Gulf Cooperation Council-dialysis outcomes and practice patterns study: An overview of anemia management trends at the regional and country specific levels in the Gulf Cooperation Council countries.

The Gulf Cooperation Council-Dialysis Outcomes and Practice Patterns Study (GCC-DOPPS) marks the joining of the six Gulf region countries including Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates to the main DOPPS study in 2012. The current review is a descriptive reporting on results related to the management of anemia from these countries. Our data demonstrate consistent anemia management patterns across the GCC countries allowing the achievement of international treatment levels. Overall, the majority of hemodialysis patients were prescribed appropriate erythropoiesis-stimulating agents (ESAs) and supplemental iron, enabling the attainment of mean hemoglobin (Hb) level of 10.9 g/dL. Comparisons of the individual country profiles reveal individual differences in the choice and mode of ESA and iron administration. However, all countries displayed good compliance with guideline recommendations. The same challenges as elsewhere are faced in the GCC, with respect to optimizing Hb levels and judiciously using ESA and iron supplements. Some opportunities exist for focused efforts to fine tune inter-facility variability in anemia management based on continued data tracking. The latter is vital in enabling adopting new trends to further improve not only anemia management but also the wholesome care of dialysis patients.

T-regulatory cells in chronic rejection versus stable grafts.

OBJECTIVES: Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. MATERIALS AND METHODS: The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. RESULTS: The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. CONCLUSIONS: The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

Human leukocyte antigen G and renal allograft transplant.

OBJECTIVES: Studying immune tolerance induced by HLA-G in kidney allograft acceptance may help understanding of its mechanisms, hoping in the future to boaster it and decrease the immunosuppressive drugs given that are well known to have serious adverse effects. MATERIALS AND METHODS: The current study sought to evaluate soluble HLA-G in 3 groups: kidney transplanted patients with no rejection episodes, transplanted patients with biopsy-proven renal rejection, and healthy age-matched non transplanted individuals. Three groups were studied: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); healthy, age-matched, nontransplanted individuals as controls (n = 42). Soluble HLA-G level was measured in the serum by a quantitative sandwich enzyme linked immunosorbent assay. RESULTS: sHLAG level was significantly higher in the transplanted patients compared with the control. Prograf and not cyclosporine or Rapamune had positive effects on sHLAG levels. Patients with chronic rejection had a significant lower level of sHLAG compared with a graft stable group. No effect of donor type, infection or duration posttransplant, on sHLAG levels was found. CONCLUSIONS: The results of the current study are consistent with previous studies addressing the role of sHLAG in inducing immunotolerance postkidney transplant. The findings from the current study on the chronic rejection group, supports the on-going research of having a treatment with HLA-G/or derivate, which may constitute in the future a novel efficient antigraft rejection therapy.

Immunological aspects of biopsy-proven lupus nephritis in Bahraini patients with systemic lupus erythematosus.

Lupus nephritis (LN) is a frequent and potentially serious complication of systemic lupus erythematosus (SLE) that may influence morbidity and mortality. Immunological investigations are aiding tools to the kidney biopsy findings in early diagnosis, in addition to monitoring the effect of therapy. The aim of the present study is to highlight the role of these investigations in a group of Bahraini patients and to determine whether there is any positive association between these findings and the outcome of LN. The current study is a retrospective case-control study of randomly selected 88 SLE patients, 44 with biopsy-proven LN and 44 without, acting as controls. All renal biopsies performed during the period from 1996 to 2012 were classified according to the World Health Organization classification. Immunological investigations analyzed are: Antinuclear antibodies (ANA), anti-ds DNA, anti-ENA, anti-cardiolipin antibodies (abs) and complement components C3, C4. Human leukocyte antigen (HLA) typing class II was performed on selected cases. All patients had positive ANA (100%). A significantly high frequency of anti-Smith abs among the non-LN group (43.18%) compared with the LN group (18.18%) was found (P <0.001). On the other hand, the anti-Ro/SSA abs in the non-LN group was also found at a statistically higher frequency (20.45%) compared with that in the LN group (4.54%) (P <0.01). Anti-ds-DNA abs were found to be higher in the LN group (84.09%) compared with the non-LN group (70.45%), but the difference was not statistically significant (P = 0.082). There was a positive association of ANA positivity and low C3 and or C4 in the studied group. In our study, 88.2% of the HLA typed patients had HLADR2, DR3 or both. In conclusion, in our Arabic Bahraini SLE patients, the presence of anti-Smith, anti-Ro/SSA and anti-RNP antibodies and the absence of anti-dsDNA antibodies are independent predictive markers for renal involvement. However, more prospective studies with a larger number of patients are essential to ascertain those findings.

Risk factors and outcomes of new-onset diabetes after transplant: single-centre experience.

