Adarsh Babu M CSE-2019-23 - Academia.edu (original) (raw)

Papers by Adarsh Babu M CSE-2019-23

Indian Journal of Nephrology, 2013

We report a case of 68-year-old Caucasian man who presented with cerebral infarcts secondary to a... more We report a case of 68-year-old Caucasian man who presented with cerebral infarcts secondary to arterial thrombosis associated with nephrotic syndrome. His initial presentation included edema of legs, left hemiparesis, and right-sided cerebellar signs. Investigations with computed tomography and magnetic resonance imaging of brain showed multiple cerebral infarcts in middle cerebral and posterior cerebral artery territory. Blood and urine investigations also showed impaired renal function, hypercholesterolemia, hypoalbuminaemia, and nephrotic range proteinuria. Renal biopsy showed minimal change disease. Cerebral infarcts were treated with antiplatelet agents and nephrotic syndrome was treated with high dose steroids. Patient responded well to the treatment and is all well till date.

Case Reports in Gastroenterology, 2008

A 56-year-old male was admitted with symptoms of belching, abdominal pain and weight loss of 2 we... more A 56-year-old male was admitted with symptoms of belching, abdominal pain and weight loss of 2 weeks duration. Examination revealed hepatosplenomegaly which was confirmed by computed tomography (CT). CT images also revealed filling defects in the portal vein and intrahepatic branches consistent with thrombosis and hepatosplenic infarcts. Alkaline phosphatase was elevated at 688 units, all other investigations, including full blood count, coagulation screen and tumour markers, were normal. Magnetic resonance cholangiopancreatography did not reveal any mass in the porta hepatis. Upper gastrointestinal endoscopy and colonoscopy were normal. Liver biopsy was normal and did not reveal any evidence of lymphoma. The raised alkaline phosphatase settled to reference range over a period of 3 weeks. Thrombophilia screen was negative. Contrast CT of the abdomen performed after 4 weeks displayed revascularisation of the previously thrombosed portal vein and intrahepatic branches. The patient has...

Purpose: Complement deposition in renal allograft biopsies and native kidneys may represent an on... more Purpose: Complement deposition in renal allograft biopsies and native kidneys may represent an ongoing inflammatory process. We studied the significance of incidental finding of predominant Clq deposits in the renal allograft biopsies on renal function, proteinuria, and graft survival. Methods: Retrospectively, patients who have undergone renal biopsies either proto-col or for cause were retrieved for the last five years. Eight patients were found to have dominant or codominant Clq deposits. Patients without Clq deposits (n=21) were selected from the same time period as a control group. Demographic data, creatinine, proteinuria, graft survival data were collected from the electronic medical records: Results: Our analysis included 8 cases with predominant Clq deposits and 21 controls without Clq deposits. Cause of end stage renal disease included type 2 diabetes in 4 cases, type 1 diabetes 1 case, 2 cases had chronic GN, 1 case APRT enzyme deficiency. There were no differences in age, duration on dialysis, HLA mismatch. or induction/maintenance immunosuppressive agents. At one year follow up there was no difference in creatinine or incidence of proteinuria. There were no graft loss in the cases. Potentially deceptive pathologic findings included kappa light chain predominance in deposits of 1 case (without glomerular morphologic alterations) and tubuloreticular structures by electron microscopy in another (without clinical evidence of lupus). Conclusions: In this well-characterized cohort of patients with dominant Clq deposits in the mesangium, there was no association with renal allograft dysfunction or proteinuria. In this short follow up there was no effect on allograft survival. We conclude that there is no clinical relevance of isolated predominant Clq deposit in short-term follow-up. This is in line with one other published study. Further studies are needed to look for long-term effects of Clq deposits and if these lesions persist or disappear in subsequent biopsies

