Diagnosis Of IgA Nephropathy Research Articles

A complement to kidney disease: CFHR5 nephropathy

Isolated microscopic haematuria of glomerular origin in the context of normal renal function without proteinuria has traditionally been managed conservatively.1 Among the conditions that are included in this rubric, IgA nephropathy and thin-basement-membrane disease account for most cases. Although the precise worldwide prevalence of these two disorders is unknown, one is frequently the culprit in this setting. The clinical diagnosis of IgA nephropathy—the most common glomerulonephritis worldwide—is strongly supported when microscopic haematuria is accompanied by macroscopic haematuria after an upper respiratory tract infection.

Identification of a uromodulin fragment for diagnosis of IgA nephropathy

IgA nephropathy (IgAN) is one of the most common types of glomerulonephritis worldwide and is diagnosed only with a renal biopsy. The purpose of the present studies was to identify the potential biomarkers for the non-invasive diagnosis of IgAN. The combination of a magnetic bead separation system with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to analyze urinary peptides of IgAN patients, other glomerulopathy patients, and healthy controls. ClinProTools v.2.0 software was also applied to establish a diagnostic model for IgAN. Our results demonstrated that 11 features had optimal discriminatory performance (p <0.00001). Among these features, the peptide with m/z 1913.14 was identified as a fragment of uromodulin. Receiver operating characteristic (ROC) analysis for m/z 1913.14 showed that the area under the curve (AUC) was 0.998 for distinguishing IgAN versus healthy controls, and 0.815 for distinguishing IgAN versus other glomerulopathy. Analysis of urine peptides patterns by the magnetic bead separation system and MALDI-TOF-MS was a non-invasive diagnostic tool. We conclude that the urinary peptide with m/z 1913.14, which was identified as a uromodulin fragment, may be used as a biomarker for the non-invasive diagnosis of IgAN clinically.

A Library of Mutated Maackia amurensis Hemagglutinin Distinguishes Putative Glycoforms of Immunoglobulin A1 from IgA Nephropathy Patients

Ten genetically modified Maackia amurensis hemagglutinin (MAH) clones at the carbohydrate-recognition loop were found to bind glycophorin A and a mucin mimetic with NeuAcalpha2-3Galbeta1-3GalNAcalpha (monosialyl-T antigen) in different relative intensity. Binding profiles of these lectins to human serum IgA1 from healthy individuals and from IgA nephropathy patients were subjected to the cluster analysis. Two large groups, one with only healthy individuals and another with all IgA nephropathy patients, were generated. The results strongly suggest that the library of genetically modified MAH is a useful tool for serum diagnosis of IgA nephropathy.

Episcleritis: An association with IgA nephropathy

To report an unusual case of recurrent episcleritis secondary to IgA nephropathy. Observational case report. A 39-year-old man was seen with recurrent episodes of red and painful left eye suggestive of episcleritis. On routine investigations the patient was found to have haematuria and proteinuria. Further investigations led to the diagnosis of IgA nephropathy on kidney biopsy. IgA nephropathy may present with various eye signs without any other systemic clues. This case highlights the importance of some of the basic tests in clinical practice such as urine examination. This can be conveniently done with testing strip and should be considered in the routine investigation of patients with inflammatory eye diseases.

