Time course of asymmetric dimethylarginine and symmetric dimethylarginine levels after successful renal transplantation.

BACKGROUND: Although renal transplantation (Tx) improves the outcome of patients with renal disease, cardiovascular (CV) risk remains high. Recently, it was demonstrated that asymmetric dimethylarginine (ADMA) levels predict CV events and graft survival in renal transplant recipients (RTRs). Little is known about the impact of renal Tx on the plasma levels of ADMA and symmetric dimethylarginine (SDMA). The present study aimed to define the time course of ADMA and SDMA after Tx. METHODS: We prospectively followed 167 incident RTRs with visits at the time of Tx and 3 and 12 months thereafter. At all visits, demographics and relevant biochemistry were recorded and blood was sampled for analysis of ADMA and SDMA (high-performance liquid chromatography). Eighty-four patients had an additional sampling in the immediate postoperative period. In a case-controlled substudy (n = 31), we compared ADMA and SDMA levels between RTRs and chronic kidney disease (CKD) patients, matched for glomerular filtration rate, gender, age, CV history and diabetes. RESULTS: Overall, plasma ADMA and SDMA levels decreased after Tx. The decline of SDMA was more pronounced and paralleled the recovery of renal function. Interestingly, the decline of ADMA was preceded by an increase in the immediate postoperative period. In the case-controlled substudy, SDMA levels were similar, whereas ADMA levels were significantly higher in RTRs compared with the CKD counterparts (P = 0.003). CONCLUSION: ADMA levels follow a biphasic pattern after successful renal Tx with a transient rise in the immediate postoperative period followed by a decline. Levels remain elevated compared with CKD patients, matched for age, gender, diabetes, CV history and renal function.

Postimplantation X-ray parameters predict functional catheter problems in peritoneal dialysis.

Functional catheter problems are a major challenge for peritoneal dialysis (PD) programs. Here we performed a retrospective single-center study of 110 consecutive patients receiving a first PD catheter (swan neck double-cuff Missouri curled catheters, open surgical technique). Using postimplantation X-ray, the following categories were defined: swan neck angle (posterioanterio view (PA): under 45°, 45-90°, over 90°), inclination (angle between intramural part of catheter and horizontal line; lateral view: greater than/equal to 30°, under 30°), and the position of silicone bead relative to spine (PA view: L1-2, L3-4, lower) and catheter tip (PA view: hypogastric, umbilical, subcostal). Covariates included demographics, body size, previous abdominal surgery, and abdominal wall hernias. During a mean follow-up of 36 months, the time to first functional catheter problem was significantly associated with both the swan neck angle and inclination. The need for surgical intervention was significantly associated with inclination only. Technique failure was not associated with any parameter. In multivariate analysis, inclination was the sole variable significantly associated with functional catheter problems (hazard ratio 3.65 [1.98-6.72]) and the need for surgical intervention (hazard ratio 2.86 [1.19-6.88]). Thus, our study defines a set of X-ray variables that predict functional PD catheter problems and can be used for troubleshooting in individual cases as well as for education and internal audit purposes.

Serum concentrations of p-cresyl sulfate and indoxyl sulfate, but not inflammatory markers, increase in incident peritoneal dialysis patients in parallel with loss of residual renal function.

