Effects In Kidney Transplant Recipients Research Articles

#6369 RESULTS OF KIDNEY TRANSPLANTATION IN PATIENTS WITH LOW MFI PREFORMED DONOR SPECIFIC ANTIBODIES

Abstract Background and Aims Preformed DSA at transplantation, significantly increase risk of antibody-mediated rejection (ABMR). While pre-existing positive DSA with concomitant positive cross-match is a general contra-indication to kidney transplantation, DSA presence with negative crossmatch is still a controversial topic. The presence of DSA with Mean Fluorescence Index (MFI) up to 3.000 and a negative cross-match is not valued as a contraindication to transplantation and is widely accepted. In some transplant centers the chance of transplantation is also offered to DSA positive patients, with MFI up to 5.000. Aim of this study was to analyze graft and patient survival, acute cellular rejection, humoral rejection, renal function and side effects in kidney transplant recipients (KTR) with positive DSA (MFI up to 3.000) and negative cross-match. Method Nineteen pts (age 53+/-11) with chronic renal failure on chronic hemodialysis treatment (8+/-6 years) received a kidney transplant between May 2017 and December 2020. Median PRA was 66%; 100% pts had DSA with average MFI 2122 (min 1039, max 3779). As immunosuppressive therapies all pts received induction with Thymoglobuline plus Rituximab, followed by maintenance immunosuppression with Tacrolimus, MofetilMycoFenolate and Steroids. All patients were on periodic follow up in our Transplant Clinic. Mean follow up was 26.5+/-14.4 months. Results were compared to a concomitant KTR group DSA and crossmatch negative. Results After 2y follow-up, 17/19 pts are alive (89.5%), one patient died (1/19, 5.2%) after treatment for ABMR. Three patients returned to dialysis treatment (15.8%) during the first year post-tx, because of: PNF 1pt; irreversible ABMR rejection 2 pts. One other patient had reversible ABMR. Cumulative one year graft survival was 79% and the cumulative incidence of ABMR was 15.8%. Average 2 years follow-up creatinine was 1.46+/-0.88 mg/dl, median 2 year GFR was 51+/-25 ml/min. Comparing the matched control group (19 pts DSA and cross-match negative) 2 years patient survival, graft survival, GFR, acute rejection were not significantly different. Incidence of acute rejection was higher in the DSA positive group (16% vs 0%), as well as graft loss (21% vs 12%). Conclusion Our data suggest that low dose Thymoglobuline plus Rituximab induction allow kidney transplantation in recipient with high PRA (69%) and positive DSA with low MFI (< 3.000), with higher risk of acute rejection, and graft loss.

Effect of Mammalian Target of Rapamycin Inhibition on Activated Regulatory T-Cell Expansion in Kidney Transplantation

The mammalian target of rapamycin (mTOR) plays a critical role in the host immune response in organ transplantation. This study evaluates the regulatory benefits of mTOR inhibitors in kidney transplant recipients (KTRs). The mTOR-dependent immune-regulating effects in KTRs were evaluated by examining T-cell subsets among peripheral blood mononuclear cells from 79 KTRs. Recipients included an early introduction of everolimus (EVR) and reduced-exposure tacrolimus group (n=46) and a standard tacrolimus-based without EVR (non-EVR) group (n=33). Trough concentrations of tacrolimus at 3 months and 1 year were significantly lower in the EVR group than the non-EVR group (both P < .001). In addition, the respective proportions of patients without estimated glomerular filtration rate < 20% in the EVR and non-EVR groups were 100% and 93.3% at 1 year, 96.3% and 89.7% at 2 years, and 96.3% and 89.7% at 3 years after blood collection, respectively (P=.079). The frequencies of CD3+ T cells and CD4+ T cells among peripheral blood mononuclear cells were comparable between groups. Total CD25highCD127-CD4+ regulatory T (Treg) cells were similar in the EVR and non-EVR groups. In contrast, circulating CD45RA-CD25highCD127-CD4+ activated Treg cells were significantly higher in the EVR group (P= .008). These results suggest that the early introduction of mTOR benefits long-term kidney graft function and circulating activated Treg-cell expansion in KTRs.