Role of tonsillectomy in the management of IgA nephropathy

Background :The tonsils represent a site of local immunity where immunoglobulin-bearing cells are capable of producing IgA. The tonsils have been considered the foci of abnormal IgA production in IgAN, thus, a relationship is suggested between the tonsillar immune response and the pathogenesis of IgAN. IgAN, then, is considered a tonsillar focal infection. Patients and methods :This study was done on 15 patients their ages ranged between 15 and 35 (10 males and 5 females). All patients were already diagnosed by renal biopsy-proven IgA nephropathy by the nephrologists and under medical treatment by conventional steroid. The diagnosis of IgA nephropathy was based on histologic assessment of percutaneous renal biopsy tissue. The main problem in all patients is that development of gross haematoria, deterioration of urinary findings and deterioration of the general condition of the patient after any acute attack of upper respiratory tract infection especially acute tonsillitis. Tonsillectomy was done after one month from controlling the acute infection. Postoperative follow up for all patients was done at 1st, 3rd, 6th, 12th month by clinical examination and laboratory investigations Results :The gross haematoria was completely stopped in all patients after tonsillectomy except two patients one of them was complicated by hypertension and the other one was complicated by nephritic syndrome. Also there was marked reduction in proteinuria, microscopic haematoria, marked reduction in the serum IgA concentration, urinary abnormalities disappeared and also improvement of renal function for the patients with serum creatinin less than 2mg/dl while in the two patients with serum creatinin more than 2mg/dL there was no much improvement after tonsillectomy with more deterioration of renal function of both patients with the development of chronic renal failure in the patient with nephritic syndrome 9 month postoperative Conclusion :Tonsillectomy is effective in improving renal function ,urinary symptoms, gross haematoria and decreasing the level of IgA in patients with IgAN if it is done in mild to moderate cases with serum creatinin less than 2mg/dL while has no much efficacy on moderate to severe cases with serum creatinin more than 2mg/dL or complicated cases.

Role of tonsillectomy in the management of IgA nephropathy

Background :The tonsils represent a site of local immunity where immunoglobulin-bearing cells are capable of producing IgA. The tonsils have been considered the foci of abnormal IgA production in IgAN, thus, a relationship is suggested between the tonsillar immune response and the pathogenesis of IgAN. IgAN, then, is considered a tonsillar focal infection. Patients and methods :This study was done on 15 patients their ages ranged between 15 and 35 (10 males and 5 females). All patients were already diagnosed by renal biopsy-proven IgA nephropathy by the nephrologists and under medical treatment by conventional steroid. The diagnosis of IgA nephropathy was based on histologic assessment of percutaneous renal biopsy tissue. The main problem in all patients is that development of gross haematoria, deterioration of urinary findings and deterioration of the general condition of the patient after any acute attack of upper respiratory tract infection especially acute tonsillitis. Tonsillectomy was done after one month from controlling the acute infection. Postoperative follow up for all patients was done at 1st, 3rd, 6th, 12th month by clinical examination and laboratory investigations Results :The gross haematoria was completely stopped in all patients after tonsillectomy except two patients one of them was complicated by hypertension and the other one was complicated by nephritic syndrome. Also there was marked reduction in proteinuria, microscopic haematoria, marked reduction in the serum IgA concentration, urinary abnormalities disappeared and also improvement of renal function for the patients with serum creatinin less than 2mg/dl while in the two patients with serum creatinin more than 2mg/dL there was no much improvement after tonsillectomy with more deterioration of renal function of both patients with the development of chronic renal failure in the patient with nephritic syndrome 9 month postoperative Conclusion :Tonsillectomy is effective in improving renal function ,urinary symptoms, gross haematoria and decreasing the level of IgA in patients with IgAN if it is done in mild to moderate cases with serum creatinin less than 2mg/dL while has no much efficacy on moderate to severe cases with serum creatinin more than 2mg/dL or complicated cases.

IgA Nephropathy: A Twenty Year Retrospective Single Center Experience

IgA nephropathy (IgAN) is a common glomerular disease whose etiology is unknown. Previous studies have described the clinical and laboratory features but none have specifically compared patients during different time periods. This 20 year retrospective study was performed to assess trends in the severity of IgAN from 1989-2008. We reviewed 57 patient charts that contained a confirmed biopsy diagnosis of IgAN and recorded data at the time of diagnosis and the final follow-up appointment. Clinical data included physical examination, urine, and blood tests. Patients were separated into two cohorts, Cohort 1 1989-1998 and Cohort 2 1999-2008. An increase in severity was noted in Cohort 2 based on a significantly higher Up/c and lower serum albumin level. Other prognostic indicators including GFRe, hematocrit, and glomerular injury score also demonstrated a trend towards more severe disease over the past 20 years. The patients in both Cohorts received similar treatments and had comparable renal function at the last follow-up visit. Based on our findings, we suggest that although a kidney biopsy is required to diagnose IgAN, the procedure may not be necessary in patients clinically suspected of having the disease but who have normal kidney function and minimal urine abnormalities.

