Cascading renal injury after brain death: Unveiling glycocalyx alteration and the potential protective role of tacrolimus.

Brain death (BD) is a complex medical state that triggers systemic disturbances and a cascade of pathophysiological processes. This condition significantly impairs both kidney function and structural integrity, thereby presenting considerable challenges to graft viability and the long-term success of transplantation endeavors. Tacrolimus (FK506), an immunosuppressive drug, was used in this study to assess its impact as a pretreatment on brain death-induced renal injury. This study aimed to investigate changes associated with brain death-induced renal injury in a 4-month-old female porcine model. The experimental groups included brain death placebo-pretreated (BD; n = 9), brain death tacrolimus-pretreated using the clinical dose of 0.25 mg/kg the day before surgery, followed by 0.05 mg/kg/day 1 hour before the procedure (BD + FK506; n = 8), and control (ctrl, n = 7) piglets, which did not undergo brain death induction. Furthermore, we aimed to assess the effect of FK506 on these renal alterations through graft preconditioning. We hypothesized that immunosuppressive properties of FK506 reduce tissue inflammation and preserve the glycocalyx. Our findings revealed a series of interconnected events triggered by BD, leading to a deterioration of renal function and increased proteinuria, increased apoptosis in the vessels, glomeruli and tubules, significant leukocyte infiltration into renal tissue, and degradation of the glycocalyx in comparison with ctrl group. Importantly, treatment with FK506 demonstrated significant efficacy in attenuating these adverse effects. FK506 helped reduce apoptosis, maintain glycocalyx integrity, regulate neutrophil infiltration, and mitigate renal injury following BD. This study offers new insights into the pathophysiology of BD-induced renal injury, emphasizing the potential of FK506 pretreatment as a promising therapeutic intervention for organ preservation, through maintaining endothelial function with the additional benefit of limiting the risk of rejection.

Influence of homocysteine and its major genetic and nutritional determinants on bone mineral density.

INTRODUCTION: A potential role of hyperhomocysteinemia in bone metabolism has been considered from the observation of high prevalence of osteoporosis in subjects with homocystinuria about 50 years ago. AIM: To examine the association of homocysteine level and its determinants Methylenetetrahydrofolate Reductase [MTHFR] C677T Polymorphism, folates and vitamin B12 levels with bone mineral density [BMD] and the prevalence of vertebral fractures [VF] on postmenopausal women. METHODS: Through a cross-sectional study, one hundred and twenty-two healthy postmenopausal women gave their informed consent to participate in this study. Women were recruited through advertisements and mouth to ear between January 2017 and May 2017. One serum tube and one EDTA tube were collected from fasting patients. Bone mineral density was determined by a Lunar Prodigy® Vision DXA system®. Vertebral fracture [VF] assessment image was inspected visually by 2 clinicians. RESULTS: We found that a high level of homocysteine and low vitamin B12 and folate levels are not associated with bone mineral density and are not risk factors for VF in healthy postmenopausal women. Whereas, the presence of VF was associated with the number of years since menopause and with the osteocalcin levels. CONCLUSION: The MTHFR C677T polymorphism, the high levels of HCY, or low levels of folate and vitamin B12 would not be risk factors for osteoporosis and VF in healthy postmenopausal women.

Dilated cardiomyopathy: A rare and late complication of the hemolytic-uremic syndrome.

Hemolytic uremic syndrome (HUS) is a non-exceptional, progressive complication of acute gastroenteritis in children, especially secondary to Escherichia coli infection. It is responsible for significant morbidity and significant mortality (10% of deaths) because of acute renal failure which often complicates it. Dilated cardiomyopathy is a rare but critical extra renal manifestation of the HUS. This article highlights the importance of considering the diagnosis of associated cardiomyopathy in the acute phase of HUS and the following months. A five-year-old boy presented with HUS with acute renal failure requiring peritoneal dialysis for 24 days. No cardiac signs appeared during the acute phase of the disease. After dialysis and normalization of blood pressure, fluid, and electrolyte disturbance, severe dilated cardiomyopathy with cardiac failure appeared three months later without definite etiology. A review of the literature confirmed the rare and severe nature of cardiac lesions occurring in HUS. Dilated cardiomyopathy is a rare but important extra renal manifestation of the HUS and is best demonstrated by echocardiography. A cardiac manifestation should also be screened for in the acute phase of HUS and several months later. .