EFFECTS OF DIET AND ANTIHYPERTENSIVE THERAPY ON CREATININE CLEARANCE AND SERUM CREATININE CONCENTRATION IN THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY

Factors other than the glomerular filtration rate (GFR) can affect cre atinine clearance (C-cr) and serum creatinine concentration (P-cr). Th e effect of dietary protein and antihypertensive therapy on C-cr, the reciprocal of the P-cr (1/P-cr), and their determinants (GFR, creatini ne clearance from tubular secretion (C-TScr), and creatinine excretion (UcrV) values) was assessed in patients participating in the Modifica tion of Diet in Renal Disease (MDRD) Study. This study compared the ef fects of assignment to a low versus usual-protein diet and to a low ve rsus usual-blood pressure goal on the decline in these measurements ov er 3 yr in 585 patients with baseline GFR of 25 to 55 mL/min per 1.73 m(2) (Study A). This study also assessed correlations and associations of these measurements with each other and with protein intake, blood pressure, class of antihypertensive agents, and renal diagnosis in 840 patients with baseline GFR of 13 to 55 mL/min per 1.73 m(2) (Studies A and B). In Study A, the estimated mean decline in GFR at 3 yr did no t differ significantly between the low and usual-protein diet groups ( -10.9 versus -12.1 mL/min). In contrast, C-TScr declined more in the l ow-protein diet group (-7.8 versus -3.6 mL/min, P < .05). Consequently , the low-protein diet group had a greater decline in C-cr (-17.6 vers us -14.4 mL/min, P < .05). The low-protein diet group also had a great er decline in UcrV (-306 versus -92 mg/day, P < .05). The decline in U crV was proportionately greater than the decline in C-TScr, hence the decline in 1/P-cr was less in the low-protein diet group (-0.091 versu s -0.122 dL/mg, P < .05). Similarly, in Study A, there was no signific ant difference in the decline in GFR at 3 yr between the low and usual -blood pressure groups (-10.7 versus -12.3 mL/min). However, there was a lesser decline in C-TScr in the low blood pressure group (-4.7 vers us -6.7 mL/min, P < .05). Consequently, the decline in C-cr was less i n the low blood pressure group (-14.2 versus -17.8 mL/min, P < .05). T here was no significant difference in UcrV between the blood pressure groups (-192 versus -205 mg/day). Hence, the decline in 1/P-cr paralle led the decline in C-cr; it was less in the low blood pressure group ( -0.091 versus -0.122 dL/mg, P < .05). In Studies A and B, correlations of rates of decline in C-cr and GFR were 0.64 and 0.79, respectively (P < 0.001). Correlations of rates of decline in 1/P-cr and GFR were 0 .79 and 0.85, respectively (P < 0.001). In Studies A and B combined, b aseline GFR, C-TScr, and UcrV correlated significantly with protein in take (r = 0.45, 0.47, and 0.36, respectively; Pt intake (r = 0.45, 0.4 7, and 0.36, respectively; P < 0.001), but not with blood pressure. Ba seline C-TScr was significantly lower in patients with polycystic kidn ey disease and tubulointerstitial diseases or urinary tract diseases, compared with glomerular and other diseases (P < 0.05). It was also lo wer in patients who were taking calcium channel blockers, compared wit h patients not taking these agents, and in patients not taking diureti cs, compared with patients taking diuretics (P < 0.05). These results show that creatinine secretion and excretion are affected by protein i ntake. Creatinine secretion is also affected by antihypertensive thera py and renal diagnosis. In the MDRD Study, the low-protein diet reduce d creatinine secretion and excretion, and the low blood pressure goal slowed the decline in creatinine secretion. These effects caused diffe rences between the diet groups and between the blood pressure groups i n C-cr and 1/P-cr that were not the result of differences in GFR. Stud ies assessing the effects of these interventions on the progression of renal disease should measure GFR in addition to C-cr and P-cr.