Evaluating the Safety and Rationale for Cinacalcet Posttransplant Hyperparathyroidism and Hypercalcemia.

unboundmedicine.com Evaluating the Safety and Rationale for Cinacalcet Posttransplant Hyperparathyroidism and Hypercalcemia.

Unbound MEDLINE

Links

Publisher Full Text

Authors

Coyne DW, Santos RD

Source

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons : 2014 Sep 15 pg

Pub Type(s)

EDITORIAL

Language

ENG

PubMed ID

25223316

Related Citations

• Hypercalcemia of primary hyperparathyroidism was treated by cinacalcet in a patient with liver cirrhosis.
• Hypercalcemia secondary to persistent hyperparathyroidism in kidney transplant patients: analysis after a year with cinacalcet.
• Cinacalcet for the treatment of hyperparathyroidism in kidney transplant recipients: a systematic review and meta-analysis.
• Cinacalcet improves bone density in post-kidney transplant hyperparathyroidism.
• Treatment with cinacalcet of secondary hyperparathyroidism after renal transplantation.
• Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism.
• Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride.
• Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism.

More

http://www.unboundmedicine.com/medline/citation/25223316/Evaluating_the_Safety_and_Rationale_for_Cinacalcet_Posttransplant_Hyperparathyroidism_and_Hypercalcemia_

Sent with Reeder

Alberto Reino Buelvas

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism.

unboundmedicine.com A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism.

Abstract

Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value <10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcet- versus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p < 0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p = 0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p < 0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.

Links

Publisher Full Text

Authors

Evenepoel P, Cooper K, Holdaas H, Messa P, Mourad G, Olgaard K, Rutkowski B, Schaefer H, Deng H, Torregrosa JV, Wuthrich RP, Yue S

Source

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons : 2014 Sep 15 pg

Pub Type(s)

JOURNAL ARTICLE

Language

ENG

PubMed ID

25225081

http://www.unboundmedicine.com/medline/citation/25225081/A_Randomized_Study_Evaluating_Cinacalcet_to_Treat_Hypercalcemia_in_Renal_Transplant_Recipients_With_Persistent_Hyperparathyroidism_

Sent with Reeder

Alberto Reino Buelvas

Prevalence and Risk Factors of Noncontrolled and Resistant Arterial Hypertension in Renal Transplant Recipients.

Transplantation - Published Ahead-of-Print Prevalence and Risk Factors of Noncontrolled and Resistant Arterial Hypertension in Renal Transplant Recipients.

Background: Arterial hypertension (HT) is common in renal transplant recipients (RTRs). Control of HT is not optimal in this high-risk population despite recommendations for target blood pressure levels under 130/80 mm Hg. Methods: We performed a cross-sectional analysis of the prevalence of uncontrolled HT, and using a Cox regression model, we identified the risk factors associated with resistant HT. Results: Eight hundred eleven RTRs (>1 year after transplantation) were included. A total of 10.5% were normotensive (<130/80 mm Hg without treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT. In univariate analysis, compared to controlled HT, the RH group had significantly higher body mass index and older donors, delayed graft function, prevalence of metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin, albuminuria, triglycerides and uric acid levels, and worse measured glomerular filtration rate (mGFR). In multivariate analysis, recipient age (P<0,001), mGFR (P=0.037), albuminuria (P<0.001), and metabolic syndrome (P=0.007) were significantly associated with RH. Association of metabolic syndrome with RH was much stronger than each of its components. Conclusion: Our data show that despite the recommendations issued by scientific societies, blood pressure control in RTRs is far from the recommended targets. At least a third of our patients (uncontrolled HT) did not receive optimal treatment and suffered therapeutic inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion emerged as strong predictors of poor HT control. Whether prevention and management of the metabolic syndrome and reduction of albuminuria could help to more consistently reach the blood pressure recommended targets deserves further investigation. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Prevalence_and_Risk_Factors_of_Noncontrolled_and.97957.pdf

Sent with Reeder

Enviado desde mi iPhone

Diarrhea After Kidney Transplantation: A New Look at a Frequ... : Transplantation

journals.lww.com Diarrhea After Kidney Transplantation: A New Look at a Frequ... : Transplantation

Diarrhea After Kidney Transplantation: A New Look at a Frequent Symptom

Aulagnon, Florence^1,2; Scemla, Anne^1,2; DeWolf, Susan³; Legendre, Christophe^1,2,4,5,6; Zuber, Julien^1,2,3,4,6,7

Abstract

Diarrhea is a frequent but overlooked complication of kidney transplantation. Diarrhea is repeatedly neglected, often considered by patients and clinicians an unavoidable side effect of immunosuppressive regimens. It is, however, associated with a significant impairment in life quality. Severe and chronic posttransplant diarrhea may lead to dehydration, malabsorption, rehospitalization, immunosuppression, noncompliance, and a greater risk of graft loss and death. There is thus a need to optimize and standardize the management of posttransplant diarrhea with consistent diagnostic and therapeutic strategies. A recent study has suggested that the increased sensitivity of molecular tools might help in early pathogen identification and guidance of antimicrobial treatment. Most bacterial and protozoan infections are readily curable with appropriate antimicrobial agents; cryptosporidiosis and C. difficile infections may however be complicated by relapsing courses. In addition, identification of enteric viral genomes in stool has further reduced posttransplant diarrhea of unknown origin. Chronic norovirus-related posttransplant diarrhea, arising from the interplay of the virus and immunosuppressive drugs, has emerged as a new challenge in the field. Prospective and controlled studies are necessary to evaluate the efficacy and safety of innovative anti-norovirus therapeutics, as well as optimal immunosuppressive regimens, to enable viral clearance while preventing rejection and donor-specific antibody formation. This review seeks to provide a basis for the design of future clinical prospective studies.

