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Background: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients., Methods: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b)., Results: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively)., Conclusions: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.

Purpose: In this retrospective study with case-control design, we aimed to determine the clinical and pathological characteristics of post-transplant glomerulonephritis (GN), and their effects on transplant recipients., Methods: One hundred and twenty renal transplant recipients with biopsy-proven recurrent or de novo primary GN were compared with two matched control groups including 120 transplant recipients with nonrecurrent primary GN (nonrecurrent GN group) and 120 transplant recipients with non-GN etiology (non-GN group). Primary outcome was allograft loss, and secondary outcomes were biopsy-confirmed cellular or antibody-mediated rejection., Results: In recurrent/de novo GN, nonrecurrent GN and non-GN groups, 54.2% (n = 65), 16.7% (n = 20) and 8.3% (n = 10) of patients reached primary outcome after a median follow-up of 96 (IQR: 56-149) months, respectively. Allograft loss was significantly higher in recurrent/de novo GN group compared to nonrecurrent GN and non-GN groups (p < 0.001). At 10 years, allograft loss rates in recurrent/de novo GN group were 54.2% for focal segmental glomerulosclerosis, 53.2% for membranoproliferative glomerulonephritis, and 33.4% for IgA nephropathy cases. Biopsy-confirmed rejection rate was significantly higher in the recurrent/de novo GN group (n = 25, 20.8%) compared to non-GN (n = 8, 6.7%) group (p = 0.001)., Conclusions: Recurrent/de novo GN is associated with higher risk of rejection and worse allograft survival.

Background: Antibody-mediated rejection is a frequent cause of graft failure; however, prognostic indications of this complication have not been well defined. The aim of this study was to evaluate the association of histopathological and clinical features and to determine the effect of these findings on allograft survival in patients with AMR., Methods: Fifty-two patients suffered from AMR (30 male; mean age 39 ± 11 years) were included in the study. Data were investigated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff 2009 classification., Results: Of the 52 cases, 45 were transplanted from living-donors. Twenty-one patients were diagnosed in the first 3-months after transplantation. Graft survival was 65% at 12 months and 54% at 36 months. Mean serum creatinine at time of biopsy was 3.8 ± 3.6 mg/dL. Thirty-five of the 52 cases showed diffuse C4d positivity, 12 cases showed focal and 5 remained C4d negative. One of the patients died, 13 experienced graft loss and 38 survived with functioning grafts. Serum creatinine levels at time of biopsy were correlated with graft survival (p = .021: OR = 1.10: 95 % CI = 1.015-1.199). In terms of the impact of pathological findings; tubulitis (p=.007: OR = 2.62: 95 % CI = 1.301-5.276), intimal arteritis (p=.017: OR = 2.85: 95% CI = 1.205-6.744) and interstitial infiltration (p=.004: OR = 3.37: 95% CI = 1.465-7.752) were associated with graft survival., Conclusions: Serum creatinine at time of biopsy, tubulitis, intimal arteritis and interstitial infiltration were significantly associated with graft survival. Antibody-mediated rejection is associated with reduced long-term graft survival.

Introduction: The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients., Materials and Methods: The primary outcome variable was reduced renal function. Secondary endpoints were incidence of biopsy-confirmed chronic antibody-mediated rejection (CAMR) and recurrent glomerulonephritis (GN)., Results: There were no differences regarding initial serum creatinine levels between the study and control groups (P = .441). Patients who had positive auto-B FCXM had a significantly reduced renal function compared with the control group (P = .016). Four patients developed biopsy-confirmed CAMR in the study group and 1 patient in the control group (P = .047). Five patients had biopsy-confirmed recurrent GN in the GN study group, and only 1 patient had recurrent GN in the GN control group (P = .026)., Discussion: Kidney transplant recipients with positive auto-FCXM test had significantly reduced renal function and a higher incidence of recurrent GN and CAMR compared with the control group. The findings of this study suggest a potential role of auto-antibody causing positive auto-FCXM test result, meanwhile increasing the risk of CAMR, recurrent GN, and new-onset diabetes after tx., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts., Methods: 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups., Results: The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p&lt;0.001 and p&lt;0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p&lt;0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p&lt;0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3., Conclusions: Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