Serum Bicarbonate and Graft and Patient Outcomes Among Kidney Transplant Recipients: A Retrospective Cohort Study Evaluating Changes in Serum Bicarbonate Over Time

Identification of treatable risk factors for kidney allograft failure is necessary to improve graft longevity. Metabolic acidosis with either low serum bicarbonate or normal serum bicarbonate (eubicarbonatemic metabolic acidosis) is implicated in native kidney disease progression but its effects in kidney transplant recipients are unclear. Retrospective cohort study. An Integrated Claims-Clinical dataset of US patients with chronic kidney disease (estimated glomerular filtration rates<60mL/min/1.73m2) and serum bicarbonate data were used to generate a cohort of kidney transplant recipients with data from≥1 year before and after transplantation. The primary independent variable was a change in serum bicarbonate from baseline. The primary outcomes were graft failure and all-cause mortality. The secondary outcomes were major adverse cardiac events and all-cause hospitalization. We used adjusted time-dependent Cox proportional hazards models to assess the risk of graft failure, all-cause mortality, major adverse cardiac events, and time to first hospitalization. In this US community-based cohort of 1,915 kidney transplant recipients with a median follow-up of ∼2.5 years, each 1-mEq/L increase in serum bicarbonate was associated with significantly lower hazard of graft loss, death, major adverse cardiac events, and hospitalization by 10%, 8%, 4%, and 8%, respectively. Possible residual confounding. In a US community-based population of kidney transplant recipients, even small incremental increases in serum bicarbonate (1 mEq/L) were significantly associated with reduced hazard of graft loss, all-cause mortality, cardiovascular events, and hospitalization. Interventional trials evaluating the potential benefits of treating metabolic acidosis in kidney transplant recipients are warranted.

Cytomegalovirus Disease, Short-Term Cardiovascular Events and Graft Survival in a Cohort of Kidney Transplant Recipients With High CMV IgG Seroprevalence.

Both cytomegalovirus (CMV) infection and CMV disease have been linked with several long-term indirect effects in kidney transplant recipients. Research questions: We conducted a retrospective study to assess the association between cytomegalovirus disease and risks of death, shortterm cardiovascular events and graft loss in a cohort of renal transplant recipients. The associations between CMV disease and death and cardiovascular events were determined using Cox regression models, while the association between viral disease and graft loss risk was analyzed through a competing risks regression according to the Fine and Gray method. Death with a functioning graft was considered as a competing risk event. A total of 865 consecutive renal transplant recipients were included. The prevalence of seropositive donor/seronegative recipient (D+/R-) group was 89.9% with the remaining patients classified as seropositive recipient (R+). After median follow-up time of 24.4 months, CMV disease was not a risk factor for all-causes mortality (HR = 1.75; 95% CI 0.94-3.25), early cardiovascular events (HR = 0.54; 95% CI 0.16-1.82) or graft loss (subhazard ratio [the HR adjusted for competing risk of death with functioning graft] = 0.99; 95% CI 0.53-1.84). In this cohort with high prevalence of CMV IgG antibodies, we found no association between cytomegalovirus disease and risk of death or graft loss. The relationship between CMV and cardiovascular disease remains to be unraveled and probably corresponds to a multifactorial phenomenon involving individual risk factors and the immune response to infection rather than the virus effect itself.

Effects of Ringer Lactate Normal Saline Combination Vs Normal Saline during Renal Transplantation Surgery on Early Postoperative Outcome

Background: Traditionally normal saline is the most common crystalloid solution that is used in transplant surgery. Normal saline (NS) because of the higher risk of acidosis and higher levels of serum chloride may have more deleterious effects in kidney transplant recipients Thus; the aim of this study was to determine the safety of ringer lactate normal saline combination if used during a renal transplant.&#x0D; Methods: One Hundred adults undergoing kidney transplantations were enrolled in a double-blinded randomized prospective clinical trial. They were divided into two groups in order to receive RL&amp; NS and NS infusion as intraoperative IV fluid replacement therapy. All patients received 40 ml/kg fluid during surgery. Serum chloride, sodium, Cr and BUN were checked before operation and 6hour after surgery. Urine output BUN and Cr was also checked in 1, 3 and 7 day after surgery. At the end of surgery, we corrected the acid base status with bicarbonate according to base excess&lt; -15 or PH&lt;7.15 if needed in both groups.&#x0D; Results: There was a significant difference in the serum chloride level (p= 0.001) and urine output (p= 0.003) between the two groups at the 6 hours after transplantations. Postoperative BUN and Cr level at 2,3 and 7 days in RL&amp;NS group was significantly lower than group of NS (P= 0.011). Also, urine output during this study time was significantly higher in RL&amp;NS group (p=0.001).&#x0D; Conclusion: Combination of Ringer lactate &amp;normal saline crystalloid solutions are associated with higher urinary output and most favorited out come in the early post-operative days after renal transplantation surgeries.

