Association between glomerular filtration rate and extracellular fluid volume in normal subjects and patients with renal impairment

The aim of the study was to determine the extent to which glomerular filtration rate (GFR) measured with one filtration marker is associated with extracellular fluid volume (ECV) measured independently with another. Cr-51-EDTA and iohexol were injected simultaneously into opposite arms in 20 normal volunteers and 60 patients. Cubital samples taken bilaterally at 20, 40, 60, 120, 180 and 240 min were assayed for marker injected contralaterally. GFR was scaled to body surface area of 1.73 m(2) (GFR/BSA). GFR was also expressed as marker transit time (GFR/ECV) and ECV as the product of marker transit time and GFR/BSA. In normal subjects, changes between fasting and non-fasting ECV/BSA correlated positively with changes in GFR/BSA, but not GFR/ECV. GFR/BSA and GFR/ECV correlated positively (regression slope approximately 4 ml.min(-1).litre(-1)) and negatively (-2.7 ml x min(-1) x litre(-1)), respectively, with ECV/BSA. The difference, 6.7 ml x min(-1) x litre(-1), expressed as a fraction of average scaled GFR ( approximately 90 ml x min(-1)) is close to the reciprocal of average ECV/BSA (13.5 litres.1.73 m(-2)), consistent with the expected slope of the regression on ECV/BSA of the difference-to-average ratio of GFR/BSA and GFR/ECV. In contrast, in 29 patients with impaired GFR (estimated from plasma creatinine), ECV/BSA correlated inversely with GFR/ECV (slope approximately -5 ml x min(-1) x litre(-1)) but showed no relation with GFR/BSA. We conclude that in normal subjects GFR/BSA increases in response to increasing ECV/BSA, but the increase is not proportionate, leading to a weak inverse association between GFR/ECV and ECV/BSA. When ECV is expanded in patients with renal impairment, however, there is no GFR response, leading to a reduction in GFR/ECV.     

Follow-up study of peritoneal fluid kinetics in infants and children on peritoneal dialysis.

OBJECTIVES: To study longitudinal changes in transcapillary ultrafiltration (TCUF) and marker clearance (MC), as a reflection of lymphatic absorption, in children on peritoneal dialysis (PD). To present data on fluid kinetics in infants younger than 2.5 years, using an intraperitoneal volume of 1200 mL/m2 body surface area (BSA). DESIGN: The study involved a 4-hour dwell of 1200 mL/m2 BSA of dialysis fluid containing 3.86% glucose with Dextran 70 as volume marker. Cumulative TCUF and cumulative MC were measured. SETTING: A tertiary-care university hospital. PATIENTS: A follow-up period of 33 months of serial (1 - 4) peritoneal equilibration tests (PETs) was studied in 20 children with a median age of 6.4 years (range 2.1 - 15.4 years). Fluid kinetics in 5 additional infants with a median age of 1.4 years (range 0.5 - 2.5 years) was measured. RESULTS: Cumulative TCUF was 1041 mL/1.73 m2 at 1 - 3 months after start of PD, 1026 mL/1.73 m2 at 7 - 9 months, 1021 mL/1.73 m2 at 11 - 13 months, and 756 mL/1.73 m2 at 26 - 33 months (NS). Cumulative MC was 235 mL/1.73 m2 at 1 - 3 months after start of PD, 311 mL/1.73 m2 at 7 - 9 months, 395 mL/1.73 m2 at 11 - 13 months, and 509 mL/1.73 m2 at 26 - 33 months (NS). In infants, cumulative TCUF was 755 +/- 237 mL/1.73 m2; cumulative MC was 400 +/- 214 mL/1.73 m2. CONCLUSIONS: Transcapillary ultrafiltration and marker clearance do not change in children > 2.5 years during the period studied. Fluid kinetics does not differ between infants < 2.5 years and older children when intraperitoneal volumes of 1200 mL/m2 BSA are used.     

