Racial perspectives on kidney transplant donors and recipients

Prior to undertaking a campaign to increase organ donation, demographic patterns of kidney recipients and donors were examined for our transplant center--the city and state in which it is located (Detroit and Michigan respectively). From 1984 to 1986 there were 964 kidney recipients in Michigan; 28% were black and 69% were white, whereas only 13% of the population in Michigan is black. As has been shown elsewhere in the United States, blacks have more end-stage renal disease than whites and thus require renal transplantation more often. There were 413 kidney donors from Michigan during the same period, 13% were black and 85% were white. In contrast to studies from other parts of the United States, our data show that blacks and whites in Michigan donate kidneys at a similar rate--i.e., 1.5 per 100,000 population. Data such as these should be obtained for areas where campaigns are to be conducted to increase organ donation. This information can be used to educate the public about the needs of the community.     

BK virus infection in kidney transplant recipients

INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.     

Nocardial infection in immunosuppressed kidney transplant recipients

OBJECTIVE: Nocardiosis is a very rare, opportunistic infection caused by microorganisms of the genus Nocardia, and is associated with significant morbidity and mortality in kidney transplant patients receiving immunosuppressive therapy. MATERIAL AND METHODS: Since 1980, our Renal Transplant Unit has carried out 1239 kidney transplants, and five cases of Nocardia infection have occurred during this time. In this retrospective study, special consideration is given to clinical manifestations, treatment response (efficacy and side-effects) and the evolution of both the patient and the graft. Microbiological factors studied included biochemical profiles and antimicrobial sensitivity. RESULTS: Nocardiosis was observed in five men with a mean age of 49.2 years who had received immunosuppressive therapy (generally cyclosporin/azathioprine and prednisone) for a mean of 47.8 months (range 1-148 months). Four of the patients had good previous renal function. The clinical presentation of nocardiosis was as follows: pleuropulmonary pattern of infection, n = 3; subcutaneous abscess, n = 1; and fulminant multi-organ disseminated nocardiosis, n = 1. In all cases, direct observation using modified Ziehl-Neelsen staining proved positive, and in vitro culture revealed good sensitivity to trimethoprim-sulfamethoxazole and variable sensitivity to the other groups of antibiotics. Nocardia brasiliensis was isolated in two cases, and Nocardia asteroides in three. Two patients died, one due to multiple organ involvement and the other due to acute respiratory failure associated with severe hepatopathy caused by hepatitis C virus. The remaining cases improved. CONCLUSION: A low incidence of nocardiosis following kidney transplantation was observed. Fatal cases occurred in patients with bacteremia and serious comorbid medical conditions, in whom early diagnosis and specific treatment was required.     

Human herpesvirus 7 primary infection in kidney transplant recipients

The aims of the study were to evaluate the incidence and the clinical implications of human herpesvirus (HHV)-7 primary infection in patients undergoing kidney transplantation and the probable interactions between the three beta-herpesviruses (cytomegalovirus [CMV], HHV-6, and HHV-7). Sixty kidney transplant recipients had sequential plasma and whole blood samples collected prior to transplantation and at 7, 14, 21, 28, 45, 60, 75, 90, and 180 days posttransplantation. We used indirect immunofluorescence assays to detect HHV-7 immunoglobulin (Ig) G antibodies in plasma and quantitative real-time polymerase chain reaction to assess CMV, HHV-6 and HHV-7 viral loads. Sixteen out of 60 patients (27%) did not show HHV-7 IgG antibodies prior to transplantation and they were selected for this study. Whereas 3 (18.75%) out of the 16 HHV-7 seronegative patients seroconverted after transplantation, only one patient (6%) had a high HHV-7 viral load from the seventh day posttransplantation in consecutive blood samples during follow-up without clinical manifestations. In our study, the incidence of posttransplant HHV-7 primary infection was low and asymptomatic.     

