Clinical presentation and outcomes of patients with rhabdomyolysis: A tertiary care center experience.

OBJECTIVES: To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. METHODS: Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. RESULTS: Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5 kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. CONCLUSION: This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.

Uric acid in predicting the traumatic rhabdomyolysis induced acute kidney injury; a systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to assess the value of uric acid in predicting acute kidney injury caused by traumatic rhabdomyolysis. METHODS: The search was conducted in MEDLINE, Scopus, Embase and Web of Science until November 1, 2023. Based on the inclusion and exclusion criteria, the articles were included by two independent researchers. Data regarding study design, patient characteristics, number of patients with and without AKI, mean and SD of uric acid and prognostic characteristics of uric acid were extracted from relevant studies. STATA version 17.0 was used to compute pooled measures of standardized mean differences, odds ratios, and diagnostic accuracy. I2 and chi-square tests were used to assess heterogeneity between studies. RESULTS: We found 689 non-redundant studies, 44 of them were potentially relevant. Six articles met the inclusion criteria and were included in the review. The results of the meta-analysis confirmed that there was a significant correlation between serum uric acid levels and the occurrence of AKI (SMD = 1.61, 95% CI = 0.69 to 2.54, I2 = 96.94%; p value = 0.001). There were no significant publication biases. CONCLUSION: According to this meta-analysis, uric acid levels could be considered as a predictor of acute kidney injury following traumatic rhabdomyolysis.

Kidney replacement and conservative therapies in rhabdomyolysis: a retrospective analysis.

BACKGROUND: Toxic renal effects of myoglobin following rhabdomyolysis can cause acute kidney injury (AKI) with the necessity of kidney replacement therapy (KRT). Fast elimination of myoglobin seems notable to save kidney function and intensify kidney repair. Clinical data regarding efficacy of KRT in critical care patients with rhabdomyolysis and AKI are limited. This retrospective analysis aimed to identify differences between conservative therapy and different modalities of KRT regarding myoglobin elimination and clinical outcome. METHODS: This systematic, retrospective, single-center study analyzed 328 critical care patients with rhabdomyolysis (myoglobin > 1000 µg/l). Median reduction rate of myoglobin after starting KRT was calculated and compared for different modalities. Multivariate logistic regression models were established to identify potential confounder on hospital mortality. Filter lifetime of the various extracorporeal circuits was analyzed by Kaplan-Meier curves. RESULTS: From 328 included patients 171 required KRT. Health condition at admission of this group was more critical compared to patient with conservative therapy. Myoglobin reduction rate did not differ between the groups (KRT 49% [30.8%; 72.2%] vs. conservative treatment (CT) 61% [38.5%; 73.5%]; p = 0.082). Comparison between various extracorporeal procedures concerning mortality showed no significant differences. Hospital mortality was 55.6% among patients with KRT and 18.5% with CT (p < 0.001). Multivariate logistic regression model identified requirement for KRT (OR: 2.163; CI: 1.061-4.407); p = 0.034) and the SOFA Score (OR: 1.111; CI: 1.004-1.228; p = 0.041) as independent predictive factors for hospital mortality. When comparing specific KRT using multivariate regression, no benefit was demonstrated for any treatment modality. Life span of the extracorporeal circuit was shorter with CVVH compared to that of others (log-Rank p = 0.017). CONCLUSIONS: This study emphasizes that AKI requiring KRT following rhabdomyolysis is accompanied by high mortality rate. Differences in myoglobin reduction rate between various KRTs could not be confirmed, but CVVH was associated with reduced filter lifetime compared to other KRTs, which enable myoglobin elimination, too.

Perioral Paresthesia, Generalize Muscle Cramps, and Rhabdomyolysis After a Socotra Island Blue Baboon Tarantula (Monocentropus Balfouri) Bite.

BACKGROUND: Literature on systemic envenomation caused by tarantula bites, particularly from the Theraphosidae family, is relatively scarce. This case report provides a formal description of the first known instance of systemic envenomation caused by the Socotra Island Blue Baboon Tarantula (Monocentropus balfouri). CASE REPORT: In this case, a 23-year-old employee of an exotic pet shop suffered from perioral paresthesia, generalized muscle cramps, and rhabdomyolysis because of a Monocentropus balfouri bite. His symptoms were successfully relieved with oral benzodiazepines. EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the potential for serious complications resulting from the bite of Monocentropus balfouri, a species gaining popularity among global exotic pet collectors.

