Influence of Paclitaxel and Heparin on Vitality, Proliferation and Cytokine Production of Endometrial Cancer Cells.

BACKGROUND: Cancer patients have a higher risk for thromboembolic events compared to healthy individuals and are often treated with heparins. A beneficial effect of heparins on tumor patients above and beyond the classic anticoagulation effect has been reported, leading to an increased focus on the use of heparins in anticancer treatment. In recent years, it has become apparent that microenvironments greatly affect tumor development and can be a major source of tumor-promoting factors. Cytokines play an important role in tumor microenvironments, inducing carcinogenesis and influencing tumor progression by promoting angiogenesis, metastatic potential and immunosuppression. The possible interaction of heparins and cytokines could also have an effect on cancer cells. METHODS: This study investigated the effect of paclitaxel (PTX) combined with heparins on the vitality of endometrial cancer cells using viability and cytotoxicity assays. The study also examined whether treatment with paclitaxel and heparin influences cytokine secretion or expression. RESULTS: Heparin treatment did not influence cell viability, and no influence of heparins in combination with paclitaxel was seen for the evaluated cancer cell lines HEC-1-A, KLE, RL 95-2 and AN3-CA compared to untreated cells. Secretion of the cytokines CCL5, CCL2 and IL-6 increased after paclitaxel treatment in several endometrial cancer cell lines, but no general effect on cytokine secretion was detected after heparin treatment. A significant decrease in CCL5 expression was only detected in KLE cells following treatment with heparin and paclitaxel, and an increase in the expression of CCL5 in RL 95-2 cells. CONCLUSION: Further in-depth studies are needed to investigate the functions of cytokines CCL2, CCL5 and IL-6 in endometrial cancer cells treated with paclitaxel. Although no general effect on cytokine secretion was detected following heparin treatment, a selective modulatory impact could exist.

Selection for biopsy of kidney transplant patients by diffusion-weighted MRI.

OBJECTIVES: To assess retrospectively whether diffusion-weighted magnetic resonance imaging (DW-MRI) allows physicians to determine the severity of histopathologic findings in biopsies of renal allograft patients with deteriorating renal function. METHODS: Forty consecutive kidney transplant patients underwent DW-MRI and biopsy. Patients were assigned to one group with severe and to another group with normal or mild histopathologic findings. These two groups were compared based on a qualitative DW-MRI assessment (homo-/heterogeneity) and the combination of qualitative and quantitative DW-MRI parameters (ADC, and intravoxel incoherent motion, IVIM, parameters: D, f, D*). Sensitivity, specificity, and accuracy were determined for each parameter. RESULTS: Biopsy findings were severe in 25 patients and normal or mild in 15 patients. Qualitative DW-MRI led to a sensitivity of 44.0% and a specificity of 93.3%. Combined qualitative and quantitative DW-MRI led to an accuracy of 80% for both the minimal ADC (ADCmin) and the minimal perfusion fraction (fmin) with a sensitivity of 84.0% and 92.0% and a specificity of 73.3% and 60.0%, respectively. CONCLUSION: Combined qualitative and quantitative DW-MRI might allow physicians to determine the severity of histopathologic findings in biopsies of a high number of kidney transplant patients. KEY POINTS: • Qualitative DW-MRI is highly specific when predicting the severity of kidney transplant biopsy. • Allografts appearing heterogeneous on ADC are associated with severe histopathologic findings. • Combining qualitative and quantitative DW-MRI parameters improves the classification's sensitivity and accuracy. • Kidney transplant biopsies might be spared by combining qualitative and quantitative DW-MRI.

