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The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

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 (P0.0001) 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 (P0.001) occurred after indexing for basal surface area, which disappeared after correction for height, as well as for lean body weight.

Patients with advanced heart failure commonly develop simple or mixed acid-base disturbances. The altered acid-base homeostasis can occur as a consequence of the heart failure itself, the therapeutic interventions, or associated conditions. The present study examined acid-base disorders in patients with heart failure who received successful heart transplantation. The information collected should provide light on the determinants of acid-base disorders in this patient population. Seventy status 2 UNOS (United Network Organ Sharing) patients listed for heart transplantation were enrolled in this study. All patients received loop diuretics, spironolactone, ACE inhibitors, carvedilol and digitalis as needed. Patients were studied again at discharge after transplantation, under cyclosporine, azathioprine, steroids, loop diuretics and ACE inhibitors. After heart transplantation, a significant increase of ejection fraction from 19.7 ± 0.63 to 53.6 ± 0.9% (p < 0.0001) occurred along with a concomitant reduction of central venous pressure (p < 0.0001) from 12.6 ± 0.20 to 6.9 ± 0.21 mm Hg. Before heart transplantation there was high-normal pH (7.43 ± 0.009), slight loss of hydrogen ions (35.4 ± 0.4 nmol/l), slightly reduced pCO2 (37.6 ± 1.1 mm Hg). After heart transplantation a stability of blood pH and hydrogen ion concentrations was found but bicarbonate increased significantly (p < 0.02) from 24.2 ± 0.61 to 26.2 ± 0.51 mmol/l and pCO2 from 37.6 ± 1.1 to 39.3 ± 0.7 mm Hg (p < 0.05). Plasma renin activity averaged 3.80 ± 0.6 pg/ml before heart transplantation and 2.82 ± 0.4 pg/ml after (p < 0.01). Aldosterone concentration averaged 380 ±15 pg/ml before heart transplantation and 280 ± 10 pg/ml after (p < 0.01). These data suggest that in patients before heart transplantation there is a mixed acid-base imbalance that includes respiratory alkalosis and metabolic alkalosis. After transplantation the recovery of the abnormal circulatory status erased the initial respiratory alkalosis but metabolic alkalosis persisted and accounted for a further rise in plasma bicarbonate.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting. Copyright © 2001 by W.B. Saunders Company.

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×1.73 m2 in HC and 71.9±8.8 ml/min×1.73 m2 in ESHF. Renal plasma flow averaged 540±27 ml/min×1.73 m2 in HC and 235±47 ml/min×1.73 m2 in ESHF. The filtration fraction was significantly higher in ESHF (p2 in HC and 27.2±7.12 ml/min×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

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-dietlyl-enetriaminepentacetic 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 99mTcDTPA, 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.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p

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.

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 ± 7.0ml/min × 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. © 1997 S. Karger AG, Basel.

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).

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.

In this study Bioelectrical Impedance Analysis was performed in 5 patients with end stage heart failure in whom a left ventricular assist device (Novacor) was successfully implanted. Whole body measurements of bioelectrical indices resistance and reactance were taken before surgery and 3, 7, 12, and 15 days after it. After surgery there was a significant decrease in reactance, indicating a shift of body fluids from intra- to extra-cellular space.

The study was devised to establish the role of prostaglandin E(2), prostaglandin(In), and thromboxane A(2) 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 A(2) in the hemodynamic response to acute protein loading.

Background/Aims: Little information is available about the tubular functions and the renal adjustments that take place in obese subjects after a protein meal. How the excess fat may affect renal response to dietary proteins is currently only partially understood. This paper aims to address (i) whether severe obesity, in the absence of other comorbidities, is responsible of kidney dysfunction at either the glomerular or the tubular level and (ii) whether it compromises renal adaptations to a large protein meal. Methods: Twenty-eight obese subjects without albuminuria, along with 20 control subjects, age and gender matched, have been studied. The glomerular filtration rate (GFR; inulin clearance), renal plasma flow (p-aminohippurate clearance), the proximal tubular function (lithium clearance), the fractional excretion of sodium (FPRNa) have been measured at the basal level (steady state) and after a protein meal (perturbation). Results: Under steady state conditions, filtration fraction, proximal tubular sodium handling and the FPRNa were not significantly different in non proteinuric obese subjects compared with controls. However, a protein meal led to a delayed glomerular hyperfiltration in obese patients compared with controls. Conclusion: This study shows that obese patients, in the absence of significant comorbidities, have a normal proximal tubule Na+ absorption at basal; conversely, these subjects showed a different response to a protein meal compared with normal subjects in terms of changes of GFR. Overall, these results suggest that the modified hemodynamic response to a protein meal might be the earliest hallmark of future kidney dysfunction in obese subjects.