Natural History and Renal Pathology in Patients with Isolated Microscopic Hematuria

Background/AimsNo definite conclusions have been reached about the natural history of patients with isolated microscopic hematuria (IMH). In this study, we observed the natural history of patients with IMH and examined factors related to a pathologic diagnosis and subsequent prognosis.MethodsWe retrospectively evaluated 156 subjects with IMH who had a renal biopsy performed. Of the 156 subjects, 33.3% were diagnosed with IgA nephropathy, 23.7% with mesangial proliferative glomerulonephritis, 15.4% with glomerular minor lesion, and 12.8% with thin basement membrane nephropathy; 6.4% had normal biopsies.ResultsWe followed up with 100 subjects for about 31 months. During this follow-up period, two subjects who had received a pathologic diagnosis of IgA nephropathy developed chronic kidney disease. During the course of the study, one of these subjects presented with proteinuria and hypertension and the other with proteinuria. The overall incidences of proteinuria and hypertension were 6% and 5% respectively.ConclusionsThe prognosis for patients with IMH was relatively favorable, but patients developing proteinuria and/or hypertension require careful observation and management during the follow-up period.

Prediction of diagnosis of immunoglobulin a nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic grading

Several clinical markers correlate well with the diagnosis and prognosis of IgA nephropathy (IgAN). In the present study, we re-evaluated the usefulness of these four clinical markers for prediction of the diagnosis of patients with IgAN through a comparison between many more patients with IgAN and those with other types of renal diseases. 364 patients with IgAN and 289 with other types of renal disease were examined. An analysis was performed prior to renal biopsy, using clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood cells in urinary sediments, and urinary protein. Patients with IgAN were divided into four groups according to histopathological findings. Presence of microscopic hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratios are useful for prediction of diagnosis of IgAN and distinguishing it from other renal diseases. Blood pressure, urinary protein, serum uric acid, renal function, and urinary sediment findings may be useful for prediction of prognostic grading in patients with IgAN.

Obesity-Related Nephropathy Associated with a History of IgA Nephropathy

This report describes the case of a 57-year-old man who underwent a repeated renal biopsy 25 years after the first biopsy in which the diagnosis of IgA nephropathy was made. Although the patient exhibited gradually increasing proteinuria and a slowly progressive renal impairment, the histological findings of the repeat biopsy revealed no evidence of either glomerular inflammatory changes or IgA deposition. Instead, a marked decrease in the glomerular density and hypertrophy of the remnant glomeruli were noted. Almost a complete disappearance of urinary protein excretion by a calorie-restricted diet indicated that the patient's obesity and its related factors may have contributed to the present nephropathic development.

Should a renal biopsy be performed at the first relapse of ‘clinical nephrotic syndrome’?

Immunoglobulin A (IgA) nephropathy is considered to be the commonest primary glomerulonephritis worldwide. The commonest clinical presentation of the disease is macroscopic hematuria, and nephrotic syndrome (NS) at the time of onset of symptoms is a predictor of poor outcome in both adults and children. In this report we describe a case of IgA nephropathy in a 15-year-old girl with a diagnosis of NS who was admitted to our hospital following 15 days of remarkable weight gain, and eyelid and pretibial oedema. NS was diagnosed when she was 3 years old. During the period between diagnosis and our observation the patient presented with three episodes of relapse. After the third episode a renal biopsy was performed and, together with clinical data, this enabled us to make the diagnosis of IgA nephropathy. NS is now recognized as a possible clinical manifestation of an IgA nephropathy, even at onset. Based on this case report, we suggest that a more vigilant management of children with NS may be necessary, even if they do not have atypical characteristics at onset. We suggest that it may be better to perform a renal biopsy at the time of first relapse.