Hepatitis E virus infection and rejection in kidney transplant recipients

BackgroundHepatitis E virus (HEV) infection has been associated with immune-mediated kidney diseases in developing countries. However, its relationship with kidney transplant outcomes has never been studied. We investigated the association between HEV infection and kidney graft rejection among kidney transplant recipients (KTRs).MethodsWe conducted a matched cohort and longitudinal study utilizing banked sera following kidney transplantation during 1988–2012. Studies with evidence of post-transplantation HEV infection were identified by positive ELISA tests (anti-HEV IgM or anti-HEV IgG seroconversion) or positive HEV PCR and matched to KTR controls with negative HEV ELISA and PCR tests in a 1:5 ratio by age, sex, crossmatch status, immunosuppression era, and time of HEV testing. Outcome data collected included time to first kidney graft rejection, transaminases, and glomerular filtration rates. Log-ranked test was used to analyze survival.ResultsOf 271 KTRs, 9 (3%) had evidence of post-transplantation HEV infection and were compared to 45 negative, matched controls. Median age at transplantation was 46 years. Kidney graft rejection was reported in 8 (89%) of cases and 21 (47%) of controls. Median time to first episode of kidney graft rejection was 17.4 months in cases and 30.8 months in controls (p = 0.029), with a higher hazard of developing kidney graft rejection in cases (HR = 3.23, 95% CI: 1.19–8.79). Lower mean glomerular filtration rates over time were observed in cases (35 mL/min/1.73m²) versus controls (42.4 mL/min/1.73m²) but did not reach significance (p = 0.24).ConclusionSubjects with evidence of post-transplantation HEV infection demonstrated earlier kidney graft rejection compared to controls.     

肾移植术后并发病毒感染和泌尿系统肿瘤

肾移植术后恶性肿瘤的发病率明显高于正常人群,是移植患者长远期的严重并发症之一.在不同地区、不同种族之间,肾移植术后恶性肿瘤的发生率、类型及特征都有很大不同.欧美报道以皮肤癌、淋巴瘤多见,而我国最常见的恶性肿瘤为泌尿系统肿瘤,其中又多表现为移行上皮肿瘤,且女性发病率明显高于男性.移植后病毒感染和肿瘤的发生有密切关系,常见的如人类乳头瘤病毒(HPV)、BK病毒、人类疱疹病毒(HHV) 和Epstein Barr病毒等,各种病毒与肿瘤的关系需要不断深入的研究.     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Hepatitis C virus infection among kidney transplant recipients.

The extent of hepatitis C virus (HCV) infection among kidney recipients was investigated in 67 patients by testing for anti-HCV paired serum samples, collected at time of transplantation and during follow-up (average 32 +/- 20 months). Prevalence of anti-HCV at transplant time was 48%, and was related to the time on dialysis and to the amount of blood transfusions. Following transplantation, nine (28%) seropositive patients lost anti-HCV and five (14%), previously seronegative, seroconverted. Anti-HCV was found to be positive in 92% of the patients with chronic liver disease who were on hemodialysis, but in 56% in kidney recipients with chronic hepatitis. Anti-HCV was positive in 50% of patients with resolving hepatitis before transplantation, but only in 21% of those with acute hepatitis following transplantation. This study confirms the high risk of HCV infection among hemodialysis and kidney recipient populations, and also that HCV is closely related with the length of time the patient is on hemodialysis as well as the number of blood units transfused. HCV is the main cause of acute and chronic liver disease in hemodialysis patients and of chronic liver disease in kidney recipients, but does not clearly influence the survival of the allograft nor that of patients.     

Dyadic adjustment and psychological concordance of kidney transplant recipients and donors after spousal transplantation

The aim of this study was to compare depression and anxiety levels of kidney transplant recipients and of their donor spouses seeking to show whether their dyadic adjustment levels related to their psychological states in the posttransplantation period. We selected 30 donor-recipient pairs who underwent spousal kidney transplantation. The study was performed while participants were in the hospital for routine examinations. Both donors and recipients were administered The Dyadic Adjustment Scale, The Hospital Anxiety and Depression Scale, and The Beck Depression Inventory. Our results showed correlations between donor and recipient postoperative depression levels (P < .01). For donors, dyadic adjustment and depression levels were correlated, but not for recipients. Pretransplantation psychological assessment of a spousal donor is necessary to provide pretransplantation interventions for possible depressive disorders and marital dysfunction. In this way, recipient depression and anxiety levels may be reduced in the posttransplantation period with better treatment compliance and improved graft survival.     

