Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

Evaluation of pharmacist counseling in improving knowledge, attitude, and practice in chronic kidney disease patients.

BACKGROUND: Chronic kidney disease is a public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Patient involvement forms the keystone in the management of chronic kidney disease. This study evaluated effects of pharmacist-provided counseling in dialysis patients in terms of their knowledge, attitude, and practice outcomes. METHODS: A total of 64 patients with chronic kidney disease were enrolled into the prospective, pre-post study based on the inclusion and exclusion criteria. The knowledge, attitude, and practice of patients regarding chronic kidney disease were assessed and recorded via baseline questionnaire. Case group patients were counseled regarding chronic kidney disease, their medication, diet, and lifestyle, and they were also provided with informative leaflet, whereas in the control group patients, the pharmacist did not intervene. After 1-month intervention, knowledge, attitude, and practice scores of patients of both groups were measured using the same knowledge, attitude, and practice questionnaire. Effectiveness of counseling on case group patients was evaluated by comparing the mean knowledge, attitude, and practice scores before and after counseling by paired t-test. RESULTS: Mean knowledge, attitude, and practice scores before intervention were 8.16 ± 4.378, 38.19 ± 3.217, and 6.69 ± 0.896, respectively, and these scores were changed to 13.75 ± 3.510, 38.78 ± 3.035, and 6.91 ± 0.777, respectively, after the intervention (p < 0.05). CONCLUSIONS: The pharmacist-provided counseling is effective in improving knowledge, attitude, and practice of patients toward the disease management.

Evidence for the immunosuppressive potential of calcineurin inhibitor-sparing regimens in liver transplant recipients with impaired renal function.

Patients requiring liver transplantation (LT) frequently experience renal insufficiency (RI), which affects their survival. Although calcineurin inhibitor-sparing immunosuppressive regimens (CSRs) are well known to prevent RI, the immune state in recipients receiving CSR remains to be intensively investigated. Among 60 cases of living-donor LT at our institute, 68% of the patients had none to mild RI (non-RI group) and 32% of the patients had moderate to severe RI (RI group). The RI group received a CSR comprising reduced dose of tacrolimus, methylprednisolone, and mycophenolate mofetil, while the non-RI group received a regimen comprising conventional dose of tacrolimus and methylprednisolone. One year after LT, the mean estimated glomerular filtration rate (eGFR) in the RI group had significantly improved, although it was still lower than that of the non-RI group. Serial mixed lymphocyte reaction assays revealed that antidonor T-cell responses were adequately suppressed in both groups. Thus, we provide evidence that CSR leads to improvement of eGFR after LT in patients with RI, while maintaining an appropriate immunosuppressive state.

Prevalence of risk factors for coronary artery disease in the community in eastern Nepal--a pilot study.

INTRODUCTION: Coronary artery disease is a major cause of morbidity and mortality in Nepal, however, there are very few published reports of prevalence of various risk factors for coronary artery disease in the community from Nepal. METHOD: We evaluated 140 adult subjects by simple randomization from all wards in the community in Dharan, a small city located in the foothills in eastern Nepal. After exclusion of subjects with insufficient data, 119 subjects were included for the final analysis. Age ranged from 35 to 86 (mean 54.1+ 10.5) years and there were 63 males and 56 females. Various parameters which were studied included :history of diabetes mellitus, hypertension, coronary artery disease, smoking, hereditary history, family history, measurement of blood pressure, anthropometric parameters such as body mass index and waist hip ratio and biochemical parameters such as random blood sugar and serum cholesterol. RESULTS: The prevalence of various risk factors for coronary artery disease was found to be: hypertension 42 (35.3%), diabetes mellitus--19 (15.9%), history of current smoking--46 (38.7%), hypercholesterolemia--15 (12.6%), sedentary life style 56 (47.1%), body mass index>25 kg/m2--40 (33.6%) and central obesity 50 (42.1%). Approximately one third of the subjects had more than one risk factor. CONCLUSIONS: The study highlights prevalence of various risk factors for coronary artery disease in the community. Since majorly of the risk factors are modifiable, timely intervention can help in reducing morbidity and mortality due to this disease.

Deficiency of N-glycolylneuraminic acid and Galα1-3Galß1-4GlcNAc epitopes in xenogeneic cells attenuates cytotoxicity of human natural antibodies.