A case of nephrotic syndrome 11 yr post‐kidney transplantation

Abstract: We present here a male patient who had developed nephrotic syndrome 11 yr after kidney transplantation. Nephrotic syndrome suddenly occurred after severe sunburn he got in Hawaii. Such a clinical course seemed very rare in kidney transplantation, and multifactorial etiology was suspected. The histological findings of graft biopsy were intricate. On light microscopy, there were mesangial expansion and endocapillary proliferation with duplication of GBM and crescent formation. Deposits of IgM in mesangium were the most prominent finding on immunofluorescence microscopy, but IgA and C3 deposits were also detected. Electron microscopy revealed paramesangial and a few subepithelial dense deposits. Additionally, small organized deposits were found in the subepithelial space. Based on these findings, a provisional diagnosis of IgA nephropathy superimposed on chronic transplant glomerulopathy was made. However, hepatitis C virus related nephropathy could not be excluded.

The genetics of IgA nephropathy

IgA nephropathy is the most common form of primary glomerulonephritis. Variations in clinical manifestations indicate that a diagnosis of IgA nephropathy encompasses multiple disease subsets that cannot be distinguished on the basis of renal pathology or clinical variables alone. Familial forms of the disease have been reported throughout the world, but are probably under-recognized because associated urinary abnormalities are often intermittent in affected family members. IgA nephropathy has complex determination, with different genes probably causing disease in different patient subgroups. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently implicated. Here, we present the evidence for genetic contributions to the disease, review clinical patterns of familial disease, and summarize some of the most promising genetic studies conducted to date. Linkage-based approaches to the study of familial forms of the disease have identified significant or suggestive loci on chromosomes 6q22-23, 2q36, 4q26-31, 17q12-22 and 3p24-23, but no causal gene has yet been identified. Many interesting, but poorly replicated, genetic association studies have also been reported. We discuss recent developments in analytic tools that should enable genetic studies of sporadic forms of disease by the genome-wide association approach.

Absence of Increased α1-Microglobulin in IgA Nephropathy Proteinuria

To search for biomarkers of IgA nephropathy, protein profiles of urine samples from patients with IgA nephropathy and normal volunteers were compared using two-dimensional DIGE. Most of the 172 spots identified in the urine were serum proteins, and their amounts in IgA nephropathy urine were much higher than those in normal urine; this can be explained as proteinuria caused by glomerular dysfunction. However, only alpha(1)-microglobulin, also one of the major serum proteins, in IgA nephropathy urine was not higher in amount than that in normal urine. We confirmed using ELISA analysis that the amounts of transferrin and albumin in IgA nephropathy and diabetic nephropathy urine were much higher than those in normal urine, whereas the amount of alpha(1)-microglobulin in IgA nephropathy urine was not higher than that in normal urine and was much lower than that in diabetic nephropathy urine. Approximately 50% of alpha(1)-microglobulin forms a complex with IgA in serum. These results suggest that alpha(1)-microglobulin in IgA nephropathy urine is a characteristic protein and might be a biomarker for IgA nephropathy and that alpha(1)-microglobulin might have a relationship with IgA nephropathy pathology.

