First Year Of Renal Transplantation Research Articles

Incidence and risk factors for urinary tract infections in the first year after renal transplantation.

BackgroundThe most common infections among renal transplant patients are urinary tract infections (UTI). Our main objective in this study is to determine the incidence of UTIs in patients who have undergone renal transplantation in our hospital, to identify the causative microbiological agents, risk factors and determine the effects of UTI on short-term graft survival.MethodsUrinary tract infections, which developed within the first year of renal transplantation, were investigated. Patients were compared regarding demographic, clinical, laboratory characteristics and graft survival.Results102 patients were included in our study. Fifty-three patients (53%) were male and 49 (48%) were female. Sixty-seven urinary tract infection attacks in 21 patients (20.5%) were recorded. Age (p = 0.004; 95% Confidence Interval [CI]: 1.032–1.184), longer indwelling urinary catheter stay time (p = 0.039; 95% Confidence Interval [CI]: 1.013–1.661) and urologic complications (p = 0.006; 95% Confidence Interval [CI]: 0.001–0.320) were found as risk factors for UTI development in the first year of transplantation. Escherichia coli and Klebsiella pneumoniae were the most frequently isolated microorganisms. Of these bacteria, 63.2% were found to be extended spectrum beta lactamase (ESBL) positive. Multidrug resistant microorganisms (MDROs) were more frequent in male patients (32 episodes in males vs. 14 episodes in females, p = <0.001). UTI had no negative impact on short-term graft survival.ConclusionOur study results represent the high incidence of UTI with MDROs in KT recipients. Infection control methods should be applied even more vigorously especially in male transplant patients since a higher incidence of UTI caused by resistant microorganisms was reported in male patients.

Evaluation of post-transplant complications, patient and graft survival in patients with autosomal dominant polycystic kidney disease after renal transplantation; A single center experience

Aim: Autosomal dominant polycystic kidney disease (ADPKD) is systemic, progressive hereditary disease, characterized by cyst formation in multiple organs. Patients with ADPKD mostly develop end stage renal disease (ESRD) and require renal replacement therapy, preferably renal transplantation (RT). In this study, we aimed to compare the post-RT complications, patient and graft survivals in patients with ADPKD and other etiologies of ESRD.Materials and Methods: We retrospectively evaluated patients’ baseline characteristics, post-RT complications, patient and graft survival in patients with ESRD underwent renal transplantation due to ADPKD and other etiologies. We included 28 patients in ADPKD and 28 patients in the control group.Results: The mean survival time was 224.83 ± 7.53 months in all patients. During follow-up period 1 patient died in both groups and 10 years patients and graft survivals were similar for both groups. The graft survival, acute and chronic rejections and glomerular filtration rate levels were similar in both groups end of the first year of RT but total cholesterol and glucose levels were significantly higher in the ADPKD group. Moreover, developing of ischemic heart disease was significantly higher in ADPKD (32% vs 0%, p=0.002), the other complication rates were similar in both.Conclusion: As a comparesion to patients with ESRD underwent RT due to ADPKD and different etiologies, both groups have similar patient and graft survival rates. Patients with ADPKD after transplantation may have a higher incidence of ischemic heart disease.

Factors Influencing Emergency Department Utilization and Hospital Re-Admissions in a Predominantly Obese, Racially Diverse Urban Renal Transplant Population.

Early emergency department and hospital re-admissions are common in renal transplant recipients, but data are lacking in unique populations. Study Aim: The purpose of this study was to identify patient risk factors for multiple acute care utilization events within the first year of renal transplantation. This was a single-center, retrospective cohort study of adult renal transplant recipients between 9/2013-9/2016. Patients were compared across number of emergency department visits and by hospital re-admissions. Diagnoses were categorized. Univariate and multivariate logistic regression was used to assess risk for multiple acute care utilization events within the first 12 months post-transplant. A total of 216 patients were analyzed and were on average 50.5 (SD 13.9) years old, redominantly Black (49.77%) with an average body mass index of 33.33 (9.8) and were recipients of deceased donor renal transplants (61.11%). A total of 105 (48.6%) patients visited the emergency epartment and 119 (55.1%) patients had a hospital readmission. Patients having a body mass index >35 kg/m2 did not differ across emergency department visit or hospitalization groups. Delayed graft function (OR 2.86, 95% CI 1.07-7.65) and previous renal transplant (OR 2.77, 95% CI 1.04-7.39) were significantly associated with multiple acute care utilizations. Acute care utilization following renal transplantation was similar to previously reported experiences. Obesity did not impact use of acute care resources or patient outcomes. Strategies addressing potential preventable emergency visits and hospital re-dmissions should be promoted.