Purpose: Anti-HLA antibodies, both pre-formed and de novo are associated with worse graft surviva... more Purpose: Anti-HLA antibodies, both pre-formed and de novo are associated with worse graft survival. Complement activation is an important mechanism of antibody mediated immunological injury. We hypothesised that anti-HLA antibodies may differentially induce expression of complement regulatory proteins thus resulting in differential injury. Methods: Human primary renal glomerular endothelial cells (HRGEC) were HLA typed. Cells at passage 3-6, were stimulated with Gamma Interferon for 48hours. Cells were then exposed to sera with cell HLA specific anti-HLA class I, Class II and Class I+n antibodies in separate experiments. Sera with no antibodies acted as a negative control. Expression of mRNA for CD46, CD55, and CD59 were studied by qPCR for all these 4 conditions. Cell lysates collected for Western blot and Flow cytometry were also studied for all the 4 conditions. Results: mRNA isolated from endothelial cells, was quantified for CD46, CD55 and CD59 expression by qPCR and there was no difference in expression levels after 48hours under 4 conditions. There was also no difference in surface expression of CD46, CD55 and CD59 by western blot. In the Figure la overlay graph CD46 expression is not altered under 3 different conditions compared to negative control. Similar findings are presented for CD55 and CD59 expression in Figures lb and lc respectively. Conclusions: In these experiments, we clearly show that CD46, CD55 and CD59 expression on renal glomerular endothelial cells do not change in the presence of anti-HLA Z antibodies. Different susceptibility of anti HLA class l and class II anti-bodies are not explained by this mechanism. Upregulation of these underutilized targets may confer additional endothelial protection in the presence of antibodies, especially if the immune-mediated damage is related to complement activation

Purpose: Anti-HLA Zantibodies, both pre-formed and de novo are associated with worse graft surviv... more Purpose: Anti-HLA Zantibodies, both pre-formed and de novo are associated with worse graft survival. Glomerular endothelial cells are the targets for antibody mediated rejection. We hypothesized that there are differences in the mechamsms of endothelial cell activation by of anti-HLA Zclass I and II antibodies. Also, this may explain differences in pathogenicity. Methods: Human primary renal glomerular endothelial cells (HRGEC) were HLA typed. Cells at passage 3-6, were stimulated with Gamma Interferon for 48hours. Cells were then exposed to sera with cell HLA specific anti-HLA Zclass I and II antibodies in separate experiments for a serial time period starting from 2 minutes to maximum of 120mmutes. Cell lysates were collected and studied for Phospho AKT and MAP Kinases by Western Blotting. Results: In these experiments, we demonstrate differential activation of phospho-kinases in the presence of anti-HLA Zclass I and class II antibodies. With anti-HLA Zclass I antibodies progressive activation of phospho AKT and MAP Kinases were noted beginning at 15 minutes [Figure la]. Anti-HLA Zclass II antibodies caused activation phospho AKT for 1 Ommutes beginning at 2 minutes, then activation was not seen till 60 minutes. MAPK were activated from 2-10 minutes with no further activation [Figure lb]. Conclusions: This differential activationmay lead to different downstream pathways that determine the endothelial cell susceptibility. Studies have shown that Phospho AKT activation promotes cell growth and prevents apoptosis. Continuous activation of pAKT by class I antibodies in contrast to class II antibodies may stimulate cell survival signals. Further studies on endothelial cell signaling pathways are needed to elucidate specific markers that are upregulated

Antibodies against donor HLA determine access to solid organ transplantation and in many cases th... more Antibodies against donor HLA determine access to solid organ transplantation and in many cases the outcome of transplantation, but graft failure is not an inevitable consequence of their presence. Much research has been performed with two main aims – which antibodies represent the highest risk factor prior to transplantation, and second to understand how donor specific HLA antibodies behave after transplantation, with a long-term aim of being able to manipulate their production. HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity. Integral to the understanding of the large datasets generated is sophisticated mathematical analysis using techniques such as decision tree analysis and unsupervised machine ...

Transplant International, 2020

Anti-HLA-antibody characteristics aid to risk-stratify patients and improve long-term renal graft... more Anti-HLA-antibody characteristics aid to risk-stratify patients and improve long-term renal graft outcomes. Complement activation by donor-specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross-match-positive). We explored the role of C3d-positive DSAs in sub-stratification of crossmatch-positive cases and relate to the graft outcomes. We investigated 139 cross-match-positive living-donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post-transplant. C3d-positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post-transplant. Median follow-up of patients was 48 months (IQR 20.47-77.57). In the multivariable analysis, pretreatment C3d-positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37-7.86). The relative risk of death-censored five-year graft failure was 2.83 (95% CI 1.56-5.13). Patients with both pretreatment and Day 14 C3d-positive DSAs had the worst five-year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d-negative DSA patients with the relative risk of death-censored five-year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub-stratify the risk of poor graft outcome in cross-match-positive living-donor renal transplantation.

