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.     

Coronary Artery Calcification in Renal Transplant Recipients

Cardiovascular disease is the leading cause of mortality in renal transplant recipients. Although renal transplant recipients frequently undergo cardiac functional tests prior to surgery, coronary atherosclerosis can remain undetected. Coronary artery calcification (CAC), an early marker of atherosclerosis can be quantified using EBCT. The purpose of this study was to determine the extent and characteristics of CAC at the time of renal transplantation. We evaluated 79 consecutive incident asymptomatic renal transplant recipients. Patients were mostly White (62%), male (54%) and had a deceased donor renal transplant (61%). The mean age was 47 (12.1) years. Sixty-five percentage of subjects had CAC. The mean CAC score was 331.5 (562.4) with a median of 43.3. Older age, presence of diabetes, not having a preemptive transplant, deceased donor transplantation and hypercholesterolemia were significantly associated with presence of CAC univariately. Median CAC scores were significantly increased in subjects with diabetes (127.8 vs. 28.9, p=0.05), exposed to dialysis (102.9 vs. 3.7, p<0.001) and deceased donor recipients (169.7 vs. 7.5, p=0.02). Using multiple logistic regression, age and time on dialysis were significantly associated with the presence of CAC at the time of transplant. In summary, CAC is prevalent in patients undergoing kidney transplant. CAC may be a method to identify renal transplant recipients at increased risk for future cardiovascular events.     

Urinary Retinol-Binding Protein 4 is Associated With Renal Function and Rapid Renal Function Decline in Kidney Transplant Recipients

BackgroundUrinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs).MethodsA total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m²/year or initiation of dialysis, and 19 (38%) were included in rapid renal function decline group.ResultsUrinary RBP4/creatinine was inversely correlated with allograft function (r = –0.54, P < .001 with eGFR, and r = 0.49, P < .001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P = .017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P = .005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P = .010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P < .001) for rapid renal function decline.ConclusionsUrinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.     

Pre-Transplant IFN-γ ELISPOTs Are Associated with Post-Transplant Renal Function in African American Renal Transplant Recipients

Final crossmatch testing is routinely used to assess the risk of antibody-mediated graft injury/rejection post-transplant. Analogously, we postulated that quantitative measurements of anti-donor effector/memory T cells pre-transplant would independently assess post-transplant risk. To address this hypothesis, we determined the frequencies of pre-transplant, donor-specific interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spots (ELISPOTs) and correlated the results with post-transplant outcomes in 37 African American recipients of deceased donor kidney transplants treated with tacrolimus- and sirolimus-based immunosuppression. A positive ELISPOT test (>25 spots/300,000 cells) was detected in 14 (38%) of 37 patients. The incidence of biopsy-proven acute rejection was 50% (7/14) in ELISPOT-positive versus 17% (4/23) in ELISPOT-negative patients (p=0.036). Calculated glomerular filtration rate (MDRD) at 12 months was 37+/-16 mL/min in ELISPOT-positive versus 55+/-20 mL/min in ELISPOT-negative patients (p=0.01). ELISPOT status remained a correlate of allograft function at 12 months by linear regression analysis (p=0.001), independent of rejection and other contributing variables. Pre-transplant donor-directed IFN-gamma ELISPOT assessment of anti-donor cellular immunity may function as a 'cellular crossmatch' and independently correlates with renal allograft function in African Americans receiving tacrolimus- and sirolimus-based immunosuppression.     

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.     

Early Assessment of Renal Resistance Index and Long-Term Renal Function in Renal Transplant Recipients

Background. The effect of the intrarenal arterial resistance index (RI) on long-term renal functions is not well known. We examined the predictive value of intrarenal RI on long-term allograft outcomes. Methods. We retrospectively investigated 121 stable renal transplant recipients, followed for a mean of 63.21?±?19.9 months after renal transplant. Patients with complications during the first six months after transplant were not included. Color Doppler ultrasonography was done to calculate the intrarenal RI within the first four weeks after transplant. Results. Older recipient age, high pulse pressure, active smoking, and proteinuria were associated with a higher intrarenal RI. Multivariate analyses revealed that renal RI and donor age were independent predictors of allograft outcome. Kaplan-Meier estimates of cumulative graft survival were significantly worse in patients who had an RI of 0.7 or more than they were in patients who had an RI of less than 0.7 (p?=?.005). Development of chronic allograft nephropathy (CAN) was significantly higher in patients who had an RI of 0.7 or more (p?=?.02). Conclusions. Renal RI determined within the first month after renal transplant predicts long-term allograft function and development of CAN in renal 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.     

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.     

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.     

Impaired Renal Allograft Function is Associated with Increased Arterial Stiffness in Renal Transplant Recipients

It is important whether impairment of renal allograft function may deteriorate arterial stiffness in renal transplant recipients. In a cross-sectional study, arterial vascular characteristics were non-invasively determined in 48 patients with renal allograft using applanation tonometry and digital photoplethysmography. Mean age was 51 ± 2 years (mean ± SEM), and studies were performed 17 ± 1 months after transplantation. The stage of chronic kidney disease was based on the glomerular filtration rate. We observed a significant association between the stage of chronic kidney disease and arterial stiffness of large arteries S1 and small arteries S2 in renal transplant recipients (each p < 0.05 by non-parametric Kruskal–Wallis test between groups). Multivariate linear regression analysis showed that male gender of patients with renal allograft (p < 0.01) reduced glomerular filtration rate (p = 0.01), and older age of kidney donor (p = 0.04) were independently associated with an increase of large artery stiffness S1. Furthermore, a significant association between the stage of chronic kidney disease and arterial vascular reactivity during reactive hyperemia was observed (p < 0.05 by non-parametric Kruskal–Wallis test between groups). It is concluded that impairment of renal allograft function is associated with an increased arterial stiffness in renal transplant recipients.     

