Myoglobinuric Acute Renal Failure Research Articles

A histological examination of the effects of Ferula elaeochytris extract on kidney and liver tissues in myoglobinuric acute renal failure

ABSTRACT Myoglobinuric acute renal failure (MARF) is a structural and functional disorder that occurs in the kidney following the release of muscle cell contents into the circulation. In this present study, possible protective and curative effects of Ferula elaeochytris extract against kidney and liver damage in experimentally induced MARF in a rat model were investigated. 3–4 Month-old, 200–250 g Sprague Dawley rats were divided into 8 equal groups with 7 rats per group. Group I was a no-intervention Control group. All groups except for the Group I were dehydrated for 16 hours. Following this dehydration, 50% v/v aqueous glycerol solution was injected into both hind leg muscles of the animals, at a dose of 8 ml/kg. The rats were given physiological saline (SF) once orally before the model was administered (Group II) and after the model was administered (Group V). Similarly, two different doses of Ferula elaeochytris root extract (40 mg/kg and 80 mg/kg) were dissolved in 2 ml of SF and administered orally before (Groups III and IV) and after (Group VI, VII) the model was created. Following the experimental period, kidney and liver tissues were removed from all groups, and fixed in 10% neutral formaldehyde solution for light microscopic examinations. Intracellular vacuolization, enlargement in the Bowman’s space, widespread atrophy in the tubular structures, luminal enlargement, and desquamation were detected in the kidney tissue sections of all the experimental model groups. In the liver tissue sections, was detected hepatocyte degeneration, intracellular vacuolization, irregularity in cell membrane borders, and apoptotic bodies. These histopathological consequences of MARF were evaluated for all groups, and whereas a curative effect of Ferula elaeochytris could be seen, its protective effect was higher than its curative effect.

Efficacy of orally administered montmorillonite in myoglobinuric acute renal failure model in male rats.

Acute kidney injury can be associated with serious consequences and therefore early treatment is critical to decreasing mortality and morbidity rate. We evaluated the effect of montmorillonite, the clay with strong cation exchange capacity, on the AKI model in rats. Glycerol (50% solution, 10 ml/kg) was injected in the rat hind limbs to induce AKI. 24 hr after induction of acute kidney injury, the rats received oral doses of montmorillonite (0.5 g/kg or 1 g/kg), or sodium polystyrene sulfonate (1 g/kg) for three consecutive days. Glycine induced acute kidney injury in rats with high levels of urea (336.60± 28.19 mg/dl), creatinine (4.10± 0.21 mg/dl), potassium (6.15 ± 0.28 mEq/L), and calcium (11.52 ± 0.19 mg/dl). Both doses of montmorillonite (0.5 and 1 g/kg) improved the serum urea (222.66± 10.02 and 170.20±8.06, P<0.05), creatinine (1.86±0.1, 2.05± 0.11, P<0.05), potassium (4.68 ± 0.4, 4.73 ± 0.34, P<0.001) and calcium (11.15 ± 0.17, 10.75 ± 0.25, P<0.01) levels. Treatment with montmorillonite especially at a high dose reduced the kidney pathological findings including, tubular necrosis, amorphous protein aggregation, and cell shedding into the distal and proximal tubule lumen. However, administration of SPS could not significantly decrease the severity of damages. According to the results of this study, as well as the physicochemical properties of montmorillonite, such as high ion exchange capacity and low side effects, montmorillonite can be a low-cost and effective treatment option to reduce and improve the complications of acute kidney injury. However, the efficacy of this compound in human and clinical studies needs to be investigated.

Amelioration of Rhabdomyolysis-Induced Myoglobinuric Acute Renal Failure by Citrullus lanatus Seeds

