Nada Alachkar | Johns Hopkins University School of Medicine (original) (raw)
Papers by Nada Alachkar
American Journal of Transplantation
We have previously described strong associations between frailty, a measure of physiologic reserv... more We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015
We have previously described strong associations between frailty, a measure of physiologic reserv... more We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respec...
Néphrologie & thérapeutique, 2012
Acute rejection (AR) is a common medical problem among kidney transplant recipients, which may ca... more Acute rejection (AR) is a common medical problem among kidney transplant recipients, which may cause a significant impact on patients' and allografts' survival. Kidney allograft biopsy remains the "gold standard" for assessing the cause of kidney transplant dysfunction. However, there are limitations for the allograft biopsy; these include the risk of bleeding, injury to the adjacent organs, and the possibility of sampling error leading to misdiagnosis. We conducted a comprehensive review of the literature and main published data that discussed the most relevant serum and urine biomarkers in acute allograft dysfunction, along with their clinical significance. There have been significant discoveries of several important biomarkers that correlated with biopsy findings, clinical outcomes and possibly graft survival. Proteomic and genomic have been utilized in this area with some success, along with a growing discoveries of cytokines surrogate makers. The discovery of ...
Frontiers in Medicine, 2014
Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by over-activation and... more Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by over-activation and dysregulation of the alternative complement pathway. Its estimated prevalence is 1-2 per million. The disease is characterized by thrombotic microangiopathy, which causes anemia, thrombocytopenia, and acute renal failure. aHUS has more severe course compared to typical (infection-induced) HUS and is frequently characterized by relapses that leads to end stage renal disease. For a long time, kidney transplantation for these patients was contraindicated because of high rate of recurrence and subsequent renal graft loss. The post-kidney transplantation recurrence rate largely depends on the pathogenetic mechanisms involved. However, over the past several years, advancements in the understanding and therapeutics of aHUS have allowed successful kidney transplantation in these patients. Eculizumab, which is a complement C5 antibody that inhibits complement factor 5a and subsequent formation of the membrane-attack complex, has been used in prevention and treatment of post-transplant aHUS recurrence. In this paper, we present two new cases of aHUS patients who underwent successful kidney transplantation in our center with the use of prophylactic and maintenance eculizumab therapy that have not been published before. The purpose of reporting these two cases is to emphasize the importance of using eculizumab as a prophylactic therapy to prevent aHUS recurrence post-transplant in high-risk patients. We will also review the current understanding of the genetics of aHUS, the pathogenesis of its recurrence after kidney transplantation, and strategies for prevention and treatment of post-transplant aHUS recurrence.
Transplant International, 2014
Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transpla... more Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8(+) T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3(+) INF-γ responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8(+) T-cell lymphopenia with deficient post-transplant antiviral responses.
Nephron Clinical Practice, 2011
Acute kidney injury (AKI) is a common medical problem among kidney transplant recipients, which m... more Acute kidney injury (AKI) is a common medical problem among kidney transplant recipients, which may cause a significant impact on patient and allograft survival. Currently, an allograft biopsy remains the 'gold standard' for assessing the cause of impaired kidney function. Limitations of the allograft biopsy include the risk of bleeding, injury to the adjacent viscera, and the possibility of sampling error leading to an inadequate diagnosis. We conducted a comprehensive review of the literature and main published data that discussed the most relevant biomarkers in acute allograft dysfunction, along with their clinical significance. There have been significant discoveries of several important biomarkers that correlated with biopsy findings, clinical outcomes and possibly graft survival. The discovery of surrogate biomarkers in kidney transplantation is an evolving field of crucial importance that mandates further collaborative efforts.
Science Translational Medicine, 2014
Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause ... more Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of accelerated graft loss. To evaluate pathogenic antibodies (Abs) in rFSGS, we processed 141 serum samples from 64 patients with and without primary rFSGS and 34 non-FSGS control patients transplanted at four hospitals. We screened about 9000 antigens in pretransplant sera and selected 10 Abs targeting glomerular antigens for enzyme-linked immunosorbent assay (ELISA) validation. A panel of seven Abs (CD40, PTPRO, CGB5, FAS, P2RY11, SNRPB2, and APOL2) could predict posttransplant FSGS recurrence with 92% accuracy. Pretransplant elevation of anti-CD40 Ab alone had the best correlation (78% accuracy) with rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression in FSGS compared to non-FSGS controls. Anti-CD40 Abs purified from rFSGS patients were particularly pathogenic in human podocyte cultures. Injection of anti-CD40/rFSGS Ab enhanced suPAR (soluble urokinase receptor)-mediated proteinuria in wild-type mice, yet no sensitizing effect was noted in mice deficient in CD40 or in wild-type mice that received blocking Ab to CD40. In conclusion, a panel of seven Abs can help identify primary FSGS patients at high risk of recurrence before transplantation. Intrarenal CD40 (and possibly other specific glomerular antigens) is an important contributor to FSGS disease pathogenesis. Human trials of anti-CD40 therapies are warranted to evaluate their efficacy for preventing rFSGS and improving graft survival.