Low protein alimentation normalizes renal haemodynamic response to acute protein ingestion in type 1 diabetic children

The effect of an acute protein load (2 g kg-1 bodyweight [BW]) was studied in nine type 1 diabetic children. Patients were maintained on two different dietary regimens. In study one, patients were on a high protein diet providing from 2.7 to 1.8 g of protein/kg of BW per day. In study two, patients were reevaluated after three weeks of a diet providing from 1.0 to 1.2 g kg-1 of BW per day of protein. In study one (High Protein Diet), we failed to observe any rise in GFR and RPF following the protein meal (137 +/- 21 basal vs. 110 +/- 14 and 472 +/- 93 basal vs. 494 +/- 93 ml/1.73 m2 of SA min-1 at 60 min. This is in contrast with results from seven age matched controls consuming a free diet, which showed a significant rise in both GFR and RPF. In study two (low protein diet), basal GFR was significantly reduced. However after the protein load, both GFR (92 +/- 11 vs. 126 +/- 18 ml/1.73 m2 of SA min-1) and RPF (467 +/- 83 vs. 705 +/- 102 ml/1.73 m2 min-1) rose significantly (P less than 0.05 vs. basal). The data indicate that: 1. short term protein restriction reduces significantly GFR in type 1 diabetic children; 2. diabetic children maintained on an high protein intake show an altered haemodynamic response to protein ingestion; 3. a normal response to protein ingestion can be restored by short term dietary protein restriction.     

Glomerular filtration rate and kidney volume in normoalbuminuric non-insulin-dependent diabetics--lack of glomerular hyperfiltration and renal hypertrophy in uncomplicated NIDDM

Glomerular filtration rate (GFR) and kidney volume were evaluated in 18 healthy normoalbuminuric non-insulin-dependent diabetic patients and compared to 12 healthy controls matched for sex, age and body mass index (BMI). The patients (12 males, six females) were 61.6 +/- 3.4 (mean +/- SD) years old, the known diabetes duration was 5 +/- 4.8 years, fasting plasma glucose 8.6 +/- 2.3 mmol/l, urinary albumin excretion rate 7.9 x/divided by 2.0 micrograms/min, BMI 26.8 +/- 2.8 kg/m2 and blood pressure systolic/diastolic 145 +/- 19/82 +/- 7 mmHg. The GFR was measured by the plasma clearance of [51Cr]EDTA, using a single shot procedure. The kidney volume was measured by ultrasonic scanning. The GFR was not increased in diabetics: 100.4 +/- 16.7 ml/min/1.73 m2 as compared to controls: 93.8 +/- 11.4 ml/min/1.73 m2. The kidney volume was similar in the two groups. Diabetics: 231.1 +/- 33.4 ml/1.73 m2. Controls: 236.3 +/- 45.7 ml/1.73 m2. There was a borderline significant correlation between kidney volume and GFR (r = 0.40, p = 0.10) in diabetics. No correlation between glycosylated haemoglobin and GFR was found in diabetics. In contrast to the findings in insulin-dependent diabetes renal hypertrophy and hyperfunction were not characteristic features in this series of non-insulin-dependent diabetics. It is suggested that diabetic glomerulopathy is not always a consequence of long-standing hyperfiltration.     

Estimating glomerular filtration rate in HIV-infected adults in Africa: comparison of Cockcroft-Gault and Modification of Diet in Renal Disease formulae

BACKGROUND: Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae are recommended for glomerular filtration rate (GFR) estimation, but neither has been validated or directly compared longitudinally in HIV-infected patients or in Africa. METHODS: We investigated differences between formulae in baseline GFR, GFR changes and incidence of impaired GFR after initiation of antiretroviral therapy (ART) in 3,316 HIV-infected adults in Africa, considering sex, age, body mass index and baseline laboratory parameters as predictors. RESULTS: Participants were 65% women, median age 36.8 years, median weight 56.7 kg. Baseline GFR was lower using CG (median 89 ml/min/1.73 m2, 7.4% <60 ml/min/1.73 m2) versus MDRD (103 ml/min/1.73 m2, 3.1% <60 ml/min/1.73 m2). At 36 weeks, median CG-GFR increased (92 ml/min/1.73 m2), whereas MDRD-GFR decreased (96 ml/min/1.73 m2). Weight (explicitly a factor in CG only) concurrently increased to 62.0 kg. GFR changes from weeks 36-96 (after weight stabilization) were similar across formulae. By 96 weeks, 56 patients developed severe GFR impairment (<30 ml/min/1.73 m2) using one or both formulae (both n=45, CG n=7, MDRD n=4) compared with only 24 by serum creatinine alone. Multivariate models identified different sets of predictors for each formula. CONCLUSIONS: Although severe GFR impairments are similarly classified by different formulae, moderate impairments were more frequently identified using CG-GFR versus MDRD-GFR (with Black ethnicity correction factor 1.21), and creatinine alone had low sensitivity. Given overestimation in underweight patients and sensitivity to weight changes, this MDRD formula might not necessarily be superior for monitoring ART in African HIV-infected adults.     

