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Coding variants in apolipoprotein L1 (APOL1), termed G1 and G2, can explain most excess kidney disease risk in African Americans; however, the molecular pathways of APOL1-induced kidney dysfunction remain poorly understood. Here, we report that expression of G2 APOL1 in the podocytes of Nphs1rtTA/TRE-G2APOL1 (G2APOL1) mice leads to early activation of the cytosolic nucleotide sensor, stimulator of interferon genes (STING), and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. STING and NLRP3 expression was increased in podocytes from patients with high-risk APOL1 genotypes, and expression of APOL1 correlated with caspase-1 and gasdermin D (GSDMD) levels. To demonstrate the role of NLRP3 and STING in APOL1-associated kidney disease, we generated transgenic mice with the G2 APOL1 risk variant and genetic deletion of Nlrp3 (G2APOL1/Nlrp3 KO), Gsdmd (G2APOL1/Gsdmd KO), and STING (G2APOL1/STING KO). Knockout mice displayed marked reduction in albuminuria, azotemia, and kidney fibrosis compared with G2APOL1 mice. To evaluate the therapeutic potential of targeting NLRP3, GSDMD, and STING, we treated mice with MCC950, disulfiram, and C176, potent and selective inhibitors of NLRP3, GSDMD, and STING, respectively. G2APOL1 mice treated with MCC950, disulfiram, and C176 showed lower albuminuria and improved kidney function even when inhibitor treatment was initiated after the development of albuminuria.

Objective: SYNTAX score is now increasingly used as an index to guide further revascularization measures in patients with coronary artery disease. This study is aimed at finding association of glycated hemoglobin (HbA1c) and coronary artery disease severity and lesion complexity as assessed by SYNTAX score in non-diabetic patients who ultimately underwent coronary artery bypass grafting (CABG). Methods: A total of 587 non-diabetic patients who underwent CABG after coronary angiography from January 2007 to March 2010 were included in the study. Each patient’s SYNTAX score was calculated based on the coronary angiography. They were divided into four groups based on quartiles of HbA1c. Multivariate logistic regression analysis was performed to evaluate association of HbA1c to SYNTAX score and areas of lesions in individual coronary arteries. Results: The mean age of our population was 65 years with 77.3% males. The 4 quartiles of HBA1c were: HbA1c>=5.6%, HbA1c 5.7%-5.8%, HbA1c 5.9%-6.1% & HbA1c>=6.2%. There was no statistically significant association between HbA1c quartiles and SYNTAX score (p=0.54 for 4th vs. 1st quartile of HbA1c). Similarly, there was no statistically significant association between HbA1c and total number of diseased vessels (p=0.72) or total number of grafts used during CABG (p=0.40). We also found no statistically significant association between HbA1c levels and lesions at different anatomical sites: left main coronary artery (p=0.47), proximal left anterior descending (LAD) artery (p=0.92), mid-LAD artery (p=0.89), left circumflex artery (p=0.52) and right coronary &/or posterior descending artery (p=0.44). Conclusion: In non-diabetic patients undergoing CABG, there is no statistically significant association between HbA1c and location of coronary artery disease, number of diseased vessels or SYNTAX score.

Proton pump inhibitors (PPI), commonly used medications for peptic ulcer prophylaxis, have been recently described to cause hypomagnesemia through both urinary and gastrointestinal losses. Very few reports have linked hypomagnesemia with life-threatening ventricular arrhythmias. However, these reports included patients with other complex medical problems that may have also contributed to these arrhythmias. To our knowledge, ventricular arrhythmias associated with hypomagnesemia induced by proton pump inhibitors have never been reported. We present a case of a 53-year-old chronic alcoholic male patient, who was started on a proton pump inhibitor for peptic ulcer prophylaxis, which resulted in resistant hypomagnesemia associated with a storm of life-threatening arrhythmias, namely Torsades de Pointes (TdP). A 53-year-old man with no previous cardiac history was brought by Emergency Medical Services with a chief complaint of palpitations and dizziness for 1 day. His only significant medical history was chronic alcohol abuse and was not taking any medications before his admission. His physical examination was normal, except for an irregularly irregular rapid pulse and a blood pressure of 157/104 mm Hg. The ECG on admission showed atrial fibrillation with rapid ventricular response at an average of 190 beats per minute. Admitting routine labs showed normal complete blood counts. Electrolyte laboratory values revealed 136 mEq/L of sodium, 4.6 mmol/L of potassium, 100 mEq/L of chloride, 16 mEq/L of bicarbonate, 11 mg/dL of blood urea nitrogen, 0.68 mg/dL of creatinine, 9 mg/dL of calcium, and 1.5 mg/dL of magnesium. He was started on intravenous diltiazem for rate control and intravenous heparin for anticoagulation. Routine oral pantoprazole 40 mg once daily was also prescribed for peptic ulcer prophylaxis. Seven hours later, while on telemetry, the patient became unresponsive. The telemetry rhythm …