Ambulatory 24-hour blood pressure and peptide balance in hemodialysis patients.

Blood pressure regulation during intermittent hemodialysis treatment involves many different mechanisms. Eight normotensive patients without antihypertensive drugs on intermittent hemodialysis treatment, mean age 50 years, were studied with 24-hour blood pressure measurements. Atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) were determined concomitantly. Eight control individuals matched for age and sex were investigated in the same way. A significant increase of both systolic and diastolic blood pressure, heart rate and pathological circadian rhythm was seen among the dialysis patients. High levels of ANP were found before and after dialysis. NPY showed steady state levels through the 24 hours and did not differ between the two groups. Overhydration is a probable cause of the disturbed blood pressure regulation and increased ANP-values.

Ribosome and free amino acid content in muscle during hemodialysis.

Patients (N = 8) with chronic renal failure and uremia treated with hospital hemodialysis were in a pilot study investigated before and after a single hemodialysis session. The extracorporeal dialysis circuit was flushed regularly with saline to avoid clotting and the use of heparin. Percutaneous skeletal muscle biopsies were taken before and after the dialysis to determine the content of free amino acids together with the concentration and size distribution of ribosomes before and after dialysis. After dialysis the alanine concentration in muscle decreased by 20% (P less than 0.05), while all other amino acids were unaffected. The total ribosome concentration per mg of DNA decreased by 31% (P less than 0.01) and the relative proportion of polyribosomes by 7% (P less than 0.05) after the dialysis compared to predialytic values. All individual plasma amino acids decreased during the dialysis procedure except for threonine and arginine, which were unaltered, and leucine and isoleucine, which increased. The decline in ribosome and polyribosome content together with the changes in amino acid levels indicate a low capacity for protein synthesis and increased catabolism in muscle of hemodialyzed patients.

The wish for renal transplantation.

The authors studied the wish for renal transplantation in 268 patients on chronic dialysis. One hundred forty (66%) of 268 patients wished for a transplant, while 71 (34%) did not wish to have one; the wish was not known in 57 (22%) of the patients. Sixty-five percent of the women and 67% of the men wanted to be transplanted. The wish for transplantation was negatively correlated with age. Thus, 78% of the patients below 50 years of age wished for a transplant, versus only 37% of those more than 70. Center patients wished more often for a transplant than patients on self dialysis (68% vs. 59%), but the difference was not significantly different except in patients over the age of 50. The chance of fulfillment (the % transplanted over the % of those who wished to have a transplant) declined with age. While 90% of the patients below age 50 who wished for a transplant could expect to receive one, only 41% of the patients over age 70 who wished for one could expect to receive one. Older patients were also less often asked about their wish. While the wish for a transplant was known in more than 90% of the patients under 50 years of age, it was known in less than one half of those over 70. This investigation shows that the wish for renal transplantation is related to age and mode of dialysis, but not sex. Old patients are often not asked about their preference for mode of treatment.

Cardiac function and cardiovascular hormone balance during hemodialysis with special reference to atrial natriuretic peptide.

Echocardiographically determined left ventricular function and cardiovascular hormone balance were assessed before and after hemodialysis in 10 patients who had been on hemodialysis for 4 months to 15 years. Plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), renin activity and aldosterone were determined. All patients had vector- and echocardiographic evidences of slight to moderate left ventricular hypertrophy. The body weight decreased 2.0 kg (3.3 +/- 0.5%) with dialysis. Nine out of ten patients showed a slightly reduced ejection fraction that normalized after dialysis (p less than 0.05). Left atrial and ventricular systolic dimensions were around the upper reference limit before dialysis with a decrease after dialysis (p less than 0.05 and p less than 0.02, respectively). The levels of ANP decreased with dialysis from 2-17 times to 1 to 15 times the upper reference value in nine out of the ten patients. In the whole group the decrease was 117 +/- 35% (p less than 0.005). A significant regression was obtained between percentage decrease of body weight and percentage change of ANP (r = 0.67; p less than 0.05). The plasma concentration of ADH did not change following dialysis but the mean value was significantly higher than the mean value of the reference group of the laboratory (p less than 0.05 before and p less than 0.005 after dialysis). Renin activity and aldosterone levels were low and did not change during dialysis. In conclusion, the slight left ventricular hypertrophy may partly be a response to volume overload with hyperdynamic circulation and partly to metabolically depressed myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Lithium and renal function in relation to concomitant theory.

