Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

Background

Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy.

Methods

From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 ± 27.5 to 93.7 ± 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 ± 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 ± 0.9 mg/dL, 54.2 ± 18.1 mL/mins and 44.3 ± 16.5 mL/min/m², respectively.

Results

We observed a significant reduction in creatinine levels (from 1.9 ± 0.9 to 1.4 ± 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 ± 18.1 to 69.0 ± 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 ± 16.5 to 57.1 ± 16.3 mL/min/m², P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement.

Conclusions

These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.     

Mycophenolate Mofetil Dose Reduction in Renal Transplant Recipients: A 5-Year Follow-up Study

Objective

Mycophenolate mofetil (MMF), an immunosuppressant that is widely used in renal transplantation, is associated with several dose-dependent hematologic and gastrointestinal side effects that may require dose reduction or even discontinuation. The aim of this study was to compare renal allograft function and acute rejection episodes among kidney allograft recipients who were on 2 regimens of MMF for at least 5 years.

Materials and Methods

This prospective cohort of 55 kidney allograft recipients was followed for deterioration of allograft function, evidence of acute rejection, and allograft survival. Twenty-two patients (40%) underwent MMF dose reduction to 1.35 to 0.23 g/d due to perceived side effects or economic reasons (group 1). The mean time for this change was 4.2 ± 2.1 months after kidney transplantation. The remaining patients (group 2, n = 33) were continued on MMF (2 g/d). All patients were followed for at least 5 years after transplantation. Renal function tests (blood urea and serum creatinine) were measured monthly for 2 years and then every 2 months. Statistical analysis was performed using SPSS 11.0 (Student t test). P ≤ .05 was considered significant.

Results

The 2 groups were comparable regarding age, gender, and immunosuppressive medications. The renal function tests were comparable at the end of the study. Mean blood urea values were 44.8 ± 5.8 and 46.8 ± 6.8 mg/dL in groups 1 and 2 (P > .05); mean serum creatinine values were 1.32 ± 0.14 and 1.38 ± 0.21 mg/dL, respectively (P > .05). There were 2 graft losses and 1 patient loss in group 2. There were also 2 graft losses among group 1 patients.

Conclusion

Our study showed that MMF dose reduction was not associated with an increased risk of acute renal allograft rejection or impaired allograft function at 5 years.     

Improvement of Renal Function After Conversion to Mycophenolate Mofetil Combined With Low-Level Calcineurin Inhibitor in Liver Transplant Recipients With Chronic Renal Dysfunction

Introduction

Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction.

Patients and Methods

We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 ± 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4-1.7 mg/dL (group I; n = 41); 1.8-2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5-2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria.

Results

Creatinine values after conversion were 1.4 ± 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected.

Conclusion

Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.     

Long-term evolution of the mineral metabolism after renal transplantation: a prospective, single-center cohort study

Background

Abnormalities in bone and mineral metabolism are common after renal transplantation (RT) but information on their long-term time course is scarce.

Objectives

(1) Evaluate the time course of biochemical parameters of bone and mineral metabolism over 60 months after RT; (2) identify predictors for persistent hyperparathyroidism (HPT).

Design

Prospective, longitudinal, single-center cohort study.

Methods

We determined serum levels (mean values ± standard deviations) of intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (APh), calcitriol, and creatinine (Cr) preoperatively as well as 6, 12, 24, 36, 48, and 60 months after cadaveric RT in 49 patients. We in addition recorded demographic, clinical, and therapeutic data.

