tacrolimus and Hypertension--Renal

Drugs used to modify the immune response in solid organ transplantation or autoimmune disease may cause dose-related nephrotoxicity. Cyclosporine, FK506, cyclosporine G, and rapamycin have all been studied experimentally and to a more limited extent in patients. This paper summarizes this literature using data from clinically relevant animal models.

Topics: Acute Kidney Injury; Animals; Cyclosporine; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Failure, Chronic; Polyenes; Sirolimus; Tacrolimus

In the past, enteric drainage or the omission of induction immunotherapy has been shown to be predictive of suboptimal outcomes of simultaneous pancreas-kidney (SPK) transplantation. We have reassessed the need for bladder drainage and induction immunotherapy to optimize the outcome of SPK transplantation.. One hundred consecutive recipients of SPK transplants who received mycophenolate mofetil and tacrolimus immunosuppression were studied. The first 50 recipients had bladder-drained pancreas allografts and received induction immunotherapy. The results were compared with the next 50 recipients who had enteric-drained pancreas allografts, which included a subgroup (n = 17 patients) who were randomized to receive no induction immunotherapy.. The 1-year actuarial patient, kidney, and pancreas survival rates in the bladder-drainage group were 98.0%, 94.0%, and 94.0%, respectively. The 1-year actuarial patient, kidney, and pancreas survival rates in the enteric-drainage group were 96.8%, 96.8%, and 89.4%, respectively. In the enteric-drainage group, the incidence of rejection at 1 year was 6.1% in recipients who received induction therapy versus 23.5% in recipients who did not receive induction therapy. The average number of readmissions per recipient was 1.8 in the bladder-drainage group versus 0.9 in the enteric-drainage group.. Primary enteric drainage of the pancreas allograft in recipients of SPK transplantation is the preferred surgical technique in the tacrolimus/mycophenolate mofetil era.

Topics: Adult; Bacterial Infections; Drainage; Female; Graft Rejection; Graft Survival; Humans; Hypertension, Renal; Immunosuppressive Agents; Incidence; Intestines; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pancreas Transplantation; Patient Readmission; Postoperative Complications; Survival Analysis; Tacrolimus; Treatment Outcome; Urinary Bladder

Arterial hypertension, which represents a common problem in patients with renal transplant, contributes to the cardiovascular morbidity and mortality of these patients. The most usual immunosuppressive drugs (cyclosporine and FK-506) collaborate on the development of hypertension. Calcium channel blockers are the most habitually used antihypertensive drugs in this population, although its long-term hemodimamycs effects could be deleterious especially in transplanted patients with chronic graft nephropathy. Losartan, a specific blocker of angiotensin II (AT1) receptors, has demonstrated a potent antihypertensive effect with a good safety and tolerance profile. The glomerular effects of losartan could be useful in transplanted patients. The present open, prospective and multicenter study evaluated the efficacy and safety of losartan in the treatment of hypertension in a group of patients with a renal transplant. Seventy-six patients with systolic blood pressure > or = 140 and/or diastolic blood pressure > or = 90 mm Hg, and/or patients on therapy with one antihypertensive drug and related side effects were included. After inclusion, therapy with losartan 50 mg/24 hr was started, discontinuing the previous antihypertensive therapy and/or therapy which caused the side effects. At four weeks, if blood pressure (BP) was not controlled, hydrochlorothiazide 25 mg or furosemide 40 mg/24 hr was added. At baseline and at weeks 2, 4, 8 and 12, the following parameters were monitored: BP, creatinine, hematocrit, hemoglobin, glucose, ions, uric acid, cholesterol, triglycerides, bilirubin, SGOT, SGPT, GGT, LDH, calcium, phosphate, alkaline phosphatase, proteinuria, and both cyclosporine and FK-506 levels in whole blood. Sixty-seven patients completed the 12-week study period. Mean blood pressure decreased from 113 +/- 10 to 102 +/- 9 mm Hg at the end of the study (P < 0.0001); 38 of the 67 patients (56.7%) who completed the study had a SBP lower than 140 mm Hg and a DBP lower than 90. These blood pressures were obtained in 30 patients on monotherapy with losartan (78.9%). Proteinuria decreased significantly at week 4 and was confirmed at week 12, especially in patients with proteinuria > or = 300 mg/24 hr. Nine patients were withdrawn during the study period for different reasons. Serum creatinine showed a slight, non-clinically significant increase at week 4, remaining stable until the end of the study. Two patients developed a mild normocytic anemia, and three others

