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Biomedical subjects

N Grefberg

Publications and source records attributed to N Grefberg.

At least 19 recordsLinked to original sources

Protein intake and glomerular hyperfiltration in insulin--treated diabetics without manifest nephropathy.

Protein intake in relation to glomerular filtration rate (GFR) and urinary albumin excretion (UAE) has been studied in 96 insulin-treated diabetic patients, 20-40 years of age and without nephropathy. They had diastolic blood pressure (DBP) not exceeding 90 mmHg and a GFR exceeding -2 SD of the age-related value. They were without medications except for insulin. There were no significant differences in protein intake between diabetic patients with and without hyperfiltration (1.18 +/- 0.26 g/kg/d vs 1.21 +/- 0.42 g/kg/d, p = 0.75) or between diabetic patients with or without increased UAE (1.16 +/- 0.41 g/kg/d vs 1.24 +/- 0.37 g/kg/d, p = 0.37). No relations were found between protein intake and GFR or UAE in the whole sample, but a positive relation was found between UAE and protein intake in patients with increased UAE. Protein intake correlated with UAE in hyperfiltrators who use tobacco (n = 8, r = 0.85, p = 0.01), but not in non-users (n = 11, r = 0.24, p = 0.48). In conclusion our findings give no support for a relation between high protein intake and glomerular hyperfiltration in insulin-treated-diabetic patients. However, in contrast to non-users of tobacco, a positive relation was found between UAE and protein intake in tobacco users with hyperfiltration.

Adult↗

Cigarette smoking and urinary albumin excretion in insulin-treated diabetics without manifest nephropathy.

The frequency of microalbuminuria and glomerular hyperfiltration in insulin-treated diabetics without manifest nephropathy was studied in 76 patients, 20-40 years of age and with a diabetes duration not exceeding 20 years. Clinical determinants of urinary albumin excretion (UAE) with regard to smoking were studied further in a sample of male diabetics (n = 49) without manifest nephropathy. All patients had an age-related glomerular filtration rate (GFR) exceeding -2 SD, and their diastolic blood pressure (DBP) did not exceed 90 mmHg. GFR was assessed by 51Cr-EDTA-clearance, and UAE was analysed using an immunochemical method. Diabetic smokers with a long diabetes duration (10-20 years) had a significantly higher UAE (39.5 +/- 2.4 mg 24 h-1 vs. 17.1 +/- 2.4 mg 24 h-1; P = 0.03), a higher mean arterial blood pressure (MAP) (97.9 +/- 7.5 mmHg vs. 91.5 +/- 6.3 mmHg; P = 0.02) and a higher frequency of micro-albuminuria (85.7% vs. 37%; P = 0.028) than non-smoking diabetics. Smokers with a short diabetes duration (0-10 years) had a significantly higher frequency of glomerular hyperfiltration (64% vs. 15%; P = 0.005) than non-smokers. The frequency of microalbuminuria or blood pressure did not differ significantly. In male non-smokers (n = 35) UAE was positively correlated with HbAlc and negatively correlated with age of onset. In male smokers (n = 14) regression analysis showed that UAE was positively correlated only with duration of smoking. We conclude that smoking is associated with two accepted risk factors for nephropathy in insulin-treated diabetics, namely hyperfiltration and microalbuminuria. A positive linear relationship between smoking parameters and UAE in male diabetics also supports the view that smoking may increase the risk of nephropathy development in insulin-treated diabetics.

Adult↗

Cigarette smoking and glomerular filtration rate in insulin-treated diabetics without manifest nephropathy.

