Features Of IgA Nephropathy Research Articles

Clinical and pathological findings of IgA nephropathy following SARS-CoV-2 infection

The features of IgA nephropathy (IgAN) after SARS-CoV-2 infection have not been well characterized. In this study, we compared the clinical and pathological characteristics of patients with IgAN who had experienced SARS-CoV-2 infection to those who had not. We conducted a retrospective study that enrolled 38 patients with biopsy-proven IgAN following SARS-CoV-2 infection with 4 months (post-SARS-CoV-2 infection group) and 1154 patients with IgAN prior to the pandemic (pre-SARS-CoV-2 infection group). Among the SARS-CoV-2 group cases, 61% were females. The average duration from SARS-CoV-2 infection to renal biopsy was 78.6 days. Prior to SARS-CoV-2 infection, the patients had different presentations of nephropathy. One patient had isolated hematuria, two had isolated proteinuria, twenty presented with both hematuria and proteinuria, and one patient had elevated serum creatinine. Additionally, there were eight cases with uncertain nephropathy history, and six cases did not have a history of nephropathy. Following SARS-CoV-2 infection, five patients experienced gross hematuria, one case exhibited creatinine elevation, and five cases showed an increase in proteinuria. The group of patients infected with SARS-CoV-2 after the COVID-19 pandemic exhibited older age, higher hypertension ratio and lower eGFR values compared to the pre-SARS-CoV-2 infection group. As for pathological parameters, a higher proportion of patients in the post-SARS-CoV-2 infection group exhibited a higher percentage of sclerotic glomeruli and glomerular ischemic sclerosis. There were no significant differences observed between the two groups in terms of therapy involving steroids, immunosuppressants, or RAS inhibitors. IgA nephropathy patients who were infected with SARS-CoV-2 were generally older and experienced more severe kidney damage compared to those without SARS-CoV-2 infection.

Glomerular Galactose-Deficient IgA1(KM55) Positive May Predict Poorer Prognosis in Coexisting Primary Membranous Nephropathy and IgA Nephropathy Patients.

Primary membrane nephropathy (PMN) and IgA nephropathy (IgAN) are the most common glomerular diseases in China. Because of different pathogenesis, prognosis is significantly different. When the two diseases coexist (PMN/IgAN), the clinicopathological manifestations and prognosis remain unclear. In the present study, we analyzed the clinicopathological characteristics of PMN/IgAN patients, with only IgA deposition (PMN/IgA deposition) patients as controls. Galactose-deficient IgA1(KM55) and M-type Phospholipase A2 Receptor(PLA2R), both in circulation and renal tissues, were detected. Furthermore, prognosis of PMN/IgAN was explored. We found that PMN/IgAN also had some clinical features of IgAN in addition to PMN, such as higher serum albumin, along with a similar heavy proteinuria and lower titers of serum anti-PLA2R antibody. The positive rate of glomerular KM55 in PMN/IgAN was 23.5% (20/85), and 0% (0/29) in PMN/IgA deposition. Among those glomerular KM55 positive patients, KM55 and IgA colocalized mainly along the glomerular mesangial and capillary areas. Unfortunately, there was no significant difference in serum level of Gd-IgA1 between KM55+ and KM55- subgroups in PMN/IgAN patients, similar to the PMN/IgA deposition group. Notably, glomerular KM55 positive may predict a poorer prognosis in PMN/IgAN patients. In conclusion, our study suggested that, when glomerular KM55 staining was positive, this special coexisting PMN/IgAN disorder was prone to have more characteristics of IgAN besides PMN, and may predict poorer prognosis, while the mechanism requires further investigation.

The difference between patients with nephrotic syndrome and nephrotic-range proteinuria in IgA nephropathy: a propensity score matched cohort study

