Function In Renal Transplant Recipients Research Articles

Hyposplenism in Long-Standing Renal Transplant Recipients

Background: In our unit, the routine screening for kidney recipients include surveillance with sonography/Doppler after surgery, irrespective of graft function, and at least once a year later on. Almost all studies are performed by an experienced trained nephrologist, who noticed that patients soon after post-transplant showed a larger spleen than patients with long-standing functioning renal graft. These findings, together with the report that in chronic graft versus host disease in bone marrow transplant recipients develop spleen size reduction associated with hyposplenism, and hyposplenism is known to increase susceptibility to infections with encapsulated bacteria, prompted the authors to decide to study splenic function in renal transplant recipients based on sonographic/Doppler and haematological parameters. Methods: The study design was a cross-sectional survey based on single samples. We enrolled two groups: one in the immediate postoperative days (early group) and the other with functioning long-standing kidney graft (late group). To evaluate splenic function, two studies were carried out. First, longitudinal diameter of the spleen and resistivity index of splenic artery at hilum and intrasplenic were measured. All sonograms were performed by a single observer. Second, stained with Giemsa peripheral blood smears (PBS) were reviewed for the presence of Howell-Jolly bodies, using a light microscope viewing. All blood samples were examined by a single observer. Examination of the PBS for Howell-Jolly bodies was restricted to the late group. According to the result, late group was further divided in Howell-Jolly bodies positive (HJ+) or negative (HJ−). Spleen size determination by ultrasonography and Doppler studies were performed in both groups. Immunosuppressive drug regimen used corticosteroid, azathioprine or mycophenolate mofetil and calcineurin inhibitor or mTOR inhibitor. Results: We studied 52 unselected adult patients who had undergone kidney transplantation from a deceased donor and 24 from living donor. The mean age was 48.4±11.5 years (range: 23-74 years). Mean follow up was 11.4±14.2 days for early group (range: 1-68 days) and 2698±1177 days for late group (range: 215-6446 days). Late group had smaller spleen than early group (95.8±16.5 vs 106.3±16.3 mm, p=0.010). Howell-Jolly bodies were found in 52% (24/46) of patients. Intrasplenic resistivity index tended to be higher in HJ+ patients (0.57±0.09 vs 0.51±0.09, p=0.055). There was no correlation between Howell-Jolly detection and immunosuppressive drug regimen. Serum creatinine level was the same despite Howell-Jolly detection or not. Discussion: The presence of Howell-Jolly bodies in the peripheral blood red cells is considered an indicator of hyposplenism. Our findings that a group of transplant patients may develop significant spleen size reduction and detection of Howell-Jolly bodies associated with increased intrasplenic resistivity index suggest splenic dysfunction in these patients, yet the clinical significance of these findings to the outcome of the graft is unknown. Nevertheless, poor splenic function may play a role in the vulnerability to infections in transplant recipients.

Neither Cyclosporine nor Tacrolimus Deteriorate Endothelial Function in Renal Transplant Recipients Assessed with Reactive Hyperaemia Index

Neither Cyclosporine nor Tacrolimus Deteriorate Endothelial Function in Renal Transplant Recipients Assessed with Reactive Hyperaemia Index

Influence of Erythropoietin on Arterial Stiffness and Endothelial Function in Renal Transplant Recipients

Background/Aims: Recent retrospective studies suggest an association of therapy with erythropoiesis-stimulating agents (ESAs) and increased mortality in renal transplant recipients (RTR). Large artery structure and function are significantly impaired in RTR which contributes to their high cardiovascular morbidity and could be altered by erythropoietin. We aimed to examine the influence of ESA therapy on large artery stiffness and endothelial function in RTR. Methods: 63 RTR with chronic allograft dysfunction and renal anemia were randomized to a group receiving darbepoetin alfa (Dar) and a control group (Co). At baseline and after 8 months of treatment (cumulative Dar dose 11.1 µg/kg b.w.) brachial and common carotid artery distensibility coefficients, aortic pulse wave velocity, brachial artery flow-mediated and nitroglycerin-mediated vasodilation were measured as well as the following biomarkers of vascular function: vWF, sVCAM, sICAM, E-selectin, t-PA and PAI-1. Results: 23 patients in the Dar group and 17 patients in the Co group were available for per-protocol analysis. Hemoglobin increased significantly from 10.9 to 12.6 g/dl after 8 months in the Dar group, whereas it remained stable at 11.3 g/dl in the Co group. Effects on large artery stiffness, endothelial function and biomarkers of vascular function did not differ significantly between the two groups. Conclusion: Therapy with Dar during 8 months did not significantly impact parameters of large artery stiffness and endothelial function in RTR. These data suggest that therapy with erythropoietin does not deteriorate arterial stiffness and endothelial function in RTR.