Results

Pretransplantation iPTH stabilized from 194.2 ± 273.5 to 71.5 ± 50.7 ng/L at 6 months. Serum Ca (9.5 ± 1.1 mg/dL) and APh (81.9 ± 42.1 U/L) did not change. Baseline serum P (5.7 ± 1.8 mg/dL) and serum Mg (2.4 ± 0.4 mg/dL) decreased to normal ranges from month 6 onward. Low baseline calcitriol (22.4 ± 21.8 pmol/L) normalized slowly by 12 months (95.4 ± 46.7 pmol/L). Stable graft function (53.2 ± 15.8 mL/min) was achieved from 6 months onward. By 60 months, 26.5% of patients had a serum Ca above 9.8 mg/dL and serum P below 2.7 mg/dL; 22.4%, an Mg below 1.7 mg/dL and 8.2%, a serum iPTH more than 2.5-fold the upper limit of normal. Upon multiple regression analyses the iPTH at 60 months was influenced by a dialysis duration ≥ 2 years (β = 0.259, P = .003), body mass index > 25 kg/m² (β = 0.257, P = .006), baseline iPTH (β = 0.182, P = .036), serum Cr (β = 0.268, P = .002) and Mg (β = − 0.242, P = .006).

Conclusions

Hypercalcemia, hypophosphatemia, hypomagnesemia, and elevated iPTH persist in a subset of post-RT patients. Pretransplantation iPTH and obesity, dialysis duration, and posttransplant serum creatininemia and hypomagnesemia independently contribute to persistent HPT.     

Mycophenolate Mofetil Monotherapy in Patients Who Underwent Liver Transplantation for Hepatitis C Cirrhosis

Introduction

Mycophenolate mofetil (MMF) monotherapy has recently been proposed for liver transplant recipients with adverse events (nephrotoxicity, hypertension) related to calcineurin inhibitors. We analyzed the influence of MMF on the clinical course of recurrent hepatitis C.

Methods

Among 1038 patients who underwent liver transplantation (OLT) from April 1986 to October 2006, we analyzed 48 adult recipients (4.6%) whose diagnosis was hepatitis C virus (HCV) cirrhosis and who were converted from calcineurin inhibitors to MMF monotherapy.

Results

The 36 men and 12 women, had a mean age at OLT of 52.9 ± 7.2 years; the time elapsed from OLT to the onset of MMF monotherapy was 72.5 ± 47.6 months (range = 11-210). The mean follow-up after monotherapy was 19 ± 16.1 months (range = 2-67). Indications for conversion were: chronic renal dysfunction with HCV in 45 patients; HCV recurrence in two; and hypertension plus HCV recurrence in one subject. When the indication was renal dysfunction (excluding three patients who underwent hemodialysis), the mean creatinine values decreased significantly from baseline to 6 months of monotherapy from 1.63 ± 0.61 mg/dL to 1.51 ± 0.78 mg/dL (P < .03). The creatinine clearance only improved significantly from the baseline value of 56.6 ± 16.8 mL/min to the value at 3 months of monotherapy—63.6 ± 18.4 mL/min (P < .001). At the last outpatient visit, creatinine and creatinine clearances had not changed significantly. The mean diastolic blood pressure did improve significantly at the end of the study. The mean glucose levels decreased but not significantly at the last outpatient visit. Liver function tests did not change significantly after conversion to MMF monotherapy. The acute rejection rate was 8.3%, and adverse events related to MMF monotherapy were present in 9 patients (18.7%).

Conclusions

Conversion from calcineurin inhibitors to MMF monotherapy in patients who underwent OLT for HCV transiently improved renal function and hypertension. The acute rejection rate was low, and adverse events were usually well tolerated.     

Urinomas protect renal function in posterior urethral valves—a population based study

Background/Purpose

Urinomas have been thought to protect renal function in boys with posterior urethral valves (PUVs), although recent reports have disputed this. This study tested the hypothesis that urinomas protect global renal function in boys with PUV.

Methods

A retrospective analysis of all boys with PUV presenting to a tertiary unit derived from a region with an estimated population of 5.5 million was performed. Comparisons of the initial nadir creatinine, current creatinine, and renal status score (RSS) were made between those with and without urinomas. The RSS was derived from nephrology assessment of current renal status (0 = normal to 4 = end-stage renal failure or transplantation). Results were given as median (range), except for RSS, which was given as mean ± SEM. P ≤ .05 was regarded as significant.