BACKGROUND: High serum concentrations of the protein-bound uremic retention solutes p-cresyl sulfate (PCS) and indoxyl sulfate (IndS) and inflammation are associated with increased cardiovascular morbidity and mortality in chronic kidney disease. Renal clearance contributes to up to 80% of the total clearance of PCS and IndS in peritoneal dialysis (PD) patients. Cross-sectional studies evaluating the impact of residual renal function (RRF) on serum concentrations of PCS, IndS, and circulating inflammatory markers have yielded conflicting results. ♢ METHODS: To clarify this issue, we carried out a prospective observational cohort study in incident PD patients (n = 35; 19 men; mean age: 55 ± 17 years). Midday blood samples were collected and analyzed for total serum PCS, IndS, C-reactive protein, and high-sensitivity interleukin 6. Peritoneal and renal clearances were calculated from urine and dialysate collections, and RRF was calculated as the mean of renal urea nitrogen and creatinine clearances. Patients were assessed 1, 6, 12, and 24 months after PD start. Differences between time points were analyzed using linear mixed models (LMMs). ♢ RESULTS: Residual renal function declined significantly over time (LMM p < 0.0001). Peritoneal clearances of both toxins tended to increase, but did not compensate for the declining renal clearances. Serum concentrations of PCS and IndS increased significantly over time (LMM p = 0.01; p = 0.0009). In contrast, total mass removal of both toxins remained stable. Circulating inflammatory markers did not change over time. ♢ CONCLUSIONS: Our data indicate that serum concentrations of PCS and IndS, but not inflammatory markers, increase in incident PD patients in parallel with loss of RRF.

Intrarenal resistive index after renal transplantation.

BACKGROUND: The intrarenal resistive index is routinely measured in many renal-transplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear. METHODS: In a single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation. RESULTS: Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 [95% confidence interval {CI}, 2.14 to 12.64; P<0.001]; 3.46 [95% CI, 1.39 to 8.56; P=0.007]; and 4.12 [95% CI, 1.26 to 13.45; P=0.02], respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 [95% CI, 0.39 to 9.82; P=0.42]; 0.44 [95% CI, 0.05 to 3.72; P=0.45]; and 1.34 [95% CI, 0.20 to 8.82; P=0.76], respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87 ± 0.12 vs. 0.78 ± 0.14 [P=0.05], and 0.86 ± 0.09 vs. 0.78 ± 0.14 [P=0.007], respectively). CONCLUSIONS: The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft. (ClinicalTrials.gov number, NCT01879124 .).

Impact of CYP3A5 genotype on tacrolimus versus midazolam clearance in renal transplant recipients: new insights in CYP3A5-mediated drug metabolism.

BACKGROUND & AIM: In vitro studies have identified both midazolam and tacrolimus as dual CYP3A4 and CYP3A5 substrates. In vivo; however, the CYP3A5 genotype has a marked impact on tacrolimus pharmacokinetics, whereas it seems not to affect midazolam pharmacokinetics. The aim of the current study was to explore this paradigm in a relevant clinical setting. PATIENTS & METHODS: A case-control study in 80 tacrolimus-treated renal transplant recipients comparing systemic and apparent oral midazolam clearance and tacrolimus pharmacokinetics in CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (CYP3A5*3/*3) was performed. RESULTS: CYP3A5 expressers display an approximately 2.4-fold higher tacrolimus clearance as compared with CYP3A5 nonexpressers, whereas there are no differences in systemic and apparent oral midazolam clearance. CONCLUSION: These data confirm that in vivo CYP3A5 plays an important role in tacrolimus metabolism, while its contribution to midazolam metabolism in a relevant study population is limited. Furthermore, these data suggest that midazolam is to be considered as a phenotypic probe for in vivo CYP3A4 activity rather than combined CYP3A4 and CYP3A5 activity.

The predictive value of kidney allograft baseline biopsies for long-term graft survival.