Correlation between Inflammatory Biomarkers and Red Blood Cell Life Span in Chronic Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: The pathogenesis of anemia in hemodialysis (HD) patients is dependent on multiple factors, with decreased red blood cell life span (RBCLS) being a significant contributor. Although the impact of reduced RBCLS on anemia is recognized, it is still a subject that is not well researched. The objective of this study was to investigate the relationship between RBCLS and inflammatory biomarkers in chronic HD patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: RBCLS was calculated from alveolar carbon monoxide concentrations measured by gas chromatography. Interleukins (IL) IL-6, IL-18, IL-10, and high sensitivity C-reactive protein were measured using bead-based multiplex assay. Measurements were carried out at baseline and during follow-up. The associations between RBCLS and inflammatory biomarkers were evaluated using linear mixed effects models. RESULTS: RBCLS measurements were available for 54 HD patients. Their average age was 58.5 ± 14.4 years, 68.5% were males, 48.1% were diabetics, and the HD vintage was 51 ± 48 months. In 4 patients, RBCLS was measured once, while in 50 patients, up to 5 repeated RBCLS measurements were available. RBCLS was 73.2 ± 17.8 days (range 37.7-115.8 days). No association was found between RBCLS and any of the inflammatory biomarkers. Of note, RBCLS was positively correlated with levels of uric acid (p = 0.02) and blood urea nitrogen (BUN; p = 0.01), respectively. CONCLUSION: Our study suggests that inflammation pathways reported by these biomarkers only have a limited role in causing premature RBC death. The positive correlation with uric acid and BUN warrants further studies.

Novel Bone-Anchored Vascular Access on the Mastoid for Hemodialysis: Concept and Preclinical Trials.

GOAL: We present the development of a bone-anchored port for the painless long-term hemodialytic treatment of patients with renal failure. This port is implanted behind the ear. METHODS: The port was developed based on knowledge obtained from long-term experience with implantable hearing devices, which are firmly anchored to the bone behind the ear. This concept of bone anchoring was adapted to the requirements for a vascular access during hemodialysis. The investigational device is comprised of a base plate that is firmly fixed with bone screws to the bone behind the ear (temporal bone). A catheter leads from the base plate valve block through the internal jugular vein and into the right atrium. The valves are opened using a special disposable adapter, without any need to puncture the blood vessels. Between hemodialysis sessions, the port is protected with a disposable cover. RESULTS: Flow rate, leak tightness, and purification were tested on mockups. Preoperative planning and the surgical procedure were verified in 15 anatomical human whole head specimens. CONCLUSION: Preclinical evaluations demonstrated the technical feasibility and safety of the investigational device. SIGNIFICANCE: Approximately 1.5 million people are treated with hemodialysis worldwide, and 25% of the overall cost of dialysis therapy results from vascular access problems. New approaches toward enhancing vascular access could potentially reduce the costs and complications of hemodialytic therapy.

[A new bone anchored hemodialysis access]. / Neuartiger knochenverankerter Hämodialysezugang.

When classic arteriovenous fistulas or grafts fail, dialysis patients have a vital requirement for a catheter to ensure vascular access. Permanent central venous catheters penetrate the cervical and thoracic soft tissues and the skin without rigid fixation. The infection rate for such devices is high, often requiring explantation. Bone anchored hearing aids are an established treatment in patients with conductive hearing loss. The implant is firmly fixed on the temporal bone and the abutment permanently penetrates the skin. Severe infections requiring explantation are very rare. We suppose that one of the main reasons for the low complication rate is the firm fixation of the implant to the temporal bone, which minimizes the movement of the skin relative to the underlying bone. Based on the experience with implantable hearing devices we developed a percutaneous bone anchored port fixed to the skull in the region of the temporal bone. Such a bone anchored port could be a beneficial alternative to conventional central venous catheters for patients undergoing hemodialysis. In the course of the development process we investigated the individual anatomy to locate the correct implantation site with sufficient bone thickness; we studied screw stability in bone; we developed the titanium implant that houses the port system as well as the surgical tools and procedure for save implantation; we tested flow rate, leak tightness and purification on mockups; we defined the Seldinger-insertion of the catheter into the internal jugular vein via a small neck incision. Our results show the technical feasibility of a temporal bone anchored port and form the basis of a now-approved clinical pilot study.

Inflammatory Response to Sorbent Hemodialysis.