Background: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time., Methods: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency., Results: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively., Conclusions: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 +/- 71 months. Mean serum creatinine level was 1.63 +/- 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 +/- 0.58 mg/dL (P = 0.67), 1.52 +/- 0.53 mg/dL (P = 0.414), 1.62 +/- 0.62 mg/dL (P = 0.734), and 1.48 +/- 0.58 mg/dL (P = 0.065), 1.58 +/- 0.53 mg/dL (P = 0.854), 1.88 +/- 0.77 mg/dL (P = 0.083), respectively. Daily proteinuria levels increased from 0.04 +/- 0.11 g/day at baseline to 0.55 +/- 1.33 g/day (P = 0.037) after conversion, in the responders group. In the nonresponders group, baseline proteinuria was 0.13 +/- 0.25 g/day, and increased to 1.44 +/- 2.44 g/day after conversion (P = 0.008). SRL was discontinued in 16 patients (31%) because of the occurrence of severe side effects. The proportion of patients remaining on SRL therapy over time was 43.1% at 1 year, 15.5% at 2 years after conversion, and 10.3% at 3 years after conversion. SRL conversion may be very useful in patients suffering from neoplasia; however, frequent side effects related with this intervention should be considered, and routine conversion from CNI to SRL to reduce nephrotoxicity should be discouraged.

Background: The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aimed to compare the nutritional status and its relation with inflammation in patients on HD with and without previous kidney transplantation., Methods: Forty-three patients with failed renal allografts (27 males; mean age 36±9 yr) and 40 never transplanted HD patients (24 males; mean age 39±9 yr) were included in the study. Body weight, triceps (TSF), biceps (BSF), subscapular (SSSF), and suprailiac skinfold thicknesses (SISF); mid-arm, mid-arm muscle, hip and waist circumferences; as well as body mass indices (BMIs) were determined as anthropometric parameters. Moreover, biochemical markers of nutritional status, including serum cholesterol and albumin as well as high-sensitive C-reactive protein (hs-CRP), as a marker of inflammation, were measured. Associations among these variables were analyzed., Results: There were no significant differences considering age, gender or duration of renal replacement therapy between the two groups. The TSF (p<0.0001), BSF (p=0.005), SSSF (p=0.001), SISF (p<0.0001) skinfold thicknesses; mid-arm (p=0.003) and mid-arm muscle circumferences (p=0.037) and BMIs (p=0.001) of the patients with failed renal allografts were significantly lower than those of the never transplanted HD patients. Waist circumference was significantly lower as well (p=0.028). Patients with failed transplants were characterized by lower serum albumin (p<0.0001) and higher hs-CRP levels (p=0.001) as compared with never transplanted HD patients., Conclusions: This study confirms the concept that retained failed allografts may induce chronic inflammation in chronic HD patients which may result in a worse nutritional status., (© 2009 John Wiley & Sons A/S.)

Background: Although many transplanted women who were previously infertile can conceive during the posttransplant period, maternal and fetal complications are likely. We evaluated the effect of pregnancy after renal transplantation in this study., Methods: We retrospectively evaluated female renal transplant recipients who became pregnant. Age- and transplantation time-matched nonpregnant patients were used as a control group. We analyzed data regarding the demographic features of the pregnant patients, their serum creatinine levels before pregnancy, during pregnancy and during the postpartum period until now, immunosuppressive drugs, complications during pregnancy and fetal complications., Results: In total 57 patients were included in this study. We divided the transplanted patients into two groups: 22 deliveries in 19 patients (delivery group) and 38 nonpregnant patients (control group). The mean follow-up durations and ages of transplantation were similar in the two groups. There was no significant difference in the mean serum creatinine values of the two groups (p = 0.42). Regarding immunosuppressive drugs, there was no significant difference between the two groups (p = 0.23). The frequencies of chronic hypertension, proteinuria, use of erythropoietin, and urinary tract infection were not statistically significantly different between the two groups (p = 0.31, 0.59, 0.36, 0.28, respectively). There were also no significant differences noted in graft and patient survival between the groups (p = 0.577)., Conclusion: Female transplant recipients who have stable creatinine levels, insignificant proteinuria, and normal blood pressure or controlled hypertension may become pregnant, and they can have successful pregnancies. Their graft functions and survivals are not affected by gestation.

