Predictive markers for severe hypocalcemia in dialysis patients with secondary hyperparathyroidism after near-total parathyroidectomy.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is common in dialysis patients with end-stage renal disease (ESRD). Parathyroidectomy (PTX) is an effective treatment for SHPT. Postoperative severe hypocalcemia (SH) is a common and severe complication after PTX. This study aimed to investigate the potential predictive markers of SH in dialysis ESRD patients with SHPT after near-total PTX (near-tPTX) without autotransplantation (AT). METHODS: A retrospective analysis involving 131 dialysis patients with SHPT who were treated with near-tPTX without AT between January and August 2018 was performed. Demographic characteristics (age, gender, type of dialysis modality, etc.) and perioperative laboratory parameters [serum calcium, phosphorus, alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), and bone metabolism markers] were collected and analyzed. Postoperative serum calcium level <1.875 mmol/L (7.5 mg/dL) was defined as postoperative SH. RESULTS: Among the 131 patients, 73 (55.7%) had postoperative hypocalcemia and 43 (32.8%) had postoperative SH. Univariate analysis showed that values of preoperative serum iPTH, calcium, ALP, bone-specific alkaline phosphatase (BAP), and osteocalcin (OC) were significantly different between the SH and non-SH groups. In the multivariate logistic regression model, preoperative serum ALP was an independent risk predictor of postoperative SH. The receiver operating characteristic (ROC) curve for preoperative serum ALP was 277 U/L. The sensitivity of preoperative serum ALP was 73.8% and the specificity was 63.2%. CONCLUSIONS: The incidence rates of postoperative hypocalcemia and SH in dialysis patients with SHPT after near-tPTX without AT were 55.7% and 32.8%, respectively. Preoperative serum ALP was an independent predictor for the occurrence of postoperative SH, and dialysis patients with SHPT were susceptible to postoperative SH when preoperative serum ALP level was >277 U/L. Hence, we recommend that preoperative serum ALP be utilized to complement clinical protocols for postoperative SH management of dialysis ESRD patients with SHPT after near-tPTX without AT.

HMGB1-TLR4-IL-23-IL-17A axis accelerates renal ischemia-reperfusion injury via the recruitment and migration of neutrophils.

Renal ischemia-reperfusion injury (IRI) is an important cause of setting off acute kidney injury. Neutrophil-mediated immunomodulation has a pivotal role in the evolving of IRI. The HMGB1-TLR4-IL-23-IL-17A axis gives rise to neutrophil activation. Therefore, in the study, the role of the HMGB1-TLR4-IL-23-IL-17A axis in IRI was evaluated. Cell viability, inflammation, apoptosis, oxidative stress, survival, renal function and pathology, and the activation of macrophages and neutrophils were measured. Moreover, we evaluated the acetylation, translocation, and secretion of HMGB1 as well as levels of TLR-4, IL-23, IL-17A, and neutrophil chemokines (KC, LIX, and MIP-2). In vivo, anti-HMGB1 antibody decreased the acetylation, translocation, and secretion of HMGB1, reduced the expression of TLR-4, IL-23, IL-17A, KC, LIX, and MIP-2, alleviated the activation of macrophages and neutrophils, improved the survival rate and renal dysfunction, and decreased inflammation, apoptosis, oxidative stress, and pathological injury of the kidney. However, the intervention with recombinant HMGB1(R-HMGB1) significantly abolish the above effect of anti-HMGB1 in IRI. Neutralization IL-23 or IL-17A can alleviated the neutrophils mediated renal dysfunction by suppressing inflammation, apoptosis, and oxidative stress in IRI. In vitro, we confirmed that hypoxic/deoxygenation (H/R) induces the secretion of HMGB1 though acetylation on HK-2 and HMGB1 promotes the secretion of IL-23 in a HMGB1/TLR-4-dependent manner on macrophages. Together, these results implied that the HMGB1-TLR4-IL-23-IL-17A axis regulates inflammation, oxidative stress, apoptosis, and renal injury in IRI by promoting the recruitment and migration of neutrophils.