Proteomic analysis of multiple organ dysfunction induced by rhabdomyolysis.

Rhabdomyolysis (RM) leads to dysfunction in the core organs of kidney, lung and heart, which is an important reason for the high mortality and disability rate of this disease. However, there is a lack of systematic research on the characteristics of rhabdomyolysis-induced injury in various organs and the underlying pathogenetic mechanisms, and especially the interaction between organs. We established a rhabdomyolysis model, observed the structural and functional changes in kidney, heart, and lung. It is observed that rhabdomyolysis results in significant damage in kidney, lung and heart of rats, among which the pathological damage of kidney and lung was significant, and of heart was relatively light. Meanwhile, we analyzed the differentially expressed proteins (DEPs) in the kidney, heart and lung between the RM group and the sham group based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, Serpina3n was significantly up-regulated in the kidney, heart and lung. Serpina3n is a secreted protein and specifically inhibits a variety of proteases and participates in multiple physiological processes such as complement activation, inflammatory responses, apoptosis pathways, and extracellular matrix metabolism. It is inferred that Serpina3n may play an important role in multiple organ damage caused by rhabdomyolysis and could be used as a potential biomarker. This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis. SIGNIFICANCE: This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis.

Status epilepticus resulted in rhabdomyolysis-induced AKI associated with hepatotoxicity induced by synergistic carbamazepine and diazepam: A case report.

RATIONALE: Rhabdomyolysis is a serious complication of status epilepticus (SE) caused by muscle cell damage and can lead to a life-threatening acute kidney injury (AKI). PATIENT CONCERNS: A 35-year-old man with a history of seizures treated with 3 different antiepileptic drugs (carbamazepine, lamotrigine, and levetiracetam) presented with SE. The patient received 5 doses of diazepam to control the SE in another hospital and was transferred to our emergency due to AKI. DIAGNOSES: Laboratory tests corresponded with rhabdomyolysis-induced AKI and disseminated intravascular coagulation. Thereafter, the decrease in renal excretion of both drugs (diazepam and carbamazepine) caused acute liver injury and neurotoxicity. The carbamazepine concentration was 16.39 mcg/mL, which considered in toxic level, despite using the usual dose. INTERVENTIONS: The patient was treated with hydration and sodium bicarbonate, however; severe AKI mandated a hemodialysis session. OUTCOMES: The diuresis started to increase, kidney and liver functions improved, and altered mental status reversed. LESSONS: This case alerts physicians to consider the synergistic drug side effects and interactions, especially when patients present with impaired liver or kidney functions. The reduction in metabolism or excretion of drugs can cause an increase in serum concentrations and induce toxicity, even when the drug intake at the usual dose.

Clinical outcomes of rhabdomyolysis & validation of McMahon Score for risk prediction.

BACKGROUND OBJECTIVES: Rhabdomyolysis in tropics has a unique aetiology and clinical profile. The objective of this study was to determine the aetiology and clinical outcomes of rhabdomyolysis and validate the McMahon risk prediction score in affected individuals from south India. METHODS: A retrospective study of affected individuals with rhabdomyolysis admitted to a tertiary care hospital in south India, between January 2015 and June 2020, was undertaken. In-patients who were ≥15 yr in age and had creatinine phosphokinase ≥5000 U/l were included in the study. Cardiac, stroke, chronic muscular diseases and chronic kidney disease on maintenance haemodialysis were excluded. The incidence of acute kidney injury (AKI) in this group was calculated. Other clinical outcomes determined were 28-day mortality, proportion of individuals who required renal replacement therapy (RRT), intensive care unit (ICU) admission, vasopressors, mechanical ventilation (MV), number of days on mechanical ventilator and length of stay in ICU and hospital. Validation of McMahon risk prediction score for the requirement of RRT and mortality was performed. RESULTS: Major aetiologies identified in the 75 study participants included were infections, trauma and seizures. Twenty eight-day mortality was 24 per cent (n=18). AKI incidence was 68 per cent, out of which 43.1 per cent had RRT. AKI in all survivors became dialysis independent. Vasopressors, MV and ICU requirement were 30.7, 32 and 77.3 per cent, respectively. Receiver operator characteristic curve for RRT and mortality risk prediction based on the McMahon Score showed a sensitivity of 71.4 per cent and specificity of 77.8 per cent for a cut-off ≥7.8. INTERPRETATION CONCLUSIONS: Rhabdomyolysis in tropics is associated with significant organ dysfunction and mortality. Although the incidence of AKI and RRT is high, the overall renal outcome is good among survivors. The wide confidence intervals for the area under curve for McMahon Score limit its predictability for RRT and mortality.