Inflammation is common and associated with morbidity and mortality in hemodialysis (HD) patients. Exposure to endotoxin contained in the dialysate may trigger inflammation. Dialysate volume is substantially reduced in sorbent HD compared with standard single-pass dialysis. In this prospective study (Clinicaltrials.gov, number: NCT00788905), we compared the inflammatory response to single-pass and sorbent HD. Patients receiving single-pass HD were studied during 1 week of sorbent HD (Allient system; Renal Solutions, Warrendale, PA) and 1 week of single-pass HD. Patients were dialyzed using high-flux polysulfone dialyzers. Midweek pre- and post-HD serum levels of high-sensitivity C-reactive protein, interleukin (IL)-1ß, IL-6, IL-10, interferon gamma, tumor necrosis factor alpha (TNF-α), and eotaxin were determined and their intradialytic change corrected for hemoconcentration during single-pass HD and sorbent HD compared by paired t-test. We enrolled 18 patients, nine completed the study. Although TNF-α decreased during both single-pass and sorbent HD (p < 0.001), none of the other biomarkers changed significantly during HD. We observed no difference between single-pass and sorbent HD. For the markers investigated in this study, there was no difference in the acute intradialytic inflammatory response to single-pass or sorbent HD.

Arterial stiffness depends on serum ionized calcium levels during dialysis with regional citrate anticoagulation.

Hemodynamic effects related to changes in serum ionized calcium (iCa) are difficult to determine during conventional hemodialysis (HD) using a fixed dialysate concentration of calcium. Regional citrate anticoagulation (RCA) allows the study of the effects of predefined iCa changes on arterial stiffness and blood pressure (BP) during a single dialysis session. In a crossover study, 15 patients with end-stage renal disease underwent two HD sessions with RCA. Each session was divided into two study phases in which iCa was titrated either to 0.8-1.0 mm or to 1.1-1.4 mm. The sequence of phases was randomly chosen and alternated for the second session. After reaching a stable iCa level, pulse wave velocity (PWV), arterial BP, and heart rate were measured. iCa levels were modified during sequence 1 (iCa low-high) from a predialysis baseline value of 1.15 ± 0.09 mm, first to 0.92 ± 0.05 mm (time point 1; P < 0.001 vs. baseline) and then to 1.18 ± 0.05 (time point 2; ns). During sequence 2 (iCa high-low), iCa levels were modified from 1.15 ± 0.12 mm first to 1.20 ± 0.05 mm (time point 1; ns vs. baseline) and then to 0.93 ± 0.03 (time point 2; P < 0.001). Assuming a basic linear repeated measures model, PWV was positively related to iCa levels (P < 0.03) independent of systolic or diastolic BP, heart rate, or ultrafiltration rate. PWV is closely related to acute changes in serum iCa levels in HD patients using RCA. RCA provides an interesting opportunity to study the effects of acute iCa changes during one dialysis procedure.

Clinical evaluation of a model for prediction of end-dialysis systemic ionized calcium concentration in citrate hemodialysis.

BACKGROUND/AIM: Citrate anticoagulation in hemodialysis (HD) is increasingly drawing attention in the nephrology community. One of the major deterrents to a more widespread use are the monitoring requirements for fear of systemic calcium derangements. Means of accurately predicting systemic ionized calcium (iCa) may help to overcome this challenge. We have previously presented a mathematical model of regional citrate anticoagulation (RCA) to address this need. Here, we present a refined model and show results in an independent validation cohort of maintenance HD patients on Citrasate®, a calcium- and citrate-containing dialysate. METHODS: A hybrid RCA model was developed, comprising the previously published 'native' RCA model and a statistical correction based on levels of alkaline phosphatase as a marker of bone turnover. The model was validated in 120 patients on Citrasate, a dialysate containing 0.8 mmol/l citrate and 1.125 mmol/l calcium. Systemic iCa was measured at the beginning and end of one HD treatment in each subject. Serum iCa predictions were compared between our previously published model and the new hybrid model. RESULTS: On average, the hybrid model predicted end-HD systemic iCa with an error (predicted - measured) of 0.028 mmol/l, compared to -0.051 mmol/l with the previously published model. There were only 4 subjects out of the 120 analyzed in whom the prediction error was <-0.1 mmol/l, and only 6 in whom the error was >+0.1 mmol/l (max: +0.13 mmol/l). CONCLUSION: This study demonstrates that the novel hybrid model is an improvement over the previously published model and that it is capable of predicting end-dialysis systemic iCa levels with improved accuracy and precision even in a citrate dialysis setting which was much different from the original derivation cohort.

Metabolic effects of dialyzate glucose in chronic hemodialysis: results from a prospective, randomized crossover trial.