Observation of Infections during First Year of Renal Transplantation: Etiology, Risk Factors and Outcome

Observation of Infections during First Year of Renal Transplantation: Etiology, Risk Factors and Outcome

An extension of the RITUX-ERAH study, multicenter randomized clinical trial comparing rituximab to placebo in acute antibody-mediated rejection after renal transplantation.

The treatment of active antibody-mediated rejection (ABMR) is still a matter of debate, the place of rituximab remaining controversial. The French multicenter double-blind RITUX-ERAH study included 38 patients with ABMR in the first year of renal transplantation. All patients received plasma exchanges, intravenous immunoglobulins, and corticosteroids and were randomly assigned rituximab or placebo infusion at day 5. Additional rituximab infusions were allowed. In the intention-to-treat analysis, 12-month graft survival and renal function were not different between the rituximab and placebo groups. Long-term data are needed to conclude. Evaluation of the 7-year outcomes of the RITUX-ERAH study patients according to the rituximab or placebo treatment received. Eleven patients received placebo and 27 at least one infusion of rituximab. Seven years after ABMR, death-censored kidney allograft survival and renal function were not different between the groups. The evolution of anti-HLA sensitization was similar. There was no statistically significant difference in the incidence of infectious or neoplastic complications, but to be noted, seven cancers developed in six patients treated with rituximab (mean period of 44months post-ABMR). In this cohort, there was no benefit 7years after ABMR of rituximab in addition to plasma exchanges, intravenous immunoglobulins, and steroids.

Impact assessment and investigation of factors associated with herpesviruses viremia in the first year of renal transplantation.

The increased risk for opportunistic infections after a renal transplant requires monitoring of viral infections to avoid future complications. Our goal was to investigate the impact and factors associated with Epstein-Barr virus (EBV), human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) viremia in renal transplant recipients. Whole blood samples were collected monthly from 82 patients during the first semester and then quarterly up to 1 year after transplantation. EBV, HCMV, and HHV-6 were detected and quantified by TaqMan real-time polymerase chain reaction. The results showed that EBV and HCMV viremia were detected in 32 patients (39% each), while HHV-6 viremia in only 3 patients (3.7%). EBV was significantly associated with age (P = .050), thymoglobuline induction (P = .019), mTOR inhibitor-based therapy (P = .003), and female gender (P = .044). HCMV was significantly associated with basiliximab induction (P = .015), mycophenolate mofetil (MMF)-based therapy (P = .003) and allograft acute rejection (P = .033). Moreover, HCMV-disease was correlated with MMF-based therapy (P = .021) and female gender (P = .003). In conclusion, EBV and HCMV viremia were associated with different immunosuppressive induction and maintenance strategies. Additionally, higher HCMV viremia (> 10 4 copies/mL) was related to acute allograft rejection.

Prognostic Value of the Persistence of C1q-Binding Anti-HLA Antibodies in Acute Antibody-Mediated Rejection in Kidney Transplantation.

The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs helps in better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. We included patients from the French multicenter RITUX ERAH study diagnosed with acute ABMR within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange). We centrally analyzed serum samples at the time of ABMR, 3 and 6 months after ABMR, with anti-HLA DSAs specificities and C1q-binding capacity assessment. Twenty-five patients were included: 68% had C1q-binding DSAs at the time of ABMR. The presence of C1q-binding DSAs was associated with a poorer evolution of chronic glomerulopathy at 6 months (P = 0.036). The persistence of C1q-binding DSAs at 3 and/or 6 months after ABMR was associated with more severe chronic glomerulopathy (P = 0.006), greater C4d score deposition score at 6 months after ABMR (P = 0.008), and graft loss 5 years after ABMR (P = 0.029). C1q-binding capacity was associated with the DSA MFI but 5 C1q-binding DSAs in 4 patients had low MFI values without a prozone effect. The presence and persistence of anti-HLA C1q-binding DSAs after ABMR is a detrimental marker, leading to transplant glomerulopathy and graft loss. Assessment of the complement-binding capacities of DSAs could help decide treatment intensification.

