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Biomedical subjects

J Delmez

Publications and source records attributed to J Delmez.

18 recordsLinked to original sources
PubMed1999

Association of acidosis and nutritional parameters in hemodialysis patients.

There is extensive literature supporting an important role for acidosis in inducing net protein breakdown, both in experimental animals and humans. However, the clinical importance of the moderate intermittent metabolic acidosis frequently observed in hemodialysis patients has not been determined. We performed a cross-sectional analysis of the baseline laboratory data in the first 1,000 patients recruited to the Hemodialysis Study, looking for correlations between predialysis serum total carbon dioxide levels and parameters related to dietary intake and nutritional status. We found the mean predialysis serum total carbon dioxide level was moderately low (21.6 +/- 3.4 mmol/L; mean +/- SD) despite the use of bicarbonate dialysate and an average single-pool Kt/V of 1.54. Predialysis serum total carbon dioxide level correlated negatively with normalized protein catabolic rate (P < 0.001), suggesting patients with lower serum total carbon dioxide levels have a greater protein intake. The degree of acidosis observed in our patients does not seem to have a deleterious effect on the nutritional status of these patients because correlation of serum total carbon dioxide level with nutritional parameters, such as serum creatinine and serum albumin levels, was either negative or not statistically significant. Further investigation of the effect of modifying serum bicarbonate concentration on nutritional markers is needed to test these hypotheses.

Acidosis↗
PubMed1998

Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2.

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.

Adolescent↗
PubMed1997

Impaired delivery of hemodialysis prescriptions: an analysis of causes and an approach to evaluation.

Serial kinetic modeling is commonly used in hemodialysis to assess the adequacy of dialysis. A variety of problems lead to declining Kt/V in previously stable patients. These include noncompliance, vascular access recirculation, and dialyzer dysfunction. The purpose of this study was to find the relative frequencies of these problems in a group of patients undergoing routine hemodialysis. Simultaneous urea kinetic modeling and access recirculation were tested during 3 consecutive months. The baseline Kt/V was defined as the average of each patient's Kt/V values obtained during the previous 4 mo. A clinically important fall in Kt/V was defined as a decline of > or =0.2 if the baseline Kt/V was > or =1.2, or a decline of > or =0.1 if the baseline Kt/V was <1.2. Ninety-three of 375 (25%) sessions met the criteria for a significant decline in urea kinetic modeling. The baseline Kt/V in this group was 1.33 +/- 0.20 (mean +/- SEM) and declined to 1.02 +/- 0.18 in the abnormal month (P < 0.05). In 42% of instances with a decline of Kt/V, reduced blood processing due to a lower blood flow or shorter time than prescribed was responsible. Recirculation of >12% was found in 25% of sessions with a decrease in Kt/V. These patients most often had access dysfunction or reversed needles. The remaining one-third of patients with decreases in Kt/V had no problem identified, and subsequent monthly kinetic modeling results returned to baseline. These results suggest that analysis of falling urea kinetic modeling results should include a careful review of the dialysis record for reductions in prescribed time or blood flow rates followed by vascular access testing. If these evaluations are unrevealing, urea kinetic modeling results usually return to baseline in the next month.

Adult↗
PubMed1995

Kinetics of monocyte 1 alpha-hydroxylase in renal failure.

