Comparative Analysis of Determinants and Outcome of Early and Late Acute Antibody Mediated Rejection (ABMR).

Introduction: Antibody-mediated rejection (ABMR) is one of the major determinants of graft survival. Although diagnostic precision and treatment options have improved, response to therapy and graft survival has not improved very significantly. The phenotypes of early and late acute ABMR differ in many ways. In this study, we assessed the clinical characteristics, response to therapy, DSA positivity, and outcomes of early and late ABMR. Methods: During the study period, 69 patients with acute ABMR diagnosed on renal graft histopathology were included with a median follow-up of 10 months after rejection. Recipients were stratified into early acute ABMR (<3 months of transplant; n = 29) and late acute ABMR (>3 months of transplant; n = 40). Graft survival, patient survival, response to therapy, and doubling of serum creatinine were assessed and compared between the two groups. Results: Baseline characteristics and immunosuppression protocols were comparable between the early and late ABMR groups. Late acute ABMR had an increased risk of doubling of serum creatinine than the early ABMR group (P = 0.002). Graft and patient survival were not statistically different between the two groups. Response to therapy was inferior in the late acute ABMR group (P = 0.00). Pretransplant DSA was present in 27.6% in the early ABMR group. Late acute ABMR was frequently associated with nonadherence or suboptimal immunosuppression and low DSA positivity (15%). Infections such as CMV, bacterial, and fungal infections were similar in the earlier and late ABMR groups. Conclusion: Late acute ABMR group had a poor response to anti-rejection therapy and also an increased risk of doubling of serum creatinine compared to the early acute ABMR group. There was also a tendency toward increased graft loss in late acute ABMR patients. Late acute ABMR patients are more frequently associated with nonadherence/suboptimal immunosuppression. There was also a low incidence of anti-HLA DSA positivity in late ABMR.

One-Year Outcomes with Use of Anti-T-Lymphocyte Globulin in Patients Undergoing Kidney Transplantation: Results from a Prospective, Multicentric, Observational Study from India.

INTRODUCTION: Large-scale Indian data on the use of anti-T-lymphocyte globulin (ATLG) (Grafalon®) as induction therapy in kidney transplantation (KT) patients is lacking. The aim of this study was to determine the 1-year patient and graft survival outcomes with the use of ATLG as induction regimen in KT. METHODS: In a prospective, multicentric, observational study, adult patients who underwent ABO-compatible KT and had received ATLG as a part of induction were included in the study. The primary outcome measure was overall survival and death-censored graft survival at 12 months. The primary safety outcome was assessed by development of infectious complications and graft rejection. RESULTS: In total, 359 patients were included in this study. The mean age was 42.77 ± 12.30 years and 83% were male. The average ATLG dose per patient was 6.2 ± 2.2 mg/kg whereas average cumulative dose per patient was 389.6 ± 149.8 mg. The rate of graft dysfunction was 13.4% of patients and 6.7% had biopsy-proven acute rejection (BPAR). There were a total of 12 (3.3%) deaths and one graft loss. Overall survival and death-censored graft survival at 12 months were 96.65% and 99.44%, respectively. The rate of infections was 13.6% with urinary tract infections being most common. CONCLUSION: ATLG at an average dose of 6 mg/kg is an effective and safe induction regimen immunosuppressant for ABO-compatible KT with favourable impact on survival and graft function in Indian patients.

Anatomical and Visual Outcomes of Scleral Buckling Surgery in Rhegmatogenous Retinal Detachment.

PURPOSE: The aim of this study is to evaluate the short anatomical and visual outcomes of scleral buckling surgery in relation to the pattern of presentation of rhegmatogenous retinal detachment (RRD) in the presence of different situations and risk factors. METHODS: A total of 206 eyes of 203 patients who underwent scleral buckling surgery for RRD were evaluated in this retrospective study. Information retrieved included patient demographics, duration of symptoms, and presenting vision, lens status, site of a retinal break, extent of retinal detachment, the involvement of the fellow eye, macular involvement, presence of lattice degeneration, and associated refractive errors. Postoperative retinal reattachment, postoperative visual acuity, the need for further surgical intervention, intraoperative, and postoperative complications were also evaluated. Proportions and percentages were used to analyze data. RESULTS: Primary anatomical reattachment was seen in 172 eyes (83.5%) after the complete resolution of the tamponade used. The mean best-corrected visual acuity improved from 2.81 logarithms of the minimum angle of resolution (LogMar) preoperatively to 1.21 LogMar postoperatively, the most important factors that appeared statistically significantly affecting the anatomic and visual outcome were the duration of macular detachment (P = 0.036), the status of the lens; phakic eyes gave better visual outcome than aphakic and pseudophakic eyes (P < 0.05). CONCLUSION: Scleral buckling procedure showed high structural and visual success rates, improvement of visual acuity was found to correlate well with the shorter duration of macular detachment and pseudophakic eyes. We believe that scleral buckling, when done appropriately in the appropriate cases, gives the maximum visual outcome with the least cost and need for consecutive procedures.