Results

During 1989-2009, 9 of 89 PUV boys were diagnosed with urinomas. Initial nadir creatinine was statistically lower in boys with urinomas (31 [18-44] vs 45 [20-574] μmol/L, P < .01). Length of follow-up was similar (5.1 [2.2-17.3] vs 5.9 [1.8-19.7] years, P = .59). Follow-up creatinine was significantly lower in urinoma boys (44 [25-77] vs 61 [29-1227] μmol/L, P < .05), as was the RSS (0.14 ± 0.14 vs 0.91 ± 0.14, P < .01). No urinoma boys progressed to end-stage renal failure or required transplant.

Conclusion

This population-based study of PUV boys demonstrates that urinomas reduce nadir creatinine and significantly protect long-term global renal function.     

Preemptive kidney transplantation: experience in two centers

Introduction

End-stage renal disease (ESRD) is a prevalent, important cause of death. Transplantation increases survival and improves the quality of life of patients with ESRD while long-term dialysis is related to poor outcomes even among patients who undergo subsequent transplantations.

Objectives

To compare the advantages of preemptive procedures with kidney transplants among patients on renal replacement therapy.

Methods

This retrospective study was performed in two Córdoba city transplantation centers. Patients were divided into three groups: preemptive kidney transplant (PKT), patients on hemodialysis who received living donor kidney transplants (LDT), and subjects who received grafts from deceased donors (DDT). Serum creatinine, delayed graft function (DGF), subclinical rejection, and interstitial fibrosis/tubular atrophy (IF/TA) were evaluated at 6 months.

Results

Eighty patients were included: PKT (n = 28), LDT (n = 27), DDT (n = 25) mean age 29, 30, and 35 years, respectively. Women predominated among PKT and men in the other groups. In all groups, cyclosporine was the calcineurin inhibitor mostly used. Creatinine at 6 months was lower in the living donor groups (1.26 mg/dL PKT and 1.32 mg/dL LDT; P = NS) in relation to the deceased donor group (1.96 mg/dL; P < .05). DDT had the highest rate of DGF: 44% DDT versus 11.5% LDT vs 0% PKT (P < .05). Subclinical rejection was significantly lower among preemptive transplantations: PKT 7.6% versus LDT 18.5% versus DDT 24% (P < .05). IF/TA was higher in transplants from deceased donors: PKT 11.1%; LDT 11.5%; DDT 32%.

Conclusions

Preemptive kidney transplantation offered the advantages of a lower creatinine, no DGF, as well as a reduced incidence of subclinical rejection and chronic allograft nephropathy at 6 months posttransplantation.     

Progressive development of renal vascular dysfunction in brain death implicates reversible alterations of nitric oxide metabolism

Background

Vascular endothelial dysfunction occurs in the kidney graft from marginal brain death (BD) donors and may be responsible for a low success rate after transplantation.

Methods

BD was induced in 16 dogs for 6 hours. Immediately after the inflation of the intracranial balloon, the treated group (n = 8) received 40 mg/kg bolus followed by 3 mg/kg/min infusion of L-arginine for 30 minutes. Renal vascular function and hemodynamic and biochemical parameters were determined.

Results

BD caused vasoconstriction, increase in renal venous nitrite (4.9 ± 0.8 versus 2.6 ± 0.1, P < .05) and myeloperoxidase levels (1.43 ± 0.04 versus 2.43 ± 0.23, P < .001), and reduced vasodilatation of renal artery to acetylcholine. Larginine diminished the renal vasoconstriction induced by 6 hour BD (RVR = 0.92 ± 0.06 versus 1.38 ± 0.003 in controls, P < .05), maintained renal oxygen extraction in physiological range (17.5 ± 4.6% versus 25.4 ± 2.9% in controls, P < .05) and prevented the rise of myeloperoxidase (1.69 ± 0.19, P < .05 versus controls) and nitrite levels (3.3 ± 0.5, P < .05), followed by preservation of endothelium dependent vasodilatation (P < .05 versus controls).

Conclusions

The findings suggest that exogenous L-arginine supplementation may preserve endothelial vascular function in the kidney before prelevation from marginal BD donors.     

Gonadal function and immunosuppressive therapy after renal transplantation

End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents.