Relationship between glomerular filtration rate and the adipokines adiponectin, resistin and leptin in coronary patients with predominantly normal or mildly impaired renal function

BACKGROUND: Due to their molecular weight, it is possible that the adipokines adiponectin, resistin and leptin accumulate when glomerular filtration rate (GFR) is decreased. In reduced renal clearance, altered serum concentrations of these proteins might affect cardiovascular risk. The objective of the study was to investigate the relationship between adipokine concentrations and GFR. METHODS: The association between GFR, as determined by the abbreviated MDRD equation, and the concentrations of the adipokines adiponectin, resistin and leptin was assessed in a cohort of coronary patients (n=538; 363 male, 165 female). After calculation of correlations between GFR and adipokine concentrations, the association was further assessed by analysis of covariance following adjustment for age, gender, BMI, presence of type 2 diabetes, presence of hypertension, history of smoking as well as for serum lipid concentrations. RESULTS: Mean GFR in our study population was 68.74+/-15.27 ml/min/1.73 m(2). 74.3% of the patients had a GFR >60 ml/min/1.73 m(2), 24% of the patients had a GFR between 30 and 60 ml/min/1.73 m(2), and 1.7% of the patients had a GFR <30 ml/min/1.73 m(2). There were significant inverse correlations between adiponectin (r=-0.372; p<0.001), resistin (r=-0.227; p<0.001) and leptin (r=-0.151; p=0.009) concentrations and GFR. After multivariate adjustment, the associations remained significant for adiponectin and resistin. Subgroup analysis in patients with GFR >60 ml/min/1.73 m(2) showed a significant correlation between GFR and adiponectin as well as leptin concentrations. However, after adjustment, these associations no longer were significant. CONCLUSIONS: There is an independent association between GFR and the serum concentrations of adiponectin and resistin. However, this association is not present at GFR >60 ml/min/1.73 m(2). This finding suggests that adipokine concentrations in mildly impaired and normal renal function are influenced by factors other than GFR.     

Renal function in an elderly population. A study of S-creatinine, 51Cr-EDTA clearance, endogenous creatinine clearance and maximal tubular water reabsorption

There has been reported a decline in renal function with age, a decline that seems to accelerate after the age of 50. A systemically chosen sample of 70- and 75-year-old probands from the study '70-year-olds in G?teborg' have previously been examined with respect to GFR. The present study is a longitudinal follow-up of GFR in the previously examined 75-year-old probands at age 79. Renal tubular water absorption was also determined. In order to make a longitudinal comparison, S-creatinine was determined in a subsample of 166 probands, who had attended the study at 70, 75 and 79 years of age, by using frozen sera from these three examinations. S-creatinine increased slightly but statistically significant in both sexes between 70 years and 79 years of age. The reference values for EDTA clearance at age 79 calculated as M +/- 2 SD were 46-94 ml/min X 1.73 m2 BSA without any difference between the sexes. There was no change in GFR between 75 years and 79 years of age. We did not find any correlation between EDTA clearance and creatinine clearance. The tubular water reabsorption for probands without disorders was 843 +/- 92.6 (range 709-982). The results suggest that the renal filtration rate at age 79 is still good and that the ageing of the tubular function is not as pronounced as that of the GFR.     

How reliable is estimation of glomerular filtration rate at diagnosis of type 2 diabetes?