Co-Administration of Soluble Fibres and Lactobacillus casei NCDC19 Fermented Milk Prevents Adiposity and Insulin Resistance Via Modulation of Lipid Mobilization Genes in Diet-Induced Obese Mice.

BACKGROUND: Numerous reports explaining the beneficial health effects of soluble fibres and probiotics on lifestyle disorders have been published. However, a little information is available on coadministration of soluble fibres such as gum acacia & inulin and probiotic lactobacilli. Therefore, in the present study, we have evaluated the synergistic effects of soluble fibres and probiotic fermented milk on adiposity, insulin resistance and dyslipidemia in C57BL/6 mice fed high-fat and sucrose diet for 18 weeks. OBJECTIVE: To explore the synergistic effect of soluble fibres (gum acacia/inulin) and Lactobacillus casei NCDC19 fermented milk on adiposity, insulin resistance and lipid mobilization genes in dietinduced obese mice. METHODS: C57BL/6 mice were divided randomly into three groups (n = 9/group) according to their body weights. The HFS group was fed high-fat and sucrose diet, the HFS-GFM group was fed HFS diet incorporated with gum acacia (7%, w/w) along with L. casei NCDC19 fermented milk and HFSIFM group was fed HFS diet incorporated with inulin (7%, w/w) along with L. casei NCDC19 fermented milk. RESULTS: At the end of the experiment, final body weight, epididymal fat (E.fat) weight, and adipocyte size were found to be lower in groups received either gum acacia or inulin in combination with L. casei NCDC19 fermented milk (HFS-GFM or HFS-IFM). Also, fasting blood glucose, serum insulin, triglycerides, and VLDL-cholesterol levels were decreased significantly in both HFS-GFM and HFSIFM fed groups. Furthermore, relative mRNA expression of genes (cpt1, foxa2, pgc1ß, and pparα) related to fatty acid oxidation enhanced significantly in the liver. In E.fat pad, expression of adiponectin was upregulated, whereas, leptin expression was reduced considerably. Also, expression of fasting-induced adipose factor enhanced significantly in the distal ileum of mice in HFS-GFM and HFS-IFM groups. CONCLUSION: Overall, we demonstrate that co-administration of soluble fibres viz. gum acacia, inulin and L. casei NCDC19 fermented milk exhibited the anti-adiposity effects, improved insulin sensitivity and dyslipidemia in mice via modulation of lipid mobilization genes.

Vitamin D Receptor Activity, Vitamin D Status, and Development of De-novo Donor-specific Antibody after Renal Transplantation.

INTRODUCTION: Vitamin D has immunomodulatory properties and could have a role in allograft outcome. METHODS: Fifty-two chronic kidney disease patients going for transplantation were studied for vitamin-D receptor (VDR) activity, 25(OH)D, estimated glomerular filtration rate (e-GFR), and de-novo donor-specific antibody (d-DSA). RESULTS: Vitamin D deficiency was seen in 25% of recipients before transplant (26.09 ± 12.19 ng/ml), in 48.1% at 6 months posttransplant (23.36 ± 15.11 ng/ml). VDR activity before the transplant was 15.41 ± 31.41 ng/ml, which was similar to control group (13.24 ± 9.78 ng/ml), and after transplantation showed an increase at 3 months to 21.91 ± 38.80 ng/ml and at 6 months to 26.03 ± 53.90 ng/ml. d-DSA developed in 27.3% and 6.7% patients of vitamin D-deficient patients (levels <31 ng/ml) and non-deficient (levels ≥20 ng/ml) patients respectively (P < 0.042). Low VDR activity at 3 months posttransplant was associated with significantly higher d-DSA positivity (33.3%) as compared to the group with normal VDR activity where d-DSA developed only in 5.9% of patients (P < 0.009). Patients with vitamin D levels <20 ng/ml and the group with low VDR activity at 3 months had significantly less e-GFR at 1 year after transplant. CONCLUSION: d-DSA was associated with vitamin D deficiency and low VDR activity with decreased graft GFR at 12 months posttransplant.

