The efficacy of tonsillectomy on long-term renal survival in patients with IgA nephropathy

BACKGROUND: Little information has been available until now about the clinical efficacy of tonsillectomy on long-term renal survival of patients with idiopathic immunoglobulin A nephropathy (IgAN). METHODS: To investigate the effect of tonsillectomy on long-term renal survival, we reviewed the clinical course of 118 patients with idiopathic biopsy-diagnosed IgAN from 1973 to 1980. Of those, 48 patients received tonsillectomy and 70 patients did not. The starting point of observation was defined as the time of the diagnostic renal biopsy, and the end point as when requiring the first dialysis. Up to 2001, the mean observation time was 192.9 +/- 74.8 months (48-326 months). Renal survival and impact of covariates were evaluated by Kaplan-Meier analysis and Cox proportional hazards regression model. RESULTS: Age, gender, amount of urinary protein excretion, serum creatinine, serum IgA, blood pressure, and histopathologic findings at the time of renal biopsy and treatments during the observation period were not significantly different between patients with and without tonsillectomy. Five (10.4%) of the patients with tonsillectomy and 18 (25.7%) of the patients without tonsillectomy finally required dialysis therapy (chi-square test, P = 0.0393). By Kaplan-Meier analysis, renal survival rates were 89.6% and 63.7% at 240 months in the patients with and without tonsillectomy, respectively, and were significantly different (log-rank test, P = 0.0329). In the multivariate Cox regression model, tonsillectomy (hazard ratio, 0.22; 95% CI, 0.06 to 0.76; P = 0.0164) had a significant effect on renal outcome. CONCLUSION: These results indicate that tonsillectomy has a favorable effect on long-term renal survival in patients with IgAN.     

Improved renal survival in Japanese children with IgA nephropathy

Since the beginning of the 1990s, Japanese medical practitioners have extensively prescribed angiotensin-converting enzyme (ACE) inhibitors for children with mild IgA nephropathy (IgA-N) and steriods for those with severe IgA-N. We have performed a retrospective cohort study to clarify whether the long-term outcome has improved in Japanese children with IgA-N. Renal survival was defined as the time from onset to end-stage renal disease (ESRD). We divided the study period into two time periods based on the occurrence of the initial renal biopsy:1976–1989 and 1990–2004. Actuarial survivals were calculated by Kaplan–Meier method, and comparisons were made with the logrank test. The Cox proportional hazard model was used for multivariate analysis. Between 1976 and 2004, 500 children were diagnosed as having IgA-N in our hospitals. The actuarial renal survival from the time of apparent disease onset was 96.4% at 10 years, 84.5% at 15 years and 73.9% at 20 years. Renal survival in the 1990–2004 period was significantly better than that in 1976–1989 (p = 0.008), and a marked improvement in renal survival in patients with severe IgA-N was also observed (p = 0.0003). Multivariate analysis indicated that diagnosis year was a significant factor for ESRD-free survival independently of baseline characteristics. The results of this study show that there has been an improvement in terms of renal survival in Japanese children with IgA-N.     

CC-chemokine receptor five gene polymorphism in primary IgA nephropathy: the 32 bp deletion allele is associated with late progression to end-stage renal failure with dialysis

The chemokine (CK) receptor 5 (CCR5) is necessary for two adjacent cysteines (CC)-CKs such as Regulated upon Activation Normal T cell Expressed and Secreted, a/o Macrophage Inflammatory Protein 1alpha/beta to mediate their inflammatory properties. The CCR5 gene polymorphism with 32-basepair deletion (d32) leads to receptor inactivation/dysfunction in homo/heterozygous individuals. We have evaluated its role in both initiation and/or progression of primary immunoglobulin A (IgA) nephropathy (IGAN) in a case-control study involving a prospective cohort of 318 IGAN patients and a matched group of 294 controls. Genotyping was performed by a two-specific primers single polymerase chain reaction technique: normal allele (nl) vs d32 allele. The d32 allele frequency was not different in patients (11.0%) vs controls (8.3%), indicating no significant influence on IGAN initiation. Genotype to clinical phenotype correlation demonstrated that progression to renal/patient death was associated with the d32 allele: 18.2% (12 out of 66 with d32) vs 8.3% (21 out of 252); chi(2)=6.73; P=0.017. The Kaplan-Meier survival without renal/patient death was worse in d32-positive patients (log-rank test; P=0.002). The Cox regression analyses confirmed that the nl/nl genotype was a significant and independent protective factor for progression to end-stage renal failure (ESRF)/dialysis: beta/standard error (s.e.)=-3.1; chi(2)=9.5; relative risk=0.31 (95% confidence interval 0.15-0.65); P=0.002. The d32-CCR5 polymorphism played a significant role in the progression of primary IGAN, with the nl/nl genotype being an independent protective factor for late progression towards ESRF/dialysis. These data raise question about the usefulness of systematic CCR5 genotyping in IGAN patients.     

