Hospital, Chiba, JapanSearch for more papers by this author M HAGIWARA, M HAGIWARA Sakura National Hospital, Chiba, JapanSearch for more papers by this authorS SUZUKI, S SUZUKI Sakura National Hospital, Chiba, JapanSearch for more papers by this authorK JOH, K JOH Sakura National Hospital, Chiba, JapanSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1440-1797.2002.tb00543.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume7, Issues3June 2002Pages A104-A104 RelatedInformation

Evaluation on the effect of steroid therapy for the outcome of IgA nephropathy in adults on the basis of histological scoring: A clinicopathologic study of 104 cases

Application criteria of steroid therapy for the patients of IgA nephropathy (IgAN) have not yet been established. The purpose of the present study was to establish retrospectively the clinical and pathological criteria for the steroid therapy by using a histological scoring on 104 adult patients of IgAN. Steroid therapy was designated as an administration of prednisolone in the amount of more than 30 mg per day in the period of more than 4 weeks within 1 year of kidney biopsy.We developed our own scoring system for the following main glomerular and tubulointerstitial changes as shown in Table 1. The histological scoring was expressed by evaluating semiquantitatively the extent of glomerular and tubulointerstitial lesions in terms of activity index (AI) and chronicity index (CI). Activity index is the sum of graded score according to the extent of glomeruli with mesangial hypercellularity, intracapillary macrophagic infiltration and cellular crescent as well as to the extent of interstitial inflammation and tubulitis. Chronicity index is the sum of graded score according to the extent of glomeruli with global sclerosis, increase of extracellular matrices or periglomerular fibrosis, and tuft adhesion or fibrous (or fibrocellular) crescent as well as to the extent of interstitial fibrosis (Table 1). Histological scoring Score 0 1 2 3 AI: Activity Index G: glomerular m: mesangial hypercellularity − &lt; 40% &lt; 80% ≥ 80% i: intracapillary macrophage infiltration − + ++ e: cellular crescent 0 &lt; 30% ≥ 30% I: tubulointerstitial i: interstitial inflammation − + ++ t: tubulitis − + ++ CI: Chronicity Index G: glomerular s: global sclerosis &lt; 10% &lt; 30% &lt; 50% ≥ 50% i: increase of extracellular matrix &lt; 10% &lt; 30% &lt; 50% ≥ 50% e: fibrous (or fibrocellular) crescent, adhesion &lt; 10% &lt; 30% &lt; 50% ≥ 50% I: tubulointerstitial interstitial fibrosis &lt; 10% &lt; 30% &lt; 50% ≥ 50% AI: AGm + AGi + AGe*2 + AIi + Ait, CI: CGS + CGi + CGe + CI For the applicability of steroid therapy, three groups were categorized by evaluating the statistical significance for the correlation of AI, CI and daily amount of urine protein to the outcome of the patients as follows (Table 2). In group A (inappropriate indication of steroid therapy) which showed CI ≥ 5 alone, 10 out of 11 cases revealed decline of renal function (Cr ≥ 1.2 mg/dL and Ccr &lt; 80 mL/min) within 2.2–19.3 years (mean 9.0 ± 6.4 years) without respect to steroid therapy. In group B (unnecessary indication of steroid therapy) which showed CI &lt; 5, AI &lt; 5, and UP &lt; 1 g/day, 58 out of 60 cases showed normal renal function (Cr &lt; 1.2 mg/dL and Ccr ≥ 80 mL/min) within 4.2–21.6 years (mean 10.1 ± 4.7 years). In group C (necessary indication of steroid therapy) which showed CI &lt; 5 and AI ≥ 5 or UP ≥ 1 g/day, patients with steroid therapy revealed significantly higher incidence of outcome with normal renal function (12 out of 13 patients, final evaluation of renal function in 6.8 ± 2.3 years after renal biopsy) than that of the patient without steroid therapy (seven out of 20 cases, evaluation of renal function in 9.2 ± 4.0 years after renal biopsy) (P &lt; 0.01) (Table 3). In the 13 patients with steroid therapy in group C (steroid pulse in four patients, prednisolone 40 mg/day internally in three patients, predonisolone 30 mg/day internally in six patients) showed a significant decrease of proteinuria and remained until final evaluation time (Table 4). Application criteria of steroid therapy image Comparison of steroid (−) with steroid (+) in the group of ‘necessary’ steroid therapy + − P no. 13 20 At Renal Biopsy age (years) 31.5 ± 12.9 36.3 ± 13.0 ns UP (g/day) 2.3 ± 1.9 1.3 ± 0.5 &lt; 0.05 Cr (mg/dL) 0.8 ± 0.3 0.9 ± 0.1 ns CCr (mL/min) 111 ± 43 92 ± 34 ns Hypertension (n) 1 9 ns + ACEI (n) 4 10 ns Follow‐up years from renal biopsy 6.8 ± 2.3 9.2 ± 4.0 ns End of follow‐up Cr (mg/dL) 0.8 ± 0.3 5.5 ± 6.6 &lt; 0.01 Normal renal function (n) 12 7 Renal insufficiency (n) 1 6 &lt; 0.01 Dialysis (n) 0 7 Change of urine protein in the 13 cases with steroid treatment in the group of 'necessary' image From the results above, our evaluation system using histological scoring together with grading proteinuria was proven to be useful in estimating the applicability of steroid therapy for adult IgAN patients.

Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features.

The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild proteinuria or mild histological alternations. A population of 735 IgAN patients whom we were able to observe for more than two years was examined. A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild proteinuria included 197 patients (26.8%). Forty-seven patients of this group showed minor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild proteinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (11.2%). Forty-seven patients of this group showed mild proteinuria, of whom 12 patients showed moderate proteinuria. However, three patients with minor glomerular abnormalities who were not on dialysis showed loss of renal function. These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed.

ROLE OF PROTEINURIA REDUCTION IN THE PROGRESSION OF IgA NEPHROPATHY

Proteinuria has been shown to play a causal role in the progression towards ESRD of IgA nephropathy (IgAN). We demonstrated that steroids are effective in reducing proteinuria and preserving renal function. Aim: to evaluate the long-term effect of steroids in IgAN patients (6th year evaluation) and better clarify the role of proteinuria reduction in slowing down the progression. Methods: multicenter randomized controlled trial of 86 adult IgAN patients with serum creatinine ≤1.5 mg/dL and moderate proteinuria. They received either supportive therapy or methylprednisolone 1-gi.v. for three days at months 1, 3, and 5, plus oral prednisone (0.5 mg/kg every other day for six months). Results: Proteinuria significantly decreased in the treated patients (from 2.0 ± 0.60 g/24 h at baseline to 1.0 ± 0.68 g/24 h at six months) and remained stable till the 6th year (0.67 ± 0.5 g/24 h); it slightly decreased in the control group. Six-year renal survival was significantly better in the steroid than in the control group: 9 patient (20.9%) in the steroid group and 15 (34.8%) in the control group reached the primary end point of a 50% increase in serum creatinine from baseline. Five controls and none of the steroid-treated patients started dialysis. Steroid-treated patients did not experience any major side effects during follow- up. Conclusions: Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN patients. Early reduction of proteinuria could also be marker of a persistent reduction in its levels over time and of a better outcome in the long term.

Urinary transforming growth factor‐β1 is an indicator of histological chronicity in IgA nephropathy

SUMMARY: This study examined urinary excretion of transforming growth factor‐β1 (TGF‐β1) in adult IgA nephropathy and compared this with clinical and histological parameters. TGF‐β1 was measured by enzyme‐linked immunosorbent assay in 24‐h urine specimens from 25 patients with IgA nephropathy (17 men, eight women). Urine from eight age‐matched control subjects served as the control. Serum TGF‐β1 was also measured in 16 out of the 25 patients and six age‐matched control subjects. TGF‐β1 was detected in the urine in 72% of IgA nephropathy patients(18/25), but was not detected in any of the control subjects. Patients with decreased renal function (creatinine clearance (Ccr) &lt; 80 mL/min) had higher urine levels of TGF‐β1 than those with normal renal function (Ccr ≥ 80 mL/min) (141.8 ± 60.0 ng/day vs 39.7 ± 33.2 ng/day, P &lt; 0.01). The level of TGF‐β1 gave a negative correlation with Ccr (r = −0.62, P = 0.001), but not with proteinuria (r = 0.11, P = 0.58). Twenty‐two of the patients were evaluated histologically. The urinary TGF‐β1 levels correlated with both global sclerosis and interstitial volume (r = 0.52, P &lt; 0.05, and r = 0.51, P &lt; 0.05, respectively). However, there was no correlation between TGF‐β1 levels and glomerular intracapillary inflammatory cell score, mesangial proliferation score or the matrix score. No correlation was found between TGF‐β1 levels and the number of glomerular or interstitial CD68+ cells. No significant differences in serum TGF‐β1 levels were observed between patients with normal Ccr and those with decreased Ccr. Also, its levels were found to be independent of the urine levels. In conclusion, 24‐h urinary TGF‐β1 excretion was found to correlate with Ccr, global sclerosis and interstitial volume, demonstrating that urinary TGF‐β1 is an indicator of chronicity in adult IgA nephropathy.

