Effects of peritoneal dialysis on protein metabolism.

Protein-energy wasting is relatively common in renal patients treated with haemodialysis or peritoneal dialysis (PD) and is associated with worse outcome. In this article, we review the current state of our knowledge regarding the effects of PD on protein metabolism and the possible interactions between PD-induced changes in protein turnover and the uraemia-induced alterations in protein metabolism. Available evidence shows that PD induces a new state in muscle protein dynamics, which is characterized by decreased turnover rates and a reduced efficiency of protein turnover, a condition which may be harmful in stress conditions, when nutrient intake is diminished or during superimposed catabolic illnesses. There is a need to develop more effective treatments to enhance the nutritional status of PD patients. New approaches include the use of amino acid/keto acids-containing supplements combined with physical exercise, incremental doses of intraperitoneal amino acids, vitamin D and myostatin antagonism for malnourished patients refractory to standard nutritional therapy.

Anterior tension-free repair under local anesthesia of abdominal wall hernias in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: A 10-year experience of abdominal wall hernia repair performed with anterior tension-free mesh or plug technique under local anesthesia in end-stage renal failure patients submitted to continuous ambulatory peritoneal dialysis (CAPD) is described in order to assess the safety and effectiveness of this approach. METHODS: Between January 1993 and December 2002, 18 hernia repairs were performed under local anesthesia in 16 patients (14 males and two females) with a mean age of 70 years (48-78). One umbilical and three unilateral inguinal hernias were observed and repaired before starting peritoneal dialysis (PD), while two umbilical, eight unilateral, and two bilateral groin hernias developed and were then treated during PD. Repairs were performed electively in all but one case, which was an emergency operation for strangulation. An ipsilateral scrotal swelling was also present in two indirect unilateral inguinal hernias. In these cases, the hernia sac was ligated before entering, while in the others it was simply dissected and inverted. RESULTS: Patients were discharged the same day or the day after surgery. No local or general immediate or late complications occurred. CAPD in subjects operated on during PD treatment was resumed the same day of surgery. In no instance was hernia recurrence or leak of dialysis solution observed at follow-up examinations. CONCLUSIONS: The absence of surgical and general complications and the nearly immediate resumption of PD indicate the anterior tension-free repair under local anesthesia as a safe and effective technique for CAPD patients even in an ambulatory or day-surgery setting.

[Acute effects of peritoneal dialysis on muscle protein turnover]. / Effetti acuti della dialisi peritoneale sul metabolismo proteico.

BACKGROUND: Despite continuing glucose absorption and stimulation of insulin secretion, wasting is common in patients with chronic renal failure (CRF) treated with peritoneal dialysis. METHODS: To evaluate if peritoneal dialysis per se has any effect(s) on muscle protein turnover we employed the forearm perfusion method associated with the kinetics of 3H-phenylalanine in seventeen patients with CRF in the basal state and: a) during the systemic hyperinsulinemia associated with peritoneal dialysis (6 patients) (200-240 min); b) during locally-induced hyperinsulinemia, without systemic effects on aminoacid (AA) availability (6 patients) (80-120 min); c) in time-controls (5 patients) (80-240 min). RESULTS: Peritoneal dialysis and local infusion of insulin in the brachial artery (0.01 mU/min/kg) induced a similar degree of systemic or local, moderate hyperinsulinemia (19+/-4 e 21+/-3 microU/ml, respectively). During both protocols an insulin-related inhibition of muscle protein degradation occurred; however peritoneal dialysis caused a 20% decrease in forearm phenylalanine rate of disposal (an index of muscle protein synthesis), which correlated with the decline of arterial BCAA and potassium, which were removed via the peritoneal fluid. Furthermore, a persistent negative net phenylalanine and AA balance across the forearm was observed during peritoneal dialysis, while the negative basal net phenylalanine and AA balance was reversed to a positive or neutral one during local hyperinsulinemia. CONCLUSIONS: We conclude that in CRF patients even a modest elevation in local insulin levels is followed by an anabolic muscle response, while the same effect is not observed during the systemic hyperinsulinemia associated with substrate removal which occurs during peritoneal dialysis. In this setting the antiproteolytic effect of hyperinsulinemia is offset by a decrease in muscle protein synthesis which is accounted for by a decrease in AA availability. Our data indicate that protein metabolism during peritoneal dialysis is characterized not only by decreased, but also less efficient, turnover rates.