Acute renal failure associated with hematuria in IgA nephropathy

Severe acute deterioration of renal function, which occurred during the episode of massive gross hematuria, is described in two patients with IgA nephropathy (IgAN). The renal failure abated gradually after dialytic support. Renal pathology in each case revealed focal proliferative glomerulonephritis with less than 14% of the glomeruli affected by crescents or sclerosis. In contrast to the mild glomerular lesions, acute tubular cell injury in relation to phagocytosis of erythrocytes or pigments and/or tubular obstruction was prominent. We think our observations support the previous reports that tubular lesions in relation to heavy glomerular bleeding may be a cause of severe acute renal failure in patients with IgAN.     

The prognostic value of platelet-to-lymphocyte ratio on the long-term renal survival in patients with IgA nephropathy

Purpose

Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN).

Methods

We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR?<?15 mL/min/1.73 m², initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients.

Results

330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR?<?106, 106?≤?PLR?≤?137, and PLR?>?137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR?>?137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR?>?137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m².

Conclusions

Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m².

     

Megsin 2093T-2180C haplotype at the 3' untranslated region is associated with poor renal survival in Korean IgA nephropathy patients

AIMS: Megsin is a mesangial cell-predominant gene which belongs to the serpin superfamily. The expression of megsin was upregulated and coincided with mesangial proliferation and extracellular matrix expansion in IgA nephropathy (IgAN). In the present study, we evaluated the influence of the C2093T and C2180T polymorphism within the 3' untranslated region (3'UTR) of megsin gene and its haplotypes on the development and progression of Korean IgAN patients. METHODS: Korean IgAN patients (n = 260) with a minimal follow-up of 4 years were recruited. Healthy subjects with normal renal function, normal urinalysis and normotension (n = 315) were included as controls. The polymorphisms were determined by the 5' nuclease allelic discrimination assay, and the haplotypes were constructed using the Phase program. RESULTS: The C2093T and C2180T genotype and allele frequencies were not different significantly between IgAN patients and controls. In C2093T polymorphism, patients with CC genotype showed a better renal survival than those with CT or TT genotypes by Kaplan-Meier analysis (p = 0.027). The megsin C2093T polymorphism remained an independent risk factor for progression (Cox regression model, HR for TT genotype: 3.52, 95% CI 1.69 - 7.34; HR for CT genotype: 2.15, 95% CI 1.30 - 3.57). In C2180T polymorphism, patients with TT genotype showed a better outcome than those with CC or CT genotypes (p = 0.025). The C2180T polymorphism was also an independent risk factor for progression (HR for CC genotype: 4.05, 95% CI 1.93 - 8.51; HR for CT genotype: 2.35, 95% CI 1.40 - 3.94). The two alleles showed linkage disequilibrium in phased haplotype. The patients with 2093T-2180C haplotype showed a poor renal survival compared to those with 2093C-2180T haplotype (p = 0.028). The haplotype remained an independent risk factor for progression (HR for 2093T-2180C haplotype: 2.01, 95% CI 1.44 - 2.81). CONCLUSIONS: Our results suggest that the 2093T-2180C haplotype at the 3'UTR of megsin gene is associated with rapid disease progression in Korean IgAN patients. This is the reverse of the results from the Chinese IgAN patients. Further studies are strongly needed to elucidate the reasons of disparity.     

肾功能不全的IgA肾病患者临床表现与病理特点分析

目的分析肾脏活体组织检查（简称：肾活检）时肾功能异常的IgA肾病患者的临床表现与病理特点。方法选择我院经肾活检确诊的190例IgA肾病患者为研究对象,以其患者血肌酐（SCr）130μmol／L为界分为2组：肾功能正常组（SCr〈130μmol／L）128例和肾功能异常组（SCr≥130μmol／L）62例。同时对其肾脏病理进行半定量评分,比较2组患者的临床病理特点,并且通过回归分析与其肾功损害相关的因素。结果与肾功能正常组相比,肾功能异常组男性比例明显增高（72．6％1;L28．9％,P〈0．01）,年龄更大[（34±10）岁比（30±9）岁,P〈0．01],病程更短[（11±17）]个月比（20±41）个月],同时收缩压更高[（141±19）比（123±17）mmHg,P〈0．01],24h尿蛋白定量增多[（3．31±2．70）g比（2．25±2．19）g,P〈0．01]。同时其患者肾脏病理反映慢性病变的指数均明显增高。多因素分析还显示,与肾活检时肾功能异常密切相关的危险因素包括男性,年龄增大,收缩压增高,24h尿蛋白定量增多,以及肾小管萎缩和间质纤维化指数增高。结论肾活检时肾功能异常的IgA。肾病患者临床表现和肾脏病理改变均明显加重,肾小管萎缩和间质纤维化指数增高与IgA肾病患者肾活检时肾功能异常独立相关。     

The level of serum secretory IgA of patients with IgA nephropathy is elevated and associated with pathological phenotypes.

