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Introduction: Usual treatment for patients with aldosteroneproducing adrenal adenoma is adrenalectomy, whereas adrenal hyperplasia is generally treated medically. Selective adrenal venous sampling (AVS) has been adopted to differentiate between adenoma and hyperplasia. A previous ratio used in our institution for the diagnosis of adenoma proved to be too low. As a result, a disproportionate number of patients with a preoperative diagnosis of adenoma were operated and subsequently found to have hyperplasia. Materials and methods: This prospective study evaluated the long-term outcomes of unilateral laparoscopic adrenalectomy in the setting of lateralizing aldosterone hypersecretion caused by adrenal hyperplasia. Results: Twelve patients with unilateral excess aldosterone production due to hyperplasia underwent dominant side adrenalectomy. Long-term follow-up (mean 12 years) of these patients showed that blood pressure decreased from a mean of 163.4 ± 17.5/100 to 131.5 ± 9.7/80 mm Hg (p < 0.05), and the number of antihypertensive drugs decreased from 4.3 ± 0.7 to 2.2 ± 0.9 (p < 0.05). Mean potassium level increased from 3.7 to 4.2 mEq/L and the plasma aldosterone level decreased from 26.5 to 10.1 ng/dL. Conclusion: Dominant side adrenalectomy in patients with primary aldosteronism (PA) due to hyperplasia results in long-term clinical improvement. This procedure should be considered in selected patients with lateralization confirmed by venous sampling. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular-protective factor which may control vascular calcification. Endothelial cells were stimulated with 10-12 to 10-10 mol/l PTH. PKC and PKA are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine whether these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In nonstimulated cells, a PKC activator significantly stimulated OPG secretion, while a PKA activator was associated with a decline. These effects were blunted in the presence of calphostin C and Rp-cAMP, respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to the decrease observed with PTH, suggests that the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway. [ABSTRACT FROM AUTHOR]

Background: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation., Objectives: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles., Methods: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the β-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay., Results: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015)., Conclusions: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.

Background: Chest-pain patients with no evidence of acute coronary syndrome might still be at risk for adverse outcomes. Adding renal function to the classic scoring of CHADS and CHA 2 DS 2 VASC may improve risk stratification of chest-pain patients discharged from internal medicine wards after acute coronary syndrome (ACS) rule-out., Methods: We accessed medical records of patients admitted to internal medicine wards during 2010-2016 and discharged following ACS rule-out. A R 2 CHA 2 DS 2 -VASc score model that included higher scores as kidney function deteriorated was calculated and compared to CHADS and CHA 2 DS 2 VASC scores. The primary endpoint was the composite of 30-day ACS and mortality. One-year ACS and 1-year mortality were the secondary endpoints. The study included 12,449 patients, stratified into three risk groups according to their R 2 CHA 2 DS 2 -VASc score., Results: Participants were stratified into 3 groups according to R 2 CHA 2 DS 2 -VASc score. R 2 CHA 2 DS 2 -VASc score predicted better the composite outcome of ACS and 30-day and 1-year mortality after discharge (OR: 4, 95%, CI 2.3-7, p < 0.01 and OR: 13.3, 95% CI 7.8-22.7, p < 0.01, respectively). Receiver operating characteristic curve analysis showed better risk stratification of the R 2 CHA 2 DS 2 -VASc compared with both CHADS and CHA 2 DS 2 VASC score., Conclusions: The R 2 CHA 2 DS 2 -VASc score is a better predictor of short- and long-term cardiovascular morbidity and mortality after hospital discharge., (Copyright © 2020. Published by Elsevier Ltd.)

Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Background: Diabetes mellitus (DM) is the leading cause of end-stage kidney disease. Inflammation, fibrosis, coagulability and oxidative stress exacerbate kidney disease. The glycoprotein, Von Willebrand Factor (VWF) has a crucial role in platelet thrombus formation. The enzyme ADAMTS13 is responsible for VWF cleavage. Both are important in the interface between diabetic nephropathy, hypercoagulability and atherosclerotic cardiovascular disease. Vitamin D inhibits endothelial proliferation, blunts angiogenesis and is a cardioprotective agent. This study evaluated the role of vitamin D on ADAMTS13 activity in human umbilical vein endothelial cells (HUVEC) exposed to a diabetic-like environment., Methods: HUVEC were stimulated with 200µg/µl AGE-HSA, 250mg/dl glucose, and 10-10mol/l vitamin D for 24 hours. Western blot and ELISA techniques were used to determine ADAMTS13 protein expression and IL6 and IL8 protein secretion., Results: ADAMTS13 protein expression decreased and IL6 and IL8 protein secretion increased in HUVEC exposed to a diabetic-like environment. The addition of vitamin D significantly down-regulated IL6 and IL8 secretion and up-regulated ADAMST13 expression., Conclusions: Decreased ADAMTS13 expression in HUVEC exposed to a diabetic-like environment may contribute to the pathogenesis of hypercoagulability observed in DM. Normalization of ADAMTS13 by vitamin D may contribute to improvement in hypercoagulability.