The effect of baseline histology and individual histologic lesions at the time of transplantation on long-term graft survival has been evaluated using different scoring systems, but the predictive capacity of these systems has not been adequately validated. All kidney recipients transplanted in a single institution between 1991 and 2009 who underwent a baseline kidney allograft biopsy at transplantation were included in this prospective study (N=548). All baseline biopsies were rescored according to the updated Banff classification, and the relationship between the individual histologic lesions and donor demographics was assessed using hierarchical clustering and principal component analysis. Survival analysis was performed using Cox proportional hazards analysis and log-rank testing. Mean follow-up time was 6.7 years after transplantation. Interstitial fibrosis, tubular atrophy, and glomerulosclerosis associated significantly with death-censored graft survival, whereas arteriolar hyalinosis and vascular intimal thickening did not. Notably, donor age correlated significantly with interstitial fibrosis, tubular atrophy, and glomerulosclerosis and associated independently with graft survival. On the basis of these findings, a novel scoring system for prediction of 5-year graft survival was constructed by logistic regression analysis. Although the predictive performance of previously published histologic scoring systems was insufficient to guide kidney allocation in our cohort (receiver operating characteristic area under the curve ≤0.62 for each system), the new system based on histologic data and donor age was satisfactory for prediction of allograft loss (receiver operating characteristic area under the curve = 0.81) and may be valuable in the assessment of kidney quality before transplantation.

Renal clearance and intestinal generation of p-cresyl sulfate and indoxyl sulfate in CKD.

BACKGROUND AND OBJECTIVES: p-Cresyl sulfate and indoxyl sulfate contribute to cardiovascular disease and progression of renal disease. Renal clearance of both solutes mainly depends on tubular secretion, and serum concentrations are widely dispersed for any given stage of CKD. From this information, it is inferred that estimated GFR is not a suitable proxy of the clearance of these solutes. Formal clearance studies have, however, not been performed to date. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study analyzed renal clearances of p-cresyl sulfate and indoxyl sulfate in the Leuven CKD cohort (NCT00441623; inclusion between November of 2005 and September of 2006) and explored their relationship with estimated GFR. Multivariate linear regression models were built to evaluate contributions of estimated GFR, demographics, and generation rates to p-cresyl sulfate and indoxyl sulfate serum concentrations. RESULTS: Renal clearances were analyzed in 203 patients with CKD stages 1-5. Indoxyl sulfate clearances (median=17.7, interquartile range=9.4-33.2 ml/min) exceeded p-cresyl sulfate clearances (median=6.8, interquartile range=3.4-12.0 ml/min) by about threefold. A linear relationship was observed between estimated GFR and clearances of p-cresyl sulfate (R(2)=0.50, P<0.001) and indoxyl sulfate (R(2)=0.55, P<0.001). In multivariate regression, p-cresyl sulfate concentrations were associated (R(2)=0.75) with estimated GFR and generation rate (both P<0.001). Indoxyl sulfate concentrations were associated (R(2)=0.74) with estimated GFR, generation rate (both P<0.001), age (P<0.05), and sex (P<0.05). CONCLUSIONS: Estimated GFR provides an acceptable estimate of renal clearance of p-cresyl sulfate and indoxyl sulfate. Remarkably, clearances of indoxyl sulfate exceed clearances of p-cresyl sulfate by approximately threefold, suggesting substantial differences between tubular transporter affinities and/or involvement of separate transporter systems for p-cresyl sulfate and indoxyl sulfate.

Aortic calcifications and arterial stiffness as predictors of cardiovascular events in incident renal transplant recipients.

Renal transplant recipients have an increased risk of cardiovascular (CV) disease. Arterial stiffness (AS) and aortic calcifications (ACs) are well-known CV risk factors in patients with chronic kidney disease. We aimed to determine the prognostic value of AS and AC in incident renal transplant recipients (RTRs). We conducted a prospective study in 253 single RTR. AC were scored by means of lumbar X-ray. Carotid-femoral pulse wave velocity (PWV) was assessed in a subgroup of 115 patients. AC were present in 61% of patients. After a mean follow-up of 36 months, 32 CV events occurred in the overall group and 13 events in the PWV subgroup. When we accounted for age, gender, and CV history, AC score (HR, hazard ratio 1.09 per 1 unit increase; 95% CI 1.02-1.17) and PWV (HR 1.45 per 1 m/s; 95% CI 1.16-1.8) remained an independent predictor of CV events in Cox-regression analyses. Using receiver operating characteristics, the area under the curve for predicting CV events amounted to 0.80 and 0.72 for sum AC and PWV, respectively. Both AS and AC are strong predictors of future CV events in an incident RTR population. These vascular assessments are readily available and easy to perform, making them ideal tools for further risk stratification. (ClinicalTrials.gov number: NCT00547040).

