Xiao-Nong Chen

Changing spectrum of biopsy-proven primary glomerular diseases over the past 15 years: a single-center study in China.

The prevalence of chronic kidney disease (CKD) is reported to be 10.8-11.8% of the Chinese population. With economic development and longer life expectancy, the spectrum of CKD etiology has kept changing. Primary glomerular diseases (PGD) are still the most common renal diseases in China. To investigate the changing pattern of PGD in China, we retrospectively analyzed consecutive native renal biopsies performed in our hospital from 1997 to 2011. The patients were grouped according to a 3-year interval, 1997-1999 (period 1), 2000-2002 (period 2), 2003-2005 (period 3), 2006-2008 (period 4), 2009-2011 (period 5), and divided into three age groups (<20, 20-59, and ≥60 years old). 8,909 qualified cases were enrolled in this study. Among 8,909 specimens, 6,337 (71.13%) were diagnosed as PGD, while this prevalence decreased significantly from 77.61% in 1997-1999 to 66.73% in 2006-2008. IgA nephropathy (IgAN) was the most common PGD (36.66%), without any significant difference in the 5 periods (p = 0.185). IgAN was the most common PGD both in patients between the 20- to 59-year-old group (45.58%) and <20-year-old group (19.29%) as well. Membranous nephropathy (MN) was the most frequently found PGD in patients at age ≥60 years (39.64%). The frequency of MN was increased significantly from 6.48% in 1997-1999 to 22.79% in 2009-2011 (p < 0.001). The proportion of elderly patients increased significantly from 3.18% in 1997-1999 to 15.21% in 2009-2011 (p < 0.001). The prevalence of endocapillary proliferative glomerulonephritis (EnPGN) has decreased since 1997. PGD has remained the most common renal disease in China, although with a descending trend. The spectrum of PGD is different in different age groups. The frequency of EnPGN has decreased significantly, while that of MN has increased significantly.

Analyzing fatal cases of Chinese patients with primary antineutrophil cytoplasmic antibodies-associated renal vasculitis: a 10-year retrospective study.

Background/Aims: Primary antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) used to have poor prognosis, and renal involvement is its most common manifestation. Few studies have been published focusing on AASV patients with poor prognosis. Methods: From 1997 to 2006, 101 patients with ANCA-associated renal vasculitis (70 microscopic polyangiitis, MPA; 14 Wegener’s granulomatosis, WG; 3 Churg-Strauss syndrome, CSS; 14 renal limited vasculitis, RLV) were diagnosed in Shanghai Ruijin Hospital and 26 deaths were recorded among them. Patients’ data were retrospectively analyzed. Results: Patients with WG, MPA and RLV made up for 23.1% (6/26), 65.4% (17/26) and 11.5% (3/26) of all deaths. No deaths were observed among CSS patients. Infection alone accounted for 13 deaths. Infection together with pulmonary involvement of active vasculitis accounted for 3. Organ-specific involvement of active vasculitis alone caused 8 deaths. Others died of acute myocardial infarction or gastric carcinoma. Compared with patients who survived, nonsurvivors had more severe renal insufficiency and older age (p < 0.01). There was no significant difference regarding clinical presentation at diagnosis and cause of death between patients who survived first remission-induction treatment and those who did not. Infection remained the major cause of death. Conclusion: Infection is the major cause of death in patients with ANCA-associated renal vasculitis, and treatment response might not correlate to severity of disease in patients with poor prognosis. Rational use of immunosuppressants could improve the prognosis.

Propylthiouracil-induced Antineutrophil Cytoplasmic Antibody (ANCA)-associated Renal Vasculitis Versus Primary ANCA-associated Renal Vasculitis: A Comparative Study

