Michael H. Humphreys

A gamma-melanocyte stimulating hormone-like peptide causes reflex natriuresis after acute unilateral nephrectomy.

Previous studies have shown that acute unilateral nephrectomy stimulates sodium (UNaV) and potassium (UKV) excretion by the remaining kidney through reflex pathways requiring an intact pituitary gland, and the natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the adrenocorticotropic hormone-beta-endorphin precursor molecule pro-opiomelanocortin. We tested the hypothesis that gamma-melanocyte stimulating hormone (gamma-MSH) was such a peptide involved in the postnephrectomy natriuresis. In six rats undergoing sham nephrectomy, no change in UNaV or UKV occurred and plasma immunoreactive gamma-MSH-like material was 40 +/- 18 (SD) fmol/ml 2 hours after the sham procedure. In 10 rats undergoing acute unilateral nephrectomy, UNaV and UKV from the remaining kidney increased significantly, and immunoreactive gamma-MSH was 81 +/- 36 fmol/ml (p less than 0.02). In individual studies, the increase in UNaV after nephrectomy correlated with the postnephrectomy concentration of immunoreactive gamma-MSH (r = 0.75, p less than 0.001). In 17 rats injected with serum or globulin from control rabbits, unilateral nephrectomy led to the expected increases in UNaV and UKV. In 23 rats injected with serum or globulin from rabbits immunized against gamma-MSH, no postnephrectomy natriuresis occurred and the kaliuresis was blunted. In hydropenic, mineralocorticoid-treated rats, intravenous infusion of synthetic gamma-MSH led to natriuresis and kaliuresis with no change in inulin clearance; pretreatment with rabbit anti-gamma-MSH antiserum blocked this effect of peptide infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Near Infra-Red Interactance for Longitudinal Assessment of Nutrition in Dialysis Patients

OBJECTIVEnSerial nutritional assessment of dialysis patients is important because of the high incidence and prevalence of malnutrition in these patients. Near-infrared interactance (NIR) technology may provide a practical and reliable method to evaluate body fat and its changes over time in dialysis patients.nnnDESIGNnLongitudinal study consisting of 2 cross-sectional measurements, 2 months apart.nnnSETTINGnOutpatient dialysis unit affiliated to a tertiary care community medical center.nnnPATIENTSnSeventy-one dialysis patients (35 men, 36 women), 57 +/- 15 years old, who have been on dialysis between 5 months and 11 years (43 +/- 30 months). Twelve additional patients with similar features were studied during the second round.nnnINTERVENTIONnNone.nnnMAIN OUTCOME MEASURESnNIR was used to estimate the body fat percentage. Other simultaneous measurements included subjective global assessment, anthropometric indices including midarm circumference, triceps and biceps skinfold thickness, and body mass index, and some laboratory values including albumin, transferrin, and cholesterol. NIR measurement was performed by placing a Futrex sensor on the nonaccess upper arm for several seconds, after logging the required individual data (sex, weight, height, and body frame), along with uniform physical activity levels for all patients, into a mini-computer.nnnRESULTSnSeventy-one dialysis patients underwent nutritional and laboratory measurements. A second measurement round was performed 8 to 9 weeks after the first one and included 12 additional patients. Within each cross-sectional round, Pearson correlation coefficients (r) between the NIR score and nutritionally relevant variables were significant for anthropometric values (0.56 to 0.82) as well as low cholesterol and creatinine (0.22 to 0.30). The two serial NIR measurements on the same patients were highly consistent over the 2-month study interval (r = 0.96), whereas anthropometric values showed greater variability. The within-person coefficient of variation for NIR was low, indicating high consistency between 2 measurements. Moreover, the timing of the NIR measurement (predialysis v postdialysis) did not have any impact on consistency of the NIR results. The longitudinal changes of NIR had significant correlations with anthropometric and laboratory changes over time.nnnCONCLUSIONnThe NIR, which can be performed within seconds, may serve as a reliable and practical tool for objective measurements of nutritional status in hemodialysis patients. The NIR not only seems to have a high degree of reproducibility but may also be an optimal tool to detect longitudinal changes in body fat over time. The NIR measurement is independent of the fluid status in dialysis patients. More comparative and longitudinal studies are needed to confirm the validity of NIR measurements in longitudinal evaluation of dialysis patients.

Modulation of endothelin effects on blood pressure and hematocrit by atrial natriuretic peptide.

Infusion of endothelin has been observed to increase hematocrit, and the peptide also stimulates release of atrial natriuretic peptide (ANP) both in vitro and in vivo. We studied the relation of these two actions of endothelin in anesthetized, bilaterally nephrectomized Sprague- Dawley rats. Infusion of endothelin (25 ng/kg/min) for 45 minutes produced a modest increase in blood pressure of 12% from a baseline of 99 ±5 mm Hg and an increase in hematocrit of 8.0±0.6%, reflecting a reduction in plasma volume of 13.1 ±0.9%. These changes each exceeded greatly those observed after 45 minutes of vehicle infusion. Plasma protein concentration, however, increased only by 4.2 ±0.6%, suggesting protein extravasation, which was confirmed by finding an endothelin-dependent increase in the accumulation of Evans blue dye in heart, skeletal muscle, and intestine, but not liver, lung, brain, or testis. Endothelin infusion increased plasma immunoreactive ANP concentration from 196±50 to 722±203 pg/ml (p<0.02), and a close correlation existed between the increase in plasma immunoreactive ANP and immunoreactive endothelin concentrations as a result of the infusion (r=0.84, p<0.01). Pretreatment of rats with rabbit anti-rat ANP antiserum did not affect baseline variables but led to an exaggerated increase in blood pressure (25.3±2.9%, p<0.002 versus endothelin alone). No change in hematocrit occurred. Thus, the increase in plasma immunoreactive ANP concentration resulting from endothelin infusion mediates the increase in hematocrit through an increase in vascular permeability to whole plasma. The exaggerated pressor effect of the infused endothelin in the presence of ANP antiserum suggests that ANP may modulate the vasoconstrictor actions of endothelin in vivo.

Peptide hormones and the regulation of sodium excretion.

TWENTY years ago, intensive research led to the delineation of the role played by alterations in blood composition in mediating the natriuresis that resulted from the infusion of colloidfree isotonic saline solutions into humans and experimental animals. Results of this research indicated that changes in renal hemodynamics (glomerular filtration rate [GFR], renal blood flow, renal vascular resistance, filtration fraction) and hematocrit and plasma protein concentration occurring in response to saline infusion led to inhibition of tubular sodium reabsorption through changes in hydrostatic and oncotic pressures in the peritubular capillary circulation, the socalled physical factor effects. Because of these findings, the view emerged that, regardless of the extrarenal consequences of saline expansion, the natriuresis resulted from strictly intrarenal mechanisms. This viewpoint was later strengthened by in vitro studies on isolated perfused rabbit proximal convoluted tubule segments that demonstrated a direct effect of bath protein concentration on fluid transport.

Resin hemoperfusion in ethchlorvynol overdose

An 18‐yr‐old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD‐4 resin hemoperfusion. Plasma ECV concentrations declined 33% during a 3.5‐hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/l/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (CI =270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (CI = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 ± 0.04 and fraction free in plasma, 0.38 ± 0.02; neither changed as a function of blood concentration between 27 and 108 mg/l. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD‐4 hemoperfusion may be clinically useful.