Peritoneal protein losses and cytokine generation in automated peritoneal dialysis with combined amino acids and glucose solutions.

OBJECTIVES: Protein-energy malnutrition as a consequence of deficient protein intake frequently occurs in peritoneal dialysis (PD) patients. Previously, we showed that peritoneal dialysate containing a mixture of amino acids (AA) and glucose has anabolic effects. However AA-dialysate has been reported to increase intraperitoneal protein and AA losses and the release of proinflammatory cytokines (interleukine-6 (IL-6) and tumor necrosis factor alpha (TNFalpha)). We investigated the effect of AA plus glucose (AAG) solutions on peritoneal protein losses and cytokine generation. METHODS: In 6 patients on standard automated peritoneal dialysis (APD) 12 APD sessions of 6 cycles each were performed during the night using dialysate containing 1.1% AA plus glucose or glucose alone as control. Protein losses and TNFalpha and IL-6 concentrations were measured in dialysates separately collected from nightly cycling and daytime dwell. RESULTS: The 24 hour-protein losses with AAG (median 6.7 g, range 4.7-9.4 g) were similar to control dialysate (median 6.0 g, range 4.2-9.2 g). Daytime dialysate IL-6 levels were higher after nightly AAG dialysis than after control dialysis (142 pg/ml and 82 pg/ml, respectively, P<.05). TNFalpha concentrations were very low. CONCLUSION: Nightly APD with amino acids containing dialysate was associated with an increase in peritoneal IL-6 generation during the day. The addition of AA to standard glucose dialysis solutions did not induce a significant increase of peritoneal protein losses.

Activation of inactive plasma renin by tissue kallikreins.

It has been reported that inactive (acid-activable) human renin could be converted into the active form by adding urinary kallikrein to acid-pretreated plasma. Without prior acidification, however, only a small portion of the total amount of inactive renin present in plasma was converted (activated) by kallikrein, probably because native plasma contains protease (kallikrein) inhibitors that are destroyed by acid. We have separated inactive and active renin by DEAE-Sepharose column chromatography of normal human plasma at pH 7.5 and a linearly increasing sodium gradient. Inactive renin isolated in this way could be activated at pH 7.5 by highly purified pancreas and urinary kallikreins. With the semipurified preparation of inactive renin, prior acidification was not required for obtaining virtually complete activation by kallikrein. The kallikreins were effective at concentrations as low as 1 x 10(-8) mol/liter. It is therefore possible that one or more tissue kallikreins act as physiological activators of inactive renin.

Unstable glycosylated hemoglobin in patients with diabetes mellitus.

Incubation of washed erythrocytes for 4 h at 37 degrees C in saline resulted in the disappearance of an unstable glycosylated fraction. In a reference group, its amount was very small, but its presence had a significant influence on the upper level of the reference range. In non-diabetic pregnant women, the unstable fraction was significantly higher than in the non-pregnant individuals, which resulted in a lower reference range for the stable HbA1. In diabetic patients, the average unstable HbA1 was about 10% of the "unincubated" level, with marked differences between individuals (0--30%), even in patients with a slightly elevated HbA1. Therefore it is important to determine the concentration of stable HbA1.

A patient with megaloblastic anaemia and idiopathic intracranial hypertension. Case history.

A young woman with idiopathic intracranial hypertension (IIH) was found to have a severe megaloblastic anaemia due to multiple alimentary vitamin deficiencies. After correction of the anaemia the idiopathic intracranial hypertension disappeared.

Albumin and whole-body protein synthesis respond differently to intraperitoneal and oral amino acids.

Patients with peritoneal dialysis are at risk for malnutrition and hypoalbuminemia, which are indicators of poor outcome. Recently, it was shown that dialysis solutions containing amino acids (AAs) and glucose improve protein anabolism in peritoneal dialysis patients. We determined if the same solutions could increase the fractional synthesis rate of albumin along with whole-body protein synthesis. Changes in the fractional albumin synthetic rate reflect acute change in hepatic albumin synthesis. A random-order cross-over study compared the effects of Nutrineal (AA source) plus Physioneal (glucose) dialysate with Physioneal alone dialysate. Eight patients in the overnight fasting state were compared to 12 patients in the daytime-fed state. Fractional albumin synthetic rate and whole-body protein synthesis were determined simultaneously using a primed-continuous infusion of L-[1-(13)C]-leucine. Fractional albumin synthesis on AAs plus glucose dialysis did not differ significantly from that on glucose alone in the fasting or the fed state. Protein intake by itself (fed versus fasting) failed to induce a significant increase in the fractional synthetic rate of albumin. Conversely, the oral protein brought about a significant stimulation of whole-body protein synthesis. Our findings show that the supply of AAs has different effects on whole-body protein synthesis and the fractional synthetic rate of albumin.

Bronchial asthma improved after removal of a phaeochromocytoma.