Clinical Characteristics, Patient and Technique Survival in Elderly Patients on Peritoneal Dialysis.

The outcomes of the elderly population on peritoneal dialysis (PD) in developing countries are less known. In this study, we intended to study the clinical characteristics and patient and technique survival of elderly patients on PD. In this study, data of 148 elderly patients with end-stage renal disease who initiated PD between January 2001 and December 2015 were collected. Baseline clinical characteristics and events during the study period were recorded. Overall patient and technique survival rates of diabetic and non-diabetic elderly patients on PD were analyzed. Around 128 patients who were initiated PD during the study period were included for final analysis. The mean age of the study group was 70.3 ± 5.1 years, and 94 (80%) were males. Among these, 79 (65.8%) had diabetes. At the end of the study period, only 20 (16.6%) patients were remained on PD. Eighty-four (70%) patients died during PD and 15 (12.5%) patients were transferred to hemodialysis during the study period. The main reasons for death were cardiovascular (56.6%) and sepsis due to peritonitis (18.8%). The mean patient survival time was 38.2 ± 2.6 months. The patient survival rates were 91.2%, 45.3%, and 22.8% at 1, 3, and 5 years, respectively. Predictors of mortality were increased serum phosphorus, peritonitis episodes, urine output <400 mL, and ultrafiltration <1000 mL/day at beginning of PD. The mean technique survival time was 92.0 ± 5.1 months. Technique survival rates at 1, 3, and 5 years were 94.8%, 85.3%, and 71.7%, respectively. None of the factors was found to be predictive of technique survival. We found no significant difference between diabetic and non-diabetic patients in terms of technique and patient survival. Mortality was higher in elderly patients on PD. Factors affecting mortality in elderly patients on PD are low urine output, low ultrafiltration at beginning of PD, high serum phosphorus, and presence of peritonitis episodes. Patient and technique survival rates were comparable between diabetic and non-diabetic elderly patients on PD.

Daclatasvir and reduced-dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min.

AIM: Sofosbuvir is a key agent for HCV treatment. It is not recommended for patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 mL/min. We report real-life experience of treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half-daily dose of sofosbuvir. METHODS: Adults patients who (i) had eGFR<30 mL/min and detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA based regimens were included. All patients were treated with daily doses of daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12 weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or on immunosuppressive drugs. The end-points of the study were: (i) 12 weeks of follow-up after treatment completion, (ii) treatment discontinuation, or (iii) death or loss to follow-up. RESULTS: Thirty-six (88%) among 41 included patients (median [range] age: 48 [19-75] years; 25 [61%] male; genotype 1/3/4 were 17/ 22/2; cirrhosis 5) completed the treatment, two discontinued and three died during treatment. On an intention-to-treat basis, HCV RNA were undetectable at 4 weeks of treatment, treatment completion and after 12 weeks of follow-up in 40/41 (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had a relapse. CONCLUSIONS: Daclatasvir and half-daily dose of sofosbuvir was effective against genotype 1 and 3 HCV infection in patients with eGFR <30 mL/min. This combination could be a pangenotypic treatment option for such patients.

Procalcitonin as a diagnostic biomarker of sepsis: A tertiary care centre experience.

INTRODUCTION: Despite the advancement in diagnostic modalities of sepsis, it is still a leading cause of morbidity and mortality. Differentiation between sepsis and non-infectious disease states remains a diagnostic challenge. Procalcitonin (PCT) is useful for the diagnosis of sepsis but it varies in cut-off ranges at different clinical settings. The aim of this study was to correlate serum PCT levels with cultures and to evaluate the best cut-off values with high sensitivity and specificity for PCT. METHODOLOGY: This prospective study included 305 patients from different medical wards; the patients were classified into group I: controls (n=46), group II: culture-negative sepsis (n=76) and group III: culture-positive sepsis (n=196). Mean p value <0.05 was considered significant. RESULTS: PCT levels were significantly higher in group II and group III as compared with group I. In group II, the best cut-off point for PCT was 1.3ng/ml with 87.30% sensitivity and 78.26% specificity (area under curve 0.86). In group III, the best cut-off value of 2.20ng/ml with 98.47% sensitivity and 89.13% specificity was found (AUC 0.96). CONCLUSION: Procalcitonin can accurately differentiate culture-negative and culture-positive sepsis from non-infectious diseases, thus making it a promising biomarker in diagnosis of bacterial sepsis.

