Tomas Jogestrand

Effects of exercise training in predialytic uremic patients

We examined the effects of physical training in 10 predialytic uremic patients (7 men, 3 women, mean age 47 +/- 8 years) with an average glomerular filtration (GFR) of 15 +/- 7 ml/min x 1.73 m2. All 10 patients participated in an exercise programme 3 times/week for 3 months and were compared to a control group of 9 patients with comparable baseline variables. The exercise group increased its maximal exercise capacity measured by standardized exercise test on a bicycle ergometer, from an average 159 +/- 49 to 174 +/- 57 W (p less than 0.01). They also showed a decrease in heart rate at equal load (138 +/- 29-123 +/- 18 beats/min, p less than 0.05). The control group did not change its exercise capacity (171 +/- 60 and 171 +/- 65 W, respectively, NS), nor its heart rate at equal load (124 +/- 24 and 123 +/- 24 beats/min, respectively, NS). Thigh muscular function assessed by static endurance increased from a median 77 s (range 27-197) to 113 s (range 66-201), p less than 0.002. Dynamic muscular endurance increased from a median number of 41 movements (range 28-105) to 93 movements (range 45-139), p less than 0.001. The corresponding figures for the controls were: static endurance 60 (range 20-209) and 47 s (range 9-203), respectively, NS; dynamic endurance 53 (range 19-190) and 43 movements (range 10-126), respectively, NS. Total hemoglobin, blood volume, GFR, blood pressure and echocardiographic variables remained unchanged during the observation period. We conclude that in predialytic uremic patients, physical training improves exercise capacity mainly due to an improved muscular function.

Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients

Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients. We examined the effects of erythropoietin (EPO) treatment in 12 predialytic uremic patients (EPO group: mean age 46 +/- 12 years; 6 men, 6 women) with a mean glomerular filtration rate (GFR) of 10 +/- 4 ml/min x 1.73 m2. These patients were compared to a control group of 8 patients (5 men, 3 women). The observation period was 3 months. The EPO group received 300 U/kg body weight i.v. once a week. The EPO group increased their total hemoglobin (THb) from 323 +/- 89 to 466 +/- 128 g (p less than 0.001) and their hemoglobin concentration from 86 +/- 8 to 117 +/- 11 milligrams (p less than 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 +/- 45 to 147 +/- 57 W (p less than 0.01). The control group did not change their THb (349 +/- 124 and 357 +/- 131 g), hemoglobin (93 +/- 8 and 94 +/- 10 milligrams) or exercise capacity (98 +/- 49 and 101 +/- 50 W) during the observation period. There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group (r = 0.81, p less than 0.005). The GFR was unchanged in both groups (EPO group: 10 +/- 4 and 10 +/- 6 ml/min x 1.73 m2; control group: 8 +/- 3 and 8 +/- 3 ml/min x 1.73 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive decline in renal function induces a gradual decrease in total hemoglobin and exercise capacity

We examined 58 patients (38 men, 20 women; mean age: 45 +/- 12 years; body mass index: 24 +/- 4 kg/m2) with a glomerular filtration rate (GFR) ranging from 3 to 32 ml/min, in order to determine the effects of a progressive decline in renal function on total hemoglobin (THb) and exercise capacity. The THb ranged from 185 to 759 g and the hemoglobin concentration ranged from 66 to 151 g/l. Maximal exercise capacity ranged from 50 to 260 W (40-143% of the expected norm). Nearly all the patients interrupted their exercise tests due to general fatigue, leg tiredness or a combination of these factors. There was a significant partial correlation between THb and GFR after sex and age had been accounted for (r = 0.39; p < 0.005). Maximal exercise capacity and THb showed a significant partial correlation after sex, age and GFR had been accounted for (r = 0.27; p < 0.05). Maximal exercise capacity showed a significant partial correlation with GFR after sex, age and THb had been accounted for (r = 0.30; P < 0.05). In conclusion, there is a gradual decline in THb and maximal exercise capacity as uremia progresses. Anemia appears to be a contributory cause responsible for the decrease in maximal exercise capacity along with other factors pertinent to uremia per se.

Effects of Renal Failure on Skeletal Muscle

In this cross-sectional study, we examined biopsies from the vastus lateralis muscle of 13 predialytic uremic men (mean age 46 +/- 8 years). Their average glomerular filtration rate was 14 +/- 7 ml/min x 1.73 m2 and their maximal exercise capacity, measured by standardized exercise test on a bicycle ergometer, was 184 +/- 45 W (94% of the expected norm). The proportion of type I fibers (type I%) in the uremic group was similar to that of the reference group (42 +/- 11 vs. 41 +/- 8% NS). The proportion of type IIA fibers (type IIA%) in the uremic group was higher than in the reference group (44 +/- 10 compared to 35 +/- 9%, p < 0.05). The proportion of type IIB fibers (type IIB%) was lower than in the reference group (13 +/- 8 vs. 21 +/- 8%, p < 0.05). Type I fiber area was similar to that of the reference group (4,768 +/- 1,033 vs. 4,627 +/- 1,112 microns 2, NS). Type IIA and type IIB fiber areas tended to be smaller than those of the reference group (type IIA fiber area: 4,515 +/- 929 vs. 5,213 +/- 1,288 microns 2, NS; type IIB fiber area: 3,953 +/- 1,066 vs. 4,406 +/- 1,582 microns 2, NS) with a type IIA area/type I area ratio which was significantly lower than in the reference group. Citrate synthase activity was 0.48 +/- 0.08 mu kat/g in the uremic group and 0.50 +/- 0.08 mu kat/g in the reference group, NS.(ABSTRACT TRUNCATED AT 250 WORDS)

