The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

Vitamin D for Recovery of COVID-19 in Patients With Chronic Kidney Disease.

The severity of coronavirus disease 2019 (COVID-19) is determined not only by viral damage to cells but also by the immune reaction in the host. In addition to therapeutic interventions that target the viral infection, immunoregulation may be helpful in the management of COVID-19. Vitamin D exerts effects on both innate and adaptive immunity and subsequently modulates immune responses to bacteria and viruses. Patients with chronic kidney disease (CKD) frequently have vitamin D deficiency and increased susceptibility to infection, suggesting a potential role of vitamin D in this vulnerable population. In this paper, we review the alterations of the immune system, the risk of COVID-19 infections and mechanisms of vitamin D action in the pathogenesis of COVID-19 in CKD patients. Previous studies have shown that vitamin D deficiency can affect the outcomes of COVID-19. Supplementing vitamin D during treatment may be protective against COVID-19. Future studies, including randomized control trials, are warranted to determine the effect of vitamin D supplementation on the recovery from COVID-19 in CKD patients.

Hypokalemic paralysis in hyperthyroidism: Not all that glitter are gold.

Abnormal acid-base status (metabolic acidosis or alkalosis), inappropriate urine electrolytes excretion (high or low Na+ and Cl-), and higher required dose of potassium supplement (4-5 mmol/kg) are suggestive of non-TPP causes of hypokalemia.

Comparison of short-term efficacy of iron sucrose with those of ferric chloride in hemodialysis patients: An open-label study.

BACKGROUND: It is intriguing and imperative that the comparison of the iron preparations in hemodialysis (HD) patients. This study aimed to observe the short-term efficacy of parenteral iron sucrose and ferric chloride in HD patients. MATERIALS AND METHODS: This was a consecutive 10-week single-blind study in Taiwan. An intravenous iron supplement of 100 mg/week was administered as an infusion in 100 ml of normal saline, until a total dose of 1000 mg was achieved. The primary outcome was evaluated by the changes in serum hematocrit (Hct) levels. The changes in serum Hct and iron indices were evaluated every 2 weeks for 10 weeks. The results were collected from 21 April to 4 July 2013. RESULTS: A total of 56 HD patients completed the study. Subjects were randomized into an iron sucrose group (26 patients) and a ferric chloride group (30 patients). Between the two treatment groups, there were no statistically significant differences in the change in serum Hct, ferritin, iron, or total iron binding capacity (P > 0.05). In the iron sucrose group, the increase in Hct levels was statistically significant at weeks 4, 8, and 10. In the ferric chloride group, the increase in Hct levels was statistically significant at week 8. No obvious major side effects were observed in both groups. CONCLUSION: In the study subjects, parenteral iron sucrose was as effective and safe as ferric chloride for treating anemia in HD patients.

Etiologic and therapeutic analysis in patients with hypokalemic nonperiodic paralysis.

BACKGROUND: Hypokalemic nonperiodic paralysis represents a group of heterogeneous disorders with a large potassium (K(+)) deficit. Rapid diagnosis of curable causes with appropriate treatment is challenging to avoid the sequelae of hypokalemia. We prospectively analyzed the etiologies and therapeutic characteristics of hypokalemic nonperiodic paralysis. METHODS: Over an 8-year period, patients with hypokalemic nonperiodic paralysis were enrolled by excluding those with hypokalemic periodic paralysis due to acute shift of K(+) into cells. Blood and spot urine samples were collected for the measurements of electrolytes, pH, and biochemistries. Intravenous potassium chloride (KCl) at a rate of 10-20 mmol/h was administered until muscle strength recovered. RESULTS: We had identified 58 patients with hypokalemic nonperiodic paralysis from 208 consecutive patients with hypokalemic paralysis, and their average K(+) concentration was 1.8 ± 0.2 mmol/L. Among patients with low urinary K(+) excretion (n = 17), chronic alcoholism, remote diuretic use, and anorexia/bulimia nervosa were the most common causes. Among patients with high urinary K(+) excretion (n = 41) and metabolic acidosis, renal tubular acidosis and chronic toluene abuse were the main causes, while primary aldosteronism, Gitelman syndrome, and diuretics were the leading diagnoses with metabolic alkalosis. The average KCl dose needed to restore muscle strength was 3.8 ± 0.8 mmol/kg. Initial lower plasma K(+), volume depletion, and high urinary K(+) excretion were associated with higher recovery KCl dosage. During therapy, patients with paradoxical hypokalemia (n = 32) who required more KCl supplementation than patients without (4.1 ± 0.7 vs 3.4 ± 0.7 mmol/kg, P < 0.001) often exhibited significantly higher plasma renin activity and received a higher volume of normal saline before its appearance. CONCLUSIONS: Understanding the common etiologies of hypokalemic nonperiodic paralysis may aid in early diagnosis. Patients with initial lower plasma K(+), renal K(+) wasting, and hypovolemia required higher recovery K(+) dosage. Paradoxical hypokalemia is prone to develop in hypovolemic patients even during K(+) supplementation with volume repletion.

