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Aims Diabetes mellitus (DM) is the leading cause of chronic kidney disease. Albuminuria is associated with an increased risk of cardiovascular mortality. Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) and mineralocorticoid receptor antagonists (MRAs) protect against albuminuria; however, their combined effects on albuminuria are unclear. We performed a network meta‐analysis to investigate the effects of SGLT2‐Is, MRAs and their combination on albuminuria in type 2 DM. Methods We systematically searched PubMed, Medline, EMBASE and the Cochrane Library from inception up to 20 November 2022. We selected randomized control and crossover trials that compared MRAs, SGLT2‐Is, MRAs + SGLT2‐Is, or a placebo in patients with type 2 DM with a urinary albumin‐creatinine ratio (UACR) ≥30 mg/g creatinine. The primary outcome was the change in the UACR. Results This meta‐analysis analysed 17 studies with 34 412 patients. The use of combination treatment with SGLT2‐Is and MRAs was associated with lower albuminuria compared with the use of SGLT2‐Is, MRAs, or the placebo alone [mean difference (95% CI): −34.19 (−27.30; −41.08), −32.25 (−24.53; −39.97) and −65.22 (−57.97; −72.47), respectively]. Treatment with SGLT2‐Is or MRAs alone caused a significant reduction in UACR compared with the placebo [mean difference (95% CI): −31.03 (−28.35; −33.72) and −32.97 (−29.68; −36.27), respectively]. The effects of MRAs on the UACR are comparable with those of SGLT2‐Is. Sensitivity analyses showed similar results. Conclusion Combination therapy with SGLT2‐Is and MRAs was associated with lower albuminuria in patients with type 2 DM compared with monotherapy with SGLT2‐Is or MRAs alone.

Angiotensin receptor-neprilysin inhibitor (ARNI) is an emerging therapeutic strategy for cardiorenal syndrome. Although the treatment with ARNI for hypertension is covered by governmental insurance systems in Japan, a putative position of ARNI in clinical hypertension guidelines is yet to be determined. However, clinical and experimental evidence is now accumulating concerning the therapeutic effects of ARNI for hypertension, in addition to heart failure, in Japan. Here we would like to present a case in which treatment with ARNI for hypertension was effective to beneficially control cardiorenal syndrome as well as hypertension. A 51-years-old man with a history of hypertension since 35 years-old experienced shortness of breath on exertion and on supine position visited Yokohama City University Hospital. Severely elevated blood pressure (234/165 mmHg) with hypertensive retinopathy (Keith-Wagner IIb, Scheie S2H3), as well as cardiorenal dysfunction (LVEF 39% on UCG, eGFR 25.4 mL/min/1.73m2, UPCR 0.56 g/gCr), were noted, and he was admitted to the hospital due to accelerated-malignant hypertension. On admission, the patient was administered with intravenous nicardipine to achieve blood pressure level around 160/110 mmHg, and then treated with oral nifedipine (40–80 mg daily) with tapering of intravenous nicardipine administration. After treatment transition to single oral nifedipine therapy (80 mg daily), his blood pressure was still around160/110 mmHg. Thus, treatment with ARNI (sacubitril/valsartan) was initiated with a starting dose of 50 mg daily on Day 9. On Day 10, his blood pressure was improved to around 130/90 mmHg without evident worsening of kidney function or elevation of serum potassium level. The patient was successfully treated with appropriate control of blood pressure without initiation of dialysis. This case suggests that ARNI is an interesting therapeutic strategy to treat cardiorenal syndrome with severe hypertension.

Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme 1 (UBA1) gene and is characterised by the overlap of multiple autoinflammatory and haematologic disorders. It is a rare disease first described in December 2020. Case presentation: We report the case of a 67-year-old Japanese man undergoing peritoneal dialysis (PD) for recurrent aseptic peritonitis caused by VEXAS syndrome. He presented with an unexplained fever, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed a high serum C-reactive protein concentration and an increased white blood cell count in the PD effluent. He was treated with antibiotics for PD-related peritonitis but to no avail. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography demonstrated intense FDG uptake in the left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and the patient was treated with oral prednisolone (PSL) 15 mg daily, with a good response. However, the PSL dose could not be tapered to less than 10 mg daily because of auricular pain, skin lesions, and PD effluent turbidity. Tocilizumab was administered every two weeks as a steroid-sparing agent; hence, the PSL dose could be tapered to 2 mg daily without any symptoms. Sanger sequencing of his peripheral blood sample revealed a mutation affecting methionine-41 (c.122 T > C; p.Met41Thr) of the UBA1 gene. We made the final diagnosis of VEXAS syndrome. He had a flare of VEXAS syndrome at a PSL of 1 mg daily with cloudy PD effluent, conjunctival hyperaemia, arthralgia, auricular chondritis, and inflammatory skin lesions, such as Sweet's syndrome, on his upper limbs and neck. Increasing the PSL dose to 11 mg daily relieved the symptoms within a few days. Conclusions VEXAS syndrome causes turbid PD effluent without infection. When peritonitis is observed in patients on PD, nephrologists and general physicians should consider the possibility of aseptic peritonitis due to autoimmune diseases, including VEXAS syndrome, and pay attention to their systemic findings.

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