BACKGROUND: Mucosal infection associated episodic macroscopic haematuria is observed in many patients with IgA nephropathy (IgAN), however, the mechanism has not been elucidated. Recent study suggested that secretory IgA (SIgA) might play an important role in the pathogenesis of IgAN. The aim of this study is to investigate the level of serum SIgA and the deposition of SIgA in glomeruli in IgAN patients with different pathological phenotypes. METHODS: The levels of serum SIgA were detected in 57 patients with IgAN and 48 normal controls. The associations between the levels of SIgA and the pathological phenotypes of IgAN as well as clinical parameters were investigated. Frozen renal sections from 34 of the 57 patients without IgM deposition were immunofluorescence stained and examined by confocal microscopy to detect the co-deposition of IgA and secretory component (SC). The association between deposition of SIgA and the level of serum SIgA was analysed. RESULTS: The level of serum SIgA in patients with IgAN was significantly higher than that of normal controls. The level of serum SIgA in patients with focal proliferative sclerosing IgAN (fpsIgAN) was much higher than that in patients with mild mesangial proliferative IgAN (mIgAN) (P<0.001). The level of serum SIgA correlated with the level of serum creatinine (R=0.509, P<0.001), degree of proteinuria (R=0.643, P<0.001) and creatinine clearance (R= -0.454, P=0.002) in patients with IgAN. Significant co-deposition of SC and IgA were found in 11 of the 34 patients. Although the level of serum SIgA in patients with SC deposits was higher than those without SC deposits, the difference was not significant. CONCLUSIONS: It was concluded that mesangial IgA, at least partly, was originated from mucosal immune sites. The levels of serum SIgA were significantly increased in patients with IgAN and were closely associated with pathological phenotypes.     

Macroscopic hematuria and proteinuria preceding renal IgA deposition in patients with IgA nephropathy

Although the clinical onset of IgA nephropathy is frequently impossible to define, macroscopic hematuria apparently heralds the onset of the disease in some patients. We describe the clinical course and renal histologic findings of four adults with IgA nephropathy who were diagnosed by the characteristic immunohistologic features in a second renal biopsy specimen. IgA was not detected in the initial renal biopsy specimens obtained 9 months to 4 years earlier. The first renal biopsy had been performed to evaluate macroscopic hematuria (recurrent in three patients), accompanied by pathologic proteinuria in two patients. Our observations suggest that the pathognomonic immunohistologic findings of IgA nephropathy may follow the clinical onset and raise questions about the presumed pathogenetic role of IgA in the early stages of this disease.     

The association of 5-year therapeutic responsiveness with long-term renal outcome in IgA nephropathy

Clinical and Experimental Nephrology - Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis. Since most patients have a relatively benign renal prognosis,...     

Selective elevation of monomeric IgA1 in IgA nephropathy patients with normal renal function

The molecular form of the pathognomonic IgA in IgA nephropathy (IgAN) remains controversial. Because characterization of the molecular form of IgA molecules can lend insight into their origin (systemic v mucosal), we developed immunoassays to measure both total and J chain-containing (polymeric) IgA1 and IgA2. These assays were used to measure IgA in sera from two groups of IgAN patients (with normal or decreased renal function), as well as from a group of normal individuals. IgA1 levels were higher in both groups of patients with IgAN when compared with the controls. The elevation appeared to be restricted to non-J chain-containing (monomeric) IgA1 in patients with normal renal function, whereas polymeric IgA1 was also slightly elevated in patients whose renal function was diminished. While there were no significant differences between the groups in terms of the levels of total IgA2, the patient group with normal kidney function appeared to have lower levels of polymeric IgA2. The observation that the elevation in serum IgA appears to be restricted to the monomeric form of IgA1, at least when renal function is normal, implies a systemic origin of the pathognomonic IgA in IgAN and further suggests an abnormality in the regulation of IgA secretion by immunoglobulin-producing cells in bone marrow, the site of systemic IgA synthesis.