Mycophenolate mofetil maintenance therapy in renal transplant patients: long‐term results of the TranCept STAY study

This prospective observational study documented long-term renal function in transplant recipients receiving mycophenolate mofetil (MMF). Kidney allograft recipients>6 months post-transplantation, with a glomerular filtration rate (GFR)>20 mL/min, receiving MMF from time of transplantation were enrolled and followed for four yr. Subgroups were identified based on time between transplantation and enrollment: Y<1 (6 months-1 yr); Y1-2 (>1-2 yr); Y2-5 (>2-5 yr) and Y>5 (>5 yr). A total of 2040 patients were analyzed; 780, 410, 541 and 309 in subgroups Y<1, Y1-2, Y2-5 and Y>5. For all patients combined GFR decreased during the observational period by approximately 1 mL/min/yr (median GFR (mL/min) was 50.8, 50.5, 48.7, and 47.6 at one, two, three, and four yr). Survival estimates for decline in renal function (>20% GFR decline at one time point) were 78%, 66%, 57%, and 51% at one, two, three and four yr, with no significant differences between subgroups (p>0.05). In adult patients, higher doses of MMF (≥1 g/d) were associated with better GFR outcomes (median GFR (mL/min) 48.1 vs. 39.9 at four yr post-enrollment; p=0.0037). When comparing the effects of MMF combined with calcineurin inhibitors (CNIs), GFR was increased with lower doses of tacrolimus or cyclosporin. There were no major tolerability or acute rejection problems and graft survival was similar in all subgroups (graft survival estimates for all patients combined were 99%, 95%, 92%, and 90% at one, two, three, and four yr). Long-term MMF immunosuppression preserves renal function and higher MMF doses combined with lower CNI doses may provide better patient outcomes.

Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

BackgroundRecently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetate)that indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients.Methods120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE) measurements to achieve the normal values of BE (−5 to +5 mEq/L). In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15). Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days.ResultsIn group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed.ConclusionIntra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

Peripherally Circulating CD4+ FOXP3+ CXCR3+ T Regulatory Cells Correlate with Renal Allograft Function

Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4⁺ FOXP3⁺ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation analysis of chemokine receptor expression and glomerular filtration rate as calculated by MDRD (eGFR) was performed. Expression of the peripheral homing receptors CXCR3 (r = 0.44, P < 0.05) and CCR5 (r = 0.45, P < 0.05) on FOXP3⁺ Tregs correlated with renal allograft function (eGFR) in patients receiving tacrolimus (n = 28), but not cyclosporine A (CsA) (n = 26). CsA but not tacrolimus reduced surface expression of CXCR3 on FOXP3⁺ Tregs in renal transplant recipients as correlated to trough levels (r = -0.42, P < 0.05). In contrast to CD4⁺ CXCR3⁺ CD25(lo) T cells, flow-sorted CD4⁺ CXCR3⁺ CD25(hi) Tregs isolated from healthy individuals did not produce IFNγ or IL-17 ex vivo and expressed high levels of GARP mRNA both at baseline as well as after TCR activation indicating functional regulatory activity. Expression of the peripheral trafficking receptors CXCR3 and CCR5 on FOXP3⁺ Tregs is associated with renal allograft function. These results suggest that Treg trafficking may also depend on the interaction of CXCR3 or CCR5 and their respective ligands.

