Animals with experimental renal disease maintained on diets restricted in protein develop less severe renal lesions and less proteinuria than do animals maintained on a normal or high protein diet. To determine whether restriction of dietary protein will reduce urinary albumin excretion in patients with established nephrosis and whether such dietary restriction will result in decreased albumin pools, we performed paired studies on nine nephrotic patients. They were fed sequential diets with a protein content of 1.6 and then 0.8 g/kg body wt, each for 2 weeks. Caloric intake remained constant at 35 Kcal/kg. In six patients the high protein diet was fed first; in three the order of dietary administration was reversed. Urinary albumin excretion was reduced on the low protein diet in all patients regardless of dietary order. Both the renal clearance of albumin and the fractional renal albumin clearance were reduced significantly on the low protein diet. The rate of albumin synthesis was greater on the high protein diet, but so was the rate of albuminuria. Despite the higher rate of albumin synthesis during the period of high protein intake, serum albumin concentration and plasma albumin mass were both less than during the period of low protein intake. Thus, dietary protein restriction in patients with established nephrosis results in decreased urinary albumin excretion in excess of any reduction in creatinine clearance. Total albumin mass is preserved and plasma albumin mass is actually increased during the period of dietary protein restriction. Protein restriction may be feasible in nephrotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased TG levels in both NS and NAR are the result of decreased TRL clearance. TG levels are greater in NS because of the presence of a combined defect: (1) a decrease in endothelial-bound LpL that occurs as a consequence of reduced serum albumin concentration, and (2) a defect in VLDL binding to endothelial-bound LpL. This latter defect occurs only in the presence of proteinuria and is conferred by HDL.

A quantitative measure of the effectiveness of lung ventilation and the significance of unequal mixing of the gases in the lung is of interest in many problems such as the measurement of lung volume and in studies of such processes as tissue denitrogenation which involve transport of gases through the lung.The present study involves the determination of the turnover rates attained in the lung from measurements of the rate at which nitrogen is washed out of the lungs while the subject is breathing pure oxygen. It has been recognized (1) that this rate depends upon the distribution of the tidal breath to the deeper pulmonary structures and that it offers a means of measuring the ventilatory process. Use of the method has, however, led to a number of different expressions for the effectiveness of ventilation none of which we believe is definitive of the process.Because the function of lung ventilation is to maintain physiological partial pressures of oxygen and of carbon dioxide in the alveoli it seems to us that the measure of the effectiveness of ventilation should be reciprocally related to the average time that a molecule remains in those spaces. The replacement rate or turnover rate, defined as the ratio of the number of new molecules which enter a space in unit time to the number present at the end of expiration is such a measure.Without attempting here to survey the extensive literature upon this subject we shall mention a few papers which bear most directly upon the interpretation of the present results.Cournand and his associates (1, 2) in testing the adequacy of the assumption of even pulmonary ' This work was supported in part by the Life Insurance Medical Research Fund and in part by the Army Air Force.2 Present address: Medical Department, Brookhaven National Laboratory, Upton, Long Island, New York. mixing found evidence of unequal mixing in emphysematous subjects and to some extent in normal ones. They develop the "pulmonary emptying rate" as a criterion for the effectiveness of lung ventilation. This is based upon the concentration of nitrogen remaining in the alveoli after seven minutes of oxygen breathing. In effect this establishes two points on the curve representing the concentration of nitrogen as a function of time, the initial point and the seven-minute one. This function is not, however, defined by these two points unless it is a simple function having only two constants, such as a single-termed exponential. Non-uniform mixing is not consistent with any simple function; with different degrees of mixing two curves differing appreciably can both pass through these two points but be quite different at other times. In a later paper Darling, Cournand, and Richards (3) compare the concentration of nitrogen remaining after a period of oxygen breathing to the concentration they predict would have been obtained had mixing been perfect and they express the effects of unequal mixing as the percentage failure of ventilation.Meneely and Kaltreider (4) consider the effects of mixing upon the time require...

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A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We use two novel multiplex assays to quantify biomarker concentration in multiple urine collections made prior to and following administration of cisplatin, a common nephrotoxicant, to rats. We investigate the correlation of the magnitude of biomarker changes with the severity of histopathological observations and explore the relationship of these to both dose and sex. The novel biomarkers evaluated are urinary albumin, alpha glutathione s-transferase (α-GST), glutathione S-transferase-yb1 (GSTYb1), lipocalin-2, kidney injury molecule-1 (KIM-1), osteopontin, and renal papillary antigen 1 (RPA-1) and plasma cystatin C, alongside the traditional biomarkers of plasma urea, creatinine, and urinary n-acetyl-beta-d-glucosaminidase (NAG), total protein, and glucose. We show for all time points, and for almost all doses, that male rats consistently had either more severely graded or a higher incidence of histologically observed lesions than females; that changes in urinary glucose, total urinary protein, NAG, and the novel urinary biomarkers albumin, osteopontin, and KIM-1 are clearly temporally associated; and that changes are related to the severity of injury. We also found that receiver operating characteristic curve analysis and area under the curve are significantly higher than urea or creatinine for all new biomarkers except aGST, GSTYb1, cystatin c, and total protein in both sexes.