Pioglitazone alleviates cisplatin nephrotoxicity by suppressing mitochondria-mediated apoptosis via SIRT1/p53 signalling.

Pioglitazone (PIO) attenuates cisplatin nephrotoxicity whereas the underlying mechanism remains unknown. Apoptosis is associated with mitochondrial dysfunction and SIRT1 activation can decrease cell apoptosis in cisplatin nephrotoxicity. Therefore, we explored whether the protective effect of PIO in cisplatin nephrotoxicity is achieved by suppressing mitochondria-mediated apoptosis through SIRT1/p53 signalling regulation. Cell viability, apoptosis, survival rate, renal pathology and function were examined. Moreover, we also analysed the expression of SIRT1, Acetyl-p53, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP) opening, adenosine triphosphate (ATP) and apoptosis-related protein in vivo and in vitro. Pioglitazone treatment significantly increased cell viability, promoted SIRT1-p53 interaction, upregulated Bcl-2 expression, activated SIRT1 and elevated mitochondrial ATP synthesis after cisplatin treatment. However, PIO decreased the generation of ROS, opening of mPTP, dissipation of MMP and translocation of cytochrome c after cisplatin treatment. Pioglitazone also reduced the activation of caspase-3 and caspase-9, lowered the ratio of Bax/Bcl-2, attenuated kidney pathological damage and dysfunction, down-regulated the expression of Acetyl-p53, PUMA-α and Bax and abated cell apoptosis after cisplatin treatment. The SIRT1 inhibitor, EX527, clearly reversed the protective effects of PIO. These results implied PIO attenuated cisplatin nephrotoxicity by suppressing mitochondria-mediated apoptosis through regulating SIRT1/p53 signalling.

Clinical characteristics of 31 hemodialysis patients with 2019 novel coronavirus: a retrospective study.

AIM: Novel coronavirus pneumonia (COVID-19) has become pandemic. It brings serious threat to hemodialysis (HD) patients. Therefore, we carried out a study on the clinical characteristics of HD patients with COVID-19. METHODS: We retrospectively analyzed the data of 31 HD patients with COVID-19. The clinical features of patients include epidemiology, clinical symptoms, laboratory and imaging test, treatment and prognosis. RESULTS: 61.3% were severe, and 38.7% were mild. 83.9% had a close contact history with COVID-19 patients. The average age was 62.3 years comprising of 58.1% men and 41.9% women. Ninety percent had chronic diseases except ESRD. Clinical symptoms include cough (85%), fever (43%), and shortness of breath (48.4%), etc. Complications included ARDS (25.8%), AHF (22.6%), and septic shock (16.1%), etc. 64.5% of patients had remission, and 35.5% of patients had no remission with 6.5% deaths. Compared with the baseline before infection, HD patients with COVID-19 had lower lymphocytes, albumin and glucose, and higher D-dimer, albumin, phosphorus, lactate dehydrogenase, and CRP. There was no significant correlation between the neutrophils/lymphocytes ratio and the severity of the disease. CONCLUSIONS: Compared with the reported general population, the HD patients are susceptible to COVID-19 infection, especially older men and those with other underlying diseases. Moreover, HD patients have more severe infection and inflammation with less symptoms and worse outcome. COVID-19 infection can cause dialysis patients lower immunity, stronger inflammation, malnutrition, and internal environment disorder. Neutrophils/lymphocytes ratio does not reflect the severity of the HD patients with COVID-19.

Executive Summary: Clinical Practice Guideline for Autosomal Dominant Polycystic Kidney Disease in China.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, with a prevalence of 1/2,500-1/1,000, and it affects 1.25 million people in China. ADPKD is responsible for nearly 5% of end-stage renal disease cases, which leads to a major burden on public health. In 2016, the Chinese working group developed guidelines for the diagnosis and treatment of ADPKD, which promoted the clinical management of ADPKD in China. In the last 3 years, Chinese clinicians have deepened their understanding and standardized the management of ADPKD, and several basic and clinical studies on ADPKD have been conducted. In combination with international guidelines and research results, the working group updated the ADPKD guidelines in China. This guideline includes 5 chapters: introduction, diagnosis, kidney disease progression monitoring, treatment, and family planning. We highlight the main recommendations and suggestions of the ADPKD guidelines in this summary.

