Left Ventricular Hypertrophy in Renal Transplant Recipients in the First Year After Transplantation

Background

Left ventricular hypertrophy (LVH) is a significant risk factor for cardiovascular complications in renal transplant recipients. The study objective here was to assess LVH and related factors in renal transplant recipients in the 1st year after transplantation.

Methods

Echocardiographic examinations were performed in the early post-transplantation period in 43 patients (age, 43.9 ± 12.4 years; male, 53.5%) and at 1 year after transplantation in 40 patients. At the same time, basic blood tests, N-terminal pro–B-type natriuretic peptide (NT-proBNP) level tests, and ambulatory blood pressure measurements were performed. LVH was diagnosed when LV mass index was >95 g/m² in women and >115 g/m² in men. Statistical analyses were performed with the use of the R Package.

Results

LVH (mainly concentric) was found in 51.2% of the patients in the early period and in 50% of the patients at 1 year. In 30% of the patients with baseline LVH it regressed at 1 year and in another 30% LVH developed de novo. In the early period, LV mass was influenced by age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), and a history of cardiovascular disorders during dialysis therapy, whereas at 1 year after transplantation it was influenced by age, sex, BMI, 24-hour systolic blood pressure, a history of hypertension during dialysis therapy, and abnormal 24-hour blood pressure profile. Weight gain interfered with LVH regression during the 1st year after transplantation, whereas no improvement in blood pressure control contributed to de novo development of LVH. All other patients (those without LVH) had a morphologic abnormality of the left ventricle, the so-called concentric remodeling. Higher NT-proBNP levels were observed in patients with LVH.

Conclusions

LVH is present in one-half of renal transplant recipients in the 1st year after transplantation, and concentric remodeling is present in the remaining patients of this group. An echocardiographic examination is indicated in every renal transplant recipient. Measurements of NT-proBNP levels are helpful in LVH diagnostics.     

Cardiac Valve Calcifications and Left Ventricular Hypertrophy in Hemodialysis Patients

Cardiac valve calcification (VC) is a common finding in end-stage renal disease patients. It was shown recently that VC is an independent predictor for all-cause and cardiovascular mortality in peritoneal dialysis patients. In hemodialysis (HD) patients, VC was associated with all-cause and cardiovascular mortality, but after adjusting for other cardiovascular risk factors and complications, as well as left ventricular mass index (LVMI), it lost significance. The aim of the study was to assess the relationship between VC and left ventricular hypertrophy in hemodialysis patients. Echocardiographic examination with mitral and aortic valves assessment and LVMI calculation was performed in 65 HD patients ages 49 ± 12, with duration of HD therapy 38 ± 32 months. VC were found in 32 of 65 patients (49%)—Group VC(+), mitral valve calcifications (MVC) in 10, aortic valve calcifications (AVC) in 9, and both valves calcifications (MVC + AVC) in 13 patients. Patients with VC were older, on HD therapy were longer, had higher systolic and pulse pressure, and had higher LVMI. Patients with both VCs had the highest LVMI. No significant differences were found with respect to Ca, P, PTH, and mean Ca × P product, but the incidence of Ca × P product above 4.43 mmol²/L² was higher in VC(+) compared with those without VCs. VC coexists with left ventricular hypertrophy, particularly when both valves are calcified. Even short-lasting incidents of increased Ca × P product may lead to cardiac VC.     

Left Ventricular Mass Is Associated With Ventricular Repolarization Heterogeneity One Year After Renal Transplantation

Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m² compared with 40 patients with eGFR ≥60 mL/min/1.73 m² (248 ± 61 g and 86% vs. 210 ± 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R²= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R²= 0.10; p = 0.034), and QTRR (R = 0.55; R²= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function .     

