[Outcome of ABO-incompatible living-donor kidney transplants : A plea for crossover living-donor kidney transplantation]. / Outcome von ABO-inkompatiblen Lebendnierenspenden : Ein Plädoyer für Crossover-Lebendnierenspenden.

BACKGROUND: The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20 years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned. OBJECTIVE: In the sense of a critical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants. MATERIALS AND METHODS: A retrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed. RESULTS: Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241 ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and a reduced longevity of the grafts. CONCLUSION: Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs.

Late Steroid Withdrawal Following AB0-Incompatible Renal Transplantation.

BACKGROUND: Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. METHODS: Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal. RESULTS: Baseline characteristics, including observation times, were not different between groups W and M. Graft survival was 100% in group W compared with 84% (16/19) in group M (P = .15). In group M, 1 patient experienced graft failure because of suspected antibody-mediated rejection (ABMR) following temporary cessation of mycophenolate treatment after a diagnosis of cryptococcal pneumonia. Two patients died with functioning graft because of sepsis. In group W, we observed 1 episode of ABMR following steroid withdrawal. At the end of follow-up, estimated glomerular filtration rates (eGFR) were 54 (19-91) versus 60 (15-85) mL/min/1.73 m2 in group W versus M, respectively (P = .67). CONCLUSIONS: Late steroid withdrawal following AB0i transplantation is feasible at a moderate risk of rejection. We recommend close monitoring of renal function and HLA antibodies during and after steroid withdrawal. On the other hand, the occurrence of severe infections causing death and graft loss in patients on triple maintenance immunosuppression including steroids should remind us to consider the overall immunosuppressive burden.

Successful Recovery of Acute Renal Transplant Failure in Recurrent Hepatitis C Virus-Associated Membranoproliferative Glomerulonephritis.

Recurrence of hepatitis C virus (HCV)-associated membranoproliferative glomerulonephritis (MPGN) in the kidney transplant may lead to continuous graft deterioration and the need for further renal replacement therapy. The novel direct-acting antiviral agents (DAAs) allow a highly effective and interferon-free treatment option for chronic HCV-infected patients. Data on the therapeutic safety and efficacy in HCV-infected renal transplant patients are sparse, especially for patients with severe renal impairment. We report the case of a 63-year-old female HCV-positive renal transplant patient with biopsy-proven recurrence of MPGN in the renal graft 3 years after transplant. Because of rapid loss of transplant function and consecutive need for hemodialysis, we initiated a combined anti-HCV-directed therapy regimen consisting of daclatasvir and simeprevir over 12 weeks. Viral clearance of HCV was obtained as early as 2 weeks after start of treatment. No adverse therapy-associated side effects were observed, and immunosuppressive dosing remained unchanged. Importantly, graft function fully recovered and hemodialysis was stopped 2 mo after the end of daclatasvir/simeprevir treatment. We report the first case of successful recovery of dialysis-dependent renal transplant failure after treatment of recurrent HCV-associated MPGN in a kidney transplant recipient by curing the underlying HCV infection with a combination of novel DAAs.

Living Donor Transplantation: Long-Term Evolution Related to Age Matching.

The lack of donors is favoring living kidney donor (LKD) transplantation worldwide, quite often beyond the classic age-matching rules. We analysed renal function (RF) at 1 and 5 years in all donor and recipients as well as death-censored graft and patient survival. LKD recipients were divided into 4 subgroups: young recipients-young donors (YR-YD; N = 355), elderly recipients-young donors (ER-YD; N = 13), young recipients-elderly donors (YR-ED; N = 67), and elderly recipients-elderly donors (ER-ED; N = 38). "Elderly" was defined as ≥60 years. RF was better in those who received a young allograft (YR-YD/ER-YD) at any time (P < .001). There was a trend toward higher proteinuria among the recipients of an old allograft (YR-ED/ER-ED) at any time (P = not significant [NS]). However, our population showed low levels of proteinuria and this was not a risk factor for graft failure. Logistic regression model showed that creatinine level at 1 year is a good predictor of graft losses. Graft survival was worse in the allografts from elderly donors (P < .001). Analysing the young recipients, renal survival was inferior in those who received an old kidney (YR-ED; P < .00005) as well as mortality rates at 14 years (P = .03). The RF of young (N = 295) and elderly donors (N = 98) was optimal with no progression to ESRD or deaths registered during follow-up. In conclusion, young recipients of elderly kidneys pay the price of a worse RF, allograft prognosis, and patient prognosis. The pair YR-ED is a doable option, but we recommend age matching when it is possible.