Dietary protein, blood pressure and renal function in renal transplant recipients

Hypertension is highly prevalent among renal transplant recipients (RTR) and a risk factor for graft failure and cardiovascular events. Protein intake has been claimed to affect blood pressure (BP) in the general population and may affect renal function. We examined the association of dietary protein with BP and renal function in RTR. We included 625 RTR (age 53 (SD 13) years; 57% male). Protein intake was assessed with a FFQ, differentiating between animal and plant protein. BP was measured according to a strict protocol. Creatinine clearance and albuminuria were measured as renal parameters. Protein intake was 83 (SD 12) g/d, of which 63% derived from animal sources. BP was 136 (SD 17) mmHg systolic (SBP) and 83 (SD 11) mmHg diastolic (DBP). Creatinine clearance was 66 (SD 26) ml/min; albuminuria 41 (10-178) mg/24 h. An inverse, though statistically insignificant, association was found between the total protein intake and both SBP (β = - 2·22 mmHg per SD, P= 0·07) and DBP (β = - 0·48 mmHg per SD, P= 0·5). Protein intake was not associated with creatinine clearance. Although albuminuria was slightly higher in the highest tertile of animal protein intake compared with the lowest tertile (66 v. 33 mg/d, respectively, P= 0·03), linear regression analyses did not reveal significant associations between dietary protein and albuminuria. Protein intake exceeded the current recommendations. Nevertheless, within the range of protein intake in our RTR population, we found no evidence for an association of dietary protein with BP and renal function. Intervention studies focusing on different protein types are warranted to clarify their effect on BP and renal function in RTR.

Effects of Hyperuricemia on Renal Function of Renal Transplant Recipients: A Systematic Review and Meta-Analysis of Cohort Studies

BackgroundHyperuricemia is an independent risk factor of nephropathy, but its role in renal transplant recipients (RTRs) is controversial.MethodsBased on the methods of Cochrane systematic reviews, we searched MEDLINE (1948–2011.6), EMBASE (1956–2011.6), CBM (Chinese Biomedicine Database) (1978–2011.6) to identify cohort studies assessing the association between uric acid level and kidney allograft. Two authors independently screened the studies, assessed the risk of bias of included studies and extracted data. Unadjusted odds ratio(OR), mean difference (MD), adjusted hazard ratio (aHR) and their corresponding 95%CI were pooled to assess the effects of hyperuricemia on kidney allograft.ResultsTwelve cohort studies were included and the quality was moderate to high based on the NEWCASTLE-OTTAWA quality assessment scale. RTRs with hyperuricemia had lower eGFR (P<0.0001, 95%CI−16.34∼6.14) and higher SCr (P<0.00001, 95%CI 0.17∼0.31) than those with normal uric acid level. Meta-analysis showed that hyperuricemia was a risk factor of chronic allograft nephropathy (Unadjusted OR = 2.85, 95%CI 1.84∼4.38, adjusted HR = 1.65, 95%CI 1.02∼2.65) and graft loss (Unadjusted OR = 2.29, 95%CI 1.55∼3.39; adjusted HR = 2.01, 95%CI 1.39∼2.94).ConclusionsCurrent evidence suggests that hyperuricemia may be an independent risk factor of allograft dysfunction. Hyperuricemia may modestly increase the risk of poor outcomes of RTRs. Future research is needed to verify whether lowering uric acid level could improve the kidney function and prognosis of RTRs with hyperuricemia.

Plasma bilirubin and late graft failure in renal transplant recipients

Exogenous bilirubin has been shown to protect against oxidative stress in ischemia-reperfusion injury. Oxidative stress has been implicated in the pathophysiology of chronic transplant dysfunction leading to late graft failure after renal transplantation. We prospectively investigated whether high endogenous bilirubin is protective against development of late graft failure in renal transplant recipients (RTR). Baseline data were collected between August 2001 and July 2003 in nonicteric outpatient RTR with a functioning graft for >1 year. At baseline, bilirubin and liver enzymes were measured using routine assays on a Merck Mega analyzer. Graft failure was prospectively recorded until May 19 2009. During follow-up for 7.1 [6.2-7.2] years, 55 RTR developed graft failure. We found that circulating levels of bilirubin are inversely associated with late graft failure in RTR (HR = 0.29 [95% CI: 0.16-0.52], P < 0.001). This association was independent of potential confounders, including creatinine clearance, urinary protein excretion, calcineurin inhibitors, and gender (HR = 0.31 [95% CI: 0.15-0.62] P = 0.001). Our findings are consistent with a protective effect of increased endogenous bilirubin against development of late graft failure in RTR. If our findings are confirmed by other studies, intervention with endogenous or exogenous bilirubin may be of interest for long-term preservation of renal function in RTR.