OBJECTIVE: The Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations previously have been recommended to estimate glomerular filtration rate (GFR). We compared both estimates with true GFR, measured by the isotopic (51)Cr-EDTA method, in newly diagnosed, treatment-na?ve subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 292 mainly normoalbuminuric (241 of 292) subjects were recruited. Subjects were classified as having mild renal impairment (group 1, GFR <90 ml/min per 1.73 m(2)) or normal renal function (group 2, GFR >/=90 ml/min per 1.73 m(2)). Estimated GFR (eGFR) was calculated by the CG and MDRD equations. Blood samples drawn at 44, 120, 180, and 240 min after administration of 1 MBq of (51)Cr-EDTA were used to measure isotopic GFR (iGFR). RESULTS: For subjects in group 1, mean (+/-SD) iGFR was 83.8 +/- 4.3 ml/min per 1.73 m(2). eGFR was 78.0 +/- 16.5 or 73.7 +/- 12.0 ml/min per 1.73 m(2) using CG and MDRD equations, respectively. Ninety-five percent CIs for method bias were -11.1 to -0.6 using CG and -14.4 to -7.0 using MDRD. Ninety-five percent limits of agreement (mean bias +/- 2 SD) were -37.2 to 25.6 and -33.1 to 11.7, respectively. In group 2, iGFR was 119.4 +/- 20.3 ml/min per 1.73 m(2). eGFR was 104.4 +/- 26.3 or 92.3 +/- 18.7 ml/min per 1.73 m(2) using CG and MDRD equations, respectively. Ninety-five percent CIs for method bias were -17.4 to -12.5 using CG and -29.1 to -25.1 using MDRD. Ninety-five percent limits of agreement were -54.4 to 24.4 and -59.5 to 5.3, respectively. CONCLUSIONS: In newly diagnosed type 2 diabetic patients, particularly those with a GFR >/=90 ml/min per 1.73 m(2), both CG and MDRD equations significantly underestimate iGFR. This highlights a limitation in the use of eGFR in the majority of diabetic subjects outside the setting of chronic kidney disease.     

Measurement of glomerular filtration rate in children with insulin-dependent diabetes mellitus

51Cr-EDTA, inulin and creatinine clearances were measured simultaneously in 11 diabetic children and 12 healthy young adults. The clearances in all individuals were 115 +/- 24 ml/min per 1.73 m2SA for 51Cr-EDTA, 118 +/- 25 ml/min per 1.73 m2SA for inulin and 157 +/- 35 ml/min per 1.73 m2SA for creatinine. Values were higher in the diabetic children but the differences were not significant. 51Cr-EDTA clearance significantly underestimated that of inulin by a mean of -7.4 +/- 2.5 (SEM) ml/min per 1.73 m2SA (p less than 0.01) and creatinine clearance significantly overestimated that of inulin by 37.6 +/- 3.3 (SEM) ml/min per 1.73 m2SA (p less than 0.0001). Similarly, the mean ratio of 51Cr-EDTA to inulin clearance was 0.94 (95% CI 0.90-0.98) and that of creatinine to inulin clearance was 1.32 (95% CI 1.27-1.37); the differences between diabetics and controls were not significant. Correlation coefficients were 0.93 between 51Cr-EDTA and inulin clearances, and 0.95 between inulin and creatinine clearances. The pooled coefficient of variation between clearances within an individual was higher with inulin, 10.3 +/- 6.5% (SD), than 51Cr-EDTA, 7.3 +/- 5.1% (p less than 0.001, t test). These results show that 51Cr-EDTA clearance underestimates that of inulin to a similar extent in both diabetic children and healthy controls and creatinine clearance overestimates inulin clearance to a greater but similar extent in both groups. The methodological variation in 51Cr-EDTA measurement is less than with the other 2 methods. Therefore, we recommend the use of the renal clearance of 51Cr-EDTA for the measurement of GFR in diabetic children.     

Enhancement of glomerular filtration rate and renal plasma flow by oral glucose load in well controlled insulin-dependent diabetics

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in 27 patients with uncomplicated insulin-dependent diabetes (IDDM) before and after an oral glucose load of 1.1 g glucose/kg body wt. In the 18 patients showing near-normoglycaemia (blood glucose less than or equal to 8 mmol/l) before the glucose challenge the increase in blood glucose from 4.2 +/- 1.7 to 15.2 +/- 2.3 mmol/l was accompanied by an enhancement of GFR from 128 +/- 15 to 132 +/- 14 ml/min X 1.73 m2 (2p = 0.030) and of RPF from 534 +/- 116 to 562 +/- 105 ml/min X 1.73 m2 (2p = 0.023). By contrast oral glucose load to the nine patients with hyperglycaemia (greater than 8 mmol/l) during baseline conditions raising blood glucose from 11.9 +/- 2.0 to 19.6 +/- 1.5 mmol/l was accompanied by a reduction in GFR from 149 +/- 15 to 139 +/- 9 ml/min X 1.73 m2 (2p less than 0.001) while RPF was unchanged. No changes in blood pressure or urinary albumin excretion rates took place in either group. The reduction in plasma protein and in plasma growth hormone concentration were similar in the two groups. No change was seen in plasma arginine vasopressin concentration. There was no difference in the qualitative GFR response in patients with high initial GFR values (greater than or equal to 130 ml/min X 1.73 m2) as compared to patients with initial values below 130 ml/min X 1.73 m2. It is concluded that the induction of moderate hyperglycaemia in IDDM patients is followed by an enhancement of GFR and RPF-provided near-normoglycaemia before the glucose challenge.     