Pre-operative assessment of living renal transplant donors with state-of-the-art imaging modalities: computed tomography angiography versus magnetic resonance angiography in 118 patients.

PURPOSE: To compare current technology multislice computed tomography angiography (CTA) with magnetic resonance angiography (MRA) in the pre-operative evaluation of vascular anatomy of living renal transplant donors. METHODS AND MATERIALS: Two hundred and thirty-six kidneys were included in the CTA and MRA analysis. Renal vasculature was evaluated independently by two readers in each modality with a delay of 4 weeks between reading sessions. Surgical correlation on the operated side was available in all patients. The reference standard was defined by surgical correlation and consensus reading of both modalities. RESULTS: Detection rate of CTA for arteries was 99.1 and 95.0 % for reader 1 and reader 2, respectively. Detection rate of MRA for arteries was 95.0/94.3 %. Most of the undetected arteries were ≤ 1 mm diameter (reader 1: 2 of 3 in CTA and 9 of 16 in MRA; reader 2: 11 of 16 in CTA, and 8 of 18 in MRA). Detection rates for arteries ≥ 2 mm for reader 1/reader 2 were 99.7/98.7 % in CTA and 99.1/97.8 % in MRA, respectively. Detection rates for veins were 99.6/97.4 % in CTA and 97.8/96.9 % in MRA, respectively. Both readers misdiagnosed between 0 and 1 non-present arteries and between 2 and 3 non-present veins in both modalities. CONCLUSIONS: Modern multislice CT and MRI scanners allow highly accurate evaluation of the vascular anatomy, especially for vessels of ≥ 2 mm diameter. CTA may provide slightly better depiction of very small arteries; however, this may be reader-dependent. Additional factors affecting the choice of imaging modality should include local availability, cost, and the desire to avoid ionizing radiation in healthy transplant donors.

Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation.

Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR.

De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression.

Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient's current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

Effects of transgenic endothelin-2 overexpression on diabetic cardiomyopathy in rats.

BACKGROUND: Transgenic overexpression of human endothelin-2 in rats was used to characterize the contribution of endothelin to diabetic cardiomyopathy. MATERIALS AND METHODS: Diabetes mellitus was induced by streptozotocin in transgenic rats and transgene-negative controls. Nondiabetic animals were included as well to form a 4-group study design. Heart morphological and molecular alterations were analysed following 6 months of hyperglycaemia. RESULTS: Plasma endothelin concentrations were significantly higher in both transgenic groups than in wild-type groups (nondiabetic: 3.5 +/- 0.4 vs. 2.1 +/- 0.2, P < 0.05; diabetic: 4.5 +/- 0.4 vs. 2.5 +/- 0.4 fmol mL(-1), P < 0.01). Diabetes induced cardiac hypertrophy in both wild-type and transgenic rats and showed the highest myocardial interstitial tissue volume density in diabetic transgenic rats (1.5 +/- 0.07%) as compared with nondiabetic transgenic (1.1 +/- 0.03%), nondiabetic wild-type (0.8 +/- 0.01%) and diabetic wild-type rats (1.1 +/- 0.03%; P < 0.01 for all comparisons). A similar pattern with the most severe changes in the enothelin-2 transgenic, diabetic animals was observed for hypertrophy of the large coronary arteries and the small intramyocardial arterioles respectively. Cardiac mRNA expression of endothelin-1, endothelin receptors type A and B were altered in some degree by diabetes or transgenic overexpression of endothelin-2, but not in a uniform manner. Blood pressure did not differ between any of the four groups. CONCLUSIONS: Overexpression of the human endothelin-2 gene in rats aggravates diabetic cardiomyopathy by more severe coronary and intramyocardial vessel hypertrophy and myocardial interstitial fibrosis. This transgenic intervention provides further and independent support for a detrimental, blood pressure-independent role of endothelins in diabetic cardiac changes.

Citrate anticoagulation protocol for slow extended hemodialysis with the Genius dialysis system in acute renal failure.

