pituitrin and Proteinuria

Topics: Absorption; Acetylglucosaminidase; beta 2-Microglobulin; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Kidney Tubules, Distal; Kidney Tubules, Proximal; Molecular Weight; Proteinuria; Vasopressins

Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

Topics: Adult; Animals; Arginine Vasopressin; Biomarkers; Blood Pressure; Disease Models, Animal; Early Diagnosis; Endothelium, Vascular; Female; Glycopeptides; Humans; Hypertension; Kidney Glomerulus; Male; Mice; Mice, Inbred C57BL; Pre-Eclampsia; Pregnancy; Proteinuria; ROC Curve; Time Factors; Vasopressins

The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with l-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HT+T rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V(2) vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.

Topics: Amitrole; Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 1; Aquaporin 2; Aquaporin 4; Aquaporins; Biological Transport, Active; Blotting, Western; Echocardiography; Hemodynamics; Hypothyroidism; Kidney; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Sodium-Potassium-Exchanging ATPase; Vasopressins

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Creatinine; Diabetes Insipidus; Disease Models, Animal; Disease Progression; Kidney; Kidney Failure, Chronic; Male; Proteinuria; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Uremia; Vasopressins

The effect of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on chronic progressive glomerular disease was investigated in Wistar rats with Adriamycin-induced nephropathy. At weeks 0 and 3, Adriamycin was injected twice, and at week 3 drugs started to be given as follows: groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as control. To block the effects of vasopressin totally, both V1 and V2 antagonists were simultaneously administered (group 4). At weeks 8 and 10, V1 and V2 antagonists given either alone or combined significantly reduced the urinary protein excretion to the same levels. Urinary volume increased in groups 3 and 4 from week 4. Systolic blood pressure did not significantly increase in all groups during the study. Histological alterations in the kidney of groups 2, 3 and 4 were significantly attenuated compared to the control. These results suggest that both vasopressin V1 and V2 agonism plays a role in the pathophysiology of Adriamycin-induced nephropathy despite plasma levels of vasopressin within the normal range. These findings also lead to the notion that in some types of nephrotic patients these orally available V1 and/or V2 receptor antagonists may be effective for reduction of proteinuria and for retardation of progression of renal failure.

Topics: Animals; Antibiotics, Antineoplastic; Blood Pressure; Body Weight; Doxorubicin; Eating; Kidney; Kidney Diseases; Male; Proteinuria; Rats; Rats, Wistar; Receptors, Vasopressin; Vasopressins

1. Partial (5/6) renal ablation was performed in Long Evans rats treated with vehicle or a vasopressin V1-receptor antagonist, in control Long Evans rats, and in homozygous Brattleboro rats which lack endogenous vasopressin. 2. In control and vasopressin-blocked Long Evans rats, 3 weeks following partial renal ablation, systolic blood pressure was 215 +/- 5 and 199 +/- 9 mmHg and, urinary protein excretion was 54 +/- 4 and 50 +/- 3 mg day-1, respectively. 3. The pressor response to exogenous vasopressin was significantly (P less than 0.05) reduced in rats treated with the V1-receptor antagonist (ED50 mmHg 5.0 +/- 1.6 vs. 0.09 +/- 0.01 micrograms kg-1). 4. In control Long Evans and in Brattleboro rats, 3 weeks following renal ablation, systolic blood pressure was 204 +/- 10 and 191 +/- 7 mmHg, and urinary protein excretion was 97 +/- 27 and 71 +/- 5 mg day-1, respectively. 5. Histological examination of the remaining kidney tissue demonstrated significant glomerular hyalinization following renal ablation but no differences between any of the groups. 6. The data indicate that neither vasopressin nor the urinary concentrating mechanism is likely to be involved in the hypertension and proteinuria associated with partial renal ablation.