A sample of 120 insulin-treated diabetics, 20-40 years of age, with a glomerular filtration rate (GFR) exceeding -2 SD of the age-adjusted value and without albuminuria greater than 300 mg 24 h-1, and with a diastolic blood pressure not greater than 90 mmHg, were studied in order to evaluate the possible effect of smoking on glomerular filtration rate. The patients reported their smoking habits, use of oral snuff, use of alcohol, physical exercise and heredity for hypertension in a simple questionnaire. GFR was assessed with 51Cr-EDTA-clearance and glomerular hyperfiltration was defined as a value exceeding +2 SD of the age-adjusted normal value. We found a significantly higher prevalence of glomerular hyperfiltration in smokers than in non-smokers (41% vs. 18%), but no increased prevalence in users of oral snuff. In cigarette smokers a multivariate analysis revealed that GFR was positively related to body mass index (BMI), and negatively related to the number of cigarettes smoked per week and the mean blood pressure. In non-smokers GFR was dependent only on age. We conclude that in insulin-treated diabetics glomerular hyperfiltration is related to smoking, and that the GFR in smoking diabetics is directly dependent on the smoke doses. As glomerular hyperfiltration is regarded as a risk factor for diabetic nephropathy, our findings should be relevant to preventive measures in clinical work.

Adult↗

Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients.

The pharmacokinetics of azathioprine (AZA) and 6-mercaptopurine (6-MP) was studied in uremic patients after 100 mg AZA intravenously (fifteen patients) and orally (eight patients). 6-MP was analysed with gas chromatography mass spectrometry following extractive alkylation. AZA was determined indirectly assuming quantitative conversion to 6-MP in whole blood. The plasma concentration of AZA fell rapidly after i.v. administration. The mean half-time of elimination for the first rapid phase (t1/2 alpha) was 6.1 min (S.D. +/- 4.1) and for the terminal phase (t1/2 beta) 50 min (+/- 31). The total plasma clearance (Cl) was 6.9 1./min (+/- 3.0). AZA was rapidly converted to 6-MP in vivo, and maximal plasma concentrations of 6-MP were found as early as 5 min after i.v. injection of AZA. The mean t1/2 alpha was 4.6 min (+/- 2.2), t1/2 beta 74 min (+/- 58) and Cl 8.0 1./min (+/- 5.8). The plasma levels of both AZA and 6-MP were either low or undetectable 4-6 h after dose. In erythrocytes AZA levels were low or undetectable indicating rapid conversion to 6-MP in these cells. 6-MP concentration - time curve in erythrocytes was similar to that in plasma, except for a somewhat slower terminal phase of elimination. Oral administration of AZA generated flat plasma curves for AZA and 6-MP. The area under the concentration - time curve (AUC) was considerably smaller than after i.v. administration, 18 and 41% for AZA and 6-MP, respectively. There seems to be little danger of accumulation of AZA/6-MP in uremia. We also studied inhibition of Leucoagglutin (LA) stimulated lymphocyte proliferation by patient plasma at different times in six of the patients following AZA i.v. Sera drawn at 5, 10 and 30 min significantly inhibited the LA-induced proliferation, with an estimated minimum effective concentration of 6-MP in the cultures of about 0.02-0.04 microM. This suggests the possibility of a therapeutic effect even of the low plasma levels of 6-MP obtained after AZA orally. The combined use of sensitive pharmacokinetic and immunological assays as described should be useful in studying the relationship between plasma levels of AZA/6-MP and their immunosuppressive effect and toxicity.

Administration, Oral↗

Vitamin A losses during continuous ambulatory peritoneal dialysis.

Since continuous ambulatory peritoneal dialysis (CAPD) causes losses of certain plasma proteins and their ligands, we examined the serum concentrations of vitamin A and retinol-binding protein (RBP), as well as the concentrations of vitamin A in the skin and dialysis fluid from 32 patients on CAPD over a period of 1-30 months (mean 7.5). The mean values of vitamin A and RBP in serum were 2-4 times higher than those in the healthy controls; a consistent finding in patients with chronic renal failure. Similarly, the vitamin A concentrations in skin were elevated in the CAPD patients (p less than 0.01). The vitamin A content of the dialysate (mean 1.4 mumol/24 h), which correlated significantly with the serum vitamin A concentration (r = 0.67), was constant during CAPD treatment. RBP was present in the dialysate and its concentration closely correlated with that of vitamin A (r = 0.95), indicating that the transperitoneal diffusion involved retinol-RBP. This conclusion was supported by calculations of clearance rates. Despite the considerable losses of vitamin A in CAPD fluid, the patients' vitamin A concentrations in serum and skin remained elevated. Whether extended CAPD treatment (greater than 30 months) may eventually affect the vitamin A situation in chronic renal failure warrants further observations.