Reasons for dose reduction of mycophenolate mofetil during the first year after renal transplantation and its impact on graft outcome.

UNLABELLED: Mycophenolate mofetil (MMF) decreases the risk of acute rejection and is associated with improved graft survival in renal transplant recipients. However, MMF-related side effects often necessitate dose reduction, which may expose patients to a higher risk of acute rejection and graft loss. This study's aim was to examine the reasons for MMF dose reduction during the first post-transplant year and its impact on acute rejection, overall and death-censored graft loss. METHODS: Single-center retrospective analysis of 749 renal transplant recipients treated with MMF in their initial maintenance immunosuppressive protocol. RESULTS: In 365 patients (48.7%) a total of 530 MMF dose reductions were done. Reasons for reduction were hematologic toxicity (46.5%), infection (16.1%), gastrointestinal side effects (12.3%), malignancy (2.1%), study protocol (14.6%), and unknown (13.5%). MMF dose reduction as such was not an independent predictor of acute rejection or graft survival, although reductions in ≥ 50% of initial dose were significantly associated with acute rejection. CONCLUSIONS: In this retrospective cohort, by far the most important reason for MMF dose reduction during the first post-transplantation year was hematologic. MMF dose reductions in ≥ 50% increased the risk of acute rejection but did not compromise graft survival.

Improved adherence to tacrolimus once-daily formulation in renal recipients: a randomized controlled trial using electronic monitoring.

BACKGROUND: With effective agents available to prevent posttransplantation acute organ rejection, medication adherence becomes a key factor for successful treatment outcomes after renal transplantation. A once-daily, modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence. METHODS: Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a randomized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake. After enrolment, all patients continued the twice-daily regimen for 3 months and then were randomized 2:1 between the two formulations and followed for 6 months. Adherence was decomposed into patients' persistence and implementation of each regimen. RESULTS: Two hundred nineteen patients (45% male; 3±2 years after transplantation) were analyzed (145 once daily and 74 twice daily). At 6 months after randomization, 81.5% of the once-daily group and 71.9% of the twice-daily group remained persistent with the treatment (P=0.0824). Among patients who remained engaged with the regimen, 88.2% of the once-daily group and 78.8% of the twice-daily group (P=0.0009) took the prescribed number of daily doses. When the patients took the twice-daily regimen, the average percentage of missed doses was 11.7% in the morning and 14.2% in the evening (P=0.0035). CONCLUSIONS: Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen. There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification. Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management.

Renal cell carcinoma in the allograft: what is the role of polyomavirus?

BK virus (BKV) is known to cause subclinical infection in childhood. The virus remains latent in the human body, mainly in the urinary tract epithelium. After initiation of an immunosuppressive treatment, reactivation can occur in renal transplant recipients. BKV can cause hemorrhagic cystitis, ureteral stenosis and BKV nephropathy in immunocompromised patients. Furthermore, a number of case reports suggest an association between BKV infection and the development of urinary tract cancer. So far, an oncogenic potential of BKV has been observed in vitro and in animal models; however, its oncogenic capacity in humans remains unclear. We report the case of a 59-year-old patient who developed a poorly differentiated renal cell carcinoma in her renal allograft, with pulmonary and abdominal metastasis. Surgical removal of the allograft and cessation of the immunosuppressive therapy resulted in complete resolution of the metastatic disease.

A multicenter, randomized, double-blind study comparing different FK778 doses (manitimus) with tacrolimus and steroids vs. MMF with tacrolimus and steroids in renal transplantation.

