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Biomedical subjects

P O Attman

Publications and source records attributed to P O Attman.

At least 19 recordsLinked to original sources
PubMed2000

Angiotensin I-converting enzyme gene polymorphism in non-diabetic renal disease.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene determines the concentration of ACE in serum and local tissues. The role of this polymorphism in progressive chronic renal disease is still not fully clear. METHODS: We analysed the impact of the D/D polymorphism on the rate of decline in renal function in patients with non-diabetic, chronic progressive renal insufficiency. Seventy non-diabetic patients, aged 21-69 years at baseline, with moderately advanced renal insufficiency due to primary chronic renal disease were followed for an average of 3 years with repeated measurements of their glomerular filtration rate (GFR). Their mean GFR at baseline was 41 ml/min/1.73 m(2) body surface area (BSA). The polymerase chain reaction (PCR) amplification method was used to detect the I/D polymorphism of the ACE gene. GFR was measured as the clearance of (51)Cr-EDTA and the individual rate of progression was calculated using linear regression. RESULTS: The distributions of the genotypes were: D/D 30%, I/D 49%, and I/I 21%. The rates of progression in the three ACE genotype groups were an annual decline in renal function of -4.2 (SD 4.6) ml/minx1.73 m(2) BSA in the D/D group, -2.7 (SD 3. 4) in the I/D group and -1.7 (SD 3.4) in the I/I group (ANOVA P=0. 12). In patients with proteinuria below 3.5 g/24 h, the D/D group had a significantly higher rate of progression than patients with the I allele. The same was found in a separate analysis when only patients with normal apoliprotein B (below 155 mg/dl) levels were analysed. Furthermore, the D/D genotype was a significant predictor of a more rapid decline in renal function in male, but not female, patients. CONCLUSION: The results in this study in non-diabetic patients with chronic renal disease indicate that the presence of the D allele in the ACE genotype may be of particular importance as a predictor of a high rate of progression in male patients who otherwise do not have a major burden of documented and important prognostic factors for progressive renal insufficiency.

Adult↗
PubMed2000

Dimensions of arteriovenous fistulas in patients with autosomal dominant polycystic kidney disease.

BACKGROUND/AIM: Aneurysms are known manifestations of autosomal dominant polycystic kidney disease (ADPKD). We investigated whether the dimensions of arteriovenous fistulas created for performance of haemodialysis were affected by the original disease. METHODS: The lumen diameter of the fistula was studied by ultrasound in 19 patients with ADPKD and in 19 control patients. The patients' sex, age, the duration of their fistulas, haemoglobin values and blood pressure levels were similar in both groups. The monitoring was performed along the forearm part of the vein, and the maximal diameter was measured. The diameters at the two needle insertion sites were also measured. RESULTS: The ADPKD patients had a significantly higher fistula diameter than the control patients: 12 (range 8-19) mm versus 8 (range 6-24) mm at the widest level (p = 0. 003). There were no significant differences in the diameters at the needle insertion sites. CONCLUSION: The receiving veins of arteriovenous fistulas in patients with ADPKD have an abnormality that causes a greater than normal dilatation in response to the arterialization. We postulate that this phenomenon is linked with the increased prevalence of aneurysms in ADPKD.

Adult↗
PubMed1999

Apolipoprotein B-containing lipoproteins in renal failure: the relation to mode of dialysis.