ObjectiveTo date, nephrotic syndrome (NS) has not been well characterized in patients with IgA nephropathy (IgAN). Whether decline in serum albumin is an ominous sign in IgAN patients with massive proteinuria remains unknown. In this study, we evaluated clinical and pathological features of IgAN with NS and compared the differences for these features and long-term outcomes between patients with nephrotic syndrome and nephrotic-range proteinuria.MethodsA retrospective study was conducted, enrolling 1013 patients with biopsy-proven IgAN. The primary endpoint was the composite of a doubling of the base-line serum creatinine, 50% reduction in eGFR, ESKD (eGFR < 15 ml/min per 1.73 m2) or death.ResultsA total of 59 patients were presented with NS (5.8%). The patients with NS showed lower levels of hemoglobin, albumin and higher levels of serum creatinine, serum uric acid and urinary protein than patients without NS. As for pathological parameters, more patients with NS showed a higher prevalence of E1 lesions, T1/2 and C1/2 lesions. Furthermore, we used the propensity score matching method to select 57 patients with nephrotic-range proteinuria and normal serum albumin (NR group) who were comparable to 59 patients with NS. Patients with NS had lower levels of hemoglobin, albumin and IgG and higher levels of TC, LDL, FIB and D-dimer as well as more severe E1 and C1/2 lesions than those in NR group. The S1 lesion was more severe in the NR group than that in the NS group. There was no significant difference in long-term outcome between the two groups. In addition, we found that serum albumin level or the presence of hypoalbuminemia was not a risk factor affecting long-term outcome in patients with massive proteinuria.ConclusionsA prevalence of 5.8% of NS was presented in IgAN adult patients in our study. IgAN with NS patients had low levels of hemoglobin, albumin, high levels of serum creatinine, serum uric acid, urinary protein and more acute lesions. The prognosis of NS in patients with IgAN was not inferior to that of patients with nephrotic range proteinuria and normal serum albumin.

Serum homocysteine is associated with tubular interstitial lesions at the early stage of IgA nephropathy

BackgroundThe association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients.MethodsA total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 μmol/L or > 10 μmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy.ResultsSerum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) μmol/L, P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) [9.9 (7.6,12.4) vs. 8.8 (7.5,10.6) μmol/L, P < 0.001]. Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR.ConclusionsPathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.

The Related Factors of Hyperuricemia in IgA Nephropathy

Many factors, such as increased serum creatinine, increased blood pressure and abnormal urine protein, may lead to poor prognosis of IgA nephropathy (IgAN). The features of IgAN are also affected by uric acid, but its effect on the prognosis is less reported. We therefore systematically investigated the possible correlation of IgAN with hyperuricemia (HUA) and their prognosis. Two groups (HUA group and uric acid normal group) were included of 178 IgAN patients. The indexes in the clinic and pathology were compared; logistic regression and renal survival were used to speculate the correlated factors of HUA in IgAN and their prognosis. HUA group had higher serum urea nitrogen, serum creatinine, total cholesterol, 24-hour urinary protein quantity, percentage of CKD3⁃5, the thickness of arteriole, glomerular mesangial hyperplasia, tubular atrophy, glomerulosclerosis, interstitial fibrosis and the area of infiltration of inflammatory cells (ICI), lower eGFR and serum albumin-to-creatinine ratios (P < .05). Total cholesterol and ICI in X2 were independent related factors of HUA given by the analysis of logistic regression (P < .05). No correlation was found in HUA and normal group used by Kaplan- Meier (P > .05). Severer renal pathological injures (glomeruli, tubules or interstitium) were found in IgAN. Besides, total cholesterol and the area of infiltration of inflammatory cells were independent related factors of hyperuricemia in IgAN.

Clinicopathological feature analysis of IgA nephropathy complicated with acute kidney injury in children

Objective To investigate the clinicopathological features of IgA nephropathy(IgAN) complicated with acute kidney injury (AKI) in children. Methods The clinical and pathological data of children with biopsy-proven primary IgAN and complicated with AKI from January 2012 to December 2016 in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively, and the data of macroscopic hematuria (MH) associated AKI(15 cases) and other MH without AKI(99 cases) were compared. Results (1) Among 211 patients diagnosed with IgAN, 21 (9.95%) patients were complicated with AKI.Among the 21 cases, the average age was (9.5±2.1) years old, in which 17 cases(80.9%) were males, 19 cases with MH, and the range of the peak serum creatinine was 93-627 μmol/L.In histology, cellular/fibrocellular crescents were found in 11 cases, while high proportion of tubules filled with red blood cell(RBC) casts were observed in 8 cases, and moderate to severe acute tubular injury (ATI) were observed in 16 cases.In 2 cases, extensively mixed inflammatory cell infiltration with eosinophils was present in the interstitium.(2) According to the clinical and pathological characteristics, the 21 cases were divided into 3 groups: 15 cases with MH related AKI, 4 cases with crescentic glomerulonephritis, and 2 cases with acute interstitial nephritis.Compared with MH without AKI group(99 cases), the MH associated AKI group(15 cases) had significantly longer duration of MH, higher proteinuria level, urinary levels of β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG), and greater frequency of RBC casts and ATI, and the differences were statistically significant(all P<0.05). In 2 acute interstitial nephritis cases, one had a history of taking weight loss drug with unknown ingredients, while the specific cause of the other was not clear.(3) None of the patients was on dialysis, but corticosteroid was prescribed in 17 cases (including methylprednisolone pulse therapy in 6), and 3 cases were combined with cyclophosphamide.Almost all patients achieved normal renal function except for one who had no response within 2 months after treatment.The median follow-up period was 24 months, in which 1 patient with crescentic glomerulonephritis progressed to end-stage renal disease. Conclusions AKI is commonly seen in children with IgAN, and complete recovery of renal function was seen in all patients with MH associated AKI and acute interstitial nephritis. Key words: IgA nephropathy; Acute kidney injury; Macroscopic hematuria; Child

