Herschel R. Harter

Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients.

Current evidence suggests that administration of 1,25(OH)2D3 to patients with chronic renal insufficiency results in suppression of secondary hyperparathyroidism only if hypercalcemia occurs. However, since the parathyroid glands possess specific receptors for 1,25(OH)2D3 and a calcium binding protein, there is considerable interest in a possible direct effect of 1,25(OH)2D3 on parathyroid hormone (PTH) secretion independent of changes in serum calcium. Recent findings indicate substantial degradation of 1,25(OH)2D3 in the intestine, therefore, it is possible that while oral administration of the vitamin D metabolite increases intestinal calcium absorption, the delivery of 1,25(OH)2D3 to peripheral target organs may be limited. We therefore compared the effects of orally or intravenously administered 1,25(OH)2D3 on the plasma levels of 1,25(OH)2D3 and the effects of these two modes of treatment on PTH secretion. Whereas oral administration of 1,25(OH)2D3 in doses adequate to maintain serum calcium at the upper limits of normal did not alter PTH levels, a marked suppression (70.1 +/- 3.2%) of PTH levels was seen in all 20 patients given intravenous 1,25(OH)2D3. Temporal studies suggested a 20.1 +/- 5.2% decrease in PTH without a significant change in serum calcium with intravenous 1,25(OH)2D3. In five patients the serum calcium was increased by the oral administration of calcium carbonate, the decrement in serum i-PTH was only 25 +/- 6.65% when compared with 73.5 +/- 5.08% (P less than 0.001) obtained by the administration of intravenous 1,25(OH)2D3. Thus, a similar serum calcium achieved by intravenous 1,25(OH)2D3 rather than calcium carbonate has a greater suppressive effect in the release of PTH. These studies indicate that 1,25(OH)2D3 administered intravenously rather than orally may result in a greater delivery of the vitamin D metabolite to peripheral target tissues other than the intestine and allow a greater expression of biological effects of 1,25(OH)2D3 in peripheral tissues. The use of intravenous 1,25(OH)2D3 thus provides a simple and extremely effective way to suppress secondary hyperparathyroidism in dialysis patients.

Superiority of the Internal Jugular over the Subclavian Access for Temporary Dialysis

We studied angiographically the access route 1-27 months after the insertion temporary dialysis catheters in 52 patients: 32 subclavian and 20 internal jugular. The two groups were statistically similar with respect to age, sex and race. The subclavian catheters were left in for a mean of 11.5 days (2-22) while the internal jugular ones were inserted for 15.8 days (5-25; p = 0.0015). One hundred percent of the internal jugular patients were free of any venogram abnormalities in their venous access return. In marked contrast, 50% of the subclavian sites had mild to severe stricutures with 90% having 70-100% occlusion of the subclavian vein. Six patients had bilateral severe strictures. The long-term stricture rate of subclavian catheters in the subclavian vein was unacceptably high compared to the internal jugular route.

Prevention of Thrombosis in Patients on Hemodialysis by Low-Dose Aspirin

Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis, we conducted a randomized, double-blind trial of aspirin (160 mg per day) vs. placebo in 44 patients on chronic hemodialysis. The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months. Thrombi occurred in 18 of 25 (72 per cent) of patients given placebo and 16 of 19 (32 per cent) of those given aspirin (P less than 0.01). The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group (p less than 0.005). A dose of 160 mg of aspirin per day is an effective, nontoxic antithrombotic regimen in patients on hemodialysis.

Diverticular Disease in Patients with Chronic Renal Failure Due to Polycystic Kidney Disease

Twelve patients with chronic renal failure and polycystic kidney disease represent 8% of the 151 hemodialysis patients followed up at the Chromalloy American Kidney Center, Washington University School of Medicine. Ten (83%) of these patients have diverticulosis, and four of these patients developed gross colonic perforation secondary to diverticulitis. Barium enemas on 31 chronic renal failure patients without polycystic kidney disease revealed diverticulosis in 10 (32%). None had diverticulitis. Barium enemas in 120 age-matched non-renal failure control patients revealed diverticulosis in 45 (38%). None had diverticulitis. These findings suggest that patients with chronic renal failure due to polycystic kidney disease have a high incidence of diverticulosis and diverticulitis, that diverticulosis occurs in patients with chronic renal failure without polycystic kidney disease at a rate similar to that in the general population, and that diverticulitis should be an initial consideration in the differential diagnosis of abdominal pain in patients with polycystic kidney disease.

Upper Gastrointestinal Bleeding in Patients with Chronic Renal Failure

Endoscopy to evaluate upper gastrointestinal bleeding was done for 482 patients over a 42-month period. Fifty-nine patients (12%) had chronic renal failure and upper gastrointestinal bleeding; the remaining 423 did not have renal failure. Angiodysplasia of the stomach or duodenum was the most frequent source of bleeding in patients with renal failure. Angiodysplasia (p less than 0.001) and erosive esophagitis (p less than 0.01) were significantly commoner causes of bleeding in the renal failure population than in the group without renal failure. Recurrent bleeding was also more frequent in patients with renal failure (25%) than in the other patients (11%). Angiodysplasia was the most frequent source of recurrent bleeding in patients with renal failure (53%) whereas peptic lesions were the most likely sources in those without renal failure (51%). These data show that the differential diagnoses of first and subsequent upper gastrointestinal bleeding sites differ for patients with and without chronic renal failure.