BACKGROUND: The Genius dialysis system is increasingly used as an intermittent hemodialysis device in the setting of acute renal failure. Slow extended hemodialysis is preferred in the case of critical ill patients. In this study we established a safe and feasible citrate anticoagulation protocol for slow extended hemodialysis (SLED) with the Genius system. METHODS: We compared six anticoagulation protocols using SLED in 34 critically ill patients with acute renal failure. One group (A) received only citrate anticoagulation. Four groups (B - D) were treated with citrate and different additional systemic anticoagulation. Patients in the last group (F) were anticoagulated with heparin and were free of citrate anticoagulation. The total number of treatments was 103. A 4% sodium citrate solution was infused into the arterial line of the dialysis device for citrate anticoagulation. The dialysis solution contained one mmol/L of calcium. No additional calcium supplementation was done. We monitored electrolyte, acid-base and cardiovascular status prospectively. RESULTS: Hemodialysis was well tolerated hemodynamically. Electrolytes remained stable throughout hemodialysis in all groups. The decrease in ionized and total calcium was within the expected, clinically acceptable range. Bicarbonate and pH levels increased during dialysis, especially if citrate was used. CONCLUSIONS: Slow extended Genius hemodialysis with citrate is well tolerated and offers a safe and effective alternative to systemic anticoagulation.

Efficacy and safety of intermittent hemodialysis using citrate as anticoagulant: a prospective study.

BACKGROUND: The use of trisodium-citrate for regional anticoagulation of the extracorporal circuit during renal replacement therapy (RRT) has received increased interest, particularly in critically ill patients with increased risk of bleeding. Continuous renal replacement therapies are the most extensively investigated and used procedures in this regard. However, when patients recover from critical illness, RRT is often switched to intermittent procedures. In this prospective study, we investigated the efficacy and safety of citrate anticoagulation during intermittent hemodialysis (IHD) performed with a standard roller blood pump device. METHODS: We treated 11 critically ill patients with acute renal failure. These patients received a total of 31 intermittent IHD treatments. The targeted IHD treatment time was 6 h (4.5 l/h treatment dose). For anticoagulation, a 4% trisodium-citrate solution was continuously infused into the arterial line of the extracorporeal circuit. A calcium-free, lactate-based dialysis solution was used in all treatment procedures. Calcium was continuously substituted via a separate central line. Electrolyte and acid-base changes as well as the cardiovascular hemodynamics were analyzed. RESULTS: All patients achieved the targeted filter life time. Filter clotting did not occur. Electrolytes and acid base values were well-maintained throughout the study period. Particularly metabolic derangements were not observed. All treatments were hemodynamically well-tolerated. CONCLUSIONS: Intermittent hemodialysis with citrate anticoagulation can be safely applied in critically ill patients at high risk of bleeding.

Effect of mycophenolate mofetil monotherapy on T-cell functions and inosine monophosphate dehydrogenase activity in patients undergoing a kidney transplantation.

The aim of this study was to assess the effects of 1 g of mycophenolate mofetil (MMF) on T-cell function and inosine monophosphate dehydrogenase (IMPDH) activity among patients undergoing kidney transplantation. Five patients undergoing renal transplantation from a living donor were enrolled in this study. Compared to baseline (before MMF intake), CD25 and CD71 expression were significantly decreased during the first hour following MMF intake. T-cell proliferation and IMPDH activity also decreased dramatically. Thereafter, all biomarker levels increased over time. At 4 hours, CD25 and CD71 levels, as well as IMPDH activity, returned to almost baseline values, whereas T-cell proliferation remained below baseline. Intracytoplasmic IL-2 expression remained unchanged after MMF ingestions. In conclusion, administration of 1 g of MMF was associated with a transient decrease in CD25 expression in addition to a temporary dramatic decrease in both T-cell proliferation and IMPDH activity.

[Ten years of laparoscopic living kidney donation. From an extravagant to a routine procedure]. / 10 Jahre laparoskopische Lebendnierenspende. Von Rarität zu Routine.

Ten years ago the first laparoscopic living donor nephrectomy (LDN) was performed. Today, LDN is a routine operation in many US-American transplantation centers and an increasing number of centers in Europe are practicing LDN. In this article the different aspects of LDN for donor, kidney, recipient and operating surgeon are evaluated. We performed a literature research concerning LDN and the different aspects. Our own experience, as the largest LDN center in Germany, is part of the evaluation. Laparoscopic extraction of a kidney from a living donor is as safe for the donor as the open approach. At the same time, LDN offers multiple advantages like reduced pain and shorter convalescence. For the donated kidney and the recipient no disadvantages occur from the laparoscopic technique, as long as special intra- and perioperative demands are met. For the operating surgeon multiple developments have expanded the technical armentarium. LDN is safe for donor, recipient and kidney. Central issue of an optimal LDN is sufficient experience with laparoscopic urological techniques.

[Modern immunosuppression following renal transplantation. Standard or tailor made?]. / Moderne Immunsuppressiva nach Nierentransplantation Standard oder massgeschneidert?