Does intraoperative low molecular weight hydroxyethyl infusion impair immediate graft function in renal transplant recipients?

Azevedo Marques, A.; Oliveira, E.; Almeida, M. T.; Caetano, A. F.; Bastos, C. A. Author Information

Renal biomarkers for assessment of kidney function in renal transplant recipients: how do they compare?

Accurate assessment of renal function is of key importance, given its prognostic value. However, gold standard measures are cumbersome, and serum creatinine itself is an insensitive predictor, especially in renal transplant recipients. Though GFR-estimating formulae have been relied upon, they do have their own limitations. Nevertheless, renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, among others, are now emerging as potentially useful indicators of GFR. We aimed to evaluate the diagnostic performance of NGAL versus cystatin C and eGFR using CKD-EPI, MDRD and cystatin C in renal transplant recipients and non-transplant CKD patients. We found a significant correlation between NGAL, serum creatinine, cystatin C and eGFR. The latter parameters were also strong predictors of serum NGAL levels. However, performance of NGAL, based on receiver operating characteristic curves, was inferior to that of the reference tests. It appears that in renal transplant recipients NGAL correlates well with cystatin C and eGFR, most strongly with cystatin-based formula. Though this suggests potential use of NGAL as a screening test, its weaker diagnostic performance raises some concern about its clinical usefulness. Larger studies are needed to explore this further.

Renal Biomarkers for Assessment of Kidney Function in Renal Transplant Recipients: How do They Compare?

Renal Biomarkers for Assessment of Kidney Function in Renal Transplant Recipients: How do They Compare?

Renalase, A Novel Regulator of Blood Pressure, Is Predicted by Kidney Function in Renal Transplant Recipients

Background Renalase is an enzyme that catabolizes catecholamines such as adrenaline and noradrenaline in the circulation. The human kidney releases this protein into the bloodstream to regulate blood pressure. In kidney transplant recipients, the prevalence of hypertension is 60%–80%. Objective The aim of our study was to assess possible correlations between renalase, blood pressure, and kidney function among 89 prevalent kidney allograft recipients. To obtain normal ranges, we also studied renalase levels in 27 healthy volunteers. Methods Complete blood counts, urea, serum lipids, fasting glucose, and creatinine were measured by standard laboratory methods in the hospital central laboratory. Renalase was assessed with the use of a commercially available kit. Results In kidney transplant recipients renalase was significantly higher than in healthy volunteers ( P < .001). In kidney transplant recipients, renalase correlated with age ( r = 0.29; P < .05), time after transplantation ( r = 0.34; P < .01), systolic blood pressure ( r = 0.28; P < .05), diastolic blood pressure ( r = 0.27; P < .05), serum creatinine ( r = 0.49; P < .001), estimated glomerular filtration rate (Chronic Kidney Disease Endemiology collaboration: r = −0.44; P < .0001; Modification of Diet in Renal Disease: r = −0.43; P < .001; Cockcroft-Gault r = −0.39; P < .01), serum phosphate ( r = 0.34; P < .05). Upon multiple regression analysis renalase was predicted by 70% using age (beta value 0.21, P = 0.043), time after transplantation (beta value, 0.22; P = .037), serum creatinine (beta value, 0.50; P = .016), and diastolic blood pressure (beta value, 0.33; P = .027). Conclusions Renalase is highly elevated in kidney transplant recipients, predominantly dependent on kidney function, which deteriorates with time after kidney transplantation and age. Further studies are needed to establish its putative role in the pathogenesis of hypertension after transplantation and possible novel targeted therapies.

