Relationship of Renal Resistive Index and Cardiovascular Disease in Renal Transplant Recipients

Background

Cardiovascular disease is the primary cause of death in renal transplant recipients, and elevated renal allograft resistive index (RI) has been associated with patient survival.

Objective

To evaluate the predictive value of intrarenal RI on atherosclerotic disease.

Patients and Methods

Ninety-seven patients who had undergone renal transplantation between 1999 and 2001 and had stable renal function were included in the study. Patients with renal artery stenosis, urinary tract obstruction, clinical symptoms of acute rejection, or chronic allograft nephropathy were excluded. Clinical and laboratory information was obtained from the medical records and included demographic data, medications used, body mass index, blood pressure, and laboratory values. Intrarenal RI and carotid intima-media thickness (IMT) were determined using Doppler ultrasonography.

Results

At linear regression analysis, RI was significantly correlated with recipient age, C-reactive protein concentration, systolic blood pressure, pulse pressure, body mass index, smoking, and carotid IMT. At multivariate linear regression analysis, only pulse pressure was an independent predictor of intrarenal RI.

Conclusion

Intrarenal RI is associated with traditional cardiovascular risk factors and carotid IMT. Elevated intrarenal graft RI may be predictive of cardiovascular disease in renal transplant recipients without complications.     

Infective Complications Associated With Ureteral Stents in Renal Transplant Recipients

Objective

Stenting of the ureter is commonly performed during renal transplantation to avoid early complications. However, it predisposes to infections that may pose a significant threat to the graft and patient. Our study sought to investigate the incidence of infections associated with stents in renal transplant recipients.

Patients and Methods

A retrospective analysis of 100 consecutive renal transplant recipients performed over 1 year with 6 months follow-up.

Results

The median recipient age was 46 years (range, 19-71 years). Among the study group, 75 patients received an organ from deceased donor and 25 from live donor. In our study, there were 79 patients with a stent (ST) and 18 without a stent (WOST); 3 patients who required nephrectomy were excluded from the study. There were 2 ureteric stenoses that occurred following stent removal: 1 required surgical correction and 1 was treated radiologically. There were no cases of urinary leak. The incidence of urinary tract infection (UTI) was significantly greater among ST compared with WOST subjects (71% vs 39%; P = .02). New episodes of UTI following removal of the stent were more common among patients who had experienced infections while having a stent compared with infection-free stented patients (54% vs 30%; P = .04).

Conclusions

A ureteric stent may help to reduce early postoperative complications (leak and stricture), but increased the likelihood of UTI. Infection while having a ureteric stent was associated with a high recurrence rate of UTI even after stent removal.     

Calcification Propensity and Survival among Renal Transplant Recipients

Calciprotein particle maturation time (T₅₀) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T₅₀ in renal transplantation, baseline serum T₅₀ was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T₅₀ with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T₅₀ was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T₅₀, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T₅₀ values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T₅₀ improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T₅₀ was also associated with increased graft failure risk. The associations of T₅₀ with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T₅₀ was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.     

Thrombophilic Mutations: No Association With Thrombotic Events in Renal Transplant Recipients

Factor V Leiden and mutation of prothrombin gene G20210A have been associated with poor results in the early post-kidney transplantation period. Its long-term importance in stable patients has yet to be evaluated. We studied the prevalence of these inherited mutations and their relationship to thrombotic events in 82 Argentine renal transplant recipients with adequate long-term kidney function. In aggregate, 7.2% of patients were carriers of these mutations; however, their presence did not show any association with thrombotic events or renal function alterations. The routine evaluation for these mutations does not seem to be cost-effective in renal transplant patients.     

Conversion to Everolimus in Kidney Transplant Recipients With Decreased Renal Function

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1–3 mg/d that was sufficient to achieve the recommended levels of 3–8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.     