Transplant Immunology, 2018

Please cite this article as: , Correlation of C3d donor specific antibodies and IgG MFI with posi... more Please cite this article as: , Correlation of C3d donor specific antibodies and IgG MFI with positive complement dependent cytotoxicity and flow cytometry crossmatch in a cohort of HLA incompatible renal transplants: single centre experience. Trim (2018),

Clinical transplants, 2016

Immunoglobulin G (IgG) antibodies against donor human leukocyte antigens (HLA) are monitored in t... more Immunoglobulin G (IgG) antibodies against donor human leukocyte antigens (HLA) are monitored in the pre-and post-transplant period due to their established role in predicting rejection and renal allograft survival. However, the role of immunoglobulin M (IgM) anti-HLA donor-specific antibodies (DSA) is not fully understood, especially in highly-sensitized patients undergoing direct transplantation. We designed this study to determine whether IgM DSA predicts rejection episodes and/or graft failure. Samples from 92 patients who had undergone HLA-antibody incompatible transplants were tested at 5 time points: days -8 (pre-plasmapheresis), 0, 7, 14, and 30 using Luminex microbead assay with ethylenediaminetetraacetic acid containing wash buffer (LABScreen®, One Lambda, Canoga Park, CA). IgM was defined positive if the mean fluorescence values were greater than 2000. Presence of pre- and post-transplant IgM was correlated with early antibody mediated rejection episodes (within 30 days po...

CEN Case Reports, 2013

A 47-year-old Caucasian man developed mild diarrhoea associated with more than 10 kg weight loss,... more A 47-year-old Caucasian man developed mild diarrhoea associated with more than 10 kg weight loss, severe fatigue and anaemia. Endoscopy demonstrated deposits of AA amyloid within the gastrointestinal tract. He had heavy proteinuria with a serum albumin of 15 g/L consistent with systemic AA amyloidosis. He had no symptoms to suggest an underlying chronic inflammatory condition but had CRP 130 mg/L and SAA 474 mg/L. In an attempt to identify the source of his inflammatory response, he underwent a contrast-enhanced whole-body computed tomography scan, which revealed a necrotising mass lesion in the right kidney consistent with a renal cell carcinoma. It also showed non-mechanical obstruction of the small bowel and, immediately post-imaging, the patient developed intractable vomiting followed by oliguric renal failure requiring haemodialysis. Despite his renal and gut failure, he underwent right radical nephrectomy without further complications. Histology showed complete resection of a clear cell renal cell carcinoma and renal amyloid deposits. Post-surgery, his acute-phase response decreased to normal, consistent with the renal cell carcinoma acting as the inflammatory stimulus. Although he remains dialysis dependent, his gut function improved and he has regained both normal weight and serum albumin. Our case demonstrates partial resolution of AA amyloidosis with removal of the inflammatory source.

Health Expectations, 2021

Introduction: In 2020 England moved to an opt-out deceased donation law. We aimed to investigate ... more Introduction: In 2020 England moved to an opt-out deceased donation law. We aimed to investigate the views of a mixed stakeholder group comprising people with kidney disease, family members and healthcare practitioners towards the change in legislation. We investigated the expected impacts of the new legislation on deceased-donor and living-donor transplantation, and views on media campaigns regarding the law change. Methods: We undertook in-depth qualitative interviews with people with kidney disease (n = 13), their family members (n = 4) and healthcare practitioners (n = 15). Purposive sampling was used to ensure diversity for patients and healthcare practitioners. Family members were recruited through snowball sampling and posters. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. Results: Three themes with six subthemes were identified: (i) Expectations of impact (Hopeful patients; Cautious healthcare professionals), (ii) Living-donor transplantation (Divergent views; Unchanged clinical recommendations), (iii) Media campaigns (Single message; Highlighting recipient benefits). Patients expected the law change would result in more deceased-donor transplant opportunities. Conclusions: Clinicians should ensure patients and families are aware of the current evidence regarding the impact of opt-out consent: expectations of an increased likelihood of receiving a deceased-donor transplant are not currently supported by the evidence. This may help to prevent a decline in living-donor transplantation seen in other countries with similar legislation. Media campaigns should include a focus on the impact of organ receipt.

PLOS ONE, 2021

A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK’... more A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK’s LDKT activity falls behind that of many other countries, and there is evidence of socioeconomic inequity in access. We aimed to develop a UK-specific multicomponent intervention to support eligible individuals to access a LDKT. The intervention was designed to support those who are socioeconomically-deprived and currently disadvantaged, by targeting mediators of inequity identified in earlier work. We identified three existing interventions in the literature which target these mediators: a) the Norway model (healthcare practitioners contact patients’ family with information about kidney donation), b) a home education model, and c) a Transplant candidate advocate model. We undertook intervention development using the Person-Based Approach (PBA). We performed in-depth qualitative interviews with people with advanced kidney disease (n = 13), their family members (n = 4), and renal and tra...

Journal of the Endocrine Society, 2019