P. Anastasio

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).

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.

Beneficial Effects of Atrial Natriuretic Factor on Cisplatin-Induced Acute Renal Failure in the Rat

The organometal cisplatin has potent antitumor properties. However, its use is sometimes complicated by significant nephrotoxicity. This is characterized by tubular necrosis and impairment of the glomerular filtration rate (GFR). On the other hand, it has been demonstrated that atrial natriuretic factor (ANF) increases GFR in normal euvolemic rats. In the present study, we have therefore tested if this new potent natriuretic compound could restore some of the renal parameters affected by cisplatin. To investigate this issue, acute renal failure was induced in 9 rats by intraperitoneal injection of cisplatin 10 mg/kg body weight (b.w.). Renal function was studied 72 h later using the 3H-inulin clearance method and was compared with the renal function of 5 normal euvolemic rats. The cisplatin-treated rats showed high blood urea nitrogen levels, a 74% reduction of whole kidney GFR (0.308 +/- 0.047 vs. 1.17 +/- 0.08 ml/min/100 g b.w.) and a significant increase in the fractional excretion of urine, sodium and potassium. After 2 control clearances, synthetic ANF was administered intravenously as a prime (12 micrograms/kg b.w.) and then as a constant infusion (1 microgram/kg/min) to 6 cisplatin-treated rats. This promptly doubled the GFR (0.603 +/- 0.113 ml/min/100 g b.w.) and induced a significant increase in the excretion rate of urine, sodium and potassium. These results demonstrate that the administration of ANF has a beneficial effect on the experimental model of acute renal failure induced by cisplatin.

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.

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

Abstract. The effect of an acute protein load (2 g kg‐1bodyweight [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.

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.

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.

Atrial Natriuretic Factor Increases Glomerular Filtration Rate in the Experimental Acute Renal Failure Induced by Cisplatin

Cis-diamminodicloroplatinum (CP) is a recently developed antineoplaxadstic agent that has a remarkably broad spectrum of clinical activity in the treatment of solid tumors (1). Use of this drug has significantly improved the response rate in patients treated for metastatic testicular and ovarian carcinomas. Additionaly,cisplatin is an important component of many treatment programs for the management of bladder carcinoma,squaxadmous cell carcinoma of the head and neck,bronchogenic carcinoma of the lung,cervical and endometrial cancer.However the clinical use of the drug is largely hampered by its nephrotoxicity. In fact the degree of renal toxicity rather than the therapeutic response often determines the dosage of this therapeutic agent. A chronic,repetitive low dosage of cisplatin in rats also leads to kidney failure creating a situation similar to kidney insufficiency clinically observed during the prolonged chemotherapeutic regimens used for various malignancies (2). An acute single dose of CP induces in rats a non oligurie acute renal failure (ARF) that is charactexadrized by a reduction of whole animal glomerular filtration rate (GFR),with increase in serum creatinine concentration,diminished urine osmolality, decreased U/P creatinine concentration ratios,and a significant increase in the fractional excretion of sodium (3). Development of cisplatin to its present level of clinical usefulness was greatly facilitated by studies in which hydration-diuresis maneuvers were used in dogs (4) and subsequently in humans (5). Another promising approach to limit CP nephrotoxicity is pharmacologic inhibition of cisplatin tubular secretion. Administration of drugs such as probenecid may be effective in decreasing the intracellular concentration of drug by inhibiting its uptake by the contraluminal cell membrane (6).

Thyroidal Regulation of Alkaline Phosphatase Activity in Kidney Cortex Brush Border Membranes

In kidney cortex homogenates and brush border membranes of hypothyroid rats undergoing T3 substitution with 50 µg/kg BW a day for 1–4 days, a significant decrease of alkaline phosphatase ac

Renal prostaglandins and thromboxane A2 lack a functional significance in the genesis of protein-induced glomerular hyperfiltration in human renal disease.

The study was devised to assess the effects of a protein load (2 g/kg BW) on urinary prostaglandin E2 (PGE2), 6-keto-PGF1 alpha and thromboxane A2 (TxA2) in patients with renal failure of glomerular origin. To this end, 8 women with a glomerular filtration rate of 55 +/- 12 ml/min x 1.73 m2 underwent the following studies: study 1: control; study 2: meat meal; study 3: meat meal+intravenous aspirin; study 4: pretreatment with oral aspirin for 2 days+protocol in study 3. Glomerular hyperfiltration was seen after the meat meal (study 2) and was not suppressed by aspirin (studies 3 and 4). Urinary PGE2, 6-keto-PGF1 alpha and TxA2 increased after the meat meal in study 2 and were suppressed by aspirin in studies 3 and 4. The ratio between vasodilative (PGE2 + 6-keto-PGF1 alpha) and vasoconstrictive (TxA2) autacoids increased during the meat meal (study 2) and was suppressed when aspirin was injected at the time of the oral protein load, thus, the effect of aspirin was much greater for PGE2 and PGF1 alpha than for TxA2. These data do not support that urinary prostaglandin and TxA2 have a direct role in renal hyperfiltration due to an acute protein load.