BACKGROUND: There is no agreement concerning dialyzate glucose concentration in hemodialysis (HD) and 100 and 200 mg/dL (G100 and G200) are frequently used. G200 may result in diffusive glucose flux into the patient, with consequent hyperglycemia and hyperinsulinism, and electrolyte alterations, in particular potassium (K) and phosphorus (P). This trial compared metabolic effects of G100 versus G200. METHODS: Chronic HD patients participated in this randomized, single masked, controlled crossover trial (www.clinicaltrials.gov: #NCT00618033) consisting of two consecutive 3-week segments with G100 and G200, respectively. Intradialytic serum glucose (SG) and insulin concentrations (SI) were measured at 0, 30, 60, 120, 180, 240 min and immediately post-HD; P and K were measured at 0, 120, 180 min and post-HD. Hypoglycemia was defined as an SG<70 mg/dL. Mean SG and SI were computed as area under the curve divided by treatment time. RESULTS: Fourteen diabetic and 15 non-diabetic subjects were studied. SG was significantly higher with G200 as compared to G100, both in diabetic {G200: 192.8±48.1 mg/dL; G100: 154.0±27.3 mg/dL; difference 38.8 [95% confidence interval (CI): 21.2-56.4] mg/dL; P<0.001} and non-diabetic subjects [G200: 127.0±11.2 mg/dL; G100 106.5±10.8 mg/dL; difference 20.6 (95% CI: 15.3-25.9) mg/dL; P<0.001]. SI was significantly higher with G200 in non-diabetic subjects. Frequency of hypoglycemia, P and K serum levels, interdialytic weight gain and adverse intradialytic events did not differ significantly between G100 and G200. CONCLUSION: G200 may exert unfavorable metabolic effects in chronic HD patients, in particular hyperglycemia and hyperinsulinism, the latter in non-diabetic subjects.

Effects of dialysate glucose concentration on heart rate variability in chronic hemodialysis patients: results of a prospective randomized trial.

BACKGROUND: Chronic hemodialysis (HD) patients suffer from an appallingly high cardiovascular mortality. During HD, patients are exposed to dialysate glucose, which may alter blood glucose levels and thus exert effects on the autonomic nervous system. Heart rate variability (HRV) is an established indicator of autonomic nervous system activity and a predictor of cardiovascular outcomes. This study investigated the effects of two commonly used dialysate glucose concentrations [100 mg/dl (HD100), and 200 mg/dl (HD200)] on HRV in chronic HD patients. METHODS: In this prospective, randomized, controlled, single-masked, cross-over trial, subjects were randomized to receive HD100 or HD200 for a period of 3 weeks followed by a cross-over to the respective other dialysate (www.clinicaltrials.gov #NCT00618033). Blood glucose and insulin levels were measured before and after HD. Intradialytic Holter electrocardiograms were recorded and HRV time domain, frequency domain and complexity parameters analyzed. RESULTS: Twenty-three HD patients (age 56 ± 12 years, 11 male, 14 black, 11 with diabetes) were studied. Diabetic subjects showed significantly higher serum glucose levels with HD200 as compared to HD100 (HD100: 146 ± 48 mg/dl; HD200: 192 ± 57 mg/dl; p < 0.01); this hyperglycemia was accompanied by an increase of the high-frequency band of HRV (p = 0.019), a reflection of increased parasympathetic activity. HRV did not change in nondiabetic subjects. CONCLUSION: In diabetic subjects, the use of HD200 increased vagal tone. Given the importance of sympathetic activation to counteract intradialytic hypotension, our findings support the use of HD100 in diabetic HD patients.

Clearance of p-cresol sulfate and ß-2-microglobulin from dialysate by commercially available sorbent technology.