Serum Procalcitonin Correlates With Renal Function and Immune Components in Early-Stage Renal Transplant Recipients

BackgroundIn renal transplantation, monitoring procalcitonin (PCT) in the early post-transplant period can be a promising method for early tracking of infectious complications. However, the correlation between PCT and infection-related factors and immune components and renal function remains unclear.Patients and methodsBetween November 2017 and December 2018, 62 early-stage renal transplant recipients were selected, and 4 mL peripheral blood samples were collected to detect the changes of specific immune cells and cytokines. Our study was in compliance with the Helsinki Congress and the Declaration of Istanbul; no prisoners were used, and participants were neither paid nor coerced in our study.ResultsAccording to serum PCT levels, recipients were divided into a high group (PCT ≥ 0.5 ng/mL) and a low group (PCT < 0.5 ng/mL). Compared with the low group, creatinine, cystatin C, urea, T helper type (Th) 22 cells, IL-22 + Th17 cells, interleukin (IL)-22, tumor necrosis factor alpha, and IL-17A increased while estimated glomerular filtration rate (eGFR) was decreased in the high group. In addition, PCT was significantly correlated with eGFR in the high group.ConclusionsSerum PCT is related with renal function and seems to be associated with immune components in early-stage renal transplant recipients.     

Incidence of Aspirin Resistance and Its Relationship With Cardiovascular Risk Factors and Graft Function in Renal Transplant Recipients

Background

Aspirin (ASA) is frequently used to prevent cardiovascular events and improve renal graft function after renal transplantation. Clinical studies have demonstrated that decreased responsiveness to ASA therapy is associated with an increased risk of atherothrombotic events. However, no clinical trial to date has evaluated the incidence and clinical importance of ASA resistance among renal transplant recipients.

Aim

To assess the incidence of ASA resistance and its association with cardiovascular risk factors (CRF) and renal graft function after renal transplantation.

Methods

We prospectively included 40 patients undergoing living related donor renal transplantation using ASA (80 mg/d) in the study. ASA resistance was defined using a platelet function analyzer (PFA-100). Glomerular filtration rate (GFR) was measured by postoperative Tc-99m diethylenetriaminepentaacetic acid renal scintigraphy. We investigated the incidence of ASA resistance and its relationship to CRF and renal graft function.

Results

ASA resistance was noted in 11 patients (27.5%). The demographic characteristics of the patients were similar in both groups (P > .05). Compared with patients in the ASA-sensitive group, patients in the ASA-resistant group showed significantly higher total cholesterol, low-density lipoprotein cholesterol, triglyceride, C-reactive protein, and fibrinogen levels and lower GFRs (44 ± 21 mL/min vs 63 ± 26 mL/min, P = .03). The incidence of ASA resistance was higher among patients with GFRs < 60 mL/min compared with those with a GFR ≥ 60 mL/min (10% vs 1%; P = .012).

Conclusion

ASA resistance is associated with higher lipid levels and inflammatory and thrombotic cardiovascular risk factors and lower GFRs in renal transplant recipients.     

Determinants of Coronary Artery Calcification Progression in Renal Transplant Recipients

Coronary artery calcification (CAC) is associated with increased atherosclerotic burden and cardiovascular events. The objective of this study was to determine the natural history and risk factors associated with CAC progression in a cohort of incident asymptomatic renal transplant recipients with no history of coronary revascularization. Electron-beam computed tomography was performed in 82 subjects at time of transplantation and at least 1 year later. Mean (SD) and median CAC score increased for all subjects from 392.4 (747.9) and 75.8 at time of transplant to 475.3 (873.5), (p = 0.002[log]) and 98.9 (p < 0.001), respectively. Most subjects (89%) with no calcifications remained without calcification. Mean annualized rate (SD) of CAC score change was 52.5 (150) with a median of 0.5. Average yearly percent change was 67.3 (409.6) with a median of 1.4. In multivariate analysis, diastolic blood pressure at 3 months post-transplant, Caucasian race, glomerular filtration rate at 3.0, months post-transplant, body mass index and baseline CAC score were independent predictors of annualized rate of CAC change. There is significant progression of CAC post-renal transplantation in most subjects. Progression is most likely to occur in white patients and is associated with clinical factors such as blood pressure, body mass index, renal function and baseline CAC score.     

Long-term Clinical Outcome of Aortic Arch Calcification in Kidney Transplant Recipients

Introduction

Cardiovascular disease is the most common cause of death in kidney transplant recipients (KTRs). Aortic arch calcification (AoAC) is a major risk factor for cardiovascular disease in KTRs. This study aimed to evaluate the long-term outcomes of AoAC in KTRs.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Renal Transplant Recipients

Background

There is considerable controversy over the benefits of renin-angiotensin system (RAS) blockade in renal transplant recipients (RTRs). The aim of the study was to research the effects of RAS blockade on allograft and patient outcome.

