Gut microbiota–derived metabolites play important roles in health and disease. D–amino acids and their L-forms are metabolites of gut microbiota with distinct functions. In this study, we show the pathophysiologic role of D–amino acids in association with gut microbiota in humans and mice with acute kidney injury (AKI). In a mouse kidney ischemia/reperfusion model, the gut microbiota protected against tubular injury. AKI-induced gut dysbiosis contributed to the altered metabolism of D–amino acids. Among the D–amino acids, only D-serine was detectable in the kidney. In injured kidneys, the activity of D–amino acid oxidase was decreased. Conversely, the activity of serine racemase was increased. The oral administration of D-serine mitigated the kidney injury in B6 mice and D-serine–depleted mice. D-serine suppressed hypoxia-induced tubular damage and promoted posthypoxic tubular cell proliferation. Finally, the D-serine levels in circulation were significantly correlated with the decrease in kidney function in AKI patients. These results demonstrate the renoprotective effects of gut-derived D-serine in AKI, shed light on the interactions between the gut microbiota and the kidney in both health and AKI, and highlight D-serine as a potential new therapeutic target and biomarker for AKI.

OBJECTIVE Clinicopathological characteristics, renal prognosis, and mortality in patients with type 2 diabetes and reduced renal function without overt proteinuria are scarce. RESEARCH DESIGN AND METHODS We retrospectively assessed 526 patients with type 2 diabetes and reduced renal function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²), who underwent clinical renal biopsy and had follow-up data, from Japan’s nationwide multicenter renal biopsy registry. For comparative analyses, we derived one-to-two cohorts of those without proteinuria versus those with proteinuria using propensity score–matching methods addressing the imbalances of age, sex, diabetes duration, and baseline eGFR. The primary end point was progression of chronic kidney disease (CKD) defined as new-onset end-stage renal disease, decrease of eGFR by ≥50%, or doubling of serum creatinine. The secondary end point was all-cause mortality. RESULTS Eighty-two patients with nonproteinuria (urine albumin-to-creatinine ratio [UACR] <300 mg/g) had lower systolic blood pressure and less severe pathological lesions compared with 164 propensity score–matched patients with proteinuria (UACR ≥300 mg/g). After a median follow-up of 1.9 years (interquartile range 0.9–5.0 years) from the date of renal biopsy, the 5-year CKD progression-free survival was 86.6% (95% CI 72.5–93.8) for the nonproteinuric group and 30.3% (95% CI 22.4–38.6) for the proteinuric group (log-rank test P < 0.001). The lower renal risk was consistent across all subgroup analyses. The all-cause mortality was also lower in the nonproteinuric group (log-rank test P = 0.005). CONCLUSIONS Patients with nonproteinuric diabetic kidney disease had better-controlled blood pressure and fewer typical morphological changes and were at lower risk of CKD progression and all-cause mortality.

Only a few studies have focused on the relationship between vitamin intake and depressive symptoms in Japanese individuals. This cross-sectional study investigated the relationship between vitamin intake and depressive symptoms in 1634 elderly Japanese individuals (65 years and older). The consumption of fifteen vitamins including retinol, a retinol equivalent, beta-carotene equivalent, vitamin D, alpha-tocopherol, vitamin K, vitamin group B, vitamin C, and cryptoxanthine was analyzed using a brief-type self-administered diet history questionnaire (BDHQ). The short version of the Geriatric Depression Scale (GDS) was used to assess depressive symptoms. The prevalence of participants with depressive symptoms was 26.7%. The consumption of all vitamins, except for retinol and vitamin D, was lower among depressed than non-depressed participants. The consumption of vitamins was significantly less in female and overweight participants with depressive symptoms than in elderly participants without depressive symptoms. After adjustments for potential confounders, none of the fifteen vitamins were correlated with depressive symptoms in male or underweight participants. Associations between vitamin deficiencies and depressive symptoms were observed in female and overweight elderly participants. Our findings demonstrated a relationship between vitamin intake and depressive symptoms.

The aim of this cross-sectional study was to examine the relationship of mineral intake, including sodium, potassium, calcium, magnesium, phosphorus, iron, zinc, copper and manganese, with depressive symptoms in both genders in the Japanese elderly population. A total of 1423 participants who were older than 65 years old were recruited in this study. Mineral intake was analyzed using a validated and brief self-administered diet history questionnaire. Depressive symptoms were assessed with a short version of the Geriatric Depression Scale. A logistic regression model was applied to determine the relationship between mineral intake and depressive symptoms. The prevalence of depressive symptoms was 20%. Except for sodium and manganese, mineral intake was significantly lower in the depressive symptoms group. There was no difference of mineral intake between male participants with depressive symptoms and those without such symptoms. However, in female participants, mineral intake was significantly lower in participants with depressive symptoms compared to those without such symptoms. Potassium, calcium, magnesium, phosphorus, iron, zinc, and copper were significantly and negatively correlated with depressive symptoms among female participants, but not male participants. Our results suggest that the deficiencies in mineral intake may be related to depressive symptoms, especially in women.

Objective.: We retrospectively studied the risk factors associated with relapse during remission maintenance therapy for myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-positive microscopic polyangiitis (MPA).Methods.: Sixty-two patients diagnosed with MPA according to the European Medicines Agency classification algorithm during a 2-year period from January 1, 2005, to December 31, 2006, and who achieved remission after the first remission-induction therapy, were examined (registration no. UMIN000001785).Results.: The patient group comprised 25 men and 37 women aged 70.0 ± 8.9 years. The mean observation period was 30.2 ± 15.9 months. The rate of relapse was 24.2% (15/62), and mean interval between remission and relapse was 16.9 ± 13.5 months. During maintenance therapy following remission, the risk of relapse increased when the reduction rate of prednisolone increased above 0.8 mg/month (OR 12.6, 95% CI 2.2–97.9). Proteinuria at the start of maintenance therapy (regression coefficient 1.991 ± 0.758, p < 0.05) and the change in red blood cell counts in urine during the period from the start of maintenance therapy to the final observation (regression coefficient 0.126 ± 0.040, p < 0.01) were identified as risk factors influencing the vasculitis damage index.Conclusion.: In Japan, relapse of MPO-ANCA-positive MPA may be associated with the reduction rate of oral prednisolone administration during maintenance therapy.