[Show abstract][Hide abstract] ABSTRACT: Background:
The coexistence of IgA nephropathy (IgAN) and antineutrophil cytoplasmic autoantibodies (ANCAs) is relatively rare. Only a few studies have reported the features of these patients.
We studied the clinical and histological features of 20 ANCA-positive IgAN patients. They were compared with ANCA-negative IgAN patients (n = 40) and ANCA-associated systemic vasculitis (AASV) patients (n = 40) with a randomly selected and matched proportion of crescentic glomeruli. Furthermore, 9 ANCA-positive crescentic IgAN patients out of the 20 cases were compared with two control groups with crescentic nephritis.
ANCA-positive IgAN patients showed older age, lower haemoglobin and higher inflammatory indicator levels at baseline, and a higher percentage of general symptoms and pulmonary involvement, compared with ANCA-negative IgAN patients, and were comparable to AASV patients. Histologically, there was a significantly higher percentage of fibrinoid necrosis in glomeruli in ANCA-positive IgAN patients and in AASV patients compared with ANCA-negative IgAN patients (35, 25 and 0%, respectively, P = 0.003). After immunosuppressive therapy, ANCA-positive crescentic IgAN patients were more likely to withdraw from dialysis (75 versus 9.1%, P = 0.03) and not to reach end-stage renal disease within 6 months (11.1 versus 66.7%, P = 0.01) compared with ANCA-negative crescentic IgAN patients.
IgAN patients with ANCA positivity showed more severe clinical and histological features when compared with ANCA-negative IgAN patients and were comparable to AASV patients. However, renal prognosis was relatively better in ANCA-positive crescentic IgAN patients after aggressive immunosuppressive therapy in the short term, compared with ANCA-negative patients.
[Show abstract][Hide abstract] ABSTRACT: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated.
14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05-0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission.
Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered.
Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.
No preview · Article · Mar 2012 · American Journal of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Vitamin D has shown efficacy in the reduction of proteinuria in patients with chronic kidney disease. This study aimed to determine the effect of calcitriol on urinary protein excretion in patients with immunoglobulin A (IgA) nephropathy.
Open-label, non-placebo-controlled, randomized study.
50 patients with IgA nephropathy were enrolled. The main criterion for inclusion was urinary protein excretion >0.8 g/d after renin-angiotensin system-inhibitor treatment for at least 3 months.
Patients were randomly assigned (1:1) to receive 2 doses (0.5 μg) of calcitriol per week or no treatment for 48 weeks.
The primary end point was to compare change in 24-hour urinary protein excretion from baseline to last measurement during treatment.
Every 8 weeks, there was measurement of 24-hour urinary protein excretion, serum calcium, serum phosphorus, serum creatinine, and intact parathyroid hormone.
Measurement of the primary end point showed changes in urinary protein excretion of +21% (from 1.29 to 1.58 g/24 h; 95% CI, -9% to +52%) in the control group and -19% (from 1.60 to 1.30 g/24 h; 95% CI, -42% to +4%) in the calcitriol-treated group. There was a significant decrease in proteinuria in the calcitriol-treated group compared with the control group (difference between groups, 41%; 95% CI, 5%-79%; P = 0.03). The secondary end point of achieving at least a 15% decrease in proteinuria was attained by 7 of 24 (29%) controls and 17 of 26 (65%) of those treated with calcitriol (P = 0.02). No significant differences were observed in decrease in estimated glomerular filtration rate and change in blood pressure between the 2 groups. The incidence of recorded adverse events was similar between the 2 groups.
Small and non-placebo-controlled study.
The addition of calcitriol to a renin-angiotensin system inhibitor resulted in a safe decrease in proteinuria in patients with IgA nephropathy.
Preview · Article · Jan 2012 · American Journal of Kidney Diseases
[Show abstract][Hide abstract] ABSTRACT: We report a 41-year-old Chinese female with Fabry disease and diffuse thinning of the glomerular basement membrane (GBM). The patient presented with peripheral edema, mild proteinuria, microscopic hematuria, normal renal function, hypertension and tinnitus. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. Renal biopsy of the proband showed focal segmental glomerulosclerosis with cytoplasmic vacuolization of the glomerular visceral epithelial cells by light microscopy. Laminated myelin inclusions in some of the glomerular podocytes, parietal epithelia, distal tubular epithelial cells and vascular endothelial cells along with diffuse thinning of the GBM (mean thickness of GBM: 216 ± 31 nm) were identified by electron microscopy. Genetic analysis detected a de novo novel GLA mutation, 1208 ins 21 bp, while a new variant of COL4A3 SNP M1209I was carried by mother and daughter as well as the proband's father (I-1) and one sister (II-4). The coexistence of thinned GBM should be considered in patients with Fabry disease-manifested familial hematuria.
No preview · Article · Aug 2011 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: The Oxford classification of IgA nephropathy (IgAN) may aid in predicting prognosis and providing therapeutic strategy but must be validated in different ancestry.
A total of 410 patients with IgAN, enrolled from one of the largest renal centers in China, were evaluated for the predictive value of the Oxford classification to prognosis defined as end stage renal disease. A total of 294 of these patients were prospectively treated with renin-angiotensin system blockade and immunosuppressants sequentially and were evaluated separately to assess the predictive value to therapeutic efficacy (defined as time-averaged proteinuria <1 g/d). Three pathologists reviewed specimens independently according to the Oxford classification and were blinded to clinical data.
