Browsing by Author "Tamayo, Jesus"
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Item Colloid-Enhanced Flush Limits Initial Edema but Exacerbates Subsequent Edema During Hypothermic Machine Perfusion of Porcine Kidneys(2023) Tamayo, Jesus; Mohammad, Moath; Wade, Michael; Tran, Amanda; O'Hara, Collin; Yurvati, Albert; Mallet, Robert T.Purpose: The epidemic of end-stage renal disease (ESRD) has steadily increased demand for transplantable kidneys, and the widening disparity between organ supply and demand is a major public health concern. Hypothermic machine perfusion (HMP) is widely used to preserve deceased donor kidneys for transplantation. Kidneys are harvested and flushed with crystalloid solution before HMP. This study tested the hypothesis that flushing kidneys with solution containing a colloid, hydroxyethyl starch (HES), minimizes edema and improves organ perfusion during subsequent HMP. Methods: Kidneys harvested from anesthetized Yorkshire swine were flushed for 15 min with ice-cold Ringer’s solution ± 50 g/l HES, and then either biopsied or installed in a LifePort organ preservation system for 72 h hypothermic (2-4°C) machine perfusion (HMP) before biopsy. ATP contents in renal cortical biopsies were analyzed by UV-Vis spectrophotometry. Results: Kidneys gained 49 ± 5% of initial mass during flush with control solution, but only another 3% to 52 ± 5% of initial mass over 72 h HMP. Kidneys flushed with HES-enriched solution gained only 18 ± 3% of initial mass (P<0.001 vs control) during flush, but over 72 h HMP gained another 72% to 90 ± 7% above initial mass (P<0.001 vs. control). Tissue water contents paralleled the respective weight gains (Figure). The HES-flushed kidneys experienced steeper declines in perfusion during HMP than the controls. Cortical ATP content (mmol/g dry mass) fell over 72 h HMP from 2.36 ± 1.40 to 0.44 ± 0.44 (mean ± SD) in control kidneys, and from 1.36 ± 1.31 to 0.38 ± 0.16 in HES-flushed kidneys (both groups: P<0.05, pre- vs. post-HMP). Conclusion: Flushing kidneys with HES-enriched solution minimized edema before HMP, but exacerbated edema during subsequent machine perfusion, failed to preserve ATP, and was associated with a steeper decline in organ perfusion during HMP. The mechanisms responsible for edema exacerbation by HES-enhanced flush are under investigation.Item Pseudopheochromocytoma: A Case of Benign Endothelial Cyst of the Adrenal Gland(2024-03-21) Nguyen, Antoine; Tamayo, Jesus; Mohammad, Moath; Paluru, SwethaBackground: Benign endothelial cyst of the adrenal gland (ECAG) with pheochromocytoma-like symptoms, or pseudopheochromocytoma (pseudoPHEO), is an extremely rare condition. Adrenal cysts seldomly occur with an incidence of 0.06% in the general population. Most cases are asymptomatic and discovered incidentally on imaging. ECAG predominately affect females and represent approximately 45% of all cystic tumors involving adrenal glands with two subtypes: angiomatous and lymphangiomatous. The association of adrenal cysts with pseudopheochromocytoma is a rare but well-documented relationship. Occasionally, these cysts can increase pressure in the adrenal medulla leading to elevated metanephrine levels. PseudoPHEO is a diagnosis of exclusion with pheochromocytoma being an important differential diagnosis. Patients may present with pheochromocytoma-like features such as symptomatic paroxysmal hypertension. If adrenal cortical tumors are involved, elevated catecholamines can be found on evaluation, although catecholamine-secreting tumors are diagnosed in less than 0.5% of patients with hypertension. Case Information: A 63-year-old female with a past medical history of an adrenal nodule discovered in 2017 during colon resection and poorly-controlled hypertension presented for adrenalectomy for suspected pheochromocytoma. Her normetanephrine level was 342 (normal: <148pg/mL) and metanephrine was 50 (normal: <57pg/mL). CT of the abdomen demonstrated an adrenal lesion with some features of benign etiology. She underwent robotic-assisted laparoscopic right adrenalectomy during which a 3 cm cyst in the adrenal medulla was found abutting the adrenal cortex. Microscopically, a multilocular cyst associated with hemorrhage involving the adrenal medulla was present. Conclusion: To diagnose pseudoPHEO, pheochromocytoma must be excluded especially when symptomatic paroxysmal hypertension is present with or without elevated catecholamines. The cells were positive for CD31 and negative for calretinin on immunohistochemistry staining which support an endothelial cell origin consistent with benign ECAG, not pheochromocytoma. These cysts may occupy space in the adrenal gland, increasing pressure in the adrenal medulla to cause elevated metanephrines, as seen in this patient. While the prognosis for ECAG is good, ECAG with associated pseudopheochromocytoma can cause life threatening complications. Treatment of pseudoPHEO is dependent on severity and etiology of disease process. Medical management can be complicated by unpredictable episodes of hypotension as patients can be normotensive between symptomatic episodes. In cases of pseudopheochromocytoma caused by ECAG, adrenalectomy is often indicated.Item Pyruvate-enriched solution limits lactate and creatine accumulation in hypothermic machine-perfused kidney(2023) Mohammad, Moath; Tamayo, Jesus; Wade, Michael; Tran, Amanda; O'Hara, Collin; O-Yurvati, Albert; Mallet, Robert T.With a 5% annual increase in incidence, end-stage renal disease (ESRD) is a mounting epidemic. Kidney transplantation is the only definitive treatment for ESRD, but the growing demand for transplantable kidneys greatly exceeds the supply, thus improved methods of organ preservation are urgently needed. Recently, renewed interest in hypothermic machine perfusion (HMP) has prompted refinements of perfusion solutions to improve graft performance and transplant outcomes. In previous studies, solutions containing the intermediary metabolite pyruvate prevented ATP depletion, detoxified reactive oxygen species, suppressed inflammation and optimized protection of ischemic myocardium and brain. This study aimed to examine the hypothesis that pyruvate-enriched preservation fluids provide robust preservation of histological structure and energy metabolism in porcine kidneys during 72 hours HMP. The study used 7 Yorkshire swine kidneys, which were harvested and immediately flushed with ice-cold Ringer's solution and then perfused with either control or 20 mM pyruvate-enriched Ringer's solution for 72 hours in a LifePort organ preservation system. Values for renal artery flow and resistance were recorded over time. After 72 hours HMP, the renal cortex was biopsied and analyzed for metabolite content via spectrophotometry, while the cortex and medulla were biopsied for histological evaluation. The results showed that pyruvate-enriched preservation fluids lowered creatine content by 89% (P < 0.05), and surprisingly lowered lactate content while increasing glucose-6-phosphate content, a source for maintaining antioxidant reducing power. Flow and resistance were comparable between the two groups, and histological analysis revealed interstitial and intracellular edema, varying stages of acute tubular necrosis and variable loss of overall glomerular architecture in both groups. In conclusion, pyruvate-enriched preservation fluids stabilized the cellular energy state, supplied glucose-6-phosphate for sustaining antioxidants, and shunted metabolites from the glycolytic pathway leading to lower lactate accumulation in the renal cortex. Further research is warranted to understand pyruvate's impact on oxidative stress and inflammation during HMP.