Two hundred and fourteen patients (99 men, 115 women, age 21-87 years) were treated with lithium during the period 1963-1984 at the Psychiatric Unit, Danderyd Hospital. The patients were diagnosed as having bipolar depression (97), unipolar depression (54), cycloid psychosis (21), schizoaffective psychosis and depressive neurosis (42). Sixty patients were treated with lithium salt only, 73 patients received neuroleptic drugs in addition to lithium and 51 antidepressant drugs. Sixteen patients were treated with a combination of neuroleptic drugs, antidepressant drugs and lithium. Fourteen patients were treated with lithium and benzodiazepines. The aim of this retrospective lithium study was to examine the renal function in these different treatment groups. The results show that patients treated with a lithium salt and neuroleptic drugs have significantly lower urinary osmolality than those treated with a lithium salt only. Also tricyclic antidepressants in combination with a lithium salt appear to have an influence on renal function. The duration of concomitant therapy seems to be of importance for the effect on renal function. Eleven patients with the lowest osmolality values were investigated at the Renal Unit, Danderyd Hospital, but in no case was it necessary to withdraw the lithium treatment.

Intracellular free amino acids in muscle tissue of patients with chronic uraemia: effect of peritoneal dialysis and infusion of essential amino acids.

1. Free amino acids were determined in the plasma and in the muscle tissue of 14 patients with chronic uraemia; eight were not on dialysis and six were having regular peritoneal dialysis. The concentration of each amino acid in muscle water was calculated with the chloride method. 2. In both groups of patients there were low intracellular concentrations of threonine, valine, tyrosine and carnosine, and high glycine/valine and phenylalanine/tyrosine ratios. Both groups of patients had increased amounts of 1- and 3-methyl-histidine in plasma and in muscle water. 3. The non-dialysed patients had low intracellular concentrations of lysine, and the dialysed patients had high intracellular concentrations of lysine, isoleucine, leucine and of some of the non-essential amino acids. 4. After peritoneal dialysis for 22 h, the plasma concentration of several amino acids decreased but the intracellular concentrations of most amino acids did not change significantly. 5. Intravenous administration of essential amino acids and histidine during the last 4 h of dialysis increased in muscle the total free amino acids, the ratio of essential to non-essential amino acids and the valine and phenylalanine concentrations. 6. The results demonstrated that the plasma and muscle concentrations of several amino acids are grossly abnormal in chronic uraemia. Non-dialysed and dialysed patients exhibit important differences, especially in the intracellular amino acid patterns. Infusion of essential amino acids may result in enhancement of protein synthesis.

Experience with essential amino acids in the treatment of patients with chronic uremia.

Nitrogen balance studies in chronic severe uremia have shown that it is possible to convert the negative nitrogen balance on a protein-poor diet to a positive one when the diet is supplemented with the essential amino acids intravenously or orally. It has been possible to make the diet variable and good tasting. This is a great advance as the patients can remain on the diet for a long time. 15N-studies have shown that this nitrogen balance represents true protein synthesis. These studies have also shown that histidine may be an essential amino acid in chronic severe uremia and further improves the nitrogen balance. During long-term treatment with the diet supplemented with essential amino acids including histidine, no signs of progressive neuropathy, bleeding or muscle wasting have been observed. We think that this diet and amino acid regimen is a feasible way to keep chronic severe uremic patients in fairly good general condition and nutritive state until they can have a renal transplantation or a place in a home-dialysis program.

Preservation of peripheral nerve function in severe uremia during treatment with low protein high calorie diet and surplus of essential amino acids.

Twelve patients with severe chronic renal failure (serum creatinine 7.0-27 mg %), and marked uremic symptoms on a 40 g protein diet, were treated with a caloric-rich diet containing 16-20 g protein, supplemented with the 8 essential amino acids (1.1-2.2 g N) and histidine (0.23-0.45 g N)in the form of tablets for periods between 3 and 34 months. During the treatment the serum urea-N fell, and the uremic symptoms subsided or diminished without the patient exhibiting signs of malnutrition. The nerve function was followed with quantitative and semiquantitative neurological tests (among others, determination of vibratory perception thresholds and nerve conduction times). Initially all patients but 2 had signs of neuropathy as measured by these methods. During the course of treatment no deterioration of peripheral nerve function was recorded in any of the patients, several of whom had had serum creatinine conceptrations above 15 mg % for long periods. We conclude that conservative treatment with N-poor diet in far advanced chronic renal failure may prevent the further development of peripheral neuropathy provided that adequatecaloried and essential amino acids (2-3 times the minimal requirements) are supplied. The results suggest that, in addition to uremic toxines, malnutrition is a factor of importance for the developments of of uremic neuropathy.

