Level of hydration and renal function in healthy humans.

BACKGROUND: High hydration is commonly used in renal studies to improve the completeness of urine collection. The renal effects of hydration are not well defined. METHODS: Renal function was studied under fasting conditions (baseline) and after a meat meal (2 g of protein/kg body weight) in 12 healthy adults on a low and high hydration regimen of 0.5 and 4 mL of oral water per kg body weight/30 min, respectively. RESULTS: Urine flow, urinary and plasma Na, K, urea, and osmolality were stably different on low and high hydration regimens. At baseline, there were significant or borderline significant correlations of plasma and urine osmolality with glomerular filtration rate (GFR; inulin clearance) only in the low hydration regimen. GFR was higher in the low than the high hydration regimen at all time points. The difference was significant at baseline (19.2%) and at 90 to 180 minutes after the meal (14.4%). After the meal, GFR increased significantly over baseline values only in the high hydration regimen (30.0% at peak time). Urinary excretion of Na, urea, and osmoles was lower in the low than the high hydration regimen at all time points: The difference was significant for Na (at baseline) and osmoles (all time points). Urinary K excretion was not different in the two regimens. After the meal, there were significant increases in urinary excretion of Na (in the low hydration regimen) and urea (90 to 180 min after the meal). CONCLUSIONS: In fasting adults, high hydration lowered GFR and increased natriuresis. After a meat meal, GFR increased only in the high hydration regimen and natriuresis only in the low hydration regimen. Hydration affects GFR and natriuresis under fasting conditions and after a meat meal.

Glomerular filtration rate in severely overweight normotensive humans.

The study examined whether indexing glomerular filtration rate (GFR) for body surface area is appropriate for people who are severely overweight. Twenty normotensive adult men who were severely overweight but without microalbuminuria were enrolled into this study. The control group consisted of 20 healthy subjects matched for age, sex, and height. GFR was determined by measuring insulin with the continuous-infusion method. The clearance of endogenous creatinine was also measured after two daily urine collections. Renal plasma flow (RPF) was measured by p-aminohippurate clearance using the continuous-infusion method. Lean body weight was measured by impedentiometry. Adjusting for body surface area (in 1.73 m(2)) caused a significant reduction in GFR (P < 0.0001) in overweight humans (84.1 +/- 2.32 versus 109.6 +/- 3.07 mL/min/1.73 m(2)). The difference disappeared when GFR/height criteria were adopted. No difference between obese and healthy controls occurred after adjusting for lean body weight. Data for creatinine clearance paralleled those with insulin clearance; a significant reduction (P < 0.001) occurred after indexing for basal surface area, which disappeared after correction for height, as well as for lean body weight.

Renal reserve is normal in patients with dilative cardiomyopathy waiting for heart transplantation.

Renal reserve was explored by means of an oral protein load (2 g/kg body weight) under the form of cooked red meat in a group of 9 patients with end-stage heart failure (ESHF), class III of the New York Heart Association receiving loop diuretics and angiotensin-converting enzyme (ACE) inhibitors, and in a group of 18 healthy controls (HC) matched for age, gender, and height under an identical dietary regimen providing 40 cal/kg per day, 1 g/kg body weight of protein per day, Na 120 mmol/day, and K 50 mmol/day. Baseline glomerular filtration rate averaged 109.5+/-9.89 ml/min x 1.73 m2 in HC and 71.9+/-8.8 ml/min x 1.73 m2 in ESHF. Renal plasma flow averaged 540+/-27 ml/min x 1.73 m2 in HC and 235+/-47 ml/min x 1.73 m2 in ESHF. The filtration fraction was significantly higher in ESHF (p<0.01). Renal reserve averaged 26.03+/-3.28 ml/min x 1.73 m2 in HC and 27.2+/-7.12 ml/min x 1.73 m2 (not significant). Renal reserve averaged 123.9+/-2.9% in HC and 137.3+/-6.68% in ESHF (not significant). The filtration capacity was significantly higher in HC (p<0.001). The data point to a normalcy of renal reserve in ESHF which may depend on the chronic use of ACE inhibitors.

Measurement of glomerular filtration rate by the 99mTc-DTPA renogram is less precise than measured and predicted creatinine clearance.

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.

Effects of a meat meal on renal sodium handling and sodium balance.