Long‐term renal function and survival of renal transplant recipients admitted to the intensive care unit

We determined the long-term mortality and renal allograft function of renal transplant recipients admitted to the intensive care unit (ICU). A single institution retrospective observational cohort study of all renal transplant patients admitted to the ICU was performed. Serum creatinine was recorded up to one yr after hospital discharge and survival data were collected for three yr. Chest sepsis was the commonest reason for ICU admission. ICU and hospital mortality were 32% and 19% respectively. Predictors of hospital mortality included the presence of sepsis and duration of mechanical ventilation (MV). Of the patients who were discharged from ICU, three-yr mortality was 50%. Renal function at one yr was worse than that at hospital discharge and at baseline, though not statistically significant. Death-censored allograft loss was 11% over the three-yr follow up period. Sepsis and requirement for MV are independent predictors of mortality in renal transplant recipients admitted to ICU. Renal transplant recipients with chest sepsis may warrant earlier ICU admission. Any loss of renal allograft function during an episode of critical illness appears to have a lasting effect, and longterm patient and allograft survival is poor.

Impaired renal function is associated with worse self-reported outcomes after kidney transplantation

We sought to determine the association between health-related quality of life (HRQOL) and graft function in renal transplant recipients. We enrolled 577 kidney transplant recipients aged 18-74 years (response rate 87%). Recipients with multiple or multi-organ transplantation, creatine kinase >200 U/L, acute renal failure or cellular rejection (n = 64), and without creatinine assessments in 3 months pre-enrollment (n = 127) were excluded. The questionnaire included Euro QOL 5 Dimensions (EQ-5D), Health Utility Index III (HUI-III), Kidney Disease Quality of Life-36 (KDQOL36) which include a generic section (RAND SF-12). Data on medical conditions, therapy regimens, and biochemistry results were extracted from clinical charts. We used general linear models adjusted for demographic, socioeconomic, and clinical characteristics to assess the association between HRQOL and severity of chronic kidney disease (CKD). Patients with more advanced CKD were more likely to be African-American, covered by public insurance, more likely to have shorter time after transplantation, higher phosphorus and lower hemoglobin, serum albumin, and calcium levels. All HRQOL scales were inversely associated with CKD severity. All associations were robust to adjustment for possible confounders. Several health-related quality of life dimensions may be affected by poor renal function after transplantation.

Is perioperative low molecular weight hydroxyethyl starch infusion a risk factor for delayed graft function in renal transplant recipients?

Crystalloid or colloid fluids may be utilized during kidney transplantation. Histopathological and clinical data indicate that hydroxyethyl starch (HES) may have nephrotoxic potential. This retrospective single-centre cohort study screened 192 and included 113 patients who underwent renal transplantation between 2003 and 2007 at University of Leipzig Medical Faculty, Germany. The primary outcome parameter was delayed graft function (DGF). Patients were divided into two groups. Patients in group CRYS (N = 73) received crystalloid solution (acetated Ringer's or normal saline) only. Patients in the group HES (N = 40) received a minimum of 500 mL 6% HES 130/0.4 and additional crystalloid solution by discretion of the transplant team. Patients in both groups did not differ with respect to demographic data and American Society of Anesthesiologists Physical Status Classification System scores, except for the donor age, which was significantly lower in the group HES. The rate of DGF was not found to be different in group CRYS (31.5%) when compared to group HES (32.5%) (P = 1.00, n.s.). In this single-centre retrospective cohort study, infusion of low molecular weight 6% HES 130/0.4 during and after renal transplantation was found to have no significant negative effect upon the rate of DGF.

Pregnancy after renal transplantation: an evaluation of the graft function

ObjectivesTo evaluate pregnancy outcomes and graft function in renal transplant recipients. Study designThirty-four pregnancies in 31 patients were evaluated. Graft dysfunction was defined as an increase of 0.3mg/dL (215μmol/L) or more in serum creatinine (SCr) during pregnancy. Twenty-eight patients were also evaluated at one, six and twelve months after delivery to analyze the evolution of the graft function. ResultsFifteen patients experienced graft dysfunction during pregnancy, 10 related to preeclampsia, two related to rejection, one related to allograft obstruction and one related to urinary tract infection. One patient did not have an identified cause. In one patient, graft rejection ended in graft loss. The mean SCr level in the first trimester was 0.9mg/dL (range: 0.5–2.1) among women who did not have graft dysfunction and 1.1mg/dL (range: 0.5–1.9) among patients who had graft dysfunction (P=0.66). The mean SCr level one year after delivery was 1.18mg/dL in the first group and 1.21mg/dL in the second group (P=0.74). There was no difference in SCr level from the first trimester of pregnancy to one year after delivery in both groups evaluated (P=0.35 and P=0.13). ConclusionsAlthough graft dysfunction may occur during pregnancy, it seems to be temporary in the majority of the cases. It is important to emphasize that rejection is still a cause of graft loss during pregnancy.

