The worldwide coronavirus disease 2019 (COVID-19) pandemic is still in progress, but much remains unknown about the disease. In this article, we review the asso- ciation of hypertension or the renin-angiotensin system (RAS) with COVID-19 and the correlation between electrolyte disorders and disease severity. Underlying hypertension is likely to be associated with severe or critical COVID-19, but the relationship is not clear owing to confounding factors. Angiotensin-converting enzyme 2 (ACE2) plays an important role in the non-classical RAS pathway and binds to a receptor binding domain of severe acute respiratory syndrome corona- virus 2 (SARS-CoV-2). The RAS blockade is known to increase ACE2 levels, but controversy remains regarding the effect of RAS blockade therapy in the course of COVID-19. Some reports have indicated a protective effect of RAS blockade on COVID-19, whereas others have reported an association of RAS blockade therapy with the occurrence of severe complications such as acute kidney injury and admission to the intensive care unit. Electrolyte disorders are not uncommon in patients with COVID-19, and severe COVID-19 has frequently shown hypokalemia, hyponatremia, and hypocalcemia. Electrolyte imbalances are caused by alteration of RAS, gastrointestinal loss, effects of proinflammatory cytokines, and renal tu- bular dysfunction by the invasion of SARS-CoV-2.

• Angiotensin-converting enzyme 2
• COVID-19
• Electrolyte
• Hypertension
• Hypocalcemia
• Hypokalemia
• Hyponatremia
• Renin-Angiotensin system

Background: Puromycin aminonucleoside (PA) can induce nephrotic syndrome in rats, and proteinuria is an important mediator of tubulointerstitial injury in glo- merulopathy. We assumed that glomerular proteinuria may affect tubular function, such as urinary concentration, and investigated whether a urinary concentration defect is associated with proteinuria in puromycin aminonucleoside nephrosis (PAN). We also investigated the defect response to enalapril. Methods: Glomerular proteinuria was induced by a single intraperitoneal injection of PA (150 mg/kg BW) in male Sprague-Dawley rats. In a half of these rats, en- alapril (35 mg/kg BW) was administered daily in a food mixture for two weeks. After the animal experiment, kidneys were harvested for immunoblot analysis and histopathologic examination. Results: Compared with the control group, PA-treated rats had severe proteinuria, polyuria, and a lower urine osmolality. PA treatment induced remarkable tubulo- interstitial injury and significant reductions in protein abundances of aquaporin-1 and Na-K-2Cl co-transporter type 2 (NKCC2). Proteinuria significantly correlated with osteopontin expression in the kidney and inversely correlated with renal ex- pression of aquaporin-1, aquaporin-2, and NKCC2. The degree of tubulointerstitial injury significantly correlated with proteinuria, urine output, and osteopontin ex- pression and inversely correlated with urine osmolality and renal expression of aquaporin-1, aquaporin-2, and NKCC2. No significant differences in parameters were found between PA-treated rats with and without enalapril. Conclusion: In PAN, glomerular proteinuria was associated with tubulointerstitial injury and water diuresis. Downregulation of aquaporin-1 and NKCC2 can impair countercurrent multiplication and cause a urinary concentration defect in PAN.

• Enalapril
• Proteinuria
• Puromycin aminonucleoside
• Tubulointerstitial injury
• Urinary concentration

Because it is associated with mortality, hyponatremia is an important feature of pulmonary arterial hypertension. Its mechanisms remain unclear, although right heart failure resulting from pulmonary arterial hypertension may lead to systemic congestion and arterial underfilling. However, most patients with pulmonary arte- rial hypertension are clinically euvolemic and have no peripheral edema. Unlike patients with underlying heart disease, neurohumoral activation is not demonstra- ted in hyponatremic patients with pulmonary arterial hypertension, who show features of congestive heart failure only at later stages in their disease. Here, a case vignette is introduced, and the pathophysiology of hyponatremia in pulmona- ry arterial hypertension will be discussed. Syndrome of inappropriate antidiuresis (SIAD) appears to underlie hyponatremia in the initial phase of pulmonary arterial hypertension. The mechanisms by which various lung diseases can lead to SIAD remain an enigma.

• Hyponatremia
• Pulmonary arterial hypertension
• Right heart failure
• Syndrome of inappropriate antidiuresis

Encapsulating peritoneal sclerosis (EPS) is a potentially fatal complication after long-term peritoneal dialysis, and tamoxifen can be used for its prevention and treatment. However, tamoxifen is known to increase the risk of venous thrombo- embolism. A 49-year-old woman was admitted with sudden abdominal pain. The patient had received peritoneal dialysis for 20 years and switched to hemodialysis after the diagnosis of EPS. Tamoxifen (10 mg) and prednisolone (20 mg) had been administered for 8 months. On computed tomography, the left hepatic lobe was hardly illuminated, leading to a diagnosis of liver infarction. A month later, she was re-admitted due to abdominal pain and extensive deep vein thrombosis of the leg. The administration of tamoxifen was stopped and prednisolone was re- duced to 10 mg. As her malnutrition progressed, she succumbed to death of gram negative sepsis. The patient was concluded to have liver infarction and extensive venous thrombosis as a side effect of tamoxifen.

• Encapsulating peritoneal sclerosis
• Liver infarction
• Tamoxifen
• Venous thromboembolism

Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arr- hythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity indu- ced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64- year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum elec- trolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and high- degree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic com- plications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

• Cardiotoxicity
• Cisplatin
• Complete atrioventricular block