Case Report: A Case of Complicated Typhoid Fever with Rhabdomyolysis and Hemophagocytic Lymphohistiocytosis.

Typhoid fever can have diverse extra-intestinal complications including encephalitis, Guillain-Barré syndrome, endocarditis, myocarditis, osteomyelitis, renal abscess, and splenic abscesses. Secondary hemophagocytic lymphohistiocytosis with rhabdomyolysis is a rare complication of typhoid fever. Here, we present the case of an adolescent with typhoid fever complicated by rhabdomyolysis and hemophagocytic lymphohistiocytosis.

Rhabdomyolysis in older adults: outcomes and prognostic factors.

BACKGROUND: Rhabdomyolysis is a common condition in older adults, often associated with falls. However, prognostic factors for rhabdomyolysis have mainly been studied in middle-aged populations. OBJECTIVE: To test the hypothesis that age influences rhabdomyolysis prognostic factors. METHODS: This retrospective single-center observational study included all patients with a creatine kinase (CK) level greater than five times normal, admitted to Rennes University Hospital between 2013 and 2019. The primary endpoint was 30-day in-hospital mortality rate. RESULTS: 343 patients were included (median age: 75 years). The mean peak CK was 21,825 IU/L. Acute renal failure occurred in 57.7% of the cases. For patients aged 70 years and over, the main etiology was prolonged immobilization after a fall. The 30-day in-hospital mortality rate was 10.5% (23 deaths). The Charlson score, number of medications and CK and creatinine levels varied according to age. Multivariate analysis showed age to be a factor that was associated, although not proportionally, with 30-day in-hospital mortality. CONCLUSION: Factors influencing rhabdomyolysis severity were not randomly distributed according to age. The term rhabdomyolysis encompasses various clinical realities and is associated with different mechanisms. More research is needed to better understand the physio-pathological and prognostic factors of rhabdomyolysis, especially in older adults.

Adult-onset carnitine palmitoyl transferase II (CPT II) deficiency presenting with rhabdomyolysis and acute kidney injury.

Metabolic myopathies are among the treatable causes of rhabdomyolysis and myoglobinuria. Carnitine palmitoyl transferase 2 (CPT II) deficiency is one of the most common causes of recurrent myoglobinuria in adults. It is an inherited disorder of fatty acid oxidation pathway, commonly associated with elevated acylcarnitine levels. In this case report, we present a 49-year-old male patient who developed acute kidney injury after rhabdomyolysis and was thus diagnosed with CPT2 deficiency after his first episode of rhabdomyolysis. Inborn errors of metabolism should be kept in mind in patients with rhabdomyolysis. Acylcarnitine profile may be normal in CPT II deficiency, even during an acute attack, and molecular genetic diagnostics should be applied if there is high index of clinical suspicion.

Single-cell RNA sequencing identifies senescence as therapeutic target in rhabdomyolysis-induced acute kidney injury.

BACKGROUND: The role of macrophages in the development of rhabdomyolysis-induced acute kidney injury (RM-AKI) has been established, but an in-depth understanding of the changes in the immune landscape could help to improve targeted strategies. Whereas senescence is usually associated with chronic kidney processes, we also wished to explore whether senescence could also occur in AKI and whether senolytics could act on immune cells. METHODS: Single-cell RNA sequencing was used in the murine glycerol-induced RM-AKI model to dissect the transcriptomic characteristics of CD45+ live cells sorted from kidneys 2 days after injury. Public datasets from murine AKI models were reanalysed to explore cellular senescence signature in tubular epithelial cells (TECs). A combination of senolytics (dasatinib and quercetin, DQ) was administered to mice exposed or not to RM-AKI. RESULTS: Unsupervised clustering of nearly 17 000 single-cell transcriptomes identified seven known immune cell clusters. Sub-clustering of the mononuclear phagocyte cells revealed nine distinct cell sub-populations differently modified with RM. One macrophage cluster was particularly interesting since it behaved as a critical node in a trajectory connecting one major histocompatibility complex class IIhigh (MHCIIhigh) cluster only present in Control to two MHCIIlow clusters only present in RM-AKI. This critical cluster expressed a senescence gene signature, that was very different from that of the TECs. Senolytic DQ treatment blocked the switch from a F4/80highCD11blow to F4/80lowCD11bhigh phenotype, which correlated with prolonged nephroprotection in RM-AKI. CONCLUSIONS: Single-cell RNA sequencing unmasked novel transitional macrophage subpopulation associated with RM-AKI characterized by the activation of cellular senescence processes. This work provides a proof-of-concept that senolytics nephroprotective effects may rely, at least in part, on subtle immune modulation.