BACKGROUND: The aim of this study was to establish whether there is a differential effect of mode of dialysis, hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) on the dyslipidemia of renal failure. METHODS: The lipoprotein profile was determined in 61 non-diabetic patients on chronic HD (N = 30) and CAPD treatment (N = 31), and in a control group of 27 healthy subjects. The analysis included the measurement of individual apolipoprotein (apo) A- and apo B-containing lipoproteins (LPs) separated by sequential immunoaffinity chromatography. Apo A-containing lipoproteins include lipoprotein A-I with apo A-I and lipoprotein A-I:A-II with apo A-I and apo A-II as the main protein constituents, whereas apo B-containing lipoproteins comprise simple cholesterol-rich lipoprotein B (LP-B), with apo B as the only protein moiety and complex triglyceride (TG)-rich lipoprotein B complex (LP-Bc) particles with apo B, apo A-II, apo C, and/or apo E as the protein constituents. RESULTS: CAPD patients had significantly higher concentrations of total cholesterol (6.8 vs. 5.1 mmol/liter), low-density lipoprotein (LDL) cholesterol (4.6 vs. 3.2 mmol/liter), TG (2.3 vs. 1.5 mmol/liter), apo B (155.3 vs. 105.7 mg/dl), LP-B (136.0 vs. 91.9 mg/dl), and LP-Bc (19.3 vs. 13.8 mg/dl) than HD patients. Both HD and CAPD patients had significantly higher TG, VLDL cholesterol, apo C-III, and apo E and significantly lower high-density lipoprotein cholesterol, apo A-II, and lipoprotein A-I:A-II levels than control subjects. The distribution of apo C-III in high-density lipoprotein and VLDL-LDL was altered in CAPD patients in comparison with control subjects. This suggests that the removal of TG-rich lipoproteins is less efficient in patients on CAPD. Normotriglyceridemic (NTG; TG < or = 1.7 mmol/liter, 150 mg/dl) CAPD patients had significantly higher levels of TC, LDL cholesterol, apo B, and LP-B than NTG-HD patients. There was little difference in the LP-Bc levels between NTG-CAPD, NTG-HD, and controls. Similarly, hypertriglyceridemic (HTG) CAPD patients had significantly higher TC, LDL cholesterol, apo B, and LP-B levels than HTG-HD patients. The LP-Bc levels were significantly increased in HTG-HD and HTG-CAPD patients compared with controls, but the slightly higher levels in the CAPD patients did not differ significantly from the HD group. CONCLUSION: CAPD and HD patients have a lipoprotein profile characteristic of renal failure. Patients on long-term CAPD have higher levels of cholesterol-rich apo B-containing lipoproteins unrelated to TG levels. Many patients on CAPD also have a substantial elevation of the plasma concentrations of TG-rich LPs. The clinical significance of increased levels of potentially atherogenic LP-B during CAPD remains to be investigated.

Adult↗
PubMed1999

Lipoprotein abnormalities as a risk factor for progressive nondiabetic renal disease.

Renal disease is accompanied by characteristic alterations of lipoprotein metabolism, which appear as a consequence of nephrotic syndrome or renal insufficiency and are primarily reflected in an altered apolipoprotein profile rather than elevated plasma lipid levels. Their full characterization requires identification of discrete lipoprotein particles. While nephrotic syndrome results in increased concentrations of both cholesterol- and triglyceride-rich apoB-containing lipoproteins, renal insufficiency is characterized by an accumulation of intact or partially metabolised triglyceride-rich apoB-containing lipoproteins. The dyslipidemia has been discussed as a contributory factor for the progression of renal insufficiency through development of glomerulosclerosis and tubulointerstitial lesions together with accelerated atherosclerosis. Several experimental studies have shown that hyperlipidemia accelerates renal damage. Lipid-lowering treatment can reduce renal lesions and preserve renal function. The documentation in human nondiabetic progressive renal insufficiency is more limited. We have found that increased concentrations of triglyceride-rich, but not cholesterol-rich, apoB-containing lipoproteins are, associated with a more rapid loss of renal function. The underlying pathophysiological mechanisms for the relation between triglyceride-rich apoB-containing lipoproteins and progression of renal insufficiency are not fully understood. Treatment with hypolipemic drugs may attenuate the renal dyslipidemia, but thus far there have been no reports about controlled clinical trials testing the possible effect of such treatment on the progression of renal insufficiency. In summary, there is evidence to suggest that some specific lipoprotein abnormalities are a risk factor for the progression of renal dysfunction, but the final test of such assumptions still rests on the results of urgently needed controlled intervention studies.

Apolipoproteins B↗
PubMed1999

Improved clearance of iohexol with longer haemodialysis despite similar Kt/V for urea.

