増田 貴博

We previously demonstrated that combining a sodium-glucose cotransporter 2 (SGLT2) inhibitor with diuretics significantly reduces interstitial fluid volume without excessive depletion of circulating plasma volume or activation of the renin-angiotensin-aldosterone system (RAAS). However, the differential effects of SGLT2 inhibitor monotherapy versus combination therapy with diuretics on fluid dynamics in patients with pre-existing fluid retention remain unclear. This study included patients with fluid retention, defined by an extracellular water to total body water (ECW/TBW) ratio > 0.400, as measured by bioimpedance analysis. We evaluated 6-month changes in body fluid status and serum copeptin levels, a surrogate marker for vasopressin, between two groups: patients receiving SGLT2 inhibitor dapagliflozin monotherapy (SGLT2i group, n = 13; estimated glomerular filtration rate [eGFR] 25.0 ± 8.5 mL/min/1.73 m2) and those receiving dapagliflozin in combination with loop or thiazide diuretics (SGLT2i + diuretic group, n = 18; eGFR 29.8 ± 15.2 mL/min/1.73 m2). Changes in systolic blood pressure and estimated plasma volume did not significantly differ between groups. However, reductions in ECW/TBW, TBW, and interstitial fluid were significantly greater in the combination group than in the monotherapy group. Moreover, the increase in serum copeptin was significantly suppressed in the SGLT2i + diuretic group. No significant intergroup differences were observed in renin and aldosterone changes. These findings suggest that co-administration of SGLT2 inhibitor with diuretics can more effectively reduce interstitial fluid retention without inducing excessive plasma volume reduction or RAAS activation.

This case report describes an 80-year-old man with severe immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN), characterized by storiform fibrosis with diffuse lymphocytic and plasma cell infiltration observed on a renal biopsy. Steroid pulse therapy administered immediately after confirming a remarkable increase in urinary β2-microglobulin (100,948 μg/L) along with no evidence of malignancy significantly improved the renal function and reduced the urinary β2-microglobulin levels. This study highlights the potential utility of urinary β2-microglobulin as a biomarker for early treatment selection in severe IgG4-TIN and emphasizes the need for timely intervention to prevent irreversible kidney damage.

A patient with advanced colon cancer treated with ramucirumab, an anti-vascular endothelial growth factor receptor-2 agent developed nephrotic-range proteinuria and hypertension. A renal biopsy revealed hyaline occlusive glomerular microangiopathy with macrophage infiltration and focal podocyte swelling with hyperplasia. Furthermore, a circular fibrocellular crescent formation was observed. Anti-CD34 immunostaining indicated severe endothelial injury. Circulating syndecan-1, which is derived from the glycocalyx covering the endothelium, was moderately increased, similar to the plasma D-dimer level, but not as high as that in systemic endotheliopathy. This case suggests that severe kidney-specific endothelial injury may be responsible for the development of a unique extracapillary glomerulopathy as a side effect of ramucirumab.