Donor Characteristics That Are Associated With Survival in Liver Transplant Recipients Older Than 70 Years With Grafts

IntroductionThe use of grafts from donors older than 70 years of age is increasing due to the decrease in the number of donors and the increase in waiting list patients.Material and MethodsWe undertook a univariate and multivariate analysis of 980 adult recipients of whole liver grafts, 129 of them from donors aged 70 years or older.ResultsNo differences were found in patient survival compared with recipients of younger grafts. There were no higher rates of rejection, vascular or biliary complications, postoperative bleeding, or infections, but older grafts were associated with graft dysfunction (P = .01) and a higher frequency of postoperative refractory ascites (P = .007), but without a greater need for retransplantation. As graft-associated factors, the joint presence in the donor of diabetes (P = .00; confidence interval [CI] = 0.04–0.117), hypertension (P = .00; CI = 0.22–0.39), and weight of more than 90 kg (P = .031; CI = 0.05–0.104) were suggestive of poor prognostic factors in recipient survival. Survival in hepatitis C virus (HCV) recipients or recipients aged older than 60 years was worse with donors aged older than 70 years, although not significantly so. With grafts from donors aged older than 80 years (n = 15), although patient survival rate was good (70% at 10 years), there was a higher rate of retransplantation (20%) and the early mortality rate was 13.3%.ConclusionsUse of grafts from donors aged older than 70 years is safe, with similar survival to patients with younger grafts. The appearance of initial dysfunction with prolonged ascites may be due to a delay in reaching a correct functionality, but was not associated with increased mortality, complications, or need for retransplantation. It should also be avoided in recipients older than 60 years or with HCV. Grafts older than 80 years were associated with a good long-term patient survival but at the expense of a higher rate of retransplantation. However, it helps to reduce the time on the waiting list and, thus, mortality. We noted decreased survival associated with donor hypertension, diabetes, and obesity, so these donors should be selected more rigorously.     

Long Graft Cold Ischemia Time Is Associated With Increased Arterial Stiffness in Renal Transplant Recipients

Background

Increased pulse wave velocity (PWV), an indicator of arterial stiffness, is associated with greater cardiovascular risk among renal transplant recipients. PWV depends on recipient-related factors and, as shown in recent studies, also on donor age. There is a lack of information whether graft-related factors influence arterial function in recipients. Graft cold ischemia time (CIT) significantly influences renal transplant outcomes. It was shown in an experimental model of aortic grafting that increased CIT promoted arteriosclerosis. The aim of the present study was to evaluate the relationship between renal graft CIT and PWV.

Methods

Carotid-femoral PWV were measured in 103 cadaveric kidney recipients of mean age 45 ± 12 years. We analyzed clinical data of recipient and donor ages, genders, body mass index, blood pressure, CIT, delayed graft function, and type of immunosuppressive therapy to compare patients with CIT < 24 (n = 24) versus CIT ≥ 24 hours (n = 79).

Results

PWV was lower among patients with shorter CIT (8.3 ± 1.6 vs 9.2 ± 2.0 respectively; P < .05). No significant differences were observed between the groups regarding donor and recipient ages, blood pressure, glomerular filtration rate, or immunosuppressive and cardiovascular therapy. A significant positive correlation was noted between PWV and CIT (r = .23; P = .019). Multiple regression analysis demonstrated that recipient age, therapy with cyclosporine, fasting glucose, systolic blood pressure, and CIT were independently associated with PWV.

Conclusions

Long CIT was associated with increased arterial stiffness. Further studies are necessary to understand the cause effect relationship of this finding.     

Abdominal Aortic Aneurysm Surgery in Renal,Cardiac and Hepatic Transplant Recipients

With advancements in transplantation and improved long-term allograft survival, the once rare clinical scenario of an abdominal aortic aneurysm (AAA) in a patient with a functioning allograft has become much more frequent. In transplant recipients, AAA repair has the potential to cause irreversible ischaemic injury to the transplanted organ. Different case series and case reports have mentioned a variety of techniques to offer protection to the transplanted organs during aneurysm repair such as cold perfusion, shunting, temporary surgical bypass and extracorporeal circuits etc. Critical review of these adjuncts seems to suggest that that they do not give any better results than just using a “clamp and go” approach. Endovascular aneurysm repair (EVAR) may offer some advantages for transplant patients who have suitable anatomy for endovascular stent deployment. In addition to these surgical techniques, various aspects of medical management for renal, cardiac and hepatic transplant recipients undergoing AAA repair are discussed.     