Objective. Renal involvement is frequently present in primary antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) as well as propylthiouracil (PTU)-induced AAV. We analyzed the characteristics of patients with PTU-induced AAV with renal involvement and investigated the differences of the 2 diseases. Methods. Thirty-six patients with PTU-induced AAV, diagnosed from 1997 to 2010, were enrolled for study. Their data were compared with those of 174 patients with primary AAV diagnosed at the same time. Renal involvement was present in all patients. Results. There was a prominent proportion of young women with PTU-induced AAV (p < 0.01). They had lower levels of proteinuria and serum creatinine and higher estimated glomerular filtration rate (p < 0.01, p < 0.01, and p < 0.01, respectively). Clinical immunological abnormalities were less severe in patients with PTU-induced AAV. Patients with PTU-induced AAV had less organ involvement and lower Birmingham Vasculitis Assessment Score than patients with primary AAV (p < 0.01). Renal biopsies showed a lower proportion of glomeruli with crescents (p < 0.01). Interstitial inflammation was less severe in patients with PTU-induced AAV (p < 0.05). Similarly, interstitial fibrosis and tubular atrophy were less severe in patients with PTU-induced AAV (p < 0.01, p < 0.05, respectively). Renal survival and total survival were better in patients with PTU-associated vasculitis (p < 0.05, p = 0.01). Conclusion. Clinical and histopathological abnormalities were less severe in patients with PTU-induced AAV and most of them had a good prognosis.

Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain

BACKGROUNDnAlthough electroacupuncture (EA) is effective in the relief of neuropathic pain, the underlying mechanisms remain unclear. Previous studies have reported immunomodulatory effects of EA in rats. Since excessive release of interferon-γ (IFN-γ) after nerve injury transforms quiescent spinal microglia into an activated state with more neuropathic pain, associated with purinergic receptor P2X4 expression, it is possible that EA may mediate its analgesic effect by attenuating IFN-γ release and subsequent generation of P2X4R(+) microglia.nnnMETHODSnMale rats underwent chronic constriction injury (CCI) or IFN-γ intrathecal injection and von Frey tests were performed to evaluate the effect of EA on pain thresholds. Spinal IFN-γ and P2X4R expression levels were measured by immunohistochemistry, real-time PCR, enzyme immunoassay, and/or western blots. In vitro primary cultures of microglia were used to examine IFN-γ activation of P2X4R(+) cells.nnnRESULTSnIn CCI rats, EA treatment significantly increased paw withdrawal threshold relative to control. IFN-γ facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA also down-regulated both P2X4R and IFN-γ expression in the spinal cord after CCI. However, EA did not exert the same analgesic effect after intrathecal IFN-γ injection.nnnCONCLUSIONSnEA ameliorated tactile allodynia after peripheral nerve injury by down-regulating excessive expression of IFN-γ in the spinal cord and subsequently reducing expression of P2X4R.

Histopathological Classification and Renal Outcome in Patients with Antineutrophil Cytoplasmic Antibodies-associated Renal Vasculitis: A Study of 186 Patients and Metaanalysis

Objective. Renal vasculitis is one of the most common manifestations of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) and renal histology is a key predictor of the outcome. A new histopathologic classification was proposed and validated, but the results are still debated. Methods. We performed a retrospective analysis to validate the histopathologic classification and performed a metaanalysis to evaluate its predictive value. There were 186 patients with ANCA-associated renal vasculitis diagnosed at Ruijin Hospital who were enrolled in the retrospective study. The metaanalysis considered the data for 1601 patients. Results. In our retrospective study, patients with focal class had the best renal outcome while patients with mixed class had the worst (p < 0.001). Metaanalysis showed that patients with focal class had better renal outcome than did those with crescentic class [risk ratio (RR) 0.23, 95% CI 0.16–0.34, p < 0.00001], with no evidence of heterogeneity (I2 = 0%, p = 0.96). Patients with crescentic class had better renal outcome than did those with sclerotic class (RR 0.52, 95% CI 0.41–0.64, p < 0.00001), with no evidence of heterogeneity (I2 = 2%, p = 0.43). We did not find statistical significance regarding renal outcome between mixed and crescentic classes (RR 1.14, 95% CI 0.91–1.43, p = 0.27), with no evidence of heterogeneity (I2 = 23%, p = 0.19). The retrospective study showed that lung and upper respiratory tract involvement were the most common extrarenal manifestations. Conclusion. We demonstrated the clinical utility of histopathologic classification in determining renal outcome in patients with AAV. Metaanalysis showed that patients with focal class had the best outcome while sclerotic class had the worst.

ACTN4 gene mutations and single nucleotide polymorphisms in idiopathic focal segmental glomerulosclerosis.