Pseudoxanthoma elasticum and pregnancy: a case report.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare hereditary disease characterised by systemic degeneration of elastic tissue. Calcification of elastic fibres seen histologically is pathognomonic for the disorder. Most pseudoxanthoma elasticum patients show no serious complications during pregnancy. CASE: We report a case of a 29-year-old white woman with pseudoxanthoma elasticum, who delivered a healthy infant at the 35th week by cesarean section after an uneventful pregnancy. Sonographic and histological placental findings are described. CONCLUSION: Pregnancy in a patient with pseudoxanthoma elasticum presents some problems such as the evolution of the disease in the soon to be mother and the influence of the disease on the pregnancy. In our case there were no fetal-maternal complications related to the disease except skin lesion aggravation.

Hepatitis G virus infection in haemodialysis and in peritoneal dialysis patients.

The aim of this study was to detect hepatitis G virus RNA (HGV RNA) and antibodies against the virus envelope protein E2 (anti-E2) in 107 patients either on maintenance haemodialysis (n = 78) or peritoneal dialysis (n = 29) to evaluate the prevalence of HGV infection and to establish its role in liver disease. The total prevalence of HGV infection was of 15.4% among haemodialysis patients, whereas it was 10.3% among peritoneal dialysis patients. HGV RNA was detected in 2 haemodialysis patients (2.6%) and in 3 peritoneal dialysis patients (10.3%). Anti-E2 was found in 10 haemodialysis patients (7.8%), whilst all peritoneal dialysis patients resulted negative. In only 1 patient the alanine aminotransferase level was elevated. This patient underwent liver biopsy that did not reveal evidence of chronic hepatitis. The lower HGV prevalence in haemodialysis patients, when compared with data reported by other European authors, should be related to the lower rate of polytransfused patients in our series (29.5%). Multiple blood transfusions should be considered as the main factor to explain the different prevalence of HGV infection among various European dialysis centres. Detection of both antibody and viraemia is important to establish the real rate of the infection.

Low concentrations of glucose degradation products in peritoneal dialysis fluids and their impact on biocompatibility parameters: prospective cross-over study with a three-compartment bag.

The side effects of glucose degradation products (GDPs) in conventional peritoneal dialysis (PD) fluids are well described. Using the three-compartment bag concept--that is, in situ preparation of concentrated glucose solution into a standard ionic solution--a GDP-free solution can be processed. To investigate the possible impact of this product on biological and clinical parameters, we carried out a prospective cross-over study with 31 patients, comparing the short-term effects of conventional PD and GDP-free PD solutions. Classical peritoneal parameters and ultrafiltration rate did not change during the study. After three months and after six months with the three-compartment bag, cancer antigen 125 (CA125) concentration in overnight fluid increased significantly (p < 0.001) from 24.4 IU/mL to 44.4 IU/mL and 41.1 IU/mL respectively. CA125 decreased significantly (p < 0.01) to 21.7 IU/mL after three months with the conventional solution. No change in hyaluronan concentration was observed. A slight increase of procollagen III N-terminal peptide in overnight effluent with the GDP-free solution was followed by a significant reduction after three months with standard solution. In summary, our data show that the GDP-free PD fluid improves mesothelial cell mass and turnover even after a short-term period of three months. A better quality of PD solution is obtained by using the three-compartment bag.

Inter-organ leptin exchange in humans.

To assess the individual role of splanchnic organs, kidney, and peripheral tissues on leptin metabolism, leptin exchange across the splanchnic bed, kidney, and leg has been evaluated by the arterio-venous technique in post-absorptive non-obese subjects. Leptin levels in the hepatic and renal veins were significantly lower (p < 0.001), while femoral vein levels were consistently greater (p < 0.05) than in the artery. The fractional extraction of leptin, namely the percentage of arterial leptin extracted, was greater in splanchnic organs (16%) than in the kidney (9.5%). Urinary excretion of leptin was undetectable in most subjects, indicating that leptin is degraded within the kidney. There was no correlation between fractional extraction of leptin and glomerular filtration rate, whereas leptin fractional extraction was directly related to renal plasma flow (p = 0.017). Renal leptin clearance was about 50% of the glomerular filtration rate. Our data demonstrate that both splanchnic organs and the kidney cooperate in the disposal of leptin, while peripheral tissues add significant amounts of leptin to the circulation. In non-obese subjects the contribution of the kidney to whole body clearance is no more than 50%. The removal of leptin by the kidney depends on renal plasma flow but not on glomerular filtration rate or filtered leptin.