Acute Renal Failure with Severe Loin Pain and Patchy Renal Ischemia after Anaerobic Exercise in Active Duty Marines.

Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is a rare cause of exertional acute kidney injury. The proposed mechanism of injury in ALPE is renovascular spasm, in the setting of oxidative stress and muscular damage, which creates a characteristic wedge-shaped infarction pattern on delayed imaging. Patients present with nausea, vomiting, loin or abdominal pain, and fatigue within 1-2 days of anaerobic exercise, associated with an acute rise in serum creatinine, which generally plateaus within 3 days. This process is likely exacerbated by dehydration, analgesic usage, and lower baseline fitness levels. This disease process is distinct from rhabdomyolysis, in that creatine kinase levels are not significantly elevated, myoglobinuria is not seen, and aggressive fluid resuscitation is not beneficial. We present three cases of ALPE following participation in the Marine Combat Fitness Test (CFT), an anaerobic evolution. Medical workup demonstrated no additional etiology for acute renal failure. The average peak creatinine in these patients was 2.9 mg/dL, and all demonstrated return to normal renal function, without hemodialysis. One patient experienced recurrent ALPE, after short-interval CFT participation. Military medical providers should be aware of this diagnosis when evaluating service members with acute renal injury after exercise. The clinical course is benign, and affected service members are at increased risk of recurrence, with subsequent intense exercise. Service members should engage in a graduated exercise program, before intense exercise activities, and should be monitored closely for recurrent renal injury.

BREAKING NEW GROUND: STANDARDIZING RAT MODELS FOR CRUSH SYNDROME INVESTIGATIONS.

ABSTRACT: Crush syndrome (CS), alternatively termed traumatic rhabdomyolysis, is a paramount posttraumatic complication. Given the infeasibility of conducting direct simulation research in humans, the role of animal models is pivotal. Regrettably, the dearth of standardized animal models persists. The objective of this study was to construct a repeatable standardized rat CS models and, based on this, simulate specific clinical scenarios. Methods: Using a self-developed multichannel intelligent small-animal crush injury platform, we applied a force of 5 kg to the hind limbs of 8-week-old rats (280-300 g), subjecting them to a continuous 12 h compression to establish the CS model. Continuous monitoring was conducted for both the lower limbs and the overall body status. After decompression, biochemical samples were collected at 3, 6, 12, and 24 h. In addition, we created a CS model after resection of the left kidney (UNx-CS), which was conceptualized to simulate a more challenging clinical scenario to investigate the physiological and pathological responses rats with renal insufficiency combined with crush injury. The results were compared with those of the normal CS model group. Results : Our experiments confirm the stability of the crush injury platform. We defined the standardized conditions for modeling and successfully established rats CS model in bulk. After 12 h of compression, only 40% of the rats in the CS group survived for 24 h. Systemically, there was clear evidence of insufficient perfusion, reflecting the progression of CS from localized to generalized. The injured limbs displayed swelling, localized perfusion deficits, and severe pathological alterations. Significant changes were observed in blood biochemical markers: aspartate transaminase, lactate dehydrogenase, K+, creatine kinase, creatinine, and blood urea nitrogen levels rose rapidly after decompression and were significantly higher than the sham group. The kidney demonstrated characteristic pathological changes consistent with established CS diagnostic criteria. Although the UNx-CS rat model did not exhibit significant biochemical differences and pathological scores when compared with the standard CS model, it did yield intriguing results with regard to kidney morphology. The UNx-CS group manifested a higher incidence of cortical and medullary protein casts compared with the NC-CS group. Conclusion: We developed and iteratively refined a novel digital platform, addressing the multiple uncontrollable variables that plagued prior models. This study validated the stability of the platform, defined the standardized conditions for modeling and successfully established the CS model with good repeatability in bulk. In addition, our innovative approach to model a clinically challenging scenario, the UNx-CS rat model. This offers an opportunity to delve deeper into understanding the combined effects of preexisting renal compromise and traumatic injury. In summary, the development of a standardized, reproducible CS model in rats represents a significant milestone in the study of Crush syndrome. This study is of paramount significance as it advances the standardization of the CS model, laying a solid foundation for subsequent studies in related domains, especially in CS-AKI.