Course and Relevance of Arteriovenous Fistulas After Renal Transplant Biopsies

Arteriovenous fistulas (AVFs) after renal transplant biopsy are considered harmless. However, verification of the clinical course has not been thoroughly documented. We evaluated the data of our outpatient renal transplant biopsy program regarding the clinical course of AVFs after 2824 biopsies since 2000. We also reviewed all selective renal transplant embolizations. AVFs were the most frequent biopsy complications (8.3%). Seventy-seven percent of AVFs disappeared spontaneously. Renal function in patients with AVFs was not different compared to those without during 2 years of observation. There were no differences in AVFs comparing protocol or indication biopsies, needle size, the time after transplantation, the use of acetylic salicylic acid or serum-creatinine at biopsy. Living or younger donors were less likely to get postbiopsy AVFs. Ten embolizations were performed. Only one patient was from our outpatient biopsy program. Nine others were biopsied as inpatients in the course of complications during 6 weeks after transplant. Six of nine successfully embolized patients profited with improvement of renal function. Large AVFs occur most commonly shortly after transplantation in patients with poor graft function. There is no established test predicting which patient will benefit from embolization; however, Doppler-determined resistive index may help in this regard.     

参麦注射液对血液透析患者微炎症状态及左心室肥厚的影响

目的：研究参麦注射液对维持性血液透析（maintenance hemodialysis,MHD）患者微炎症状态及左心室肥厚（left ventricular hypertrophy,LVH）的影响。方法：MHD患者40例,随机分为参麦组和对照组,每组20例,治疗3个月,观察治疗前后血hs-CRP、IL-6、IL-1β水平,测定心超指标。结果：治疗后,参麦组的hs-CRP、IL-6、IL-1β水平明显降低（P〈0.05）,与对照组比较,hs-CRP、IL-6的降低差异有统计学意义（P〈0.05）;治疗后,参麦组LVM、LVMI、IVST降低,与治疗前相比差异有统计学意义（P〈0.01）;与对照组相比LVM、LVMI、IVST的降低差异均有统计学意义（P〈0.01和P〈0.05）。结论：参麦注射液可以改善MHD患者微炎症状态,逆转LVH。     

The Relationship among Asymmetric Dimethylarginine (ADMA) Levels,Residual Renal Function,and Left Ventricular Hypertrophy in Continuous Ambulatory Peritoneal Dialysis Patients

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial-based nitric oxide synthase. Its level is increased by end stage renal disease. However, most studies showing an increase in ADMA in dialysis patients have focused on hemodialysis. Results with peritoneal dialysis patients have been more inconclusive. Recent studies suggest that ADMA may be a new cardiovascular risk factor. The aim of the present study was to evaluate the relationship between ADMA levels, residual renal function, and left ventricular hypertrophy in peritoneal dialysis patients. Serum ADMA measurements and echocardiographic evaluations were performed in 54 peritoneal dialysis patients and 26 healthy volunteers. Residual renal function was measured in peritoneal dialysis patients by urea clearance from a urine collection. Thirty-two of the 54 peritoneal dialysis patients had residual renal function. ADMA levels of the peritoneal dialysis group were found to be significantly higher than those of healthy individuals (p = 0.03). Within the peritoneal dialysis group, ADMA levels of patients with residual renal function were significantly lower than those without residual renal function (p = 0.01), though they were still higher than the ADMA levels of the control group (p = 0.04). Serum levels of ADMA were positively correlated with left ventricular mass index (r = 0.29, p = 0.01) and negatively correlated with early mitral inflow velocity (Em) (r = ?0.28, p = 0.01), Em/Late mitral inflow velocity (Am) (r = ?0,32, p = 0.00), and isovolumetric relaxation time (r = ?0.30, p = 0.01). In conclusion, increased ADMA levels seem to be associated with left ventricular hypertrophy in peritoneal dialysis patients, and residual renal function may lead to a reduction of serum ADMA levels.     

