deamino-arginine-vasopressin and Albuminuria

The aim of the study was to evaluate whether normoalbuminuric type 1 diabetic patients with diabetic retinopathy (DR) have an impaired tubular response to desmopressin (dDAVP, a synthetic analog of vasopressin) administration, and its relationship with plasma and urine endothelin-1 (ET-1) levels.. This was an interventional case-control study.. The study was conducted at a referral center.. Fifteen normoalbuminuric type 1 diabetic patients with DR were compared with 30 normoalbuminuric type 1 diabetic patients without DR. Both groups were matched by age, gender, body mass index, glycosylated hemoglobin, and the main laboratory markers of kidney function.. After a 12-h period of water deprivation, dDAVP (0.3 microg/kg) was infused over 20 min. Urine was collected at baseline and 1, 2, and 3 h after dDAVP administration. ET-1 was assessed by ELISA.. dDAVP induced a lower rise in urine osmolality in patients with DR (from 650 +/- 206 to 754 +/- 224 mosmol/kg; P = 0.02) than in diabetic patients without DR (from 714 +/- 194 to 905 +/- 163 mosmol/kg; P < 0.0001). In addition, fractional excretion of Na+ decreased in patients without DR (from 0.45 +/- 0.30 to 0.29 +/- 0.29%; P = 0.04) but not in the diabetic patients with DR (from 0.36 +/- 0.22 to 0.36 +/- 0.40%; P = 0.96). Plasma ET-1 levels were inversely correlated with the response of urinary osmolality after dDAVP administration (r = -0.62; P = 0.008).. Normoalbuminuric type 1 diabetic patients with DR have impaired renal response to dDAVP that is related to plasma ET-1 levels. Further studies are required to elucidate whether this tubular resistance to dDAVP might favor dehydration in these patients.

Topics: Adult; Albuminuria; Creatinine; Deamino Arginine Vasopressin; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Endothelin-1; Female; Humans; Kidney Tubules; Male; Middle Aged; Osmolar Concentration; Young Adult

We analysed a large sample of children diagnosed with urinary tract malformations and/or infections and calculated diagnostic efficiency and quality indexes for five different functional markers, with the goal of testing which is the most sensitive for detecting a loss of renal parenchyma.. Ours was a cross-sectional retrospective study in which the clinical histories of 179 paediatric patients (91 male and 88 female) were evaluated. In 102 of these patients (57%), a scintigraphy revealed loss of parenchyma. The most commonly observed morphological type of damage was renal scarring. All patients had undergone at least one desmopressin urine concentration test. We also analysed albumin/creatinine and N-acetyl-glucosaminidase (NAG)/creatinine ratios, glomerular filtration rate (GFR), and urine volume.. By distributing patients according to normal/abnormal scintigraphy, we observed statistically significant differences between the two groups in maximum urine osmolality and GFR. Urine volume was elevated in 31.3% of cases (sensitivity: 37.9%; specificity: 81.8%) and 24% had a defect in renal concentrating ability (sensitivity: 30.4%; specificity: 84.8%). Urinary albumin excretion was high in 12.2% of patients, and 7.2% had a high NAG/creatinine ratio. GFR was low in only 5.7% of patients. These last two markers were the least sensitive but most specific for detecting a loss of renal parenchyma (100%).. In our study, the most sensitive functional tests for detecting the loss of renal parenchyma were the two that take into account the ability of the kidney to manage water, i.e. urine volume and maximum urine osmolality. These two tests had specificity >80%. However, the maximum specificity was obtained by the NAG/creatinine ratio and GFR, which were, conversely, the least sensitive tests. A normal GFR does not necessarily show normal renal function.

Topics: Acetylglucosaminidase; Adolescent; Albuminuria; Atrophy; Biomarkers; Child; Child, Preschool; Creatinine; Cross-Sectional Studies; Deamino Arginine Vasopressin; Female; Glomerular Filtration Rate; Humans; Infant; Kidney; Kidney Concentrating Ability; Male; Osmolar Concentration; Radionuclide Imaging; Retrospective Studies; Sensitivity and Specificity; Urinary Tract Infections; Urogenital Abnormalities; Vesico-Ureteral Reflux

Pyelectasis can be defined as mild to moderate dilatation of the urinary tract and is diagnosed by means of an ultrasound scan (0.5-2cm transverse diameter in the initial ultrasound performed after birth). There is some disagreement about whether cystography should be indicated as standard practice. The aim of this study was to establish if renal function tests are useful in determining which cases of mild to moderate dilatation of the urinary tract do not require an initial cystography.. The study was conducted on 79 infants (57 males, 22 females) with pyelectasis. Seventy-three were diagnosed in utero and 6 after birth. All infants underwent at least one cystography and one desmopressin urine concentration test before one year of age.. Compared to infants without vesicoureteral reflux (VUR) (n=68), infants with VUR (n=11; two with Grade I, three with Grade II, five with Grade III, two with Grade IV) showed a significantly lower (P=.006) maximum urine osmolality and a significantly higher microalbumin/creatinine ratio (P<.001) and NAG/creatinine ratio (P=.003). The negative predictive value of the first two tests was 93%. Sensitivity of the maximum urine osmolality to detect VUR was 72.7% (specificity 63.2%). Sensitivity of the microalbumin/creatinine ratio to detect VUR was 62.5% (specificity 75%). The positive probability ratio (PR) was 1.29 for the NAG/creatinine ratio, 2.03 for the maximum urine osmolality and 2.5 for the microalbumin/creatinine ratio. The negative PR was 0.95 for the NAG/creatinine ratio, 0.43 for the maximum urine osmolality and 0.5 for the microalbumin/creatinine ratio.. Pyelectasis is a benign condition. Only 2 patients required pharmacological intervention (prophylactic treatment for VUR Grade IV patients). Initially at least, cystography should not be indicated in cases of microalbuminuria and/or normal urine concentrations.