Serum Levels of Joining Chain-Containing IgA1 Are Not Elevated in Patients with IgA Nephropathy.

Background It has been suggested that mesangial IgA deposits are dimeric or polymeric in IgA nephropathy (IgAN). However, evidence concerning the molecular form of serum IgA in IgAN is controversial. And there is no direct evidence that the serum levels of joining chain- (J chain-) containing IgA (J-IgA) are elevated in IgAN. In this study, we aimed to measure serum J-IgA and glomerular J chain deposition with anti-J chain monoclonal antibody in IgAN. Methods BALB/c mice were immunized with human J chain-GST recombinant peptide to obtain anti-J chain monoclonal antibody. The levels of serum total IgA and J-IgA were measured by sandwich enzyme-linked immunosorbent assay in 115 patients with IgAN and 117 healthy volunteers. J chain deposition in kidney specimens was analyzed by immunohistochemistry staining. Results Serum levels of total IgA1 were elevated in IgAN patients compared to healthy subjects. However, serum levels of IgA, J-IgA, and J chain-containing IgA1 (J-IgA1), the J-IgA to total IgA ratio, and the J-IgA1 to total IgA1 ratio were not significantly different between IgAN patients and healthy subjects. Western blot analysis and gel filtration analysis using purified IgA1 also showed that the proportion of J chain-containing polymeric IgA1 was lower in IgAN patients compared to healthy subjects. No correlation was found between serum J-IgA or J-IgA1 and clinical features in IgAN. Immunohistochemistry analysis showed that glomerular J chain was positive in 12 IgAN patients (57.1%). The values of the J-IgA to IgA ratio and J-IgA1 to IgA ratio were significantly higher in IgAN patients with glomerular J chain deposition than those without. However, the serum levels of J-IgA and J-IgA1 and the J-IgA1 to IgA1 ratio were not significantly higher in two subgroups. Conclusions Although serum levels of total IgA1 were elevated in IgAN, the serum levels of J-IgA1 were not elevated. And serum J-IgA, serum J-IgA1, and J chain deposition were not correlated with disease severity in IgAN.

Comprehensive evaluation of the significance of immunofluorescent findings on clinicopathological features in IgA nephropathy.

The clinicopathological significance of immunofluorescent findings in IgA nephropathy remains controversial. The relations of the deposition of IgA, IgG, IgM, C3, C1q and fibrinogen (Fib) with pathological findings, baseline clinical findings, and renal outcome were evaluated in 688 patients with IgA nephropathy. Pathological features included cellular or fibrocellular crescents, endocapillary or mesangial hypercellularity, segmental or global glomerulosclerosis and the Oxford classification. The median age at biopsy was 30years. There were 289 men. With 74months median follow-up, 32% of patients received steroids. Twelve percent of patients developed end-stage renal disease (ESRD). The degree of IgA was closely related to the degree of C3, IgG and IgM deposition. The degree of IgA, C3, IgG and Fib deposition was significantly related to the percentage of glomeruli with crescent, endocapillary and mesangial hypercellularity. IgM deposition showed significant association with crescent, mesangial hypercellularity, segmental sclerosis, global glomerulosclerosis and tubular atrophy/interstitial fibrosis. In the patients treated with steroids, the risk for ESRD in patients with 2-3+ IgA deposition was significantly lower with reference of 1+ IgA deposition. We found the different roles of glomerular immune reactants' deposition in the inflammatory process from acute to chronic stage. IgA deposition together with IgG, Fib and C3 may produce acute inflammatory injury. IgM deposition might occur in the early stage of inflammation and remains until late sclerotic stage. The prominent deposition of IgA related to low risk for ESRD in patients who received steroids might suggest effectiveness of steroids in such patients.

Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area

To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area. The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups. Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (P<0.05) and lower eGFR (P<0.05); more of these patients were in Lee's grade IV-V, had renal tubular atrophy and/or interstitial fibrosis, and had MEST scores more than 3 (P<0.05). Patients with IgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.

Clinical and pathological analysis of IgA nephropathy with chronic renal failure

Objective: To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure.Method: Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function.Results: Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p < 0.05, respectively). The most common pathological type was proliferative sclerosis glomerulonephritis (PSGN) and M1S1E0T0 according to WHO definition and Oxford Classification, respectively, and most of the 65 cases had glomerulosclerosis. Simple IgA deposition was the most common immunopathologic type. Of all the cases, 44.6% accompanied with C3 while 4.6% with C1q. Further analysis revealed there were no relationships between severity of pathological lesion and levels of clinical indexes (Scr and eGRF) (p > 0.05).Conclusion: IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.

Clinical pathological features of IgA nephropathy with nephrotic syndrome and the risk factors for impairment of renal pathology

Objective To investigate the clinical pathological features of IgA nephropathy with nephrotic syndrome and risk factors for impairment of renal pathology. Methods 121 cases of IgA nephropathy with nephrotic syndrome were selected, all patients had been diagnosed with biopsy.The clinical pathological features wer analyzed, they were divided into two groups according to different kidney disease.The minor pathological changes which Lee's classification grade Ⅰ and grade Ⅱ patients belong to group A, with a total of 36 cases, while Lee's pathology heavier grade for grade Ⅲ, Ⅳ and Ⅴ grade level in patients belonging to group B, with a total of 85 cases.Clinical characteristics and clinical laboratory indicators of two groups were compared, and risk factors for renal pathological damage were analyzed in multivariate analysis. Results The average duration of group B was significantly longer than the average duration of group A, the difference was statistically significant (t=12.74, P 5.0×107/L were dangerous aggravating factors. Conclusion Hemoglobin protective factors for IgA nephropathy with nephrotic syndrome, the mean arterial pressure, 24h urinary protein excretion and urine red blood cells are their risk aggravating factors, they can make a more accurate judgment of the patient's condition. Key words: Nephrotic syndrome; IgA nephropathy; Pathology, clinical; Factor analysis, statistics

The Prevalence and Clinicopathological Characteristics of IgA Nephropathy in Shenzhen—A Single-center Biopsy Study

The Prevalence and Clinicopathological Characteristics of IgA Nephropathy in Shenzhen—A Single-center Biopsy Study

Characteristics of IgA nephropathy in advanced-age patients.

The susceptible age for IgA nephropathy (IgAN) is <30 years. However, IgAN sometimes develops in people aged >60 years, and its characteristics remain unknown. We divided 600 IgAN patients into three groups: advanced-age group (AAG, n=31, ≥60 years); middle-aged group (MAG, n=162, 40-59 years); and young-aged group (YAG, n=407, 20-39 years). We analyzed clinical and histological background, renal outcome, and risk of progression. In the AAG, mean arterial pressure (MAP) and the number of hypertensive patients were significantly higher than in the YAG. Total protein, serum albumin, and estimated glomerular filtration rate were significantly lower, and blood urea nitrogen, proteinuria, and N-acetyl-β-D-glucosaminidase were significantly higher in the AAG than in MAG and YAG. In histological findings, interstitial fibrosis/tubular atrophy by Oxford classification and arteriosclerosis were more severe in the AAG than the in YAG. Renal survival rate analyzed by Kaplan-Meier method was significantly lower in the AAG (22.9%/19 years in the AAG vs. 69.2 and 84.9%/20 years in the MAG and YAG, p<0.0001). The patients who progressed to end-stage renal disease (ESRD) in the AAG had higher MAP and more severe proteinuria compared with the patients who did not progress to ESRD in the AAG. The characteristics of IgAN in advanced-age were lower renal function, high levels of proteinuria, severe interstitial change, and arteriolosclerosis caused by glomerulopathy and concomitant diseases, such as hypertension, dyslipidemia, and hyperuricemia. Prognosis was poor, and >70% developed ESRD within 20 years.