早期慢性肾病患者动态血压变化与左心室肥厚的关系

目的：分析早期慢性肾脏病（CKD1期）患者24h动态血压变化与左心室肥厚（LVH）的关系。方法：以25例正常人作为对照组（N组）,71例肾功能稳定的CKD1期患者作为疾病组（D组）。收集肾功能、血脂、24h动态血压监测（ABPM）等临床资料;采用超声心动图检测早期CKD患者LVH有关指标,分析ABPM指标与LVH的关系。结果：（1）与N组相比,D组夜间收缩压,昼、夜及24h平均舒张压均升高（P均〈0.05）;夜间收缩压下降率（nDRS）及舒张压下降率（nDRD）均明显下降（P均〈0.05）;舒张末期左室内径（LVDd）及左心室质量指数（LVMI）均升高（P均〈0.05）。（2）D组高血压及非杓型血压发生率分别达47.9%、62.0%。（3）与杓型血压组（Dip组）相比,非杓型血压组（non-Dip组）LVMI值及LVH发生率均显著增高（P均〈0.05）。（4）与非高血压组（non-LVH组）相比,高血压组（LVH组）nDRS和nDRD均明显下降,血红蛋白（Hb）显著降低（P均〈0.05）。（5）相关性分析显示LVMI值与nDRS、nDRD和Hb均呈负相关（P均〈0.01）,昼间平均收缩压（dSBP）、夜间平均收缩压（nSBP）、夜间平均舒张压（nDBP）和24h平均舒张压（mSBP）均呈正相关（P均〈0.05）。多因素逐步回归分析显示：nDRS、Hb、nDRD和血肌酐（Scr）进入回归方程：y=123.429-2.290x1-0.47x2-0.768x3＋0.178x4（y=LVMI;123.429=常数,t=8.41,P=0.000;x1=nDRS,t=-5.43,P=0.000;x2=Hb,t=-4.77,P=0.000;x3=NDRD,t=-3.47,P=0.001;x4=Scr,t=2.08,P=0.041）。结论：早期CKD患者即已出现血压升高及血压节律改变;LVH发生与早期CKD患者夜间高血压及非杓型血压关系更为密切;贫血和肾功能减退本身也与早期CKD患者LVH发生有关。     

Long-Term Outcomes of Immunosuppressed Renal Transplant Recipients with Malignancies

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor. Received: April 17, 2000 / Accepted: November 20, 2000     

Uncommon Side Effect of MMF in Renal Transplant Recipients

Mycophenolate mofetil (MMF) is a potent immunosuppressive agent used in renal transplantation. Gastrointestinal and hematological side effects are commonly observed, but hepatotoxicity has not been reported. In this study, we assessed MMF-related hepatotoxicity in renal transplant recipients. A total of 124 renal transplantation recipients (RTRs) were evaluated for elevated liver enzymes associated with MMF, and 79 patients were enrolled to the study. Patients used MMF 2 g/day. The patients who had progressive increase in liver enzymes after renal transplantation and their AST, ALT, GGT, ALP, bilirubin levels, hepatitis, cytomegalovirus (CMV), abdominal ultrasonography, duration of hepatotoxicity, and decreased dosage or withdrawal of MMF were recorded. Also, we evaluated their liver enzymes while the patients were on the waiting list. Of the 79 patients, 11 patients (13.9%) had a progressive increase in liver enzymes. The median (min–max) age of the patients with MMF-hepatotoxicity was 29 (19–54) and 72.7% of them were male. None of the patients had hepatitis B or C, CMV infection, or other possible causes for elevated liver enzymes and their abdominal ultrasonography were normal. High liver enzyme levels regressed after the withdrawal (n = 6) or reduce dosage (n = 5) of MMF. The median time of the increase in liver enzymes was 28 (4–70) days and after 50% reduction or withdrawal of MMF, returned to normal values in 16 (4–210) days. The median levels of ALT in waiting list (I), before (II), and after (III) reduction dosage or withdrawal of MMF were 22.0 (3–22), 222.0 (51–508), and 33.0 (21–64) U/L, respectively (p I–II = 0.004, p I–II = 0.013, and p II–III = 0.005). There were no differences for ALP, GGT, total bilirubin, and direct bilirubin levels. Also, the correlation between recovery time of ALT and persistence time of ALT elevation before adjustment of MMF was significant (r = 0.739, p = 0.009). Consequently, after renal transplantation, hepatotoxicity can occur due to a lot of reason including MMF usage. If hepatotoxicity related to MMF is not considered, especially in the early period of renal transplantation, resolution of hepatotoxicity can be required long term.     