Rapid and Effective Elimination of Myoglobin with CytoSorb® Hemoadsorber in Patients with Severe Rhabdomyolysis.

INTRODUCTION: Rhabdomyolysis is characterized by destruction of muscle fibers by various causes and is diagnosed by increased creatine kinase concentrations in the blood. Myoglobin released into the blood may cause acute kidney injury. In this randomized controlled study, we hypothesized that myoglobin elimination would be faster when a hemoadsorber was added to a continuous veno-venous hemodialysis (CVVHD). METHODS: Four patients in the control group received CVVHD with a high cut-off hemofilter using high blood and dialysate flows for 48 h. Four patients in the CytoSorb group received the same treatment, but in addition, the hemoadsorber CytoSorb® was inserted in front of the hemofilter and replaced once after 24 h. Blood samples were drawn simultaneously before (pre) and after (post) the hemofilter or else the hemoadsorber, after 5 and 30 min, as well as after 2, 4, 8, and 24 h. All measurements were repeated the next day after the hemoadsorber had been renewed in the CytoSorb group. Primary outcome was the area under the curve (AUC) of the relative myoglobin concentrations as percent of baseline. To evaluate the efficacy of myoglobin removal, relative reductions in myoglobin concentrations during one passage through each device at each time point were calculated. RESULTS: Patients in the CytoSorb group had a significantly lower AUC during the first 24 h (42 ± 10% vs. 63 ± 6%, p = 0.029) as well as during the observation period of 48 h (26 ± 7% vs. 51 ± 12%, p = 0.029). The relative reductions for myoglobin were considerably higher in the CytoSorb group compared to the control group during the first 8 h. CONCLUSION: Myoglobin concentrations declined considerably faster when CytoSorb was added to a CVVHD. When compared to a high-cut-off hemofilter, efficacy of CytoSorb in myoglobin elimination was much better. Because of saturation after 8-12 h an exchange may be necessary.

Raised CK and acute kidney injury following intense exercise in three patients with a history of exercise intolerance due to homozygous mutations in SLC2A9.

Acute rhabdomyolysis (AR) leading to acute kidney injury has many underlying etiologies, however, when the primary trigger is exercise, the most usual underlying cause is either a genetic muscle disorder or unaccustomed intense exercise in a healthy individual. Three adult men presented with a history of exercise intolerance and episodes of acute renal impairment following intense exercise, thought to be due to AR in the case of two, and dehydration in one. The baseline serum CK was mildly raised between attacks in all three patients and acutely raised during attacks in two of the three patients. Following referral to a specialized neuromuscular centre, further investigation identified very low serum urate (<12 umol/L). In all three men, genetic studies confirmed homozygous mutations in SLC2A9, which encodes for facilitated glucose transporter member 9 (GLUT9), a major regulator of urate homeostasis. Hereditary hypouricaemia should be considered in people presenting with acute kidney injury related to intense exercise. Serum urate evaluation is a useful screening test best undertaken after recovery.

Traumatic Rhabdomyolysis: Crush Syndrome, Compartment Syndrome, and the 'Found Down' Patient.

Traumatic rhabdomyolysis is a systemic manifestation of muscle injury and can occur from various traumatic etiologies, including crush syndrome (CrshS) and compartment syndrome (CS). Although historically described in natural disaster survivors trapped under collapsed structures, the frequency of CrshS has increased in the setting of 'found down' patients from opioid overdoses. Signs and symptoms of the injured limb in CrshS may range from pressure-induced skin changes to neurologic deficits and paralysis. Although its pathophysiology differs from CS, severe injuries may lead to an associated CS. Identifying CS in a patient with CrshS can be difficult but is important to distinguish because it affects treatment. The degree of muscle damage, viability of the remaining muscular compartment, and presence of elevated compartment pressures dictate the need for surgical intervention in the form of fasciotomy. Surgical outcomes from CrshS and delayed CS result in similar high morbidity and surgical complications. This review defines and classifies the types of traumatic rhabdomyolysis and summarizes the outcomes to facilitate timely diagnosis and appropriate management for this population to reduce morbidity associated with these conditions.