Disruption of Smad4 Expression in T Cells Leads to IgA Nephropathy-Like Manifestations

The link between glomerular IgA nephropathy (IgAN) and T helper 2 (Th2) response has been implicated, however, the mechanisms are poorly defined because of the lack of an appropriate model. Here we report a novel murine model characterized by lineage-restricted deletion of the gene encoding MAD homologue 4 (Smad4) in T cells (Smad4co/co;Lck-cre). Loss of Smad4 expression in T cells results in overproduction of Th2 cytokines and high serum IgA levels. We found that Smad4co/co;Lck-cre mice exhibited massive glomerular IgA deposition, increased albumin creatinine ratio, aberrant glycosylated IgA, IgA complexed with IgG1 and IgG2a, and polymeric IgA, all known features of IgAN in humans. Furthermore, we examined the β1, 4-galactosyltransferases (β4GalT) enzyme which is involved in the synthesis of glycosylated murine IgA, and we found reduced β4GalT2 and β4GalT4 mRNA levels in B cells. These findings indicate that Smad4co/co;Lck-cre mice could be a useful model for studying the mechanisms between IgAN and Th2 response, and further, disruption of Smad4-dependent signaling in T cells may play an important role in the pathogenesis of human IgAN and contributing to a Th2 T cell phenotype.

Oxford classification of IgA nephropathy: Broadening the scope of the classification

Oxford classification of IgA nephropathy: Broadening the scope of the classification

Relationship between the number of podocytes in glomerulus and the clinical manifestations and renal pathological features in IgA nephropathy

Relationship between the number of podocytes in glomerulus and the clinical manifestations and renal pathological features in IgA nephropathy

Clinical Pathological Analysis and Treatment of Iga Nephropathy with a Few Quantity of Renal Crescent Formation

Background: IgA nephropathy was a syndrome of uniform morphology, diverse clinical features and uncertain prognosis, presence of crescents around blood vessels indices the unfavorable long-term prognosis, if the proportion of crescent in glomeruli exceeding ratio of 50%, we give the active treatment of prednisone pulse therapy, but in most condition, IgA nephropathy was diagnosed with a few of the proportion of crescent, these patients are the precondition of crescent IgA nephropathy or a special group of disease? Steroid therapy is suitable for these patient, especially for the patient with bulk fibrous crescent in renal tissue? How about the prognosis of IgA nephropathy with a few quantity of crescent formation, so we extended our original study to aim directly at above assumption. In this study, we report the results of an extended 2-year follow-up of our original randomized cohort of IgAN subjects who had crescentic formation using either steroid therapy alone or steroid pulse one kind of immunodepressant. Objective: To observe the clinical and pathological characteristics of IgA nephropathy ( IgAN) with a few quality crescent formation in 63 patients. Methods: Clinic pathological data of 63 patients with IgAN accompanied by crescents were analyzed. These patients were accepted in the group and were renal biopsied according to the percentage of glomeruli affected by crescents less than 50% during 2007-2008, and their clinical and laboratory data were collected. Results: (1) Clinical features: all the patients aged 28.3 ± 5.6 years had hematuria and proteinuria and gross hematuria (28.6%) and large mounts of proteinuria were also common, protein excreted in urine was more than 3.5 g per day in 14.2% of the patients. The patient's accompained by hypertension was 60.3% and five patients present with malignant hypertension, and acute renal insufficiency were found by 7.9%. 38 patients present with increased serum level of IgA immuglobin. (2) Renal pathology: the glomeruli were affected by crescents from 5% to 47%.Most crescents were cellular. All the cases had a diffuse mesangial proliferation and all the patients presented deposition of IgA, IgM and C3 in mesangial area. There were 9 specimens combined with the deposition of IgA around capillary. 18 patients were given steroid therapy with renal function ameliorated, serum creatinine of 3 patients with fibrous crescent formation were obviously decreased after large amount of steroid invention. Conclusion: The main clinical features of IgAN with crescent formation were hematuria combined with proteinuria, especially persistent gross hematuria and severe proteinuria and some patients with AKI. However, the severity of clinical features and number of crescent was not positively relative. The hematuria, elevated plasma IgA and tonsils edema were independent risk factors of crescent formation in renal tissue. The steroid therapy for the patient with fibrous crescent in renal tissue showed a promising clinical effect, especially for the patients with fibrous crescent formation, so the clinical manifestation combined with pathological injury of renal tissue may contribute to the decision of therapy protocol.