Protein ingestion increases renal blood flow and glomerular filtration rate (GFR). This study investigated in healthy adults if the renal response to protein ingestion includes changes in urinary sodium (Na) excretion rate and Na balance. Renal clearance of Na and inulin (used as index of GFR) were measured in 25 healthy adults before (90 min) and after (180 min) a standard meal and, as control, before and after administration of water and Na-chloride (saline). The meal consisted of red lean meat (2 g protein/kg body weight); in control experiments, water and Na were given to match water and Na content of the meal. ANOVA for repeated measures, Student's t-test, and linear regression were used for statistical analysis. GFR and urinary Na excretion increased over baseline after the meal (p < 0.001), not after saline. The post-meal natriuretic response was accounted for an early (0-90 min) increase in glomerular filtered load of Na (p < 0.001) and a late (90-180 min) reduction in tubular Na reabsorption (p < 0.02). Urine flow rate and plasma Na did not significantly change after the meal and in control experiments. Analysis of Na balance showed that post-meal Na excretion was significantly higher than baseline also after Na balance returned to pre-meal values. In healthy individuals, a meat meal stimulates natriuresis and causes a net decrease in Na balance. The renal natriuretic response to the meal appears secondary to the meal-induced changes in renal hemodynamics. The data are in keeping with the hypothesis that dietary protein intake affects also renal Na handling.

Effect of an acute oral protein load on renal acidification in healthy humans and in patients with chronic renal failure.

The effect of a meat load on the renal handling of acid-base balance was studied in ten healthy subjects (GFR by inulin clearance = 98.5 +/- 8.14 ml.min-1.1.73 m-2) and in ten patients affected by chronic renal failure (CRF) (GFR = 39.9 +/- 5.3 ml.min-1.1.73 m-2). After the meat load (2 g.kg-1 body weight of cooked unsalted red meat), GFR increased by 26.9% (peak value) over baseline in healthy subjects and by 32% in CRF patients. The acid-base status of the healthy subjects was in the normal range, whereas the CRF patients disclosed a slight metabolic acidosis. After a meat load, there was, in the healthy subjects, an increase in the filtered load of bicarbonate coupled to an enhanced tubular reabsorption and urinary excretion. The time course between bicarbonate load and urinary excretion was coincident. In CRF patients, the increase of bicarbonate tubular load after the meal was associated with an increase in tubular reabsorption but not in urinary excretion of this anion. The relationship between bicarbonate load and reabsorption was linear in both groups up to the highest filtered loads. Baseline titratable acidity (TA) and ammonium (NH4+) excretion (expressed per ml GFR) were increased in CRF patients as compared with control subjects, but no changes were found after the meat load in both groups in these experimental conditions. The data indicate that the renal tubules contribute to the maintenance of acid-base balance both in healthy subjects and in CRF patients by reabsorbing most of the additional bicarbonate load. The transient, but significant, increase in bicarbonate excretion observed in healthy subjects could be related to the increased tubular load of bicarbonate. In CRF patients, tubular bicarbonate reabsorption was more complete, possibly because of the stimulation of H+ secretion by the mild metabolic acidosis. TA and NH4+ did not participate in tubular compensation of the increased buffer load.

The renal hemodynamic response to an oral protein load is normal in IgA nephropathy.

The study was devised to explore the effects of an acute oral protein load on renal hemodynamic response in patients with IgA nephropathy (IgAN). The study was performed in 10 proteinuric IgAN patients (800 +/- 300 mg/day) and in 20 healthy controls (matched by sex, age, BMI, BSA, plasma creatinine, plasma urea, urinary urea and protein intake). Blood pressure and creatinine clearance were nearly identical in the two groups. GFR and RPF, measured as the clearance of inulin and of p-aminohippurate (PAH) were studied before and after a meat meal which provided 2 g of protein/kg BW. Following the protein load, renal reserve, percent renal reserve and postmeal cumulative changes of GFR were not significantly different in IgAN and controls. Filtration fraction (FF) at baseline was significantly higher (p < 0.01) in IgAN than in controls (25.5 +/- 1.41 vs. 19 +/- 2%). Postmeal hyperemia and hyperfiltration did not affect FF in either group. Filtration capacity in IgAN was lower (p<0.02) than in controls (117 +/- 5.6 vs. 137.9 +/- 7.0 ml/min x 1.73 m2), whereas the percent of filtration capacity utilized at rest was identical in controls and in IgAN. Creatinine clearance overestimated GFR in IgAN. The data indicate that renal hemodynamic response to proteins in IgAN is normal.

Renal reserve is normal in adults born with unilateral renal agenesis and is not related to hyperfiltration or renal failure.