Fmoc-phenylalanine displays antibacterial activity against Gram-positive bacteria in gel and solution phases.

In the quest for new antimicrobial materials, hydrogels of Fmoc-protected peptides and amino acids have gained momentum due to their ease of synthesis and cost effectiveness; however, their repertoire is currently limited, and the mechanistic details of their function are not well understood. Herein, we report the antibacterial activity of the hydrogel and solution phases of Fmoc-phenylalanine (Fmoc-F) against a variety of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Fmoc-F, a small molecule hydrogelator, reduces the bacterial load both in vitro and in the skin wound infections of mice. The antibacterial activity of Fmoc-F is predominantly due to its release from the hydrogel. Fmoc-F shows surfactant-like properties with critical micelle concentration nearly equivalent to its minimum bactericidal concentration. Similar to Fmoc-F, some Fmoc-conjugated amino acids (Fmoc-AA) have also shown antibacterial effects that are linearly correlated with their surfactant properties. At low concentrations, where Fmoc-F does not form micelles, it inhibits bacterial growth by entering the cell and reducing the glutathione levels. However, at higher concentrations, Fmoc-F triggers oxidative and osmotic stress and, alters the membrane permeabilization and integrity, which kills Gram-positive bacteria. Herein, we proposed the use of the Fmoc-F hydrogel and its solution for several biomedical applications. This study will open up new avenues to enhance the repertoire of Fmoc-AA to act as antimicrobial agents and improve their structure-activity relationship.

Interplay of Gut Microbiota, Probiotics in Obesity: A Review.

BACKGROUND AND OBJECTIVE: Excess caloric intake and less energy expenditure (e.g. physical inactivity) are associated with acquired metabolic disorders due to sedentary life style. Pharmacological treatments are less effective in preventing obesity. Type of diet influences the gut microbiome alteration and it is interrelated with obesity, insulin resistance and type 2 diabetes. Modified gut microbiota by the harmful bacterial components (e.g: lipopolysaccharides) is linked with the metabolic endotoxemia (low-grade inflammation) which results in damage to the gut barrier function. Administration of probiotics (lactobacilli and bifidobacteria) as live micro-organisms or fermented products achieves proper gut environment. In addition, administration of prebiotics along with probiotics improves the body weight, abdominal fat and intestinal barrier function. METHODS: We compiled all the available literature in the present review in relation to altered gut microbiota by different type of diets, effect of probiotics on obesity and its accompanying diseases in animal and clinical studies. CONCLUSION: Studies are indicating that anti-hyperglycemic and hyperlipidemic effects of probiotics are strain dependent as well as type of animal models. To improve against metabolic disorders, probiotics, need to be administered through prebiotics and requires more clinical studies in this area.

A Randomized Clinical Trial Comparing the ELLIPTA and HandiHaler Dry Powder Inhalers in Patients With COPD: Inhaler-Specific Attributes and Overall Patient Preference.

This randomised, open-label, cross-over, placebo-containing inhaler study assessed patient preference indicators for ELLIPTA and HandiHaler dry powder inhalers in patients with COPD (NCT02786927; GSK identifier: 204983). The primary objective of this study was to assess patient preference between ELLIPTA and HandiHaler based on the number of steps needed to use the inhaler. Eligible patients ≥40 years of age with COPD were randomised 1:1 to receive their current COPD medication plus a placebo-containing ELLIPTA or HandiHaler inhaler once daily for 7 ± 2 days (treatment period 1); this was followed by a 7 ± 2-day placebo treatment with the alternative inhaler. A 5-item questionnaire assessed inhaler-related patient preferences. A total of 212 patients (mean age, 65.1 years) were enrolled at 22 US sites; 73% had a COPD duration ≥5 years. Median (range) exposure was 8 ( 5 , 13 ) days for ELLIPTA and 8 ( 1 , 16) days for HandiHaler. Significantly more patients preferred ELLIPTA to HandiHaler in terms of the number of steps to use and all secondary attributes (size, comfort of the mouthpiece, remaining doses, and ease of use of the two inhalers; all p < 0.001). Similar results were observed irrespective of the order of inhaler use. Eighteen patients (8%) reported at least one AE and two (<1%) patients reported four non-fatal SAEs; none were related to the study treatment. Patient attitude toward a particular inhaler and their experiences in using it can affect adherence to therapy, which can in turn strongly influence effectiveness of inhaled medications. This study uses a robust methodology to assess patient preference.

