Obesity and Diabetic Kidney Disease

Maric‐Bilkan, Christine

doi:10.1016/j.mcna.2012.10.010

Cited by 147 publications

(131 citation statements)

References 110 publications

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“…Although the exact mechanisms leading to DN are still being elucidated, they are believed to include chronic hyperglycemia and hyperinsulinemia/insulin resistance, intraglomerular and systemic hypertension, production of advanced glycation end products, intrarenal oxidative stress and inflammation, and possibly contributory factors related to obesity like fatty infiltration and altered adipokine production (3,(16)(17)(18)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). We observed that large weight loss within a 3-month period ameliorated several of these risk factors.…”

Section: Discussionmentioning

confidence: 75%

Short-Term Changes after a Weight Reduction Intervention in Advanced Diabetic Nephropathy

Friedman

Chambers

Kamendulis

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Obesity precedes and is strongly linked to the development of type 2 diabetic nephropathy in most patients, yet little is known about the effects of weight reduction on this disease. This study aimed to establish proof of concept for the hypothesis that weight reduction ameliorates diabetic nephropathy.Design, setting, participants, & measurements Six obese individuals with advanced diabetic nephropathy (estimated GFR ,40 ml/min per 1.73 m 2 , urine albumin excretion .30 mg/d) currently taking a reninaldosterone axis inhibitor underwent a 12-week very low calorie ketogenic weight reduction diet with encouragement of exercise between March and September 2012. Albuminuria and other parameters of kidney health were the main outcome measures.Results There was a 12% reduction in weight (median 118.5 versus 104.3 kg, P=0.03). The intervention was associated with a 36% reduction in albuminuria that did not reach statistical significance (2124 versus 1366 mg/24 h, P=0.08) and significant reductions in the filtration markers serum creatinine (3.54 versus 3.13 mg/dl, P,0.05) and cystatin C (2.79 versus 2.46 mg/l, P,0.05). Improvements were also noted for the diabetes markers fasting glucose (166 versus 131 mg/dl, P,0.05), fasting insulin (26.9 versus 10.4 mU/ml, P,0.05), and insulin resistance (9.6 versus 4.2, P=0.03). Physical function, general health, and the number of diabetes medications also showed statistically significant signs of improvement.Conclusions After a short-term intensive weight reduction intervention in patients with advanced diabetic nephropathy, improvements were observed in markers of glomerular filtration, diabetes status, and risk factors for kidney disease progression, as well as other general indicators of health and well-being.

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Section: Discussionmentioning

confidence: 75%

Short-Term Changes after a Weight Reduction Intervention in Advanced Diabetic Nephropathy

Friedman

Chambers

Kamendulis

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…4,6,10,11,18 The modality of stone removal could also add to this risk if it results in deterioration in renal function due to loss of renal parenchyma.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 This animal model has features of MetS (e.g., obesity, hypertension, insulin resistance, hyperglycemia, and dyslipidemia), which show a strong association with human CKD. 4,18 A recent study characterized juvenile MetS Ossbaw pig kidneys as having several risk factors for the development and progression of CKD: glomerular hyperfiltration; hyperperfusion; microvascular proliferation; adiposity; increased oxidative stress; inflammation; marked proximal tubule vacuolization; and mildly elevated interstitial fibrosis. 25 However, the nontreated pole of the SWtreated kidney or control (no SWs) kidneys of our adult MetS pigs did not show any renal pathology.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is limited information on whether SWL treatment may exacerbate the risk for renal functional impairment in patients with MetS-obesity, hypertension, insulin resistance, and other features of MetS being risk factors for CKD. 4,18 We examined this issue in a swine model of diet-induced obesity and MetS that develops similar features of human MetS. 19,20 …”

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confidence: 99%

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Shock Wave Lithotripsy Does Not Impair Renal Function in a Swine Model of Metabolic Syndrome