It is uncommon for bronchial asthma to be a symptom of phaeochromocytoma. We describe a patient with a phaeochromocytoma who presented with worsening of her asthma and persistent dyspnoea between attacks. She had markedly elevated levels of catecholamines. After surgical resection of the phaeochromocytoma there was a lasting improvement of the bronchial asthma. We hypothesize that worsening of bronchial asthma in phaeochromocytoma patients may be due to catecholamine-induced deterioration of asthma.

Phlegmonous gastritis: an unusual presenting symptom of Sjögren's syndrome.

This case report describes the histological and macroscopic changes seen within a few months in the gastric mucosa of a 28 year old woman patient with upper abdominal symptoms. With hindsight these changes were the first signs of Sjögren's syndrome.

Renal vein immunoreactive renin in patients with renal artery stenosis and essential hypertension.

In 36 patients with unilateral renal artery stenosis and in 24 with essential hypertension the plasma levels of total immunoreactive renin, and enzymatically active renin were measured in both renal veins (V) and in the aorta (A) by direct RIA by using monoclonal renin antibodies. Active renin and trypsin-activatable inactive renin were also measured by indirect RIA with angiotensin-I antibodies. The V/A ratio for the different forms of renin calculated from the results of direct and indirect RIA were not different. The V/A ratio of active renin for the kidney with the stenotic artery was 3.04 +/- 0.28 (mean +/- sem) with direct and 3.02 +/- 0.25 with indirect RIA. The contralateral ratio was 1.04 +/- 0.02 with the direct and 1.05 +/- 0.02 with the indirect RIA. In essential hypertension it was 1.28 +/- 0.04 with direct RIA and 1.28 +/- 0.04 with indirect RIA. Chronic treatment with captopril had no influence on this ratio in both patients groups. The V/A ratio of total immunoreactive renin was lower than that of active renin and this ratio had lost discriminative power for lateralization. This ratio was significantly greater than one on the affected side in renal artery stenosis but not contralaterally and in essential hypertension. This study shows that renin activity after trypsin-activation of plasma is an accurate measure of the total renin concentration, i.e. active renin plus prorenin. It also shows that a kidney with a stenotic artery secretes inactive renin, which is immunologically related to active renin and is likely to be prorenin. Direct RIA for measuring active renin is technically more simple than indirect RIA. Direct RIA however is somewhat less sensitive. For measuring the V/A ratio for active renin in patients with renal artery stenosis this can be overcome by stimulating the renin-angiotensin system for instance by captopril.

Activation of inactive plasma renin by plasma and tissue kallikreins.

1. Normal human plasma contains a proactivator of inactive renin. The pro-activator is activated at physiological pH in plasma that has been pretreated with acid. This activation in vitro leads to the conversion of inactive renin into the active form with simultaneous generation of kallikrein activity. 2. The endogenous activator of inactive renin has the same pH profile and inhibitor spectrum as plasma kallikrein. 3. Inactive renin can also be activated by exposure of plasma to exogenous trypsin, and in normal plasma the quantities of inactive renin that are activated after acidification and with trypsin are identical. Prekallikrein (Fletcher factor)-deficient plasma, however, has much lower renin activity after acidification than with trypsin. Thus acid activation of inactive renin depends on plasma prekallikrein, whereas the action of trypsin is independent of prekallikrein. 4. Highly purified tissue (pancreatic) kallikrein, in a concentration of less than 2 X 10(-8) mol/l, activates inactive renin that has been isolated from plasma by ion-exchange chromatography. In this respect it is at least 100 times more potent than trypsin. 5. It is therefore possible that plasma and/or tissue (renal) kallikreins are also involved in the activation of inactive renin in vivo.

Splint renal function after captopril in unilateral renal artery stenosis.

The renal extraction ratios of 131I-sodium iodohippurate (131I-Hippuran) and 125I-thalamate were greatly reduced on the affected side by 50 mg captopril in seven out of 14 patients with unilateral renal artery stenosis. With long term captopril 150 mg daily the uptake of 99mTc-diethylenetriaminepenta-acetic acid by the affected kidney, which was determined by scintillation camera renography, became almost zero in these seven patients, indicating severe reduction of the glomerular filtration rate. Function of the affected kidney returned on discontinuing treatment. The reduced extraction of sodium iodohippurate probably reflected a shortened plasma transit time through the kidney due to intrarenal vasodilatation. The reduced extraction of thalamate reflected a low filtration fraction, suggesting that the vasodilatation was, at least in part, at the level of the postglomerular arterioles. Captopril had little effect on the contralateral kidney and on the kidneys of 17 patients with essential hypertension, and serum creatinine concentrations showed minor changes. Radioisotope renography should be performed after beginning captopril treatment in patients with renal artery stenosis. This is also recommended for patients given captopril as a third line drug when renal artery stenosis has not been excluded. Hypertension is these patients is often severe and difficult to control. Renal artery disease is not rare in this difficult group and finding seriously impaired renal function on one side during captopril treatment may be diagnostic.