Luigi Bellini

Predicted creatinine clearance to assess glomerular filtration rate in chronic renal disease in humans

The work was designed to assess the suitability of both measured endogenous creatinine clearance (CCR) and predicted creatinine clearance (P-CCR) to evaluate GFR in chronic renal disease (CRD) by utilizing the renal clearance of inulin (CIN) as gold standard. A total of 124 subjects were studied (62 healthy, 62 with CRF). CCR significantly overestimated GFR in healthy subjects as well as in CRF, whereas P-CCR was identical to GFR. The CCR/CIN ratio which calculates the fractional creatinine clearance and provides a rough estimation of the contribution of creatinine secretion in explaining the differences between CCR and GFR was increased in CRD and especially in CRD of glomerular origin. The ration P-CCR/CIN was significantly lower than CCR/CIN in healthy subjects and in patients with CRD of glomerular origin. The data are against the use of CCR in assessing GFR in healthy subjects and in patients with CRD.

The Renal Hemodynamic Response following a Meat Meal in Children with Chronic Renal Failure and in Healthy Controls

The renal hemodynamic response to a meat meal (2 g/kg BW) was studied in 11 healthy children and in 10 children with a mean plasma creatinine concentration of 2.6 +/- 0.1 mg/dl due to chronic renal failure (CRF) of various etiologies. In the healthy status, after a meat meal, the glomerular filtration rate (GFR) increased significantly from a baseline value of 119.0 +/- 5.0 to a peak of 159 +/- 5.8 ml/min x 1.73 m2; in CRF baseline GFR averaged 49 +/- 4.0 and at peak 76.6 +/- 7.2 ml/min x 1.73 m2 (p less than 0.005). The peak GFR response was reached earlier in healthy subjects than in CRF (p less than 0.05) and did not correlate with age or with baseline GFR. Renal plasma flow (RPF) in healthy controls increased from 532 +/- 32 at baseline to 646 +/- 42.9 ml/min x 1.73 m2 after the meal (p less than 0.005). Also in CRF after a meat meal there was a significant increase in RPF from 278 +/- 51 to 65 +/- 66 ml/min x 1.73 m2 (p less than 0.005). The filtration fraction was not affected. The percent increase over baseline values of GFR and RPF at the peak was significantly higher in diseased children. Renal reserve averaged 28.1 +/- 5.3 ml/min in diseased children and 39.7 +/- 5.2 ml/min (p less than 0.01). The data indicate that (1) a meat meal is a suitable method to recruit renal reserve in normal children and in children with chronic renal failure, and (2) the renal reserve is normal in chronic renal failure.

Tubular Function by Lithium Clearance, Plasma Amino Acids and Hormones following a Meat Meal in Childhood

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90 min) in glomerular filtration rate (GFR) following a meat meal (2g protein/kg body weight) in 12 normal children. Three baseline and 4 clearances after the meal were obtained, each lasting 30 min. The mean baseline CLi was 23.1 +/- 1.64 ml/min/1.73 m2. At peak GFR response (60 min from starting the meal), CLi averaged 27.6 +/- 2.4 ml/min/1.73 m2 (p less than 0.025 vs. baseline) and it was further increased (32.2 +/- 5.04 ml/min/1.73 m2, p less than 0.01 vs. baseline) 120 min after starting the meal, while GFR returned to baseline values. Fractional lithium excretion averaged 0.23 +/- 0.04 at baseline and increased continuously after the meat meal and, at completion of the study, it averaged 0.38 +/- 0.07 (p less than 0.025 vs. baseline). The distal absolute and fractional sodium reabsorption increased throughout the studies following the meal and peaked at 120 min. The functional changes were associated with a statistically significant increase in the plasma concentration of insulin, glucagon, and total amino acids after the meal. The latter at the end of the study was almost doubled (5,600 +/- 780 versus 3,200 microM at baseline, p less than 0.01). The data indicate that the tubulo glomerular feedback mechanism operates normally after a meat meal. The finding on increased distal sodium reabsorption might point to the existence of an insulin-dependent mechanism.

Pancreatectomy Abolishes the Renal Hemodynamic Response to a Meat Meal in Man

N.G. DeSanto, MD, Via Pansini 5, Policlinico Università, Pad 17, I-80131 Naples (Italy) Dear Sir, According to Brenner et al. [1], the hyperfiltration response which follows intravenous amino acid administration [2–4] of ingestion of a meat meal [5, 6] may be due to a circulating hormone or some other intermediate effector among which glucagon may be a good candidate. We report on the absence of the hyperfiltration response to a meat meal in man after total pancreatectomy. This finding points to the role of a factor of pancreatic origin in the genesis of the renal hemodynamic response to protein load. We studied a 45-year-old man, weighing 72 kg, who, because of severe acute pancreatitis, had undergone total pancreatectomy 4 years earlier. After surgery he had strictly adhered to an appropriate protocol of insulin administration and to a dietary regimen providing 40 g of protein and 2,000 cal/day. Protein intake was controlled before the study on 3 consecutive days by means of urea generation rates. At the time of the study, plasma creatinine was 0.99 mg/dl, creatinine clearance 84 ml/min × 1.73 m2, blood urea 48 mg/dl, and fasting blood glucose 1.55 g/l. Microalbuminuria was absent. The patient was studied before (3 clearance studies (C1-C3) and after a meat meal MM 5 clearance studies (C4-C8) at 30, 60, 90,120 and 180 min). Each clearance lasted 30 min with the exception of C8 lasting 60 min. The meat meal provided 2 g of protein/kg body weight in the form of cooked red meat. All data measured inCι-C3 Table 1. Effects of a meat meal in a pancreatectomized man