Topics: Adult; Antihypertensive Agents; Blood Pressure; Cyclosporine; Drug Interactions; Female; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Losartan; Male; Postoperative Complications; Tacrolimus

The CONCERTO study results showing the beneficial effects of conversion from cyclosporine to tacrolimus prolonged-release (tacrolimus PR) in stabilised patients after kidney transplantation, were first published in 2011. This communication describes our first experience of conversion from cyclosporine to tacrolimus PR in stabilised kidney transplant patients. The aim was to determine whether it could be used in routine clinical practice in the Czech and Slovak Republics.. Evaluation was carried out at five transplantation centres in the Czech Republic and Slovakia. In all participating Centres, the drug conversion was conducted according to the ICH/GCP guidelines. A total of 104 patients stabilised after kidney transplantation were converted from maintenance therapy with cyclosporine to treatment with tacrolimus PR. The data were collected 26 weeks after the switch. The primary endpoint was change in kidney graft function measured from the estimated glomerular filtration rate (GFR). The effect of conversion on blood pressure, metabolic parameters and cosmetic changes was also recorded. Special attention was paid to the safety and tolerability of treatment with tacrolimus PR.. GFR increased after six months by 10 % (P = 0.040). In addition a significant decrease in serum creatinine and triglycerides level was found together with major reduction in the incidence and severity of gingival hyperplasia and hirsutism. 3% of patients developed new onset of diabetes mellitus. Otherwise, the switch was very well-tolerated, without serious adverse events or acute rejections.. Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.

Topics: Cyclosporine; Delayed-Action Preparations; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Substitution; Dyslipidemias; Female; Gingival Hyperplasia; Glomerular Filtration Rate; Hirsutism; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Tacrolimus; Treatment Outcome

The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, program directors of United States nephrology training programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. They compared their answers in real time using audience response devices with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the audience responses and the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for the readers of CJASN. Enjoy the clinical cases and expert discussions.

Topics: Anemia; Calcineurin Inhibitors; Female; Humans; Hypertension, Renal; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephritis; Nephrology; Neuroimaging; Parvoviridae Infections; Parvovirus B19, Human; Posterior Leukoencephalopathy Syndrome; Radiography; Surveys and Questionnaires; Tacrolimus

A substantial number of patients with lupus nephritis (LN) are refractory to conventional glucocorticoid (GC) treatment. Although many of these patients respond to immunosuppressive drugs such as intravenous cyclophosphamide (IVCY), azathioprine (AZA), mizoribine, tacrolimus, cyclosporine A (CSA) and mycofenolate mofetil (MMF), some remain refractory to such therapies. Recent studies of multi-target therapies have reported effective outcomes for immunosuppression following renal transplantation and refractory LN when therapy consists of two or more immunosuppressive drugs with different mechanisms of action. We herein report a case of LN unresponsive to IVCY that was successfully treated with the addition of tacrolimus and discuss the usefulness of multi-target therapy for LN.

Topics: Adolescent; Antihypertensive Agents; Biphenyl Compounds; Cyclophosphamide; Cyclosporine; Drug Therapy, Combination; Female; Humans; Hypertension, Renal; Immunosuppressive Agents; Infusions, Intravenous; Irbesartan; Lupus Erythematosus, Systemic; Lupus Nephritis; Nephrotic Syndrome; Prednisolone; Pulse Therapy, Drug; Recurrence; Ribonucleosides; Severity of Illness Index; Tacrolimus; Tetrazoles

After the completion of a double-blind placebo-controlled trial, tacrolimus (TAC) was approved for the treatment of lupus nephritis (LN) in Japan. However, the approved maximal dose, 3 mg/day, is almost half the dose used for induction therapy outside Japan. In this study, we retrospectively evaluated the efficacy and safety of low-dose TAC (≤3 mg/day) for induction therapy in 13 adult patients (2 men and 11 women) with active LN. Eight patients were treated for LN flares. Twelve patients underwent renal biopsies: 8 with class IV, 2 with class III + V, 1 with class IV + V, and 1 with class V renal histology, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. The mean initial doses of prednisone and TAC were 34.6 ± 14.5 and 2.7 ± 0.6 mg/day, respectively. All the patients achieved a complete remission (CR) at 7.7 ± 6.7 months (mean ± SD) after the last administration of TAC, except for 2 patients who discontinued TAC treatment; 1 because of worsening systemic lupus erythematosus and 1 because of hypertension. Two patients experienced a flare-up after achieving CR. The mean blood TAC concentration 12 h after the last administration (C12) was significantly lower among the patients with flare-ups than among those with a sustained CR (1.5 ± 1.5 vs. 5.1 ± 1.9 ng/mL, P = 0.034). These data showed that low-dose TAC was effective for induction therapy in patients with active LN, although a lower TAC concentration may be associated with a poor outcome.