Prevalence and associated factors of depressive symptoms among chronic kidney disease patients in China: Results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

OBJECTIVE: Depression is the most common mental disorder in patients with chronic kidney disease (CKD), and previous studies have found that: (a) depression can accelerate the progression of CKD; and (b) depression is an independent risk factor for hospitalization and death among patients with CKD. Therefore, the objective of the current study was to investigate the prevalence of depression in Chinese patients with CKD, and to identify variables associated with depression. METHODS: The study analyzed baseline data from a multicenter prospective cohort study of Chinese patients with chronic kidney disease (the C-STRIDE study). In all, 2995 participants in CKD stages 1 to 4 who completed a survey of depressive symptoms were included in the analyses. Depressive symptoms were assessed by the Zung Self-Rating Depression Scale (ZSDS). A ZSDS ≥50 was used as the cut-off score for the presence of depressive symptoms. Multivariable logistic regression was used to identify variables associated with depression. RESULTS: The mean estimated glomerular filtration rate (eGFR) in the study sample was 51.59±29.49 ml/min/1.73 m2. The prevalence of depressive symptoms was 37.8% and increased significantly with CKD stage. Being female, a higher level of education, a low income, a larger economic impact of disease cost, comorbid cardiovascular disease, anemia, and impaired physical ability were independently associated with depressive symptoms. CONCLUSION: Our study revealed that depressive symptoms were common among patients with CKD in China. Sociodemographic variables and the clinical characteristics of disease severity were strongly associated with depressive symptoms.

Microarray-based analysis of whole-genome DNA methylation profiling in early detection of breast cancer.

Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.

Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway.

Breast cancer is ranked as the second leading cause of cancer-related deaths among women. Accumulating evidences have revealed that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis owing to the regulation of essential pathways for tumor initiation and progression. Herein, the current study aimed to explore the regulatory mechanism of lncRNA ZFHX4-AS1 in breast cancer in relation to the Hippo signaling pathway. Initially, microarray analysis was conducted to screen out differentially expressed lncRNAs related to breast cancer. Next, the functional role of lncRNA ZFHX4-AS1 in breast cancer was determined using ectopic expression, knockdown, and reporter assay experiments. Subsequently, lncRNA ZFHX4-AS1, TAF4, TAZ, and YAP expressions were determined, followed by verification of the targeting relationship between lncRNA ZFHX4-AS1 and TAF4. Then cell proliferation, invasion, migration, cell cycle, and apoptosis were measured. Lastly, tumor growth and metastasis were detected by tumor xenograft in nude mice. LncRNA ZFHX4-AS1 was found to be highly expressed while FAT4 was poorly expressed in breast cancer tissues. FAT4 was the target gene of lncRNA ZFHX4-AS1, and lncRNA ZFHX4-AS1 silencing increased FAT4 expressions, while decreased YAP and TAZ expressions. In addition, knockdown of lncRNA ZFHX4-AS1 suppressed breast cancer cell proliferation, migration, and invasion as well as tumor growth, blocked cell cycle entry, while promoted cell apoptosis by inhibiting the Hippo signaling pathway. In conclusion, our findings reveal that lncRNA ZFHX4-AS1 silencing exerts an inhibitory effect on breast cancer development by suppressing the activation of the Hippo signaling pathway via FAT4.

Nephrotic syndrome associated with Kimura's disease: a case report and literature review.

