Cyclosporine versus tacrolimus in kidney transplantation: are there differences in nephrotoxicity?

Martins, La Salete; Ventura, Alessandra; Branco, Anabela; Carvalho, Maria João; Henriques, António Castro; Dias, Leonídio; Sarmento, António; Amil, Morgane

doi:10.1016/j.transproceed.2004.03.083

Cited by 34 publications

(17 citation statements)

References 14 publications

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“…In the longer-term CNIs cause chronic non-reversible changes that are characterised by interstitial fibrosis and obliterative arteriolar changes due to fibrous intimal thickening [90]. Although both cyclosporine and tacrolimus are nephrotoxic, recent studies suggest this may be less of a problem with tacrolimus [89,91,92]. Hypertension is a common consequence of CNI treatment, in part secondary to the renal effect [93] and again may be less common with tacrolimus.…”

Section: Side Effectsmentioning

confidence: 99%

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Taylor

Watson

Bradley

2005

Critical Reviews in Oncology/Hematology

380

250

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Section: Side Effectsmentioning

confidence: 99%

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Taylor

Watson

Bradley

2005

Critical Reviews in Oncology/Hematology

380

250

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“…[2324] Although early reports in transplant recipients supported these findings,[2526] a recent meta-analysis showed that the risk of nephrotoxicity in transplant allografts was similar for CyA and tacrolimus. [27] Although there are no comparative reports, the present retrospective review did not show differences in histological changes and proportion of patients with nephrotoxicity following therapy with either agent.…”

Section: Discussionmentioning

confidence: 99%

Calcineurin inhibitor induced nephrotoxicity in steroid resistant nephrotic syndrome

et al. 2013

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Prolonged therapy with calcineurin inhibitors (CNI) is effective in patients with difficult nephrotic syndrome. However, information on prevalence and risk factors for nephrotoxicity in children with steroid-resistant nephrotic syndrome is limited. This retrospective observational study was conducted on 40 patients with steroid-resistant nephrotic syndrome treated with cyclosporine (CyA) (n = 28) or tacrolimus (n = 12) for more than 2 years. Nephrotoxicity was defined by the presence of striped fibrosis involving ≥10% of the interstitium or nodular hyalinosis in more than one arteriole. Ten additional parameters were graded semi-quantitatively. Continuous data are presented as median and interquartile range (IQR). The median (IQR) age at onset of nephrotic syndrome and CNI therapy were 30 (21-45) and 49.5 (40-102.5) months. A second renal biopsy, following 30 (26-35) months of CNI therapy, showed histological toxicity in 10 (25%) patients. Toxicity was seen in 7 and 3 patients receiving CyA and tacrolimus, respectively, and 5 patients each with minimal change and focal segmental glomerulosclerosis. Therapy with CNI was associated with significant increases in scores for global glomerulosclerosis, tubular atrophy, interstitial fibrosis, nonnodular arteriolar hyalinosis (P < –0.001 for all), arteriolar smooth-muscle vacuolization (P = –0.02), juxtaglomerular hyperplasia (P = –0.002), and tubular microcalcinosis (P = –0.06). Risk factors for nephrotoxicity were initial resistance (OR 9; 95% CI 1.0-80.1; P = –0.049); dose of CyA (OR 9.2; 95% CI 1.1-74.6; P = –0.037); duration of heavy proteinuria (OR 1.2; 95% CI 1.0-1.4; P = –0.023); and hypertension during therapy (OR 6; 95% CI 1.3-28.3; P = –0.023). Following prolonged CNI therapy, one in four biopsies show features of toxicity. Prolonged duration of heavy proteinuria, hypertension, initial steroid resistance and high CyA dose predict the occurrence of nephrotoxicity.

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“…Both one-and two-compartment models with or without a lag time and first-order absorption and elimination were compared in this study [20][21][22]. Typical value of the absorption rate constant (Ka) could not be estimated because of the lack of concentration data in absorption and distribution phase.…”

Section: Structural Model Buildingmentioning

confidence: 99%

Population Pharmacokinetic Analysis of Oral Tacrolimus in Patients with Glomerulonephritis

Shim¹,

Kim²,

Choi³

et al. 2016

Int J Clin Pharmacol Pharmacother

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Objective: Tacrolimus as an immunosuppressant is used to treat for several types of glomerulonephritis. Narrow therapeutic window and huge interindividual variability of tacrolimus make it impossible to predict its serum level. Hence, the purpose of this study was to derive population pharmacokinetic model for tacrolimus in glomerulonephritis patients. Materials and methods: Adult patients diagnosed with glomerulonephritis and treated with oral tacrolimus were included. Electronic medical records were reviewed retrospectively to access clinical findings and demographic data. Population pharmacokinetics of tacrolimus was evaluated using nonlinear mixed effect model by first-order conditional estimation with interaction algorithm. Results: One hundred and forty-five patients were included in this study and one thousand and nine hundreds thirty-eight blood samples were analyzed. The estimated apparent clearance (CL/F) was 19.5 L/h, and apparent volume of distribution (V/F) was 380 L. The final model suggested that serum creatinine levels were negatively correlated with both CL/F and V/F whereas serum albumin levels were positively associated with V/F. Conclusion: Various factors affecting tacrolimus pharmacokinetics were explored. The findings of this study pointed out that tacrolimus pharmacokinetics were related to patients' kidney function and serum albumin level in glomerulonephritis patients. Developed model may guide individualized tacrolimus therapy in glomerulonephritis patients and improve therapeutic outcomes in glomerulonephritis patients.

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Cyclosporine versus tacrolimus in kidney transplantation: are there differences in nephrotoxicity?

Cited by 34 publications

References 14 publications

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Calcineurin inhibitor induced nephrotoxicity in steroid resistant nephrotic syndrome

Population Pharmacokinetic Analysis of Oral Tacrolimus in Patients with Glomerulonephritis

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