Short-term moderate sodium restriction induces relative hyperfiltration in normotensive normoalbuminuric Type I diabetes mellitus

Abstract

Diabetic nephropathy is one of the most serious complications of diabetes mellitus. Nephropathy develops in approximately 35 % of diabetic patients [1].Preventive measures include good metabolic control and rigorous antihypertensive treatment, preferably by renin-angiotensin system (RAS) blocking agents [2]. Early abnormalities preceding overt nephropathy include microalbuminuria, a rise in blood pressure and an increase in intraglomerular pressure [3,4]. Volume expansion is probably relevant in these processes because renal sodium excretion is known to be blunted in diabetic patients [5,6,7,8,9], an effect that might be mediated by the sodium retaining effects of insulin [10,11].Considering the abnormalities in extracellular volume, dietary sodium restriction would seem a logical form of treatment. However, low sodium intake acti- Diabetologia (2002) Abstract Aims/hypothesis. Type I (insulin-dependent) diabetes mellitus is associated with an increased extracellular volume. Sodium restriction might seem a logical form of treatment but data on its renal effects is conflicting. We therefore studied the effects of sodium restriction on renal haemodynamics in uncomplicated Type I diabetes mellitus. Methods. Uncomplicated Type I diabetic patients (n = 24) and matched control subjects (n = 24) were studied twice in random order: after a week of 50 mmol or after 200 mmol sodium intake, respectively. The diabetic patients were studied under normoglycaemic clamp conditions. Glomerular filtration rate and effective renal plasma flow were measured as the clearances of iothalamate and hippuran, respectively. Results. During liberal sodium intake, glomerular filtration, effective renal plasma flow and filtration fraction were similar between the diabetic patients and the control subjects. Sodium restriction decreased the effective renal plasma flow in both groups, whereas glomerular filtration rate only decreased in the control subjects. Consequently, in the diabetic patients, the filtration fraction was increased on low sodium (4.1 8.4 %, p < 0.05 vs liberal sodium). As a consequence, filtration fraction (24.0 2.6 vs 22.1 2.0 %, p < 0.05) and glomerular filtration (119 14 vs 110 13 ml/min, p < 0.05) were higher in the diabetic patients than in the control subjects during sodium restriction. Conclusion/interpretation. Short-term moderate sodium restriction induces relative hyperfiltration in uncomplicated Type I diabetes. This could indicate an increased intraglomerular pressure. Sodium restriction could be an unfavourable preventive approach in diabetes mellitus but its long-term effects are not known. [Diabetologia (2002) 45:535±541]

Non-invasive investigation of kidney disease in type 1 diabetes by magnetic resonance imaging

“…The MRI-derived values for renal blood flow in our control participants are of the same order of magnitude as previously reported using MRI [27] and clearance methods [8]. Clearance studies have suggested increased [28] or normal [26,29] effective renal plasma flow in younger normoalbuminuric type 1 patients with relatively short disease duration. However, our normoalbuminuric patients were older, with much longer durations of diabetes.…”

Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration

“…The preferential effect of SGLT2 inhibition on R A , rather than R E , is important in light of how these agents could potentially be used in patients taking renin-angiotensin-aldosterone system (RAAS) inhibitors [7]. The renal effects of SGLT2 inhibition could be complementary to the well described changes in R E achieved with RAAS blockade, an intriguing concept for the design of future renal protection studies using the combination of dual SGLT2-RAAS inhibition (ACE inhibition or angiotensin II receptor blockade) to normalise glomerular hyperfiltration (ESM Fig.…”

Renal function in relation to sodium intake: a quantitative review of the literature

“…Of these, 11 were crosssectional studies, [10][11][12][13][14][15][16][17][18][19][20] 5 were longitudinal cohort studies, [21][22][23][24][25] and 20 were intervention trials. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] The weighted means of sodium intake were similar among studies in which consumption was assessed by means of spot urine samples 13,16,17,19 (mean, 156 mmol/d; range, 96-209 mmol/ d) 16,17 and 24-hour urine collections 10,11,14,15,20,22,24,…”