OBJECTIVES: We sought to study the prevalence, risk factors, and long-term prognosis of posttransplant diabetes mellitus. MATERIALS AND METHODS: We studied all patients with end-stage renal disease without diabetic nephropathy who received a kidney transplant and were followed-up at our center since 1983 (n=218; age, 44.3 ± 13.1 y). Patients with new-onset diabetes after transplant were compared to kidney transplant recipients without risk factors for diabetes mellitus. Patients with new-onset diabetes after transplant were divided into subgroups according to time of onset (early; < 90 d vs late, ≥ 90 d). RESULTS: In total, 73/218 patients (33%) developed new-onset diabetes after transplant. Patients with new-onset diabetes after transplant were significantly older (51.2 ± 11.4 vs 40.7 ± 12.5 y; P < .001) and had a tendency to have a higher body mass index (29.6 ± 8.7 vs 21.6 ± 7.8 kg/m2; P =.05) than those that did not have new-onset diabetes after transplant. In multivariate analysis, age (P < .001), hepatitis C virus infection (P < .05), family history of diabetes mellitus (P < .03), and tacrolimus use (P < .001) were independent risk factors. Five- and 10-year death censored patient survival rates were worse in those that had new-onset diabetes after transplant compared with controls (log rank, 0.04), whereas there was no difference in outcomes between the early and late subgroups. CONCLUSIONS: The prevalence of new-onset diabetes after transplant was 33%. Age, body weight at time of transplant, tacrolimus use, family history of diabetes mellitus, and hepatitis C virus infection are independent risk factors for new-onset diabetes after transplant. New-onset diabetes after transplant has a negative effect on patient survival, irrespective of the time of onset and duration of diabetes.

Why does kidney allograft fail? A long-term single-center experience.

We studied the characteristics and the predictors of survival in Bahraini renal transplant recipients with an allograft that functioned for more than 10 years. Seventy-eight patients underwent renal transplantation between 1982 and 1999. Among them, 56 patients maintained functioning allografts for more than 10 years (range 10-30 years). Characteristics of the surviving patients, data on graft survival, and determinants of outcome were obtained by reviewing all medical records. The mean age at time of renal transplantation was 33.6 ± 15.3 years. The source of the graft in 42 (75%) recipients was from living related donors with a mean age of 31.4 ± 7.7 years, and it was the first graft in 48 recipients. The primary immunosuppression regimen consisted of cyclosporine (CsA) and prednisolone. Azathioprine (AZA) was given to 52 (92.9%) recipients, while four patients received steroids and AZA only. Induction therapy was administered to 30 patients in the CsA group. Acute rejection episodes occurred in eight (14.3%) patients, of whom two experienced two episodes. During the last follow-up in January 2010, the mean serum creatinine was 118.3 ± 46.5 µmol/L. A history of cancer was noted in one patient, whereas hypertension was encountered in 54% and diabetes mellitus in 20.5%. We compared the graft functioning group with the graft failure group and found that the independent determinants of long-term graft survival included time of late acute rejection episodes and histopathologic findings of chronic allograft damage, post-transplant hypertension and serum creatinine at one year. We conclude that renal transplantation even in its earliest years and despite the associated numerous complications has provided a ten-year or more of near-normal life to patients with end-stage renal disease.

Impact of early chronic kidney disease on maternal and fetal outcomes of pregnancy.

BACKGROUND: Elevated serum creatinine is associated with higher maternal and fetal risks; however, the influence of milder degree of renal impairment diagnosed on basis on estimated glomerular filtration rate (eGFR) is less well defined. This study assesses the impact of early chronic kidney disease (CKD) utilizing eGFR in predicting adverse outcomes in women with CKD. METHODS: We analyzed outcomes of 98 pregnant women with CKD. Women with CKD stage 1 were used as control. RESULTS: Women with eGFR of 60?89 ml/min were at an increased risk for deterioration of renal function, preeclampsia, and cesarean section. The odd ratios for composite maternal complication of worsening of renal function or preeclampsia were 6.75 (95% confidence interval (CI), 1.84-24.80) in women with eGFR of 60?89. Similarly, women with an eGFR of 60?89 had a significantly increased risk for intrauterine growth restriction (38.5%), preterm birth (31.2%), and intrauterine fetal death (15.8%). The odds for composite fetal adverse outcomes were 2.91 (95% CI, 1.19-7.09) in women with eGFR of 60?89. CONCLUSIONS: Early CKD increases the risk of adverse outcomes in pregnancy. Estimated GFR ranging between 60?89 ml/min/1.73 m(2) is associated with significant maternal and fetal complications. The risk of adverse outcomes in pregnant women with early CKD can be more accurately stratified by using estimated GFR than the serum creatinine alone.

Sirolimus-based calcineurin inhibitor withdrawal immunosuppressive regimen in kidney transplantation: a single center experience.

