Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease with renal involvement being one of the most frequent and serious manifestations of the disease. The aim of the study is to analyze the treatment and renal outcome of patients with lupus nephritis (LN) WHO class III and IV on cyclophosphamide (CYC). We retrospectively identified 41 patients with biopsy proven LN who was given either oral or intravenous CYC. The male: female ratio was 4:37; with a mean age of 31.7 +/- 9.8 years at presentation. 36 patients (87.8%) had LN class IV and only five patients (12.2%) with LN class III. The mean serum creatinine at presentation was 87.4 +/- 37.2 micromol/L with mean follow-up of 84 +/- 78 months. A total of 30 patients (73.2%) completed 12 courses of IV CYC and one patient (2.4%) completed three months of oral CYC. 71.0% (n = 22) had complete response (CR), 25.8% (n = 8) had partial response and 3.2% (n = 1) had no response (NR). Of the remaining 11 patients, two patients (4.9%) died during the treatment, three patients (7.3%) defaulted treatment and five patients (12.2%) are still receiving ongoing treatment. Presence of hypertension (p < 0.003) and evidence of chronicity on renal biopsy (p < 0.016) were significantly correlated with the progressive deterioration of renal function in our population. In conclusion, hypertension and evidence of chronicity on renal biopsy, proved to be risk factors for progressive renal impairment in our study population. The achieved global outcome can be considered good.
Study site: Hospital Ipoh, Ipoh, Perak, Malaysia
There were 72 pregnancies in 46 renal transplants (RTs) between 1984 and 2001, 89% from living donors, 11% cadaveric. Mean age at RT was 26.9 +/- 4.3 years and at pregnancy 30.7 +/- 4.7 years. Mean time to pregnancy after RT was 4.5 +/- 3.1 years. 54% were unplanned. 45 (63%) resulted in surviving infants, 37% delivered by Caesarean section. 35% were premature. Mean birth weight was 2.38 +/- 0.57 kg. 64% were on cyclosporine. No patient had an acute rejection during pregnancy; 38% had pre-existing hypertension. Complications include urinary infection (13%), proteinuria (15%) and preeclampsia (15%). Mean serum creatinine before pregnancy was 112.7 +/- 32.6 umol/l, 1 year post-pregnancy it was 119.4 +/- 38.7. The mean time of follow up of mothers is 4.9 +/- 3.5 years. 10 year graft survival was 83% and patient survival 94%.
We report here a case of a kidney transplant recipient in whom the ureter was initially implanted into the peritoneum. Excessive ultrafiltration volume and reversal of serum vs dialysate creatinine ratio when the patient was recommenced on continuous ambulatory peritoneal dialysis first suggested the diagnosis which was subsequently confirmed by a plain abdominal x-ray demonstrating placement of ureteric stent in the peritoneum. This rare complication was successfully corrected with surgical re-implantation of ureter into the bladder and 5 years later, the patient remains well with good graft function.
Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)<0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by McCarroll et al. (2008) in the 10 populations.
BACKGROUND: The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis.
METHODS: Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75-1 g/m(2) monthly for 6 months in addition to corticosteroids.
RESULTS: Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side-effects.
CONCLUSIONS: MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.
Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.