Methods

Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine <2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n = 15), group II, sirolimus without calcineurin inhibitors (SRL; n = 15), group III, sirolimus in combination with calcineurin inhibitors (SRL * CI; n = 29).

Results

Testosterone was significantly lower in group II versus group I (3.12 ± 1.23 versus 4.39 ± 1.53 ng/mL; P < .0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes.

Conclusion

Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect.     

Hepatic Changes During Various Periods of Reperfusion After Induction of Renal Ischemia in Rats

Background

Recent studies have suggested that ischemic damage to the kidneys causes liver tissue alterations. Thus, the morbidity and mortality in patients with acute renal failure (ARF) may be related to liver complications as well as to renal injury. The aim of the present study was to assess the hepatic changes during various periods of reperfusion after induction of renal ischemia.

Methods

Forty male rats were subjected to either a sham operation or to a 45-minute ischemia followed by 1, 3, 6, or 24 hours of reperfusion. Arterial pressure was continuously monitored. Blood samples were drawn to measure serum creatinine and blood urea nitrogen (BUN).

Results

We evaluated hepatic concentrations of interleukin (IL)-10 and tumor necrosis factor (TNF)-α. Ischemia reperfusion (IR) caused significant reductions in renal function as demonstrated by increased values of serum creatinine and BUN. These rats also showed significant increases in hepatic TNF-α and IL-10 concentrations. The most significant changes among inflammatory factors in the liver were observed at 3 hours of reperfusion: TNF-α, 616 ± 41 vs 215 ± 16, and IL-10, 926 ± 73 vs 125 ± 34, pg/100 mg tissue (P ≤ .05). Twenty-four-hour reperfusion reduced the extent of liver injury.

Discussion

Renal IR affects liver inflammatory status, possibly due to increased renal production or impaired clearance of mediators of tissue injury, namely proinflammatory cytokines. The reduction in liver injury at 24 hours of reperfusion compared with the other groups, suggested activation of late-protective mechanisms. These observations may be important for clinical interventions to reduce the morbidity and mortality of ARF.     

Duplex sonographic measurements in allografted kidneys: a cross-sectional study

Objectives

The measurement of color Doppler sonography indices, such as resistive index (RI) and pulsatility index (PI), can help in the evaluation of an transplanted kidney. The aim of this study was to determine the correlation between Doppler sonography indices and demographic paraclinical findings in transplanted kidneys.

Methods

A cross-sectional study was performed on 47 (27 male and 20 female) unrelated living renal transplanted patients.

Results

The mean age, body mass index (BMI), time since transplantation, pulse pressure index (PPI), intrarenal RI and PI were 38 ± 13 years, 25 ± 4.5, 48 ± 31 months, 0.34 ± 0.06, 0.69 ± 0.06, and 1.3 ± 0.3, respectively. There were significant negative correlations between time since transplantation and intrarenal RI and PI (r = −.38, P < .01; r = −.4, P < .01, respectively). There was a significant correlation between patient age, creatinine clearance, and intrarenal RI (r = .30, P = .039; r = .3, P = .043, respectively). There were no significant correlations between intrarenal RI, PI, and BMI, cyclosporine trough level, PPI, recipient and donor sexes, and rejection episodes. Diabetic patients displayed higher RI (0.76 ± 0.02 vs 0.68 ± 0.06, P = .048) and patients with serum high-density lipoprotein (HDL) level < 40 mg/dL had higher PI than patients with HDL ≥ 40 mg/dL (1.6 ± 0.4 vs 1.2 ± 0.3, P = .006).

Conclusions

Intrarenal RIs did not decrease over a few years after transplantation. They can be a useful, feasible predictor of graft function. However, future multicenter trials should be performed to prove the predictive power of RI determination as a marker of renal function.     

Safety and efficacy of conversion from twice-daily tacrolimus (prograf) to once-daily prolonged-release tacrolimus (graceptor) in stable kidney transplant recipients

Background

Graceptor is a new modified-release once-daily formulation of tacrolimus with an efficacy and safety profile similar to twice-daily tacrolimus (Prograf), as identified by clinical trials, offering a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily Prograf to once-daily Graceptor in stable kidney transplant recipients.