Development of Immunoglobulin A Nephropathy- Like Disease in β-1,4-Galactosyltransferase-I-Deficient Mice

Beta4 galactosylation of glycoproteins plays important roles in protein conformation, stability, transport, and clearance from the circulation. Recent studies have revealed that aberrant glycosylation causes various human diseases. Here we report that mice lacking beta-1,4-galactosyltransferase (beta4GalT)-I, which transfers galactose to the terminal N-acetylglucosamine of N- and O-linked glycans in a beta-1,4 linkage, spontaneously developed human immunoglobulin A nephropathy (IgAN)-like glomerular lesions with IgA deposition and expanded mesangial matrix. beta4GalT-I-deficient mice also showed high serum IgA levels with increased polymeric forms as in human IgAN. IgAN is the most common form of glomerulonephritis, and a significant proportion of patients progress to renal failure. However, pathological molecular mechanisms of IgAN are poorly understood. In humans, abnormal character of serum IgA, especially serum IgA1 with aberrant galactosylation and sialylation of O-glycans in its hinge region is thought to contribute to the pathogenesis of IgAN. Mouse IgA has N-glycans but not O-glycans, and beta4-galactosylation and sialylation of the N-glycans on the serum IgA from beta4GalT-I-deficient mice was completely absent. This is the first report demonstrating that genetic remodeling of protein glycosylation causes IgAN. We propose that carbohydrates of serum IgA are involved in the development of IgAN, whether the carbohydrates are O-glycans or N-glycans.

A clinicopathologic study of thrombotic microangiopathy in the setting of IgA nephropathy

IgA nephropathy is the most common glomerulonephritis in the world. Thrombotic microangiopathy occurs in a number of clinical settings, including but not limited to thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, malignant hypertension, anti-phospholipid antibody syndrome and radiation nephropathy. Renovascular complications, such as thrombotic microangiopathy, in the setting of IgA nephropathy may be overlooked and their significance as a concomitant histologic finding is unclear. We conducted a clinicopathologic study to understand the possible relationship between IgA nephropathy and a concurrent thrombotic microangiopathy injury process. We identified 10 patients with an established diagnosis of IgA nephropathy and concurrent findings of thrombotic microangiopathy based on their renal biopsies. Six patients presented with malignant hypertension, while three others had severe hypertension (> or = 100 mmHg, diastolic). Five patients had nephrotic-range proteinuria. Seven patients had occasional arteriolar thrombi identified by light microscopy and prominent glomerular subendothelial space widening by electron microscopy, while three patients demonstrated only ultrastructural features of thrombotic microangiopathy. Other possible etiologic causes of thrombotic microangiopathy were not identified with the available clinical information. Our study suggests that a thrombotic microangiopathy injury, when present, is usually found in advanced stages of IgA nephropathy and can be associated with severe proteinuria. Although other possible causes of thrombotic microangiopathy, such as anti-phospholipid antibody syndrome, were excluded in only two patients, the thrombotic microangiopathy injury process may be a cause or a consequence of the severe hypertension encountered in most of the patients which, in turn, may be a consequence of the disease progression of IgA nephropathy.

IgA Nephropathy

IgA Nephropathy

Examination of the molecular diversity of alpha1 antitrypsin in urine: deficit of an alpha1 globulin fraction on cellulose acetate membrane electrophoresis.

In the clinical field of nephrology, a noninvasive approach employing the analysis of electrophoretic patterns in urinary protein has been established. In this study a total of 52 urine samples with IgA nephropathy (IgAN), anti-neutrophil cytoplasmic antigen-associated crescentic glomerulonephritis (GN), and other types of GN were analyzed. Patients with high alpha1 globulin (alpha1G) fractions, which contained alpha1AT in cellulose acetate membrane electrophoresis (CAE), tended to have alpha1 antitrypsin (alpha1AT) of normal molecular weight (57 kDa and 49 kDa), while patients with a deficit alpha1G fraction tended to have alpha1AT of low molecular weight (<49 kDa) (P < 0.01). The alpha1G fraction was significantly higher in patients with IgAN, and there were significantly more patients with normal molecular weight alpha1AT compared to patients with other diseases (P < 0.01). The isoelectric point of alpha1AT with lower-weight molecules was more on the alkali side compared to higher-weight molecules in two-dimensional electrophoresis. Detecting changes in alpha1G fractions in CAE may support the differential diagnosis of IgAN from other types of GN.