Biological Transport, Active↗

Secondary hyperparathyroidism in diabetic and nondiabetic patients on long-term continuous ambulatory peritoneal dialysis (CAPD).

Serum values of calcium, phosphate, alkaline phosphatases and parathyroid hormone (PTH) are reported for 24 diabetic and 26 nondiabetic patients treated with continuous ambulatory peritoneal dialysis (CAPD) for a total of 779 months, without the use of vitamin D or calcium supplements. Radiographic data are reported for 25 patients followed on CAPD for at least 12 months. Serum calcium was well maintained and control of hyperphosphataemia acceptable, but phosphate-binding therapy had to be continued in the majority of patients. Diabetic patients had lower serum phosphate levels and higher serum calcium than nondiabetic patients during the first year of CAPD. In nondiabetic patients the institution of CAPD was followed by a fall in PTH, possibly largely reflecting transperitoneal PTH elimination. No patient achieved normalization of serum PTH on CAPD. Although no symptomatic bone disease was observed, radiographic evidence of progressive hyperparathyroid bone disease developed in 3 of the 25 examined patients, all nondiabetic. In summary, long-term CAPD with a dialysate calcium concentration of 1.75 mmol/l seems to be compatible with normocalcaemia and a steady-state situation with regard to secondary hyperparathyroidism in the majority of patients. Despite transperitoneal elimination, serum PTH remains elevated, and definite progression of hyperparathyroidism is observed in some patients, however, probably making a case for vitamin D therapy and/or intraperitoneal or peroral calcium supplementation in these patients.

Adult↗

Continuous ambulatory peritoneal dialysis in the treatment of end-stage diabetic nephropathy.

The results of treatment with continuous ambulatory peritoneal dialysis (CAPD) of 24 unselected patients with end-stage diabetic nephropathy are reported. The total treatment time was 346 months. Six patients died, eight received a kidney allograft, two returned to CAPD after graft failure, six were transferred to other forms of dialysis and one to another centre. Five patients remained on CAPD. Good control of symptoms, biochemical values and hypertension was achieved. Intraperitoneal administration of insulin resulted in very good metabolic control of diabetes. In view of the unfavourable prognosis of uremic diabetics, the results of this study indicate that CAPD is a suitable method for treatment of uremia in end-stage diabetic nephropathy.

Adult↗

Elevated circulating levels of eosinophil cationic protein in uremia as signs of abnormal eosinophil homeostasis.

Circulating levels of eosinophil cationic protein (ECP), an eosinophil-specific granule protein, and peripheral eosinophils were determined in 56 patients with uremia. The patients were on a chronic hemodialysis or CAPD program or treated with diet only. They had normal counts of peripheral eosinophils but on average a threefold increase of the serum ECP concentrations compared with healthy subjects. The intracellular content of ECP in eosinophils isolated from 6 patients on maintenance hemodialysis was normal. The management or duration of the uremic condition did not influence the circulating ECP levels or eosinophil counts. Neither was any relation found between total IgE levels and peripheral eosinophils or serum ECP. The present results are compatible with an accelerated turnover of peripheral eosinophils in uremia. Such a proposed abnormal eosinophil homeostasis should demand an accelerated marrow eosinophil production, thereby explaining the previously reported marrow eosinophilia in azotemic patients.

Adult↗

Peritonitis in patients on continuous ambulatory peritoneal dialysis. A changing scene.

