The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted...The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.展开更多
Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasiveindicators of biologic processes represents a useful tool ...Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasiveindicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.展开更多
Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in...Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.展开更多
Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients(RTRs) remain at an increased risk of fatal and non-fatal cardiovascular(CV) events comp...Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients(RTRs) remain at an increased risk of fatal and non-fatal cardiovascular(CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease(CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Nontraditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.展开更多
AIM: To investigate the long-term results of ABOincompatible(ABOi) kidney transplantation in a single center in Greece.METHODS: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December...AIM: To investigate the long-term results of ABOincompatible(ABOi) kidney transplantation in a single center in Greece.METHODS: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B Ig G antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus(TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible(ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the followup period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications.RESULTS: The mean follow-up period was 6 years(range 1 to 9 years). A mean of 5.0 ± 3.0(range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly(100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points(100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibodymediated rejection evidenced by histological signs. Four patients(13.3%) in the ABOi group and 3(10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups.CONCLUSION: ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceaseddonor waiting lists.展开更多
Acute kidney injury(AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome(HRS), a functional form of kidney failure, is ...Acute kidney injury(AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome(HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.展开更多
AIM To investigate the incidence and the determinants of cardiovascular morbidity in Greek renal transplant recipients(RTRs) expressed as major advance cardiac event(MACE) rate. METHODS Two hundred and forty-two adult...AIM To investigate the incidence and the determinants of cardiovascular morbidity in Greek renal transplant recipients(RTRs) expressed as major advance cardiac event(MACE) rate. METHODS Two hundred and forty-two adult patients with a functioning graft for at least three months and availabledata that were followed up on the August 31, 2015 at two transplant centers of Western Greece were included in this study. Baseline recipients' data elements included demographics, clinical characteristics, history of comorbid conditions and laboratory parameters. Follow-up data regarding MACE occurrence were collected retrospectively from the patients' records and MACE risk score was calculated for each patient. RESULTS The mean age was 53 years(63.6% males) and 47 patients(19.4%) had a pre-existing cardiovascular disease(CVD) before transplantation. The mean estimated glomerular filtration rate was 52 ± 17 mL /min per 1.73 m2. During follow-up 36 patients(14.9%) suffered a MACE with a median time to MACE 5 years(interquartile range: 2.2-10 years). Recipients with a MACE compared to recipients without a MACE had a significantly higher mean age(59 years vs 52 years, P < 0.001) and a higher prevalence of pre-existing CVD(44.4% vs 15%, P < 0.001). The 7-year predicted mean risk for MACE was 14.6% ± 12.5% overall. In RTRs who experienced a MACE, the predicted risk was 22.3% ± 17.1% and was significantly higher than in RTRs without an event 13.3% ± 11.1%(P = 0.003). The discrimination ability of the model in the Greek database of RTRs was good with an area under the receiver operating characteristics curve of 0.68(95%CI: 0.58-0.78).CONCLUSION In this Greek cohort of RTRs, MACE occurred in 14.9% of the patients, pre-existing CVD was the main risk factor, while MACE risk model was proved a dependable utility in predicting CVD post RT.展开更多
Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affect...Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.展开更多
