Sustained Renal Response to Mycophenolate Mofetil and CNI Taper Promotes Survival in Liver Transplant Patients with CNI-Related Renal Dysfunction

Kornberg, Arno; Küpper, B.; Thrum, Katharina; Krause, B.; Büchler, Peter; Kornberg, Jennifer; Sappler, A.; Altendorf-Hofmann, A.; Wilberg, J.; Friess, Helmut

doi:10.1007/s10620-010-1386-z

Cited by 16 publications

(10 citation statements)

References 42 publications

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“…These observed differences in renal function between each group were not unexpected, particularly as acute renal failure is common directly after LT, and GFR has been shown to decrease and then stabilize at around nine months after transplantation . For patients in Groups C and D, the change in GFR mirrored the results observed in several clinical trials, where improvements in renal function have occurred following introduction of MMF and a marked reduction in doses of CNIs . The greatest improvement in renal function was observed for Group D, where a change of +11.1 mL/min/1.73 m 2 was noted at 12 months.…”

Section: Discussionsupporting

confidence: 59%

“…Mycophenolate mofetil (MMF) is a frequent constituent of low toxicity, CNI‐sparing immunosuppressive regimens. Several studies have demonstrated that MMF does not cause nephrotoxicity and can improve renal function in patients following LT, concomitant with a reduction in CNI . Data from controlled clinical trials or registries indicate that MMF may benefit patients following LT with respect to renal function and by reducing metabolic abnormalities .…”

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confidence: 99%

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Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non‐interventional, multicenter study (LOBSTER)

Jonas

Ganten

Grannas

et al. 2013

Clinical Transplantation

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The benefits of calcineurin inhibitor (CNI)-sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real-life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety-seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n = 263): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A-D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m(2) in Groups A-D. At 12 months, this decreased to 66 mL/min/1.73 m(2) in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m(2) ). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non‐interventional, multicenter study (LOBSTER)

Jonas

Ganten

Grannas

et al. 2013

Clinical Transplantation

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“…Long‐term follow‐up data over 60 months from a study by Kornberg et al . demonstrated sustained renal response after conversion to reduced CNI and MMF therapy .…”

Section: Strategies For Avoiding/improving Chronic Renal Dysfunctionmentioning

confidence: 99%

Calcineurin inhibitors in liver transplantation – still champions or threatened by serious competitors?

Beckebaum

Cicinnati

Radtke

et al. 2013

Liver International

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Current strategies for immunosuppression in liver transplant (LT) recipients include the design of protocols targeting a more individualized approach to reduce risk factors such as renal failure, cardiovascular complications and malignancies. Renal injury in LT recipients may be often multifactorial and is associated with increased risk of post-transplant morbidity and mortality. The quest for low toxicity immunosuppressive regimens has been challenging and resulted in CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil (MMF) and/or mammalian target of rapamycin inhibitor-based immunosuppressive regimens. Use of antibody induction to delay CNI administration may be an option in particular in immunocompromized, critically ill patients with high MELD scores. Protocols including MMF introduction and concomitant CNI minimization have the potential to recover renal function even in the medium and long term after LT. We review on hot topics in the prevention and management of acute and chronic renal injury in LT patients. For this purpose, we present and critically discuss results from immunosuppressive studies published in the current literature or presented at recent LT meetings.Prevention and treatment of side effects of immunosuppressive drugs, namely calcineurin inhibitors (CNI), have gained an important role in the liver transplant (LT) setting. CNI are deemed to be associated with acute and chronic nephrotoxicity, de novo malignancies and cardiovascular or metabolic complications (1-3). In addition, causes of structural renal damage before and after LT may include chronic liver diseases associated with concomitant kidney injury (e.g. glomerulonephritis in viral hepatitis) and cardiovascular risk factors (arterial hypertension, diabetes).In acute CNI-induced nephrotoxicity, vasoconstriction in the afferent arterioles followed by a decrease in renal blood flow and reduced urinary excretion plays an essential role (Fig. 1) (4). Vasoconstriction is caused by an imbalance in the release of vasodilatory factors (prostaglandin E2, nitric oxide) and vasoconstrictive factors (thromboxane A2, endothelin 1, angiotensin II) and activation of the sympathetic nervous system. Renal function usually improves upon CNI cessation, whereas prolonged CNI-induced vasoconstriction may cause histological damage.

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“…There was significant improvement in eGFR over a 1 year follow-up period in the MMF and low dose CNI arm, without episodes of rejection. Furthermore, two other observational studies demonstrated significant GFR increases with conversion from standard CNI to reduced-dose CNI + MMF without adverse events (67, 70). The main benefit of this CNI reduction strategy was seen in applying this regimen within 1–2 years of LT.…”

Section: Key Points and Recommendationsmentioning

confidence: 92%

“…Renal protection late (>12 months) after LT Despite evidence of using mTOR-Is and MMF early after LT to minimize CNI nephrotoxicity, this strategy does not seem to apply as well later after LT (62)(63)(64)(65)(66)(67)(68)(69) (62). There was significant improvement in eGFR over a 1-year follow-up period in the MMF and low-dose CNI arm, without episodes of rejection.…”

Section: Key Points and Recommendationsmentioning

confidence: 99%

Protecting the Kidney in Liver Transplant Recipients: Practicee-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

Levitsky

O’Leary

Asrani

et al. 2016

American Journal of Transplantation

117

104

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Acute and chronic kidney disease after liver transplantation is common and results in significant morbidity and mortality. The introduction of MELD has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplants performed. Thus, kidney dysfunction in this population is typically multifactorial and related to pre-existing conditions, pre-transplant renal injury, peri-operative events, and post-transplant nephrotoxic immunosuppressive therapies. The management of kidney disease following liver transplantation is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Also, immunological factors such as antibody-mediated rejection have become of greater interest given the rising liver-kidney transplant population. Therefore this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

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Sustained Renal Response to Mycophenolate Mofetil and CNI Taper Promotes Survival in Liver Transplant Patients with CNI-Related Renal Dysfunction

Abstract: Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.

Cited by 16 publications

References 42 publications

Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non‐interventional, multicenter study (LOBSTER)

Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non‐interventional, multicenter study (LOBSTER)

Calcineurin inhibitors in liver transplantation – still champions or threatened by serious competitors?

Protecting the Kidney in Liver Transplant Recipients: Practicee-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

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