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients

Whether influenza vaccination in solid-organ transplant recipients is efficacious remains a controversial issue. Furthermore, theoretical concerns have been raised regarding the safety of vaccination as it might trigger rejection of the allograft. The present prospective trial is aimed at investigating the antibody response and safety of influenza vaccination in renal transplant recipients (RTR).
A total of 165 RTR and 41 healthy volunteers were vaccinated with a standard trivalent inactivated influenza vaccine. Hemagglutination-inhibiting (HI) antibodies were quantified before and 1 month after vaccination. Seroprotection (SP) and seroresponse (SR) were defined as a titer ≥40 and a 4-fold rise in HI titer, respectively. Similar SR rates were observed in both groups. Postvaccination SP rates in RTR amounted to 92.7%, 78.7% and 82.9% for A/H1N1, A/H3N2 and B, respectively. High baseline SP rates, most probably reflecting frequent preimmunizations, explain partly the high postvaccination SP rates. SR rate was independently and inversely associated with baseline SP rate. Mycophenolate mofetil ( MMF ) usage was associated with a 2.6–5-fold lower SR. Nonetheless, these patients showed good postvaccination SP rates. A booster dose did not enhance SP or SR rates. Influenza vaccination neither affected allograft function nor caused rejection episodes. In conclusion, influenza vaccination is efficacious and safe in renal transplantation.     

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.     

Osteonecrosis in Renal Transplant Recipients: Early Radiological Detection and Course

Early radiologic signs and the radiologic course were examined retrospectively in 20 renal transplant patients who developed osteonecrosis after transplantation. Osteonecrosis appeared in 25 hips, 8 knees, 9 shoulders and 1 elbow. In most patients who developed osteonecrosis of the hip the early radiologic signs of osteonecrosis, with areas of lucencies and increased densities, were preceded by a thin fracture line in the immediate subchondral bone, parallel to the articular surface, appearing within a mean of 14 months after renal transplantation. This change seems to be a specific and very early finding in patients who subsequently develop osteonecrosis after renal transplantation. The initiation of collapsing phenomena of the articular surface was preceded by architectural changes near the articular surface with areas of lucencies and sclerosis. At the time of this investigation 26 per cent of the bones showed signs of regression of the changes with rebuilding of the former shape; 32 per cent showed progression and in 42 per cent the condition was stationary.     

Fumagillin for Treatment of Intestinal Microsporidiosis in Renal Transplant Recipients

We report 10 cases of intestinal microsporidiosis due to Enterocytozoon bieneusi in renal transplant (RT) recipients who were treated with fumagillin. All patients presented with afebrile subacute diarrhea (median of 2 weeks), associated with abdominal cramps (n = 5), and weight loss (n = 6), a mean of 68 months after RT. The diagnosis was made by the identification of microsporidial spores in stools with the use of appropriate staining and confirmed by a specific polymerase chain reaction assay for E. bieneusi in 7 patients. Median CD4 cell count was 292 cells/mm³. All patients received a median of 14 days of oral fumagillin (20 mg tid), and four patients also discontinued or tapered their immunosuppressive regimen (mycophenolate mofetil in 3, and azathioprine in 2). Clinical symptoms resolved rapidly with the clearance of microsporidial spores from stools in all patients. A severe but reversible thrombocytopenia was observed in one patient during fumagillin therapy, and another patient presented with abdominal cramps. Trough levels of tacrolimus measured in seven patients dropped below 5 ng/mL in six of them after 7–14 days of fumagillin. Intestinal microsporidiosis can cause subacute diarrhea in RT recipients. Fumagillin is an effective treatment with an acceptable safety profile, but monitoring of tacrolimus levels is warranted.     

