[Show abstract][Hide abstract] ABSTRACT: To quantify changes of left ventricular (LV) torsion in patients' pre and post kidney transplantation.
A prospective study was conducted on 48 patients who received kidney transplantation for end stage renal disease and without myocardial infarction. The rotation, twist and torsion of LV were studied pre and post kidney transplantation (6 months post transplantation) using velocity vector imaging by echocardiography. The data is expressed as mean ± standard deviation and compared by paired t-test at the p < 0.05 significance level.
Six months post kidney transplantation, left ventricular ejection fraction (from 40.33 ± 11.42 to 61.00 ± 13.68%), ratio of mitral early and late diastolic filling velocity (from 1.04 ± 0.57 to 1.21 ± 0.52), rotation of basal LV (from 4.48 ± 2.66 to 5.65 ± 2.64 degree), rotation of apical LV (from 4.27 ± 3.08 to 5.50 ± 4.25 degree), LV twist (8.75 ± 4.45 to 11.14 ± 5.25 degree) and torsion (from 1.06 ± 0.54 to 1.33 ± 0.61 degree/cm) were increased significantly (p < 0.05). Interventricular septum thickness (from 11.67 ± 2.39 to 9.67 ± 0.48 mm), left ventricular mass index (from 104.00 ± 16.47 to 95.50 ± 21.44 g/m(2)), systolic blood pressure (from 143.50 ± 34.99 to 121.50 ± 7.09 mmHg), serum blood urea nitrogen (from 42.40 ± 7.98 to 30.43 ± 13.85 mg/dL) and creatinine (from 4.53 ± 1.96 to 2.73 ± 2.57 mg/dL) were decreased significantly (p < 0.05).
Kidney transplantation in end stage renal disease without myocardial infarction results in improvement in left ventricular structure, function and myocardial mechanics as detected by echocardiography and velocity vector imaging. Velocity vector imaging provided valuable information for detection and follow-up of cardiac abnormalities in patients with end stage renal disease.
Journal of cardiovascular ultrasound 12/2013; 21(4):171-6. DOI:10.4250/jcu.2013.21.4.171
[Show abstract][Hide abstract] ABSTRACT: Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.
American Journal of Transplantation 04/2013; 13(6). DOI:10.1111/ajt.12227 · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship.
This was a cross-sectional study of 100 patients with the nephrotic syndrome. Multivariate linear regression was used to evaluate for independent predictors of elevated D-dimer levels. Patients were observed for a period of 2 years after the baseline measurement of D-dimer level to assess for subsequent clinically evident thrombosis.
On univariate linear regression, D-dimer elevation was associated with age in years β (95% CI) 0.02 (0.016, 0.03), log-transformed urinary protein:creatinine ratio in g/g 0.439 (0.32, 0.558) and inversely with serum albumin in g/l -0.05 (-0.073, -0.035) and estimated glomerular filtration rate (eGFR) in ml/min/1.73 m(2) -0.01 (-0.016, -0.003). On multivariate linear regression, age in years β (95% CI) 0.019 (0.012, 0.026), serum albumin in g/l -0.023 (-0.043, -0.003), and log-transformed urinary protein:creatinine ratio in g/g 0.266 (0.124, 0.408) were independently associated with elevated D-dimer levels.
D-dimer levels are commonly raised in the nephrotic syndrome in the absence of clinically evident thrombosis, and are independently associated with age, degree of proteinuria and serum albumin, but not with eGFR. Baseline levels of D-dimer did not predict subsequent episodes of clinically evident thrombosis after 2 years of follow-up.
American Journal of Nephrology 12/2012; 36(6):554-560. DOI:10.1159/000345475 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Polyomavirus reactivation can cause significant morbidity in solid organ transplant recipients, particularly BK virus (BKV) in kidney transplant patients. Less is known about dynamics of John Cunningham virus (JCV) in nonkidney organ transplant patients. Methods. We examined the frequency of urinary shedding of polyomaviruses BKV and JCV and their rela-tionship to creatinine clearance (CrCl) in a longitudinal study of 41 kidney and 33 liver transplant recipients. Results. Any polyomavirus urinary shedding was more frequent in liver than kidney recipients (64% vs 39%; P = .03). JCV was excreted more frequently by liver than kidney recipients (71% vs 38%), whereas BKV was shed more often by kidney than liver patients (69% vs 52%). Mean JCV loads were significantly higher than those of BKV in both patient groups (P < .0001). Lower mean CrCl values were significantly associated with JCV shedding in both kidney and liver recipients (P < .001). Conclusions. These findings suggest that BKV and JCV display different patterns of reactivation and shedding in kidney and liver transplant patients and that JCV may have a role in renal dysfunction in some solid organ transplant recipients. BK virus (BKV) and John Cunningham virus (JCV) are nonenveloped icosahedral DNA viruses, members of the family Polyomaviridae. Studies have estimated that the adult population worldwide is approximately 80% seropositive for BKV and approximately 50%– 70% seropositive for JCV, with JCV seropositivity in-creasing with age [1–3]. Primary infection normally occurs during childhood, with the viruses then estab-lishing latency/persistence in different organs, including the kidney [4, 5]. BKV and JCV undergo periodic reactivation and replication, and may cause disease in immunosuppressed hosts [6–10]. It is not known exactly which factors control the balance between latency and reactivation of BKV and JCV, but available data suggest that the cellular immune response exerts important control over these viruses [6, 11–14]. BKV is known to cause diseases of the genitourinary tract, such as hemorrhagic cystitis in bone marrow and hematopoietic stem cell transplant recipients and ureteric stenosis in renal transplant patients. However, the virus is most frequently implicated with the devel-opment of polyomavirus-associated nephropathy (PVAN) in kidney transplant patients [6, 9, 15, 16]. Reduced host immunity seems to play an important role, as studies indicate that lowering of the level of immunosuppression is associated with a decrease in BKV viral load and reduction of allograft inflamma-tion in kidney transplant patients [6, 8, 15, 16]. Pro-gressive multifocal leukoencephalopathy is a disease of the central nervous system, characterized by multiple
The Journal of Infectious Diseases 09/2012; 206(6). · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Polyomavirus reactivation can cause significant morbidity in solid organ transplant recipients, particularly BK virus (BKV) in kidney transplant patients. Less is known about dynamics of John Cunningham virus (JCV) in nonkidney organ transplant patients.