MON-181 A PILOT STUDY OF SPIRONOLACTONE ON THE ENDOTHELIAL GLYCOCALYX IN KIDNEY TRANSPLANT RECIPIENTS

The endothelial glycocalyx lines the lumen of blood vessels and has protective effects on the microvasculature. Damage to this layer can be detected as an increase of its shed constituents in blood, and an increase in the perfused boundary region (PBR) in sublingual vessels using the novel GlycoCheckTM device. In vitro studies have shown toxic effects of aldosterone and a high-salt environment on the glycocalyx that are attenuated by spironolactone. Spironolactone is known to have antiproteinuric and vasculoprotective effects in kidney transplant recipients (KTR).

Proton pump inhibitors and adverse effects in kidney transplant recipients: A meta-analysis.

BACKGROUNDThe adverse renal effects of proton pump inhibitors (PPIs) are increasingly recognized in both the general population and patients with chronic kidney disease. Several pharmacokinetic studies have also raised concerns regarding the interaction between PPIs and immunosuppressive drugs in transplant patients. Whether the adverse effects of PPIs have a clinical significance in kidney transplant recipients remains unclear. We performed this meta-analysis to assess the risk of adverse effects in kidney transplant recipients on PPI compared with those without PPI exposure.AIMTo investigate the risk of acute rejection, graft loss, hypomagnesemia, renal dysfunction, and overall mortality in kidney transplant recipients on PPI compared with those without PPI exposure.METHODSA systematic review was conducted in MEDLINE, EMBASE, and Cochrane databases from inception through October 2018 to identify studies that evaluated the adverse effects of PPIs in kidney transplant recipients, including biopsy-proven acute rejection, graft loss, hypomagnesemia, renal function, and overall mortality. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO, No. CRD42018115676.RESULTSFourteen observational studies with 6786 kidney transplant recipients were enrolled. No significant association was found between PPI exposure and the risk of biopsy-proven acute rejection at ≥ 1 year [pooled odds ratio (OR), 1.25; 95% confidence interval (CI), 0.82-1.91, I2 = 55%], graft loss at 1 year (pooled OR = 1.30, 95%CI: 0.75-2.24, I2 = 0%) or 1-year mortality (pooled OR = 1.53, 95%CI: 0.90-2.58, I2 = 34%). However, PPI exposure was significantly associated with hypomagnesemia (pooled OR = 1.56, 95%CI: 1.19-2.05, I2 = 27%). Funnel plots and Egger regression asymmetry test were performed and showed no publication bias.CONCLUSIONPPI use was not associated with significant risks of higher acute rejection, graft loss, or 1-year mortality. However, the risk of hypomagnesemia was significantly increased with PPI use. Thus, future studies are needed to assess the impact of PPIs on long-term outcomes.

Patient-reported outcome measures for life participation in kidney transplantation: A systematic review.