Tuberous sclerosis complex (TCS) is a genetic disorder with a variable clinical presentation. It is commonly characterized by seizures, mental retardation and cutaneous angiofibromas. Renal manifestations frequently include angiomyolipomas and cysts which lead to chronic kidney disease. We report a case of valproic acid-induced acute pancreatitis in a dialysis patient affected by TCS. The case demonstrates the importance of assessing antiepileptic drug treatment in dialysis patients. © 2012 Società Italiana di Nefrologia.

This article reviews bone adaptation to microgravity, during manned space missions, in humans undergoing Head Down Tilt (HDT) and in Hind-Limb-Suspended Rats. Under microgravity conditions, bone loss occurs in association with hypercalciuria, which in turn modulates Aquaporin 2 (AQP2) excretion in urine, thus avoiding stone forming in space. This report discloses the need to prevent bone loss in order to prepare for long stays at lunar bases or voyages to Mars. (C) 2005 by the National Kidney Foundation, Inc.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Remarkably, due to the high heterogeneity of the Fabry phenotype, both diagnostic testing and treatment decisions are more challenging in females than in males; thus, reliable biomarkers for Fabry disease are needed, particularly for female patients. Here, we use a proteomic approach for the identification of disease-associated markers that can be used for the early diagnosis of FD as well as for monitoring the effectiveness of ERT. Our data show that the urinary proteome of Fabry naïve patients is different from that of normal subjects. In addition, biological pathways mainly affected by FD are related to immune response, inflammation, and energetic metabolism. In particular, the up-regulation of uromodulin, prostaglandin H2 d-isomerase and prosaposin in the urine of FD patients was demonstrated; these proteins might be involved in kidney damage at the tubular level, inflammation and immune response. Furthermore, comparing the expression of these proteins in Fabry patients before and after ERT treatment, a decrease of their concentration was observed, thus demonstrating the correlation between the identified markers and the effectiveness of the pharmacological treatment. © The Royal Society of Chemistry.

We need a new health care system that is based on patients' needs. The present cadre of health managers who acquired power by cutting expenditures must be removed from office. We need to educate a new cadre of health managers who are 1) convinced that safeguarding health does not use up the resources of the next generations; 2) capable of switching the system from curative to preventive medicine; and 3) able to reinforce clinical research. Such principles have been recently adopted by the French President Sarkozy in devising the national health care program.

Background: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate.Methods: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated.Results: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1mEq/L, whereas it averaged 21.1 +/- 0.7mEq/L in patients on calcium carbonate (p < 0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p < 0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

Renal dysfunction is a constant feature of congestive heart failure and is a stronger predictor of mortality than left ventricular ejection fraction or New York Heart Association classification. In heart failure, a reduction of glomerular filtration rate and renal plasma flow occurs, although the filtration fraction increases. There are many reason for this pattern. A reduction in effective circulating volume stimulates sympathetic activity and the renin-angiotensin-aldosterone system, and it is associated with increased concentrations of atrial natriuretic peptide, brain natriuretic peptide, and tumor necrosis factor α. Because in chronic kidney disease heart dysfunction commonly is present, an efficient cardiologist-nephrologist interaction should be promoted. © 2005 Elsevier Inc. All rights reserved.