Dialysate regeneration by sorbents is an alternative to conventional single-pass dialysis. Little is known about the capacity of sorbents to clear dialysate of "middle molecules" and protein-bound uremic toxins. We studied p-cresol sulfate (PCS) and ß-2-microglobulin (ß2M) removal from dialysate by a sorbent: 1. PCS (40 mg PCS dissolved in 4 L of fresh dialysate) was recirculated through a sorbent cartridge (SORB Technology, Inc.) for analysis of PCS removal. 2. Spent peritoneal dialysate was recirculated on the "blood" side of a high-flux dialyzer. On the "dialysate" side of the membrane, bicarbonate dialysate was recirculated through a sorbent cartridge. ß2M was measured in both streams. Two results are of particular importance for the use of regenerated fluid in chronic dialysis: 1. PCS was virtually completely removed from the dialysate. On average, PCS concentration was reduced to 1.4% of the starting concentration after 60 minutes. PCS extraction across the sorbent was nearly complete at any time. 2. ß2M was on average reduced to 14.3% of the starting concentration after 60 minutes. Postsorbent concentrations were consistently below the validated range of the test method. We conclude that PCS and ß2M are efficiently removed from the dialysate by commercially available sorbent technology. Spent peritoneal dialysis fluid can be cleared of ß2M when circulated against sorbent-regenerated dialysate using a high-flux membrane.

A mathematical model of regional citrate anticoagulation in hemodialysis.

BACKGROUND/AIMS: Regional citrate anticoagulation (RCA) during hemodialysis (HD) has several advantages over heparin anticoagulation, but calcium (Ca) derangements are a major concern necessitating repeated monitoring of systemic ionized Ca (Ca(2+)). We developed a mathematical model of Ca and citrate (Ci) kinetics during RCA. METHODS: Using patient- and treatment-related parameters, including pre-HD serum Ca and protein concentrations, hematocrit, blood and dialysate flow rates, dialysate composition and access recirculation, the model computes all relevant aspects of RCA based on physicochemical, biochemical and physiological principles such as chemical Ca and Ci equilibria, transmembrane solute fluxes and Ci metabolic rate. The model was validated in 17 treatments using arterial Ci infusion, Citrasate dialysate, and no postdialyzer Ca substitution. RESULTS: Measured and predicted systemic Ca(2+) before HD was 1.08 +/- 0.06 and 1.05 +/- 0.05 mmol/l, respectively (difference -0.03 +/- 0.046, 95% confidence interval, CI, -0.055 to -0.007), and at 15 min into the treatment 1.01 +/- 0.05 and 1.02 +/- 0.05 mmol/l, respectively (difference 0.012 +/- 0.054, 95% CI -0.015 to 0.04). At 15 min, the measured and predicted predialyzer Ca(2+) was 0.33 +/- 0.06 and 0.39 +/- 0.05 mmol/l, respectively (difference 0.06 +/- 0.03; 95% CI 0.044-0.077), and the measured and predicted postdialyzer Ca(2+) was 0.7 +/- 0.05 and 0.61 +/- 0.05 mmol/l, respectively (difference -0.09 +/- 0.04; 95% CI -0.11 to -0.07). Bland-Altman analysis showed no systematic bias in these predictions. CONCLUSION: This novel model of RCA shows excellent accuracy in predicting systemic, pre- and postdialyzer Ca(2+) concentrations and may prove valuable in both research and clinical applications of RCA.

[Hereditary nephrogenetic diabetes insipidus--case report and discussion]. / Kongenitaler nephrogener Diabetes insipidus--Fallbericht und Diskussion.

The history of a patient with hereditary nephrogenic diabetes insipidus is discussed. The pathogenesis and the therapeutic approach is revised.

Glycyrrhetinic acid food supplementation lowers serum potassium concentration in chronic hemodialysis patients.

Hyperkalemia is a common life-threatening problem in hemodialysis patients. Because glycyrrhetinic acid (GA) inhibits the enzyme 11beta-hydroxy-steroid dehydrogenase II and thereby increases cortisol availability to the colonic mineralocorticoid receptor, it has the potential to lower serum potassium concentrations. To test this, 10 patients in a 6 month prospective, double-blind, placebo-controlled crossover study were given cookies or bread rolls supplemented with glycyrrhetinic acid or placebo. Twenty-four-hour blood pressure measurements were performed at baseline and week 6 and 12 of each treatment period. The ratio of plasma cortisol/cortisone was significantly increased in all patients on GA as compared to baseline or placebo, indicating appropriate enzyme inhibition. Nine of the 10 patients had a persistent decrease in predialysis serum potassium concentration. On GA, mean predialysis serum potassium was significantly lower than at baseline or on placebo. On placebo, serum potassium was significantly elevated above the upper limit of normal in 76% compared to 30% of measurements during GA treatment. Furthermore, on this treatment the frequency of severe hyperkalemia significantly decreased from 9% to 0.6%. No differences were found in parameters reflecting sodium retention. Although these studies show that prolonged GA supplementation persistently lowers serum potassium in dialysis patients, a long-term toxicity study will be mandatory before we recommend the routine use of this treatment.