Thyrotoxic periodic paralysis triggered by ß2-adrenergic bronchodilators.

Hypokalemic periodic paralysis is the most common form of periodic paralysis and is characterized by attacks of muscle paralysis associated with a low serum potassium (K+) level due to an acute intracellular shifting. Thyrotoxic periodic paralysis (TPP), characterized by the triad of muscle paralysis, acute hypokalemia, and hyperthyroidism, is one cause of hypokalemic periodic paralysis. The triggering of an attack of undiagnosed TPP by ß2-adrenergic bronchodilators has, to our knowledge, not been reported previously. We describe two young men who presented to the emergency department with the sudden onset of muscle paralysis after administration of inhaled ß2-adrenergic bronchodilators for asthma. In both cases, the physical examination revealed an enlarged thyroid gland and symmetrical flaccid paralysis with areflexia of lower extremities. Hypokalemia with low urine K+ excretion and normal blood acid-base status was found on laboratory testing, suggestive of an intracellular shift of K+, and the patients' muscle strength recovered at serum K+ concentrations of 3.0 and 3.3 mmol/L. One patient developed hyperkalemia after a total potassium chloride supplementation of 110 mmol. Thyroid function testing was diagnostic of primary hyperthyroidism due to Graves disease in both cases. These cases illustrate that ß2-adrenergic bronchodilators should be considered a potential precipitant of TPP.

Hypokalemic paralysis in a middle-aged female with classic Bartter syndrome.

Inherited classic Bartter syndrome (cBS) is an autosomal recessive renal tubular disorder resulting from inactivating mutations in the asolateral chloride channel (C1C-Kb) and usually presents in early infancy or childhood with mild to moderate hypokalemia. Profound hypokalemic paralysis in patients with cBS is extremely rare, especially in middle age. A 45-year-old Chinese female patient was referred for evaluation of chronic severe hypokalemia despite regular K+ supplementation (1 mmol/kg/d). She had had two episodes of muscle paralysis due to severe hypokalemia (K+ 1.9 - 2.1 mmol/l) in the past 3 years. She denied vomiting, diarrhea, or the use of laxatives or diuretics. Her blood pressure was normal. Biochemical studies showed hypokalemia (K+ 2.5 mmol/l) with renal potassium wasting, metabolic alkalosis (HCO3- 32 mmol/l), normomagnesemia (Mg2+ 0.8 mmol/l), hypercalciuria (calcium to creatinine ratio 0.5 mmol/mmol; normal < 0.22 mmol/mol), high plasma renin activity, but normal plasma aldosterone concentration. Abdominal sonography revealed neither renal stones nor nephrocalcinosis. Acquired causes of cBS such as autoimmune disease and drugs were all excluded. Molecular analysis of the CLCNKB gene, encoding ClC-Kb, and SLC12A3, encoding the thiazide-sensitive sodium chloride cotransporter (NCC), revealed compound heterozygous mutations in CLCNKB (L335P and G470E) inherited from her parents; her SLC12A3 was normal. These two mutations were not identified in 100 healthy subjects. Her plasma K+ concentration rose to 3 - 3.5 mmol/l after the addition of spironolactone. Inherited cBS may present with hypokalemic paralysis and should be considered in adult patients with hypokalemia and metabolic alkalosis.