For many patients with end-stage kidney disease, transplantation improves survival and quality of life compared with dialysis. However, complications and side effects in kidney transplant recipients can limit their ability to participate in activities of daily living including work, study, and recreational activities. The aim of this study was to identify the characteristics, content, and psychometric properties of the outcome measures used to assess life participation in kidney transplant recipients. We searched MEDLINE, Embase, PsycINFO, and CINAHL from inception to July 2018 for all studies that reported life participation in kidney transplant recipients. Two authors identified instruments measuring life participation and reviewed for characteristics. In total, 230 studies were included: 19 (8%) randomized trials, 17 (7%) nonrandomized trials, and 194 (85%) observational studies. Across these studies, we identified 29 different measures that were used to assess life participation. Twelve (41%) measures specifically assessed aspects of life participation (eg, disability assessment, daily activities of living), while 17 (59%) assessed other constructs (eg, quality of life) that included questions on life participation. Validation data to support the use of these measures in kidney transplant recipients were available for only 7 measures. A wide range of measures have been used to assess life participation in kidney transplant recipients, but validation data supporting the use of these measures in this population are sparse. A content relevant and validated measure to improve the consistency and accuracy of measuring life participation in research may inform strategies for transplant recipients to be better able to engage in their life activities.

The effect of aspirin on kidney allograft outcomes; a short review to current studies.

Context: The use of aspirin in chronic kidney disease (CKD) patients has been shown to reduce myocardial infarction but may increase major bleeding. However, its effects in kidney transplant recipients are unclear. Evidence Acquisitions: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through September 2016. We included studies that reported odd ratios, relative risks or hazard ratios comparing outcomes of aspirin use in kidney transplant recipients. Pooled risk ratios (RR) and 95% confidence interval (CI) were assessed using a random-effect, generic inverse variance method. Results: We included 9 studies; enrolling 19759 kidney transplant recipients that compared aspirin with no treatment. Compared to no treatment, aspirin reduced the risk of allograft failure (4 studies; RR: 0.57, 95% CI: 0.33 to 0.99), allograft thrombosis (2 studies; RR: 0.11, 95% CI: 0.02 to 0.53), and major adverse cardiac events (MACEs) or mortality (2 studies; RR: 0.72, 95% CI: 0.59 to 0.88), but not allograft rejection (3 studies; RR: 0.86, 95% CI: 0.45 to 1.65) or delayed graft function (DGF) (2 studies; RR: 1.00, 95% CI: 0.58 to 1.72) in kidney transplant recipients. The data on risk of major or minor bleeding were limited. Conclusions: Our meta-analysis demonstrates that administration of aspirin in kidney transplant recipients is associated with reduced risks of allograft failure, allograft thrombosis, and MACEs or mortality, but not allograft rejection or DGF. Future studies are needed to assess the risk of bleeding, and ultimately weigh the overall risks and benefits of aspirin use in specific kidney transplant patient populations.

Effect of FTY720 (fingolimod) on graft survival in renal transplant recipients: a systematic review protocol

IntroductionStudies have shown that FTY720 has inconsistent effects in kidney transplant recipients. Several review articles on FTY720 have been published, but most have focused on the mechanism of action of...

Oscillatory mTOR inhibition and Treg increase in kidney transplantation

Intracellular metabolic pathways dependent upon the mammalian target of rapamycin (mTOR) play a key role in immune-tolerance control. In this study, we focused on long-term mTOR-dependent immune-modulating effects in kidney transplant recipients undergoing conversion from calcineurin inhibitors (CNI) to mTOR inhibitors (everolimus) in a 1-year follow-up. The conversion to everolimus is associated with a decrease of neutrophils and of CD8(+) T cells. In addition, we observed a reduced production of interferon (IFN)-γ by CD8(+) T cells and of interleukin (IL)-17 by CD4(+) T lymphocytes. An increase in CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) [regulatory T cell [(Treg)] numbers was also seen. Treg increase correlated with a higher proliferation rate of this regulatory subpopulation when compared with the CD4(+) FoxP3(-) effector counterpart. Basal phosphorylation level of S6 kinase, a major mTOR-dependent molecular target, was substantially maintained in patients treated with everolimus. Moreover, oscillations in serum concentration of everolimus were associated with changes in basal and activation-dependent S6 kinase phosphorylation of CD4(+) and CD8(+) T cells. Indeed, T cell receptor (TCR) triggering was observed to induce significantly higher S6 kinase phosphorylation in the presence of lower everolimus serum concentrations. These results unveil the complex mTOR-dependent immune-metabolic network leading to long-term immune-modulation and might have relevance for novel therapeutic settings in kidney transplants.