IgA nephropathy: recent developments.

IgA nephropathy (IgAN), a mesangial proliferative glomerulonephritis (GN), is the most common GN in all parts of the world where renal biopsy is widely practiced. It is unique among glomerular diseases in being defined by immunohistochemical findings, i.e., mesangial deposition of IgA, rather than by light microscopy. Because the clinical features of IgAN were discussed in 1997 (1), we focus on recent developments in IgAN. Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic vasculitis in which the glomerular disease may be indistinguishable from IgAN. IgAN seems to be a kidney-restricted form of HSP. HSP is not discussed in detail here; the reader is referred to the recent review by Rai and colleagues (2). Clinical Presentation In the great majority of cases, IgAN is an isolated renal disease with no apparent clinical antecedent or association— primary IgAN. As well as the association with IgA-mediated systemic vasculitis in HSP, there are a number of other clinical contexts that seem to predispose to IgAN, usually called secondary IgAN. Among the best characterized associations are those with rheumatoid arthritis, ankylosing spondylitis, and Reiter’s syndrome; celiac disease and dermatitis herpetiformis; chronic liver disease (especially alcohol induced); and viral diseases, particularly HIV infection and hepatitis B (in endemic areas). However, caution should be exercised in interpreting some other associations as causal. There are many anecdotal reports of single cases that may reflect merely chance associations with a disease as common as IgAN. Approximately 40 to 50% of patients present with recurrent macroscopic hematuria, which usually coincides with mucosal infection or exercise. This feature is virtually never seen after the age of 40 yr. Asymptomatic hematuria with or without proteinuria is the presentation in 30 to 50% of most series. There is an “iceberg” effect in the apparent prevalence of this presentation—the extent to which only the tip of the iceberg is identified as having IgAN being decided by local attitudes toward urine testing and renal biopsy. Nephrotic syndrome is unusual, being the presentation in only 5% of all IgAN. Uncommon but well described is the coincidence of IgAN and minimal change disease in both adults and children. Acute renal insufficiency is uncommon in IgAN, occurring in only 5% of cases. It is described in association with macroscopic hematuria, although this is an infrequent clinical problem even when hematuria is heavy. Alternatively, it may be due to crescentic IgAN. To distinguish between these two clinical settings, renal biopsy is mandatory in acute renal insufficiency unless recovery of renal function is rapid. By analogy with pauci-immune crescentic nephritis, a number of investigators have sought evidence of IgA-antineutrophil cytoplasmic antibodies (ANCA) in both IgAN, particularly crescentic IgAN, and HSP. Although there are a number of cases in which IgA-ANCA seems to be associated with active disease, overall findings are inconsistent. This may in part reflect methodologic differences. However, on occasion, patients with IgAN or HSP have circulating IgG-ANCA, and in some the diagnostic criteria for microscopic polyangiitis or Wegener’s granulomatosis are met. These patients respond to immunosuppressive therapy (3). A few patients with linear capillary wall IgA deposition have also been described, presumably an IgA-mediated variant of Goodpasture syndrome (4). Approximately 10 to 20% of patients with IgAN present with established chronic renal insufficiency. It is usually assumed that these patients have long-standing disease that differs from the classic presentations only because the patient did not come early to medical attention.