Background. Previous studies have shown conflicting data on accuracy of equations for kidney function prediction. The present work analysed the relationship of gender, age and body mass index (BMI) to error of predictions by the Cockcroft–Gault equation (CGeq), the simplified equation of the Modification of Renal Diseases Study (MDRDeq) and the Mayo Clinic equation (Mayoeq). Methods. Inulin clearance (glomerular filtration rate; GFR) and other variables were measured in 380 subjects of both sexes, aged 18–88 years, with and without kidney disease. GFR was defined as low when

Clinical studies indicate that indices of glomerular filtration rate (GFR) as serum creatinine or creatinine clearance can predict the risk of death in congestive heart failure (CHF) and in heart transplantation. The study reports data on creatinine clearance before and after heart transplantation in 160 patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance averaged 83.5*32 mL/min * 1.73 m2 and was not significantly associated with 5-year mortality. Creatinine clearance significantly decreased after heart transplantation with a linear trend up to 3 years for patients with complete follow-up. Data suggest that the relation between kidney function and mortality after heart transplantation is affected by several confounders with inclusion of cause of heart disease, co-morbidity, anemia, and post-transplant decrease in kidney function. Clinical studies indicate that indices of glomerular filtration rate (GFR) as serum creatinine or creatinine clearance can predict the risk of death in congestive heart failure (CHF) and in heart transplantation. The study reports data on creatinine clearance before and after heart transplantation in 160 patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance averaged 83.5±32 mL/min × 1.73 m 2 and was not significantly associated with 5-year mortality. Creatinine clearance significantly decreased after heart transplantation with a linear trend up to 3 years for patients with complete follow-up. Data suggest that the relation between kidney function and mortality after heart transplantation is affected by several confounders with inclusion of cause of heart disease, co-morbidity, anemia, and post-transplant decrease in kidney function. © 2005 Elsevier Inc. All rights reserved.

Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non–systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition, there was a reduction of factor XII during the treatment. It is possible to assume in the TC group and, to a lesser extent, also in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen, which causes hypofibrinolysis. In addition, an excess of factor VIII is activated by endothelial dysfunction with subsequent activation of the coagulation cascade as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of interfering with the system of protein C, a potent anticoagulant factor that inactivates cofactors Va and VIIIa. They also induce the expression of procoagulant factors on the surface of the endothelial cells. In conclusion, the hypercoagulable state caused by alterations of coagulation and fibrinolytic factors is a cause of vascular access dysfunction and thrombosis of other vessels.

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 (2g of protein/kg body weight) in 12 healthy adults on a low and high hydration regimen of 0.5 and 4mL of oral water perkg 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 180min 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.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures. (C) 2001 by the National Kidney Foundation, Inc.

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.

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. 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

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

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90min) 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 30min. The mean baseline CLi was 23.1 ± 1.64ml/min/1.73m2. At peak GFR response (60min from starting the meal), CLi averaged 27.6 ± 2.4ml/min/1.73m2 (p < 0.025vs. baseline) and it was further increased (32.2 ± 5.04ml/ min/1.73m2, p < 0.01 vs. baseline) 120min 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 < 0.025vs. 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 µM at baseline, p < 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.

Background: The purpose of this study was to explore the renal acid-base response to acute protein load in patients with heart failure (HF). It was prompted by the fact that there are no data available regarding the role of renal tubules in maintaining acid-base balance following protein loading in HF patients.Methods and Results: Nine male patients with HF and 12 healthy subjects (controls) were enrolled in this study. In the HF patients, average blood pH was 7.42 (0.03), average PCO2 was 36.6 mmHg (6.3) and average bicarbonate was 24.2 mmol/L (4.3). The acid-base status of patients was unaffected by meat ingestion. The values at peak glomerular filtration rate (GFR) did not differ significantly from baseline levels. An oral protein load did not influence the urinary pH, titratable acidity (TA) and ammonium excretion in the patients with HF, contrary to the findings in the controls. On the other hand, ammonium excretion in patients with HF reduced significantly compared with values from controls at baseline and following oral protein loading. Filtered and reabsorbed bicarbonate increased significantly in HF patients following meat ingestion, whereas there was no change in absolute and fractional bicarbonate excretion and fractional bicarbonate reabsorbed.Conclusions: This study demonstrated that in patients with HF, bicarbonate reabsorption increases following an oral protein load without a significant enhancement in bicarbonate excretion. The difference can be explained by the presence of respiratory alkalosis leading to bicarbonate conservation.

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.

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.

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.