Exercise training reduces coronary risk and effectively rehabilitates hemodialysis patients

This study examines the effects of 12 months of endurance exercise training (cycling, walking and jogging) on lipid profiles, glucose metabolism, blood pressure, anemia and psychological function in 14 hemodialysis patients. Maximal aerobic capacity (VO2max) increased 18% in the exercisers (p less than 0.01), but did not change in 11 controls. This was associated with a reduction in depression, a decrease in dosages of antihypertensive medications, a significant increase in hematocrit and hemoglobin levels (red cell mass rose, plasma volume did not change), a decrease in plasma triglyceride by 23% (p less than 0.05) and an increase in high-density lipoprotein cholesterol (HDL-C) levels by 21% (p less than 0.01) (both HDL-C and triglyceride levels worsened in the sedentary controls), and an 18% increase in glucose disappearance rates (p less than 0.05) in spite of a 52% decrease in fasting insulin levels (p less than 0.01), suggesting that insulin sensitivity improved. These results demonstrate that some of the complications present in hemodialysis patients may be caused by their sedentary life-style, rather than endstage renal disease itself. This suggests that rehabilitation through exercise is possible for these patients. By reducing coronary risk factors in hemodialysis patients, exercise training may also decrease their heightened morbidity and mortality from atherosclerotic complications. These possibilities need to be examined in a longitudinal study.

Exercise Training Improves Hypertension in Hemodialysis Patients

6 patients with end-stage renal disease, hypertension and anemia were studied to determine the effect of endurance exercise training on their blood pressure. Initial exercise capacities were low (VO2 max = 18 +/- 2 ml/kg/min); however, their capacities increased (17 +/- 9%, p less than 0.05) after 14 +/- 5 months of training. This was associated with reductions in the antihypertensive medications in the 5 patients initially requiring them, and decreases in both predialysis systolic and diastolic blood pressures. There were significant increases in hemoglobin concentrations (7.3 +/- 0.4 to 9.8 +/- 0.9 g%) and hematocrit levels (23 +/- 2 to 30 +/- 3%) during training with no changes in body weights, interdialysis weight gains or serum albumin concentrations. 6 nonexercising dialysis patients had no changes in these same variables over the same period of time. These results suggest that endurance exercise training will reduce blood pressure and improve anemia in some hemodialysis patients.

Racial differences in plasma high-density lipoproteins in patients receiving hemodialysis. A possible mechanism for accelerated atherosclerosis in white men.

Among 346 nondiabetic patients receiving long-term hemodialysis, cardiovascular mortality was higher in white than in black men (P less than 0.02) but was similar between black and white women, despite the higher incidence of nephrosclerosis in black men and women (59 and 58 per cent vs. 8 and 10 per cent, respectively; P less than 0.0001). There were significant racial differences in plasma lipid and apoprotein levels in a subset of 100 of these patients. The white men had higher levels of plasma triglyceride and lower levels of high-density-lipoprotein (HDL) cholesterol, apoprotein A-I, and apoprotein A-II than black men; concentrations of HDL, apoprotein A-I, and apoprotein A-II were also lower in white than in black women. The distribution of the HDL subfractions HDL2, HDL3, and HDL3D, as determined by zonal ultracentrifugation, was normal in black and abnormal in white men receiving hemodialysis. HDL2 concentrations were higher in black than in white men by both zonal analysis (P less than 0.05) and polyanionic precipitation of the HDL subfractions (P less than 0.01). The distributions and concentrations of HDL2 and HDL3L were similar in black and white women. Thus, there are marked racial differences in HDL in male patients receiving hemodialysis. The abnormalities in HDL and the hypertriglyceridemia in the white men may explain their high rate of cardiovascular mortality.

Peripheral Nerve Entrapment Syndromes in Chronic Hemodialysis Patients

15 of 271 patients (6%) treated with chronic hemodialysis developed peripheral nerve entrapment syndrome of the median or the ulnar nerve. The majority of these patients were female (p less than 0.03). Fistulas located in arms with nerve entrapment tended to have higher flow rates than fistulas located in arms without nerve entrapment (57%) vs. 4.4%, p less than 0.001). There was no correlation with the renal diagnosis, previous access surgery in the involved arm, the type of vascular access used, the duration of hemodialysis, the adequacy of dialysis, calcium or phosphate homeostasis, plasma parathyroid levels, or thyroid function. Surgical intervention successfully relieved all symptoms. Return of normal renal function dose not reverse this disorder. Peripheral nerve entrapment is a common surgically correctable cause of neuropathy of the upper extremities in hemodialysis patients.

Psychological effects of exercise training in hemodialysis patients.

To assess the psychological effects of exercise training in hemodialysis patients 4 dialysis patients, matched by age, sex, and medical history with 4 controls, received psychological testing before and after a 6-month period of exercise training. The trained patients had a 28% improvement in graded exercise treadmill stress test duration and a 13% improvement in aerobic capacity. This was associated with a significant reduction in anxiety and depression (p less than 0.06), but no measurable change in these moods occurred in the control groups. These results suggest that exercise training may improve psychological functioning in dialysis patients.