Assessment of Cardiovascular Risk During Peritransplant Period in Renal Transplant Recipients

Background

Cardiovascular (CV) diseases are the leading cause of death among patients with chronic kidney disease, including patients on dialysis and after kidney transplantation. The aim of study was the retrospective assessment of CV risk in renal transplant recipients during the peritransplant period.

Material and Methods

Evaluation of CV risk was made using the Revised Cardiac Risk Index (RCRI). One hundred kidney transplant recipient (60 males/40 females) participated in the study. In 82 recipients (82%), the RCRI index was 2 points, which was associated with a 6.6% risk of cardiac events. The remaining 18 patients (18%) had ≥3 RCRI points, which was associated with an 11% risk. The median RCRI score in the study group was 2.26, which was related to a risk of 7.39%.

Results

In the perioperative period, there were no CV events. The study group was observed for 5 years after transplantation, and during this time, 11 CV incidents occurred. Most of CV incidents occurred during the first 25 months after transplantation. Among patients, who underwent a CV incident, the RCRI was 3 and 2 points in 4 and 5 patients, respectively. Significant correlations were found between RCRI and both age and time spent on dialysis (P < .001).

Conclusions

Patients who qualify for a transplant are at a significant risk of having a CV incident in the peri- and postoperative periods. CV incidents did not occur in the perioperative period, although as many as 6% of patients experienced CV incidents within 2 years after transplant. Four (44%) of the 9 patients who experienced CV incidents after transplantation had a very high RCRI. This indicates the need for a very thorough long-term cardiologic supervision of transplanted patients.     

Assessment of Cardiovascular Risk in Renal Transplant Recipients: Preliminary Results

Background

Cardiovascular (CV) diseases are the most common cause of death in patients with chronic kidney disease, including patients after kidney transplantation. The aim of the study was to do a retrospective analysis of CV risk in renal transplant recipients (RTRs).

Immunosuppressive Agents and Metabolic Factors of Cardiovascular Risk in Renal Transplant Recipients

Cardiovascular disease (CVD) accounts for 35% to 50% of deaths among renal transplant recipients. Beside the atherogenic risk factors related to hemodialysis, renal function, and use of immunosuppressive agents, other relevant risk factors for CVD include acute rejection episodes, microalbuminuria (μAlb), diabetes, arterial hypertension, lipid disorders, inflammatory triggers, hyperhomocysteinemia, anemia, erythrocytosis, obesity, and hyperuricemia. We studied the prevalence of risk factors and the impact of various drugs on CVD among 103 renal transplant recipients with measured glomerular filtration rates showing values >45 mL/min. We measured uric acid, triglycerides (TG), low-density lipoprotein (LDL)/high-density lipoprotein (HDL) LDL/HDL ratio, homocysteine (HOMO), insulin resistance, μAlb, C-reactive protein (CRP), and fibrinogen. Subsequently, patients were divided into 8 groups based on the immunosuppressive protocol to evaluate its impact on CVD risk factors. Insulin resistance and hyperhomocysteinemia were present in >2/3 of patients. Considering the impact of protocols, the combination of cyclosporine (CsA) + everolimus (EVL) resulted in the most favorable profile in terms of reduction of hyperuricemia, hyperlipidemia, and hyperhomocysteinemia. Insulin resistance tended to be more frequent among patients treated with protocols including calcineurin inhibitors (CNI) and steroids. The prevalence of hyperhomocyteinemia was similar among patients on CsA and on tacrolimus (Tac). Sirolimus (SRL) was associated with higher levels of HOMO. The combination of CNI and proliferative signal inhibitors (PSI) seemed to be the most promising one to reduce the impact of CVD risk factors. The reduction in CVD morbidity can improve expectancy and quality of life, as well as graft function and survival among renal transplant patients.     

Factors Associated With the Development of Sarcopenia in Kidney Transplant Recipients

Introduction

Sarcopenia is characterized by an involuntary loss of skeletal muscle mass, strength, and function. Previous studies suggest that it is generally associated with aging and chronic kidney diseases. The focus of this study was on the association between sarcopenia and pre-sarcopenia in kidney transplant recipients.

Therapeutic Effect of Tripterygium wilfordii on Proteinuria Associated With Sirolimus in Renal Transplant Recipients

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.