Citrullus lanatus (Thunb.) (Cucerbitaceae) is a trailing annual herb native to India, Nigeria, and Africa, commonly known as Matsum and Nakai. It thrives in all tropical, subtropical, and warm temperate areas with hot summers. In India, seeds have long been used to treat hypotensive and diuretic effects, as well as kidney stones and urinary passages. This study looked at the effects of a methanol extract of C. lanatus seeds (MCL) on rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) in Wistar rats. Five groups (n = 5) of male Albino Wistar rats weighing 150–200 g were formed. A single intramuscular injection of glycerol (GL) (8 ml/kg) was used to induce ARF. Following GL injection, all animals were sacrificed and blood was collected. Renal function tests utilizing blood urea nitrogen (BUN) and creatinine were performed on freshly separated serum. The right kidney was stored in 10% buffered formalin for histological sectioning, and the amount of lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) activity were all measured. The data were analyzed using a one-way ANOVA and Dunnett’s test. *P &gt; 0.05 was considered statistically significant. Animals pre-treated with MCL (100 and 300 mg kg-1, p.o.) for 7 days before GL dramatically altered and restored serum creatinine, BUN, creatinine clearance, urea clearance, and renal morphology in comparison to the GL-treated group. Oxidative stress markers such as lipid peroxidation, SOD, CAT, and GSH were also dramatically improved. The findings of this study suggest that C. lanatus seed has a possible anti-GL-induced ARF effect, verifying its ethnomedicinal use.

Donepezil protects glycerol-induced acute renal failure through the cholinergic anti-inflammatory and nitric oxide pathway in rats

Objectives Inflammation as well as oxygen metabolite play important roles in renal injury during pathogenesis of rhabdomyolysis induced myoglobinuric acute renal failure (ARF). The aim of this study was to investigate the protective effects of donepezil on immune responses in rats with glycerol-induced ARF. Methods Sixty male rats were randomly divided into six groups, the rats were given normal saline (10 ml/kg, i.m.), glycerol (50%, 10 ml/kg, i.m.), glycerol plus dexamethasone (0.1 mg/kg, i.g.), and glycerol plus donepezil (1, 5 and 10 mg/kg, i.g.) respectively. After two weeks of glycerol injections, the kidney tissues and blood samples were harvested for future biochemical and pathology analysis. The levels of creatinine (Cr) and urea nitrogen (BUN) in plasma, the content of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity, total nitric oxide synthase (TNOS), inducible nitric oxide synthase (iNOS), endothelial NO synthase (eNOS) were evaluated in renal tissues. In addition, interleukin-6 (IL-6), tumor necrosis factors-α (TNF-α) in renal tissues were also determined. Results Donepezil treatment protected rats from renal dysfunction in a dose-dependent manner and through the cholinergic anti-inflammatory pathway. Additionally, donepezil significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the IL-6, TNF-α, nitric oxide content and oxidative damage. Conclusions These data indicate that donepezil exerts a protective anti-inflammatory effect during ARF through the cholinergic pathway and Nitric oxide pathway. In addition, this study could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation and other injury.

The curative effects of methylsulfonylmethane against glycerol-induced acute renal failure in rats

The present study was performed to explore the curative effect of Methylsulfonylmethane (MSM) in an experimental model of myoglobinuric acute renal failure (ARF). In this experimental model, Rats were injected with 50% glycerol (10 mL/kg, im) followed by an hour later and daily in the next six days by MSM (400 mg/kg) or saline. Kidney’s function (urea and creatinine), and reduced glutathione were analyzed. A renal failure produced by glycerol injection, with a significant increase of blood urea and serum creatinine was observed. Rats that received MSM in addition to glycerol had significantly lower blood urea and serum creatinine levels compared to those receiving glycerol alone. However, glutathione has markedly increased after MSM treatment. The effect is probably due to the antioxidant activity of MSM. This may provide therapeutic opportunities for treating humans, myoglobinuric ARF.

The Effects of Baicalin on Myoglobinuric Acute Renal Failure in Rats.