BACKGROUND: Kimura's disease (KD) is a rare chronic inflammatory disorder with a high incidence of renal involvement. In this report, we present a case study of KD-associated nephrotic syndrome combined with minimal change disease (MCD) and acute renal tubular injury. Meanwhile, the clinical and histopathological characteristics of 26 patients with KD presenting with renal involvement were retrospectively evaluated. CASE PRESENTATION: Here, we report a case study of a 59-year-old male patient with KD confirmed by a lymph node biopsy. He developed widespread edema and decreased urine output. A palpable swollen mobile and non-tender lymph node behind the left ear was observed upon admission. A renal biopsy revealed minimal-change lesions and acute renal tubular injury. The patient received hemodialysis because of the oliguria and renal insufficiency, and an initial dose of 40 mg/d methylprednisolone and then continued treatment with 40 mg/d prednisolone. He exhibited a good clinical response to the steroid after 6 weeks of treatment. Of the other 26 patients included in the review, 13 patients presented with mesangial proliferative glomerulonephritis, 4 with membranous nephropathy, 3 with MCD, 3 with focal segmental glomerulosclerosis, 2 with IgA nephropathy and 1 with acute tubular injury. With the exception of 2 patients who progressed to end-stage renal disease and received hemodialysis, the majority of patients responded well to treatment with corticosteroids alone. CONCLUSIONS: MCD combined with acute renal tubular injury is rare in patients with KD presenting with renal involvement. Corticosteroids may be a beneficial treatment for renal injury in patients with KD.

The anti-inflammatory effects of curcumin on renal ischemia-reperfusion injury in rats.

The present study aimed to explore the protective mechanism of curcumin-precondition in renal ischemia-reperfusion (I/R) injury. Thirty male SD rats were randomly equally divided into Sham, IRI, and Curcumin groups (n = 10). The model of IRI was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. ELISA was used to examine the expression of Cr, BUN, IL-8, TNF-α, and IL-6 in the serum; RT-PCR was used to detect the mRNA level of IL-8,TNF-α, and IL-6 in the kidney; The morphology of kidney was examined by Periodic Acid-Schiff stain (PAS). The expression of JAK2, p-JAK2, STAT3, p-STAT3, p65, and p-p65 in kidney were detected by Western blotting. The result displayed that Curcumin pretreatment can significantly increase the expression of p-JAK2 and p-STAT3 and reduce the expression of Cr, BUN, IL-8, TNF-α, IL-6, and p-p65. In addition, Curcumin can attenuate the kidney pathological injury and have no effect on the expression of JAK2, STAT3, and p65. Our findings showed the protective effect of Curcumin in I/R injury is associated with suppressing NF-κB mediating inflammation by activating JAK2/STAT3 signal pathway.

Serum levels of WNT1-inducible signaling pathway protein-1 (WISP-1): a noninvasive biomarker of renal fibrosis in subjects with chronic kidney disease.

WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD). We first measured the WISP-1 expression levels using a transforming growth factor-ß (TGF-ß)-induced renal fibrosis tubular epithelial cell (TEC) model and a mouse model of obstructive nephropathy. We then evaluated the correlation between serum WISP-1 levels and fibrosis scores in biopsy-proven renal fibrosis of patients with CKD. Based on the findings from both in vivo and in vitro studies, the levels of WISP-1 and fibrotic parameters (collagen I, fibronectin and α-smooth muscle actin) were significantly increased in the fibrotic models. Consistently, patients with focal proliferative IgA nephropathy, focal segmental glomerular sclerosis and diabetic nephropathy displayed markedly elevated serum WISP-1 levels and fibrosis scores of renal biopsies compared with normal subjects and patients with minimal change disease (P<0.05). Importantly, the serum WISP-1 levels were positively correlated with fibrosis scores in the renal biopsies of these patients (r=0.475, P=0.0001). Thus, serum WISP-1 levels may be used as a potential noninvasive biomarker of renal fibrosis in patients with CKD.

Clinical Predictors of Outcome in Patients with Anti-neutrophil Cytoplasmic Autoantibody-related Renal Vasculitis: Experiences from a Single-center.

