Natale G. DeSanto

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.

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

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.

Tumor Markers in Uremia: Carcinoembryonic Antigen, Neuron-Specific Enolase, Carbohydrate Antigen CA-50 and α-Fetoprotein

The incidence of the tumor markers was studied in 140 patients aged between 18 and 84 years who had been on dialysis for 4-188 months. Neuron-specific enolase increased in 81 cases, CA-50 carbohydrate antigen in 44, while alpha-fetoprotein was within the normal range. Carcinoembryonic antigen (CEA) with 2 monoclonal assays was increased in 7 cases. When polyclonal assays were used, CEA was found to be elevated in 12 cases with one set and in 72 cases with another kit set. The data point to the potential usefulness of these markers for the detection of malignancy and possibly neuropathy in uremia; to the importance of renal tubules in the metabolism of proteins, glycoprotein and peptides, and to the activation/inhibition in various enzyme systems in the uremic state.

Renal synthesis of prostaglandins and thromboxane has no causative role for protein-induced glomerular hyperfiltration in healthy humans.

The study was devised to establish the role of prostaglandin E2, prostaglandin1 alpha and thromboxane A2 in the genesis of glomerular hyperfiltration response to a meat meal in healthy humans. To this end, a group of 8 healthy women was studied 4 times: in the control state (study 1), after a meat meal (study 2), following a meat meal associated with intravenous aspirin (study 3) and finally after a meat meal associated with intravenous aspirin following 2-day pretreatment with oral aspirin (study 4). Urinary excretion of prostaglandins and thromboxane increased during the glomerular hyperfiltration response to a meat meal and was suppressed by aspirin administration which did not suppress the renal hemodynamic response to the meat meal. The data do not support a causal role for prostaglandins and thromboxane A2 in the hemodynamic response to acute protein loading.