Incidence and factors of post-adrenalectomy hyperkalemia in patients with aldosterone producing adenoma.

BACKGROUND: Hyperkalemia is a potentially serious complication following adrenalectomy of aldosterone-producing adenomas (APA). We analyzed the incidence and risk factors for hyperkalemia after adrenalectomy in patients with APA. METHODS: We retrospectively analyzed the records of 55 patients who underwent adrenalectomy for APA between 2002 and 2011. Demographic features, biochemical and hormonal profiles, imaging, and relevant medications were reviewed. RESULTS: Sixteen of 55 APA patients (29.1%) developed hyperkalemia (mean serum K(+) 5.6±0.3 mmol/l) after adrenalectomy and 3 had persistent hyperkalemia requiring mineralocorticoid supplementation for more than nine months. Compared with normokalemic patients, hyperkalemic patients were characterized by male predominance, older age, longer duration of hypertension (12.8±9.3 vs. 6.7±5.0 y, p<0.05), lower nadir serum K(+) (p<0.05), higher preoperative serum creatinine (p<0.01), and higher likelihood of residual hypertension. Using multivariate regression analysis, longer duration of hypertension and impaired renal function were the most important factors of post-adrenalectomy hyperkalemia. CONCLUSIONS: Post-adrenalectomy hyperkalemia in patients with APA is not rare and associated with impaired renal function and longer duration of hypertension. Serum K(+) must be cautiously monitored in patients with long-term hypertension and kidney disease.

A hypokalaemic woman with nephrocalcinosis: rebirth of old knowledge.

The coexistence of hypokalaemia and nephrocalcinosis poses a challenge in rapid diagnosis and appropriate management. We describe a 38-year-old woman who presented with thirst, intermittent carpopedal spasm, paresthaesia of both hands and progressive weakness of lower extremities for two years. She had a history of chronic hypokalaemia of unknown cause with intermittent potassium supplementation for 7-8 y and bilateral nephrocalcinosis notable for one year. She denied vomiting, diarrhoea or use of laxatives, alcohol or diuretics. Her blood pressure was normal. Laboratory investigations showed hypokalaemia (2.7 mmol/L) and metabolic alkalosis (HCO3(-) 32.6 mmol/L, pH 7.46). Two random urine samples both showed a consistently high urine K(+) excretion but with excretion rates of Na(+), Cl(-) and divalent cations which were high in one sample but not the other. Ingestion of furosemide 120 mg daily for body image for 7-8 y was uncovered. With furosemide cessation and potassium supplementation, her hypokalaemia with neuromuscular symptoms was corrected but nephrocalcinosis persisted. Surreptitious use of diuretics for various purposes should be kept in mind as an important cause of hypokalaemia and/or nephrocalcinosis. Measurement of electrolyte concentrations in at least two random urine samples is warranted to distinguish it from true renal tubular disorders and extrarenal causes.

Hypokalemic paralysis in a young obese female.

BACKGROUND: Profound hypokalemia with paralysis usually poses a diagnostic and therapeutic challenge. METHODS: We report on a 28-y-old obese Chinese female presenting with sudden onset of flaccid quadriparesis upon awaking in the morning. There is no family history of hyperthyroidism. She experienced body weight loss of 7 kg in 2 months. RESULTS: The most conspicuous blood biochemistry is marked hypokalemia (1.8 mmol/l) and hypophosphatemia (0.5 mmol/l) associated with low urine K(+) and phosphate excretion. Surreptitious laxatives and/or diuretics abuse-related hypokalemic paralysis were tentatively made. However, her relatively normal blood acid-base status and the absence of low urine Na(+) and/or Cl(-) excretion made these diagnoses unlikely. Furthermore, she developed rebound hyperkalemia (5.7 mmol/l) after only 80 mmol K(+) supplementation. Thyroid function test confirmed hyperthyroidism due to Graves' disease. Control of the hyperthyroidism completely abolished her periodic paralysis. CONCLUSIONS: Thyrotoxic periodic paralysis (TPP) should be kept in mind as a cause of paralysis in female, even with obesity, despite its predominance in adult males.