Impact of residual renal function on clinical outcome and quality of life in patients on peritoneal dialysis.

We studied the impact of residual renal function (RRF) on clinical outcome and quality of life in 61 patients on peritoneal dialysis (PD). They were assigned to two groups, at the time of initiation of PD, based on their estimated glomerular filtration rate (eGFR). The high RRF group had eGFR ≥5 mL/min/1.73 m[2] and the low RRF group hade GFR <5 mL/min/1.73 m[2]. All patients were followed up at regular intervals for clinical and biochemical variables. Baselines characteristics including age, sex, body mass index and cause of the kidney disease were similar in both groups. The high RRF group had a higher rate of continuous ambulatory peritoneal dialysis discontinuation. The incidence of peritonitis was higher in the low RRF group. Other infections (cellulitis, gastroenteritis, sepsis) were more common in patients with low RRF, compared to the high RRF group. The quality of life as assessed by depression score, restless leg syndrome, and sleep quality were poor in patients with reduced RRF. We found that a high RRF at the time of initiation of PD, significantly decreased the incidence of infections, depression, better nutrition, and lower levels of alkaline phosphatase; providing indirect evidence of better renal clearance of phosphorous, in those with preserved RRF.

A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices.

Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57-70%) made no errors using ELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other devices (all P⩽0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers.

FGF23 is associated with early post-transplant hypophosphataemia and normalizes faster than iPTH in living donor renal transplant recipients: a longitudinal follow-up study.

BACKGROUND: We aimed to longitudinally analyse changes in the levels of serum fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH) and associated minerals in patients undergoing renal transplantation. METHODS: Sixty-three patients with end-stage renal disease (ESRD) who underwent living donor transplantation were recruited. Serum FGF23, iPTH, uric acid, inorganic phosphorous (iP), blood urea nitrogen and serum creatinine were measured pre-transplant and at 1 (M1), 3 (M3) and 12 months (M12) post-transplantation. RESULTS: FGF23 levels were decreased at M1, M3 and M12 by 93.81, 96.74 and 97.53%, respectively. iPTH levels were decreased by 67.95, 74.95 and 84.9%, respectively. The prevalence of hyperparathyroidism at M1, M3 and M12 post-transplantation was 63.5, 42.9 and 11.1%, respectively. FGF23 and iP levels remained above the normal range in 23 (36.5%) and 17 (27%) patients at M1, 10 (15.9%) and 5 (8%) at M3 and in none at M12 post-transplantation, respectively. A multivariate regression model revealed that, pre-transplant, iP was positively associated with iPTH (P = 0.016) but not with FGF 23; however, post-transplant, iP level was negatively associated with FGF23 (P < 0.001) but not with iPTH. CONCLUSIONS: Post-transplant FGF23 levels settle faster than those of iPTH. However, 11% of patients continued to have hyperparathyroidism even after 12 months.

Real-time ultrasound-guided percutaneous renal biopsy with needle guide by nephrologists decreases post-biopsy complications.

BACKGROUND: Percutaneous renal biopsy (PRB) can result in serious complications. The study is aimed to compare the biopsy yield and complications rate of the real-time ultrasonagram (USG)-guided PRB and needle tracking with and without needle guide in two different study periods. METHODS: We compared the yield and complications of 2138 kidney biopsies performed in two different periods, 1510 biopsies during the first period from April 2004-December 2010 and 628 biopsies during second period from January 2011-March 2013. All biopsies in both periods were performed by nephrologists. Radiologists provided the real-time image without needle guide during the first period while nephrologists performed both imaging and biopsy with needle guide during the second period. RESULTS: Of all the 2138 patients, 226 (10.5%) patients developed 118 minor and 108 major complications. Only 13 (2.1%) major complications occurred in the second period and 95 (6.7%) in the first period (P < 0.001). The relative risk of developing a major complication without guide was 3.04 times greater than that of the biopsies performed with use of the guide. The mean number of glomeruli per biopsy obtained during the second period (17.98 ± 6.75) was significantly greater than that of the first period (14.14 ± 6.01) (P = 0.004). The number of passes to acquire adequate tissue (P = 0.001) and percentage of cortex on biopsy (P = 0.001) were also significantly better in the second period. The optimal observation period post biopsy is 24 h. CONCLUSIONS: Real-time USG imaging supported by needle guide device is associated with better biopsy yield and fewer complications.