This study was carried out to examine the renal hemodynamic response in adult patients with single kidneys born with unilateral renal agenesis. A group of 21 patients with unilateral renal agenesis were divided into three groups according to their glomerular filtration rate (GFR): 112 +/- 3 ml/min x 1.73 m2 in group A, 68 +/- 3.2 ml/min x 1.73 m2 in group B, and 40.7 +/- 3.3 ml/min x 1.73 m2 in group C. Mean arterial blood pressure was significantly higher in the patients of group C who were also proteinuric. The renal hemodynamic response to an oral protein load (2 g/kg of protein as beefsteak) was normal in all groups and unrelated to hyperfiltration or to renal failure and proteinuria. The study indicates that in patients with renal agenesis, the hemodynamic response to a protein challenge is similar to that of kidney donors, renal transplant recipients and uninephrectomized patients. The paper also demonstrates that the renal response to a protein challenge is inadequate to identify patients with renal agenesis who are at risk of developing renal disease. Finally, in renal agenesis with renal disease, creatinine clearance overestimated the GFR by an average of 32.7%.

Renal response to an acute oral protein load in healthy humans and in patients with renal disease or liver cirrhosis.

This article analyzes 57 reports published in the years 1983 through 1964 that addressed the issue of the renal hemodynamic response to an oral protein load. Seventy-three groups are reported in those studies: 52 were healthy subjects (n = 627) and 21 had renal disease (n = 256); 47 were studied using inulin (n = 407 healthy people and 112 renal patients); 26 groups were studied using creatinine (n = 220 healthy people and 144 renal patients). Patients with liver cirrhosis were also analyzed. There was great heterogeneity in methodology used, emphasizing the need for standardization. The role of plasma amino acids, glucagon, insulin, growth hormone, PGE2, 6-ketoPGA1 alpha, brain-gut peptides, ANP, AVP, dopamine, and kinins in promoting the renal hemodynamic response to an oral protein load is discussed.

Renal functional reserve in children.

Renal reserve in children is related to changes in renal plasma flow (RPF) in health and renal disease. Peak glomerular flow rate (GFR) correlates with peak RPF. The renal hemodynamic response to protein is associated with a decrease in renal vascular resistance. Studies in children are less numerous than in adults. The main findings of the studies on renal reserve in children have disclosed the following: (1) the lack of an age dependency, (2) the normalcy of renal reserve in renal disease, (3) the return of renal reserve in type 1 diabetes mellitus by a reduction in protein intake, and (4) the suppressibility of renal reserve by somatostatin infusion.

Creatinine clearance: an inadequate marker of renal filtration in patients with early posthepatitic cirrhosis (Child A) without fluid retention and muscle wasting.

Glomerular filtration rate (GFR) was measured in 19 patients with Child A liver cirrhosis by comparing the endogenous creatinine clearance with inulin clearance. Inulin clearance averaged 90 +/- 4.4 ml/min x 1.73 m2, while creatinine clearance averaged 122 +/- 7 ml/min x 1.73 m2 (p < 0.001). The overestimation of GFR by creatinine was present in 18 of 19 patients and was inversely correlated with inulin clearance (r = -0.452, p < 0.04). The data point to the unsuitability of creatinine as a marker of filtration in early posthepatitic cirrhosis (Child A).

Sequential analysis of variation in glomerular filtration rate to calculate the haemodynamic response to a meat meal.

BACKGROUND: The renal haemodynamic response to a meat meal is usually measured as either filtration capacity (maximal achieved GFR), or renal reserve (maximal GFR increase over baseline), or percent renal reserve (maximal GFR increase as a percentage of baseline). The time-course of GFR response to a meat meal varies in different individuals as the peak GFR tends to occur late in renal disease. This study proposes a new method to measure the GFR response independently of differences in peaking time. METHODS: The study is based on measurement of GFR (inulin clearance, ml/min x 1.73 m2 BSA) in three 30-min pre-meal clearance periods (baseline) followed by analysis of the GFR changes for up to 180 min (four 30-min and one 60-min clearance periods) after a meat meal (2 g of protein/kg of BW as red cooked meat). Data were analysed from 85 healthy people (GFR > or = 100) and 273 individuals with renal disease (RD) who were divided into three groups based on their baseline GFR (RD1, n = 115, GFR 99-66; RD2, n = 85, GFR 65-33; RD3, n = 73, GFR < 33). RESULTS: In healthy people after the meat meal GFR peaked between 30 and 60 min and returned to baseline by 120 min. In the three RD groups GFR peaked later than in healthy people (P < 0.001) and remained higher than baseline for up to 180 min (P < 0.001). Cumulative post-meal GFR changes, calculated as cumulative GFR increase over baseline up to 120 min after meal (ml/120 min x 1.73 m2 BSA), were significantly different (P < 0.01) in the four groups (healthy people, 937 +/- 141; RD1, 1222 +/- 141; RD2, 587 +/- 104; RD3, 361 +/- 89). Interindividual variability in cumulative GFR increase was only partially explained by the value of filtration capacity (r2 = 0.285), renal reserve (r2 = 0.640), and percent renal reserve (r2 = 0.175). CONCLUSION: The data indicate that commonly used parameters are poor indices of the actual total time-course of the renal response to a protein load.