Topics: Animals; Blood Pressure; Body Weight; Hypertension, Renal; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Male; Osmolar Concentration; Proteinuria; Rats; Rats, Brattleboro; Urodynamics; Vasopressins

Topics: Blood Volume; Catecholamines; Diuresis; Humans; Immersion; Kallikreins; Kidney; Natriuresis; Natriuretic Agents; Prostaglandins E; Proteinuria; Renin-Angiotensin System; Vasopressins

We observed idiopathic light-chain proteinuria in a patient with multiple abnormalities of proximal-tubule transport mechanisms (Fanconi syndrome), nephrogenic diabetes insipidus, and distal renal tubular acidosis. Seventeen of the 19 urinary amino acid levels measured were elevated. Uric acid and phosphate clearances were greater than 60 per cent and 50 per cent, respectively, of the simultaneous inulin clearance. When water deprivation was coupled with vasopressin administration, the maximum urinary concentration observed was 384 mOsm per kilogram of water. During ammonium-chloride loading, the level of hydrogen-ion concentration in the urine remained less than 100 times that in the blood. Kappa light-chain excretion was 149 mg per 24 hours. It appears that the concurrence of proximal tubular dysfunction, distal tubular dysfunction and light-chain proteinuria represents a distinct syndrome, which we call "combined light-chain nephropathy." Available evidence indicates that excessive light-chain production with subsequent filtration, reabsorption and catabolism, causes the complex tubular dysfunctions observed.

Topics: Acidosis, Renal Tubular; Ammonium Chloride; Bence Jones Protein; Diabetes Insipidus; Fanconi Syndrome; Female; Follow-Up Studies; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Kidney Concentrating Ability; Kidney Diseases; Kidney Tubules; Kidney Tubules, Distal; Middle Aged; Proteinuria; Renal Aminoacidurias; Syndrome; Vasopressins

A single case of gastric plasmacytoma showing unusual clinical and pathological features is described. The patient had gluten sensitive enteropathy, and showed increased circulating IgA levels prior to gastrectomy. Progression of the disease was associated with both K and L light chain proteinuria, hypoalbuminaemia, and vasopressin resistant polyuria. Pathological investigation revealed the coexistence of IgA secreting soft tissue plasmacytoma, with IgG secreting myeloma. The significance of these findings is discussed.

Topics: Autopsy; Blood Transfusion; Celiac Disease; Gastrectomy; Glutens; Humans; Immunoglobulin Fragments; Immunoglobulins; Kanamycin; Lymph Nodes; Male; Middle Aged; Multiple Myeloma; Osmolar Concentration; Plasmacytoma; Polyuria; Proteinuria; Serum Albumin; Sodium; Stomach; Stomach Neoplasms; Vasopressins

Topics: Adolescent; Adult; Amino Acids; Body Weight; Calcium; Cyclophosphamide; Cystitis; Diuresis; Female; Glomerular Filtration Rate; Humans; Hyponatremia; Kidney; Kidney Concentrating Ability; Male; Middle Aged; Natriuresis; Neoplasms; Osmolar Concentration; Phosphorus; Potassium; Proteinuria; Uric Acid; Vasopressins

Topics: Animals; Diuresis; Feeding Behavior; Hypothalamo-Hypophyseal System; Hypothalamus; Kidney Concentrating Ability; Obesity; Proteinuria; Rats; Species Specificity; Vasopressins; Water-Electrolyte Balance

Topics: Aldosterone; Blood Proteins; Body Fluids; Edema; Heart Function Tests; Humans; Kidney Function Tests; Liver Function Tests; Proteinuria; Vasopressins

Topics: Adult; Anemia, Sickle Cell; Bicarbonates; Blood Cell Count; Creatinine; Cystoscopy; Diuresis; Erythrocytes; Ethacrynic Acid; Furosemide; Glucose; Hematocrit; Hematuria; Hemoglobins, Abnormal; Hemoglobinuria; Hemolysis; Humans; In Vitro Techniques; Injections, Intravenous; Male; Mannitol; Osmolar Concentration; Oxygen; Oxygen Inhalation Therapy; Proteinuria; Sodium; Tromethamine; Vasopressins; Water

Topics: Adult; Aminohippuric Acids; Diuresis; Electrophoresis; Glomerular Filtration Rate; Heart Rate; Humans; Inulin; Male; Physical Exertion; Posture; Proteinuria; Ribonucleases; Vasopressins

Topics: Humans; Hyponatremia; Porphyria, Acute Intermittent; Porphyrias; Proteinuria; Seizures; Urine; Vasopressins

Topics: Blood Pressure; Body Weight; Diuresis; Edema; Female; Glomerulonephritis; Humans; Hypertension; Hypertension, Renal; Inulin; Kidney; Kidney Function Tests; Nephrosclerosis; Osmolar Concentration; Pathology; Pharmacology; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Vasopressins