Treatment of pre-eclampsia and eclampsia as a hypoperfusion syndrome.

A therapeutical program in pre-eclampsia and eclampsia is presented. The results in 10 patients suggest that the same basic program as is used in the hypoperfusion syndrome can be used in pre-eclampsia and eclampsia: Chlorpromazin to combat vasoconstriction and dilate the vascular bed. Plasma expanders, plasma, albumin and glucose with electrolytes to fill up the dilated vascular bed and restore the tissue perfusion. Buffers to combat acidosis, oxygen to combat hypoxemia, hypertonic Mannitol to mobilize edema. Furosemide to force diuresis.

Treatment of chronic uremic patients with protein-poor diet and oral supply of essential amino acids. I. Nitrogen balance studies.

Twenty-six nitrogen balance studies were performed in 15 patients with severe uremia (Ccr mean value 5.1, range 2.3-8.5 ml/min) treated with an unselected protein-poor (16-20 g protein/day corresponding to 2.6-3.2 g N/day) diet and oral supply of the essential amino acids including histidine (2.6 g N/day). The general condition improved and the concentration of serum urea nitrogen decreased. The nitrogen balance, corrected for changes in total urea pool, was negative on the diet alone,-1.46 plus or minus 1.15 g N/day (mean plus or minus SD), but was positive when the essential amino acids were supplied, plus 0.84 plus or minus 0.68 g N/day. In four patients studied after 3 to 26 months of diet and amino acid therapy, during which time a further deterioriation of the renal function had occurred, the nitrogen balance was around zero in three and negative in one patient (-1.2 g N/day). The results show that it is possible with our new regimen to attain positive nitrogen balance or nitrogen equilibrium in severely uremic patients without excessive accumulation of urea in the body fluids.

Treatment of chronic uremic patients with protein-poor diet and oral supply of essential amino acids. II. Clinical results of long-term treatment.

Twenty-six uremic patients - serum urea nitrogen (SUN) 110 MG/100 ml plus or minus 22.8 (mean plus or minus SD), serum cretinine (S-Creat) 13.2 mg/100 ml plus or minus 2.27, ratio SUN/S-Creat 8.6 plus or minus 2.26, and endogenous creatinine clearance (Ccr) 3.86 plus or minus 1.41 ml/min - were treated for three months or longer with an unselected protein-poor (16-20 g protein/day) diet with oral supply of the essential amino acids including histidine in high doses as coated tablets. The amino acids were instituted after an initial diet only period (mean 0.4 months). The average treatment time was 8.4 months (range 2.7-33.6). An improvement of the general condition was obtained, persisting for several months. SUN and SUN/S-Creat decreased on the diet alone, continued to decrease after one month, and increased slightly again after three months of treatment, but did not reach the initial levels for several months in spite of an almost doubled nitrogen intake. S-Creat increased after six months indicating a further deterioration of the renal function. In patients with initially low serum total protein (smaller than 6.5 g/100 ml, 9 patients), albumin (smaller than 3.5 g/100 ml, 10 patients), and total iron-binding capacity (smaller than 260 mug/100 ml, 11 patients) the values increased after one month on amino acids and were thereafter stable. No signs of bleeding tendency, progressive muscle atrophy, or progressive peripheral neuropathy were observed. - Five patients died due to cardiovascular maladies. A further 13 patients were withdrawn for medical reasons (overhydration, 4 patients; hypertension, 1 patient; nausea and vomiting, 7 patients; and pericarditis, 1 patient). - The renal function improved in one patient. Four patients received home dialysis training, three a kidney transplant. - The results indicate that it is possible to keep severely uremic patients free from uremic symptoms, counteract protein depletion, and even improve the nutritional status during long-term treatment with an unselected protein-poor diet supplementd with essential amino acids.