High Alternative Health Eating Index-Taiwan Scores Are Associated With Prevention of Graft Dysfunction in Taiwanese Renal Transplant Recipients

BackgroundVarious dietary quality indices demonstrate that a higher dietary quality score is associated with a reduced risk of several chronic diseases. However, creating an index tailored to the national population is crucial. The study investigated the association between the Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan) and graft dysfunction in Taiwanese renal transplant recipients (RTRs).MethodsA prospective cohort study recruited 102 RTRs with a functioning allograft without acute rejection in the last 3 months from September 2016 to June 2018. Laboratory data were obtained from the medical records of patients. Graft dysfunction was indicated by an estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m² in accordance with the Kidney Disease Outcomes Quality Initiative guideline. The dietary quality index AHEI-Taiwan was adapted from the AHEI based on Taiwanese dietary recommendations.ResultsMean age, renal transplant time, and eGFR were 48.9 ± 12.8 years, 8.5 ± 5.8 years, and 54.9 ± 17.8 mL/min per 1.73 m², respectively, in 102 RTRs. The RTRs with the highest quartile of AHEI-Taiwan scores were older and had a higher eGFR. Logistic regression analysis adjusted for age, sex, calories, Charlson comorbidity index, transplant time, and dialysis time showed that the highest quartile of the AHEI-Taiwan was associated with an 88% (odds ratio, 0.12; 95% CI, 0.03-0.59, P < .01) lower risk of graft dysfunction.ConclusionA high AHEI-Taiwan score was associated with a reduced risk of graft dysfunction in Taiwanese RTRs.     

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.

Catecholamine Vasopressor Exposure Is Associated With Early Poor Allograft Function and Adverse Events in Living Donor Kidney Transplant Recipients

BackgroundHypoperfusion leads to allograft injury during kidney transplantation. Catecholamine vasopressors are used to maintain blood pressure in the perioperative period but have demonstrated negative outcomes in the deceased-donor kidney transplant population. Little is known regarding living donor kidney transplants (LDKTs) and vasopressor use. The aim of this study is to describe the incidence of vasopressor use in LDKT and characterize its effects on allograft function and patient outcomes.MethodsThis retrospective, observational cohort study included adult patients who underwent an isolated LDKT between August 1, 2017, and September 1, 2018. Patients were divided into those who received perioperative vasopressors and those who did not. The primary objective was to compare allograft function between LDKT recipients that received vasopressors and those who did not. Secondary outcomes included safety endpoints and the identification of clinical variables associated with vasopressor use.ResultsA total of 67 patients received an LDKT during the study period. Of those, 25 (37%) received perioperative vasopressors, and 42 (62%) did not. Poor graft function, as defined by the development of slow or delayed graft function, occurred more frequently in patients receiving perioperative vasopressors compared with those who did not (6 [24%] vs 1 [2.4%], P = .016). In multivariable regression modeling, only perioperative vasopressors were statistically significantly associated with poor graft function. In addition, patients exposed to vasopressors experienced more postoperative arrhythmias (8 [32%] vs 1 [4.8%], P = .0025).ConclusionUsing perioperative vasopressors was independently associated with worsened early renal allograft function, including delayed graft function and adverse events in the LDKT population.     

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.

Obesity is Associated with Worsening Cardiovascular Risk Factor Profiles and Proteinuria Progression in Renal Transplant Recipients

Obesity is associated with adverse cardiovascular (CV) parameters and may be involved in the pathogenesis of allograft dysfunction in renal transplant recipients (RTR). We sought the spectrum of body mass index (BMI) and the relationships between BMI, CV parameters and allograft function in prevalent RTR. Data were collected at baseline and 2 years on 90 RTR (mean age 51 years, 53% male, median transplant duration 7 years), categorized by BMI (normal, BMI < or = 24.9 kg/m2; pre-obese, BMI 25-29.9 kg/m2; obese, BMI > or = 30 kg/m2). Proteinuria and glomerular filtration rate (eGFR(MDRD)) were determined. Nine percent RTR were obese pre-transplantation compared to 30% at baseline (p < 0.001) and follow-up (25 +/- 2 months). As BMI increased, prevalence of metabolic syndrome and central obesity increased (12 vs 48 vs 85%, p < 0.001 and 3 vs 42 vs 96%, p < 0.001, respectively). Systolic blood pressure, fasting blood glucose and lipid parameters changed significantly with BMI category and over time. Proteinuria progression occurred in 65% obese RTR (23 (13-59 g/mol creatinine) to 59 (25-120 g/mol creatinine)). BMI was independently associated with proteinuria progression (beta 0.01, p = 0.008) but not with changing eGFR(MDRD.) In conclusion, obesity is common in RTR and is associated with worsening CV parameters and proteinuria progression.     

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.