The “ad hoc” estimation of outflow does not predict patency of infrainguinal reconstructions*

OBJECTIVES This prospective study was performed to evaluate the clinical implication of the adhoc estimation (also called SVS score) of outflow on patency of infrainguinal in situ femoropopliteal or -distal bypasses. METHODS The bypasses were followed with Duplex scanning at 1, 3, 6, and 12 months after surgery. Fifty-three bypasses were recruited for the study, 20 of which were performed in 17 diabetics. In 47% the adhoc scoring was < or = 4.5 and in 53% it was between 5 and 10 (1 corresponds to an excellent outflow and 10 to a blind segment). RESULTS Within the first 30 days eight occlusions occurred, all of which were surgically corrected. The adhoc score for these bypasses was 4.2 vs. 4.9 (NS) for those who did not occlude. During follow-up, revisions were performed in 21 cases (40%) with 30 interventions. At the end of 1 year, 68% of the bypasses were patent (80% among diabetics and 64% among non-diabetics, NS). Patency at 1 year was not influenced by the adhoc classification. CONCLUSION The estimation of outflow from angiography seems to be of no value in predicting graft patency in infrainguinal grafting.

Decreased Cyclosporine Levels during Gemfibrozil Treatment of Hyperlipidemia after Kidney Transplantation

Ingela Fehrman-Ekholm, MD, Department of Renal Medicine, Karolinska Institute, Huddinge Hospital, S-141 86 Huddinge (Sweden) Dear Sir, Hyperlipidemia following renal transplantation is a newly recognized problem, which may be associated with an increased risk of atherosclerosis as well as early graft loss [1]. However, the choice of treatment and advantages/disadvantages of treatment are not yet determined. We performed a double-blind randomized study in kidney recipients with hyperlipidemia to determine whether atherosclerosis, measured by sonography in the carotid vessels, was changed by the treatment. Gemfibrozil was chosen as the hypolipidemic drug, since no interaction with cyclosporine had been reported and hyperlipidemia in kidney recipients is often combined. However, the trial was stopped after 6 months because of a suspected interaction between the study drug and cyclosporine. The cyclosporine whole blood concentrations were determined with a specific monoclonal ra-dioimmunoassay (Incstar, cyclo-trac RIA). Altogether 19 patients (11 males and 8 females) with serum cholesterol levels of > 6.5 mmol/l after at least 3 months of diet were included. The dosage of gemfibrozil was 450 mg once when serum creatinine was > 200 μmol/l and 450 mg twice when the serum creatinine level was < 200 μmol/l. Fifteen patients were treated for > 3 months: 7 with gemfibrozil, and 8 with placebo. They all had severe hyperlipidemia, the mean pre-treatment values ( ± SE) being 9.0 ± 0.46 mmol/l for cholesterol and 3.7 ± 0.3 mmol/l for triglycerides. After 6 weeks of treatment, we found a significant decline in the 12-hour trough whole blood cyclosporine concentrations in the treatment group from 93 ± 8.5 to 76 ± 5.2 ng/ml (p < 0.05, Wilcoxon rank test). After 3 months, the mean cyclosporine level was 88 ± 9.3 ng/ml, adjusted by an increase in dosage in 3 of 7 patients. In the placebo group, the mean blood concentrations of cyclosporine were 99 ± 7.4 ng/ml at the start of treatment, 98 ± 19 after 6 weeks and 123 ± 17 ng/ml at 3 months (NS). The doses were not increased. The mechanisms responsible for this phenomenon are not yet known, but the change in lipoprotein distribution during treatment may cause changes in the free fraction of cyclosporine [2]. A low free fraction has been associated with acute rejection [2]. In 2 patients there was a significant rise of serum creatinine requiring kidney biopsy. One biopsy showed chronic rejection and the other cyclosporine toxicity. There is also a possibility that absorbtion of cyclosporine is diminished during therapy. In this case the new microemulsion of cyclosporine (neoral) might solve the problem.

The effect of erythropoietin treatment on arteriovenous haemodialysis fistula/graft: A prospective study with colour flow doppler ultrasonography

To determine the effect of erythropoietin (EPO) on patency the haemodynamics and morphology in haemodialysis fistula/graft were prospectively assessed using ultrasonographic two-dimensional imaging and colour flow Doppler together with pulsed Doppler, prior to and during partial correction of anaemia with EPO. Nineteen radiocephalic fistula and 11 loop grafts in 30 patients on routine maintenance haemodialysis were investigated prior to EPO treatment. A significant stenosis defined as a localised 100% increase in flow velocity was found in the arterial inflow in seven (23%) patients, in the loop graft in seven (64% of loop grafts) patients, and in the venous segments in 23 (77%) patients. Fourteen patients were rescanned after more than 200 days of EPO therapy. There was a significant increase in haemoglobin (84 +/- 14 g/l to 104 +/- 18 g/l) and haematocrit (24 +/- 4 to 31 +/- 5%) during this time. One arterial, four loop grafts and two venous stenoses appeared or increased in severity, and one venous return flow segment had occluded. Blood flow according to ultrasonography was unchanged. Of the 16 patients lost to follow-up, three underwent surgical intervention (clinical failure rate 0.20 access/year). EPO therapy may contribute to minor changes in access haemodynamics but does not seem to be detrimental to patency.