Clinicopathological study of IgA nephropathy in adults: The influence of onset age on clinical and renal histological findings and on the effect of steroid therapy

Background. The prognosis of IgA nephropathy (IgAN) varies according to the patient's age. It usually affects children or young adults. However, the onset age for IgAN may be at middle-age or older. The influence of onset age on the clinical and renal histological findings of adult IgAN was investigated. Methods. We selected 39 IgAN patients in whom renal biopsy was performed within 2 years from the onset. The patients were divided into two groups according to onset age; early-onset group (under 35 years; group E) and late-onset group (over 35 years; group L). The clinical and histological findings and the response to steroid therapy were compared in the two groups. Results. (1) Clinically, the levels of proteinuria and hematuria in groups E and L were not different, but the creatinine clearance was lower in group L than in group E. Hypertension was frequent in group L (66.7%), but not in group E. (2) Histologically, the rate of glomerular obsolescence and the grades of interstitial fibrosis and arterio- and arteriolosclerosis were more advanced in group L than in group E. However, there were no differences in the grade of mesangial cell proliferation or mesangial matrix increase, nor were the rates of glomerular crescent and tuft adhesion formation different between the two groups. (3) The reduction of proteinuria and hematuria after 1-year steroid therapy was similar in the two groups. Conclusion. Onset age does not affect the severity of glomerular lesions and the effect of steroid therapy in the early phase of adult IgAN. However, advanced interstitial fibrosis and arterio- and arteriolosclerosis, which may be related to hypertension or the aging process, lead to impaired renal function in late-onset IgAN patients.

IgA Nephropathy in Adults

IgA Nephropathy in Adults

Clinicopathological correlations, predictive indicators and treatments of adult IgA nephropathy

NephrologyVolume 4, Issue s1 p. A39-A39 Clinicopathological correlations, predictive indicators and treatments of adult IgA nephropathy J MERA, J MERA Department of Medicine, Teikyo University School of Medicine, Tokyo, JapanSearch for more papers by this authorS UCHIDA, S UCHIDA Department of Medicine, Teikyo University School of Medicine, Tokyo, JapanSearch for more papers by this authorM NAGASE, M NAGASE Department of Medicine, Teikyo University School of Medicine, Tokyo, JapanSearch for more papers by this author J MERA, J MERA Department of Medicine, Teikyo University School of Medicine, Tokyo, JapanSearch for more papers by this authorS UCHIDA, S UCHIDA Department of Medicine, Teikyo University School of Medicine, Tokyo, JapanSearch for more papers by this authorM NAGASE, M NAGASE Department of Medicine, Teikyo University School of Medicine, Tokyo, JapanSearch for more papers by this author First published: 28 March 2007 https://doi.org/10.1111/j.1440-1797.1998.tb00450.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume4, Issues1June 1998Pages A39-A39 RelatedInformation

A clinicopathological study of adult Japanese IgA nephropathy patients: Early stage cases and cases with exacerbation

Summary: Most cases of adult type IgA nephropathy (IgAN) have an insidious onset and asymptomatic course. However, some patients reveal recurrent macroscopic haematuria following episodes of respiratory or urinary tract infections. In order to clarify the correlation between clinical features and histological alterations or prognosis, 42 cases of early stage IgAN and 40 cases with acute exacerbation episodes were investigated and compared with a control group. Early stage cases were defined as having had a renal biopsy within 1 year after the first detection of urinary abnormalities, and had normal urinary findings within the 12 months before the first detection of urinary abnormalities. Acute exacerbation cases were defined as macroscopic haematuria or worsening of urinary abnormalities after acute infectious episodes and undergoing a renal biopsy within 120 days after the onset of these episodes. the early stage cases had better renal function and lower systolic and diastolic blood pressure than that of control group. They also showed milder changes in mesangial cell proliferation, mesangial matrix increase, totally sclerotic glomeruli, and tubulo‐interstitial changes. However, it is important to note that glomerular and interstitial sclerotic changes were observed even in early stage cases. Endothelial detachment was noticed more frequently in the early stage cases. Acute exacerbation cases revealed lesions of endocapillary proliferation, mesangiolysis and endothelial detachment more frequently, although these changes were segmental in each glomerulus. There was no statistical difference in disease prognosis between cases with and without acute exacerbation. These data indicated that there are characteristic histological changes in early stage cases and acute exacerbation cases of IgAN.