Methods

We switched 33 Japanese patients who had undergone kidney transplantation ≥1 years before from twice-daily Prograf to once-daily Graceptor. The dose conversion ratio between Prograf and Graceptor was 1:1. We compared the following parameters: minimum tacrolimus concentration (C_min); concentration dose per weight (CDW); serum creatinine (sCr); blood urea nitrogen (BUN); total cholesterol (TC); high-density lipoprotein cholesterol (HDL-C); uric acid (UA); fasting blood sugar (FBS). Time points for measurements were 1 month before study start and 1 and 2 months afterward.

Results

The mean age of the subjects in this study was 46.5 ± 13.1 years. Mean C_min decreased from 4.55 ± 1.79 to 3.20 ± 1.22 ng/dL. The mean CDW also decreased, from 99.8 ± 69.5 to 75.0 ± 55.1 mg/dL/kg over the 2 months. There were no significant changes in sCR, BUN, UA, and FBS. Mean TC increased from 187.5 ± 51.4 to 194.3 ± 43.4 mg/dL, and mean HDL-C changed from 53.7 ± 12.0 to 56.1 ± 11 mg/dL. There were no episodes of rejection or infection.

Conclusions

We conclude that switching from Prograf to Graceptor is safe and has the advantage of improving adherence. It could also have a beneficial effect in controlling glycemic levels and the adverse effects of tacrolimus. In many cases (25%-30%), the minimum concentration of tacrolimus decreased after changing tablets. With Graceptor, the ratio of area under trough level to area under the curve (AUC) is low compared with Prograf, resulting in low C_min values of 1-2 ng/mL, and the AUC for Graceptor is very similar to that for Prograf.     

Ambulatory blood pressure monitoring in renal transplant patients: should it be routinely performed?

Introduction

Arterial hypertension is common among kidney transplant patients. It increases cardiovascular risk and is a factor for progression of renal failure. Our objective was to perform ambulatory blood pressure monitoring (ABPM) in renal transplant patients with office hypertension.

Methods

Patients were divided into 2 groups according to their mean ABPM blood pressures with treatment: well-controlled hypertension (blood pressure [BP] <130/85 mmHg), and poorly controlled hypertension (BP > 130/85 mmHg). A “nondipper pattern” was defined as a decrease of <10% or an increase, and a “raiser pattern,” in which mean blood pressure was greater during the nocturnal than the diurnal period. “White coat effect” was considered when the mean of 3 BP measurements in the clinic was >140/90 mmHg among well-controlled hypertensive patients as documented by ABPM.

Results

ABPM was performed in 53 patients: 25 (47%) “well-controlled hypertensives” and 28 (53%) “poorly controlled hypertensives.” Of the latter, 24 (85%) showed a nondipper or raiser pattern with only 4 revealing dipper patterns. We compared well-controlled with poorly controlled hypertensives. The latter cohort were older (54.4 ± 9.3 vs 45.5 ± 13.8 years; P = .009), received grafts from older donors (56.7 ± 15.0 vs 45.8 ± 17 years; P = .02); had worse renal function measured by serum creatinine (1.7 ± 0.5 vs 1.4 ± 0.4 mg/dL, P = .03) or the Modification of Diet in Renal Disease (MDRD) = 4 formula (41.8 ± 14.0 vs 55.4 ± 20.5 mL/min/1.73 m²; P = .009), and displayed more proteinuria (0.30 ± 0.33 vs 0.18 ± 0.10 g/d, P = .08). Nondipper or raiser patients showed a higher mean body mass index (27.1 vs 21.7 kg/m²; P = .04). Among 25 well-controlled patients, 11 presented “white coat phenomenon.”

Conclusion

We observed an important “white coat” effect, a large prevalence of uncontrolled nocturnal hypertension, and a small but important incident of “masked hypertension.” Factors related to hypertension control were patient age, donor age, renal function, induction use, and proteinuria.     