To explore the age-related changes in tubular function and in the renal reserve (RR) a total of 98 healthy subjects were studied while on free living conditions. Enrolled people were divided into 3 groups: group A (n = 40, age range 5-18 years, Na intake 80 +/- 20 mM/day, protein intake 1.30 +/- 0.76 g/kg BW); group B (n = 34, age range 19-60 years, Na intake 110 +/- 12 mM/day, protein intake 1.32 +/- 0.75 g/kg BW), and group C (n = 24, age range 61-89 years, Na intake 159 +/- 12 mM/day (p less than 0.01 vs. A and B), protein intake 1.26 +/- 0.23). Glomerular filtration rate (GFR) (inulin), renal plasma flow (p-aminohippurate), the amount of filtrate and sodium delivered from the proximal tubule (lithium clearance), endogenous creatinine clearance, and predicted creatinine clearance were measured. The RR was evaluated after a meat meal (providing 2 g/kg BW of proteins) by subtracting baseline GFR from the peaking postprandial GFR. GFR was age-related and was identical in groups A and B and significantly lower in group C (p less than 0.0001). The drop in GFR averaged 7% per decade in the age range 61-89 years. The RR was not statistically different in groups A and B and increased significantly in group C (p less than 0.0001). In groups A and B the filtration fraction was constant after the meat meal and significantly increased over baseline GFR in group C (p less than 0.01), while the percentage of filtration capacity utilized at rest was lower in group C (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Lithium clearance (CLi) was studied in the healthy subjects (H) and in patients with chronic renal failure (CRF) with a mean GFR of 36.08 +/- 3.8 ml/min x 1.73 m2 in order to evaluate (1) the variability of CLi measurements; (2) the changes of CLi during the hyperfiltration response to a meat meal (2 g/kg b.w. of protein), and (3) the effects on CLi of different protein intakes. CLi correlated with GFR and with urinary sodium, FeLi correlated with FeNa in H and CRF. The intraindividual standard deviation (IISD) of GRF, CLi and FeLi assessed in triplicate studies in the course of a single experiment averaged 4.70, 7.15 and 10.69% in CRF and 1.77, 4.09 and 4.61% in H. When IISD for GFR, CLi, and FeLi was assessed in triplicate measurements in the course of 3 studies performed at 1-week intervals (day 1, day 8, day 15), it averaged 7.36, 9.21 and 15.72% in CRF and 1.83, 5.08 and 5% in H. During the hyperfiltration response to a meat meal, CLi and FeLi did not change in CRF and increased significantly in H. In 10 patients with CRF who were switched for 3 weeks from a protein intake of 0.85 g/kg to a protein intake of 0.60 g/kg, GFR was significantly (p less than 0.001) reduced by 29%, while CLi was stable. The data indicate that because of its variability, CLi is of little use in experiments designed to study subtle changes in renal Na transport.

Thyroid hormones affect the functions of several organs including the heart and kidney. Using isolated left papillary muscles we have investigated the action of thyroid hormones on the mechanical and electrical properties of the heart. We found that pure hypothyroidism causes a depression in contractile and electrical parameters, but we noticed that superimposed hypoparathyroidism accounts for the marked prolongation in contractile kinetics and action potential duration. At kidney level we have shown that thyroid hormones affect proximal tubular sodium transport and this effect is only partially mediated by the action of thyroid hormones on Na-K-ATPase activity. Using the micropuncture technique, we hypothesized that the early effect of thyroid hormone action is on the potassium permeabilty of proximal tubular cell membrane. This latter effect would explain the increase in isotonic fluid reabsorption through an increase in the driving force for sodium. Finally, hypothyroid patients have a decrease in glomerular filtration rate and renal plasma flow that are completely reversed by thyroxine administration. On the other hand, hyperthyroid subjects exhibit a significant increase in both parameters.

The available data on renal reserve and on the fraction of filtration capacity utilized at rest in childhood are analyzed both in healthy state and in renal disease. The methodological problems which might have biased available information are also discussed.

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%.

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.

Urinary urea was measured, under normal living conditions, in children aged 3-16 years, from Cimitile, a small town near Naples in Southern Italy. Urinary urea correlated with age, height, weight, body mass index and body surface area, and was independent from sex. Urinary urea also correlated with urinary creatinine, uric acid, oxalate, sodium and phosphate. Protein intake assessed from urea excretion was 2.66 +/- 0.66 g/kg at 3 years of age and 1.49 +/- 0.31 g/kg at 16 years, and exceeded Italian standards for recommended intake. Also, the height and weight of the children living in Cimitile, with few exceptions, were in excess of national reference standards.