Background: Kidney biopsies are not routinely performed for diabetic patients with chronic kidney disease. However in some cases, a biopsy is carried out to exclude other treatable Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients. e renal diseases. The prevalence and the nature of non diabetic renal disease (NDRD) among diabetic patients in Israel have not yet been evaluated., Objective: To assess pathological findings of kidney biopsies conducted in patients with diabetes mellitus., Methods: A total of 200 native kidney biopsies were performed during the study period. Patients who had a diagnosis of diabetes mellitus were included in the study. Clinical data and pathological findings were retrospectively collected and analyzed., Results: The cohort included 34 patients, median age 61.8 years. The male to female ratio was 25:9; mean serum creatinine was 1.8 ± 1.2 mg/dl The duration of diabetes was significantly shorter in patients with NDRD (6.8 ± 7.1 years vs. 13.0 ± 9.6 years in diabetic nephropathy (DN) or combined), whereas insulin therapy was significantly more common in patients with DN (72% vs 5% in NDRD). Diabetic retinopathy was documented in 57% of patients with diabetic nephropathy but wasn't documented in any patient with NDRD. Prevalence of NDRD, DN and combined pathology was 58.8%, 32.4% and 8.8% respectively. Neither the level of proteinuria nor the rate of renal function deterioration could predict pathological findings in the biopsy. The most common NDRD disease was nephrosclerosis., Conclusions: Non-diabetic renal disease was common. Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients.

Background: Halofuginone is a novel antifibrotic agent that can reverse the fibrotic process by specific inhibition of collagen type I synthesis., Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/6 nephrectomy rat model, Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure, proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, sirius red staining and in situ hybridization, Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen alpha1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo., Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.

Background: Primary aldosteronism is a common cause of non-renal secondary hypertension. A correct diagnosis results in curing the hypertension or targeting appropriate pharmacotherapy. In patients with low renin resistant hypertension (after treatment with three or more different anti-hypertensive drugs the blood pressure remains above 140/90 mmHg), screening for aldosteronism is mandatory., Objectives: To demonstrate that normal blood levels of potassium in resistant hypertensive patients do not exclude the possible presence of hyperaldosteronism, and to suggest the use of the plasma aldosterone concentration (ng/dl)/plasma renin activity (ng/ml/hour) ratio in screening for hyperaldosteronism., Methods: Blood tests, suppression and stimulation tests (2 L normal saline i.v./4 hours and 20 mg furosemide i.v. for 60 minutes in a standing position) were systematically performed in 20 low renin normokalemic resistant hypertensive patients. None had renal disorders, known endocrine abnormalities or heart failure. They did not receive anti-hypertensive drugs affecting PAC or PRA. Basal PRA and PAC were measured twice: PAC after saline infusion and PAC/PRA after stimulation., Results: PAC/PRA above 50 was used to denote hyperaldosteronism. Serum K was 4 +/- 0.07 mM/L, PAC 22.8 +/- 1.8 ng/dl, PRA 0.13 +/- 0.02 ng/ml/hour, PAC/PRA 190 +/- 22 (above 100 in 17). After suppression PAC decreased from 25 +/- 1.8 to 11 +/- 1 ng/dl (normal < 5 ng/dl). Stimulation did not affect PRA and PAC/PRA. Abdominal computed tomography scan revealed normal adrenal glands in 15 patients. Spironolactone (116 +/- 60 mg/day) normalized blood pressure in all patients; it was used as a single therapy in 8, and in association with only one anti-hypertensive drug in the remaining 12 patients. In one patient the treatment was discontinued due to the presence of hyperkalemia., Conclusions: Low renin resistant hypertension associated with normokalemia may be due to hyperaldosteronism. Normal aldosterone levels in the basal condition do not exclude the possibility of hyperaldosteronism. Using a PAC/PRA ratio above 50 as a screening test can aid the physician in deciding when to perform dynamic tests, thus increasing the sensitivity of the diagnosis of hyperaldosteronism. CT scan is frequently normal. Targeted pharmacotherapy leads to a normalization of blood values.