In chronic uremia, the requirement of supraphysiological doses of serum 25-hydroxyvitamin D3 [25(OH)D3] for the normalization of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels has been attributed to impaired substrate availability to renal 1 alpha-hydroxylase. Because serum 1,25(OH)2D3 can also be corrected by 25(OH)D3 supplementation in bilaterally nephrectomized patients, we examined the role of substrate availability on 1,25(OH)2D3 production by peripheral blood monocytes (PBM). In hemodialysis patients (HP), 25(OH)D3 uptake was 50% lower than normal, and the maximal velocity (Vmax) and apparent Michaelis constant (Km) for 25(OH)D3 of 1 alpha-hydroxylase were 2.7- and 4-fold above normal, respectively. When serum 1,25(OH)2D3 of HP was corrected by intravenous 1,25(OH)2D3, 25(OH)D3 uptake, Km, and Vmax returned to normal values. The effect of 25(OH)D3 supplementation was also examined. In normal adults, 25(OH)D3 administration had no effect on serum 1,25(OH)2D3 levels nor on the Km or the Vmax of PBM 1 alpha-hydroxylase but caused a 11-fold increase in serum 24R,25-dihydroxyvitamin D3[24R, 25(OH)2D3]. In HP, 25(OH)D3 therapy raised serum 1,25(OH)2D3 and reduced the Km and Vmax of PBM 1 alpha-hydroxylase, which correlated negatively with serum 1,25(OH)2D3. However, serum 24R,25(OH)2D3 only increased slightly above basal. These results demonstrate that, in HP, 1) impaired uptake of 25(OH)D3 and low affinity for substrate determine the need for high 25(OH)D3 levels to normalize serum 1,25(OH)2D3, despite higher enzymatic activity; 2) 1,25(OH)2D3 deficiency plays a role in enhanced 1,25(OH)2D3 synthesis and impaired access of 25(OH)D3 to PBM 1 alpha hydroxylase; and 3) abnormal 25(OH)D3 delivery also affects 24-hydroxylation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1995

Physiologic mechanisms of action of lovastatin in nephrotic syndrome.

The effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the metabolism of apolipoprotein (apo) B-containing lipoproteins appear to differ according to the predominant lipoprotein profiles present and the condition being treated. In familial hypercholesterolemia, with isolated low density lipoprotein (LDL) elevations, the LDL-apoB elimination rate is increased by up-regulated LDL-receptors. In familial combined hyperlipidemia where very low density lipoprotein (VLDL) and LDL both may be increased and enhanced production of LDL-apoB may be present, HMG-CoA reductase inhibitors seem to diminish increased LDL-apoB production. The drug-induced decreases in LDL-apoB production could be due to decreased production of precursor VLDL-apoB or due to decreased conversion of VLDL-apoB to LDL-apoB after enhanced removal of VLDL by up-regulated LDL-receptors. To distinguish between these possibilities, we assessed the effects of HMG-CoA reductase inhibitors in another condition in which there is both apoB overproduction and accumulation of VLDL and LDL in plasma, the nephrotic syndrome. We used endogenous labeling of apoB with [13C]leucine and a multicompartmental model to calculate the metabolic parameters of apoB-containing lipoproteins. Only subjects with focal segmental glomerular sclerosis (FSGS) were included, as FSGS is a chronic, very slowly progressive form of nephrotic syndrome. A double-blind, randomized, placebo-controlled, crossover design was used. Treatment periods of 6 weeks were separated by a 2-week washout period. Of the four men studied, three had high triglyceride levels and four had high cholesterol levels. Lovastatin (20 mg/day) significantly decreased cholesterol (27.6 +/- 6%), LDL-cholesterol (27.6 +/- 9%) and plasma apoB (17.9 +/- 2.9%) (P < 0.01 for all). During the placebo period, calculation of kinetic parameters revealed VLDL-, intermediate density lipoprotein (IDL)-, and LDL-apoB overproduction and decreased VLDL-apoB fractional catabolic rate. Lovastatin significantly decreased LDL-apoB production rate in all cases (34.1 +/- 14%, P = 0.03). The decreased LDL-apoB was mainly due to a channelling of LDL precursors away from conversion to LDL (conversion of VLDL to LDL decreased from 80.6 +/- 8.3% to 55.9 +/- 17.2%, P = 0.05). Thus, lovastatin decreased LDL-cholesterol in nephrotic subjects mainly by inhibiting LDL-apoB production from VLDL.

Apolipoproteins↗
PubMed1991

Extrarenal production of calcitriol in normal and uremic humans.

We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3. The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3. In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism. Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects. These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1990

Extrarenal production of calcitriol.

Under normal circumstances extrarenal sources of calcitriol probably constitutes a microendocrine system involved in cell differentiation and local intercellular communication with no influence on systemic calcium homeostasis. Under pathological conditions such as chronic renal failure, extrarenal sources have the potential to normalize serum calcitriol after adequate stimulation (such as, 25(OH)D administration). Extrarenal 1,25-(OH)2D3 synthesis is controlled by physiological levels of calcitriol. However, in sarcoidosis and other granulomatous diseases, 1,25-(OH)2D3 production by macrophages is deregulated, causing severe alterations in systemic calcium homeostasis.

