Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium is the best available marker of proximal tubular reabsorption of fluid. The first part of the present thesis reviews the background for the use of the lithium clearance (CLi) method. Micropuncture studies on proximal reabsorption of lithium, showed that CLi is a reasonably correct measure of end-proximal fluid delivery rate, even during osmotic diuresis. During severe salt restriction, distal reabsorption of lithium renders the CLi method inappropriate in animals, but this problem does probably not occur in humans. The major current issue is whether a quantitatively significant reabsorption of lithium occurs in the loop of Henle. Available evidence is in accord with the interpretation that it does not occur. The interpretation of results form CLi studies depends to a surprising degree on the investigators beliefs about renal physiology. In the evaluation of proximal tubular function, the relevant parameter is the absolute proximal reabsorption rate of fluid and sodium. In the evaluation of integrated distal tubular reabsorption of sodium, the relevant parameter is the fractional distal reabsorption rate of sodium. The fractional CLi does not give meaningful information, and calculated absolute distal reabsorption rate of sodium is inherently not suited to detect modest changes in distal reabsorption leading to large changes in sodium excretion. Results from the use of the CLi method in relation to diabetes are reviewed in the second section. Even in IDDM patients with early diabetic nephropathy, the proximal reabsorption rate is elevated, resulting in a normal CLi despite glomerular hyperfiltration. Overnight euglycemia did not change GFR in IDDM patients, but during maintained euglycemia, GFR was normalized. A few hours of hyperglycemia prevented the decline in GFR, whereas CLi was unchanged. Thus hyperglycemia produced changes in renal function similar to those observed previously, but the time-course of the effect of euglycemia on kidney function is delayed. Plasma levels of atrial natriuretic peptide, renin and glucagon were not importantly affected by plasma glucose. In NIDDM patients CLi was normal, despite slight hyperfiltration, although this observation must be confirmed in a study with larger sample size. Prompted by the clinical observation of a marked decline in the GFR induced by carbonic anhydrase inhibitors, we studied the renal effects of acetazolamide in a controlled study.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Lithium clearance in the evaluation of segmental renal tubular reabsorption of sodium and water in diabetes mellitus. 818 64

The aim of this study was to determine the influence of metabolic control of diabetes on natriuresis, the effect of natriuretic peptides and renal kallikrein on the kidney and the participation of proximal and distal tubules in natriuresis. The study was done in 41 individuals: 27 IDDM patients and 14 healthy controls. The patients were on insulin only, had normal blood pressure, and were prescribed a standard diabetic diet without sodium or protein restriction. Diabetic patients were assigned to subgroups, depending on the stage of nephropathy and level of metabolic control. Urine collection was done three times daily in all participants. The first collection was done after 500 mg lithium carbonate (p.o.) and was followed by 10 mg amilorid (Midamor, Thomas Morson Pharmaceuticals). The third collection of urine was used to evaluate excretion of cGMP. In addition to sodium, lithium, potassium and creatinine clearances, excretion of renal kallikrein, and levels of microalbuminuria, fructosamine and glycated hemoglobin were also determined. Lithium clearance was used to evaluate tubular sodium transport. The influence of diuretic peptides--ANP and urodilatin, on natriuresis was reflected by urinary cGMP excretion. Function of the kallikrein-kinin system was studied on the basis of excretion of kallikrein. Amilorid was used to test the effect of blocking amiloride-sensitive sodium channels in distal tubules on natriuresis (Tab. 1). A statistically significant decrease in mean lithium clearance was observed in IDDM patients as compared to healthy controls. Creatinine clearance was the same in both groups (Tab. 2). Lower lithium clearance was observed in the subgroup of diabetic patients with "silent" nephropathy. Diabetic patients with "silent" and early nephropathy had significantly higher levels of fractional sodium reabsorption in the proximal tubule when compared with controls (Tab. 3). Moreover, lower daily excretion of kallikrein was observed in patients with stage II nephropathy in comparison to the control group (Tab. 4). Amilorid uptake had no influence on urinary kallikrein. However, natriuresis after amilorid was significantly higher in diabetic patients than in controls. In conclusion, reabsorption in the proximal tubule is increased in patients with "silent" diabetic nephropathy, as revealed by decreased lithium clearance and unchanged creatinine clearance. Hyperactivity of the proximal tubule in stage II and III of diabetic nephropathy results in increased sodium reabsorption in the proximal tubule, as reflected by the increase in fractional sodium reabsorption in this tubule. Amilorid, a distal tubule blocker, reduces distal tubule activity independently of urinary kallikrein excretion. Elevated natriuresis was observed after amilorid without any change in urinary kallikrein excretion.
 ...
PMID:[Regulation of natriuresis in diabetic nephropathy]. 1171 8