Gastroenterology and Hepatology
Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Althoug... more Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Although HCV mainly causes hepatitis, a significant portion of chronic HCV patients manifests with at least 1 extrahepatic involvement during the course of their illness. Chronic HCV infection can cause various types of renal diseases. The most common renal manifestations of HCV infection are essential mixed cryoglobulinemia leading to membranoproliferative glomerulonephritis (MPGN), MPGN without cryoglobulinemia, and membranous glomerulonephritis. On the other hand, patients with end-stage kidney disease are at an increased risk of acquiring HCV due to their frequent exposure to potentially contaminated devices in dialysis units and their long-term use of vascular access. Among dialysis patients or patients undergoing renal transplantation, the presence of HCV is associated with higher rates of mortality. The optimal antiviral therapy in patients with severe renal insufficiency is not yet well...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2014
We compared survival outcomes among simultaneous liver-kidney transplants after model for end-sta... more We compared survival outcomes among simultaneous liver-kidney transplants after model for end-stage liver disease (MELD) according to their specific diagnosis and hepatitis C virus versus nonhepatitis C virus. Clinical data review was performed for all patients who underwent combined liver-kidney transplants at Johns Hopkins Hospital from January 31, 1995, to October 31, 2012. Differences in demographics and characteristics among 2 groups were compared using independent samples t test. Survival analysis and distributions were calculated using Kaplan-Meier and Mantel-Cox log-rank test. Of 48 combined liver-kidney transplants, 31 simultaneous liver-kidney transplants cases were included; nonsimultaneous liver-kidney transplants and patients with prior transplants were excluded. Proportions of age, sex, ethnicity, pre-MELD score, pretransplant renal replacement therapy requirement, hypertension, diabetes mellitus, and follow-up were similar in both groups. Median follow-up was 30 month...
Néphrologie & Thérapeutique, 2012
Transplantation Journal, 2012
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015
Unlike antibody-mediated rejection (AMR) with clinical features, it remains unclear whether subcl... more Unlike antibody-mediated rejection (AMR) with clinical features, it remains unclear whether subclinical AMR should be treated, as its effect on allograft loss is unknown. It is also uncertain if AMR's effect is homogeneous across donor (deceased/live) and (HLA/ABO) antibody types. We compared 219 patients with AMR (77 subclinical, 142 clinical) to controls matched on HLA/ABO-compatibility, donor type, prior transplant, panel reactive antibody (PRA), age and year. One and 5-year graft survival in subclinical AMR was 95.9% and 75.7%, compared to 96.8% and 88.4% in matched controls (p = 0.0097). Subclinical AMR was independently associated with a 2.15-fold increased risk of graft loss (95% CI: 1.19-3.91; p = 0.012) compared to matched controls, but not different from clinical AMR (p = 0.13). Fifty three point two percent of subclinical AMR patients were treated with plasmapheresis within 3 days of their AMR-defining biopsy. Treated subclinical AMR patients had no difference in graf...
Minerva gastroenterologica e dietologica, 2015
Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-1... more Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-150 million infected people worldwide and 350,000 to 500,000 HCV-related deaths each year. Chronic kidney disease (CKD) is also a highly prevalent public health issue as the escalating numbers of patients worldwide are developing type 2 diabetes mellitus and hypertension due to high fat diets and a growing obesity epidemic. The high incidence and prevalence of HCV infection leads to substantial morbidity and mortality among renal dialysis patients. Recommendations are to screen for HCV infection among all patients with renal failure especially prior to initiation of hemodialysis and renal transplant evaluation. HCV-antibody enzyme immunoassay (EIA) followed by confirmation with HCV RNA nucleic acid test (NAT) is recommended for low prevalence regions, but in dialysis centers with a high prevalence of HCV, initial testing with NAT is recommended due to higher false positive EIA rates. Live...