BACKGROUND: This multicenter phase II study in renal transplantation compared 3 concentration-controlled ranges of FK778 (manitimus) with mycophenolate mofetil (MMF) both given in combination with tacrolimus and corticosteroids. METHODS: 364 patients were randomized to 12-month treatment: high-level FK778 group (H, N=87) received 4 x 600 mg/day (4 days) followed by 120 mg/day; mid-level FK778 group (M, N=92) received 3 x 600 mg/day (3 days) followed by 110 mg/day, low-level FK778 group (L, N=92) received 2 x 600 mg/day (2 days) followed by 100 mg/day, and control group received MMF 1 g/day (MMF, N=93). After week 6, FK778 doses were adjusted to trough ranges of 75-125 µg/mL (H), 50-100 µg/mL (M) and 25-75 µg/mL (L). Tacrolimus and steroids were administered at the same dose in each of the 4 groups. RESULTS: Biopsy proven acute rejection (BPAR) at 24 weeks, the primary study endpoint, was comparable in the L (22.8%) and MMF (17.2%) groups but higher in the H (34.5%) and M (29.3%) groups. BPAR at 12 months was comparable in the L (23.9%) and MMF (19.4%) groups but higher in the H (34.5%) and M (31.5%) groups. Graft and patient survival were lowest in the H group and renal function was poorest in the H and M groups. Premature study withdrawal was highest in the H group. CONCLUSIONS: Efficacy was similar between the low-level FK778 and MMF groups. Increased FK778 exposure was poorly tolerated and did not improve efficacy.

Daytime rhythm and treatment-related fluctuations of serum phosphorus concentration in dialysis patients.

BACKGROUND: Serum phosphorus concentrations reflect a dynamic balance between generation, exchanges, and removal. Time-averaged phosphorus concentrations (TAC(phos)) reflect the overall exposure better than single time-point concentrations, especially in dialysis patients treated with an intermittent modality. The present study aimed to determine the daytime rhythm of phosphorus in dialysis patients and to compare the TAC(phos) in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients. METHODS: Serum concentrations of urea nitrogen, creatinine and phosphorus were determined at regular intervals in 10 healthy volunteers (HV), 8 CAPD patients and 10 HD patients. In HV and CAPD patients, blood was sampled at 08:30 (fasting), 09:30, 10:30, 12:30, 16:30, and 08:30 h the next day. In HD patients, blood was sampled before and after the midweek dialysis session and rebound was assessed at regular time-points post-dialysis. TAC(phos) were determined according to the trapezoidal rule. RESULTS: Serum phosphorus levels show a daytime rhythm in CAPD patients, similar to what is observed in HV, with a nadir around 10:30 h and a rise in the afternoon. The magnitude of this daytime fluctuation is limited as compared to the treatment-related fluctuations in HD. These important fluctuations also translate in predialysis serum phosphorus concentrations overestimating the TAC. Remarkably, TAC(phos) were significantly lower in HD as compared to CAPD patients. CONCLUSIONS: Daytime phosphorus rhythm is preserved in CAPD patients. These fluctuations are limited as compared to fluctuations in HD patients. Treatment-related fluctuation should be accounted for when comparing phosphorus exposure between different groups.

Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Symphony study.

BACKGROUND: The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation. METHODS: Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm. RESULTS: The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm. CONCLUSIONS: This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded.

Residual renal function is an independent determinant of serum FGF-23 levels in dialysis patients.

