Literature DB >> 25815268

Conversion from calcineurin inhibitors to mTOR inhibitors stabilizes diabetic and hypertensive nephropathy after liver transplant.

José M Álamo1, Claudia Olivares1, Lydia Barrera1, Luis M Marín1, Gonzalo Suarez1, Carmen Bernal1, Juan Serrano1, Jordi Muntané1, Francisco J Padillo1, Miguel A Gómez1.   

Abstract

AIM: To investigate if conversion to the mammalian target of rapamycin inhibitors (mTORi) improves renal function in diabetic and/or hypertensive liver transplant patients immunosuppressed with tacrolimus or cyclosporine.
METHODS: The study included 86 liver graft recipients immunosuppressed with mTORi treatment after orthotopic liver transplantation (OLT), including all liver recipients with worsening renal function before conversion to mTORi (n = 55 patients) and recipients with normal renal function who converted to mTORi for other reasons (n = 31 patients). We identified patients with diabetes mellitus (n = 28), arterial hypertension (n = 27), proteinuria (n = 27) and all three factors (n = 8) (some patients have hypertension and diabetes and no proteinuria). The primary endpoint was evolution in renal function defined as the development in plasma creatinine as a function of diabetes mellitus (DM), hypertension (HT) or proteinuria. We required elevated serum creatinine for at least two weeks to define renal dysfunction.
RESULTS: Only patients that converted because of renal failure with plasma creatinine levels > 1.5 mg/dL showed an improvement of renal function (2.14 to 1.77 mg/dL) (P = 0.02). Patients with DM showed no improvement of serum creatinine levels (1.31 mg/dL to 1.37 mg/dL) compared with non DM patients (1.31 mg/dL to 1.15 mg/dL) (P = 0.01), HT patients (1.48 mg/dL to 1.5 mg/dL) with non HT patients (1.21mg/dL to 1.08 mg/dL) and patients with proteinuria (1.44 mg/dL to 1.41 mg/dL) and no proteinuria (1.31 mg/dL to 1.11 mg/dL).
CONCLUSION: In OLT recipients with diabetes or hypertensive nephropathy, conversion to mTORi does not improve renal function but stabilizes plasma levels of creatinine. Proteinuria is not a contraindication to conversion to mTORi; it also stabilizes renal function. Conversion to mTORi should only be avoided in patients with diabetes, hypertension and proteinuria.

Entities:  

Keywords:  Diabetes; Hypertension; Liver transplant; Mammalian target of rapamycin inhibitors; Renal dysfunction

Year:  2015        PMID: 25815268      PMCID: PMC4371158          DOI: 10.5500/wjt.v5.i1.19

Source DB:  PubMed          Journal:  World J Transplant        ISSN: 2220-3230


  31 in total

1.  Sirolimus in patients after liver transplantation.

Authors:  D Kniepeiss; F Iberer; B Grasser; S Schaffellner; K H Tscheliessnigg
Journal:  Transplant Proc       Date:  2003-03       Impact factor: 1.066

2.  Late-onset proteinuria after antithymocyte globulin induction and de novo sirolimus monotherapy in kidney transplant recipients.

Authors:  Oliver Thomusch; Dietlind Tittelbach-Helmrich; Gabriel Seifert; Przemyslaw Pisarski
Journal:  Transplantation       Date:  2011-12-15       Impact factor: 4.939

3.  Post-transplantation proteinuria and sirolimus.

Authors:  Hassane Izzedine; Isabelle Brocheriou; Camille Frances
Journal:  N Engl J Med       Date:  2005-11-10       Impact factor: 91.245

Review 4.  Immunosuppression in liver transplantation.

Authors:  David J Post; David D Douglas; David C Mulligan
Journal:  Liver Transpl       Date:  2005-11       Impact factor: 5.799

5.  Sirolimus and proteinuria in renal transplant patients: evidence for a dose-dependent effect on slit diaphragm-associated proteins.

Authors:  Giovanni Stallone; Barbara Infante; Paola Pontrelli; Maddalena Gigante; Eustacchio Montemurno; Antonia Loverre; Michele Rossini; Francesco Paolo Schena; Giuseppe Grandaliano; Loreto Gesualdo
Journal:  Transplantation       Date:  2011-05-15       Impact factor: 4.939

Review 6.  Need for better diabetes treatment for improved renal outcome.

Authors:  Peter Rossing; Dick de Zeeuw
Journal:  Kidney Int Suppl       Date:  2011-03       Impact factor: 10.545

7.  Sirolimus-induced thrombotic microangiopathy is associated with decreased expression of vascular endothelial growth factor in kidneys.

Authors:  Hervé Sartelet; Olivier Toupance; Marianne Lorenzato; Fouad Fadel; Laure Hélène Noel; Eymeric Lagonotte; Philippe Birembaut; Jacques Chanard; Philippe Rieu
Journal:  Am J Transplant       Date:  2005-10       Impact factor: 8.086

8.  Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation.

Authors:  Brian R Stephany; Joshua J Augustine; Venkatesh Krishnamurthi; David A Goldfarb; Stuart M Flechner; William E Braun; Donald E Hricik; Vincent W Dennis; Emilio D Poggio
Journal:  Transplantation       Date:  2006-08-15       Impact factor: 4.939

9.  Rescue immunosuppression with mammalian target of rapamycin inhibitor drugs in liver transplantation.

Authors:  J M A Mártinez; L B Pulido; C B Bellido; D D Usero; L T Aguilar; J L G Moreno; G S Artacho; J S Díez-Canedo; L M M Gómez; M A G Bravo
Journal:  Transplant Proc       Date:  2010-03       Impact factor: 1.066

10.  Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols.

Authors:  Fritz Diekmann; Alex Gutiérrez-Dalmau; Sonia López; Federico Cofán; Núria Esforzado; María José Ricart; Esther Rossich; Núria Saval; José Vicente Torregrosa; Federico Oppenheimer; Josep M Campistol
Journal:  Nephrol Dial Transplant       Date:  2007-04-23       Impact factor: 5.992

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