Vitamin D Status has no Influence on the Incidence of Recurrent Urinary Tract Infections after Kidney Transplantation

Abstract Introduction. Recurrent urinary tract infections (rUTIs) after kidney transplantation (KT) are associated with significant decrease in graft survival. There is a growing body of evidence for the pleiotropic effects of vitamin D (VD), including immunomodulatory and antibacterial effect. The number of studies on VD’s pleiotropic effects in kidney transplant recipients (KTRs) however is low. The aim of our study was to assess the influence of VD on the incidence of recurrent UTIs after KT. Methods. The KTRs were tested for 25-hydroxyvitamin D (25VD) between 1.05.2012 and 30.11.2012. Patients within 12 months of transplantation, performed parathyroidectomy, concomitant intake of calcineurin inhibittors and mTOR inhibitors, advanced liver disease and VD supplementation were excluded from the study. Recurrent UTIs were defined as more than 3 episodes of active UTI within the last 12 months of testing for 25VD. Statistical analysis was carried out with SPSS version 22.0 and included descriptive statistics, Mann-Whitney U test. Determination of total 25VD was performed by a validated LC-MS/MS method. Results. A total of 275 patients met the above-mentioned criteria (males 182, females 93). The mean 25VD in patients with rUTIs (n=14) was 51.41±25.17 nmol/L, whereas in the group without rUTIs (n=261) the level was 60.35±23.29 nmol/L. After matching the two groups for seasonal factors (sampling for 25VD in July, August, September) and gender 169 patients were selected, and 11 were with rUTIs. No significant difference was detected in the 25VD level in the two groups (53.30±18.37 vs 49.08±21.04 nmol/L), p=0.342. Conclusions. Despite the higher 25VD in the KTRs without rUTIs, the difference between the two groups remained insignificant.

A Prospective Analysis of the Effects of Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil Co-medicated With a Proton Pump Inhibitor in Kidney Transplant Recipients at a Single Institute in China

BackgroundEnteric-coated mycophenolate sodium (EC-MPS) and mycophenolate mofetil (MMF), two prodrugs of mycophenolic acid (MPA), have been used in immunosuppressive regimens. After being taken orally, both of them transform to MPA to achieve immune suppression effects; however, the main site of absorption and metabolism of EC-MPS is different from that of MMF in vivo. Therefore, combined application with related drugs may result in different MPA levels and have different clinical effects in kidney transplant recipients. ObjectiveTo evaluate the efficacy of EC-MPS compared with MMF in Chinese renal transplant patients comedicated with a proton pump inhibitor (PPI). MethodsOur subjects were 88 patients who received renal transplants at the 309th Hospital of the Chinese PLA from May 2010 to April 2013. These were made up of two groups including 27 patients with EC-MPS and 61 with MMF. The immunosuppression regimen was EC-MPS/MMF + cyclosporine/tacrolimus + steroid hormone, comedicated with a PPI (omeprazole). The patients' levels of exposure of MPA within 1 week after operation were monitored. Clinical indicators such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine hemoglobin, leucocytes, and neutrophils, as well as clinical adverse drug reactions and drug conversion were analyzed retrospectively. Results and ConclusionThe kidney function of patients recovered to normal in both the EC-MPS and MMF groups. The mean concentration to peak (Cmax), the mean half-life (t1/2), and the area under the concentration–time curve (AUC0–12) of MPA in the EC-MPS group were higher than those in the MMF group (P < .05). This indicated that the pharmacokinetic parameters for MPA when EC-MPS is co-administered with a PPI in kidney transplant patients in China is better than for comedication with MMF and a PPI. The MMF group had a higher incidence of drug withdrawal because of higher infection rates, leucocyte decrease, and more gastrointestinal side effects than the EC-MPS group (P < .05). No significant differences in the clinical effect on kidney transplant recipients were observed in the limited observation time.