Enhanced GFR response to oral versus intravenous arginine administration in normal adults.

Both oral protein ingestion and intravenous amino acid infusions have been shown to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) in normal subjects. Although the mechanism of this effect is not known, the renal responses to these loads have been associated with increases in peripheral glucagon concentrations. Conflicting data exist concerning the role of glucagon in the hyperfiltration response after an oral protein meal or administration of an intravenous amino acid mixture. Using a single amino acid as the stimulus for hyperfiltration, we compared the renal responses in six normal subjects to 30 gm oral arginine-HCl, intravenous arginine-HCl, and intravenous glucagon infused at the rate of 10 ng/kg/min. GFR, RPF, and glucagon concentration, as well as levels of plasma amino acids and selected gastrointestinal hormones, were measured for six 30-minute clearance periods after each load. Significant rises in mean peak GFR were noted after both oral arginine (104 +/- 5 ml/min x 1.73 m2 to 145 +/- 9 ml/min x 1.73 m2, p less than 0.02) and intravenous arginine (118 +/- 10 ml/min x 1.73 m2 to 134 +/- 11 ml/min x 1.73 m2, p = 0.02) administration. Mean peak RPF rose significantly after oral arginine (510 +/- 26 ml/min x 1.73 m2 to 710 +/- 32 ml/min x 1.73 m2, p less than 0.01) but not after intravenous arginine (616 +/- 60 ml/min x 1.73 m2 to 687 +/- 64 ml/min x 1.73 m2, p = 0.18). Intravenous glucagon infusion also increased both mean peak GFR (99 +/- 9 ml/min x 1.73 m2 to 149 +/- 10 ml/min x 1.73 m2, p less than 0.01) and RPF (514 +/- 48 ml/min x 1.73 m2 to 771 +/- 38 ml/min x 1.73 m2, p less than 0.01) significantly. We found the mean peak percent rise in GFR (43% +/- 13%) and RPF (42% +/- 12%) after oral arginine to be notably greater than that after intravenous arginine (14% +/- 5% and 13% +/- 9%, respectively). However, the mean peak percent rise in glucagon concentration after oral arginine was significantly lower than that after intravenous arginine (62% +/- 25% versus 479% +/- 176%, respectively, p = 0.04). Infusion of glucagon increased GFR (54% +/- 13%) and RPF (55% +/- 12%) to a degree similar to that seen after oral arginine, but again with a significantly higher mean peak percent rise in peripheral glucagon concentrations when compared with the rise after oral arginine (798% +/- 348% vs 62% +/- 25%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

A new serum cystatin C-based equation for assessing glomerular filtration rate in liver transplantation

BACKGROUND: Cystatin C (CysC) has been identified to be an alternative marker of glomerular filtration rate (GFR), but no CysC-based equation has been developed for patients receiving liver transplantation. METHODS: Serum CysC and (99m)Tc-DTPA clearance (true GFR) were measured simultaneously on post-transplant days 1, 4 and 7. A new equation was constructed based on an observation group of 30 patients and its predictive ability was compared with three other CysC-based equations (Hoek, Filler and Larsson) based on a validation group of 30 patients. RESULTS: The new equation for calculating GFR was defined as 19.12+96.21x(1/CysC) and the derived GFR was estimated at 97.4+/-30.2 mL/min/1.73 m(2) and was close to the true GFR (96.8+/-32.8 mL/min/1.73 m(2)). Estimates of GFR by Hoek, Filler and Larsson formulas (61.4+/-25.4, 73.8+/-31.9 and 61.3+/-29.6mL/min/1.73 m(2), respectively) differed significantly from the true GFR. Correlation between the true GFR and all formulas showed no significant difference. Bias was neglectable for the new equation (mean difference: 0.6 mL/min/1.73 m(2)) but remarkable for the other three equations (mean difference: -22.9 to -35.4 mL/min/1.73 m(2)). Accuracy within 10%, 30% and 50% of the true GFR for the new equation (30.0%, 76.7% and 93.3%) was significantly higher than those of the other three equations (p<0.001 for all). CONCLUSIONS: A new serum CysC-based equation was established in this study and it was shown to be accurate in estimating GFR after liver transplantation, compared to the formulas of Hoek, Filler and Larsson.     