IgA NEPHROPATHY IN KIDNEY ALLOGRAFT RECIPIENTS

P389 Aims: It has been previously claimed that IgA nephropathy does not negatively influence kidney allograft survival although, in certain clinical situations, the disease is no more regarded benign. The aim of our study was to evaluate factors influencig IgA nephropathy course and it’s effect on long term graft survival. Methods: Among patients transplanted in our center between 1984-2003 27 cases of biopsy-proven post transplant IgA nephropathy (2 relapses of native kidneys disease) were diagnosed. We avaluated relation between allograft survival and native kidneys disease, basic transplantation parameters, maintenance immunosuppression, histologic type of glomerulopathy and therapeutic approach introduced after IgA nephropathy diagnosis. We also compared kidney allograft survival in tested and control groups mached for age, sex, PRA, HLA maching, optimal graft function and graft survival prior to IgA diagnosis. Kaplan Meyer estimator, log-rank test and Cox proportional hazards models were used in statistical analysis. Results: Mean time to dialysis reintroduction after IgA nephropathy diagnosis was 61 mths (95% CI 50.2-71.8). 12 mths after diagnosis 8% of pateints became dialysis-dependent, after 4yrs 20%, after 5 yrs 58%. We found signifficantly better graft function in control group at the time of IgA nephropathy diagnosis, 6 and 12 mths after its establishing, these differences were no more observable at 24 and 36 mths of follow up. In comparision to control group patients with IgA nephropathy experienced 5.8 higher risk for dialysis reintroduction (p<0.03). No correlation was found between recipient age, type of primary kidneys disease, pre-transplant dialysis dependence, HLA maching, immunisation prior to transplantation, delayed graft function, type of histopathological changes in biopsy specimen and kidney allograft survival after IgA nephropathy diagnosis. The risk for accelerated graft dysfunction in the course of IgA nephropathy was associated with higher serum creatinine (RR=2.29/1 mg/dl creatinine, p<0.01) and nephrotic syndrom (RR=4.65, p<0.05). In 19 of 27 patients maintenace immunosuppression was increased - in 15 mycophenolate mophetil, in single cases rapamycin, tacrolimus or cyclophosphamide infusions were introduced. Immunosuppression augmentation resulted in significatly diminished risk for dialysis dependence (RR=4, p<0.04). Hypolipemic and antiplatelet treatment did not influence graft survival. Conclusions: We suggest that in post transplant IgA nephropathy, especially with concomitant nephrotic syndrom, intesifying immunosuppression may prolong kidney allograft survival.

IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy

Two pathological patterns of acute poststaphylococcal glomerulonephritis are well defined and include (1) an acute proliferative and exudative glomerulonephritis closely resembling classical acute poststreptococcal glomerulonephritis in patients with Staphylococcus aureus infection and (2) a membranoproliferative glomerulonephritis in patients with Staphylococcus epidermidis infection secondary to ventriculovascular shunts. In this study, we report a novel immunopathologic phenotype of immunoglobulin (Ig) A-dominant acute poststaphylococcal glomerulonephritis occurring in patients with underlying diabetic nephropathy. Five patients with type 2 diabetes presented with acute renal failure occurring after culture-positive staphylococcal infection. Renal biopsy disclosed an atypical pattern of acute endocapillary proliferative and exudative glomerulonephritis with intense deposits of IgA as the sole or dominant immunoglobulin, mimicking IgA nephropathy. The deposits were predominantly mesangial in distribution with few subepithelial humps. All five cases occurred superimposed on well-established diabetic nephropathy. Outcome was poor with irreversible renal failure in four of five (80%) cases. The possible pathophysiological basis of this atypical form of acute poststaphylococcal glomerulonephritis in diabetic patients is explored. Proper recognition of this entity is needed to avoid an erroneous diagnosis of IgA nephropathy, with corresponding therapeutic and prognostic implications.