Background: The effect of pre-transplant dialysis modality on early graft function is a matter of debate. Although some authors deny the existence of a significant influence, others suggest that peritoneal dialysis (PD) affects early graft function favorably, possibly by contributing to a more physiologic water balance. In the present study, we evaluated the influence of pre-transplant dialysis modality on early and late graft function., Patients and Methods: We studied 745 patients who underwent a first renal transplantation during 1983-2006, comparing the records of 44 PD patients [26 male; mean age: 26 +/- 9 years (range: 8-56 years)] who received 36 living related and 8 cadaveric renal transplantations with those of a control group of 44 consecutive hemodialysis (HD) patients [26 male; mean age: 27 +/- 11 years (range: 7-49 years)] for the index cases., Results: The groups showed no significant differences in donor type, human leukocyte antigen matching, immunosuppressive protocols, and duration of dialysis. Also, neither group differed significantly with regard to incidence of delayed graft function, acute tubular necrosis, wound infection, systemic viral and bacterial infections, or acute rejection in the early post-transplant period. In the late post-transplant period, incidences of chronic rejection, graft failure, and malignancies were also similar. During the follow-up period, 3 patients in the PD group experienced acute rejection, 2 developed cytomegalovirus (CMV) disease, and 5 developed various other infections. In the HD group, 4 patients experienced acute rejection, 1 developed CMV disease, and 8 experienced other infections. Five patients in the PD group and one in the HD group died with functioning grafts (p = 0.09). No differences were noted between the groups in the incidences of post-transplant cardiovascular complications, malignancies, and diabetes mellitus. In the PD group, 33 patients with functioning grafts are still being followed, 6 have returned to dialysis, and 5 have died. In the HD group, 38 patients with functioning grafts are still being followed, 5 have returned to dialysis, and 1 has died., Conclusions: As a pre-transplant dialysis modality, neither HD nor PD affects the outcome of renal transplantation.

Fever of unknown origin (FUO) in hemodialysis (HD) patients represents a diagnostic challenge because differential diagnosis includes diverse etiologies. Causes of FUO in the general population can be classified into 3 diagnostic categories: infections, tumors, and noninfectious inflammatory diseases. Also, chronic HD patients may have additional problems such as infections, the risk for which may be increased by the immunosuppression associated with uremia, vascular access-related infections, and nosocomial infections. Moreover, patients with chronically failed kidney transplants can have low-grade fever and abdominal pain, and if inflammation of the allograft is severe enough, it may result in a spontaneous rupture. Hence, it is important to rapidly recognize, diagnose, and manage these complications. In the present study, we report a case of FUO in an HD patient with a failed graft and discuss clinical approach and management of these patients.

Background: Chronic allograft dysfunction (CAD), the major cause of the failure of kidney allografts, may be caused by immunological and non-immunological haemodynamic factors. Renin-angiotensin system has been implicated in the development of intraglomerular hypertension and has a central role on progression in chronic renal disease. Polymorphism in 16th intron of the ACE gene has been reported to predict the circulating angiotensin II levels. The aim of this study was to investigate the effect of the both recipient and donor angiotensin converting enzyme (ACE) genotype on the development of CAD in renal allograft recipients., Patients and Methods: A total of 143 renal transplant recipients (95 male, 48 female, mean age 32 +/- 10 yr) were included. In order to exclude the effect of cold ischaemia, only patients transplanted from living donors were selected. Factors analysed in the development of CAD were donor and recipient age, past history of acute rejection, presence of hypertension and hypercholesterolaemia, serum uric acid level and ACE gene polymorphism., Results: Forty of the patients (28%) had CAD. Homozygous deletion type ACE gene polymorphism was detected in 59 renal transplant recipients (42%) and in 31 donors of the patients (37%). On comparing patients with and without CAD, donor age, rate of acute rejection and hypertension and serum uric acid levels were significantly higher in CAD (+) groups. Neither recipient nor donor ACE genotype was associated with time to CAD. Cox regression analysis revealed donor age (p < 0.001), presence of hypertension (p=0.002) and serum uric acid levels (p=0.009), but neither donor nor recipient ACE genotype as independent factors for predicting development of CAD., Conclusion: Donor age, presence of hypertension and serum uric acid levels was independent factors. Donor and recipient ACE genotype seemed to have no influence on the development of CAD in living donor transplanted patients.

Introduction: Fever of unknown origin is a complex problem in dialysis patients with recently rejected renal allografts, due to the contribution of the newly withheld immunosuppressive agents to the immunosuppression of uremia, resulting in an atypical presentation of infections, a main cause of fever in these cases., Materials and Methods: Two dialysis patients with recently rejected renal allografts who were hospitalized because of fever of unknown origin are reported. Biochemical, bacteriological and imaging studies were performed for specific diagnosis., Results: Extensive laboratory investigations failed to yield any diagnosis and allograft nephrectomy was performed in one patient, with a probable diagnosis of inflammation of the allograft, which resulted in no improvement. Eventually, both patients were found to have adrenal insufficiency responsible for the fever, which improved after steroid replacement., Conclusions: Adrenal insufficiency should be suspected in all dialysis patients presenting with fever and atypical symptoms, but only after other potential causes are eliminated; since steroid administration may normalize fever regardless of the etiology, it may mask the signs and symptoms and delay the treatment of other (if any) underlying disorder(s).