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Abstract Background Familial hypokalemic periodic paralysis (HypoPP) is an uncommon genetic disorder characterized by recurrent episodes of muscle weakness and hypokalemia, typically starting in early adulthood. The existence of hyperthyroidism in the presence of HypoPP is more strongly associated with a diagnosis of thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males with pathogenic KCNJ2 or KCNJ18 variants and without a family history of the condition. This case is novel due to the combination of familial HypoPP and hyperthyroidism induced by Graves’ disease, a rare occurrence especially in non-Asian populations. Case presentation A 40-year-old African American man presented with profound muscle weakness after consuming a high-salt meal. He had a significant family history of hyperthyroidism and hypokalemia. On examination, he showed profound weakness in all extremities. Laboratory tests confirmed hypokalemia and hyperthyroidism, and genetic testing identified a pathogenic variant in the CACNA1S gene (c.1583 G > A, p. R528H), with normal SCN4A, KCNJ2 and KCNJ18 sequencing. He was diagnosed with familial HypoPP and hyperthyroidism due to Graves’ disease. He was started on PO methimazole 10 mg three times a day and PO acetazolamide 250 mg twice a day. He was advised to follow a low carbohydrate and low salt diet. Conclusions This case highlights the importance of considering a genetic basis for HypoPP in patients with a family history of the condition, even when hyperthyroidism is present. The combination of familial HypoPP and Graves’ disease is rare and emphasizes the need for careful genetic and clinical evaluation in similar cases. Management should focus on correcting hypokalemia, treating hyperthyroidism, and lifestyle modifications to prevent recurrence.

Background: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. Methods: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. Results: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were p-value: p-value: 2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. Conclusions: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients.

Abstract Globally, diabetes mellitus is the leading cause of chronic kidney disease (CKD), and it is predicted to increase in the following years. Despite its high prevalence, CKD remains under diagnosed. In this BMC Medicine collection of articles on diabetic kidney disease (DKD), we place in context the importance of screening and early detection of DKD and the most accurate tools to monitor for optimal glycemic control in this his risk population. Further, we address this population's risk for severe complications such as stroke and all-cause mortality. We close this editorial by summarizing recent advances in management of this vulnerable population of patients with DKD, including guideline-directed medical therapy, novel treatments, and predictors of treatment failure.

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.

Boron-containing compounds (BCC), particularly boronic acids and derivatives, are being increasingly tested as diagnostic and therapeutic agents. Some effects of BCC involve phenomena linked to the action of steroid or thyroid hormones; among these, are the effects on muscle mass or basal metabolism. Additionally, some toxicology reports on mammals, including humans, sound an alert concerning damage to several systems, among which are the negative effects on the induction of male infertility. Systemic and local mechanisms to explain changes in metabolism and impaired fertility were collected and presented. Then, we presented the putative pharmacodynamic and pharmacokinetic mechanisms involved and demonstrated in these events. In addition, it is proposed that there are adducts of some oxygenated BCC with cis-diols in fructose, an essential source of energy for sperm–cell motility, an uncoupling of sex hormone-binding globulin (SHBG) and its ligands, and the modulation of the DNA synthetic rate. These effects share the reactivity of boron-containing compounds on the cis-diols of key molecules. Moreover, data reporting no DNA damage after BCC administration are included. Further studies are required to support the clear role of BCC through these events to disrupt metabolism or fertility in mammals. If such phenomena are confirmed and elucidated, an advance could be useful to design strategies for avoiding BCC toxicity after BCC administration, and possibly for designing metabolism regulators and contraceptive drugs, among other purposes. Boronic derivatives and carboranes have been proposed and studied in this field.