Wen Zhang

Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis

BACKGROUND Although the use of aggressive immunosuppression has improved both patient and renal survival of patients with lupus nephritis (LN), the optimal treatment of LN remains challenging. The objective of this study is to assess the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus compared with intravenous cyclophosphamide (IVC) as induction therapies for active lupus nephritis (ALN). METHODS In this open-label, 24-week prospective study, 60 patients with biopsy-proven ALN (Classes III, IV, V or combination) were randomly assigned to receive MMF, tacrolimus or IVC in combination with corticosteroids. The remission of proteinuria, systemic lupus erythematosus disease active index and adverse events were compared. RESULTS The response rates at 24 weeks were 70% (14/20) in the MMF group, 75% (15/20) in the tacrolimus group and 60% (12/20) in the IVC group (P>0.05). The complete remission rates were also similar in the three groups (40, 45 and 30%, respectively; P>0.05). There were more cases of infection in the IVC group (8/20) and the MMF group (8/20) than the tacrolimus group (3/20) and more hyperglycemia in the tacrolimus group (5/20) than the other two groups (2 or 3/20), but the results were not statistically significant among the three groups. Proteinuria decreased and serum albumin increased more quickly in the patients treated with tacrolimus (P=0.0051 and P=0.048). CONCLUSIONS This pilot study suggests that both MMF and tacrolimus are possible alternatives to IVC as induction therapies for ALN in Chinese patients. Tacrolimus possibly results in a faster resolution of proteinuria and hypoalbuminemia. Further studies are necessary to determine the optimal dosage and duration of the therapies.

Novel SLC12A3 Mutations in Chinese Patients with Gitelman’s Syndrome

Background: Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman’s syndrome (GS), a disorder inherited as an autosomal recessive trait. In a minority of cases, GS-like phenotypes are caused by mutations in the CLCNKB gene. Methods: We searched for SLC12A3 and CLCNKB gene mutations in 13 Chinese patients (9 males and 4 females, age 35 ± 14 years) from 8 unrelated families with the clinical and biochemical features of GS. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Results: We identified 10 mutations distributed throughout the SLC12A3 gene. Seven are novel variants, including 4 missense mutations (Gly196Val, Cys430Gly, Gly439Val and Leu571Pro), 2 deletions (1384delG and 346–353delACTGATGG) and 1 in-frame insertion (997insCys). Three mutations were recurrent, including 2 missense mutations (Thr60Met and Asp486Asn) and 1 deletion (2883–2884delAG). The homozygous or heterozygous mutation Thr60Met was found in 8 of 13 patients. There were no mutations detected in the CLCNKB gene. Conclusions: Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify.

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.

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.

Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome.

Aim:  Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic metabolic alkalosis, significant hypomagnesemia, low urinary calcium, secondary aldosteronism and normal blood pressure. GS is caused by inactivating variants in the SLC12A3 gene, which encodes the thiazide‐sensitive NaCl co‐transporter. So far, more than 100 variants have been described in the SLC12A3 gene in Gitelman syndrome.

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.

Clinical experience with nadroparin in patients undergoing dialysis for renal impairment

Dialysis procedures are life‐sustaining renal replacement therapies indicated for patients with limited or no kidney function. The formation of clots in the extracorporeal circuit during dialysis is an undesirable event. Anticoagulation is therefore routinely practiced in this context. Unfractionated heparin (UFH) is largely used in dialysis patients. However, except in patients with an elevated risk of bleeding, the 2002 European Best Practice Guidelines Expert Group on Hemodialysis recommended the use of low–molecular‐weight heparins over UFH, in view of their equal efficacy, improved safety, and easy handling. Low–molecular‐weight heparins comprise several drugs, differing in a number of pharmacological and clinical properties. This manuscript reviews the data obtained with nadroparin, a low–molecular‐weight heparin studied extensively in dialysis patients. Thus, several studies investigated the benefit of nadroparin vs. UFH, other low–molecular‐weight heparins, or citrate in patients undergoing intermittent hemodialysis. Overall, they showed that a single intravenous bolus dose of nadroparin, adjusted according to body weight, was effective and safe for maintaining the patency of the extracorporeal circuit during intermittent hemodialysis sessions lasting up to 6 hours, in both adults and children with end‐stage renal failure. In contrast to UFH, nadroparin required no laboratory monitoring of anticoagulant activity owing to the reliable anticoagulant response following its administration. Compared with UFH, nadroparin was beneficial in terms of lipid and possibly bone parameters. Nadroparin administered by a bolus dose, followed by a continuous infusion was also shown to be effective and safe in patients undergoing continuous renal replacement therapy for acute renal failure.

Analyzing Chinese patients with post-operative acute kidney injury.

Abstract Background: To investigate clinical characteristics and risk factors of Chinese patients with post-operative acute kidney injury (PO-AKI). Methods: Patients with PO-AKI in Ruijin Hospital from December 1997 to December 2005 were retrospectively studied. Results: Patients’ mean age was 62.2 ± 18.1 years. There were 111 males and 57 females. The mean serum creatinine at diagnosis was 370.41 ± 320.92 μmol/L and the mean estimated glomerular filtration rate was 33.56 ± 24.24 mL/min. For the outcome of the patients, 38 died and the mortality rate was 22.6%. There were 17 patients (10.1%) with Acute Dialysis Quality Initiative-RIFLE (risk-injury-failure-loss-end classification) phase R, 21 (12.5%) with phase I, and 130 (77.4%) with phase F. There was no significant difference in mortality regarding patients who underwent different types of surgeries. For the risk factors related to PO-AKI, acute tubular necrosis (ATN) increased relative risk of mortality PO-AKI (odds ratio = 7.089, 95% confidence interval = 2.069–24.288, p < 0.001). Multivariate regression models showed that ATN had a positive correlation with mortality of PO-AKI. Conclusions: PO-AKI is one of the most common causes of AKI in patients who underwent operations. Special attention should be paid to risk factors related to PO-AKI in order to improve prognosis.

Twenty-one novel mutations identified in the COL4A5 gene in Chinese patients with X-linked Alport’s syndrome confirmed by skin biopsy

BACKGROUND The clinical and pathological features of Alport syndrome are characterized by abnormalities in the basement membrane collagen network which are composed of the α3, α4 and α5 chains of type IV collagen and usually associated with hearing loss and ocular lesions. The predominant form (85% of AS) is inherited as X-linked mode (XLAS) caused by mutations encoding the α5 chain of type IV collagen gene, COL4A5. Different mutations in the COL4A5 gene have been reported widely, but only a few mutations were identified in Chinese patients. METHODS We studied 71 Chinese patients from 35 unrelated families with XLAS confirmed by skin biopsy. Genomic DNA was extracted from peripheral blood of all patients. All 51 exons of the COL4A5 gene were screened by direct sequencing for the probands. RESULTS A total of twenty-five identified gene mutations were considered to be pathogenic, including 1 nonsense, 1 splice-site, 1 complex rearrangement, 5 small deletions, 2 small insertions and 15 missense mutations. Twenty-one mutations have not been reported previously. CONCLUSIONS We have identified 25 pathogenic mutations in 35 Chinese families with XLAS. Skin biopsy is effective for the diagnosis of XLAS.