Peritonitis is a serious and common complication in patients treated with continuous ambulatory peritoneal dialysis (CAPD). This work reports the experiences of this complication in 50 patients treated with CAPD for a total time of 844 months. 129 episodes were observed. Coagulase-negative staphylococci were found to be the causative organisms in 57% of the cases. Most episodes were acquired without any evident cause when CAPD was performed at home. Nine episodes were suspected to be the result of bacterial leakage through the intestinal wall. Six of them occurred in patients receiving corticosteroids. During the study period an increasing number of episodes of peritonitis were caused by organisms with multiple resistance to antibiotics. Thus, the microbiological spectrum in CAPD-related peritonitis must constantly be surveyed so that proper measures, e.g. regarding the choice of antibiotics used, can be taken when a change is observed.

Adult↗

Clinical outcome of 50 patients started on continuous ambulatory peritoneal dialysis in a Swedish centre.

The outcome of the first 50 patients started on Continuous Ambulatory Peritoneal Dialysis (CAPD) in one centre is reported. The total treatment time was 779 months. Ten patients died while on CAPD. Thirteen patients were transplanted, 4 of whom returned to CAPD after graft failure, 7 were transferred to other forms of dialysis and one to another centre. Twenty-three patients remained on the method. Good control of the symptoms and biochemical parameters of uremia was achieved. The patients were content with a high degree of well-being and freedom from dietary and fluid restrictions. The costs were found to be low. Peritonitis was a major complication, accounting for one death and four transfers to hemodialysis. The total incidence was one episode per every sixth patient month. CAPD represents an important contribution to the treatment of chronic renal failure. Nevertheless peritonitis remains a serious problem and the long-term metabolic effects of CAPD are unknown.

Adult↗

Comparison of two catheters for peritoneal access in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

The results obtained by means of the Tenckhoff and the Toronto Western Hospital-type (TWH) indwelling catheters for peritoneal access in patients undergoing Continuous Ambulatory Peritoneal Dialysis are reported. Fifty-nine Tenckhoff catheters were used for 592 months and 24 TWH-type for 220 months. One-year catheter survival was 71% in the Tenckhoff group and 77% in the TWH group. The difference does not reach statistical significance. Moreover no statistically significant differences as regards complications could be found between the two catheter types. A major disadvantage was noted with the TWH catheter: on two occasions TWH catheters could not be removed without a laparotomy, being firmly adherent to the intestine or omentum. It is concluded that the TWH catheter is not a superior alternative to the Tenckhoff catheter for peritoneal access in patients undergoing Continuous Ambulatory Peritoneal Dialysis.

Adult↗

Clinical aspects of continuous ambulatory peritoneal dialysis.

Clinical aspects of Continuous Ambulatory Peritoneal Dialysis (CAPD) were studied in the first fifty patients started on CAPD at our hospital. CAPD was found to achieve good control of the uremic symptoms and of the biochemical values studied. Hypertension became less pronounced. The costs were found to be low. Twenty-four diabetic subjects were studied in detail. Intraperitoneal administration of insulin resulted in good metabolic control of the diabetes. The two catheters used for peritoneal access were compared. Because of problems related to the removal of the Toronto Western Hospital catheter it was concluded that the Tenckhoff catheter was to be preferred. Peritonitis was found to be the worst complication. Coagulase negative staphylococci accounted for 57% of the cases. During the study an increasing percentage of infections were caused by bacteria with multiple resistance to antibiotics. Netilmicin, a new aminoglycoside, was evaluated for the treatment of CAPD-related peritonitis. 84% of the cases responded. One of the nineteen patients treated sustained reversible vestibular toxicity. No other side effects were noted. In two patients right-sided hydrothorax was found to be a complication of peritoneal dialysis. In one case it was demonstrated that defects in the right diaphragm was the cause of the complication. In the other CAPD was continued despite the complication.

Anti-Bacterial Agents↗