Beta-trace protein--a marker of kidney function in children: "Original research communication-clinical investigation"

OBJECTIVES: To determine the pediatric reference interval for serum beta-trace protein (beta-TP) and to compare beta-TP with established LMW markers of GFR, i.e., cystatin C (CysC) and beta(2)-microglobulin (beta(2)-M). DESIGN AND METHODS: All three LMW markers were measured immunonephelometrically. In 106 children above the age of 2 years without evidence of kidney disease, non-parametric reference intervals were calculated. The relative rise of the GFR marker concentrations above the upper reference was studied in 107 samples from 96 patients covering the entire GFR range. RESULTS: Above 2 years, the reference range of beta-TP was constant at 0.43-1.04 mg/L. With decreasing Schwartz-GFR, there was a comparable rise in beta-TP and beta(2)-M, while CysC rose less in the group with GFR below 30 mL/min/1.73 m(2) (278+/-49% [CysC] versus 336+/-65% [beta-TP] and 342+/-76% [beta(2)-M]; p=0.043 and 0.027, respectively). CONCLUSIONS: These data confirm the potential of ss-TP as an endogenous GFR marker in children.     

Vancomycin disposition following intraperitoneal administration in children receiving peritoneal dialysis.

BACKGROUND: Little information is available on the disposition of vancomycin during chronic peritoneal dialysis (PD) in children. The primary objective of this study was to investigate the disposition of vancomycin following intraperitoneal (IP) administration in children receiving short-dwell [e.g., automated PD (APD)] and long-dwell [e.g., continuous ambulatory PD (CAPD)] PD. METHODS: A 6-hour exchange containing vancomycin 500 mg/L, using an exchange volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90-minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were obtained and analyzed for vancomycin concentration by high-pressure liquid chromatography. Pharmacokinetic parameters were computed using noncompartmental methods. RESULTS: The bioavailability of vancomycin during a 6-hour IP exchange was 70% +/- 5%, resulting in a delivered dose of 12.0 +/- 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3 +/- 7.2 microg/mL. Total body vancomycin clearance measured 10.72 +/- 4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD measured 2.78 +/- 1.08 mL/min/1.73 m2 BSA and accounted for 29% +/- 11% of total vancomycin clearance. Dialysis clearance during long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 +/- 1.04 and 3.09 +/- 1.28 mL/min/1.73 m2 BSA, accounting for 25% +/- 13% and 32% +/- 12% of total body clearance respectively. CONCLUSIONS: Intraperitoneal absorption and dialysis clearance of vancomycin in children receiving PD are similar to those reported in adult dialysis patients. In contrast, total body clearance of vancomycin appears to be increased and the elimination half-life decreased in children, due to increased elimination by non-renal nondialysis routes. For intermittent IP vancomycin therapy in children with peritonitis, an IP load containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100 mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from day 2 until the end of treatment will maintain a vancomycin dialysate concentration of >4 microg/mL.     

Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans

Cystatin C has been proposed as an endogenous marker for measuring glomerular filtration rate (GFR) and is regarded as being equivalent to or better than creatinine. However, there are no published data on the production rate (Cys(pr)) or on the non-renal clearance of cystatin C (CL(nr)) in humans, which are essential parameters for GFR calculation. GFR was determined by measuring the plasma clearance of iohexol. Cystatin C, creatinine, urea and albumin were determined on the same serum samples as iohexol; 381 patients with a GFR range of 12-151 ml/min/1.73 m2, and 70 patients on haemodialysis were evaluated. Renal clearance of cystatin C (CLr) equals GFR * S (the sieving coefficient). Plasma clearance (CL) = CLr + CLnr. The relationship between Cys(pr) and the elimination rate (CL * serum-cystatin C) can be expressed as Cys(pr) = (S * GFR+CLnr) * serum-cystatin C. Assuming that the unknown values of Cys(pr) and CLnr are independent of GFR, the equation can be solved from GFR (iohexol clearance) and serum cystatin C (s-Cys) patient data. For S=1, we found Cys(pr) = 0.124 +/- 0.023 mg/min/1.73 m2 and Cl(nr)=22.3 ml/min/1.73 m2. For S = 0.94, found in rats, the values will be Cys(pr) = 0.117 mg/min/1.73 m2 and Cl(nr) = 21 ml/min/1.73 m2 and S-Cys in 70 patients on chronic haemodialysis was found to be 5.74 +/- 1.15 mg/l, in agreement with a calculated value of 5.56 mg/l (s-Cys=124/22.3) for GFR=zero. The mean value of the calculated Cl(nr) for the 70 patients was 22.7 +/- 6.6 ml/min/1.73 m2, which confirms the calculated level and indicates its biological variation. We thus propose the following formula for calculating GFR using the values found for CLnr and Cys(pr) in this study: GFR=124/s - Cys - 22.3 ml/min/1.73 m2, where serum cystatin C concentration is given as mg/l.     

Pharmacokinetics of cefonicid in uraemic patients

Eight subjects with normal renal function and 20 uraemic patients with various degrees of renal insufficiency were given a single iv dose of 1.0 g cefonicid, as a bolus injection. Five groups of subjects were studied: group I, GFR greater than 80 ml/min, group II 30 less than GFR less than 80 ml/min, group III 10 less than GFR less than 30 ml/min, group IV GFR less than or equal to 10 ml/min and group V, haemodialysis patients. Cefonicid concentrations in plasma and urine were measured by microbiological assay (MA) and HPLC method. Results were similar with the two techniques. The mean peak plasma levels were 200-300 mg/l and the apparent volume of distribution was 0.18-0.20 1/kg for all patients. The elimination half-life (T 1(2) beta) increased as renal function decreased: 5.31 +/- 1.30 h in healthy subjects and 58.92 +/- 12.38 h in patients with end-stage renal disease. Urinary elimination of cefonicid was inversely related to the degree of renal impairment: 83% of the dose in 24 h in normal subjects and 13.6% of the dose in patients with severe renal failure. Total body clearance decreased from 23.9 +/- 3.4 ml/min/1.73 m2 (group I) to 1.9 +/- 0.2 ml/min/1.73 m2 (group V). Renal clearance fell from 19.0 +/- 4.9 ml/min/1.73 m2 (group I) to 1.0 +/- 0.4 ml/min/1.73 m2 (group IV). The fractional clearance and the non renal clearance were similar in normal subjects and in uraemic patients. Cefonicid is not haemodializable because of its high protein binding. Dosage of cefonicid should be adjusted according to the degree of renal impairment. Supplemental doses are not necessary after haemodialysis.     

The rising ventilatory cost of bicycle exercise in the seventh decade: a longitudinal study of nine healthy men

Submaximal bicycle exercise tests have been performed in nine healthy men on seven annual occasions between the ages of 64 and 70 years. Ten younger men (average age 33 years) have also been studied once for comparison. The ventilatory cost of submaximal work at VO2 = 1 litre/min rises significantly from 24.3 +/- 0.8 litres/min at age 64 years to 31.8 +/- 1.8 litres/min at age 70 years; the latter value differs significantly from that of the young men (25.6 +/- 0.9 litres/min). Similar changes are seen in the ventilation at 75 W and at VCO2 = 1 litre/min. The rate of change, between 3% and 5% per year, is considerably greater than that found for the change with age in cross-sectional studies of younger men. There is also a rise in the respiratory quotient, consistent with the hyperventilation found. The cardiac frequency at 1 litre/min also rose with age in the older men, and rough estimates of the decline in their aerobic capacity suggest that progressive anaerobiosis could account for at least some of this increase in ventilation seen during submaximal work.     

Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy

OBJECTIVE: The purpose of this study was to assess agreement between glomerular filtration rate (GFR) and the decline in GFR estimated with the Modification of Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula and measured by the plasma clearance of 51Cr-EDTA. RESEARCH DESIGN AND METHODS: We followed a cohort of 156 microalbuminuric type 2 diabetic patients for 8 years with four measurements of GFR and another cohort of 227 type 2 diabetic patients with overt diabetic nephropathy for 6.5 (range 3-17) years with seven (3-22) measurements of GFR. RESULTS: For patients with microalbuminuria, mean +/- SD baseline GFR was 117 +/- 24 measured, 92 +/- 20 estimated (MDRD equation), or 103 +/- 24 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001); 95% limits of agreement were -66.1 to 20.3 (MDRD equation) and -58.7 to 30.7 (Cockcroft-Gault formula). The rate of decline in GFR was 4.1 +/- 4.2 measured, 2.9 +/- 2.8 estimated (MDRD equation), or 3.4 +/- 3.2 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). For patients with overt nephropathy, baseline GFR was 84 +/- 30 measured, 73 +/- 24 estimated (MDRD equation), or 81 +/- 28 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001) with 95% limits of agreement -47 to 25 (MDRD equation) and -39 to 33 (Cockcroft-Gault formula). The rate of decline in GFR was 5.2 +/- 4.1 measured, 4.2 +/- 3.8 estimated (MDRD equation), and 4.6 +/- 4.1 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). CONCLUSIONS: Particularly in microalbuminuric (hyperfiltering) patients, GFR is significantly underestimated with wide limits of agreement by the MDRD equation as well as by the Cockcroft-Gault formula. The rate of decline in GFR is also significantly underestimated with both equations. This makes GFR estimations based upon these equations unacceptable for monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.     

The values of estimated glomerular filtration rate calculated with creatinine and cystatin C based equations in healthy adults

The glomerular filtration rate (GFR) is widely accepted as the best overall index of kidney function. GFR can be measured as the clearance of exogenous or endogenous filtration markers or clinically estimated from serum concentrations of creatinine or cystatin C. Recently, it has been recommended that an estimated GFR (eGFR) should be reported in addition to the value of filtration markers. In this study, we determined the values of eGFR, based on creatinine and cystatin C equations, in 125 healthy volunteers aged 20-75 years. Creatinine was measured by a kinetic alkaline picrate method on an ARCHITECT ci8200 analyzer (Abbott Diagnostics, Wiesbaden, Germany). Cystatin C was determined by a latex particle-enhanced immunonephelometric assay (BNII, Dade Behring, Marburg, Germany). The eGFR values were calculated for creatinine using the Modification of Diet in Renal Disease (MDRD) study equation and Rule's quadratic equation and for cystatin C according to the equation published by Hoek et al. The reference intervals for eGFRs with MDRD, Rule's quadratic and Hoek's equations were calculated nonparametrically and were determined to be 63.5-124.6 mL/min/1.73 m2, 78.3-139.2 mL/min/1.73 m2 and 72.2-115.6 mL/min/1.73 m2, respectively. According to the US National Kidney Foundation, chronic kidney disease (CKD) can be defined as a GFR < 60 mL/min/1.73 m2. Our results showed that healthy adults had eGFR values > 63.5 mL/min/1.73 m2. However, it is important to note that these normal values overlap with values in stages 1 and 2 of CKD, thus an eGFR greater than 60 mL/min/1.73 m2 does not exclude kidney disease.     

Nonalbuminuric renal insufficiency in type 2 diabetes

OBJECTIVE: To determine the prevalence and characteristics of patients with type 2 diabetes who have impaired renal function, defined as a glomerular filtration rate (GFR) <60 ml. min(-1). 1.73 m(-2), and normoalbuminuria. RESEARCH DESIGN AND METHODS: A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic (99m)Tc-diethylene-triamine-penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria. RESULTS: A total of 109 patients (36%) had a GFR <60 ml. min(-1). 1.73 m(-2). The overall prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109 (35%), and 28 of 109 (26%), respectively. Compared with patients with macroalbuminuria, those with normoalbuminuria were more likely to be older and female. After excluding patients whose normoalbuminuric status was possibly related to the initiation of a renin-angiotensin system (RAS) inhibitor before the start of the study, the prevalence of a GFR <60 ml. min(-1). 1.73 m(-2) and normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%) unselected patients with impaired renal function were available for comparison over a 3- to 10-year period. The rates of decline in GFR (ml. min(-1). 1.73 m(-2). year(-1)) of -4.6 +/- 1.0, -2.8 +/- 1.0, and -3.0 +/- 07 were not significantly different for normo- (n = 12), micro- (n = 12), and macroalbuminuric (n = 10) patients, respectively. CONCLUSIONS: These results suggest that patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric.