Atrial natriuretic factor in the acute nephritic and nephrotic syndromes

Atrial natriuretic factor in the acute nephritic and nephrotic syndromes. Because the role of systemic hormones in the pathophysiology of edema in acute renal disease remains incompletely understood, we compared the levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA) in patients with acute glomerulonephritis (AGN), nephrotic syndrome (NS), and normal individuals during salt deprivation and salt loading. Sixteen patients with AGN (10 males) and nine patients with NS and hypoalbuminemia (7 males) were studied on admission, and after recovery (12 AGN patients) or remission (4NS patients). Eighteen normal controls were each studied after five days on a low (20mEq Na/day), regular (120mEq Na/day) and high (300mEq Na/day) dietary salt intake. Patients with AGN and NS had comparable edema (AGN 2.8 ± 0.53 kg; NS 3.36 ± 0.47 kg; SE) and urinary Na excretion (mean ± SEM: AGN 0.97 ± 0.11 mEq/hr; NS 1.06 ± 0.16 mEq/hr), but AGN patients had five times higher ANF (AGN 27.2 ± 4.06 fmol/ml; NS 5.51 ± 1.02 fmol/ml; P < 0.001) and six times lower PRA ng/liter · sec levels (AGN 0.187 ± 0.047; NS 1.144 ± 0.222; P < 0.001) than NS patients. The degree of edema was correlated with ANF levels in AGN patients (P < 0.001) but not in NS patients. There was a strong exponential negative correlation (r = -0.773, P < 0.0001) between ANF and PRA, in which AGN patients and Na-restricted controls were located in the opposite ends of the volume sensing-response, and NS patients in the middle, alongside controls with regular Na intake. Our studies suggest that intrarenal mechanisms are responsible for Na retention in AGN as well as in NS, but AGN patients have a compensatory hormonal response related to the degree of fluid retention, while volume-sensing receptors in hypoalbuminemic NS patients are neither actively stimulated nor suppressed, probably due to increased transudation of fluid out of the capillaries

Vimentin and heat shock protein expression are induced in the kidney by angiotensin and by nitric oxide inhibition

Vimentin and heat shock protein expression are induced in the kidney by angiotensin and by nitric oxide inhibition.BackgroundAngiotensin II (Ang II) infusion and nitric oxide synthesis (NOS) inhibition with Nω-nitro-L-arginine-methyl-ester (L-NAME) are experimental models of hypertension associated with renal inflammation and oxidative stress. To gain insight into the nature of the tubulointerstitial injury induced in these models, we studied lectin-binding specificities, vimentin expression, and heat shock protein (HSP) 60 and 70 in these experimental models.MethodsSprague-Dawley rats received Ang II infusion (435 ng/kg/min) for 2 weeks by subcutaneous minipumps (Ang II group, N = 5) or L-NAME in the drinking water (70 mg/100 mL) for 3 weeks (L-NAME group N = 7). The control group consisted of 10 rats. Systolic blood pressure (tail-cuff plethysmography), serum creatinine, and proteinuria were determined weekly. At the end of the treatment period, rats were sacrificed and kidneys studied. Binding specificities of fluorescein-labeled lectins were examined in frozen sections, and cellular infiltrates were identified by immunohistology and expression of vimentin and HSP 60 and 70 with immunohistochemistry and computer image analysis.ResultsTubulointerstitial accumulation of macrophages, lymphocytes, and Ang II–positive cells were present in the Ang II group and L-NAME group. Vimentin, HSP 60, and HSP 70 were increased 8 to 20 times in the cortex of the rats of the Ang II group and the L-NAME groups. Neoexpression of vimentin and HSPs was found primarily in proximal tubular cells.ConclusionAng II infusion and NOS inhibition induce tubular injury with epithelial cell transdifferentiation and expression of stress proteins. The role of these changes in the accumulation and activation of the interstitial inflammatory infiltrate merits further investigation