Background:Myoglobinuric acute kidney injury is a uremic syndrome that develops due to damage of skeletal muscle. Free radicals and nitric oxide play an important role in the pathogenesis of myoglobinuric acute kidney injury. Baicalin has multiple bioactivities, including antimicrobial, anti-inflammatory and antioxidant properties and is a potent free radical scavenger.Aims:To investigate the nephroprotective mechanism of baicalin on myoglobinuric acute kidney injury.Study Design:Animal experimentation.Methods:In our study, male Sprague Dawley rats were divided into 4 groups. Control (n=8), Baicalin (n=8), myoglobinuric acute kidney injury (n=10) and myoglobinuric acute kidney injury + baicalin (n=10). The rats were deprived of water for 24 hours before receiving intramuscular injection. The control and baicalin groups were injected intramuscularly with saline (8 ml/kg), and the myoglobinuric acute kidney injury and myoglobinuric acute kidney injury + baicalin groups were given 50% glycerol 8 ml/kg. One hour later, the control and myoglobinuric acute kidney injury groups received saline intraperitoneally, and the baicalin and myoglobinuric acute kidney injury + baicalin groups were given 200 mg/kg baicalin. Twenty-four hours after the glycerol injection, urine and blood samples were taken, and the kidneys of the rats were harvested under intraperitoneally injections of anaesthesia.Results:We found that the levels of creatinine, urea, nitric oxide, alanine transaminase, aspartate aminotransferase, creatine kinase in serum samples, malondialdehyde, nitric oxide, inducible nitric oxide synthase, and endothelial nitric oxide synthase concentrations in renal tissue were increased in the myoglobinuric acute kidney injury group compared with the control group (p<0.05). The nitric oxide and glutathione levels in the kidney were significantly decreased in the myoglobinuric acute kidney injury + baicalin group compared with the myoglobinuric acute kidney injury group (p<0.05). There were no significant differences between any other parameters.Conclusion:Our results did not show any protective effect of baicalin on myoglobinuric acute kidney injury, possibly because the different effective factors in the pathogenesis of experimental myoglobinuric acute kidney injury used in this experiment deviate from other experimental models. Moreover, detailed studies are needed to clarify the effects of baicalin in different doses and treatment durations in glycerol-induced acute kidney injury model.

The effect of hyperbaric oxygen therapy on rhabdomyolysis-induced myoglobinuric acute renal failure in rats

Myoglobinuric acute renal failure (MARF) may develop after severe muscle injury. Heme oxygenase-1 (HO-1), a stress-response protein, has been implicated as a protective agent against MARF. We hypothesized that hyperbaric oxygen therapy (HBOT) may alleviate MARF by inducing renal HO-1 expression. Wistar-Albino rats were randomly assigned into three groups: Control (n = 4), MARF (n = 8), MARF + HBO (n = 8). MARF was induced by intramuscular glycerol (50%, 8 mL/kg) injection. Saline (8 mL/kg) was injected into the hind limb of the animals in the control group. Animals in the MARF + HBO group received two sessions of HBO therapy (90 min at 2.5 atm) 2 and 18 h after glycerol injection. Serum and tissue samples were taken at 24 h. Serum urea and creatinine levels increased in the MARF and MARF + HBO groups confirming the development of MARF. But, serum urea and creatinine levels were similar in MARF and MARF + HBO groups. Oxidative stress parameters were similar among all groups. Histological renal injury score was similar in MARF and MARF + HBO groups. HO-1 level, determined by immunohistochemistry, was significantly higher in MARF and MARF + HBO groups, compared to the control group. Although HO-1 level in MARF + HBO group was higher than MARF group, it was not statistically significant. We found that HBOT did not reduce renal injury in experimental MARF model. HBOT is used to reduce the muscle damage after crush injury, which may be accompanied by MARF. Therefore, more studies are needed to understand the effects of HBO treatment on renal functions after MARF.

A study on the effect of cimetidine and l-carnitine on myoglobinuric acute kidney injury in male rats

Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF.The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats.Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations.Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings.Cimetidine and l-carnitine have protective effects – almost equally – against mARF. Using both agents together, minimises the renal injury.

Acute Tubuler Necrosis Related to Rhabdomyolysis

Rhabdomyolysis is a clinical and laboratory syndrome due to traumatic or non-traumatic injury that leads muscle cell contents participation into circulation. Dehydration and acidosis may cause myoglobinuric acute renal failure in patient with rhabdomyolysis. This case presents a 27-year-old male referred to emergency unit with weakness and abdominal ache who has a story of urine decrease and trauma exposure. Diagnosis of rhabdomyolysis in this case highlights the importance of anamnesis in early diagnosis and treatment.

Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 mL/kg body weight of 50% glycerol, glycerol + ferulic acid at the dose of 5, 10, 15, 20 and 25 mg/kg body weight. After 24 h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.