Protein turnover in the kidney and the whole body in humans.

For a better understanding of protein synthesis and degradation in the human kidney, the arteriovenous difference technique across the kidney, splanchnic organs, and leg muscle was combined with labeled leucine and phenylalanine isotope dilution models. Results indicate that in the postabsorptive state, the protein balance across the human kidney is negative because the rate of leucine release from protein degradation is greater than the amount used for protein synthesis. In the splanchnic bed, net protein balance is neutral since the amount of leucine deriving from protein degradation is similar to the amount utilized for protein synthesis. In the leg muscle, protein degradation exceeds protein synthesis. The kidney exhibits the highest leucine metabolic activity when expressed in terms of total organ leucine content. The estimated fractional protein synthesis rate in the human kidney is about 40% per day (vs. about 2% in muscle and 12% in the splanchnic bed). The human kidney presents high rates of protein turnover and accounts for a significant fraction of whole-body protein degradation, protein synthesis, and leucine oxidation.

Protein and amino acid metabolism in splanchnic organs in metabolic acidosis.

Metabolic acidosis causes a cooperative participation of different organs such as the liver, kidney, and muscle in restoring acid-base balance. In splanchnic organs, metabolic acidosis has repercussions on several nitrogen metabolism pathways. The decrease in urea synthesis due to reduced activity of urea cycle enzymes, ammonia uptake and amino acid transport, and changes in glutamine metabolism support renal ammoniagenesis thus offering a response to rid the body of excess protons. While some of the mechanisms are adaptive others may be harmful for the body. Metabolic acidosis may have effects on splanchnic protein turnover. In severe acidosis, synthesis of secreted liver proteins may be reduced. Acidosis may also modulate the response of the liver to growth hormone (GH) for insulin-like growth factor-I synthesis, thus inducing a state of GH resistance. Splanchnic abnormalities in acidosis might contribute to the malnutrition observed in uremia.

Kidney, splanchnic, and leg protein turnover in humans. Insight from leucine and phenylalanine kinetics.

The rate of kidney protein turnover in humans is not known. To this aim, we have measured kidney protein synthesis and degradation in postabsorptive humans using the arterio-venous catheterization technique combined with 14C-leucine, 15N-leucine, and 3H-phenylalanine tracer infusions. These measurements were compared with those obtained across the splanchnic bed, the legs (approximately muscle) and in the whole body. In the kidneys, protein balance was negative, as the rate of leucine release from protein degradation (16.8 +/- 5.1 mumol/min.1.73 m2) was greater (P < 0.02) than its uptake into protein synthesis (11.6 +/- 5.1 mumol/min. 1.73 m2). Splanchnic net protein balance was approximately 0 since leucine from protein degradation (32.1 +/- 9.9 mumol/min. 1.73 m2) and leucine into protein synthesis (30.8 +/- 11.5 mumol/min. 1.73 m2) were not different. In the legs, degradation exceeded synthesis (27.4 +/- 6.6 vs. 20.3 +/- 6.5 mumol/min. 1.73 m2, P < 0.02). The kidneys extracted alpha-ketoisocaproic acid, accounting for approximately 70% of net splanchnic alpha-ketoisocaproic acid release. The contributions by the kidneys to whole-body leucine rate of appearance, utilization for protein synthesis, and oxidation were approximately 11%, approximately 10%, and approximately 26%, respectively; those by the splanchnic area approximately 22%, approximately 27%, and approximately 18%; those from estimated total skeletal muscle approximately 37%, approximately 34%, and approximately 48%. Estimated fractional protein synthetic rates were approximately 42%/d in the kidneys, approximately 12% in the splanchnic area, and approximately 1.5% in muscle. This study reports the first estimates of kidney protein synthesis and degradation in humans, also in comparison with those measured in the splanchnic area, the legs, and the whole-body.

Disposal of exogenous amino acids by muscle in patients with chronic renal failure.