Rhabdomyolysis Complicated with Hyponatremia Due to Water Intoxication and Severe Aspiration Pneumonia: Description of a Patient with Chronic Schizophrenia and Literature Review.

Hyponatremia due to water intoxication is frequently observed in patients with chronic schizophrenia. We herein present a 49-year-old man who developed schizophrenia at the age of 23 and had been admitted to the closed ward of our hospital for 7 years. He was found by a round nurse standing at the bedside, covering both ears with his hands and making groaning noises. He was disoriented and immediately after being returned to bed, a general tonic-clonic seizure occurred. Severe hyponatremia (Na 104 mEq/L) was noted and intravenous sodium correction was started. A few hours later, due to glossoptosis and massive vomiting, ventilation got worse to the point where he had to be put on a ventilator. On the following day, he developed aspiration pneumonia and antimicrobial treatment was started. In addition, a blood sample taken 36 hours later revealed an extensive elevation of creatine kinase (41,286 U/L), pointing to a possibility of rhabdomyolysis as a complication. Subsequently, the general condition gradually improved with antimicrobial therapy and sodium correction. He eventually recovered without any complications including central pontine myelinolysis. He had no history of polydipsia before this event but it was later found that esophageal stricture triggered complusive fluid intake, resulting in acute hyponatremia, seizure, aspiration pneumonia and rhabdomyolysis. A brief discussion will be provided on the issues surrounding hyponatremia, rhabdomyolysis and schizophrenia.

Abcc6 deficiency prevents rhabdomyolysis-induced acute kidney injury.

Rhabdomyolysis is a risk factor for acute kidney injury, transition towards chronic kidney disease, and death. The role of calcium phosphate deposits in the mechanisms of rhabdomyolysis-induced acute kidney injury (RAKI) is still unclear. Better insight of the role calcium in RAKI could lead to new therapeutic avenues. Here, we show in a mice model of RAKI that calcium phosphate deposits were frequent in the kidney (hydroxyapatite) and partly correlated with the severity of the kidney injury. However, the intensity of deposits was highly heterogeneous between mice. Treatment with sodium chloride, sodium bicarbonate or inorganic pyrophosphate (PPi; an inhibitor of the calcium phosphate crystallization), or combinations thereof, did not improve kidney outcomes and hydroxyapatite deposition during RAKI. Unexpectedly, Abcc6 knockout mice (ko), characterized by PPi deficiency, developed less severe RAKI despite similar rhabdomyolysis severity, and had similar hydroxyapatite deposition suggesting alternative mechanisms. This improved kidney outcome at day 2 translated to a trend in improved glomerular filtration rate at month 2 in Abcc6-/-mice and to significantly less interstitial fibrosis. In addition, whereas the pattern of infiltrating cells at day 2 was similar between wt and ko mice, kidneys of Abcc6-/- mice were characterized by more CD19+ B-cells, less CD3+ T-cells and a lower R1/R2 macrophage ratio at month 2. In summary, kidney calcium phosphate deposits are frequent in RAKI but hydration with sodium bicarbonate or sodium chloride does not modify the kidney outcome. Blocking ABCC6 emerges as a new option to prevent RAKI and subsequent transition toward kidney fibrosis.

Acute myositis secondary to Epstein-Barr virus in the absence of infectious mononucleosis with severe rhabdomyolysis.

SummaryRhabdomyolysis is characterised by muscle breakdown which causes myoglobin light chain release and can result in renal injury. While some of the most common causes of rhabdomyolysis are trauma related, others include toxins, autoimmune processes or viral aetiologies. We present the case of a 20s-year-old man, with no significant medical history, who presented to the emergency department with a 1-week history of weakness, myalgias, nausea, vomiting and subjective fevers. A review of systems and physical exam were otherwise unremarkable, including being negative for sore throat, dysphagia and lymphadenopathy. On presentation, the patient was noted to have dark urine with a creatine kinase value of 452 458 U/L and an elevated creatinine at 7.23 mg/dL. The patient denied any trauma or increased physical activity. His toxin screen and autoimmune workup were negative. The patient's serological workup was significant for acute Epstein-Barr virus (EBV) infection, without additional viral coinfection or mononucleosis. During his hospitalisation course, the patient was managed with supportive care including haemodialysis. The patient made a full renal recovery and was discharged with scheduled outpatient follow-up. This case highlights the recognition of an acute EBV infection causing rhabdomyolysis in the absence of mononucleosis or concomitant infection.