Tubular dysfunction in type I diabetes mellitus.

Miltényi, M; Körner, Anna; Tulassay, Tivadar; Szabó, Antal

doi:10.1136/adc.60.10.929

Cited by 45 publications

(23 citation statements)

References 10 publications

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“…Such a phenomenon has been suggested in studies involving healthy dogs, because the mechanisms responsible for diabetes-induced reductions in FE Na are saturable (36). A similar effect may occur in T1D-H patients under hyperglycemic conditions, leading to elevated FE Na compared with HC subjects (37). Our results support the notion that T1D-H exhibit a state of tubular sodium avidity during clamped euglycemic conditions, supporting the tubular hypothesis for hyperfiltration.…”

Section: Discussionsupporting

confidence: 80%

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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Section: Discussionsupporting

confidence: 80%

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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“…Spontaneous changes of HbA1c values had negligible effects on the excretion of NAG in patients with abnormal excretion rates. Miltényi et al [12] reported on a reversible tubular enzymuria during ketoacidosis in children with diabetes. According to the present data tubular enzymuria outside of acute deteriorations of glycemic control seems to reflect a dysfunction complicating long-standing diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…no severe hypoglycemia or ketoacidosis) when delivering urine samples. The mean number of urine assessments was 11 per patient [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26].…”

Section: Methodsmentioning

confidence: 99%

Predictive Value of Tubular Markers for the Development of Microalbuminuria in Adolescents with Diabetes

Kordonouri

Hartmann²,

Müller³

et al. 1998

Horm Res Paediatr

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The predictive value of tubular proteinuria and/or enzyme excretion for the development of microalbuminuria in patients with diabetes mellitus was investigated over a period of 7.5 years in 64 children and adolescents without microalbuminuria at baseline. An abnormal urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) preceded the increase of albumin excretion in all 8 patients (12.5%) developing microalbuminuria during this period (positive/negative predictive value 0.2 and 1.0, respectively). Also both, the actual as well as the long-term glycemic control (HbA1c) up to the onset of abnormal NAG excretion were predictive for the development of microalbuminuria. Fifty percent of those patients with both an elevated NAG excretion and an HbA1c ≧9% developed micro-albuminuria within the next 5 years. Therefore, periodic monitoring of urinary NAG excretion should be incorporated into the follow-up of patients with type 1 diabetes mellitus.

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“…Tubular damage may precede glomerular damage in diabetic nephropathy and it has been suggested that tubu lar dysfunction [1] and raised sodium-lithium counter transport activity (SLC) [2] may be markers of early dia betic nephropathy. It has also been suggested that in creased SLC is a marker of disturbed protons handling in the renal proximal tubule [2], and if this is true, we may expect that such a tubular dysfunction is not limited only to the transmembrane transport of sodium and hydrogen.…”

mentioning

confidence: 99%

“…The aims of our study were: (1) to study the excretion pattern of various markers of proximal tubular function in uncomplicated insulin-dependent diabetic (IDDM) subjects and to compare them with a control group of healthy subjects; (2) to assess whether SLC is associated with glomerular and tubular function, and (3) to study whether metabolic control was associated with markers of tubular function.…”

mentioning

confidence: 99%

Measures of Tubular Function in Normoalbuminuric Insulin-Dependent Diabetic Patients and Their Relationship with Sodium Lithium Countertransport Activity

Catalano

Winocour²,

Parlongo³

et al. 1996

Nephron

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The aim of this study was to assess the relationship between markers of tubular function, markers of glycaemic control and erythrocyte sodium-lithium countertransport activity (SLC) in 40 normotensive, normoalbuminuric insulin-dependent diabetic (IDDM) subjects and 11 normal control subjects. Nine IDDM subjects had SLC > 0.40 mmol lithium h-1 litre RBC-1. Glomerular filtration rate (GFR) and the excretion rate of retinol-binding protein (RBP), N-acetyl-β-D-glucosaminidase (β-NAG) and glucose were significantly higher in IDDM subjects compared to control subjects (Mann-Whitney test, p = 0.02, < 0.001, < 0.001 and < 0.001, respectively), whilst the two groups had similar SLC and TmPO₄ levels. There was no significant relationship between SLC and the other variables in IDDM subjects, even when comparing IDDM subjects with normal and high SLC. β-NAG excretion rate was correlated to urinary glucose (r_s 0.47, p = 0.001) and, weakly, to the other markers of glycaemic control (fasting blood glucose r_s = 0.31, p = 0.03, fructosamine r_s 0.28, p = 0.04, HbA[ r_s 0.27, p = 0.04). RBP excretion rate was correlated to the excretion rate of β-NAG (r_s 0.38; p = 0.007) and albumin (r_s 0.45; p = 0.002); the excretion rates of β-NAG and albumin were significantly associated (r_s0.37, p = 0.009). Diabetes duration did not correlate to any of the aforementioned variables. In this study, β-NAG and RBP overnight excretion rates were higher in normoalbuminuric IDDM subjects compared to control subjects but no relationship was present between SLC and tubular function in IDDM patients without complications. Excretion rates of different proteins appear to be interrelated and, in IDDM, β-NAG excretion is associated with glycaemic control.

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Tubular dysfunction in type I diabetes mellitus.

Cited by 45 publications

References 10 publications

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

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

Predictive Value of Tubular Markers for the Development of Microalbuminuria in Adolescents with Diabetes

Measures of Tubular Function in Normoalbuminuric Insulin-Dependent Diabetic Patients and Their Relationship with Sodium Lithium Countertransport Activity

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