Segmental glomerulosclerosis and tubular atrophy and interstitial fibrosis were independent predictive factors of end stage renal disease. Patients who had >25% of glomeruli with endocapillary hypercellularity showed higher proteinuria, lower estimated GFR, and higher mean BP than patients with less endocapillary hypercellularity. Immunosuppressive therapy showed a protective effect to prognosis of endocapillary hypercellularity in patients with endoncapillary hypercellularity could benefit from immunosuppressive therapy. Mesangial hypercellularity and tubular atrophy and interstitial fibrosis were independent factors of inefficiency of renin-angiotensin system blockade alone. Crescents were not significant in predicting prognosis or in therapeutic efficacy.
The Oxford classification may aid in predicting prognosis and providing a therapeutic strategy in Chinese patients with IgAN.
Preview · Article · Aug 2011 · Clinical Journal of the American Society of Nephrology
[Show abstract][Hide abstract] ABSTRACT: To explore whether the analyses of urine sediment spectrum contribute to the diagnosis of crescentic nephritis and whether special cells in urine could be a biomarker for the early stage crescentic nephritis.
Thirty-five patients diagnosed as crescentic nephritis with renal biopsy were recruited. The phase-contrast microscope was used to observe the early morning urine and offer comprehensive descriptions of urine sediment spectrum. And podocalyxin antibody was utilized to detect podocytes in urine and renal specimens by immunohistochemistry.
Marked hematuria and casts were present in the urine of crescentic nephritis and "special cells" appeared in over 50% subjects. The detection rates of "special cells" were 75%, 41% and 0 respectively in early, middle and later stages of crescentic nephritis. Podocytes were identified in the urine of 8/9 subjects.
The urine sediment spectrum contributes to the diagnosis of crescentic nephritis. And special cells in urine are helpful to gauge the stage of crescentic nephritis.
No preview · Article · Jul 2010 · Zhonghua yi xue za zhi
[Show abstract][Hide abstract] ABSTRACT: To investigate whether combination of urine sediment and urine protein can predict the renal pathological changes.
We prepared 146 specimens of routine fresh fasting morning urine. Sediment analysis was performed with phase-contrast microscopy and 24-hour urine protein was measured. Both urine protein and sediment data were integrated to form three urine analysis groups. Urine group I: proteinuria, hematuira, urine white blood cells, red/white cell casts. Urine group II: proteinuria, few cell hyaline/fine granular casts. Urine group III: minor proteinuira, epithelial cells of tubule, granular/cell casts. The renal pathological lesions were predicted before and then confirmed by renal biopsy. Statistical analyses were performed using kappa test, chi-square test, and significance was accepted at P<0.05.
After renal biopsy, we identified 95 cases of glomerular lesion with proliferation, 46 cases of glomerular disease without obvious proliferation and 5 cases of tubular interstitial lesion. According to the sediment analysis, only 67 cases (46%) could be attributed to urine group I. When combined with urine protein, we could pick out another 75 cases from urine groups I and II, and 8 cases from urine group III. The combined urine analysis could predict glomerular disease (77.7%).
Clinically we can take advantage of the combined urine analysis to predict the pathological lesion of kidney disease, which is especially suitable for primary care doctor, who can not perform renal biopsy.
No preview · Article · Apr 2010 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
[Show abstract][Hide abstract] ABSTRACT: Uteroglobin is a multifunctional protein. Both uteroglobin gene knockout and antisense transgenic mouse models developed the pathological and clinical features of IgA nephropathy. Uteroglobin G38A polymorphism has been reported to be associated with the progression of IgA nephropathy in some Caucasian and Asian populations, but there are no documents on Chinese population. The present report was to investigate the associations of uteroglobin G38A polymorphism with the development and progression of IgA nephropathy in Chinese patients.
Three hundred patients with biopsy proven IgA nephropathy were identified from Renal Disease database. Ninety-three patients had been followed-up for 2-6 years. 145 healthy donors served as normal controls. Genomic DNAs were extracted from peripheral blood leucocytes. The uteroglobin G38A polymorphism was determined by PCR-RFLP. Uteroglobin G38A genotype and allele frequency were compared between patients with IgA nephropathy and normal controls. In addition, associations of G38A polymorphism with blood pressure, hematuria, proteinuria, pathological lesions and prognosis of renal function were analyzed in patients with IgA nephropathy.
Distribution of uteroglobin G38A polymorphism in patients with IgA nephropathy (38AA: 13.2%; 38AG: 57.6%; 38GG: 30.2%) and normal controls (38AA: 18.2%; 38AG: 60%; 38GG: 21.8%; P > 0.05) showed no difference. But patients with the 38AA genotype showed a higher odds ratio for progression of renal function (OR = 2.37, 95% CI = 1.12-5.01) as compared to patients with the 38AG/GG genotype.
Uteroglobin G38A polymorphism had no association with the development of IgA nephropathy, but the homogeneous 38AA genotype maybe one of the genetic markers for disease progression in Chinese IgA nephropathy.
No preview · Article · Feb 2004 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]
[Show abstract][Hide abstract] ABSTRACT: To analyze the mutation of apolipoprotein E (apoE) gene so as to investigate the pathogenesis of lipoprotein glomerulopathy (LPG).
Restriction fragment length polymorphism methods was used to analyze the apoE genotypes of three Chinese patients with LPG and 3 of their relatives. Automated DNA sequencing was performed upon their apoE genes.
A 9-bp deletion in exon 4 of apoE, resulting in a 3-amino acid deletion (residues 142-144-0) was identified.
A 3-amino acid deletion of apoE has been discovered which is associated with LPG.
No preview · Article · Jun 2003 · Zhonghua yi xue za zhi