Acute Renal Failure Following Kidney Transplantation Associated with Myoglobinuria in Patients Treated with Rapamycin

Pelletier, Ronald P.; Nádasdy, Tibor; Nadasdy, Gyongyi; Satoskar, Anjali A.; Tewari, Arun K.; Cotrill, Jeffrey A.; Henry, Mitchell L.; Rajab, Amer; Ferguson, Ronald M.

doi:10.1097/01.tp.0000230310.27913.01

Cited by 15 publications

(4 citation statements)

References 17 publications

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“…Acute tubular necrosis (ATN) is the histological diagnosis and principal cause of DGF. However, myoglobinuria and myoglobin casts have also been reported in four patients with sustained DGF (+14 days) among a series of 14 patients with myoglobin casts, and acute renal failure (ARF) was seen for 5–434 days post‐transplantation in eight of these patients, all of whom were receiving sirolimus [31].…”

Section: Delayed Graft Functionmentioning

confidence: 99%

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation

Campistol

Cockwell

Diekmann

et al. 2009

Transplant International

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Summary m‐TOR inhibitors (e.g. sirolimus) are well‐tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long‐term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side‐effects including impaired wound‐healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side‐effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.

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Section: Delayed Graft Functionmentioning

confidence: 99%

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation

Campistol

Cockwell

Diekmann

et al. 2009

Transplant International

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“…While in earlier reports it was a widely hold believe that the general cause of myoglobinuric ARF is the formation of myoglobin aggregates and renal tubular obstruction, leading to impairment of primary urine flow and reabsorption [8][9][10], recent studies have shown the development of oxidative stress under the conditions of myoglobinuria, accompanied by the increased production of ROS and lipid peroxidation [11,12]. The heme of a myoglobin molecule is thought to play the key role in this process.…”

Section: Introductionmentioning

confidence: 99%

Myoglobin causes oxidative stress, increase of NO production and dysfunction of kidney's mitochondria

Plotnikov

Chupyrkina

Pevzner

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

112

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Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the direct effect of myoglobin on renal tubules and isolated kidney mitochondria while measuring mitochondrial respiratory control, production of reactive oxygen and nitrogen species and lipid peroxidation. In parallel, we evaluated mitochondrial damage under myoglobinurea in vivo. An increase of lipid peroxidation products in kidney mitochondria and release of cytochrome c was detected on the first day of myoglobinuria. In mitochondria incubated with myoglobin we detected respiratory control drop, uncoupling of oxidative phosphorylation, an increase of lipid peroxidation products and stimulated NO synthesis. Mitochondrial pore inhibitor, cyclosporine A, mitochondria-targeted antioxidant (SkQ1) and deferoxamine (Fe-chelator and ferryl-myoglobin reducer) abrogated these events. Similar effects (oxidative stress and mitochondrial dysfunction) were revealed when myoglobin was added to isolated renal tubules. Thus, rhabdomyolysis can be considered as oxidative stress-mediated pathology with mitochondria to be the primary target and possibly the source of reactive oxygen and nitrogen species. We speculate that rhabdomyolysis-induced kidney damage involves direct interaction of myoglobin with mitochondria possibly resulting in iron ions release from myoglobin's heme, which promotes the peroxidation of mitochondrial membranes. Usage of mitochondrial permeability transition blockers, Fe-chelators or mitochondria-targeted antioxidants, may bring salvage from this pathology.

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“…However, a study has shown low sensitivity to these indicators in an early renal damage [14]. Study also found a correlation of increased serum levels of Mb and early kidney damage caused by heart attack [15], suggesting that serum Mb, Scr, blood UN index all have the advantages of accuracy and high sensitivity in the diagnosis of early renal function damage in SHR [16]. Quite a large amount of evidence suggests that pathophysiological mechanisms involved in Mb uric conditions are associated with renal dysfunction as well as important laboratory morphologic considerations [17, 18] based on high serum Mb or tissue Mb.…”

Section: Introductionmentioning

confidence: 99%

Danhong Injection Protects Against Hypertension-Induced Renal Injury Via Down-Regulation of Myoglobin Expression in Spontaneously Hypertensive Rats

Orgah

Wang

Yang

et al. 2018

Kidney Blood Press Res

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Background/Aims: High blood pressure is a major risk factor for chronic kidney disease. Currently, single-target anti-hypertensive drugs are not designed for high blood pressure-related organ damages. Danhong injection (DHI), made from the aqueous extracts of Radix Salviae miltiorrhizae and Flos Carthamus tinctorius, has various pharmacological effects, including BP lowering in SHR, mediated by the reduction of vascular remodeling and the up-regulation of Kallikrein-kinin system published recently by our team, yet if it renders renal protection remains unknown. The current study demonstrated a protective role of DHI in renal injury caused by hypertension and identified its molecular targets in the kidney of spontaneously hypertensive rats (SHR). Methods: Adult SHR and age/gender-matched normotensive Wistar-Kyoto (WKY) rats were treated with DHI, Losartan, or saline for 4 weeks. Serum levels of Creatinine (CRE), Micro-albumin (mAlb), Beta2-microglobulin (β2-MG), and Uric acid (UA) were detected using ELISA kits. Renal pathology was examined by hematoxylin and Eosin (H&E) stains. Microarray analysis was performed on kidney tissues, and gene expression changes were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Results: Renal histopathological scores showed that SHR exhibited serious kidney injury compared to normotensive WKY rats. The intervention with DHI potently suppressed the renal injury biomarker (KIM-1) and kidney lesions compared to the untreated hypertensive subjects. Microarray analysis revealed that among the 124 genes that were differentially expressed by DHI treatment in SHR kidney, down-regulation of renal myoglobin (Mb) gene was the most prominent and was subsequently confirmed by qRT-PCR and Western blot analysis. Conclusion: Hypertension-induced renal injury in SHR may be alleviated by DHI in part by local suppression of Kidney injury molecule-1 and down-regulation of Myoglobin. However, if this effect is independent of the known anti-hypertensive action of DHI in blood vessel remains to be determined.

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Acute Renal Failure Following Kidney Transplantation Associated with Myoglobinuria in Patients Treated with Rapamycin

Abstract: We conclude that myoglobinuria with myoglobin cast formation can occur following rapamycin administration, and may be a causative factor in the development of unexpected severe acute renal dysfunction.

Cited by 15 publications

References 17 publications

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation

Myoglobin causes oxidative stress, increase of NO production and dysfunction of kidney's mitochondria

Danhong Injection Protects Against Hypertension-Induced Renal Injury Via Down-Regulation of Myoglobin Expression in Spontaneously Hypertensive Rats

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