Aim: To investigate the association between mutations or single nucleotide polymorphisms (SNPs) of the gene ACTN4 in Chinese patients with idiopathic focal segmental glomerulosclerosis (FSGS). Materials and Methods: Genomic DNA of 82 Chinese idiopathic FSGS patients and 70 healthy people were used to analyze ACTN4 gene mutations by polymerase chain reaction, direct sequencing and GenBank matching. Hair follicle DNA of novel mutated patients’ parents were sequenced and α-actinin-4 expression in patients’ kidney was examined by immunofluorescence. For SNPs, after the Hardy-Weinberg equilibrium test, allele association and the frequencies of genotypes were analyzed, followed by association analysis between genotypes and clinical diagnosis. Results: We found a heterozygous candidate mutation 184T>A (S62T) in 1 patient and a 5′ UTR candidate mutation 1-34C>T in another patient. Both patients had non-nephrotic syndrome FSGS with reduced kidney α-actinin-4 expression. Promoter activity analysis suggests that the 1-34C>T candidate mutation may affect the transcriptional regulation of ACTN4 gene. Additionally, 6 novel silent variants and 2 novel SNPs were also found in this study. Novel SNP 484 + 87C>G had a significant association with the level of urine protein excretion in these idiopathic FSGS patients. Conclusions: Our data suggest that mutations and SNP of ACTN4 gene may contribute to be associated with Chinese idiopathic FSGS.

Clinicopathological Characteristics and Outcome of Chinese Patients with Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome: A 9-Year Retrospective Study

Background: The pathogenesis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is unclear and the prognosis is poor. Few studies have been published focusing on Chinese patients with TTP-HUS. We performed a retrospective study on the clinical characteristics and outcome of Chinese patients with TTP-HUS. Method: Patients with TTP-HUS, admitted to our hospital from 1998 to 2006, were retrospectively analyzed. Results: There were 26 females and 6 males in our study. Fifteen patients had systemic lupus erythematosus (SLE)-associated TTP-HUS; 2 had pregnancy-associated TTP-HUS; 1 had antiphospholipid syndrome-associated TTP-HUS; 2 had drug-associated TTP-HUS; 4 had malignant angionephrosclerosis- associated TTP-HUS; 3 had vasculitis-associated TTP-HUS, and the remaining 5 had idiopathic TTP-HUS. Twenty-six patients had acute kidney injury and 21 had nephrotic syndrome. Hypertension was found in 31 patients. For the treatment, 15 patients had plasmapheresis, 12 had continuous veno-venous hemodiafiltration and 14 had hemodialysis. Eighteen patients were treated with intravenous immunoglobulin. Corticosteroids were used in patients with idiopathic TTP-HUS. For the patients with SLE-associated TTP-HUS, corticosteroids and immunosuppressant were used. Outcome was poor: 6 patients died; 17 recovered from renal insufficiency; 5 progressed to chronic renal failure, and 4 were dependent on hemodialysis. Conclusions: Most of our patients had secondary TTP-HUS. SLE-associated TTP-HUS is the most common form of TTP-HUS. Early diagnosis and treatment can improve prognosis. An immunosuppressant together with corticosteroids could improve prognosis in some patients.

One-Year Survival and Renal Function Recovery of Acute Kidney Injury Patients with Chronic Heart Failure

Objective: To describe and analyze the clinical characteristics of acute kidney injury (AKI) patients with preexisting chronic heart failure (CHF) and to identify the prognostic factors of the 1-year outcome. Methods: A total of 120 patients with preexisting CHF who developed AKI between January 2005 and December 2010 were enrolled. CHF was diagnosed according to the European Society of Cardiology guidelines, and AKI was diagnosed using the RIFLE criteria. Clinical characteristics were recorded, and nonrecovery from kidney dysfunction as well as mortality were analyzed. Results: The median age of the patients was 70 years, and 58.33% were male. 60% of the patients had an advanced AKI stage (‘failure) and 90% were classified as NYHA class III/IV. The 1-year mortality rate was 35%. 25.83% of the patients progressed to end-stage renal disease after 1 year. Hypertension, anemia, coronary atherosclerotic heart disease and chronic kidney disease were common comorbidities. Multiple organ dysfunction syndrome (MODS; OR, 35.950; 95% CI, 4.972-259.952), arrhythmia (OR, 13.461; 95% CI, 2.379-76.161), anemia (OR, 6.176; 95% CI, 1.172-32.544) and RIFLE category (OR, 5.353; 95% CI, 1.436-19.952) were identified as risk factors of 1-year mortality. For 1-year nonrecovery from kidney dysfunction, MODS (OR, 8.884; 95% CI, 2.535-31.135) and acute heart failure (OR, 3.281; 95% CI, 1.026-10.491) were independent risk factors. Conclusion: AKI patients with preexisting CHF were mainly elderly patients who had an advanced AKI stage and NYHA classification. Their 1-year mortality and nonrecovery from kidney dysfunction rates were high. Identifying risk factors may help to improve their outcome.