We examined the frequency of urinary shedding of polyomaviruses BKV and JCV and their relationship to creatinine clearance (CrCl) in a longitudinal study of 41 kidney and 33 liver transplant recipients.
Any polyomavirus urinary shedding was more frequent in liver than kidney recipients (64% vs 39%; P= .03). JCV was excreted more frequently by liver than kidney recipients (71% vs 38%), whereas BKV was shed more often by kidney than liver patients (69% vs 52%). Mean JCV loads were significantly higher than those of BKV in both patient groups (P< .0001). Lower mean CrCl values were significantly associated with JCV shedding in both kidney and liver recipients (P< .001).
These findings suggest that BKV and JCV display different patterns of reactivation and shedding in kidney and liver transplant patients and that JCV may have a role in renal dysfunction in some solid organ transplant recipients.
The Journal of Infectious Diseases 07/2012; 206(6):875-80. DOI:10.1093/infdis/jis469 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Necrobiosis lipoidica diabeticorum (NLD) is an inflammatory skin disorder of unknown cause which can be seen in patients with diabetes mellitus. Various treatments, including immunosuppressive agents have been tried, without consistent efficacy. NLD is generally thought not to correlate well with tight diabetic control. Pancreas transplantation is the only widely and clinically used treatment that restores euglycemia in type I diabetic recipients. We report a case of resolution of NLD that had been unchanged for decades before pancreas after kidney transplantation. Another unique aspect of our case was that immunosuppression was discounted as a confounding factor, because the patient had been exposed to the same antirejection regimen for 3 years preceding the pancreas transplantation.
[Show abstract][Hide abstract] ABSTRACT: Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW).
Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups.
Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P < .0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39–24.2) and between the SR and control group (HR 4.22, 95% CI 1.30–13.7).
Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW.
Journal of Transplantation 05/2011; 2011:583981. DOI:10.1155/2011/583981
[Show abstract][Hide abstract] ABSTRACT: Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease.
To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m(2) and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT.
Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM.
SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.
[Show abstract][Hide abstract] ABSTRACT: Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established.
A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose > or = 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C > or = 6.5%, fasting venous serum glucose > or = 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus.
The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006).
Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.
Clinical Journal of the American Society of Nephrology 09/2010; 5(9):1669-75. DOI:10.2215/CJN.09481209 · 4.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared our experience with alemtuzumab induction and rapid steroid taper (RST) in simultaneous kidney and pancreas transplantation (SKPT) with a historic control group who received rabbit antithymocyte globulin (r-ATG) induction with RST. 74 SKPTs performed at our center between January 2005 to November 2008 who underwent immunosuppression with RST in combination with r-ATG induction (n = 33; 1.5 mg/kg x 4 for a total dose of 6 mg/kg) or alemtuzumab induction (n = 41; 30 mg single dose). Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil. Steroids were discontinued after postoperative day 4. Recipient and transplant characteristics were similar between the 2 groups, with 82% of the r-ATG and 80% of the alemtuzumab group steroid free at 1 year. The rate of clinical acute rejection episodes was 12% in the r-ATG group and 15% in the alemtuzumab group. The rates of cytomegalovirus (CMV) infection, BK nephropathy, and graft survival were similar between the 2 groups. There was no difference in mean serum creatinine, calculated GFR, or fasting blood sugar at 1 year between the 2 groups, whereas glycosylated hemoglobin (HbA1c) was lower at 1 year in the alemtuzumab (5.3 +/- 0.4) versus the r-ATG group (5.6 +/- 0.4; P = .0021). Induction with r-ATG or alemtuzumab with RST was safe and effective in SKPT. The incidences of acute rejection episodes, CMV infection, and BK nephropathy were similar. Mean HbA1C at 1 year was lower among the alemtuzumab group. Further long-term follow-up is needed to confirm these results.