Background: End stage renal disease (ESRD) is associated with an increase in oxidative stress, cardiovascular disease and cancer. The main treatment for ESRD is haemodialysis (HD), which itself induces repetitive bout...Background: End stage renal disease (ESRD) is associated with an increase in oxidative stress, cardiovascular disease and cancer. The main treatment for ESRD is haemodialysis (HD), which itself induces repetitive bouts of oxidative stress through membrane biocompatibility and endotoxin challenge. The resulting higher levels of reactive oxygen species in turn produce increased levels of oxidative DNA damage leading to genomic instability which may influence the higher risk of cancer reported in HD patients. Our aims were to measure levels of oxidative DNA damage in HD patients and in age and gender matched control volunteers. Methods: Thirty eight patients receiving HD in the Western Health and Social Services Trust (WHSCT) and 8 healthy volunteers were recruited. Volunteers gave informed consent and non-fasting morning blood samples were taken and assessed for DNA disruption using the comet assay modified to identify oxidative specific damage. Results: The HD patients had significantly elevated levels of alkaline DNA damage (19.46% ± 1.37% vs 3.86% ± 1.36% tail DNA, p < 0.05) and oxidative DNA damage formamidepyrimidine DNA glycosilase (5.81% ± 1.08% vs 1.23% ± 0.43% tail DNA, p < 0.01) and endonuclease III (6.04% ± 1.00% vs 1.98% ± 0.70% tail DNA, p < 0.01) compared to controls, respectively. A positive correlation was observed between the duration on dialysis (months) and levels of Endo III specific damage (p = 0.041). Conclusion: The significant increase in oxidative DNA damage and the positive correlation with duration of HD treatment and Endo III damage may contribute to the increased cancer risk observed in this patient group. Studies are required to investigate the best way to reduce this damage.展开更多
Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation.The microbiota has a relevant ...Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation.The microbiota has a relevant role in conditioning the healthy status and the diseases.In particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune system.The indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts appear.This abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic toxins.Similarly,after renal transplantation the microbiota changes with the appearance of pathobionts,principally in the first period because of the assumption of immunosuppressive drugs and antibiotics.These changes may deeply interfere with the graft outcome causing acute rejection,renal infections,diarrhea,and renal interstitial fibrosis.In addition,change in the microbiota may modify the metabolism of immunosuppressive drugs causing in some patients the need of modifying the immunosuppressant dosing.The restoration of the indigenous microbiota after transplantation is important,either to avoiding the complications that impair the normal renal graft,and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the graft.The use of prebiotics,probiotics,smart bacteria and diet modification may restore the indigenous microbiota,but these studies are just at their beginning and more data are needed to draw definitive conclusions.展开更多
Hepatitis B virus(HBV)poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates,especially in developed countries.The best preventive method is vaccination....Hepatitis B virus(HBV)poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates,especially in developed countries.The best preventive method is vaccination.Patients with chronic renal disease should ideally be vaccinated prior to dialysis,otherwise,reinforced vaccination practices and close antibody titer monitoring should be applied while on dialysis.HBV infected dialysis patients who are renal transplant candidates must be thoroughly examined by HBV-DNA,and liver enzyme testing and by liver biopsy.When needed,one must consider treating patients with tenofovir or entecavir rather than lamivudine.Depending on the cirrhosis stage,dialysis patients are eligible transplant recipients for either a combined kidney-liver procedure in the case of decompensated cirrhosis or a lone kidney transplantation since even compensated cirrhosis after sustained viral responders is no longer considered an absolute contraindication.Nucleoside analogues have led to improved transplantation outcomes with both long-term patient and graft survival rates nearing those of HBs Ag(-)recipients.Moreover,in the cases of immunized HBs Ag(-)potential recipients with concurrent prophylaxis,we are enabled today to safely use renal grafts from both HBs Ag(+)and HBs Ag(-)/antiHBc(+)donors.In so doing,we avoid unnecessary organ discarding.Universal prophylaxis with entecavir is recommended in HBV kidney recipients and should start perioperatively.One of the most important issues in HBV(+)kidney transplantation is the duration of antiviral prophylaxis.In the absence of robust data,it seems that prophylactic treatment may be discontinued in selected stable,low-risk recipients during maintenance immunosuppression and should be reintroduced when the immune status is altered.All immunosuppressive agents in kidney transplantation can be used in HBV(+)recipients.Immunosuppression is intimately associated with increased viral replication;thus it is important to minimize the total immunosuppression burden long term.展开更多