Ratlarda Gliserol ile İndüklenen Miyoglobinürik Akut Böbrek Yetmezliği Üzerine Losartanın Etkileri

Ratlarda Gliserol ile İndüklenen Miyoglobinürik Akut Böbrek Yetmezliği Üzerine Losartanın Etkileri

L-Citrulline Protects against Rhabdomyolysis -Induced Acute Renal Failure in Rats

There is increasing evidence indicating that oxidative stress plays an important role in the pathogenesis of rhabdomyolysis-induced myoglobinuric acute renal failure (ARF). In this study, protective effects of L-citrulline on glycerol-induced acute renal failure (ARF) in rats were investigated. Six groups of rats were employed in this study, after seven days of glycerol injections, the blood samples and kiney tissues were harvested for future biochemical and pathology analysis. The levels of creatinine (Cr) and urea nitrogen (BUN) in plasma, the content of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), the activity of total nitric oxide synthase (TNOS), inducible nitric oxide synthase (iNOS), endothelial NO synthase (eNOS) and superoxide dismutase (SOD) were evaluated in kiney tissues. Consequently, treatment with L-citrulline improved an impaired intrarenal oxygenation and kidney function compare with the glycerol group, and prevented the renal oxidative stress damage as well as severe functional and morphological renal deterioration.

Cytotoxic and renoprotective flavonoid glycosides from Horwoodia dicksoniae

Three flavonoid glycosides and one aglycone were isolated from the ethanol extract (EE) ofHorwoodia dicksoniae (Brassicaceae), for the first time, and their structures were established from negative ESI-MS, 1H-, 13C-NMR and DEPT as luteolin 7-O-β-D-glucopyranoside (1), luteolin 6-C-β-D-galactopyranoside (2), apigenin 6-C-β-D-galactopyranoside (3) and luteolin (4). The SRB cytotoxicity assay was used to investigate the antitumor activity of the EE, Compounds 1, 2 and 4. Compound 1 showed the highest cytotoxic activity against the three human cell lines, including HEP-G2, HCT-116 and MCF-7 (IC50 = 10.7, 9.3 and 9.9 µg/ml, respectively), compared with doxorubicin as reference drug. Compound 4 showed selective antitumor activity against the colon cell line (IC50 = 9.5 µg/ml). The present investigation also demonstrates the protective effect of Compounds 1, 2 and 4 with strong antioxidant potential, in glycerol-induced myoglobinuric acute renal failure in rats. Moreover, all tested compounds separately attenuated renal dysfunction, and restored the oxidant balance by decreasing renal MDA levels, increasing the activity of the depleted renal antioxidant enzymes, and the non enzymatic antioxidant GSH. They also, decreased the elevated serum inflammatory marker (TNF-α), and ameliorated apoptotic kidney damage by reduction in caspase-3 activity. Taken together, 1 was found to be the most biologically active compound. Key words: Rhabdomyolysis, glycerol, acute renal failure, flavone glycosides, cytotoxicity.

Preventive effects of hyperbaric oxygen treatment on glycerol-induced myoglobinuric acute renal failure in rats

Myoglobinuric acute renal failure (ARF) is a uremic syndrome caused by traumatic or non-traumatic skeletal muscle breakdown and intracellular elements that are released into the bloodstream. We hypothesized that hyperbaric oxygen (HBO) therapy could be beneficial in the treatment of myoglobinuric ARF caused by rhabdomyolysis. A total of 32 rats were used in the study. The rats were divided into four groups: control, control+hyperbaric oxygen (control+HBO), ARF, and ARF+hyperbaric oxygen (ARF+HBO). Glycerol (8 ml/kg) was injected into the hind legs of each of the rats in ARF and ARF+HBO groups. 2.5 atmospheric absolute HBO was applied to the rats in the control+HBO and ARF+HBO groups for 90 min on two consecutive days. Plasma urea, creatinine, sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatinine kinase and urine creatinine and sodium were examined. Creatinine clearance and fractional sodium excretion could then be calculated. Superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) levels were assessed in renal tissue. Tissue samples were evaluated by Hematoxylin-eosin, PCNA and TUNEL staining histopathologically. MDA levels were found to be significantly decreased whereas SOD and CAT were twofold higher in the ARF+HBO group compared to the ARF group. Renal function tests were ameliorated by HBO therapy. Semiquantitative evaluation of histopathological findings indicated that necrosis and cast formation was decreased by HBO therapy and TUNEL staining showed that apoptosis was inhibited. PCNA staining showed that HBO therapy did not increase regeneration. Ultimately, we conclude that, in accordance with our hypothesis, HBO could be beneficial in the treatment of myoglobinuric ARF.