The 4-week serum creatinine level predicts long-term renal dysfunction after adult living donor liver transplantation

Objectives

Recipients after liver transplantation. (OLT) often experience renal dysfunction. Acute kidney injury (AKI) and chronic kidney disease (CKD) after OLT occur among 20% to 50% and 30% to 90% of recipients, respectively; 2% to 5% of them deteriorate into end-stage renal disease each year. Since the predictable factors for CKD have not been well identified. We sought to investigate the incidence and predictors of CKD at 5 years after OLT.

Patients and methods

Between August 2002 and December 2005, we enrolled 77 patients who underwent adult living donor OLT with over 2 years of follow-up. The strategies to prevent renal dysfunction included induction with basiliximab to delay the use of tacrolimus: addition of mycophenolate mofetil to reduce the tacrolimus dosage; avoidance of the calcineurin inhibitor using sirolimus or administration of an angiotensin II receptor antagonist. The clinical variables were reviewed for analysis.

Results

The mean follow-up was 76 ± 14 months. The incidence of AKI (over 50% increase level of creatinine) was 29%. Ten (13.0%) patients developed CKD (creatinine > 2 mg/dL). One (1.3%) subject developed end-stage renal disease requiring hemodialysis. Upon multivariate analysis the development of CKD was significantly associated with the posttransplant 4-week creatinine level: 0.92 ± 0.23 versus 1.37 ± 0.93 mg/dL (P = .008).

Conclusion

The 4-week creatinine value was predictive of the occurence of CKD over 5 years after OLT.     

Lipid profiles of patients with a transplanted heart before and after the operation

Background

Graft coronary artery disease, a serious problem after orthotopic heart transplantation (OHT), has multifactorial etiologies with dyslipidemia as one of the major risk factors. In this study we examined lipid profiles and drug therapy of our patients before and after OHT.

Methods

Thirteen patients who underwent OHT at our center were enrolled in the study. We noted the patients’ clinical and demographic data and current medications as well as pre- and postoperative lipid values.

Results

The mean age of the study group was 32.0 ± 13.2 years with three women. Compared to the preoperative values, significant increases were detected in the mean levels of low-density lipoprotein (LDL) (81.3 ± 29.1 vs 103.5 ± 22.2 mg/dL; P = .03) and total cholesterol (142.0 ± 58.5 vs 184.0 ± 37.8 mg/dL; P = .02), while triglyceride (113.5 ± 67.3 vs 137.0 ± 69.9 mg/dL; P = .1) and high-density lipoprotein (42.7 ± 10.2 vs 48.7 ± 14.4 mg/dL; P = .2) levels did not change significantly at 2 to 3 months postoperatively. On follow-up eight patients were prescribed a statin (atorvastatin in all), one of whom was on ezetimibe in addition to statin and one, fenofibrate. The patients tolerated lipid-lowering agents well; no significant side effect was noted.

Conclusion

These findings demonstrated increased lipid values, mainly in total cholesterol and LDL levels, after OHT. Regarding the importance of dyslipidemia as a major atherosclerotic risk factor, we believe that statins in the absence of a contraindication should be part of the treatment protocol in patients with a transplanted heart.     

Short-term immunossupressive treatment of the donor does not prevent ischemia-reperfusion kidney damage in the rat

Introduction

Ischemia-reperfusion (IR) kidney damage is an important factor for allograft survival in kidney transplantation. Recently it has been shown that immune factors from donor-derived cells are important in IR injury. The aim of this article was to evaluate the impact of short-term immunosuppressive treatment of the donor over a time frame relevant to cadaveric transplantation on IR damage to the rat kidney.

Methods

Male Sprague-Dawley rats served as donors and recipients. Three experimental groups were evaluated according to the donor treatment (n = 6); control (no treatment); sirolimus (1 mg/kg orally) or FTY720 (1 mg/kg intravenously) at 6 or 1 hours prior to left nephrectomy. Kidneys were flushed with cold Euro-Collins solution and after 2 hours transplanted using microsurgical techniques concomittant with a left nephrectomy. After 48 hours (day 0), we removed the right kidney. Serum creatinine (SCr) was determined daily thereafter as well as differential leukocyte counts prior to donor nephrectomy and sirolimus plasma levels thereafter.