BACKGROUND: The efforts to improve the quality of haemodialysis (HD) has renewed the interest in the consequences of blood-flow distribution for removal of solutes. METHODS: To test the effects of HD time per se, 10 patients were studied in a cross-over fashion with HD for 3 h and 1 week later for 6 h, with similar blood urea Kt/Vs, achieved by adjusting the blood flow rate to 290 and 120 ml/min respectively. Injections of iohexol (MW 821 Dalton) were given 2 days prior to the dialysis sessions. Blood samples were taken before, during (6/HD), 1 and 24 h after the HD and analysed for concentrations of urea and iohexol. A urea on-line monitor (Gambro) was used for continuous recordings and sampling of dialysate. RESULTS: According to the study design the blood Kt/V for urea (Daugirdas II) was similar for 3 and 6 h HD, close to 1.0 (n.s), while the removed mass of urea showed that Kt/V was slightly and significantly higher for the 6 h HD. The 'apparent' mass of iohexol, defined as plasma concentration times estimated distribution volume, fell to 29% and 21% of pre-dialysis levels after 3 h and 6 h HD, respectively (P<0.01), but increased after HD, and more so after the short dialysis, reaching 46% of the predialysis mass 24 h after 3 h HD vs. 36% after 6 h HD (P<0.05). The removed mass of iohexol was 920+/-110 mg with 6h HD and 700+/-81 mg with 3h HD, (P<0.01). Thus, the longer dialysis removed 32% more iohexol despite similar blood Kt/V for urea. CONCLUSION: The treatment time per se affects solute removal despite similar blood Kt/V for urea. This is particularly true for an intermediate-size molecule like iohexol.

Aged↗
PubMed1999

The plasma levels of homocysteine are elevated in moderate renal insufficiency but do not predict the rate of progression.

BACKGROUND: Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It is also characterized by elevated plasma levels of total homocysteine (tHcy). Hyperhomocysteinemia has been shown to be a risk factor for atherosclerosis in both the general population and in patients with end-stage renal disease. AIM: To analyze whether elevated tHcy levels also may contribute to a higher rate of progression of renal insufficiency in patients with moderately advanced renal failure. METHODS: To investigate whether tHcy concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of tHcy with the progressive decline of renal function in an observational study of human chronic renal disease. RESULTS: Sixty-three nondiabetic patients (49 men, 14 women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.0 years, and the mean rate of decline in glomerular filtration rate ((51)Cr- EDTA clearance) was -3.2 +/- (SD) 3.9 ml/min x 1.73 m(2) body surface area. The mean plasma concentration of tHcy at the beginning of the study was 28.3 +/- 12.0 micromol/l. Plasma tHcy concentrations correlated significantly with the glomerular filtration rate (r = -0. 32, p < 0.01). However, there was no association between the initial plasma level of tHcy and the rate of progression as assessed by linear regression analysis (r = 0.02; NS). In contrast, increased levels of apolipoprotein B, low-density lipoprotein cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. CONCLUSIONS: Patients with moderately advanced chronic renal insufficiency have elevated plasma levels of homocysteine. The tHcy plasma levels increase in parallel with the degree of reduction in renal function. However, the hyperhomocysteinemia is not prospectively associated with a higher rate of progression of the renal functional impairment. Hence, there is no indication that elevated homocysteine levels play a contributing role for an accelerated glomerulosclerotic process.

Adult↗
PubMed1999

Cadmium, mercury, and lead in kidney cortex of the general Swedish population: a study of biopsies from living kidney donors.

Cadmium, mercury, and lead concentrations were determined in deep-frozen kidney cortex biopsies taken from 36 living, healthy Swedish kidney donors (18 males and 18 females), who were 30-71 (mean 53) years of age. Information about occupation, smoking, the presence of dental amalgam, and fish consumption could be obtained for 27 of the donors. The samples (median dry weight 0.74 mg) were analyzed using inductively coupled plasma mass spectrometry, and the results were transformed to wet-weight concentrations. The median kidney Cd was 17 micrograms/g (95% confidence interval, 14-23 micrograms/g), which was similar in males and females. In 10 active smokers, the median kidney Cd was 24 micrograms/g, and in 12 who never smoked, it was 17 micrograms/g. The median kidney Hg was 0.29 micrograms/g, with higher levels in females (median 0.54 micrograms/g) than in males (median 0.16 micrograms/g). Subjects with amalgam fillings had higher kidney Hg (median 0.47 micrograms/g, n = 20) than those without dental amalgam (median 0.15 micrograms;g/g, n = 6), but kidney Hg was below the detection limit in some samples. Nearly half of the samples had kidney Pb below the detection limit. The median kidney Pb was estimated as 0. 14 micrograms/g. This is the first study of heavy metals in kidney cortex of living, healthy subjects, and the results are relatively similar to those of a few previous autopsy studies, indicating that results from autopsy cases are not seriously biased in relation to kidney metal concentrations in the general population. Cd concentrations in those who never smoked were relatively high, indicating considerable Cd intake from the diet in Sweden. The effect of dental amalgam on kidney Hg was as expected, although the reason for the difference in Hg levels between males and females is unclear.

Adult↗
PubMed1998

The compositional abnormalities of lipoproteins in diabetic renal failure.