Cytotoxic T-lymphocyte antigen 4 gene polymorphism influences the incidence of symptomatic human cytomegalovirus infection after renal transplantation.

BACKGROUND: The role of CTLA4 gene polymorphisms in T-cell-mediated immunity in association with human cytomegalovirus (HCMV) infection after transplantation is poorly understood. In the present study, we have made an attempt to investigate the impact of CTLA4 single nucleotide polymorphisms (SNPs) (rs231775, rs5742909, rs11571317, rs16840252, rs4553808, rs3087243) and dinucleotide (AT)n repeat polymorphism on the incidence of symptomatic HCMV infection (disease) among 270 renal allograft recipients. MATERIALS AND METHODS: Genotyping of CTLA4 SNPs was performed by a PCR, followed by a restriction fragment length polymorphism assay. The detection of the dinucleotide (AT)n repeat polymorphism was carried out by PCR-polyacrylamide gel electrophoresis. RESULTS: An almost three-fold increased risk was observed for the incidence of symptomatic HCMV infection in mutant genotype carriers of rs231775 and rs3087243 SNPs under additive and recessive models, respectively. The mutant haplotype carriers of six studied SNPs (rs231775, rs5742909, rs11571317, rs16840252, rs4553808 and rs3087243) showed an almost two-fold higher risk for symptomatic HCMV cases, whereas wild-type haplotype combinations of these six SNPs showed a protective effect. Subsequently, no correlation was observed in the promoter region SNPs of CTLA4, namely, rs5742909, rs11571317, rs16840252 and rs4553808 in symptomatic HCMV cases at the genotypic/allelic level. Survival analysis showed that the mutant genotypes of rs231775 and rs3087243 SNPs were associated with the lowest HCMV disease-free survival compared with heterozygous and wild genotypes. The crude and adjusted hazard ratios showed an almost three-fold and 2.5-fold increased risk in univariate and multivariate Cox regression models, respectively, for HCMV disease-free survival against mutant genotypes of rs231775 and rs3087243 SNPs. CTLA4 dinucleotide (AT)n repeat analysis showed that the smaller allele (102 bp) was associated with a protective effect, whereas the longer (110 and 116 bp) alleles showed a susceptible effect for symptomatic HCMV cases. CONCLUSION: These results suggested that CTLA4 variants might be involved in the clinical manifestation of HCMV diseases.

Do the outcomes of living donor renal allograft recipients differ with peritoneal dialysis and hemodialysis as a bridge renal replacement therapy?

This study was undertaken to compare the outcomes of living donor renal transplant recipients using peritoneal dialysis (PD) and hemodialysis (HD) as a bridge modality for renal replacement therapy till renal transplantation. The demographic profiles of the recipients and donors, the patients' native kidney disease (diabetic versus non-diabetic), duration on dialysis, requirement of anti-hypertensive drugs, number of blood transfusions, human leukocyte antigen (HLA) mismatch status, pre- and post-transplant infectious complications, and post-transplant outcomes of patients were compared between the two groups. The demographic features of the study patients were similar in the two groups. The duration of dialysis prior to transplant was significantly longer in the PD group than in the HD group of patients. The anti-hypertensive drug requirement was lower and the hemoglobin level and residual urine volume at the time of transplant were relatively better in the PD patients compared to the HD patients. The number of acute rejection episodes, delayed graft function, surgical complications, glomerular filtration rate at one month and at the last follow-up, were also similar in both groups. The short-term and long-term graft survival was similar in both groups of patients. The one-, two-, five-, and eight-year death-censored graft survival rates of the PD patients were 98, 95, 85, and 73%, respectively, and in the HD group of patients, they were 100, 93, 84, and 79%, respectively. The one-, two-, five-, and eight-year patient survival rates in the PD group were 97, 92, 77, and 66%, respectively, and in the HD group, they were 97, 92, 79, and 69%, respectively. Our study suggests that the outcomes of the living donor renal allograft recipients did not differ between the groups of patients who used PD or HD as renal replacement therapy prior to renal transplantation.