Pregnancy in kidney transplant recipients

PURPOSE: Our aim was to investigate kidney allograft, obstetric, and maternal outcomes in pregnant women undergoing kidney transplantation in our center. METHODS: Retrospective data on 74 pregnancies in 60 patients were reviewed and completed through phone interviews were compared with information on a control group of female kidney recipients. RESULTS: Mean age of patients at transplantation was 26.55 +/- 4.72 years and the median interval between transplantation and pregnancy was 27.5 months. Gestational period was 8 months. Live birth was the outcome in 43.2% of pregnancies; 9.5% led to still birth, 24.3% were aborted, and obstetrical data of the remaining were unavailable. Among the 11 patients who became pregnant within 12 months after transplantation, we observed seven live births and four abortions. None of pregnancies that were accompanied by acute rejection episodes (ARE) were successful. Twenty-six patients experienced at least one ARE versus 23 patients of the control group (P = NS). However, the first ARE occurred later in the pregnant group (P = .028). Chronic rejection and graft loss were seen in 24 and 18 study group cases and 17 and 17 control cases, respectively (P = NS). One-, 3-, 5-, and 10-year graft survivals were 100%, 96.5%, 94.5%, and 77.1% in the pregnant group versus 93.2%, 85.7%, 81%, and 64.7% in the control group, respectively (P = .07). CONCLUSION: Pregnancy in kidney recipients seems to be safe for kidney allograft recipients even within the first year posttransplant. Nonetheless, the outcomes of pregnancy in this group of patients is not always favorable, especially when rejection occurs simultaneously.     

肾移植患者并发严重肺部感染的诊断与治疗

目的 :对肾移植并发严重肺部感染的诊断与治疗方法进行研究。方法 :对住院治疗的 32例肾移植术后严重肺部感染者的临床资料进行回顾性分析。结果 :① 2 6例治愈 ,6例死亡。②支气管肺泡灌洗的病原体检出率为 74 % (2 0 / 2 7) ,血培养结合痰、咽拭子培养病原体检出率为 4 7% (15 / 32 ) ,二者比较差异有统计学意义 (P <0 .0 5 )。③感染发生时间为术后 2周～ 11年。术后 3个月内的严重感染发生例数占所有严重感染病例的 35 %(11/ 32 ) ,术后半年内为 72 % (2 3/ 32 ) ,最长者为术后 11年发病。④治疗措施包括早期根据经验应用抗生素 ,根据检查结果及时调整抗生素 ;大胆减用免疫抑制剂 ,必要时停止应用免疫抑制剂 ;病情危重 ,免疫功能极低者可使用免疫增强剂 ;对肺渗出者应用皮质类固醇。结论 :肾移植术后并发严重肺部感染者病情危重 ,死亡率高 ,应早期应用肺泡灌洗检查病原体 ,反复胸片检查 ,应用抗生素并及时调整抗生素 ,早期减用或停用免疫抑制剂 ,并可应用免疫增强药物胸腺肽及干扰素 ,对肺渗出者应用皮质类固醇。     