Topics: Adrenal Cortex Hormones; Adult; Angiotensin II Type 1 Receptor Blockers; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypertension, Renal; Immunosuppressive Agents; Lupus Nephritis; Male; Middle Aged; Proteinuria; Remission Induction; Retrospective Studies; Tacrolimus

This is a retrospective analysis of 16 children started on tacrolimus with various types of treatment-resistant nephrotic syndrome. There are 13 patients with focal glomerulosclerosis, 1 minimal change disease, and 2 IgA nephropathy with nephrosis. The mean age of the children was 11.4 years (range 3.5-18.1 years) with a mean age at diagnosis of 5.6 years (range 1.6-13.3 years). All patients initially received prednisone 2 mg/kg per day. Other therapies for 15 of 16 included cyclosporine (n=15), chlorambucil (n=5), mycophenolate mofetil (n=5), levamisole (n=3), i.v. methylprednisolone (n=3), and cyclophosphamide (n=2). The major indication for the initiation of tacrolimus included treatment resistance/dependence (n=15) and intolerable side effects from other therapies (n=1). The average time from the diagnosis to initiation of tacrolimus was 5.3 years (range 0.3-13.3 years, median 6 years). The initial dosage of tacrolimus utilized was 0.1 mg/kg per day divided into two doses. The mean follow-up period was 6.5 months (range 2.5-18 months). Thirteen patients (81%) went into a complete remission within an average of 2 months (range 0.5-5.5 months), with 3 patients relapsing while on treatment. Three patients did not respond. Of these, 2 had partial remissions (13%) and 1 failed to respond. Adverse events included anemia (n=1), seizure (n=1), worsening or new-onset hypertension (n=5), and sepsis (n=1). All patients remain on tacrolimus. Tacrolimus is an effective, well-tolerated medication for treatment-resistant forms of nephrotic syndrome in children, with a complete remission rate of 81% and a partial remission rate of 13% (totaling 94%).

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Child; Child, Preschool; Drug Resistance; Female; Glucocorticoids; Humans; Hypertension, Renal; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrotic Syndrome; Prednisone; Retrospective Studies; Tacrolimus; Treatment Outcome

Withdrawal of corticosteroids from the immunosuppressive regimens of kidney transplant recipients has been associated with an increased risk of acute and chronic allograft rejection. Previous studies indicate that the risk of rejection is particularly high in African Americans.. We prospectively enrolled 44 African American kidney transplant recipients to participate in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids. No patient received antibody induction therapy. Prednisone was withdrawn from eligible patients free of acute rejection beginning as early as 3 months posttransplant, and followed for a minimum of 9 months posttransplant. Patients were followed for acute rejection and for changes in blood pressure, body weight, and serum creatinine concentrations before and after withdrawal of steroids.. Thirty of 44 patients (68%) were weaned off of prednisone. Follow-up after withdrawal of prednisone ranged from 3 to 26 months (mean, 14.3+/-7.7 months). Two of 30 patients (6.7%) developed acute rejection. At last follow-up, 27 of 30 patients (90%) remain steroid-free. Steroid withdrawal was associated with significant reductions in blood pressure.. Use of sirolimus and tacrolimus, without the use of induction antibody therapy, allows withdrawal of prednisone as early as 3 months posttransplant with low rates of subsequent acute rejection in African American kidney transplant recipients. Withdrawal of prednisone was associated with lower blood pressures and the need for fewer antihypertensive medications.

Topics: Adrenal Cortex Hormones; Adult; Aged; Black or African American; Diabetic Nephropathies; Drug Administration Schedule; Female; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Ohio; Retrospective Studies; Sirolimus; Tacrolimus

Topics: Adult; Female; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Liver Failure; Liver Transplantation; Renal Dialysis; Tacrolimus; Thrombosis