Evolución del peso en pacientes durante el primer año del trasplante renal

Durante el primer año de trasplante renal es frecuente una ganancia de peso, debido, entre otros a la dieta, sedentarismo, e inmunosupresores, pudiendo aumentar los factores de riesgo del síndrome metabólico. Objetivos. Conocer la evolución del peso de nuestros pacientes durante el primer año del trasplante, y analizar la influencia con las distintas variables asociadas al paciente, sexo, edad, IMC, tratamiento inmunosupresor entre otras. Determinar la asociación entre la ganancia de peso y la aparición de factores de riesgo, como hipertensión arterial, diabetes y dislipidemia. Material y Método. Estudio retrospectivo y analítico. Se estudiaron 100 pacientes con un año de evolución en el trasplante, del Hospital Virgen de la Salud de Toledo. Sé analizaron datos antropométricos, demográficos y clínicos. La ganancia de peso se distribuyo según a las variables del estudio Resultados. La ganancia de peso al año del trasplante afecto a 93 pacientes, con una media de 7,21 kg ±5,87. El 44,1% aumento su peso por encima de la media, y el 23,7% gano = 10 kg. La prevalencia de sobrepeso y obesidad antes del trasplante fue 57% y 76% después del trasplante. Los hombres ganaron ligeramente más peso que las mujeres. Los más jóvenes = 49 años ganaron más peso, media 9,3 kg. Mayor incidencia de diabetes, hipertensión y dislipemias en los pacientes con sobrepeso y obesidad. Conclusiones. La mayoría de los pacientes aumentaron significativamente de peso al año del trasplante, asociándose con varios de los factores del síndrome metabólico. - Importante la educación, por parte de la enfermería, del paciente para fomentar hábitos de vida saludable.

Clinical efficacy and safety of pamidronate therapy on bone mass density in early post-renal transplant period: a meta-analysis of randomized controlled trials.

IntroductionThe overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined.Materials and MethodsA comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate.ResultsSix randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD) = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD = −3.101 [−5.33, −0.89]; serum calcium: SMD = 2.18 [−0.8, 5.16]; serum iPTH: SMD = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine.ConclusionsThis meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate.

SLCO1B1 Genetic Polymorphism Influences Mycophenolic Acid Tolerance in Renal Transplant Recipients

This study aimed to determine the influence of gene candidates on mycophenolic acid (MPA) response during the first year of renal transplantation. A total of 218 renal transplant recipients who received MPA from the first day of transplantation at a fixed dose of 2 g/day were genotyped for ABCB1, ABCC2, UGT2B7, UGT1A9, SLCO1B1, SLCO1B3 and IMPDH1 polymorphisms. Clinical end points were MPA-related adverse drug reactions (ADRs) and acute rejection episodes during the first year post-transplantation. After correction for multiple statistical testing, SLCO1B1 (encoding the hepatic uptake transporter OATP1B1) was the only gene associated with MPA-related ADRs, showing a 75% risk reduction in favor of a protective effect of the SLCO1B1*5 allele (p = 0.002). In vitro experiments showed that MPA metabolites MPA-phenyl-glucuronide and MPA-acyl-glucuronide are substrates of OATP1B1. Their transport was decreased in the presence of the variant transporter (OATP1B1*5). These results suggest for the first time that carriers of the SLCO1B1*5 allele seem to be protected from MPA-related ADRs.

The Dynamics of Glucose Metabolism Under Calcineurin Inhibitors in the First Year After Renal Transplantation in Nonobese Patients

The incidence of glucose metabolism disturbances after transplantation often is based on the use of hypoglycemic agents and not on the results of glucose tolerance tests (GTTs), which may camouflage the real incidence. A lack of information also exists regarding the profile of glucose metabolism during the first year after transplant. Oral GTT along with insulin measurements and drugs pharmacokinetics were prospectively performed at days 30, 60, 180, and 360 after transplant to diagnose disturbances of glucose metabolism after renal transplantation, in nonobese patients receiving either tacrolimus (n=55) or cyclosporine (n=29), along with mycophenolate mofetil and steroids. The incidence of impaired glucose tolerance or diabetes mellitus reached a peak at 60 days and decreased at 1 year. It could not be adequately diagnosed using fasting plasma glucose in a decreased abnormal (>99 ng/mL) range. In both groups, insulin secretion, evaluated by the Homeostasis Model Assesment (HoMA-beta), decreased (P<0.005) from the condition of normal GTT (101+/-56%) to impaired glucose tolerance (72+/-35%) and diabetes mellitus (54+/-25%). In the cyclosporine group, insulin secretion was normal and stable throughout the study period, but in the tacrolimus group, insulin secretion recovered over time and was inversely correlated with tacrolimus exposure. Insulin resistance (HoMA-IR) did not change. This study shows the need to perform an oral GTT at 60 days and at the end of the first year of renal transplantation to adequately diagnose impaired glucose metabolism.