Renal transplantation is by far the best therapeutic option for end-stage kidney disease with respect to quality of life, psychosocial rehabilitation, and even patient survival. Optimal immunosuppressive therapy should provide effective prophylaxis of both acute rejection and chronic allograft dysfunction. Thus immunosuppressive therapy should help to maintain good renal function and could help to prevent premature death of the recipient. With the introduction of new immunosuppressants over the last decade a dramatic reduction of acute rejection rates from approximately 50% to 15-30% could be achieved. However, the search for novel immunosuppressive drugs continues, drugs which not only lead to effective prevention of acute rejection, but also have an impact on chronic allograft dysfunction and prevent further deterioration of this multifactorial process. Based on a short presentation of the "three signal model" of immunoactivation, the most important mechanisms and characteristics of the presently available immunosuppressants are described. Because the immunosuppressive objectives change over time, a phase-dependent adaptation is necessary. At present, most centers in Germany use an immunosuppressive combination therapy, consisting of a calcineurin inhibitor (CNI; cyclosporine or tacrolimus), a glucocorticoid (prednisolone or methylprednisolone), and mycophenolic acid (MPA), which is eventually combined with an antibody (e.g., IL-2R antibody) for induction. In contrast to the clear situation 10 years ago, highly specialized knowledge is required today with respect to mechanism of action, side effects, and potential interactions. This may enable the physician to adopt patient-oriented optimal immunosuppression. In the near future more individualized treatment options will be employed, which are adapted to the characteristics and side effects of the immunosuppressant, as well as to the characteristics of the donor, the recipient, and the transplanted organ such as immunology and ischemia. Another aspect is the reduction or elimination of some immunosuppressants at the earliest possible time. With new diagnostic and genetic markers the relationship between recipient and transplanted organ will be characterized better in the future and therapy will become more individualized. Altogether, these measures as well as optimized supportive therapy will help to further improve the longevity of the transplanted organ.

[Urological evaluation and follow-up of the kidney transplant patient]. / Urologische Betreuung von Patienten vor und nach Nierentransplantation.

Patients with end-stage renal disease awaiting kidney transplantation require regular urological evaluation. The urologist's main task is early diagnosis and treatment of genitourinary malignancies and evaluation of the lower urinary tract. Furthermore, urologists are often confronted with the question of whether or not to perform pretransplant urological surgery, i.e., native nephrectomy for polycystic kidney disease. Urological care after kidney transplantation involves diagnosis and treatment of ureteral complications, malignancies, lower urinary tract symptoms, and last but not least erectile dysfunction, which has a prevalence of 20-50% among kidney transplant recipients. For the evaluation and follow-up of the living kidney donor, international guidelines have been developed in recent years to also help the urologist to perform a correct evaluation and follow-up of the kidney donor.

Transgenic rats expressing the human ET-2 gene: a model for the study of endothelin actions in vivo.

Previous studies have characterized the endothelin peptides (ET-1, ET-2, ET-3) as strong vasoconstrictors which are possibly involved in the pathogenesis of cardiovascular disease. Whereas ET-1 and ET-3 have been characterized using a number of approaches, little is known about the function of ET-2. The aim of this study was to define the role of ET-2 in physiology and pathophysiology using a transgenic approach. Transgenic rats expressing a genomic construct of the human ET-2 gene were generated by microinjection of fertilized oocytes from Sprague-Dawley rats. Two transgenic lines were generated, and one line was further characterized in detail. Studies on mRNA expression demonstrated that the transgene is expressed predominantly in kidney, gastrointestinal tract, adrenal gland, lung, and brain. Plasma endothelin levels were elevated 2-fold, and big-endothelin levels were elevated 2.5-fold. Despite these alterations blood pressure in transgenic rats remained normal. Further analysis of transgenic animals revealed that endothelin receptors were not downregulated, and that infusion of exogenous human ET-2 results in an enhanced blood pressure response. These observations suggest the presence of counterregulatory mechanisms influencing the effects of endothelin on blood pressure. One of these mechanisms may involve the nitric oxide system since infusion of an inhibitor of nitric oxide synthase resulted in a greater blood pressure response than in non-transgenic littermates. Despite unchanged blood pressure, alterations were observed in organ development and function, namely of hearts and kidneys, indicating an interference between transgene expression and growth processes. Male rats seem to be more susceptible to endothelin actions. These data show that the elevation in endothelin-2 expression in this transgenic model does not induce hypertension but leads to changes at the end-organ level. Normotension is most likely due to compensatory mechanisms such as increased nitric oxide formation.