Animals↗
PubMed1989

Accelerated removal of deferoxamine mesylate-chelated aluminum by charcoal hemoperfusion in hemodialysis patients.

Although deferoxamine mesylate (DFO) is effective in removing aluminum (Al) in hemodialysis patients, treatment with this drug is associated with a number of adverse effects. In order to limit the exposure of patients to DFO-Al complexes, the efficacy of colloidin-coated microencapsulated charcoal cartridges added in series to conventional dialyzers was investigated. The clearances of Al by the sorbent system were initially 116 +/- 4.7 mL/min, but decreased to 42.5 +/- 6.6 mL/min after 120 minutes of treatment. Thereafter, the Al clearances remained constant. In contrast, the Al clearances of the dialyzer were 29.5 +/- 1.8 mL/min initially and did not change during the treatment period. Both the percent and absolute decrease in Al levels after four hours of dialysis were greater with the dialyzers plus carbon cartridges than with the dialyzers alone. This resulted in an increase in the minimum net Al removal from 1,862 +/- 174 micrograms/treatment to 3,007 +/- 43 micrograms/treatment (P less than 0.05). Treatment with sorbent hemoperfusion should be considered in selected hemodialysis patients being treated with DFO for Al overload.

Aluminum↗
PubMed1989

Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism.

Many investigators have shown that calcium carbonate (CaCO3) is an effective phosphate binder which also prevents the potential disabling effects of aluminum (Al) accumulation. However, hypercalcemia may develop in a substantial numbers of patients. Thus, to control serum phosphate (PO4) and prevent hypercalcemia, we performed studies in 21 patients on maintenance hemodialysis in which, in addition to the oral administration of CaCO3, the concentration of calcium (Ca) in the dialysate was reduced from 3.25 to 2.5 mEq/liter. The studies were divided in three periods: I. control, on Al-binders (one month); II. no Al-binders (one month); III. CaCO3 (seven months). Blood was obtained three times/week before dialysis for the first five months of the study and once a week for the remaining four months. During the control period, the mean serum calcium was 8.86 +/- 0.08 mg/dl. The value decreased to 8.65 +/- 0.07 mg/dl when phosphate binders containing aluminum were discontinued, and increased to 9.19 +/- 0.07 mg/dl (P less than 0.001 compared to period II) during oral supplementation with calcium carbonate. The mean serum phosphorus was 5.03 +/- 0.07 mg/dl during the control period, and increased to 7.29 +/- 0.91 mg/dl (P less than 0.001) after phosphate binders were discontinued. It decreased to 4.95 +/- 0.06 mg/dl (P less than 0.001) with the administration of calcium carbonate. During CaCO3 administration, serum Al decreased from 64.2 +/- 8.5 to 37.1 +/- 3.6 and 25.1 +/- 3.0 micrograms/liter (P less than 0.001) at three and seven months, respectively. Serum parathyroid hormone (PTH) decreased by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis.

Phosphate binders that contain aluminum are frequently prescribed to treat hyperphosphatemia in patients with chronic renal failure, but an accumulation of aluminum can lead to osteomalacia. To evaluate the efficacy of calcium carbonate as an alternative phosphate binder, we studied 20 patients maintained on dialysis during three consecutive periods. In period 1, the patients took aluminum hydroxide for a month (mean dose, 5.6 g per day; range, 1.5 to 14.0). In period 2, they took no phosphate binders for a month, and in period 3, they took calcium carbonate (Os-Cal) for two months (mean dose, 8.5 g per day; range, 2.5 to 17). The mean (+/- SE) serum calcium level during period 1 was 9.6 +/- 0.2 mg per deciliter; this decreased slightly (to 9.3 +/- 0.1) during period 2 and increased to 10.0 +/- 0.2 during period 3. The mean (+/- SE) serum phosphorus level during period 1 was 4.8 +/- 0.1 mg per deciliter; this increased to 7.3 +/- 0.3 during period 2, but returned to the control value (4.8 +/- 0.2) during period 3. Six of the 20 patients continued to need aluminum hydroxide during period 3 for satisfactory control of hyperphosphatemia. Calcium carbonate successfully lowered serum phosphorus levels and raised serum calcium levels in the majority of our patients, thereby confirming that this agent may be a satisfactory substitute for traditional phosphate binders that contain aluminum. The possibility that long-term treatment could cause such side effects as metastatic calcification will require further investigation.