BACKGROUND: Both poor residual renal function (RRF) and high fibroblast growth factor 23 (FGF-23) levels are associated with arterial stiffness, left ventricular hypertrophy and increased (cardiovascular) mortality. Whether FGF-23 and RRF are interrelated is unknown. METHODS: We performed a prospective observational cohort study in 35 peritoneal dialysis (PD) patients with evaluation at 1, 6, 12 and 24 months after start of PD. In addition, the role of RRF was assessed in a cross-sectional observational cohort study including 68 prevalent haemodialysis patients. RESULTS: RRF significantly declined over time in PD patients. This decline was parallelled by a significant increase of both serum phosphorus and FGF-23 levels. In the prevalent dialysis cohort, RRF was found to be inversely associated with serum FGF-23 levels, independent of dialysis vintage, dialytic creatinine clearance, estimates of dietary phosphate intake (i.e. normalized protein nitrogen appearance), active vitamin D therapy and serum phosphorus and calcium levels. RRF, serum phosphorus and calcium levels and active vitamin D therapy explain 69% of the variation in FGF-23. The 38 anuric patients had higher FGF-23 levels but similar serum phosphorus levels. CONCLUSIONS: We demonstrate an important association between RRF and FGF-23, independent of classical determinants. This favours the hypothesis that the ailing kidney directly contributes to the raised FGF-23 levels. Whether FGF-23 is associated with poor outcomes independent of RRF, or vice versa, remains to be clarified.

Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study.

BACKGROUND: The calcimimetic cinacalcet is approved for treating secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. Biochemical profiles and clinical outcomes in patients discontinuing cinacalcet at the time of transplantation are scarce. METHODS: We performed a prospective observational cohort study, including 303 incident renal transplant recipients, of whom 21 were on cinacalcet treatment at the time of transplantation. Parameters of mineral metabolism and incidence of parathyroidectomy and nephrocalcinosis in patients discontinuing cinacalcet at the time of transplantation patients ("cinacalcet +") were compared to cinacalcet-naïve patients ("cinacalcet -"). Mean follow-up was 35.6 ± 15.8 months. RESULTS: At the time of transplantation, parameters of mineral metabolism were similar in both groups. Conversely, at month 3, serum ionized calcium (p = 0.0007), calcitriol (p = 0.02), biointact parathyroid hormone (p = 0.06) levels and urinary fractional excretion of phosphorus (p = 0.06) were higher, while serum phosphorus levels (p = 0.06) were lower in "cinacalcet +." Analysis based on matching at the time of initiation showed that the course of post-transplant mineral metabolism in cinacalcet-treated patients (median treatment period 12.5 months) vs. cinacalcet-naïve patients was identical. "Cinacalcet +" patients are characterized by a high-incidence proportion of both post-transplant nephrocalcinosis (45% at month 3) and parathyroidectomy (28.6%). No difference in renal function was observed between "cinacalcet +" and "cinacalcet-" patients. CONCLUSION: Cinacalcet does not affect the course of secondary hyperparathyroidism in patients awaiting kidney transplantation. Biochemical profiles and a high parathyroidectomy rate suggest rebound hyperparathyroidism in renal transplant recipients discontinuing cinacalcet at the time of transplantation, which may be related to the short exposure time specific to this population. Risk/benefit studies are urgently required to define the role of continued calcimimetic treatment in renal transplant recipients and to determine the optimal treatment of secondary hyperparathyroidism in patients listed for transplantation.

Impact of vascular calcification on corrected QT interval at the time of renal transplantation.

BACKGROUND/AIMS: Sudden death is the major cause of cardiac mortality in dialysis patients, accounting for approximately 60% of cardiovascular deaths. A prolonged QT interval and arterial calcification have been associated with increased cardiovascular morbidity and mortality in different patient populations including patients with chronic kidney disease (CKD). In the present study, we aimed to elucidate the association of vascular calcification with corrected QT interval duration in patients with end-stage renal disease. METHODS: We performed a single-center cross-sectional study in patients referred for renal transplantation. Patients taking QT-prolonging agents or with conduction abnormalities were excluded. Aortic calcifications were scored by means of lumbar X-rays. RESULTS: In the final analysis, 193 patients (118 men, 52 years old) were included. A prolonged QT interval was observed in 26% of the patients. Multivariate analysis showed an independent and direct association between corrected QT duration and the extent of aortic calcifications (p = 0.0004) independent of age, gender, cardiovascular history, electrolytes and parameters of mineral metabolism. CONCLUSIONS: A prolonged QT interval is prevalent in patients with CKD stage 5D. Aortic calcification is associated with a prolonged QT duration, independent of traditional determinants.