Advances in chronic kidney disease, 2014
Focal and segmental glomerulosclerosis (FSGS) represents a group of glomerular disorders, identif... more Focal and segmental glomerulosclerosis (FSGS) represents a group of glomerular disorders, identified on kidney biopsy, that progress in the histopathologic pattern of sclerosis in parts of some glomeruli. Damage to podocytes usually marks the beginning of the disease, most evident in primary FSGS. In addition to genetic predisposition, there are many acquired causes that disturb normal podocyte homeostasis and allow for the development of FSGS. The aim of this review was to summarize recent findings of the most relevant circulating permeability factors that may serve as biomarkers of active primary idiopathic FSGS and aid in the diagnosis and prediction of recurrent FSGS after kidney transplantation.
Nature reviews. Nephrology, 2014
T-lymphocyte activation antigen CD80 is a B-cell costimulator and podocyte injury marker original... more T-lymphocyte activation antigen CD80 is a B-cell costimulator and podocyte injury marker originally described in lupus nephritis; CD80 blockade with abatacept disappointed in a lupus nephritis trial. A study now suggests abatacept efficacy in focal and segmental glomerulosclerosis. Small patient numbers and concurrent treatment regimens call for more definitive studies regarding this therapeutic strategy.
Gastroenterology & hepatology, 2012
Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Althoug... more Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Although HCV mainly causes hepatitis, a significant portion of chronic HCV patients manifests with at least 1 extrahepatic involvement during the course of their illness. Chronic HCV infection can cause various types of renal diseases. The most common renal manifestations of HCV infection are essential mixed cryoglobulinemia leading to membranoproliferative glomerulonephritis (MPGN), MPGN without cryoglobulinemia, and membranous glomerulonephritis. On the other hand, patients with end-stage kidney disease are at an increased risk of acquiring HCV due to their frequent exposure to potentially contaminated devices in dialysis units and their long-term use of vascular access. Among dialysis patients or patients undergoing renal transplantation, the presence of HCV is associated with higher rates of mortality. The optimal antiviral therapy in patients with severe renal insufficiency is not yet well...
Transplant international : official journal of the European Society for Organ Transplantation, 2012
American Journal of Transplantation
We have previously described strong associations between frailty, a measure of physiologic reserv... more We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015
We have previously described strong associations between frailty, a measure of physiologic reserv... more We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respec...
Néphrologie & thérapeutique, 2012
Acute rejection (AR) is a common medical problem among kidney transplant recipients, which may ca... more Acute rejection (AR) is a common medical problem among kidney transplant recipients, which may cause a significant impact on patients' and allografts' survival. Kidney allograft biopsy remains the "gold standard" for assessing the cause of kidney transplant dysfunction. However, there are limitations for the allograft biopsy; these include the risk of bleeding, injury to the adjacent organs, and the possibility of sampling error leading to misdiagnosis. We conducted a comprehensive review of the literature and main published data that discussed the most relevant serum and urine biomarkers in acute allograft dysfunction, along with their clinical significance. There have been significant discoveries of several important biomarkers that correlated with biopsy findings, clinical outcomes and possibly graft survival. Proteomic and genomic have been utilized in this area with some success, along with a growing discoveries of cytokines surrogate makers. The discovery of ...
Frontiers in Medicine, 2014
Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by over-activation and... more Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by over-activation and dysregulation of the alternative complement pathway. Its estimated prevalence is 1-2 per million. The disease is characterized by thrombotic microangiopathy, which causes anemia, thrombocytopenia, and acute renal failure. aHUS has more severe course compared to typical (infection-induced) HUS and is frequently characterized by relapses that leads to end stage renal disease. For a long time, kidney transplantation for these patients was contraindicated because of high rate of recurrence and subsequent renal graft loss. The post-kidney transplantation recurrence rate largely depends on the pathogenetic mechanisms involved. However, over the past several years, advancements in the understanding and therapeutics of aHUS have allowed successful kidney transplantation in these patients. Eculizumab, which is a complement C5 antibody that inhibits complement factor 5a and subsequent formation of the membrane-attack complex, has been used in prevention and treatment of post-transplant aHUS recurrence. In this paper, we present two new cases of aHUS patients who underwent successful kidney transplantation in our center with the use of prophylactic and maintenance eculizumab therapy that have not been published before. The purpose of reporting these two cases is to emphasize the importance of using eculizumab as a prophylactic therapy to prevent aHUS recurrence post-transplant in high-risk patients. We will also review the current understanding of the genetics of aHUS, the pathogenesis of its recurrence after kidney transplantation, and strategies for prevention and treatment of post-transplant aHUS recurrence.