BACKGROUND: A number of carbohydrate structures apart from Galα1-3Galß1-4GlcNAc (Gal) have been implicated as potential xenoantigens. Epitopes of another carbohydrate structure, namely N-glycolylneuraminic acid (NeuGc), are widely expressed on the surfaces of endothelial cells of all mammals, except humans, and are likely targets of anti-non-Gal antibodies (Abs). The purpose of this study is to assess whether deficiency of NeuGc and Gal epitopes in xenogeneic cells attenuates the cytotoxicity of naturally occurring antibodies in human sera. METHODS: We generated mice deficient in both α1,3-galactosyltransferase (GalT) and cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH). Flow cytometric and immunohistochemical studies confirmed the complete absence of Gal and NeuGc expression in hematopoietic cells and tissue sections of the heart, lungs, liver, kidney, and pancreas in GalT(-/-) CMAH(-/-) double knockout (DKO) mice. The thymocytes obtained from wild-type (WT), GalT(-/-), CMAH(-/), and DKO mice were used to capture xenoreactive Abs present in human sera from healthy volunteers of each blood group. The titers and complement-dependent cytotoxicity (CDC) of these Abs were determined by flow cytometry and the (51) Cr release assay, respectively. RESULTS: In all sera, IgM and IgG Abs bound to the thymocytes of WT, GalT(-/-), CMAH(-/-), and DKO mice. The average values of IgM Abs against thymocytes of WT and CMAH(-/-) mice were similar, but were statistically higher than those against thymocytes of GalT(-/-) and DKO mice. The average value of IgG Abs against WT mouse thymocytes was similar to that against GalT(-/-) mouse thymocytes, but was significantly higher than that against thymocytes of CMAH(-/-) and DKO mice. Remarkable CDC of human sera was observed against the thymocytes of WT and CMAH(-/-) mice, whereas thymocytes of GalT(-/-) and DKO mice were more resistant to lysis. CDC of human sera against CMAH(-/-) mouse thymocytes was significantly lower than that against WT mouse thymocytes. In addition, CDC against DKO mouse thymocytes, which appeared undetectable even at lesser serum dilutions, was significantly lower than that against GalT(-/-) mouse thymocytes. CONCLUSIONS: A DKO mice strain lacking both Gal and NeuGc antigens in several tissues has been generated. Comparing CDC of human sera against mouse thymocytes, the DKO strain shows a statistically significant but a small additional reduction in CDC compared to that already achieved in GalT(-/-) mice.

Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes.

BACKGROUND: It is acknowledged that the response of human T cells to xenogeneic targets is more potent than that to allogeneic targets. However, it is not clear whether the more vigorous T cell response to xenoantigens than to alloantigens is attributable to a higher frequency or stronger reaction of xenoreactive T cells. METHODS: We determined the precursor frequencies (PFs) and stimulation indexes (SIs) of xenoreactive human T cells by performing a mixed lymphocyte reaction (MLR) assay using a carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique. Irradiated porcine or human peripheral blood mononuclear cells (PBMCs)used as stimulator cells--were cultured with CFSE-labeled human PBMCs--used as responder cells. RESULTS: The SIs of the xenoreactive CD4(+) T cells were significantly higher than those of the alloreactive CD4(+) T cells, whereas the PFs of the alloreactive and xenoreactive CD4(+) T cell precursors were almost identical, suggesting a stronger reaction by a single xenoreactive CD4(+) T cell. In contrast, the SIs of the xenoreactive CD8(+) T cells did not differ from those of the alloreactive CD4(+) T cells, and the PFs of the allo- and xenoreactive CD8(+) T cell precursors were also identical. Addition of a soluble human CD47-Fc fusion protein in the porcine-to-human MLR assay caused a statistically significant reduction of the SIs of the xenoreactive CD4(+) T cells. Such an alteration was abrogated by further addition of blocking antibodies (Abs) against either human CD47 or signal regulatory protein-alpha in the porcine-to-human MLR assay. Addition of human CD47-Fc after the depletion of non-T cells from the population of human responder PBMCs in this MLR assay did not influence the SIs of the xenoreactive CD4(+) T cells. CONCLUSIONS: The more vigorous T cell response to xenoantigens than to alloantigens is possibly attributable to a stronger reaction of xenoreactive T cells; the interspecies incompatibility of CD47 may contribute to such xenoreactive CD4(+) T cell responses via an indirect pathway.

Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice.

The generation of pigs devoid of Galalpha1,3Galbeta1,4GlcNAc (Gal) residues has stimulated interest in non-Gal Ags as potentially important targets for Ab binding leading to rejection of pig organ xenografts in humans. Although N-glycolylneuraminic acid (NeuGc) epitopes, which are widely expressed on the endothelial cells of all mammals except humans, are likely targets of anti-non-Gal Abs, this aspect has not been investigated intensively owing to the absence of an appropriate animal model. In this study, we used CMAH(-/-) mice, which are completely deficient in NeuGc and thus produce anti-NeuGc Abs. Sera obtained from CMAH(-/-) mice and healthy human volunteers having anti-NeuGc Abs initiated complement-mediated lysis against CMAH(+/+) cells in vitro. The cytotoxic activity of anti-NeuGc Abs was also determined in vivo (i.e., NeuGc-expressing CMAH(+/+) mouse splenocytes that had been i.v. injected were completely eliminated in syngeneic CMAH(-/-) mice). CMAH(-/-) mice rejected the islets transplanted from syngeneic CMAH(+/+) mice. Thus, the anti-NeuGc Ab-mediated response may be crucially involved in xenograft loss. This is the first direct demonstration of the immunogenic property of NeuGc determinants as targets of the corresponding Abs in CMAH(+/+)-to-CMAH(-/-) transplantation setting.