The incidence, management, and evolution of rapamycin‐related side effects in kidney transplant recipients

Conversion from a calcineurin-inhibitor-based immunosuppression to a rapamycin-based immunosuppression may preserve kidney graft function. The side effects of rapamycin can limit its usefulness, but their management and evolution are rarely reported in clinical trials. We performed a retrospective cohort study in patients transplanted before December 31, 2008 and who received rapamycin to replace calcineurin inhibitors. In 219 patients studied, 98% presented ≥1 side effects after starting rapamycin. Side effects occurring in ≥10% of patients were dyslipidemia (52%, 95% confidence interval (CI): 45-59%), peripheral edema (37%, 95%CI: 31-43%), cytopenia (36%, 95% CI: 30-42%), acne (29%, 95% CI: 23-35%), proteinuria (23%, 95% CI: 17-29%), and oral ulcers 14% (95% CI: 10-18%). Proteinuria, ulcers, and edema were difficult to manage and were more likely to cause cessation of rapamycin. Rapamycin was discontinued in 46% of patients (95% CI: 40-52%). Age (odds ratio [OR] per 10-yr increase: 1.29, 95% CI: 1.05-1.59) and obesity (OR: 2.57, 95% CI: 1.10-6.01) were independently associated with cessation of rapamycin. We conclude that successful control of dyslipidemia and cytopenia can be achieved without discontinuing rapamycin. Most other side effects are harder to manage. Leaner and younger patients are less likely to discontinue rapamycin due to side effects.

Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis.

Statins have uncertain benefits in persons with chronic kidney disease (CKD) because individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD. To summarize the benefits and harms of statin therapy for adults with CKD and examine whether effects of statins vary by stage of kidney disease. Cochrane and EMBASE databases (inception to February 2012). Randomized trials comparing the effects of statins with placebo, no treatment, or another statin on mortality and cardiovascular outcomes. Two independent reviewers extracted data and assessed risk of bias. Eighty trials comprising 51099 participants compared statin with placebo or no treatment. Treatment effects varied with stage of CKD. Moderate- to high-quality evidence indicated that statins reduced all-cause mortality (relative risk [RR], 0.81 [95% CI, 0.74 to 0.88]), cardiovascular mortality (RR, 0.78 [CI, 0.68 to 0.89]), and cardiovascular events (RR, 0.76 [CI, 0.73 to 0.80]) in persons not receiving dialysis. Moderate- to high-quality evidence indicated that statins had little or no effect on all-cause mortality (RR, 0.96 [CI, 0.88 to 1.04]), cardiovascular mortality (RR, 0.94 [CI, 0.82 to 1.07]), or cardiovascular events (RR, 0.95 [CI, 0.87 to 1.03]) in persons receiving dialysis. Effects of statins in kidney transplant recipients were uncertain. Statins had little or no effect on cancer, myalgia, liver function, or withdrawal from treatment, although adverse events were evaluated systematically in fewer than half of the trials. There was a reliance on post hoc subgroup data for earlier stages of CKD. Statins decrease mortality and cardiovascular events in persons with early stages of CKD, have little or no effect in persons receiving dialysis, and have uncertain effects in kidney transplant recipients.

Neither Mycophenolate Acyl-Glucuronide Levels nor Their Areas Under the Curve Are Responsible for the Gastrointestinal Side Effects in Kidney Transplant Recipients Receiving EC-MPA: A Prospective Trial

Introduction Since previous in vitro studies suspected the metabolite mycophenolate acyl-glucuronide (AcMPAG) to be responsible for the gastrointestinal side effects, we examined the correlation between AcMPAG blood levels and patient gastrointestinal satisfaction inquiries using a standardized, validated questionnaire. Patients and Methods We enrolled 63 renal transplant patients, however, two discontinued the study and 16 were excluded because of inadequate completion of the questionnaires or missing blood values or discontinuation of enteric coated mycophenolic acid (EC-MPA) therapy, severe side effects or viral infections. The final responses of 45 people were subjects to statistical analysis. Gastrointestinal side effects were examined using the Gastrointestinal Symptom Rating Scale (GSRS) completed at three times: T1 (3–5 days after transplantation), T2 (10–15 days), and T3 (3 months). The GSRS results generated two groups of patients based on cutoff values set at a score of 4 points for each item. Scores less than 4 were assumed to be “no side effects”; ≥4, “side effects.” AcMPAG was measured by mass spectroscopy on blood samples obtained at fixed times generating three pharmacokinetic profiles per patient. Results There was no relation between high AcMPAG blood concentrations and gastrointestinal dissatisfaction. Neither Ac-MPAG area under the curve (AUC) in the absorption phase nor AcMPAG peak values correlated with gastrointestinal dissatisfaction. Conclusion There was no significant correlation between mean AcMPAG and GSRS scores, although previous studies had suggested AcMPAG maximum values or alternatively AcMPAG AUC in the absorption phase to relate to side effects.