Transplant International, 2014
Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transpla... more Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8(+) T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3(+) INF-γ responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8(+) T-cell lymphopenia with deficient post-transplant antiviral responses.
Nephron Clinical Practice, 2011
Acute kidney injury (AKI) is a common medical problem among kidney transplant recipients, which m... more Acute kidney injury (AKI) is a common medical problem among kidney transplant recipients, which may cause a significant impact on patient and allograft survival. Currently, an allograft biopsy remains the 'gold standard' for assessing the cause of impaired kidney function. Limitations of the allograft biopsy include the risk of bleeding, injury to the adjacent viscera, and the possibility of sampling error leading to an inadequate diagnosis. We conducted a comprehensive review of the literature and main published data that discussed the most relevant biomarkers in acute allograft dysfunction, along with their clinical significance. There have been significant discoveries of several important biomarkers that correlated with biopsy findings, clinical outcomes and possibly graft survival. The discovery of surrogate biomarkers in kidney transplantation is an evolving field of crucial importance that mandates further collaborative efforts.
Science Translational Medicine, 2014
Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause ... more Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of accelerated graft loss. To evaluate pathogenic antibodies (Abs) in rFSGS, we processed 141 serum samples from 64 patients with and without primary rFSGS and 34 non-FSGS control patients transplanted at four hospitals. We screened about 9000 antigens in pretransplant sera and selected 10 Abs targeting glomerular antigens for enzyme-linked immunosorbent assay (ELISA) validation. A panel of seven Abs (CD40, PTPRO, CGB5, FAS, P2RY11, SNRPB2, and APOL2) could predict posttransplant FSGS recurrence with 92% accuracy. Pretransplant elevation of anti-CD40 Ab alone had the best correlation (78% accuracy) with rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression in FSGS compared to non-FSGS controls. Anti-CD40 Abs purified from rFSGS patients were particularly pathogenic in human podocyte cultures. Injection of anti-CD40/rFSGS Ab enhanced suPAR (soluble urokinase receptor)-mediated proteinuria in wild-type mice, yet no sensitizing effect was noted in mice deficient in CD40 or in wild-type mice that received blocking Ab to CD40. In conclusion, a panel of seven Abs can help identify primary FSGS patients at high risk of recurrence before transplantation. Intrarenal CD40 (and possibly other specific glomerular antigens) is an important contributor to FSGS disease pathogenesis. Human trials of anti-CD40 therapies are warranted to evaluate their efficacy for preventing rFSGS and improving graft survival.
Gastroenterology and Hepatology
Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Althoug... more Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Although HCV mainly causes hepatitis, a significant portion of chronic HCV patients manifests with at least 1 extrahepatic involvement during the course of their illness. Chronic HCV infection can cause various types of renal diseases. The most common renal manifestations of HCV infection are essential mixed cryoglobulinemia leading to membranoproliferative glomerulonephritis (MPGN), MPGN without cryoglobulinemia, and membranous glomerulonephritis. On the other hand, patients with end-stage kidney disease are at an increased risk of acquiring HCV due to their frequent exposure to potentially contaminated devices in dialysis units and their long-term use of vascular access. Among dialysis patients or patients undergoing renal transplantation, the presence of HCV is associated with higher rates of mortality. The optimal antiviral therapy in patients with severe renal insufficiency is not yet well...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2014
We compared survival outcomes among simultaneous liver-kidney transplants after model for end-sta... more We compared survival outcomes among simultaneous liver-kidney transplants after model for end-stage liver disease (MELD) according to their specific diagnosis and hepatitis C virus versus nonhepatitis C virus. Clinical data review was performed for all patients who underwent combined liver-kidney transplants at Johns Hopkins Hospital from January 31, 1995, to October 31, 2012. Differences in demographics and characteristics among 2 groups were compared using independent samples t test. Survival analysis and distributions were calculated using Kaplan-Meier and Mantel-Cox log-rank test. Of 48 combined liver-kidney transplants, 31 simultaneous liver-kidney transplants cases were included; nonsimultaneous liver-kidney transplants and patients with prior transplants were excluded. Proportions of age, sex, ethnicity, pre-MELD score, pretransplant renal replacement therapy requirement, hypertension, diabetes mellitus, and follow-up were similar in both groups. Median follow-up was 30 month...