Objective: This study aims to determine surgical complications and graft outcome in children undergoing renal transplantation at Cayetano Heredia National Hospital (CHNH). Materials and Methods: A case study series fo...Objective: This study aims to determine surgical complications and graft outcome in children undergoing renal transplantation at Cayetano Heredia National Hospital (CHNH). Materials and Methods: A case study series focused on the incidence of surgical complications and graft outcome in pediatric patients with end stage renal disease (ESRD) who underwent renal transplant (RT) between December 2007 and March 2011. Results: The study described 29 pediatric transplant patients whose average age was 13.69 ± 3.38 (6.2-17.9) years. The etiology of end stage renal disease (ESRD) was renal hypoplasia in 12 patients (41.38%), primary glomerulopathy in 10 patients (34.48%), obstructive uropathy in 4 patients (13.79%), vasculitis in 2 patients (6.9%) and hemolytic uremic syndrome (HUS) in 1 (3.45%) patient. There were 11 surgical complications (34.48%): 2 cases of arterial thrombosis, 3 cases of urinary fistula, 3 of lymphocele, 1 of venous thrombosis, urinoma and perineal collection. The follow-up time was 15.84 ± 12.19 months. Graft survival at 12, 24, and 40 months was 89.29%, 77.16% and 77.16%, respectively. Conclusion: Surgical complications and graft survival in pediatric renal transplantation in our series did not differ from other published series.展开更多
The increased awareness of systemic sclerosis(SS)and its pathogenetic background made the management of this disease more amenable than previously thought.However,scleroderma renal crisis(SRC)is a rarely seen as an as...The increased awareness of systemic sclerosis(SS)and its pathogenetic background made the management of this disease more amenable than previously thought.However,scleroderma renal crisis(SRC)is a rarely seen as an associated disorder that may involve 2%-15%of SS patients.Patients presented with earlier,rapidly progressing,diffuse cutaneous SS disease,mostly in the first 3-5 years after non-Raynaud clinical manifestations,are more vulnerable to develop SRC.SRC comprises a collection of acute,mostly symptomatic rise in blood pressure,elevation in serum creatinine concentrations,oliguria and thrombotic microangiopathy in almost 50%of cases.The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis.In a scleroderma patient maintained on regular dialysis;every effort should be exerted to declare any possible evidence of renal recovery.A given period of almost two years has been suggested prior to proceeding in a kidney transplant(KTx).Of note,SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease(ESRD).KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients.Compared to other primary renal diseases,SS-related ESRD was considered for a long period of poor patient and allograft survivals.Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death.Recurrence of SRC after transplantation has been observed in some patients.However,an excellent post-transplant patient and graft outcome have been recently reported.Consequently,the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.展开更多
Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in ...Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.展开更多
文摘The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.
文摘Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasiveindicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.
文摘Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.
基金Supported by National Institute for Health Research Diet,Lifestyle and Physical Activity Biomedical Research Unit based at University Hospitals of Leicester and Loughborough University
文摘Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients(RTRs) remain at an increased risk of fatal and non-fatal cardiovascular(CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease(CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Nontraditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.
文摘AIM: To investigate the long-term results of ABOincompatible(ABOi) kidney transplantation in a single center in Greece.METHODS: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B Ig G antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus(TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible(ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the followup period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications.RESULTS: The mean follow-up period was 6 years(range 1 to 9 years). A mean of 5.0 ± 3.0(range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly(100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points(100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibodymediated rejection evidenced by histological signs. Four patients(13.3%) in the ABOi group and 3(10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups.CONCLUSION: ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceaseddonor waiting lists.
文摘Acute kidney injury(AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome(HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.
文摘AIM To investigate the incidence and the determinants of cardiovascular morbidity in Greek renal transplant recipients(RTRs) expressed as major advance cardiac event(MACE) rate. METHODS Two hundred and forty-two adult patients with a functioning graft for at least three months and availabledata that were followed up on the August 31, 2015 at two transplant centers of Western Greece were included in this study. Baseline recipients' data elements included demographics, clinical characteristics, history of comorbid conditions and laboratory parameters. Follow-up data regarding MACE occurrence were collected retrospectively from the patients' records and MACE risk score was calculated for each patient. RESULTS The mean age was 53 years(63.6% males) and 47 patients(19.4%) had a pre-existing cardiovascular disease(CVD) before transplantation. The mean estimated glomerular filtration rate was 52 ± 17 mL /min per 1.73 m2. During follow-up 36 patients(14.9%) suffered a MACE with a median time to MACE 5 years(interquartile range: 2.2-10 years). Recipients with a MACE compared to recipients without a MACE had a significantly higher mean age(59 years vs 52 years, P < 0.001) and a higher prevalence of pre-existing CVD(44.4% vs 15%, P < 0.001). The 7-year predicted mean risk for MACE was 14.6% ± 12.5% overall. In RTRs who experienced a MACE, the predicted risk was 22.3% ± 17.1% and was significantly higher than in RTRs without an event 13.3% ± 11.1%(P = 0.003). The discrimination ability of the model in the Greek database of RTRs was good with an area under the receiver operating characteristics curve of 0.68(95%CI: 0.58-0.78).CONCLUSION In this Greek cohort of RTRs, MACE occurred in 14.9% of the patients, pre-existing CVD was the main risk factor, while MACE risk model was proved a dependable utility in predicting CVD post RT.
文摘Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.
文摘Background: End stage renal disease (ESRD) is associated with an increase in oxidative stress, cardiovascular disease and cancer. The main treatment for ESRD is haemodialysis (HD), which itself induces repetitive bouts of oxidative stress through membrane biocompatibility and endotoxin challenge. The resulting higher levels of reactive oxygen species in turn produce increased levels of oxidative DNA damage leading to genomic instability which may influence the higher risk of cancer reported in HD patients. Our aims were to measure levels of oxidative DNA damage in HD patients and in age and gender matched control volunteers. Methods: Thirty eight patients receiving HD in the Western Health and Social Services Trust (WHSCT) and 8 healthy volunteers were recruited. Volunteers gave informed consent and non-fasting morning blood samples were taken and assessed for DNA disruption using the comet assay modified to identify oxidative specific damage. Results: The HD patients had significantly elevated levels of alkaline DNA damage (19.46% ± 1.37% vs 3.86% ± 1.36% tail DNA, p < 0.05) and oxidative DNA damage formamidepyrimidine DNA glycosilase (5.81% ± 1.08% vs 1.23% ± 0.43% tail DNA, p < 0.01) and endonuclease III (6.04% ± 1.00% vs 1.98% ± 0.70% tail DNA, p < 0.01) compared to controls, respectively. A positive correlation was observed between the duration on dialysis (months) and levels of Endo III specific damage (p = 0.041). Conclusion: The significant increase in oxidative DNA damage and the positive correlation with duration of HD treatment and Endo III damage may contribute to the increased cancer risk observed in this patient group. Studies are required to investigate the best way to reduce this damage.
文摘Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation.The microbiota has a relevant role in conditioning the healthy status and the diseases.In particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune system.The indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts appear.This abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic toxins.Similarly,after renal transplantation the microbiota changes with the appearance of pathobionts,principally in the first period because of the assumption of immunosuppressive drugs and antibiotics.These changes may deeply interfere with the graft outcome causing acute rejection,renal infections,diarrhea,and renal interstitial fibrosis.In addition,change in the microbiota may modify the metabolism of immunosuppressive drugs causing in some patients the need of modifying the immunosuppressant dosing.The restoration of the indigenous microbiota after transplantation is important,either to avoiding the complications that impair the normal renal graft,and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the graft.The use of prebiotics,probiotics,smart bacteria and diet modification may restore the indigenous microbiota,but these studies are just at their beginning and more data are needed to draw definitive conclusions.