Impact of Dry Weight Determined by Calf Bioimpedance Ratio on Carotid Stiffness and Left Ventricular Hypertrophy in Hemodialysis Patients

Our previous study has shown that modification of bioimpedance technique by the measurement of bioimpedance ratio in the calf (calf‐BR) was a simple and practical method in assessing fluid status in hemodialysis patients. However, the consequences of periodical dry weight (DW) adjustment under the guidance of calf‐BR on target organ damage have not been investigated. One hundred fifteen hemodialysis patients were enrolled in this pilot trial. Patients were divided into bioimpedance group and control group according to their dialysis schedule. In the bioimpedance group, DW was routinely adjusted under the guidance of calf‐BR every 3 months. In the control group, the assessment of DW remained a clinical judgment. Carotid stiffness, left ventricular mass index (LVMI), and calf‐BR were measured at baseline and at the 12th month in both groups. Home blood pressure (BP) was monitored monthly. Episodes of dialysis‐related adverse events were recorded. No significant differences were observed in parameters between the two groups at baseline. Compared with the control group, the bioimpedance group had significantly lower values in terms of the annual averages of systolic home BP (147.4 ± 15.3 mm Hg vs. 152.6 ± 16.9 mm Hg, P = 0.019), carotid stiffness index β (10.7 ± 3.3 vs. 12.2 ± 3.1, P = 0.003), LVMI (155.21 ± 15.64 g/m² vs. 165.17 ± 16.76 g/m², P < 0.001), and the percentage of individuals with calf‐BR over target range (P = 0.040) at month 12, with less annual averages of antihypertensive medications used and lower frequency of intradialytic hypotension, muscle cramps, or clotted angioaccess. Continued DW control achieved by periodical calf‐BR measurement improved arterial stiffness and left ventricular hypertrophy with good tolerability in hemodialysis patients.     

Vitamin D Status in Renal Transplant Recipients

Vitamin D plays an important role in calcium homeostasis. Renal transplant recipients may be more susceptible to reduced levels because of decreased sun exposure and steroid therapy. This study aimed to determine vitamin D status after renal transplantation and its effect on parathyroid hormone (PTH) and bone mineral density (BMD). We measured serum 25-hydroxyvitamin D levels (25-OHD) in 244 renal transplant recipients, divided into two groups, 104 recently transplanted (less than 1 year) and 140 long-term. Vitamin D status was defined according to NKF/KDOQI guidelines. Mean 25-OHD levels were 33 +/- 19 nmol/L and 42 +/- 20 nmol/L, respectively, for the recent and long-term transplant recipients. Vitamin D insufficiency was present in 29% and 43%, deficiency in 56% and 46% and severe deficiency in 12% and 5%, respectively. An inverse correlation was found between logPTH and 25-OHD (r=-0.2, p= 0.019) in long-term but not in recently transplanted patients. No correlation was found between 25-OHD levels and BMD. Hypercalcaemia was present in 40% of the recently transplanted recipients and 25% of the long-term. In conclusion 25-OHD was low in virtually all of our renal transplant recipients and may aggravate secondary hyperparathyroidism, but its correction may be difficult in patients with hypercalcaemia.     

Prognostic Value of Cardiovascular Screening in Potential Renal Transplant Recipients: A Single-Center Prospective Observational Study

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end-stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twenty-two patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow-up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 ± 0.6 years vs. listed not transplanted 4.1 ± 1.4 years vs. not listed 3.1 ± 1.7 years; p < 0.001). Ninety-nine patients underwent coronary angiography; 65 had normal or low-grade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.