Corticosteroid-Sparing Strategies in Renal Transplantation

Chronic allograft nephropathy and death with a functioning graft (mainly due to cardiovascular causes) are the most common causes of graft loss after the first year of renal transplantation. Immunosuppressants, and corticosteroids among them, contribute to an increase in cardiovascular risk because of their significant adverse effects, including hypertension, hyperlipidaemia and hyperglycaemia. Thus, corticosteroid discontinuation or avoidance has become a priority among the transplant community in order to enhance long-term graft and patient survival. Nevertheless, corticosteroid-sparing strategies may increase the risk of acute and chronic rejection and, thus, worsen the prognosis of transplant recipients. Initial attempts during the azathioprine epoch did not provide satisfactory results, as they were associated with high acute rejection rates, emphasising the risk of under-immunosuppression. The advent of new immunosuppressants, such as mycophenolate mofetil, mTOR inhibitors and anti-interleukin-2 receptor antibodies, have renewed the interest in corticosteroid-sparing protocols, and the results of new trials suggest that these corticosteroid-sparing strategies, even at an early stage after transplantation, are safe enough in view of the stable renal function and low rates of acute rejection reported. However, immunological risk factors, such as African American ethnicity, the presence of panel-reactive anti-HLA antibodies (even at low rates), and a history of previous acute rejection episodes should be taken into account and corticosteroid withdrawal strategies should be undertaken with caution. Long-term follow-up studies must be performed to confirm the encouraging short-term data.

Cost of renal replacement therapy in Turkey.

By the end 2000, 22224 patients were on renal replacement therapy (RRT) in Turkey. We investigated the cost of RRT in three medical faculties and one private dialysis centre. Yearly expenses were US dollars 22759 for haemodialysis (HD), US dollars 22350 for continuous ambulatory peritoneal dialysis (CAPD), and US dollars 23393 and US dollars 10028, respectively, for the first and second years of transplantation (Tx). In the first year, renal Tx was significantly more expensive than CAPD. However, after the first year of renal transplantation, Tx became significantly more economical than both CAPD and HD. The sum of all yearly RRT expenses for the country was US dollars 488958709, which corresponds to nearly 5.5% of Turkey's total health expenditure. Measures such as early construction of vascular access, promoting home dialysis and the reuse of the dialysers, strict control of the use of some expensive drugs like erythropoietin and active vitamin D, and also increasing the number of transplantations, especially if pre-emptive transplantation is possible, should be taken into account in order to reduce these expenses.

Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy.

Chronic allograft nephropathy is the principal cause of late graft loss after the first year of renal transplantation. Transforming growth factor-beta1 (TGF-beta1) is a key fibrogenetic cytokine involved in the fibrosis of a number of chronic diseases of the kidney and other organs, and recently evidence has shown that TGF-beta1 is involved in the pathogenesis of chronic renal allograft dysfunction. Production of TGF-beta1 in these circumstances may be modulated by the intrarenal renin-angiotensin system (angiotensin II induces TGF-beta1 production and secretion by the mesangial cells) and by a direct effect of cyclosporin A, which stimulates the synthesis and expression of TGF-beta1. In a prospective study of 14 renal transplant patients exhibiting chronic graft nephropathy, we demonstrated that treatment with losartan significantly decreased plasma levels of TGF-beta1 by >50%. There was a significant correlation (P=0.04) between the increase in circulating angiotensin II after 2 weeks and the decrease in plasma TGF-beta(1) at the end of the study period, suggesting that the degree of angiotensin II receptor blockade plays a decisive role in the synthesis of TGF-beta1. A significant decrease in circulating endothelin-1 (ET-1) levels also occurred during treatment with losartan, together with a decrease in proteinuria. In a randomized 2x2 crossover study, the effects of losartan and amlodipine on renal haemodynamics and on profibrogenetic cytokines were analysed. Whereas amlodipine increased the glomerular filtration rate (GFR) through an increase in the FF and P(G), losartan slightly decreased the GFR, but with a significant decrease in FF and P(G). With respect to the profibrogenetic cytokines, losartan decreased the plasma levels of TGF-beta1 and ET-1, while amlodipine did not significantly change TGF-beta1 and slightly increased ET-1.