Single-cell characterization of endothelin system gene expression in the cerebellum in situ.

To evaluate the expression of components of the endothelin (ET) system in single Purkinje neurons and Bergmann glial cells in situ, patch-clamp recording was combined with a multiplex RT-PCR approach. Cerebellar slices were rapidly isolated from 20- to 28-day-old mice. Cells were characterized morphologically and electrophysiologically and cell contents were aspirated and immediately reverse-transcribed. The cDNA was used as a template in a multiplex PCR reaction containing primers specific for ET-1, ET-2, and ET-3, ET-converting enzyme 1 (ECE-1) and ECE-2, and ETA and ETB receptors. The resulting PCR products were used as templates in a second PCR reaction containing only one pair of nested primers. Specific single bands were obtained from positive cells, which was confirmed by DNA sequencing of the PCR products. Of the 25 Purkinje neurons assayed, 84% were positive for ECE-1 mRNA and 68% for ECE-2 mRNA. No ET and ETA receptor mRNAs were detected, and only one cell was positive for ETB receptor mRNA. In Bergmann glial cells, ETB receptor mRNA was predominant. A total of 68% of the 25 cells assayed were positive. Sixteen percent were positive for ETA receptor mRNA, 8% for ECE-1 mRNA, and 12% for ECE-2 mRNA. Again, no ET mRNAs were detected. These results confirm the role of the ETB receptor in Bergmann glial cells and provide evidence for expression of ECE-1 and ECE-2 in Purkinje neurons.

Transcriptional regulation of endothelin-1 by erythropoietin in endothelial cells.

Recombinant human erythropoietin (rHuEpo) has been widely used in patients undergoing chronic hemodialysis treatment to correct anemia. In a subgroup of patients, i.v. administration of rHuEpo leads to manifestation or worsening of hypertension. The underlying mechanism of this remains unclear but it has been suggested that it is associated with increased expression of the vasoconstrictor endothelin (ET) in endothelial cells (ECs). There is also evidence for expression of specific rHuEpo receptors on ECs. The aim of this work was to study the time course and mechanisms of ET-1 regulation on the mRNA level in bovine aortic endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) stimulated with pharmacologic doses of rHuEpo (1-10 IU/ml). Compared to vehicle-treated controls, rHuEpo-treatment of ECs increases preproET-1 mRNA expression up to 170%, as shown by Northern blotting. To study the transcriptional regulation of ET-1 expression by rHuEpo, ECs were transfected with a luciferase construct driven by the rat ET-1 promoter and subsequently stimulated with rHuEpo. Compared to controls, luciferase activity increased up to 200% (n = 6; p < 0.05), suggesting transcriptional regulation of preproET-1 mRNA-expression by rHuEpo. Our data support the hypothesis that ET contributes to the hypertensive side effects of rHuEpo treatment and that this interaction occurs at the transcriptional level.

Bergmann glial cells in situ express endothelinB receptors linked to cytoplasmic calcium signals.

The endothelin (ET) isoforms ET-1, ET-2 and ET-3 applied at 100 nM triggered a transient increase in [Ca2+]i in Bergmann glial cells in cerebellar slices acutely isolated from 20-25 day-old mice. The intracellular calcium concentration ([Ca2+]i) was monitored using Fura-2-based [Ca2+]i microfluorimetry. The ET-triggered [Ca2+]i transients were mimicked by ETB receptor agonist BQ-3020 and were inhibited by ETB receptor antagonist BQ-788. ET elevated [Ca2+]i in Ca(2+)-free extracellular solution and the ET-triggered [Ca2+]i elevation was blocked by 500 nM thapsigargin indicating that the [Ca2+]i was released from InsP3-sensitive intracellular pools. The ET-triggered [Ca2+]i increase in Ca(2+)-free solution was shorter in duration. Restoration of normal extracellular [Ca2+] briefly after the ET application induced a second [Ca2+]i increase indicating the presence of a secondary Ca2+ influx which prolongs the Ca2+ signal. Pre-application of 100 microM ATP or 10 microM noradrenaline blocked the ET response suggesting the involvement of a common Ca2+ depot. The expression of ETB receptor mRNAs in Bergmann glial cells was revealed by single-cell RT-PCR. The mRNA was also found in Purkinje neurones, but no Ca2+ signalling was triggered by ET. We conclude that Bergmann glial cells are endowed with functional ETB receptors which induce the generation of intracellular [Ca2+]i signals by activation of Ca2+ release from InsP3-sensitive intracellular stores followed by a secondary Ca2+ influx.