BACKGROUND: Diabetic nephropathy (DN) is a common cause of chronic renal failure (CRF). Patients with DN have abnormal lipoprotein metabolism that can be influenced by both the impairment of renal function and the metabolic control of diabetes. The aim of the study was to explore the specific compositional lipoprotein abnormalities in patients with insulin-dependent DN in comparison with diabetic patients without nephropathy and non-diabetic CRF patients. METHODS: The lipid and apolipoprotein (apo) composition of major lipoprotein density classes was determined in 20 patients with insulin-dependent diabetes mellitus and nephropathy and compared with that in seven diabetic patients without nephropathy, 20 patients with non-diabetic CRF, and nine healthy control subjects. Lipoproteins isolated by preparative ultracentrifugation were very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). RESULTS: Patients with DN had a plasma lipid and apolipoprotein profile characteristic of renal dyslipoproteinaemia with increased concentrations of triglycerides and cholesterol, reduced levels of apoA-I and apoA-II and increased levels of apoB, apoC-II, apoC-III and apoE. These changes were more pronounced in diabetic than in non-diabetic patients with comparable degrees of renal failure. All density classes were characterized by abnormal concentration and composition of some lipid and apolipoprotein constituents. DN patients had a more than four-fold increase of VLDL mass, a three-fold increase of IDL mass, and a significant reduction of HDL mass compared to control subjects. They also had significantly higher concentrations of apoB, apoC-peptides and apoE particularly in VLDL and IDL, and to some extent in LDL. In HDL, DN patients had lower cholesterol, apoA-I, apoA-II and apoC-II levels than controls. The major compositional change in DN patients was a significant increase in the relative content of apoC-peptides in IDL and LDL. The lipoprotein abnormalities were more pronounced in patients with high HbA1c values. In addition, lower GFR and increased proteinuria were associated with higher concentrations of triglycerides and apoC peptides in VLDL, IDL, and LDL in DN patients. CONCLUSIONS: The results indicate that patients with DN share the characteristic features of dyslipidaemia of CRF with accumulation of intact or partially delipidized apoB-containing lipoproteins enriched in apoC-peptides and apoE, which are present not only in VLDL and IDL but also in LDL density range. The alterations are more marked in DN than in nondiabetic CRF patients reflecting the additional impact of metabolic control. Increased levels of these lipoproteins may represent risk factors for the accelerated development of atherosclerotic vascular disease in these patients.

Adult↗
PubMed1998

Body composition in patients treated with peritoneal dialysis.

BACKGROUND: Malnutrition is a common complication in uremia and during maintenance dialysis. Several factors contribute to its development. Different modes of dialysis treatment may differ in their effects on nutritional status. METHODS: In order to analyse the nutritional consequences of peritoneal dialysis (PD), body composition analyses were performed in PD patients between February 1993 and March 1996. Body cell mass (BCM) was estimated from measurements of total body potassium (TBK) in a whole-body counter. Total body water (TBW) was determined by measurement of tritiated water. Body fat (BF) was calculated from body weight (BW), TBK and TBW. Observed values were related to predicted (o/p) derived from local population studies. RESULTS: Sixty patients were repeatedly investigated during the study period. Of these, 34 were investigated during the first year of PD. At the start of dialysis, TBK o/p was 0.94 and BF o/p 0.76. No change in body composition was seen during the observation period in the group as a whole. However, within the group individual changes in BW were strongly correlated with individual changes in BF (r=0.66, P=0.0001). Twenty-six patients were examined during the second and third year of PD. In this group, BW o/p remained constant over time. However, there was a small but significant decline of TBK o/p and a concomitant increase of BF o/p (P<0.05). No correlation was observed between changes in TBK and changes in serum albumin. CONCLUSIONS: The results of this study indicate, that there may be a risk for further reduction of body cell mass during long-term PD treatment, while body energy stores are maintained or even increased.

Adipose Tissue↗
PubMed1998

Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency.

Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It has been suggested that renal dyslipoproteinemia contributes to the progression of renal dysfunction. The objective of this study was to investigate the impact of different apoB-containing lipoprotein families on the progressive decline of renal function in patients with moderately advanced chronic renal failure. As part of a larger prospective study, 44 adult nondiabetic patients with primary chronic renal disease were followed with repeated GFR measurements for an average of 2.4 (SD 1.0) yr. Patients' characteristic variables, including plasma levels of lipids, apolipoproteins (apo), and apoA- and apoB-containing lipoprotein families (LP), were determined at the beginning of the observation period. The baseline variables were prospectively related, using linear regression, to the rate of progression (deltaGFR). The patient study group had a mean GFR at baseline of 40.3 (SD 16.7) ml/min per 1.73 m2 body surface area. The average rate of progression was a yearly decline in GFR of -3.2 (SD 5.1) ml/min per 1.73 m2 body surface area. A strong association was observed between the plasma concentration of complex, triglyceride-rich apoB-containing lipoproteins (LP-Bc) and the rate of progression (r=0.43, P < 0.01), whereas there was no association between the cholesterol-rich apoB-containing lipoproteins (LP-B) and deltaGFR. The association between the levels of LP-Bc and the rate of progression was not dependent on the baseline values of GFR, BP, and the degree of proteinuria. The results of this study extend earlier observations regarding the importance of renal dyslipoproteinemia for progressive renal insufficiency. In particular, elevated levels of intact or partially metabolized triglyceride-rich apoB-containing lipoproteins of intermediate- and low-density ranges seem to promote the progression of human renal insufficiency.

Adult↗
PubMed1997

Creatinine generation rate and lean body mass: a critical analysis in peritoneal dialysis patients.

Calculation of creatinine generation rate (CGR) has been reintroduced as a method to estimate lean body mass (LBM) in dialysis patients. It has also been suggested that it be used to identify noncompliance with dialysis prescription. In order to evaluate this method, LBM calculated from CGR (LBMCGR) was compared to 48 simultaneous estimations of LBM from measurements of total body potassium (TBK) in 35 patients on peritoneal dialysis (PD). TBK (mmol) was measured in a whole body counter and LBM (kg) was calculated as TBK/68.1 (Forbes). CGR was calculated with and without inclusion of "metabolic degradation" of creatinine. LBMCGR was further estimated using two different equations based on results in healthy subjects, one from a group on an ad libitum diet, the other from a group on a meat-free diet. The intercept of the two equations differs by 13 kg. CGR systematically underestimated LBM when compared to TBK, but to a lesser degree when using the equation based on a meat-free diet. Repeated determinations of CGR in 11 stable patients revealed an unacceptably high coefficient of variation (CV%) for LBM, 14.2%, while body wt CV was 1.4%. We conclude that CGR is not a valid method to monitor LBM in PD patients. CGR is highly variable and in part dependent on meat intake, as is the relation between CGR and LBM. For the same reasons, it seems unwise to draw conclusions of noncompliance of PD-patients from determinations of CGR.

Adult↗
PubMed1997

Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency.

BACKGROUND: Chronic renal insufficiency is accompanied by specific alterations of the lipoprotein metabolism. It has been suggested that the renal dyslipoproteinaemia of renal insufficiency contributes to the progression of glomerular and tubular lesions, with subsequent deterioration of renal function. The objective of this prospective study was to investigate whether the specific lipoprotein abnormalities of renal insufficiency are associated with the rate of decline of renal function in patients with moderately advanced chronic renal failure. METHODS: A patient population of 73 adult non-diabetic patients with primary chronic renal disease were followed with repeated measurements of the glomerular filtration rate (GFR) for an average of 3.2 (SD 0.7) years. Forty-three of these patients had chronic glomerulonephritis as the underlying renal disease. Patient characteristics including plasma levels of lipids and apolipoproteins were determined at entry and were prospectively related, using linear regression, to the rate of progression. RESULTS: The mean GFR at entry was 41.3 (SD 15.3) ml/min x 1.73 m2 BSA. The average rate of progression was a decline in GFR of -2.8 (SD 3.7) ml/min x 1.73 m2 BSA per year. In the whole patient study group total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were all significantly associated with a more rapid decline in renal function, whereas triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A (apoA) were not. In the more homogeneous subgroup of patients with chronic glomerulonephritis the association between dyslipidaemia and the rate of progression was even more pronounced. In this subgroup of patients also serum triglycerides and apoE were significantly associated with a higher rate of progression. Both the initial blood pressure and proteinuria were also significantly associated with a more rapid decline in renal function in the whole study group as well as in patients with chronic glomerulonephritis. The associations between these variables with the rate of progression were all independent of the entry GFR values. CONCLUSIONS: These results indicate that the lipoprotein abnormalities of renal insufficiency contribute to the progression of renal failure in human chronic renal disease.

Adult↗