Changes in<i>N</i>-Acetyl-β-<scp>D</scp>-Glucosaminidase Activity in the Urine and Urinary Albumin Excretion in Magnesium Deficient Rats

Matsuzaki, Hiroshi; Ohdachi, Junko; Fuchigami, Masaaki; Masuyama, Ritsuko; Uehara, Mariko; Nakamura, Kotaro; Suzuki, Kazuharu

doi:10.1271/bbb.66.192

Cited by 15 publications

(7 citation statements)

References 13 publications

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“…Sakaguchi et al, in a retrospective cohort study found that hypomagnesemia was significantly associated with progression to end stage renal disease (ESRD) in patients with type 2 diabetic nephropathy but not in those with nondiabetic CKD [ 24 ]. Rats fed a magnesium deficient diet have been shown to have higher urine N-acetyl-β-D-glucosaminidase levels, reflecting that magnesium deficiency induces renal interstitial tubular injury [ 25 ]. We did not examine the magnesium levels of these patients, thus additional studies are needed to explore any substantial association between PPI induced hypomagnesemia and chronic kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

et al. 2016

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BackgroundAcute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death.MethodsTwo separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables.ResultsA total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case–control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05–1.16) and mortality (OR 1.76, 95 % CI 1.67–1.84) among patients taking PPIs versus those not on PPIs.ConclusionsUse of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

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Section: Discussionmentioning

confidence: 99%

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

et al. 2016

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“…The effect of Mg on renal function has also been investigated in a few animal experiments. For example, rats fed an Mg-deficient diet have been shown to have higher urine N -acetyl-β- d -glucosaminidase levels, indicating that Mg deficiency induces renal interstitial tubular injury (23). In a rat model of acute ischemic kidney injury, Mg supplementation has been shown to have a renoprotective effect (24).…”

Section: Discussionmentioning

confidence: 99%

Hypomagnesemia in Type 2 Diabetic Nephropathy

et al. 2012

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OBJECTIVE There is now growing evidence that magnesium (Mg) deficiency is implicated in type 2 diabetes and its complications. However, it has not been fully elucidated whether hypomagnesemia is a predictor of end-stage renal disease (ESRD) in type 2 diabetic nephropathy. RESEARCH DESIGN AND METHODS This retrospective cohort study included 455 chronic kidney disease (CKD) patients (144 with type 2 diabetic nephropathy and 311 with nondiabetic CKD) who were hospitalized at Osaka General Medical Center for a CKD educational program between April 2001 and December 2007. The primary outcome was progression to renal replacement therapy. Participants were categorized based on serum Mg level into Low-Mg (serum Mg level ≤1.8 mg/dL) and High-Mg (serum Mg level >1.8 mg/dL) groups with the previously published normal lower limit chosen as the cutoff point. RESULTS Of the subjects with type 2 diabetic nephropathy, 102 progressed to ESRD during follow-up (median, 23 months). A multivariate Cox proportional hazards model showed that after adjustment for various demographic factors and laboratory data, the Low-Mg group had a 2.12-fold higher risk of ESRD than the High-Mg group (95% CI 1.28–3.51; P = 0.004). In contrast, 135 of the nondiabetic CKD subjects progressed to ESRD during follow-up (median, 44 months). No significant difference in outcome was found between the Low- and High-Mg groups of this population (adjusted hazard ratio, 1.15; 95% CI 0.70–1.90; P = 0.57). CONCLUSIONS Hypomagnesemia is a novel predictor of ESRD in patients with type 2 diabetic nephropathy.

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“…Hypomagnesemia-induced chronic inflammation [26] and hemostatic biomarkers of hypomagnesemia have been linked to athrosclerosis. An animal study indicated that Mg deficiency induces renal interstitial tubular injury [27]. I propose that SGLT2 inhibitor reduces kidney damage due to hypomagnesemia by elevating serum Mg concentration.…”

Section: Mg Concentration Increases With Sglt2 Inhibitor Treatmentmentioning

confidence: 95%

Is the Renoprotective Effect of SGLT2 Inhibitors due to their Beneficial Effect on Hypomagnesemia?

Yanagawa¹

2017

J Diabetes Metab

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Magnesium (Mg) deficiency is linked to diabetes and cardiovascular (CV) events. Treatment with the sodiumglucose cotransporter 2 (SGLT2) inhibitor was associated with a suppressed occurrence of CV events in patients with type 2 diabetes. We recently suggested that the increase of the serum Mg level associated with SGLT2 inhibitor treatment could explain, at least in part, the reduction of the CV events. Recently SGLT2 inhibitors have also been reported to exert a renoprotective effect and various hypotheses have been proposed regarding the mechanism. Now we would like to propose another possible mechanism, namely, the role of Mg.Keywords: Magnesium; Sodium-glucose cotransporter 2 inhibitor; Diabetic nephropathy; Renoprotection Magnesium Deficiency is linked to Diabetes, Hypertension and Cardiovascular EventsMagnesium (Mg) acts as a coenzyme in the insulin secretion pathway, influences the insulin sensitivity, and acts as a modulator of Na-K ATPase. Insufficient intake of Mg can cause diabetes [1] and hypertension.Mg exerts favorable effects on the cardiovascular (CV) system, including an anti-inflammatory effect on the vascular endothelium and smooth muscle, vascular relaxant activity, and sympatholytic activity [2]. Of the total Mg content of the body, 99% is present within the cells, and only 1% is present outside cells. Thus, while hypomagnesemia reflects Mg deficiency in the whole body, Mg deficiency could be present even in the presence of serum Mg levels within the normal range [3]. Subjects with hypomagnesemia are known to be at an elevated risk of developing CV disease [4]. According to the findings of the Framingham Heart Study, hypomagnesemia is a risk factor for atrial fibrillation [5]; hypomagnesemia has also been reported to be associated with a risk of premature ventricular contractions, particularly in diabetic patients [6]. In addition, animal experiments have shown that hypomagnesemia causes reduced cardiac function [7]. Furthermore, hypomagnesemia has been reported to increase platelet aggregation, thereby facilitating thrombus formation, and to enhance coronary artery constriction, thereby increasing the risk of development of myocardial infarction [2].A high incidence of CV events and sudden death has also been reported in patients with hypomagnesemia. A meta-analysis of relevant studies, even those including patients without diabetes, revealed that elevation of the serum Mg level by 0.2 mmol/L was associated with a 30% decrease in the risk of onset of CV disease and 40% decrease in the risk of death from CV events [8]. Adequate dietary magnesium intake has been reported to be associated with a reduced risk of cardiovascular events [9]. Thus, it might be reasonable to conclude that the risk of CV disease/events decreases as the serum Mg concentration increases. Mg Concentration Increases with SGLT2 Inhibitor TreatmentSodium-glucose cotransporter 2 (SGLT-2) is expressed in the proximal renal tubules, where it reabsorbs about 80-90% of the filtered glucose. Selective and reversible inhi...

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Changes inN-Acetyl-β-D-Glucosaminidase Activity in the Urine and Urinary Albumin Excretion in Magnesium Deficient Rats

Cited by 15 publications

References 13 publications

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

Hypomagnesemia in Type 2 Diabetic Nephropathy

Is the Renoprotective Effect of SGLT2 Inhibitors due to their Beneficial Effect on Hypomagnesemia?

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