The impact of hyperfiltration on the diabetic kidney

Premaratne, Erosha; Verma, Sudhanshu Kumar; Ekinci, Elif I; Theverkalam, G; Jerums, George; MacIsaac, Richard J

doi:10.1016/j.diabet.2014.10.003

Cited by 88 publications

(81 citation statements)

References 112 publications

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“…Although AS-IV therapy reduced the glomerular tuft area, it did not prevent hyperfiltration in db/db mice. Hemodynamic, vasoactive, tubular, growth-promoting, and metabolic factors all contribute to diabetic hyperfiltration32. Enlarged glomeruli are a pathological feature of early DN, and they can increase the total surface area for filtration.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV ameliorates renal injury in db/db mice

Sun

Wang

Han

et al. 2016

Sci Rep

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Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Astragaloside IV ameliorates renal injury in db/db mice

Sun

Wang

Han

et al. 2016

Sci Rep

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“…Increased blood glucose values in T2DM result in hyperfiltration and increased renal urinary flow (121,122 …”

Section: Hyperfiltrationmentioning

confidence: 99%

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

et al. 2015

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Over the past decades, hypomagnesemia (serum Mg 2+ <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg 2+ on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.Globally, over 300 million people suffer from type 2 diabetes mellitus (T2DM), and the prevalence is predicted to rise to over 600 million over the next decades (1). T2DM is characterized by a combination of insulin deficiency and insulin resistance. The general pathophysiological concept is that hyperglycemia emerges when endogenous insulin secretion can no longer match the increased demand owing to insulin resistance (2).Since the 1940s, it has been reported that T2DM is associated with hypomagnesemia (3,4). Low serum magnesium (Mg 2+ ) levels have been reported in large cohorts of patients with T2DM (5). In T2DM, the prevalence of hypomagnesemia ranges between 14 and 48% compared with between 2.5 and 15% in healthy control subjects (4). Hypomagnesemia is associated with a more rapid, and permanent, decline in renal function in patients with T2DM (6). In addition, epidemiological studies consistently show an inverse relationship between dietary Mg 2+ intake and risk of developing T2DM (7). Several patient studies have shown beneficial effects of Mg 2+ supplementation on glucose metabolism and insulin sensitivity (8-10). Recently, Rodríguez-Morán et al. (11) published an excellent overview of the clinical studies addressing the role of Mg 2+ in T2DM. In our review, we will focus on the molecular mechanisms underlying these clinical observations. Mg 2+ is an essential ion for human health, as it is involved in virtually every mechanism in the cell, including energy homeostasis, protein synthesis, and DNA stability (12). Considering these divergent functions, it can be appreciated that serum Mg 2+ levels are tightly regulated between 0.7 and 1.05 mmol/L in healthy individuals. However, impaired intestinal Mg 2+ absorption or renal Mg 2+ wasting can lead to hypomagnesemia. A wide range of genetic and environmental factors can affect the Mg 2+ -deficient state, which have previously been extensively reviewed (12).In this review, we address the following questions that are central to the role of hypomagnesemia in T2DM: 1) Does Mg 2+ regulate insulin secretion? 2) How does Mg 2+ affect insulin resistance? 3) How does insulin regulate Mg 2+ homeostasis? Taken together, these questions will aid the understanding of whether hypomagnesemia is a causative factor for or a consequence of T2DM.

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“…Hyperfiltration is an early phenotype of DN, thought to precede microalbuminuria, and is associated with cardiovascular disease (CVD) and progression of DN [4]. The mechanisms responsible for hyperfiltration in diabetes are not completely understood, but are likely due to a combination of glomerular hemodynamic, vasoactive and metabolic factors that together increase intraglomerular pressure and flow, leading to structural changes including mesangial expansion and glomerular basement membrane thickening [5, 6]. Previous studies have for the most part supported a role for hyperfiltration in the initiation and progression of DN in T1D [7], but how hyperfiltration is associated with DN progression in T1D remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Hyperfiltration and uricosuria in adolescents with type 1 diabetes

et al. 2015

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Background Urine uric acid (UUA) has been implicated in the pathogenesis of diabetic nephropathy via its effect on tubular cells. We hypothesized that UUA would be greater in adolescents with type 1 diabetes (T1D) compared to those without. Second, we hypothesized that UUA and fractional uric acid excretion (FeUA) would be greater in adolescents with T1D and hyperfiltration (estimated glomerular filtration rate (eGFR) ≥141 mL/min/1.73m2) compared to those without hyperfiltration Methods Adolescents with (n=239) and without T1D (n=75) had UUA measured and FeUA calculated. Serum creatinine and cystatin C were used to calculate eGFR by the Zappitelli equation. Results Adolescents with T1D had higher eGFR (mean±standard deviation (SD): 120±22 vs. 112±16 mL/min/1.73m2, p=0.0006), lower urine pH (6.2±0.8 vs. 6.5±1.0, p=0.01), higher UUA (37.7±18.6 vs. 32.8±18.1 mg/dL, p=0.049) and FeUA (median, IQR: 6.2 [4.3–8.7] vs. 5.2 [3.6–7.0]%, p=0.02) compared to non-diabetic adolescents. Among adolescents with T1D, those with hyperfiltration had higher FeUA (8.6 [5.2–9.9] vs. 6.0 [4.2–8.3]%, p=0.02) compared to those without hyperfiltration. Conclusions Adolescents with T1D had higher eGFR, higher UUA and more acidic urine than non-diabetic controls, which may increase their risk of UUA crystallization. Adolescents with T1D and hyperfiltration had higher FeUA than those without hyperfiltration. These hypothesis-generating observations may suggest a potential pathophysiologic association between uricosuria and hyperfiltration.

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The impact of hyperfiltration on the diabetic kidney

Cited by 88 publications

References 112 publications

Astragaloside IV ameliorates renal injury in db/db mice

Astragaloside IV ameliorates renal injury in db/db mice

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Hyperfiltration and uricosuria in adolescents with type 1 diabetes

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