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The assessment of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF) on hemodialysis is often hampered by abnormal responses to the standard 1-mg dexamethasone suppression test. Various mechanisms have been proposed to explain this lack of suppressibility. The present study was designed to look into the mechanisms possible for these findings in patients with CRF. We studied 6 patients with CRF on hemodialysis and 5 healthy subjects utilizing the 1-mg dexamethasone suppression test as well as the 50-mg hydrocortisone suppression test. Samples were assayed for dexamethasone, adrenocorticotropic hormone, corticosterone, and cortisol by both direct radioimmunoassay (RIA) and RIA after paper chromatography. Utilizing the direct cortisol RIA, 4 of 6 patients with CRF exhibited blunted dexamethasone suppression, while all 6 patients showed normal suppressibility after dexamethasone when cortisol was measured after paper chromatography. In contrast, all controls showed normal suppressibility regardless of the cortisol assay procedure used. The hydrocortisone suppression test was unreliable in the setting of CRF. Mean dexamethasone levels were similar in both groups. Plasma adrenocorticotropic hormone levels were significantly higher in the CRF patients, possibly indicative of an underlying hypothalamic-pituitary-adrenal axis abnormality. Abnormalities in dexamethasone suppression testing in patients with CRF may be explained by the overestimation of cortisol levels by direct RIA rather than by alteration of dexamethasone absorption or metabolism. Measurement of cortisol after paper chromatography is superior to direct RIA of cortisol in patients with CRF. [ABSTRACT FROM AUTHOR]

GFR normally increases during glycine infusion. This response is absent in humans and rats with established diabetes mellitus. In diabetic patients, angiotensin-converting enzyme inhibition (ACEI) restores the effect of glycine on GFR. To ascertain the glomerular hemodynamic basis for this effect of ACEI, micropuncture studies were performed in male Wistar-Froemter rats after 5 to 6 wk of insulin-treated streptozotocin diabetes. The determinants of single-nephron GFR (SNGFR) were assessed in each rat before and during glycine infusion. Studies were performed in diabetics, diabetics after 5 d of ACEI (enalapril in the drinking water), and weight-matched controls. Diabetic rats manifest renal hypertrophy and glomerular hyperfiltration but not glomerular capillary hypertension. ACEI reduced glomerular capillary pressure, increased glomerular ultrafiltration coefficient, and did not mitigate hyperfiltration. In controls, glycine increased SNGFR by 30% due to increased nephron plasma flow. In diabetics, glycine had no effect on any determinant of SNGFR. In ACEI-treated diabetics, the SNGFR response to glycine was indistinguishable from nondiabetics, but the effect of glycine was mediated by greater ultrafiltration pressure rather than by greater plasma flow. These findings demonstrate that: (1) The absent response to glycine in established diabetes does not indicate that renal functional reserve is exhausted by hyperfiltration; and (2) ACEI restores the GFR response to glycine in established diabetes, but this response is mediated by increased ultrafiltration pressure rather than by increased nephron plasma flow.

We prospectively assessed renal function in a group of 29 renal transplant patients receiving cyclosporine (CsA) in order to determine the course of their renal function over time and the relationship between different markers of glomerular function. We measured serum creatinine, DPTA, and creatinine clearances, and urinary albumin excretion. The clinical course of 24 patients (83%) permitted repeat studies over a period of 32 +/- 1 (SEM) months, and in these patients DTPA clearance, creatinine clearance, and the serum creatinine concentration did not vary with time. Five of the patients (17%) lost their grafts and returned to dialysis. On initial evaluation patients who lost their grafts had a lower DPTA clearance than those whose function was maintained (29 +/- 3 v 46 +/- 2 mL/min/1.73 m2 body surface area [BSA], respectively, P less than 0.005) and all of them had a DTPA clearance of less than 40 mL/min/1.73 m2 BSA. There was an inverse correlation between the log of the urinary albumin excretion and the DTPA clearance (n = 33, r = -0.59, P less than 0.001), a direct correlation with the serum creatinine concentration (N = 33, r = 0.89, P less than 0.0001), but no correlation with time after transplantation. Thus, despite the continued use of CsA, renal function over time was stable in patients who underwent repeated studies, as was the relationship between the DTPA clearance and the clinically used markers of transplant function, the serum creatinine concentration, and the creatinine clearance.

An oral protein load or infusion of amino acids induces a rise in renal hemodynamics in normal subjects, but the mechanisms mediating this phenomenon are unknown. We investigated whether glucagon may mediate the increase in RPF and GFR induced by an arginine infusion and whether prostaglandins are required for this effect. In four different studies, normal subjects underwent 13 inulin and PAH clearances of 30 minutes each. During the fourth and tenth clearance periods arginine HCl, 250 mg/kg, was infused over 30 minutes. At the beginning of the fifth clearance period several subjects ingested indomethacin, 150 mg, (N = 8) or ibuprofen, 800 mg (N = 6). Control subjects (N = 4) did not receive cyclooxygenase inhibitors. Six subjects underwent a similar protocol except that they were infused with glucagon, 6 ng/kg/min, instead of arginine, for 30 minutes during the fourth and tenth periods. They also ingested indomethacin, 150 mg, in the fifth period. In all four studies, a transient and significant rise in RPF and GRF and fall in RVR occurred during the first arginine or glucagon infusion. These changes in renal hemodynamics were blocked when the arginine or glucagon infusion was repeated after administration of indomethacin or ibuprofen. Urinary excretion of 6-keto-PGF1 alpha did not rise with either arginine infusion in the control subjects or in the individuals who received indomethacin. As predicted, urinary 6-keto-PGF1 alpha fell significantly after ingestion of indomethacin before the second infusion of arginine. Plasma norepinephrine and epinephrine concentrations were unaffected by the arginine infusions or by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Although maintenance hemodialysis (MHD) patients are often wasted, little is known about their dietary energy needs. We studied four men and two women in a clinical research center while they received diets providing 45, 35 and 25 kcal/kg desirable body weight/day; diets were fed, in random order, for 21 to 23 days each. Protein intake, 1.13 +/- 0.02 (SEM) g protein/kg/day, was similar with all three diets. Body weight rose with 45 and 35 kcal/kg/day (P less than 0.05) and fell with 25 kcal/kg/day (P less than 0.05). Nitrogen balance, adjusted for estimated unmeasured losses, was neutral with 45 and 35 kcal/kg/day and negative with 25 kcal/kg/day. Balance was neutral or positive in 6 of 6, 4 of 6, and 0 of 6 patients fed 45, 35, 25 kcal/kg/day, respectively. Nitrogen balance, many plasma amino acids and changes in body weight, mid-arm circumference, mid-arm muscle area and body fat each correlated with energy intake. Resting energy expenditure was normal. The energy intake estimated from regression equations to maintain neutral nitrogen balance was 38.5 kcal/kg desirable weight/day; for body fat and weight, it was 32 kcal/kg/day. These data suggest that MHD patients have normal energy expenditure and approximately normal requirements for maintenance of protein balance, body weight and body fat. An average energy intake of about 38 kcal/kg desirable weight/day may be necessary to maintain nitrogen balance in these patients.