Results

No difference was observed in SCr on day 1: control (3.97 ± 0.73 mg/dL), sirolimus (4.02 ± 1.44 mg/dL) and FTY 720 (3.27 ± 1.79 mg/dL; P = NS), or thereafter. Mortality was 50% in each group. Animals receiving FTY 720 showed a significant reduction in lymphocyte count (8.0 ± 3.1 to 1.1 ± 0.3 (P < .01). Sirolimus levels were 9.3 ± 1.5 ng/mL.

Conclusion

We concluded that immunosuppressive treament of the donor within a time frame relevant to cadaveric kidney transplantation did not offer a benefit in terms of preventing IR injury.     

Changes in magnesium and potassium homeostasis after conversion from a calcineurin inhibitor regimen to an mTOR inhibitor-based regimen

Background

Transplant recipients treated with calcineurin inhibitors (CNIs) frequently show hyperkalemia, metabolic acidosis, and hypomagnesemia which could be deleterious for some patients. Conversion to inhibitors of mammalian target of rapamycin (mTOR) could improve these electrolytic disturbances.

Objective

To evaluate the potassium and magnesium changes due to converting patients from CNIs to mTOR inhibitors.

Methods

Retrospective review of 138 renal transplant patients who were converted from CNIs to mTOR inhibitors over a 6-month observation period. The following parameters were determined: potassium, sodium, chloride, magnesium, urea, glucose, and creatinine in blood and urine. We also analyzed plasma bicarbonate and calculated plasma and urine anion gap and plasma osmolarity.

Results

One month after conversion, a decrease was observed in serum creatinine (1.75 ± 0.68 vs 1.61 ± 0.61 mg/dL; P = .01), plasma potassium (4.60 ± 0.52 vs 4.39 ± 0.53 mEq/L; P < .001), calculated plasma osmolarity (308.7 ± 8.5 vs 307.4 ± 8.4 mOsm/L; P < .036), fractional excretion of sodium (1.55 ± 0.69 vs 1.29 ± 0.65%; P < .003), and fractional excretion of magnesium (7.15 ± 4.08 vs 15.84 ± 3.64%; P < .001), with an increase in serum magnesium (1.77 ± 0.24 vs 1.95 ± 0.29 mg/dL; P < .001). At 3 and 6 months, these differences remained unchanged. The transtubular potassium gradient did not change.

Conclusions

We observed a decrease in serum magnesium due to renal magnesium wasting before switching from CNIs to mTOR inhibitors. After conversion, an increase in serum magnesium was observed together with a drop in the fractional excretion of this cation. A decrease in plasma potassium levels, plasma osmolarity, and fractional excretion of sodium consistent with minor aldosterone resistance was also detected after changing the immunosuppressive treatment.     

Subcutaneous transplantation may not be an appropriate approach for the islets embedded in the collagen gel scaffolds

Background

Synthetic extracellular matrix (ECM) has been shown to be efficient to preserve the function of transplanted islets. In this study using a mouse model, we sought to determine whether subcutaneous transplantation was a convenient procedure for achieving normoglycemia.

Methods

We performed in vitro tests as well as morphologic observations and Western blotting to establish that embedded islets survived better than non-embedded islets. Streptozotocin-induced diabetic mice (BALB/c) were transplanted with ECM-embedded syngeneic islets via the subcutaneous (SC; n = 5) or subrenal capsule (SRC; n = 6) routes. We measured mean blood glucose levels at various points from pretransplantation to postoperative day 14, and examined immunohistochemistry staining for insulin in the transplant grafts on day 14.

Results

Islets transplanted with ECM gel retained better structure and developed a functional vasculature. Western blotting showed more caspase-3 expressed in the non-embedded islets, which indicated more islet cells undergoing apoptosis. On the first day after transplantation, glucose levels were significantly decreased in the SRC group compared with the SC group: 383.33 ± 44.50 mg/dL to 80.67 ± 16.85 mg/dL versus 414.00 ± 92.33 mg/dL to 278.28 ± 121.80 mg/dL (P < .05). Glucose levels were better maintained in the SRC group than the SC group over 14 days. Immunohistochemistry staining for insulin showed fewer islets in the SC group.