Prognostic relevance of clinical and histological features in IgA nephropathy treated with steroid and angiotensin receptor blockers

The prognostic relevance of clinical and histological features on renal outcome has not been assessed in patients with IgA nephropathy (IgAN) treated with the combination therapy of steroid and angiotensin receptor blockers (ARB). A prospective trial of a combination of steroid and ARB was performed in 50 patients with IgAN, proteinuria and serum creatinine levels < 2 mg/dl. Over a mean follow-up period of 4 years, the combination therapy reduced proteinuria and hematuria and improved renal function in most patients. The mean change in estimated GFR (eGFR) was + 0.30 +/- 0.74 ml/min/1.73 m2/month. Forty-three patients (86%) exhibited stable renal function and 7 patients (14%) reached the primary end point of a (3) 20% decrease in eGFR from baseline levels. Between the nonprogressive and progressive patients, there were significant differences in the levels of urine protein/ creatinine excretion ratio (PCR) at baseline and throughout the follow-up period as well as baseline eGFR and degree of glomerular crescents (p < 0.05). Forty (80%) and 24 patients (48%) had a urine PCR < 1 and < 0.3 g/g, respectively, at their last follow-up. Renal survival was better in patients who had initial urine PCR < 3 g/g as well as final PCR < 1 g/g. Regression analysis revealed that the final urine PCR and age were critical determinants of slope of the eGFR by both univariate and multivariate analyses. However, eGFR, pathologic findings, systolic BP, proteinuria, and body mass index at the initial presentation were not predictive of slope. Our results indicate that achieving a low urinary protein excretion is the main determinant for the good outcome in patients treated with combination therapy.

Lupus vulgaris with tubercular lymphadenitis and IgA nephropathy

A 14-year-old girl presented with a 10-year history of a large crusted plaque over the right thigh for 10 years and small reddish plaque over the left upper back for 3 months. On routine evaluation, she was found to have hematuria. Skin biopsy from the lesion was suggestive of skin tuberculosis (lupus vulgaris), and kidney biopsy showed features of IgA nephropathy (IgAN). Fine-needle aspiration from the inguinal lymph node was consistent with granulomatous disease. The patient has been on anti-tubercular treatment, and the hematuria has subsided.

Oxidative stress and non-enzymatic glycation in IgA nephropathy

Approximately 20-50% of IgA nephropathy patients develop end-stage renal disease. We have previously found enhanced oxidative stress and decreased antioxidant capacity in red blood cells of IgA nephropathy patients. In this study we assess oxidative stress, non-enzymatic glycation, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content in these patients. Non-enzymatic glycation and oxidative stress were assessed in 88 IgA nephropathy patients by measuring advanced glycation end products, Nepsilon-carboxymethyl-lysine, thiobarbituric acid reactive substances, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content. Advanced glycation end products (2659 +/- 958 a.u.) and Nepsilon-carboxymethyl-lysine (563 +/- 215 ng/ml) were significantly higher in IgA nephropathy patients with decreased renal function compared to those with normal renal function (p < 0.002) or controls (p < 0.001). Thiobarbituric acid-reactive substances in plasma and associated with low-density lipoprotein were significantly elevated and oxidative resistance of low-density lipoprotein was significantly reduced in all groups of IgA nephropathy patients. There was no significant difference in circulating fluorescent advanced glycation end products, Nepsilon-carboxymethyl-lysine, thiobarbituric acid-reactive substances levels, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content between patients with normal vs. impaired glucose metabolism. Low alpha-tocopherol content of low-density lipoprotein was accompanied with decreased oxidative resistance, depletion in polyunsaturated fatty acids, elevated saturated fatty acids and thiobarbituric acid-reactive substances within low-density lipoprotein suggesting enhanced lipid peroxidation. Decreased oxidative resistance of low-density lipoprotein and enhanced oxidative stress are common features in IgA nephropathy, while increased non-enzymatic glycation occurs as renal function declines.