Cryoglobulinemia in kidney transplant recipients

The aim of this study was to assess the presence of cryoglobulins, the constitution of the cryoprecipitate, as well as the possible etiology and clinical features in kidney transplant recipients. We excluded patients with clinical or laboratory evidence of autoimmune, liver or neoplasm disease, infections, blood transfusions or immunizations in the previous 3 months. Detection of cryoglobulins was obtained from the peripheral venous blood. In cases of cryoprecipitate formation it was analyzed using anti-IgG, anti-IgM, anti-IgA, anti-C3, and anti-C4 antibodies. The hepatitis C virus (HCV) was detected by the polymerase chain reaction. Thirty-nine patients were selected, of whom 23 were men and the overall mean age was 40.6 +/- 12.7 years. Cryoprecipitate was detected in 74.4% (29/39) patients. Among patients with or without cryoprecipitate formation, the serum creatinine values, the percentage of patients with proteinuria, and the posttransplantation times were similar. In patients with cryoglobulins, 37.9% (11/29) were HCV positive. The etiology was not determined for the other patients. The IgG, IgM, and IgA immunoglobulins and the complement fractions C3 and C4 were found in the cryoprecipitate. Their compositions were similar among patients with or without HCV. Few clinical features were associated with the presence of cryoglobulins, including deep venous thrombosis, cutaneous purpura and peripheral neuropathy. In conclusion, cryoglobulinemia was prevalent in kidney transplant recipients, but appeared to not affect graft function. HCV infection was the most frequently associated etiology and clinical features were infrequent.     

Hypertension in kidney transplant recipients

Arterial hypertension is frequently observed in renal transplant recipients. Its pathogenesis is multifactorial in most cases. Calcineurin inhibitors (CNI) can increase peripheral vascular resistance by inducing arteriolar vasoconstriction and can cause extracellular fluid expansion by reducing the glomerular filtration rate (GFR), activating the renin–angiotensin system (RAS), and by inactivating the atrial natriuretic peptide. Glucocorticoids can impair urinary water and salt excretion. Poor graft function can lead to increased extracellular volume and inappropriate production of renin. Native kidneys, older age of the donor and transplant renal artery stenosis (TRAS) may also contribute to the development of hypertension. Arterial hypertension not only can increases the risk for cardiovascular events but can also deteriorate renal allograft function. A number of studies have shown that the higher the levels of blood pressure are, the higher is the risk of graft failure. On the other hand, a good control of blood pressure may prevent many cardiovascular and renal complications. Appropriate lifestyle modification is the first step for treating hypertension. Calcium channel blockers (CCB) and renin–angiotensin system (RAS) inhibitors are the most frequently used antihypertensive agents, but in many cases, a combination of these and other drugs is required to obtain good control of hypertension.     

Fatigue in kidney transplant recipients

Fatigue is still present in approximately 40%‐50% of kidney transplant recipients (KTR), rates comparable to that of the hemodialysis population. Correlates of fatigue include inflammation, symptoms of depression, sleep disorders, and obesity. Fatigue in KTR determines a significant severe functional impairment, either when globally considered or when analyzed at the level of the single domains such as sleep and rest, homemaking, mobility, social interaction, ambulation, leisure activities, alertness behavior, and work limitations. In addition, fatigue in KTR is significantly associated with a severe deterioration of quality of life. Fatigue is very common among KTR poorly adherent to immunosuppressive therapy. Unfortunately, there is no evidence of studies about the treatments of this symptom in KTR. Efforts to detect and treat fatigue should be a priority in order to improve quality of life of KTR.     

The effect of polyimmune gammaglobulin for prophylaxis against reactivation cytomegalovirus infection in kidney and kidney/pancreas transplant recipients.

Cytomegalovirus (CMV) remains the most important infection in the renal transplant recipient. Few data are available that provide guidance for approaches that seek to reduce the reactivation of latent disease after transplantation. To test the efficacy of polyimmune gammaglobulin in kidney and kidney/pancreas transplantation, consenting recipients with serologic evidence of previous CMV disease were randomized to receive i.v. polyimmune gammaglobulin (500 mg/kg) within 3 days of transplant with 250 mg/kg at weeks 1, 2, 4, and 6 or no prophylaxis. Both groups received identical induction and rejection immunosuppressive therapy. Polyimmune gammaglobulin prophylaxis reduced CMV reactivation infections. The incidence of reactivation infections was half in patients receiving Nashville/rabbit antithymocyte serum (N/R-ATS) compared with those receiving monoclonal anti-CD-3 therapy. Patients receiving polyimmune gammaglobulin along with N/R-ATS had an incidence of infection of only 10%. Reactivation infections were twice as common in patients who had primary nonfunction and nearly three times as common in patients with acute rejection. Both risk factors were associated with longer anti-T-cell therapy. Polyimmune gammaglobulin prophylaxis should be considered in transplant patients with previous CMV exposure who will be receiving prolonged anti-T-cell therapy because of acute rejection or primary nonfunction.     