Conclusion

Embedded islets with ECM gel functioned better than non-embedded ones in vitro. However, the subcutaneous route may not be an ideal site for islet transplantation.     

Long-term outcomes of living kidney donors over the past 28 years in a single center in Taiwan

Background

The chronic shortage of kidneys for transplantation has increased the number of living donations, but demand remains high, which has created a long waiting list of end-stage kidney disease patients. Donors with decreased renal mass may suffer a higher risk of developing proteinuria, hypertension (HTN), and chronic renal disease (CKD) during long-term follow-up.

Methods

We retrospectively retrieved medical data of living kidney donors at our hospital over the past 28 years.

Results

There were 45 male and 60 female donors with a mean donation age of 46.34 ± 12.47 years (range = 20-70y). The mean follow-up duration was 4.67 ± 4.78 years. The serum creatinine (Cr) at donation was 0.93 ± 0.22 mg/dL, while the latest Cr was 1.26 ± 0.45 mg/dL (P < .001). The mean age at follow-up was 50.95 ± 14.57 years. At last follow-up, eight subjects (7.6%) displayed HTN requiring treatment, 10 (9.5%), proteinuria and 55.4%, an estimated glomerular filtration rate (eGFR) of less than 60 mL/min, including one with diabetic nephropathy at 10 years after donation who required long-term hemodialysis. Although gender did not correlate with occurrence of HTN, proteinuria, and CKD, the occurrence of CKD was associated with age at donation (P < .001, odds ratio [OR] = 1.076), and age at follow-up (P < .001, OR = 1.071). HTN donors were older (P = .036, OR = 1.057) with longer follow-up durations (P = .007, OR = 1.166) and had higher Cr values at donation (P = .044, OR = 94.4). Donors with proteinuria were not related to gender, follow-up duration, initial Cr, warm ischemic time, or duration of admission. eGFR was indeed worse after donation (P = .002).

Conclusions

Our results indicated a significant proportion of living donors may develop CKD upon long-term follow-up. The factors affecting donor risk of CKD were baseline renal function, older age, and duration after kidney donation.     

Is heparinization necessary in the early postoperative period of renal transplantation from cadaveric donors?

Introduction

Venous thromboemboli and bleeding are the complications that threaten the graft and patient's life in the early postoperative period after cadaveric renal transplantation. For this reason, heparin administration after renal transplantation should be administered carefully. The aim of this study was to evaluate the necessity for heparinization after cadaveric renal transplantation.

Methods

Between March 2009 and October 2010, we formed 2 study groups among 50 recipients who underwent either cadaveric (n = 25) or living donor transplantations (n = 25). We did not observe any risk factors for thromboembolism while group 1 did not undergo heparinization, group 2 received a prophylactic dose of low-molecular weight heparin for 1 week. Doppler ultrasonography (USG) was performed between postoperative 24-48 hours to examine the transplanted kidney vessels, and in one group 1 case for a bilateral lower extremity venous system examination. We were also compared postoperative thromboembolic and hemorrhagic complications, lymphorrhagia, and serum creatinine levels.

Results

The female/male ratios in group 1 and 2 were 14/11 and 8/17 with mean ages of 36.7 (range, 17-51) and 35.9 (range, 17-59) years, respectively. The mean preoperative serum creatinine levels were 7.9 ± 2.9 mg/dL and 6.8 ± 2.4 mg/dL, and at postoperative week 1, they were 5.1 ± 4.3 mg/dL and 1.2 ± 0.5 mg/dL, respectively. We did not encounter any partial or total thrombus upon doppler USG studies for renal and lower extremity venous systems. No clinical symptoms of pulmonary emboli were detected in any patients. Only 1 subject group 2 experienced massive postoperative bleeding.

Conclusion

Herein, we have reported that, except for the patients with risk factors for venous thromboemboli, heparinization was not necessary in the early postoperative period and did not add benefits to outcomes of cadaveric renal transplant recipients.