Low Urinary Albumin Excretion in Astronauts during Space Missions

Background: Physiological changes occur in man during space missions also at the renal level. Proteinuria was hypothesized for space missions but research data are missing. Methods: Urinary albumin, as an index of proteinuria, and other variables were analyzed in 4 astronauts during space missions onboard the MIR station and on the ground (control). Mission duration before first urine collection in the four astronauts was 4, 26, 26, and 106 days, respectively. On the ground, data were collected 2 months before mission in two astronauts, 6 months after in the other astronauts. A total of twenty-two 24-hour urine collections were obtained in space (n per astronaut = 1–14) and on the ground (n per astronaut = 2–12). Urinary albumin was measured by radioimmunoassay. For each astronaut, mean of data in space and on the ground was defined as individual average. Results: The individual averages of 24 h urinary albumin were lower in space than on the ground in all astronauts; the difference was significant (mean ± SD, space and on the ground = 3.41 ± 0.56 and 4.70 ± 1.20 mg/24 h, p = 0.017). Dietary protein intake and 24-hour urinary urea were not significantly different between space and on the ground. Conclusions: Urinary albumin excretion is low during space mission compared to data on the ground before or after mission. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).

Vasopressin, hypercalciuria and aquaporin--the key elements for impaired renal water handling in astronauts?

Accessible online at: www.karger.com/journals/nef There is growing interest in integrating various adaptations occurring in renal function during space flight in order to develop a new rationale for future research in the field. Experience derived from research programs in some of the 400 astronauts, who have been in space, indicates that significant changes in renal sodium and water handling take place under Ì-gravity conditions. We have recently reviewed in detail these components of fluid balance and kidney function in space [1–7]. An additional burden on our present understanding is added by the weightlessness-dependent bone loss, which causes hypercalciuria. Therefore, in this review we are in consecutive sections describing ‘Body Fluid Regulation in Space’, ‘Calcium and Bone Metabolism in Space’, ‘Involvement of Renal Aquaporins’, and the ‘Pathophysiology of Clinical Hypercalciuria’ with the aim to provide a rationale for the impairment in water handling as a consequence of the increase in luminal calcium concentration in the collecting duct. On this basis, we generate a new hypothesis on how the kidney function and body fluid regulation are modified during Ì-gravity. Body Fluid Regulation in Space

Brain-gut peptides and the renal hemodynamic response to an oral protein load : a study of gastrin, bombesin, and glucagon in man

With the aim of disclosing a possibility for gastrin and bombesin to participate in the postprandial regulation of the renal hemodynamic response, 10 healthy males were studied before and after a meat meal (2 g/kg BW of proteins as cooked red meat). We evaluated the time course changes of glomerular filtration rate (GFR) renal plasma flow (RPF), and the plasma concentrations of gastrin, bombesin, glucagon, and total amino acids. After the meat meal a significant increase in GFR and RPF was seen, within 30 min, along with an increase in plasma gastrin and glucagon. Bombesin and amino acid concentrations increased at a later time. The data suggest but cannot demonstrate a causal role for gastrin and glucagon in the genesis of the hyperfiltration response to acute protein administration.

Renal Handling of Sodium after an Oral Protein Load in Adult Humans

This investigation was designed to study (1) renal sodium handling after an oral protein load and (2) its relationship to some known determinants of the hemodynamic response (glucagon, insulin, growth hormone, renin, aldosterone, and plasma amino acid concentration). To this end of group of 8 adult subjects was studied before (three 30-min clearances) and after a meat meal (MM; five 30-min clearances at 30, 60, 90, 120 and 180 min). The MM provided 2 g/kg BW of protein. Within 30 min from the MM an hyperfiltration response was seen, which was paralleled by a 2-fold increase in plasma alanine concentration while total plasma amino acid concentration was not different from the baseline values. The hemodynamic response was associated with a normally operating tubuloglomerular feedback mechanism independent of renin-aldosterone activity, but possibly associated with an early increase in plasma glucagon concentration and later on with a modest increase in postmeal plasma insuling concentration.

Glucagon-independent renal hyperaemia and hyperfiltration after an oral protein load in child A liver cirrhosis

Abstract. The work was designed to study the effects of a meat meal on glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma concentrations of glucagon, insulin, growth hormone, renin, aldoster‐one, total amino acids, and NH3 in healthy humans (H) as well as in patients with Child A liver cirrhosis (LC). The meat meal produced renal hyperaemia and hyperfiltration without changes in the filtration fraction. Fractional Na excretion in urine increased significantly after the meat meal only in LC. Hyperinsulinae‐mia and hyperglucagonaemia were seen at baseline in LC and were not affected by the meat meal, whereas in H glucagon concentration increased significantly over baseline within 30 min from the meat meal and insulin within 60 min. Growth hormone concentration was normal at baseline in LC and increased significantly 120–180 min after the meal, whereas it was not affected in H. Renin and aldosterone were stable in both H and LC. Plasma amino acid concentration began to increase 60 min after the meat meal, when hyperfiltration was present. The data indicate that in human Child A cirrhosis of the liver the renal haemodynamic response to a meat meal is independent of changes in glucagon.