Hepatitis G virus infection in chronic dialysis patients and kidney transplant recipients

Background: The cloning of the hepatitis G virus (HGV), a novel RNA virus of the Flaviviridae family, has been very recently developed. HGV is known to be parenterally transmitted and has been detected in several patients with cryptogenic hepatitis. However, little information exists about the epidemiology of HGV infection in renal patients. We studied 178 chronic dialysis patients and 11 renal transplant individuals to evaluate prevalence risk factors and clinical manifestations of HGV infection in this population. Method: Hepatitis G virus infection has been detected by a modified PCR technology which incorporates digoxigenin-labelled nucleotides into the amplicon. Primers from the non-coding region and the NS-5 region of HGV are utilized for a single round amplification. Using a streptavidin surface and a biotin-labelled capture probe the labelled nucleic acid is bound through the capture probe to the surface, and the amplified nucleic acid is detected using antibody to digoxigenin. Results: HGV RNA was detected in 6% of chronic haemodialysis (HD) patients (11/172), 36% of renal transplant recipients (4/11), and 17% (1/6) of patients on peritoneal dialysis treatment (CAPD). There were no significant differences between HGV positive and negative patients on chronic HD treatment with regard to several demographic, biochemical and virological features. However, the frequency of anti-HCV antibody was significantly higher in HGV-positive than HGV-negative patients (9/11 (82%) vs 51/161 (32%), P=0.006). In the whole group of HGV RNA-positive patients, 78% (11/14) had a history of blood transfusion requirements, 14/16 (87%) had co-infection with HCV, and 1 (6%) had co-infection with HBsAg. There was no significant association between HCV genotypes and HGV RNA positivity. Six (27.5%) of 16 HGV RNA-positive patients showed raised aminotransferase values in serum. Conclusion: Patients on maintenance dialysis and kidney transplant recipients are at increased risk of HGV infection; HGV is very frequently associated to hepatitis C co-infection, regardless of HCV genotype. HGV may be transmitted by blood transfusions but transmission routes other than transfusion are possible; 37.5% of HGV RNA-positive patients showed raised serum amoinotransferase levels. Further investigations are necessary to clarify the role of HGV infection in the development of liver disease in this clinical setting.     

肾移植供者及受者肝炎等病毒和螺旋体感染的调查

目的 调查肾移植供、受者肝炎病毒及其他病毒感染和螺旋体感染的情况,研究其感染与移植术后人／肾存活率的关系。方法 对供者及移植受者群进行乙型肝炎（HBV）、丙型肝炎（HCV）、庚型肝炎病毒（HGV）及巨细胞病毒（CMV）、EB病毒、单纯庖疹病毒（HSV）、艾滋病病毒（HIV）、梅毒螺旋体（RPR）的调查。结果 361名供者中,感染HBV者8.6%,感染HCV者2.5％,感染HGV者0.6％;231名供者中,CMV－IgM阳性者16.9％,EB－IgM阳性者11.7％,HSV－IgV阳性者16.0％,HIV病毒携带者1名,RPR－IgM阳性者2名。300例移植受者中,HBV感染率为68.7％,HCV感染率为34.7％,HBV合并HCV感染率为25.0％,HGV、HBV合并HCV感染率为12.5％,CMV－IgM阳性者49.0％,EB－IgM阳性者32.7％,HSV－IgM阳性者42.0％,无HIV携带者及RPR－IgM阳性者49.0％,EB－IgM阳性者32.7％,HSV-IgM阳性者42.0％,无HIV携带者及RPR－IgM阳性者。结论 供者群及受者本身的术前病毒感染状态对移植者术后是否发生病毒感染至关重要。