Adult↗
PubMed1986

Alternative phosphate binders in dialysis patients: calcium carbonate.

Traditionally, phosphate binders containing aluminum have been used effectively to control serum phosphorus levels in patients with chronic renal failure. In these patients, however, absorption and accumulation of aluminum in plasma and tissues can lead to debilitating pathologic conditions, including aluminum-related osteodystrophy. An alternative therapeutic approach using calcium carbonate as a phosphate binder has been proven to be effective. In a recent study of 20 patients on chronic hemodialysis, the efficacy of calcium carbonate therapy was demonstrated. Serum phosphorus levels in these patients were 4.8 +/- 0.13 mg/dL with the use of aluminum-containing phosphate binders, 7.3 +/- 0.26 mg/dL when phosphate binders were discontinued, and 4.8 +/- 0.17 mg/dL with the use of calcium carbonate (Os-CaL 500) therapy. The total amount of aluminum ingested for all 20 patients combined went from 112 g/d at the beginning of the study to 22 g/d at the end of the study. The amounts of calcium carbonate administered varied because of large variations in dietary phosphorus intake between patients. In addition, the individual distribution of phosphorus intake during the day dictated the dosing schedule. There were no adverse side effects associated with calcium carbonate therapy. A few patients ingesting large amounts of calcium carbonate to control their extremely high phosphorus levels developed hypercalcemia. However, this effect was reversible after discontinuation of calcium carbonate therapy.

Aluminum↗
PubMed1984

Cardiovascular and metabolic responses to submaximal exercise in hemodialysis patients.

Eight chronic hemodialysis (cHD) patients and six healthy sedentary controls (C) were exercised for 60 minutes at 52 +/- 8% (cHD patients) and 48 +/- 4% (C) of their maximal oxygen consumption levels. Plasma lactate levels at rest and during exercise were comparable in both groups. Respiratory exchange ratios were lower in cHD patients, but they increased during exercise to levels comparable to those of the C group. Despite comparable heart rates at rest, exercise of similar intensity led to lower heart rates at 30 and 60 minutes in cHD patients compared to C (P less than 0.05). The cHD patients had higher systolic and mean arterial pressures at rest than did C (P less than 0.05), but during exercise the increments in systolic and mean blood pressures were lower in cHD patients than they were in C (P less than 0.05). In spite of these blunted cardiovascular responses, plasma catecholamines increased during exercise in both groups. Plasma glucose levels were similar in both groups during exercise in spite of significantly higher plasma levels of insulin and glucagon in cHD patients throughout the exercise session (P less than 0.01). These data demonstrate that chronic cHD patients can exercise at a modest intensity for a prolonged period of time without untoward cardiovascular or metabolic responses. Their poor exercise response does not appear to be related to an inadequate activation of the sympathoadrenal system.

Adult↗
PubMed1980

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.

Adult↗
PubMed1976

Effects of carbohydrate restriction on the hypoglycemic phase of the glucose tolerance test.

The effects of carbohydrate (CHO) restriction on the hypoglycemic phase of the glucose tolerance test were studied in ten normal subjects. The mean nadir plasma glucose was 64 +/- 4 mg/dl (x +/- SEM) for the control test, and 48 +/- 4 mg/dl (P less than 0.01) after 3 days of an isocaloric low CHO diet. Following the low CHO diet, six of ten subjects had a nadir plasma glucose less than 50 mg/dl, and five of these six had mild symptoms of hypoglycemia compared to no biochemical or symptomatic hypoglycemia during the control test. Hormone secretory patterns under the two experimental conditions were measured. CHO restriction produced a significant decrease in early insulin release followed by excessive insulin relative to the control test at 3-4 h of the test. Glucose ingestion produced a depression of plasma, glucagon from fasting levels during the control test, which was impaired following CHO restriction. Plasma growth hormone and cortisol responses were not different under the two experimental conditions. These studies demonstrate that CHO restriction followed by concentrated CHO ingestion produces hypoglycemia in normals. They emphasize the need to consider dietary history in evaluation of hypoglycemia. CHO restriction may provide a useful model for further study of the mechanisms of hypoglycemia.

Adult↗