Topics: Acetylglucosaminidase; Albuminuria; Breast Feeding; Creatinine; Cross-Sectional Studies; Deamino Arginine Vasopressin; Early Diagnosis; Female; Humans; Hydronephrosis; Infant; Infant, Newborn; Kidney Function Tests; Male; Osmolar Concentration; Predictive Value of Tests; Prospective Studies; Pyelectasis; Radiography; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography, Prenatal; Urinalysis; Urinary Bladder; Urinary Tract; Vesico-Ureteral Reflux

A recent study has revealed that acute and chronic administration of the vasopressin V2 receptor (V2R) agonist dDAVP induced a marked increase of urinary albumin excretion (UAE) in healthy rats and humans (Bardoux P et al. Nephrol Dial Transplant 2003; 18: 497-506). The occurrence of an elevation of UAE among patients with chronic syndromes of inappropriate antidiuresis has not been reported.. We looked for the elevation of UAE in 24-h urine samples of the following patients: nine chronic SIADH patients, two patients with acute post-operative SIADH, three patients of the same family with nephrogenic syndrome of inappropriate antidiuresis (NSAID) and two patients with hyponatraemia due to surdosage of dDAVP in the setting of central diabetes insipidus.. There was no elevation of UAE in our patients (whether they presented with hyponatraemia or not), apart from a patient treated with supra-physiological doses of dDAVP. When she received 80 microg/day of dDAVP, her UAE was 42 mg/day. In this patient, UAE returned to the normal range (21 mg/day) when doses of dDAVP were tapered (20 microg/day).. The present study shows that chronic V2R stimulation generally does not result in a rise in UAE. The discrepancy between our results and those of the above-mentioned study could be explained by a dose-dependent effect of V2R stimulation on UAE.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Antidiuretic Agents; Chronic Disease; Circadian Rhythm; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Incidence; Male; Middle Aged; Mutation; Receptors, Vasopressin

An increase in urinary albumin excretion (UAE) represents an early predictor of glomerular damage in diabetes mellitus (DM) and a risk factor for cardiovascular complications in hypertension. Vasopressin is elevated in DM and in some forms of hypertension. Previous studies in rats suggested that this hormone could play a role in the albuminuria observed in chronic renal failure or diabetic nephropathy, but no information is available concerning the mechanism of these effects and the possible influence of vasopressin on UAE in the healthy kidney. The present study was thus designed to evaluate whether vasopressin influences UAE in normal rats and humans, whether this effect is V(2)-receptor-dependent, and whether it is mediated by the renin-angiotensin system.. UAE was measured in normal Wistar rats and healthy humans, or in subjects with various forms of diabetes insipidus (DI), before and after acute or chronic infusion of the vasopressin V(2) receptor agonist dDAVP. Chronic dDAVP administration was also performed in normal Wistar rats previously submitted to either chronic angiotensin-converting enzyme inhibition (ACEI) or chronic blockade of AT1 receptors (ARB).. In rats, acute or chronic dDAVP infusion increased UAE significantly and reversibly (4-fold and 6-fold, respectively). In healthy subjects, acute infusion of dDAVP tripled UAE (P<0.01) but did not change creatinine and beta(2)-microglobulin excretion, thus suggesting that the rise in UAE was due to an increased glomerular leakage of albumin. dDAVP also increased UAE in patients with central DI and in patients with hereditary nephrogenic DI bearing AQP2 mutations. However, UAE was not increased in patients with hereditary nephrogenic DI bearing mutations of the V(2) receptor. In rats, ACEI and ARB blunted the dDAVP-induced rise in UAE by 70% (P<0.05) and 50% (NS), respectively.. The present studies reveal for the first time that vasopressin induces a marked increase in UAE in healthy rats and humans. This albuminuric effect seems to result from increased glomerular leakage, requires functional vasopressin V(2) receptors, and is, at least in part, mediated by the renin-angiotensin system. These results bring additional support for an involvement of vasopressin in the albuminuria observed in pathological states such as diabetes mellitus or hypertension.

Topics: Adult; Albuminuria; Animals; Blood Pressure; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Rats; Receptors, Vasopressin; Reference Values; Renal Agents; Renin-Angiotensin System; Vasopressins