Handa

Johnson

Connors

et al. 2015

Journal of Endourology

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Purpose: To determine whether shock wave lithotripsy (SWL) may be a risk factor for renal functional impairment in a swine model of metabolic syndrome (MetS). Materials and Methods: Nine-month-old female Ossabaw pigs were fed an excess calorie atherogenic diet to induce MetS. At 15 months of age, the MetS pigs were treated with 2000 SWs or an overtreatment dose of 4000 SWs targeted at the upper pole calyx of the left kidney (24 kV at 120 SWs/min using the unmodified Dornier HM3 lithotripter; n = 5-6 per treatment group). Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured in conscious pigs before and *60 days after SWL to provide a qualitative assessment of how well both kidneys were filtering (glomerular filtration rate [GFR]). Bilateral renal function was assessed at *65 days post-SWL in anesthetized pigs with GFR and effective renal plasma flow (ERPF) quantified by the renal clearance of inulin and para-amino hippurate, respectively. Results: Cr and BUN values were within normal limits before SWL and remained unchanged after lithotripsy in both the 2000 SW-and 4000 SW-treated pigs. GFR and ERPF of kidneys treated with SWL at either SW dose were similar to the contralateral nontreated kidney. Chronic histological changes in the SW-treated pole of the kidney included interstitial fibrosis, sclerotic glomeruli, and dilated and atrophic tubules. Conclusions: Our results are consistent with the view that a single SWL session does not result in renal impairment, even in the presence of MetS.

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“…Importantly, hyperfiltration is common in patients with type 2 diabetes aged younger than 40 years, affecting 50% of afflicted patients (5). Moreover, hyperfiltration has been implicated as a common pathogenic mechanism leading to chronic kidney disease progression in other conditions such as obesity-related glomerulopathy (50% prevalence) (6), sickle cell disease (30-40% prevalence) (7), low birth weight, and reduced nephron number (8). In addition, hyperfiltration is associated with systemic vascular abnormalities, which may be associated with increased risk of microalbuminuria and retinopathy (9)(10)(11).…”

mentioning

confidence: 99%

Renal Hyperfiltration Is Associated With Glucose-Dependent Changes in Fractional Excretion of Sodium in Patients With Uncomplicated Type 1 Diabetes

et al. 2014

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OBJECTIVERenal hyperfiltration is a common abnormality associated with diabetic nephropathy in patients with type 1 diabetes (T1D). In animal models, increased proximal tubular sodium reabsorption results in decreased distal sodium delivery, tubuloglomerular feedback activation, afferent vasodilatation, and hyperfiltration. The role of tubular factors is less well understood in humans. The aim of the current study was therefore to compare the fractional sodium excretion (FE Na ) in hyperfiltering (T1D-H) versus normofiltering (T1D-N) patients and healthy control (HC) subjects, as well as the role of ambient hyperglycemia on FE Na . RESEARCH DESIGN AND METHODSBlood pressure, renal function (inulin for glomerular filtration rate [GFR], and paraaminohippurate for effective renal plasma flow), FE Na , and circulating neurohormones were measured in T1D-H (n = 28, GFR ‡135 mL/min/1.73 m 2 ), T1D-N (n = 30), and HC (n = 35) subjects during clamped euglycemia. Studies were repeated in a subset of patients during clamped hyperglycemia. RESULTSDuring clamped euglycemia, T1D-H exhibited lower FE Na than T1D-N and HC subjects (0.64 6 0.06% vs. 0.91 6 0.12% and 0.90 6 0.10%, P < 0.05). During clamped hyperglycemia, FE Na increased (D + 0.88 6 0.22% vs. D + 0.02 6 0.21%; betweengroup effect, P = 0.01) significantly in T1D-H, whereas FE Na did not change in T1D-N. When treated as continuous variables, elevated GFR values were associated with hyperglycemia-induced increases in FE Na (R 2 = 0.20, P = 0.007). CONCLUSIONSPatients with uncomplicated T1D-H exhibit lower FE Na under euglycemic conditions, which may help to identify patients with hyperfiltration outside of a controlled laboratory setting. Increased FE Na in T1D-H but not T1D-N under clamped hyperglycemic conditions suggests that the mechanisms responsible for increased sodium reabsorption leading to hyperfiltration can be saturated.

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Obesity and Diabetic Kidney Disease

Cited by 147 publications

References 110 publications

Short-Term Changes after a Weight Reduction Intervention in Advanced Diabetic Nephropathy

Short-Term Changes after a Weight Reduction Intervention in Advanced Diabetic Nephropathy

Shock Wave Lithotripsy Does Not Impair Renal Function in a Swine Model of Metabolic Syndrome

Renal Hyperfiltration Is Associated With Glucose-Dependent Changes in Fractional Excretion of Sodium in Patients With Uncomplicated Type 1 Diabetes

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