Serum Cystatin C Levels in Renal Transplant Recipients

Cystatin C is an emerging parameter for the assessment of renal allograft function. The objective of the study was to compare the efficacy of serum cystatin C (SCys) with the established parameter serum creatinine (SCr) in the assessment of renal function in renal transplant recipients (RTR). The glomerular filtration rate (GFR) of 30 renal transplant patients and 29 control subjects was determined using (99m)Tc Diethylene-triamine-penta-acetate (DTPA) method. SCr was measured using an automated Jaffe's assay and SCys was measured using latex particle enhanced turbidimetric immuno assay (PETIA). The modification of diet in renal disease (MDRD) formula was used to calculate GFR from SCr, while the Le Bricon formula was used to derive GFR based on SCys. Statistical analysis was performed using MedCalc software. SCr and SCys levels were significantly higher, while DTPA clearance was significantly lower in RTR (P<0.0001) when compared with controls. The correlation coefficient (r value) between calculated GFR based on MDRD method and DTPA clearance was 0.343 (P=0.06) while the calculated GFR based on Le Bricon formula was 0.694 (P<0.001). The results have shown that SCys is a better parameter than SCr in assessing renal function in RTR. The inclusion of SCys as an additional parameter would certainly help in detection of even a marginal decline in renal function and also in adjusting the dosage of immunosuppressive drugs.

Regression of Left Ventricular Hypertrophy in Kidney Transplant Recipients: The Potential Role for Inhibition of Mammalian Target of Rapamycin

Left ventricular hypertrophy (LVH) contributes to elevated cardiac mortality with graft function in renal transplant recipients. Antihypertensive therapy, and especially angiotensin-converting enzyme (ACE) inhibitors, proved to be effective in regressing the LVH of renal transplant recipients, at least in part by interacting with immunosuppressive agents, thus raising the possibility that immunosuppressive therapy might affect changes in the left ventricular mass (LVM) of recipients. This review mainly focuses on the potential role of mammalian target of rapamycin (mTOR) inhibition to regress cardiac hypertrophy in both experimental models and in the clinical setting. We comment on the results of experimental studies conducted on animal models, which showed regression of cardiac hypertrophy by sirolimus (SRL). We also discuss clinical studies that show that conversion from calcineurin inhibitors to SRL is effective to achieve regression of LVH in both kidney and cardiac transplant recipients, mainly by reducing the true left ventricular wall hypertrophy.

Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy

Objective The present study was designed to investigate the effect of low-dose calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of rapamycin (mTOR) inhibitor on renal function in transplant recipients without allograft nephropathy. Patients and methods Twelve patients including seven men (58.3%) of overall mean age of 34.8 ± 14.1 years underwent renal transplantation and were switched to a new second-line treatment of low-dose CNI combined with an mTOR inhibitor, either sirolimus or everolimus. Results The underlying cause of renal failure was not clear in half of the cases; for the others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, or hypovolemia. After 6 months of the new therapy, there was a significant increase in calculated creatinine clearance levels compared to baseline (75.5 ± 21.9 vs 89.6 ± 19.1 mL/min; P < .001), but no significant change in serum creatinine (1.3 ± 0.4 vs 1.2 ± 0.3 mg/dL) or urinary protein excretion (187.5 ± 142.0 vs 394.0 ± 326.4 mg/g). For almost all patients, proteinuria remained stable, but in two patients, it developed but responded to enalapril treatment. Dose decrement was required for four patients with hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that responded to treatment. One patient developed a urinary tract infection that responded to antibiotic treatment. None of the patients developed an acute rejection episode. Conclusion Low-dose CNI combined with an mTOR inhibitor, as a replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium, seemed to prevent renal dysfunction for at least 6 months among renal transplant patients without allograft nephropathy.