Antihypertensives for Kidney Transplant Recipients: Systematic Review and Meta-Analysis of Randomized Controlled Trials

In nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. We performed a systematic review including random effects meta-analysis of randomized controlled trials, using Cochrane Collaboration methodology. We identified 60 trials, enrolling 3802 recipients. Twenty-nine trials (2262 patients) compared calcium channel blockers (CCB) with placebo or no treatment, 10 trials (445 patients) compared angiotensin-converting enzyme inhibitors (ACEi) with placebo or no treatment, and seven studies (405 patients) compared CCB with ACEi. CCB compared with placebo or no treatment (plus additional agents in either arm as required) reduced graft loss (risk ratio [RR] 0.75, 95% confidence intervals [CI] 0.57-0.99) and improved glomerular filtration rate (GFR; mean difference [MD] 4.5 mL/min, 95% CI 2.2-6.7). Data on ACEi versus placebo or no treatment were inconclusive for GFR (MD -8.1 mL/min, 95% CI -18.6-2.4) and inconsistent for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD 11.5 mL/min, 95% CI 7.2-15.8), proteinuria (MD 0.28 g/day, 95% CI 0.10-0.47), hemoglobin (MD 11.5 g/L, 95% CI 7.2-15.8), and increased hyperkalemia (RR 3.7, 95% CI 1.9-7.7). Graft loss data were inconclusive (RR 7.4, 95% CI 0.4-140). These data suggest that CCB may be preferred as first-line agents for hypertensive kidney transplant recipients.

Antihypertensive treatment for kidney transplant recipients.

In some nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. To assess comparative effects of different classes of antihypertensive agents in kidney transplant recipients. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings and reference lists of identified studies were searched. Randomised controlled trials of any antihypertensive agent applied to kidney transplant recipients for at least two weeks were included. Data was extracted by two investigators independently. Study quality, transplant outcomes and other patient centred outcomes were assessed using random effects meta-analysis. Risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI) were calculated. Stratified analyses and meta-regression were used to investigate heterogeneity. We identified 60 studies, enrolling 3802 recipients. Twenty-nine studies (2262 participants) compared calcium channel blockers (CCB) to placebo/no treatment, 10 studies (445 participants) compared angiotensin converting enzyme inhibitors (ACEi) to placebo/no treatment and seven studies (405 participants) compared CCB to ACEi. CCB compared to placebo/no treatment (plus additional agents in either arm as required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68). Data on ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95% CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to -7.21), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10), haemoglobin (MD -12.96 g/L, 95% CI -5.72 to -10.21) and increased hyperkalaemia (RR 3.74, 95% CI 1.89 to 7.43). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to 140.35). Other drug comparisons were compared in small numbers of participants and studies. These data suggest that CCB may be preferred as first line agents for hypertensive kidney transplant recipients. ACEi have some detrimental effects in kidney transplant recipients. More high quality studies reporting patient centred outcomes are required.

Effect of Ramadan Fasting on Moslem Kidney Transplant Recipients

This study was carried out to find out whether Ramadan fasting would affect the renal function in kidney transplant recipients with normal or impaired graft function. Twenty-three transplant recipients, 17 with a normal function and 6 with an impaired but stable function with plasma creatinine levels not exceeding 300 mmol/l, were included in this study. The mean posttransplant period was 2.0 (range 0.6–6.3) years. Urinary and serum biochemical parameters, ciclosporin A level, and hematocrit were checked weekly, during Ramadan as well as 1 week before and after. Statistical analysis showed no significant changes in all parameters before, during, and after Ramadan. In conclusion, our findings indicate that fasting during the month of Ramadan does not seem to be associated with any significant adverse effects in kidney transplant recipients with normal or impaired graft function and suggest that it is safe for those patients to fast during Ramadan after 1 year of renal transplantation.