BACKGROUND: Primary anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a chronic autoimmune disease associated with multisystem dysfunction. Renal involvement is common and closely associated with outcome. The purpose of this study was to investigate the clinical determinants of mortality of patients with AAV-related renal injury in the first 2 years after diagnosis in a single West Chinese center. METHODS: Demographic and laboratory parameters of 123 consecutive patients with AAV-related renal injury diagnosed in Renal Division and Institute of Nephrology, Sichuan Provincial People's Hospital between 2004 and 2012 were collected retrospectively. All patients were followed up for 2 years after diagnosis. Survivors were compared with nonsurvivors to identify the clinical baseline variables associated with mortality. Multivariate Cox regression model was used to determine the independent predictors of mortality. RESULTS: Of the 123 patients, 46 (37.4%) died by the end of 2 years after diagnosis, with 41 (33.3%) patients dying within the first 12 months. In comparison with the survivors, Birmingham Vasculitis Activity Score (BVAS), the incidence of pulmonary hemorrhage and digestive system (DS) involvement, serum creatinine, and erythrocyte sedimentation rate were significantly higher in nonsurvivors, whereas lymphocyte counts, hemoglobin, and complement 3 (C3) were significantly lower. Renal replacement therapy was more common in nonsurvivors. High BVAS (hazard ratio [HR] = 1.058, 95% confidence interval [CI]: 1.002-1.117; P = 0.042), pulmonary hemorrhage (HR = 1.970, 95% CI: 1.033-3.757; P = 0.04), DS involvement (HR = 2.911, 95% CI: 1.212-6.911; P = 0.017), and serum creatinine >400 µmol/L (HR = 2.910, 95% CI: 1.271-6.664; P = 0.012) were independent predictors of death in patients with AAV-related renal injury. CONCLUSIONS: Patients with AAV-related renal injury have high early mortality. Those with high BVAS (particularly with pulmonary or DS involvement) and serious renal dysfunction should receive aggressive therapy and careful monitoring to reduce the occurrence of adverse events and improve prognosis.

[The correlation between NPHS2 polymorphism and IgA nephropathy in northern Chinese patients].

OBJECTIVE: To examine the polymorphism in NPHS2 gene of IgA nephropathy in northern Chinese patients and to investigate the possible association of the NPHS2 polymorphism with the development of IgA nephropathy, as well as its clinical and histologic manifestations. METHODS: The polymorphism of NPHS2 was analyzed by direct DNA sequencing in 32 northern Chinese patients with IgA nephropathy (16 with heavy proteinuria and 16 with isolated hematuria). According to preliminary results, a total of 537 IgA nephropathy patients were genotyped for the NPHS2 C357T polymorphism by PCR combined with restriction fragment length polymorphism (PCR-RFLP). We collected clinical and histologic manifestations for gene analysis in patients with IgA nephropathy, such as age, sex, urine protein excretion and so on. RESULTS: Eight NPHS2 polymorphisms (-931A > T, -601C > T, 19G > T, 171A > G, 357C > T, IVS3-21C > T, 1023C > T and 1107A > G) were identified. The preliminary results of gene sequencing showed that the frequency of 357T allele in nephrotic syndrome group was obviously lower than isolated hematuria group (0.038 vs 0.125, P < 0.05). In 537 IgA nephropathy patients with clinical and histologic data, the average urinary protein excretion in the patients with the 357CT/TT genotype was less (P = 0.023). The incidence of urinary protein of more than 3.5 g/d was significantly lower in patients with T allele and TT/CT genotype, respectively (P = 0.017 and 0.011). The logistic regression analysis indicated that, even after adjusting for the effect of hypertension and age of patients, the CT/TT genotype of NPHS2 C357T was an independent protective factor for the urinary protein excretion more than 3.5 g/d (P = 0.012, OR = 0.485, 95%CI 0.275 - 0.84). CONCLUSIONS: Eight NPHS2 polymorphisms were identified in northern Chinese IgA nephropathy patients. The frequencies of NPHS2 T allele and TT/CT genotype were the protective factors for urinary protein, especially with that of more than 3.5 g/d.

Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome.

BACKGROUND: Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake. METHODS: One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-alpha were measured and compared between Group E and 18 patients from Group C. RESULTS: The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment. CONCLUSIONS: Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.

Genetic effect of the NPHS2 gene variants on proteinuria in minimal change disease and immunoglobulin A nephropathy.

