Abstract. The ability of the Modification of Renal Disease (MDRD) equation to predict GFR when compared with multiple other prediction equations in healthy subjects without known kidney disease was analyzed. Between May 1995 and December 2001, a total of 117 healthy individuals underwent 125 I-iothalamate or 99m Tc-diethylenetriamine-pentaacetic acid (DTPA) renal studies as part of a routine kidney donor evaluation at either Brigham and Women's Hospital or Boston Children's Hospital. On chart review, 100 individuals had sufficient data for analysis. The MDRD 1, MDRD 2 (simplified MDRD equation), Cockcroft-Gault (CG), Cockcroft-Gault corrected for GFR (CG-GFR), and other equations were tested. The median absolute difference in ml/min per 1.73 m 2 between calculated and measured GFR was 28.7 for MDRD 1, 18.5 for MDRD 2, 33.1 for CG, and 28.6 for CG-GFR in the 125 Iiothalamate group and was 31.1 for MDRD 1, 38.2 for MDRD 2, 22.0 for CG, and 31.1 for CG-GFR in the 99m Tc-DTPA group. Bias was Ϫ0.5, Ϫ3.3, 25.6, and 5.0 for MDRD 1, MDRD 2, CG, and CG-GFR, respectively, in subjects who received 125 I-iothalamate and Ϫ33.2, Ϫ36.5, 6.0, and Ϫ15.0 for MDRD 1, MDRD 2, CG, and CG-GFR, respectively, in those who received 99m Tc-DTPA studies. Precision testing, as measured by linear regression, yielded R 2 values of 0.04 for CG, 0.05 for CG-GFR, 0.15 for MDRD 1, and 0.14 for MDRD in those who underwent 125 I-iothalamate studies and 0.18 for CG, 0.21 for CG-GFR, 0.40 for MDRD 1, and 0.38 for MDRD 2 for those who underwent 99m Tc-DTPA studies. The MDRD equations were more accurate within 30 and 50% of the measured GFR compared with the CG and CG-GFR equations. When compared with the CG equation, the MDRD equations are more precise and more accurate for predicting GFR in healthy adults. The MDRD equations, however, consistently underestimate GFR, whereas the CG equations consistently overestimate measured GFR in people with normal renal function. In potential kidney donors, prediction equations may not be sufficient for estimating GFR; radioisotope studies may be needed for a better assessment of GFR. Further studies are needed to derive and assess GFR prediction equations in people with normal or mildly impaired renal function.

Determination of the amino acid sequence of bovine parathyroid hormone has led to the synthesis of a tetratriacontapeptide corresponding to the aminoterminal 1-34 residues of the native molecule. The specific biological effects of this synthetic peptide on bone and kidney are qualitatively identical to those of the native hormone in classical bioassays in vivo and in several systems in vitro. Potency of the synthetic peptide equals or exceeds that of a biologically active fragment of comparable size isolated from the native hormone; the synthetic and natural peptides show complete immunological crossreactivity. Thus, essential requirements for the physiological actions of the peptide on both skeletal and renal tissue are contained within the 34 amino-terminal amino acids. The potency of the synthetic peptide, relative to that of the native (84-amino acid) polypeptide, is greater in vitro than in vivo; this suggests that the carboxyl terminal two-thirds of the native hormone may protect the circulating polypeptide from rapid metabolic degradation.

Human placental lactogen has been found to resemble human pituitary growth hormone very closely in amino acid sequence, about 80% of the residues examined being identical in the two molecules when a revised sequence for growth hormone is used as the basis for comparison. The structural features responsible for the differing biological potency of the two hormones may therefore reside in rather limited regions of primary structure. The observation of internal sequence homologies within the pituitary growth hormone and prolactin and the placental lactogen molecules suggests that these polypeptide hormones may have evolved by genetic reduplication from a smaller common ancestral peptide. This finding directs further attention to subfragments of these molecules as possible possessors of intrinsic somatotrophic and lactogenic activity.Previous studies on pituitary growth hormone and prolactin, and on placental lactogen, have demonstrated a close structural similarity within this group of hormones, and thus provided a basis for their shared biological and immunological properties (1-6). However, complete amino acid sequences have been reported so far only for human growth hormone (1) (growth hormone) and ovine prolactin (3) (prolactin), and detailed intra-species comparisons of structure have not been possible. Recently, we have extended earlier structural studies (2, 5) on human placental lactogen (lactogen) and have determined much of its amino acid sequence. In the course of this work it was noted that discrepancies existed between the amino acid sequence of growth hormone as previously reported by Li and coworkers (1), and that which would have been predicted by homology with the structure of lactogen as determined in our laboratory. This led us to postulate an error in the previous growth hormone sequence, and to undertake a reinvestigation of its primary structure. Our results (7) showed that the previous aminoterminal structure of growth hormone was in fact incorrect, and that a sequence of 15 amino acids containing the single tryptophan of growth hormone, assigned by Li and coworkers to positions 17-31, must reside elsewhere in the molecule, most probably occupying positions 77-91. Our more recent investigations (manuscript in preparation) of the growth-hormone sequence have confirmed that this is indeed the correct location for the tryptophan sequence, and have also demonstrated the presence of the proposed (7) "missing" dipeptide sequence (Leu-Arg) at positions 92 and 93. Work in progress strongly suggests the existence of several further errors in the previous sequence for growth hormone. One of these involves residues 130-132, which we find to be Gly-Ser-Pro rather than Pro-Ser-Gly (see Fig. 4).The present report describes sequence studies on lactogen that demonstrate an extremely close homology with the revised growth hormone structure (7). More surprisingly, we also observed unequivocal internal sequence homology between four different regions of the lactogen structure. Examination of the revised ...

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