Re-Evaluation of the Classification System for Membranoproliferative Glomerulonephritis

In recent years, significant advances have been made in understanding the pathogenesis and etiology of membranoproliferative glomerulonephritis (MPGN). A new classification system based on pathological immunofluorescence findings has been proposed to replace the traditional clinical classification system in order to better identify the underlying causes of MPGN and to provide guidance for more individualized treatment. We conducted a retrospective survey of the MPGN patients treated in our hospital from 2000 to 2012 and report here the validation of this new classification system in this cohort. A total of 34 patients were diagnosed with MPGN, including 25 males and 9 females. There were 3 cases of secondary MPGN, including 1 case due to monoclonal gammopathy of undetermined significance (MGUS) and 2 cases related to hepatitis B virus (HBV) infection. Clinical presentations included nephrotic syndrome (76.5%), microscopic hematuria (79.4%), hypocomplementemia (58.8%), renal insufficiency (82.4%), hypertension (100%), and peripheral edema (100%). All patients were treated with prednisone and immunosuppressive agents, mainly cyclophosphamide. During follow-up (median 6 months, range 3-47 months), 4 patients were lost to follow-up and 2 patients progressed to end-stage renal disease. In Western countries the main cause of secondary MPGN was hepatitis C virus or HBV infection, here however we report 2 cases related to HBV infection. MGUS-associated MPGN was less frequent in the Chinese cohort. Future studies should be designed to evaluate the association of the new classification system and clinical outcomes of MPGN.

Evaluation of Anemia and Serum iPTH, Calcium, and Phosphorus in Patients with Primary Glomerulonephritis

Glomerulonephritis (GN) remains a major cause of morbidity and mortality in chronic kidney disease (CKD). Our study aimed to investigate the prevalence of anemia, abnormal serum intact parathyroid hormone (iPTH), calcium, and phosphorus in a Chinese patient population with primary GN. Medical histories and laboratory test results were collected from 2,924 patients with primary GN hospitalized in Ruijin Hospital of Shanghai between January 2003 and August 2009. The leading cause of CKD was primary glomerular diseases, which were responsible for up to 53.5% of all cases. IgA nephropathy was the most common cause, accounting for 38.7%, followed by focal segmental glomerulosclerosis (FSGS). The anemia rate of GN patients in early stages of CKD (stages 1-2 and 3) was 16-36%, and rapidly accelerated to 65.8 and 80.2% in advanced CKD stage 4 and stage 5, respectively. There was no significant decline observed in the level of serum calcium in patients with CKD stages 1-4 (p > 0.05). However, in patients with CKD stage 5 the prevalence of hypocalcaemia increased significantly (13.7%, p = 0.000). The prevalence of hyperphosphatemia did not significantly increase in patients with CKD stages 1-3 (p < 0.05), but was much higher in patients with CKD stages 4 and 5 (p = 0.001 and p = 0.021, respectively) and showed a negative correlation with renal function. Serum iPTH levels did not increase significantly in GN patients with CKD stages 1-2. The median iPTH levels were 54.7, 88.6, and 289.2 pg/ml (p = 0.000) for CKD stages 3-5, respectively, all of which showed negative correlation with renal function. The proportion of vitamin D insufficiency and deficiency increased to 29.3 and 11.2%, respectively, as the glomerular filtration rate fell below 15 ml/min/1.73 m(2). Primary glomerular disease remains the major cause of CKD in China, and complications such as anemia and metabolic bone disease are frequently present in GN patients.