Prevalence and determinants of anemia in the immediate postkidney transplant period.

At the time of renal transplantation, erythropoiesis-stimulating agents and iron supplementation are routinely discontinued in the prospect of recovery of renal function. This recovery, however, is often delayed and suboptimal. In addition, blood loss because of frequent diagnostic phlebotomies may be substantial. Renal transplant recipients may thus be considered at high risk of anemia in the immediate post-transplant period. We performed a single-center observational study, including 391 recipients of a single kidney. Hemoglobin levels and parameters of iron metabolism were monitored during the immediate post-transplant period, i.e., the first 3 months after transplantation. Hemoglobin levels decreased by 3.8 ± 1.5 g/dl to reach a nadir of 9.1 ± 1.2 g/dl at day 7. Transient severe anemia was observed in 91.3% of the patients. Donor age, gender, renal diagnosis of polycystic disease, pretransplant hemoglobin and ferritin level, estimated glomerular filtration rate at month 3, and duration of initial hospitalization were observed to be independently associated with the hemoglobin level at month 3. Transient severe anemia is an almost universal observation in incident renal transplant recipients. Poor graft function, high donor age, and low iron stores are independently associated with low hemoglobin levels at month 3.

FTY720 combined with tacrolimus in de novo renal transplantation: 1-year, multicenter, open-label randomized study.

BACKGROUND: FTY720 (fingolimod), a novel immunomodulator, has demonstrated potential for prevention of acute rejection in combination with cyclosporine. METHODS: This study evaluated FTY720 2.5 mg versus mycophenolate mofetil (MMF) in a combination regimen with standard tacrolimus and corticosteroids in de novo renal transplant recipients for the composite efficacy within 6 months of transplantation. RESULTS: Incidence of treated biopsy-proven acute rejection was 22.9% with FTY720 and 18.5% with MMF. Increased incidence of macular oedema, transient decrease in heart rate and low rate of infections were seen in the FTY720 arm. CONCLUSION: FTY720 combined with tacrolimus and steroids did not show a significant therapeutic advantage over MMF for the prevention of acute rejection in de novo renal transplant recipients.

Recurrence and graft loss after kidney transplantation for henoch-schonlein purpura nephritis: a multicenter analysis.

BACKGROUND AND OBJECTIVES: The actuarial risk at 5 years for clinical recurrence of Henoch-Schönlein purpura nephritis (HSPN) and graft loss caused by recurrence of -HSPN after renal transplantation was reported in 1994 to be as high as 35% and 11%, respectively. The aim of this study is to re-evaluate, in a large cohort of patients with a long-term follow-up, whether these rates have changed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from six transplant centers in Belgium and France with strict diagnostic criteria of HSPN and a potential post transplant follow-up of ≥3 years were included. RESULTS: Forty-three patients were included. Patient survival is excellent: 98%, 95%, and 95% at 5, 10, and 15 years, respectively. Overall graft survival rates were 84%, 66%, and 56% at 5, 10, and 15 years, respectively. Clinical recurrence in a first kidney transplant occurred in five patients. Three patients lost their first graft due to HSPN recurrence 19 to 96 months after transplantation, two of whom had systemic signs of the illness. Actuarial risk for clinical recurrence in a first graft is 2.5% and 11.5% at 5 and 10 years, respectively. Actuarial risk for graft loss caused by recurrence in a first graft is 2.5% and 7.5% at 5 and 10 years, respectively. Severity of the disease at presentation and type of immunosuppression after transplantation did not affect recurrence. CONCLUSIONS: We found that recurrence rates of HSPN after transplantation are lower than previously reported. The actuarial risk of graft loss from recurrence in a first graft is 7.5% at 10 years.