Néphrologie & Thérapeutique, 2012
Transplantation Journal, 2012
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015
Unlike antibody-mediated rejection (AMR) with clinical features, it remains unclear whether subcl... more Unlike antibody-mediated rejection (AMR) with clinical features, it remains unclear whether subclinical AMR should be treated, as its effect on allograft loss is unknown. It is also uncertain if AMR's effect is homogeneous across donor (deceased/live) and (HLA/ABO) antibody types. We compared 219 patients with AMR (77 subclinical, 142 clinical) to controls matched on HLA/ABO-compatibility, donor type, prior transplant, panel reactive antibody (PRA), age and year. One and 5-year graft survival in subclinical AMR was 95.9% and 75.7%, compared to 96.8% and 88.4% in matched controls (p = 0.0097). Subclinical AMR was independently associated with a 2.15-fold increased risk of graft loss (95% CI: 1.19-3.91; p = 0.012) compared to matched controls, but not different from clinical AMR (p = 0.13). Fifty three point two percent of subclinical AMR patients were treated with plasmapheresis within 3 days of their AMR-defining biopsy. Treated subclinical AMR patients had no difference in graf...
Minerva gastroenterologica e dietologica, 2015
Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-1... more Hepatitis C virus (HCV) infection is a rising global public health burden with an estimated 130-150 million infected people worldwide and 350,000 to 500,000 HCV-related deaths each year. Chronic kidney disease (CKD) is also a highly prevalent public health issue as the escalating numbers of patients worldwide are developing type 2 diabetes mellitus and hypertension due to high fat diets and a growing obesity epidemic. The high incidence and prevalence of HCV infection leads to substantial morbidity and mortality among renal dialysis patients. Recommendations are to screen for HCV infection among all patients with renal failure especially prior to initiation of hemodialysis and renal transplant evaluation. HCV-antibody enzyme immunoassay (EIA) followed by confirmation with HCV RNA nucleic acid test (NAT) is recommended for low prevalence regions, but in dialysis centers with a high prevalence of HCV, initial testing with NAT is recommended due to higher false positive EIA rates. Live...
Advances in chronic kidney disease, 2014
Focal and segmental glomerulosclerosis (FSGS) represents a group of glomerular disorders, identif... more Focal and segmental glomerulosclerosis (FSGS) represents a group of glomerular disorders, identified on kidney biopsy, that progress in the histopathologic pattern of sclerosis in parts of some glomeruli. Damage to podocytes usually marks the beginning of the disease, most evident in primary FSGS. In addition to genetic predisposition, there are many acquired causes that disturb normal podocyte homeostasis and allow for the development of FSGS. The aim of this review was to summarize recent findings of the most relevant circulating permeability factors that may serve as biomarkers of active primary idiopathic FSGS and aid in the diagnosis and prediction of recurrent FSGS after kidney transplantation.
Nature reviews. Nephrology, 2014
T-lymphocyte activation antigen CD80 is a B-cell costimulator and podocyte injury marker original... more T-lymphocyte activation antigen CD80 is a B-cell costimulator and podocyte injury marker originally described in lupus nephritis; CD80 blockade with abatacept disappointed in a lupus nephritis trial. A study now suggests abatacept efficacy in focal and segmental glomerulosclerosis. Small patient numbers and concurrent treatment regimens call for more definitive studies regarding this therapeutic strategy.
Gastroenterology & hepatology, 2012
Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Althoug... more Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Although HCV mainly causes hepatitis, a significant portion of chronic HCV patients manifests with at least 1 extrahepatic involvement during the course of their illness. Chronic HCV infection can cause various types of renal diseases. The most common renal manifestations of HCV infection are essential mixed cryoglobulinemia leading to membranoproliferative glomerulonephritis (MPGN), MPGN without cryoglobulinemia, and membranous glomerulonephritis. On the other hand, patients with end-stage kidney disease are at an increased risk of acquiring HCV due to their frequent exposure to potentially contaminated devices in dialysis units and their long-term use of vascular access. Among dialysis patients or patients undergoing renal transplantation, the presence of HCV is associated with higher rates of mortality. The optimal antiviral therapy in patients with severe renal insufficiency is not yet well...
Transplant international : official journal of the European Society for Organ Transplantation, 2012