[Show abstract][Hide abstract] ABSTRACT: Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal failure due to type 1 diabetes mellitus. With advances in surgical techniques and immunosuppression management, outcomes have improved, with current 1- and 10-year pancreas graft survival rates of 86% and 53%, respectively. Induction therapy with either alemtuzumab or rabbit antithymocyte globulin (rATG) in combination with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) or sirolimus appears to be safe and effective in the setting of rapid steroid withdrawal (RSW), with excellent graft survival and low rejection rates. There are no large randomized trials between alemtuzumab and rATG to determine whether one is better than the other. Anti-interleukin (IL)-2 receptor antibody induction and no induction in combination with a CNI, MMF or sirolimus, and prednisone have demonstrated excellent graft survival rates but are associated with a higher incidence of acute rejection. The efficacy of anti-IL-2 receptor antibodies or no induction in the setting of RSW is unproven. Both of the CNIs, ciclosporin and tacrolimus, are effective in preventing acute rejection in SPKT recipients; however, pancreas allograft survival may be better with tacrolimus. MMF is more effective than azathioprine in preventing acute rejection. Sirolimus appears to be effective in preventing acute rejection, but the combination of sirolimus with a CNI may accentuate the nephrotoxicity of the CNI. RSW with induction therapy is safe and effective in SPKT recipients, but longer follow-up data on outcomes are needed. Recent analysis of registry data shows that most transplant centres are using an induction agent followed by a combination of tacrolimus, MMF and corticosteroids in SPKT recipients.
[Show abstract][Hide abstract] ABSTRACT: Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function.
Journal of Transplantation 03/2010; 2010:383972. DOI:10.1155/2010/383972
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence and severity of reduced estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C (CHC).
Medical record review of 831 consecutive CHC patients seen in our clinic between July 2000 and August 2003; eGFR was estimated using the abbreviated Modification of Diet in Renal Disease (aMDRD) equation. The stage of kidney disease was determined based on eGFR expressed in milliliters per minute per 1.73 m(2): stage 1 (signs of kidney damage but normal or elevated (eGFR >or= 90), stage 2 (eGFR 60-89), stage 3 (30-59), stage 4 (eGFR 15-29), stage 5 (eGFR < 15 or dialysis-dependent).
A total of 522 patients had available data with using the aMDRD equation, 51% had abnormal eGFR (stage 1, 4.6%; stage 2, 36.4%; stage 3 or 4, 6.1%; stage 5, 3.8%). Of 190 patients with stage 2 kidney disease, 189 patients (99.5%) had normal serum creatinine and only one patient (0.5%) had elevated creatinine concentrations (>1.4 mg/dl). Of the 32 patients with stage 3 or 4 disease, 20 (62.5%) had a normal serum creatinine concentration. Of 349 patients without diseases known to cause renal insufficiency, 38% had stage 2-4 renal disease. In a subset of these patients, 95/522 (18%) the measured creatinine clearance showed good correlation with their aMDRD (R = 0.47, (p < 0.0001).
In CHC patients, a normal serum creatinine concentration does not assure normal kidney function. Estimation of eGFR with the aMDRD equation is a more accurate method of identifying patients with chronic kidney disease and reduced eGFR. Therefore, CHC patients should be screened more rigorously for chronic kidney disease because of the high prevalence of reduced eGFR. Lastly, in all CHC patients, the aMDRD eGFR should be used in each encounter with these patients when assessing their renal function irrespective of their serum creatinine.
[Show abstract][Hide abstract] ABSTRACT: Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1-year protocol biopsy in patients on rapid steroid withdrawal (RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1-year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1-year biopsy (OR 6.62, 95% CI 2.68-16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW.
American Journal of Transplantation 03/2010; 10(3):563-70. DOI:10.1111/j.1600-6143.2009.02966.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are "tipped over" to develop diabetes mellitus in the posttransplant milieu.
We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT.
The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT.
These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT.
[Show abstract][Hide abstract] ABSTRACT: With the current shortage of solid organs for transplant, the transplant community continues to look for ways to increase the number of organ donors, including extending the criteria for donation. In rhabdomyolysis, the byproducts of skeletal muscle breakdown leak into the circulation resulting in acute renal failure in up to 30% of patients. In nonbrain dead patients, this condition is reversible and most patients recover full renal function. Seven potential donors had rhabdomyolysis with acute renal failure as evidenced by the presence of urine hemoglobin, plasma creatinine kinase levels of greater than five times the normal and elevated creatinine. One donor required dialysis. At our institution, 10 kidneys were transplanted from the seven donors. Two grafts had immediate function, five grafts experienced slow graft function and three grafts had delayed graft function requiring hemodialysis. At a mean of 8.7 months posttransplant (2.4-25.2 months), all patients have good graft function, are off dialysis and have a mean creatinine of 1.3 (0.7-1.8). In conclusion, our experience suggests that rhabdomyolysis with acute renal failure should not be a contraindication for donation, although recipients may experience slow or delayed graft function.
American Journal of Transplantation 06/2009; 9(7):1666-70. DOI:10.1111/j.1600-6143.2009.02663.x · 5.68 Impact Factor