High Cut‐Off Membrane Hemodiafiltration in Myoglobinuric Acute Renal Failure: A Case Series

Acute renal failure is a major complication of rhabdomyolysis. New membranes for hemodialysis have been developed with a high cut-off pore size allowing efficient removal of myoglobin. We report on six patients treated by hemodiafiltration with a high cut-off membrane (HCO-HDF) for myoglobinuric acute renal failure. Rhabdomyolysis was caused by infection in two patients, by a statin in one patient and a non-traumatic crush in another, and followed cardiovascular surgery in two others. Ten HCO-HDF procedures were performed. A high cut-off hemofilter was used, with citrate anticoagulation and postdilutional fluid substitution of 2-3 L/h, dialysate flow 500 mL/min, and blood flow within 250-300 mL/min. Albumin losses were replaced by infusion of human albumin solution, and the mean myoglobin reduction ratio was 77% (range, 62-89%). An excellent clearance of 81 mL/min (range 42-131 mL/min) was achieved. Nearly 5 g of myoglobin was removed into the dialysate collected in one of the procedures. A high rebound in serum myoglobin, on average to 244% of the post-procedure myoglobin level, was observed. The four patients alive at the time remained anuric for a week. Slow myoglobin elimination with a mean half-time of 39 h (range 19-59 h) was observed in that period. Highly efficient myoglobin removal by high cut-off membrane hemodiafiltration was demonstrated in our patients. Rapid redistribution from the extracellular fluid and sustained myoglobin release were suggested by the high rebound observed. Elimination of myoglobin within the body was shown in our study to occur slowly during the period of anuria.

Glycerol誘発ラット急性腎不全モデルに対するK-channel opener(Y-26763)の予防効果

Y-26763, a benzopyran derivative, is a newly developed ATp-sensitive K channel opener and has been reported to protect against ischemic acute renal failure (ARF). We examined the effects of Y-26763 on glycerol-induced myoglobinuric ARF in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb intramuscular injection of 50% glycerol (5 ml/kg) after 18 hrs of water deprivation. Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n = 12) was given intravenously 15 min before glycerol injection. Glibenclamide (20 mg/kg), a K channel blocker was given prior to Y-26763 injection to see of the effects was due to the K-channel opener (GYG group, n = 6). Animals were sacrificed 24 or 96 hrs after glycerol injection. Y-26763 partially, but significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were antagonized by glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05). Renal calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/- 1.2 micrograms/mg dry weight). Histological examinations revealed that extensive tubular necrosis and cast formation seen in the G group were reduced in the GY group. At the recovery phase, 96 hrs after glycerol injection, Y-26763 accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3 +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY group (p < 0.01). In conclusion, Y-26763 partially protected against glycerol-induced ARF.

Crush injuries and crush syndrome - a review. Part 2: the local injury

Crush injuries can occur in considerable numbers following natural disasters or acts of war and terrorism. They can also occur sporadically after industrial accidents or following periods of unconsciousness from drug intoxication, anaesthesia, trauma or cerebral events. A common pathophysiological pathway has been elucidated over the last century describing traumatic rhabdomyolysis leading to myoglobinuric acute renal failure and a systemic ‘crush syndrome’ affecting many organ systems. If left unrecognised or untreated then mortality rates are high. If treatment is commenced early and the systemic effects are minimised then patients are often faced with significant morbidity from the crushed limbs themselves. We have performed a thorough review of the English language literature from 1940—2009 investigating crush injuries and crush syndrome and present a comprehensive, two-part summary. Part 1: The systemic injury, we concentrate on the systemic crush syndrome. We determine the pathophysiology, clinical and prognostic indicators and treatment options such as forced alkaline diuresis, mannitol therapy, dialysis and haemofiltration. We discuss more controversial treatment options such as allopurinol, potassium binders, calcium therapy and other diuretics. We also discuss the specific management issues of the secondary ‘renal disaster’ that can occur following earthquakes and other mass disasters. Part 2: The local injury, we look in more detail at the pathophysiology of skeletal muscle damage following crush injuries and discuss how to minimise morbidity by salvaging limb function. In particular we discuss the controversies surrounding fasciotomy of crushed limbs and compare surgical management with conservative techniques such as mannitol therapy, hyperbaric oxygen therapy, topical negative pressure therapy and a novel topical treatment called gastric pentadecapeptide BPC 157.