Temporal evolution of clinical parameters before death in dialysis patients: a new concept.

BACKGROUND: Chronic hemodialysis (HD) patients experience an appallingly high mortality in the range of 20% per year. Little is known on the dynamics of key clinical and laboratory variables in the weeks and months preceding death. In order to gain more insight into events preceding death, we embarked on a novel methodological approach which encompasses data analysis from the date of death backwards in time. METHODS: The current study investigates the dynamics of postdialytic weight and serum albumin levels in the 24 months preceding death. We performed a retrospective analysis of 2,462 maintenance HD patients who died between July 1, 2005 and April 30, 2008. Patients' monthly serum albumin levels were extracted for the 24 months preceding the date of death. Similarly, the median weekly postdialysis weight was extracted for the 104 weeks prior to death. Data were analyzed with linear mixed models. RESULTS: Both albumin levels and postdialytic body weight showed a significant decrease irrespective of gender and race in the 3 final months of life. The most pronounced decreases in postdialytic weight and albumin levels were observed in patients with infection as cause of death, the smallest changes occurred in subjects with cerebrovascular events. CONCLUSIONS: In their final 3 months of life, HD patients experience a marked decrease in body weight and serum albumin levels. A better understanding of dynamic patterns of key variables before death may be useful in developing processes which alert medical caregivers to patients at increased risk, in order to institute timely diagnostic and therapeutic interventions.

Red blood cell lifespan, erythropoiesis and hemoglobin control.

Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals.

Activation of the RET (rearranged during transfection) receptor by glial cell-line-derived neurotrophic factor (GDNF) has been identified as an important differentiation and survival factor for dopaminergic neurons of the midbrain in preclinical experiments. These encouraging results have led to clinical trials of GDNF in patients with Parkinson's disease, which have resulted in conflicting findings. To investigate the potential benefit of Ret-dependent signaling on the challenged dopaminergic system, we tested the effect of tissue-selective ablation of the Ret gene on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice, the most widely used animal model for Parkinson's disease. Ablation of Ret did not modify the MPTP-induced loss of dopaminergic neurons in the substantia nigra pars compacta and the dopaminergic innervation of the striatum at 14 days. However, Ret ablation abolished the regeneration of dopaminergic fibers and terminals, as well as the partial recovery of striatal dopamine concentrations, that was observed in control mice between days 14 and 90 after MPTP treatment. We therefore conclude that RET signaling has no influence on the survival of dopaminergic neurons in the MPTP model of Parkinson's disease but rather facilitates the regeneration of dopaminergic axon terminals.

Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Persistent hyperparathyroidism after renal transplantation affects bone and allografts. Cinacalcet, a calcimimetic, reduces serum calcium and PTH in renal transplant recipients with persistent hyperparathyroidism. Here, we address the question whether this effect of cinacalcet persists after withdrawal. METHODS: Therefore, cinacalcet was stopped after 12 months treatment in 10 stable renal transplant patients. Serum calcium, phosphate, PTH, creatinine and cystatin C were monitored for 3 months. RESULTS: Serum calcium, normalized in nine patients before cessation of cinacalcet (2.32 +/- 0.05mmol/l, mean +/- SEM), increased after 3 months of discontinuation by 0.17 +/- 0.04mmol/l, P < 0.05, but remained within the normal range in eight patients. Compared with the time point of cessation, PTH remained unchanged or decreased further after 3 months without therapy in six patients. Measurements of cystatin C suggested an improvement of the glomerular filtration rate after cessation in 9 out of 10 patients (1.55 +/- 0.09 vs 1.33 +/- 0.12 mg/l, P < 0.01). CONCLUSION: First, a beneficial effect of cinacalcet beyond the duration of a 12-month therapy appears to be present in some patients and second, the previously suspected influence of cinacalcet therapy on renal function is reversible. Thus, it is reasonable to consider a trial of cinacalcet cessation to identify these patients. The optimal time point for such a discontinuation is unknown. The present observations are preliminary. They clearly require a prospective randomized trial for definitive confirmation.