Copyright © 2014 by Lippincott Williams & Wilkins

http://journals.lww.com/transplantjournal/Abstract/2014/10270/Diarrhea_After_Kidney_Transplantation__A_New_Look.3.aspx

Sent with Reeder

Enviado desde mi iPad

A Paired Survival Analysis Comparing Hemodialysis and Kidney Transplantation From Deceased Elderly Donors Older Than 65 Years.

Transplantation - Published Ahead-of-Print A Paired Survival Analysis Comparing Hemodialysis and Kidney Transplantation From Deceased Elderly Donors Older Than 65 Years.

Background: Kidney transplantation from deceased donors aged 65 years or older is associated with suboptimal patient and graft survival. In large registries, survival is longer after kidney transplantation than when remaining on dialysis. However, whether recipients of these old grafts survive longer than their dialysis counterparts is unknown. Methods: We retrospectively assessed the outcomes of 5,230 recipients of first deceased donor grafts transplanted during the period of 1990 to 2010 in Catalonia, 915 of whom received grafts from donors 65 years or older. In a match-pair analysis, we aimed to pair each of 915 eligible cases with one control (1:1 ratio). Each pair had the same characteristics at the time of entering dialysis program: age, sex, primary renal disease, period of dialysis onset, and cardiovascular comorbidities. We found 823 pairs. Results: Patient survival of 823 recipients of elderly donors was significantly higher than that of their 823 matched dialysis waitlisted nontransplanted partners (91.6%, 74.5%, and 55.5% vs. 88.8%, 44.2%, and 18.1%, respectively at 1, 5, and 10 years; P<0.001). The probability of death after the first year was similar (8.1% transplant vs 10.3% dialysis; P=0.137); however, analyzing the whole period, the adjusted proportional risk of death was 2.66 (95% confidence interval, 2.21-3.20) times higher for patients remaining on dialysis than for transplanted patients (P<0.001). Conclusion: Our study demonstrates that despite the fact that kidney transplantation from elderly deceased donors is associated with reduced graft and patient survival, their paired counterpart patients remaining on dialysis have a risk of death 2.66 times higher. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/A_Paired_Survival_Analysis_Comparing_Hemodialysis.97979.pdf

Sent with Reeder

Enviado desde mi iPhone

Adenosine Triphosphate-Competitive mTOR Inhibitors: A New Class of Immunosuppressive Agents That Inhibit Allograft Rejection.

AJT Adenosine Triphosphate-Competitive mTOR Inhibitors: A New Class of Immunosuppressive Agents That Inhibit Allograft Rejection.

• Rosborough BR, Raïch-Regué D, Liu Q, et al. 
• Adenosine Triphosphate-Competitive mTOR Inhibitors: A New Class of Immunosuppressive Agents That Inhibit Allograft Rejection. [JOURNAL ARTICLE]
• Am J Transplant 2014 Sep; 14(9):2173-2180.

The mechanistic/mammalian target of rapamycin (mTOR) is inhibited clinically to suppress T cell function and prevent allograft rejection. mTOR is the kinase subunit of two mTOR-containing complexes, mTOR complex (mTORC) 1 and 2. Although mTORC1 is inhibited by the macrolide immunosuppressant rapamycin (RAPA), its efficacy may be limited by its inability to block mTORC1 completely and its limited effect on mTORC2. Adenosine triphosphate (ATP)-competitive mTOR inhibitors are an emerging class of mTOR inhibitors that compete with ATP at the mTOR active site and inhibit any mTOR-containing complex. Since this class of compounds has not been investigated for their immunosuppressive potential, our goal was to determine the influence of a prototypic ATP-competitive mTOR inhibitor on allograft survival. AZD8055 proved to be a potent suppressor of T cell proliferation. Moreover, a short, 10-day course of the agent successfully prolonged murine MHC-mismatched, vascularized heart transplant survival. This therapeutic effect was associated with increased graft-infiltrating regulatory T cells and reduced CD4(+) and CD8(+) T cell interferon-γ production. These studies establish for the first time, that ATP-competitive mTOR inhibition can prolong organ allograft survival and warrant further investigation of this next generation mTOR inhibitors.

http://www.unboundmedicine.com/medline/citation/25307040/Adenosine_Triphosphate_Competitive_mTOR_Inhibitors:_A_New_Class_of_Immunosuppressive_Agents_That_Inhibit_Allograft_Rejection_

Sent with Reeder

Enviado desde mi iPhone