Muscle exchange of amino acids (AAs) was evaluated by using the arteriovenous-difference technique across the leg in seven patients with chronic renal failure (CRF) and eight control subjects before and for 75 min after the ingestion of an AA mixture simulating an animal-protein meal. Total AAs increased in arterial blood much more in patients with CRF after AA ingestion than in control subjects, as a consequence of an exaggerated increase in nonessential AAs (NEAAs) (+127%). Moreover, total AAs were taken up by the leg in larger amounts than in control subjects (+71%, P < 0.0025) because of increased uptake of NEAAs (+156%, P < 0.005). Branched-chain AA uptake by the leg was, in absolute values, similar to that of control subjects; however, because of the increased uptake of total AAs, branched-chain AA uptake was only 30% of total AA extraction, compared with 46% in control subjects. Abnormalities in AA uptake by muscle paralleled those in arterial AAs. In fact the same AAs that increased abnormally in blood were taken up by the leg at higher rates than in control subjects. Variations in arterial concentrations and muscle uptake of AAs were inversely related to arterial bicarbonate concentration, suggesting a role for acid-base status in modifying both the arterial supply and muscle metabolism of AAs. Results indicate that in CRF patients the normal pattern of postprandial AA repletion is disrupted. Muscle tissue faces the increased and unbalanced postprandial supply of AAs with an augmented and unbalanced uptake. Data are consistent with an abnormal use of exogenous AAs in CRF patients, possibly induced by metabolic acidosis.

Ultrasonographic imaging and Doppler analysis of renal changes in non-insulin-dependent diabetes mellitus.

RATIONALE AND OBJECTIVES: We used ultrasonographic imaging and Doppler analysis to assess renal changes in patients with non-insulin-dependent diabetes mellitus (NIDDM) and normal renal function, as established by normal serum creatinine levels and the absence of macroalbuminuria. METHODS: Renal parenchymal echogenicity, renal volume, and resistive index (RI) were blindly evaluated for 85 NIDDM patients and 42 age-matched control subjects (C). Results were analyzed and correlated with the following clinical parameters: patient age, duration of diabetes, blood pressure, blood glucose and cholesterol levels, and the presence of microalbuminuria. RESULTS: Normal renal parenchymal echogenicity was seen in all but one NIDDM patient; however, in comparison with C, diabetic patients had significantly higher renal volume (mean +/- standard deviation, 314.01 +/- 72.74 vs 227.64 +/- 58.76) and RI (mean +/- standard deviation, 0.71 +/- 0.05 vs 0.64 +/- 0.02). An RI higher than 0.70 was found in 55 of 85 (65%) NIDDM patients; an increased RI was directly correlated with patient age, whereas an inverse correlation existed between an increased RI and renal volume. No statistically significant differences were observed for the duration of diabetes, arterial hypertension, blood levels of glucose and cholesterol, and the presence of microalbuminuria. CONCLUSIONS: NIDDM patients with normal renal function show a significant increase in renal volume and RI in comparison with C. Demonstration of these findings may aid in the detection of early renal involvement in NIDDM patients. However, further investigations are needed to understand fully the correlation of such changes with the pathology of diabetic nephropathy and to provide an interpretation of the pathophysiologic mechanisms underlying changes in intrarenal vascular impedance in NIDDM patients.

Effects of a protein meal on blood amino acid profile in patients with chronic renal failure.

Arterial whole blood levels of amino acids were determined in patients with chronic renal failure and in healthy subjects before and after 270 min after the ingestion of a grilled beefsteak (4 g/kg). In patients, total nonessential amino acids increased significantly more (+46%) than in controls owing to an exaggerated rise of serine, glutamine, proline, glycine, cyst(e)ine and alanine. Total essential amino acids increased as much as in controls; however, threonine, histidine and phenylalanine showed greater increases, while tryptophan had a smaller increment. Abnormalities in amino acid levels were even more evident in the postprandial period than in the postabsorptive state owing to reduced levels of valine, leucine, tryptophan, tyrosine, aspartate and glutamate and higher levels of glutamine, proline, glycine, cyst(e)ine, threonine, histidine and phenylalanine. Moreover, after the meal, the ratios total essential amino acids/total nonessential amino acids, valine/glycine, and branched-chain amino acids/total amino acids rose but persisted to be reduced whereas tryptophan/total amino acids and tyrosine/phenylalanine ratios increased in controls, but did not change in patients. In conclusion, in chronic renal failure, protein ingestion enhances the imbalance in amino acid levels already present in the postabsorptive state. The all data indicate that in patients with chronic renal failure, the metabolism of exogenous protein is impaired and the flow of amino acids to the organs is altered during the phase of body nitrogen replenishment.