BACKGROUND/AIM: This observational study was conducted to evaluate the safety and efficacy of the conversion from calcineurin inhibitors (CNIs) to sirolimus (SRL)-based immunosuppressive therapy in kidney transplantation. MATERIALS AND METHODS: Sixty-four kidney recipients of mean age 38.3 +/- 14.6 years were converted to SRL. The main reasons for conversion were elective in 45 (70.3%) and biopsy-proven chronic allograft nephropathy in 11 (17.2%). The primary CNI used was cyclosporine A in 51 patients. Mean time to conversion was 50.5 months. After conversion, 61 patients received mycophenolate mofetil. We evaluated the impact of conversion on renal function for 5 years post-conversion. The overall mean follow-up time was 72.8 months. RESULTS: The analysis showed significant improvement in renal function at month 3 post-conversion (P < 0.05) with stabilization thereafter. Lipid parameters and blood sugar levels were similar pre- and post-conversion. Abnormal liver function test was transient in 12.8%. Reasons for SRL discontinuation were nephrotic range proteinuria in two patients and mouth ulceration in one. We compared patients with serum creatinine <140 micromol/l and those with serum creatinine > or = 140 micromol/l, and found that serum creatinine was an independent risk factor for chronic allograft dysfunction (P = 0.02). Graft loss occurred in three patients because of cardiovascular death in two and an acute rejection episode in one. CONCLUSIONS: We concluded that conversion from CNIs to SRL is an option and of benefit without significant acute rejection episodes or chronic allograft dysfunction especially in well-selected kidney transplant recipients with good graft function.

A single-center experience of renal transplantation in elderly patients.

BACKGROUND: We retrospectively reviewed the results of renal transplantation in patients over 60 years of age at our center. MATERIAL/METHODS: A retrospective study was conducted of 212 Bahraini patients receiving renal transplants from January 1979 to December 2007. All medical records were reviewed for demographic data, graft function and survival. Patient and graft survival was compared for patients above and below the age of 60. RESULTS: Seventeen patients >60 years with a mean age of 64.1+/-3.6 years at the time of transplantation. Diabetic nephropathy (52%) was the most common causes of end-stage renal disease. Mean donor age was 26+/-6 years and most of them were unrelated (82%). Of the elderly patients, 4 died: 3 with a functioning graft, 1 within one year of transplantation. Cardiovascular causes (3 patients, 75%) were the most common cause of death. Causes of graft loss were death with a functioning graft (4) and chronic rejection (1). Cox's proportional-hazards regression analysis showed on univariate analysis that pre-transplant hypertension, diabetes mellitus and vascular surgery (CABG) before transplant significantly affected the dependent variable of graft loss. Multivariate analysis did not show these variables to be significant. Kaplan Meier patient survival curves showed statistically significant differences between study (>60 years) and control (18-59 years) patients (p=0.04) at 10 year. CONCLUSIONS: We conclude that Patients older than 60 yr of age can be transplanted safely and successfully, especially when they are properly screened for the presence of significant risk factors such as severe cardiovascular disease and diabetes.

Improvement in uremic symptoms after increasing daily dialysate volume in patients on chronic peritoneal dialysis with declining renal function.

OBJECTIVE: Patients on peritoneal dialysis (PD) can develop uremic symptoms as their residual renal function declines. In this retrospective study, we assessed the effect of increasing the dose of dialysis in patients who developed uremic symptoms. METHODS: Patients on PD who had an increase in their dialysis dose due to either the appearance of uremic symptoms or to worsening biochemical parameters were included in this study. These patients had to have been on PD for at least 6 months before and after the increase in their dialysis dose. Patients whose dialysis dose was increased after the initial Adequest (done within 2-3 months of starting PD) findings or for reasons other than underdialysis were excluded from this study. The symptoms studied in 104 patients included fatigue, anorexia, insomnia, pruritus and nausea. The presence or absence of theses symptoms was evaluated before and after the increase in the dialysis volume. Several clinical and laboratory data including the adequacy results were compared before and after the increase in dialysis dose. RESULTS: Patients were on PD for 24.6+/-16 months when dialysis dose was increased. Eighty-five (82%) of them were on continuous ambulatory peritoneal dialysis (CAPD) while the remaining were on continuous cycler peritoneal dialysis (CCPD). Fatigue was the most common symptom that led to an increase in the dialysis dose (64%). The prevalence of all the symptoms studied decreased significantly after the increase in dose of dialysis. The weekly peritoneal creatinine clearance increased from 47.35+/-0.88 to 57.34+/-1.401 (P < 0.0001) and the weekly Kt/V increased from 1.8+/-0.03 to 2.27+/-0.05 (P < 0.0001). The daily urine volume and the residual GFR decreased from 318.7+/-36.4 to 151.9+/-22.8 ml/day (P < 0.0001) and 2.05+/-0.2 to 0.82+/-0.12 ml/min (P < 0.0001) respectively during the study period. CONCLUSION: The prevalence of all uremic symptoms decreased significantly after the daily dialysate volume was increased. The improvement in symptoms despite the decline in residual function emphasizes the beneficial effect of increased dialysate volume, which produced a significantly higher peritoneal creatinine clearance and Kt/V after the change in the PD prescription.