BACKGROUND: Proteinuria varies in different glomerular diseases and even the same one. Podocin, encoded by gene NPHS2, is important in maintaining the integrity of slit diaphragm structure and avoiding proteinuria. Presently, case-control association studies were performed to investigate the genetic effect of variants in NPHS2 in a mass proteinuric glomerulopathy, minimal change disease (MCD) at first, followed by further investigation in immunoglobulin A nephropathy (IgAN). METHODS: At first, 214 northern Chinese patients with MCD and 493 geographically-matched healthy controls were enrolled. Variants of the NPHS2 were screened. SNP-2 (rs3829795:C>T, c.-670C>T) and SNP-5 (rs3738423:C>T, c.288C>T) were selected as tagging single nucleotide polymorphisms (SNP) and haplotypes were reconstructed. Association was analyzed in MCD patients. Then, the identified SNP site was analyzed in IgAN patients with mild histological changes (Haas subclass I and II). RESULTS: The C allele and CC genotype frequencies at the SNP-2 site, as well as the frequency of haplotype CC, were significantly lower in MCD patients than in healthy controls. Furthermore, they were also associated with the degree of proteinuria in MCD patients. But in IgAN patients, no such association was identified. CONCLUSION: The study suggested the polymorphism and haplotype of NPHS2 gene were associated with the genetic susceptibility and also the degree of proteinuria to MCD. Proteinuria in MCD and IgAN might occur through different mechanisms.

Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy?

BACKGROUND: The deficiency of beta1,3 galactose in hinge region of IgA1 molecule played a pivotal role in pathogenesis of IgA nephropathy (IgAN). Cosmc, encoded by C1GALT1C1 gene, was indispensable to beta1,3 galactosylation of IgA1. We designed a serial study to investigate the relationship between the mutations of C1GALT1C1 gene and the genetic susceptibility to IgAN. METHODS: Nine hundred and thirty-eight subjects, including 661 patients with IgAN and 277 healthy controls were enrolled in the study. Firstly, single nucleotide polymorphisms (SNPs) in the promoter region of C1GALT1C1 gene were screened. Then the c.-347-190G>A was analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP) for further case-control association analysis. Secondly the somatic mutations of DNAs from peripheral blood B lymphocytes were detected in 15 patients and 7 normal controls. RESULTS: No significant association was observed between the different alleles or genotypes of c.-347-190G>A and IgAN. The patients with different genotypes of C1GALT1C1 gene did not significantly associate with clinical manifestations, including hematuria, proteinuria, and serum creatinine of patients with IgAN. There was no somatic mutation detected in total 202 clones of 22 individuals. CONCLUSION: The c.-347-190G>A polymorphism and the somatic mutation of encoding region of C1GALT1C1 gene were not significantly related to the genetic susceptibility to IgAN in Northern Chinese population.

[Association of NPHS1 gene polymorphism with IgA nephropathy].

OBJECTIVE: To investigate the association of the polymorphism of NPHS1, coding gene of nephrin, with the degree of proteinuria, renal function, and prognosis of IgA nephropathy (IgAN) in patients in north China. METHODS: Peripheral blood samples were collected from 532 patients with IgAN confirmed by biopsy, 285 males and 230 females, aged (31+/-11). Genomic DNA was isolated from the peripheral blood leucocytes. Polymorphism of the exon G349A of NPHS1 was detected by polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP). 138 patients were followed up for 4-99 months. The correlation between the NPHS1 polymorphism and renal function at the time of renal biopsy, and that between NPHS1 polymorphism and the prognosis were analyzed. RESULTS: The frequency of the genotype with the allele G (AG/GG) in the patients with the estimated glomerular filtration rate (eGFR)<60 mlxmin(-1)x(1.73 m2)(-1) was significantly higher than that of the patients with the eGFR>60 ml.min(-1)x(1.73 m2)(-1) (P=0.008). Even after adjusting for the effects of proteinuria, hypertension, and age, AG/GG genotype was an independent risk factor of the exacerbation of renal damage at the time of diagnosis (P=0.011), and GG genotype was an independent risk factor of the prognosis (P<0.001). CONCLUSION: G allele and AG/GG genotype are associated with the severity of renal function at the time of diagnosis the GG genotype is associated with the prognosis of IgAN patients.