Tacrolimus (FK506)-Associated Renal Pathology

Randhawa, Parmjeet; Starzl, Thomas E.; Demetris, Anthony J.

doi:10.1097/00125480-199707000-00032

Cited by 68 publications

(55 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, other changes were observed in the kidney including swelling of proximal tubules, hyalanosis and presences of hyaline casts in proximal and distal tubules. These changes were similar to the results of Randhawa et al (1997).…”

supporting

confidence: 90%

Spirulina protects against tacrolimus-induced hepatic and renal toxicity in rats: A biochemical and histological study

Elzawahry¹,

Abass²,

El-Haleem³

et al. 2016

J. Toxicol. Environ. Health Sci.

View full text Add to dashboard Cite

Tacrolimus is a powerful immunosuppressive agent with hepatotoxic and nephrotoxic effects. It has a protective role against many toxicants. This study was conducted to evaluate the possible protective role of spirulina against tacrolimus induced hepatotoxicity and nephrotoxicity. Forty adult male albino rats divided into 4 groups. Group I, control group, Group II, spirulina group (received spirulina 500 mg/Kg body weight (bw)/day orally), Group III, tacrolimus group (received tacrolimus 12 mg/kg bw/day orally); and Group VI, prophylactic group (orally administered spirulina for 3 days before and 28 days concurrently with tacrolimus in the same previous doses). Tacrolimus induced adverse effects on both liver and kidney functions and structure that was manifested by elevated hepatic transaminases, total and direct bilirubin, albumin, blood urea nitrogen, serum creatinine and creatinine clearance. There was a significant decrease in serum total antioxidant capacity (TAC) and hepatic and renal total thiol molecules (TTM), with a significant increase in serum malondialdehyde in tacrolimus group. Histopathologically, tacrolimus induced swelling and granulation of hepatocytes, congestion of blood sinusoids and degeneration of bile ductiles, glomerular hypertrophy and segmentation, swelling, degeneration and hyalinosis of renal tubules. Spirulina pre-and co-treatment significantly improved these deleterious effects. This was accompanied by partial restoration of the expression of PCNA near to the normal level observed in control rats. Moreover, spirulina treatment did not alter the trough blood tacrolimus levels or tacrolimus-induced immunosuppression. Further studies are warranted to evaluate whether transplant patients on tacrolimus treatment may benefit from the protective effects of spirulina.

show abstract

supporting

confidence: 90%

Spirulina protects against tacrolimus-induced hepatic and renal toxicity in rats: A biochemical and histological study

Elzawahry¹,

Abass²,

El-Haleem³

et al. 2016

J. Toxicol. Environ. Health Sci.

View full text Add to dashboard Cite

show abstract

“…It is a selective anti-T-lymphocyte agent and is used to prevent allograft rejection after human liver, kidney and heart transplantation, as well as autoimmune diseases [1], [2], [3], [4]. FK506 treatment induces nephrotoxicity in 17–44% of renal transplant recipients and in 18–42% of liver transplant recipients [5]. This has limited the clinical use of FK506.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Lee

Kang

et al. 2017

Journal of Ginseng Research

View full text Add to dashboard Cite

BackgroundCompound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated.MethodsLLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay.ResultsThe reduction in LLC-PK1 cell viability by 60μM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60μM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60μM FK506 treatment, whereas it was decreased after cotreatment with KRG.ConclusionTaken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

show abstract

“…2,3 The well-known adverse effects of tacrolimus include nephrotoxicity, 4 hypertension, 5 neurotoxicity, [6][7][8][9][10] and glucose intolerance. 11,12 Posterior reversible encephalopathy syndrome was f irst reported in 1996 by Hinchey and colleagues, 13 who described a reversible syndrome associated with headache, altered mental function, seizures, and visual disturbances.…”

Section: Discussionmentioning

confidence: 99%

Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy

Kapoor¹,

Birks²,

Lenneman³

et al. 2017

Texas Heart Institute Journal

View full text Add to dashboard Cite

Posterior reversible encephalopathy syndrome (PRES) is an infrequent neurologic sequela occurring in response to tacrolimus therapy. One of our recent cases is a prime example of the difficulties faced by physicians when they attempt to balance immunosuppression and drug toxicities. We highlight the most relevant features of our case, in an attempt to bring greater understanding of the pathophysiology of PRES. Further, we discuss the methods typically used to diagnose PRES, and we attempt to consolidate previous knowledge within the scope of PRES in a patient who was receiving immunosuppression after orthotopic heart transplantation. Case ReportA 37-year-old woman with a medical history of type 2 diabetes mellitus and hypothyroidism presented with generalized tonic-clonic seizures 16 days after orthotopic heart transplantation. Her home medications included 6 mg of tacrolimus, 1,500 mg of mycophenolate mofetil, and 20 mg of prednisone, each taken orally twice daily; trimethoprim/sulfamethoxazole; and valganciclovir. She had had 3 seizures that involved tongue-biting and stool incontinence. Initially, she was treated with diazepam, intravenous phenytoin, and intravenous ceftriaxone for suspected meningitis, a frequent sequela in an immunocompromised patient. On admission, the patient was somnolent but rousable and reported a throbbing temporal headache. Her blood pressure was 130/77 mmHg, and her pulse was 110 beats/min. No focal deficits were present upon neurologic examination. Laboratory data included a white blood cell count of 16.4 ×10 9 cells/L, a potassium level of 5.4 mmol/L, a magnesium level of 1.77 mmol/L, a blood urea nitrogen level of 47 mg/dL, and a creatinine level of 1.25 mg/dL with an anion gap of 23 mmol/L. Her tacrolimus levels at the time of admission were 8.4 ng/mL. Her previous tacrolimus levels had been 9.7 to 13.9 µg/mL, which, in a normotensive patient without a tremor, made toxicity less likely. Her examination included a lumbar puncture that was negative for any infectious process, an electroencephalogram that showed no evidence of seizure activity, and a computed tomogram of the head that showed no intracranial bleeding. A brain magnetic resonance image (MRI) was ordered, and the findings suggested PRES (Fig. 1A).On the basis of these findings, we discontinued tacrolimus and replaced it with 2 mg/d of oral sirolimus. A repeat MRI showed resolution of the patient's high signal intensities (Fig. 1B). The mycophenolate mofetil was continued at 1,500 mg and the prednisone was slightly reduced to 15 mg, twice a day. The patient was discharged

show abstract

Tacrolimus (FK506)-Associated Renal Pathology

Cited by 68 publications

References 66 publications

Spirulina protects against tacrolimus-induced hepatic and renal toxicity in rats: A biochemical and histological study

Spirulina protects against tacrolimus-induced hepatic and renal toxicity in rats: A biochemical and histological study

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Posterior Reversible Encephalopathy Syndrome after Heart Transplantation: Diagnosis and Immunosuppressive Therapy

Contact Info

Product

Resources

About