文摘Hepatitis B virus(HBV)poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates,especially in developed countries.The best preventive method is vaccination.Patients with chronic renal disease should ideally be vaccinated prior to dialysis,otherwise,reinforced vaccination practices and close antibody titer monitoring should be applied while on dialysis.HBV infected dialysis patients who are renal transplant candidates must be thoroughly examined by HBV-DNA,and liver enzyme testing and by liver biopsy.When needed,one must consider treating patients with tenofovir or entecavir rather than lamivudine.Depending on the cirrhosis stage,dialysis patients are eligible transplant recipients for either a combined kidney-liver procedure in the case of decompensated cirrhosis or a lone kidney transplantation since even compensated cirrhosis after sustained viral responders is no longer considered an absolute contraindication.Nucleoside analogues have led to improved transplantation outcomes with both long-term patient and graft survival rates nearing those of HBs Ag(-)recipients.Moreover,in the cases of immunized HBs Ag(-)potential recipients with concurrent prophylaxis,we are enabled today to safely use renal grafts from both HBs Ag(+)and HBs Ag(-)/antiHBc(+)donors.In so doing,we avoid unnecessary organ discarding.Universal prophylaxis with entecavir is recommended in HBV kidney recipients and should start perioperatively.One of the most important issues in HBV(+)kidney transplantation is the duration of antiviral prophylaxis.In the absence of robust data,it seems that prophylactic treatment may be discontinued in selected stable,low-risk recipients during maintenance immunosuppression and should be reintroduced when the immune status is altered.All immunosuppressive agents in kidney transplantation can be used in HBV(+)recipients.Immunosuppression is intimately associated with increased viral replication;thus it is important to minimize the total immunosuppression burden long term.
文摘Objective: This study aims to determine surgical complications and graft outcome in children undergoing renal transplantation at Cayetano Heredia National Hospital (CHNH). Materials and Methods: A case study series focused on the incidence of surgical complications and graft outcome in pediatric patients with end stage renal disease (ESRD) who underwent renal transplant (RT) between December 2007 and March 2011. Results: The study described 29 pediatric transplant patients whose average age was 13.69 ± 3.38 (6.2-17.9) years. The etiology of end stage renal disease (ESRD) was renal hypoplasia in 12 patients (41.38%), primary glomerulopathy in 10 patients (34.48%), obstructive uropathy in 4 patients (13.79%), vasculitis in 2 patients (6.9%) and hemolytic uremic syndrome (HUS) in 1 (3.45%) patient. There were 11 surgical complications (34.48%): 2 cases of arterial thrombosis, 3 cases of urinary fistula, 3 of lymphocele, 1 of venous thrombosis, urinoma and perineal collection. The follow-up time was 15.84 ± 12.19 months. Graft survival at 12, 24, and 40 months was 89.29%, 77.16% and 77.16%, respectively. Conclusion: Surgical complications and graft survival in pediatric renal transplantation in our series did not differ from other published series.
文摘The increased awareness of systemic sclerosis(SS)and its pathogenetic background made the management of this disease more amenable than previously thought.However,scleroderma renal crisis(SRC)is a rarely seen as an associated disorder that may involve 2%-15%of SS patients.Patients presented with earlier,rapidly progressing,diffuse cutaneous SS disease,mostly in the first 3-5 years after non-Raynaud clinical manifestations,are more vulnerable to develop SRC.SRC comprises a collection of acute,mostly symptomatic rise in blood pressure,elevation in serum creatinine concentrations,oliguria and thrombotic microangiopathy in almost 50%of cases.The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis.In a scleroderma patient maintained on regular dialysis;every effort should be exerted to declare any possible evidence of renal recovery.A given period of almost two years has been suggested prior to proceeding in a kidney transplant(KTx).Of note,SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease(ESRD).KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients.Compared to other primary renal diseases,SS-related ESRD was considered for a long period of poor patient and allograft survivals.Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death.Recurrence of SRC after transplantation has been observed in some patients.However,an excellent post-transplant patient and graft outcome have been recently reported.Consequently,the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.
文摘Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.