Crush injuries and crush syndrome — a review. Part 1: the systemic injury

Crush injuries can occur in large numbers following natural disasters or acts of war and terrorism. They can also occur sporadically after industrial accidents or following periods of unconsciousness from drug intoxication, anaesthesia, trauma or cerebral events. A common pathophysiological pathway has been elucidated over the last century describing traumatic rhabdomyolysis leading to myoglobinuric acute renal failure and a systemic ‘crush syndrome’ affecting many organ systems. If left unrecognised or untreated, then mortality rates are high. If treatment is commenced early and the systemic effects are minimised then patients are often faced with significant morbidity from the crushed limbs themselves. We have performed a thorough review of the English language literature from 1940 to 2009 investigating crush injuries and crush syndrome and present a comprehensive, two-part summary. Part 1: The systemic injury: In this part we concentrate on the systemic crush syndrome. We determine the pathophysiology, clinical and prognostic indicators and treatment options such as forced alkaline diuresis, mannitol therapy, dialysis and haemofiltration. We discuss more controversial treatment options such as allopurinol, potassium binders, calcium therapy and other diuretics. We also discuss the specific management issues of the secondary ‘renal disaster’ that can occur following earthquakes and other mass disasters. Part 2: The local injury: Here we look in more detail at the pathophysiology of skeletal muscle damage following crush injuries and discuss how to minimise morbidity by salvaging limb function. In particular we discuss the controversies surrounding fasciotomy of crushed limbs and compare surgical management with conservative techniques such as mannitol therapy, hyperbaric oxygen therapy, topical negative pressure therapy and a novel topical treatment called gastric pentadecapeptide BPC 157.

Exertional Rhabdomyolysis and Acute Kidney Injury

Skeletal muscle breakdown occurs normally with exercise, followed by muscle repair and physiologic adaption. Strenuous, unaccustomed, prolonged, and repetitive exercise, particularly when associated with other risk factors such as hot and humid climate or sickle cell trait can cause clinically significant exertional rhabdomyolysis (ER). Although most cases are asymptomatic and resolve without sequelae, ER is the most common cause of exercise-related myoglobinuric acute renal injury and acute renal failure in athletes. Exercise-related muscle pain, elevated serum creatine kinase (CK), and “cola-colored” urine have been described as a classic presentation of ER. The exact mechanism of ER has not been clearly elucidated. Most studies suggest a cascade of events that include depletion of adenosine triphosphate (ATP), impaired function of the Na+- K+ ATPase system, intracellular excess calcium accumulation, sarcolemma damage, and release of intracellular proteins and other substances into blood. Excess myoglobin that is filtered at the glomerulus can lead to myoglobinuric acute renal injury. Cessation of physical activity, relative rest during clinical recovery, and early aggressive fluid replacement are mainstays of treatment. Return to play after recovery from ER is influenced by associated risk factors that may predispose the athlete to recurrence and is guided by signs, symptoms, and CK levels. This article reviews the definitions, pathophysiology, diagnosis, and management of ER with specific relevance to acute kidney injury.

L-Carnitine Ameliorates Glycerol-Induced Myoglobinuric Acute Renal Failure in Rats

There is increasing evidence indicating that oxidative stress plays an important role in the pathogenesis of rhabdomyolysis-induced myoglobinuric acute renal failure (ARF). During times of war and natural disasters, myoglobinuric ARF can assume epidemic proportions. Thus, early and effective renoprotective treatments are of utmost importance. It has been shown that L-carnitine, used as a safe and effective nutritional supplement for more than three decades, is effective in preventing renal injury in many renal injury models involving oxidative stress. The present study was performed to investigate the effects of L-carnitine in an experimental model of myoglobinuric ARF. Four groups of rats were employed in this study: group 1 served as a control; group 2 was given glycerol (10 mL/kg, i.m.); group 3 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting at the same time as the glycerol injection; group 4 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting 48h before the glycerol injection. After glycerol injections, the i.p. injections of L-carnitine were repeated every 24h for four days. Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma, N-acetyl-beta-D-glucosaminidase activity in urine, and malondialdehyde levels and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress, as well as severe functional and morphological renal deterioration. L-carnitine, possibly via its antioxidant properties, ameliorates glycerol-induced myoglobinuric kidney injury.