Increased nitric oxide production in hypotensive hemodialysis patients.

A subset of patients on long-term hemodialysis have sustained hypotension, defined as a predialysis systolic pressure of < 100 mmHg. To determine the role of nitric oxide (NO), an important vasodilator, in this condition, the authors measured the plasma levels of nitrite (NO2-) and nitrate (NO3-), the known NO metabolites taken as an index of NO production, in 10 hypotensive patients on long-term hemodialysis. None of them had diabetes, cirrhosis of the liver, congestive heart failure, or infection. Fifteen age and gender-matched normotensive patients on hemodialysis were selected as control subjects. Measurements of plasma levels of nitrite and nitrate based on the Greiss reaction were made. There was no significant difference in hematocrit, serum intact parathyroid hormone, total calcium, inorganic phosphorus, albumin, heart rate, cardiac index, or interdialysis weight gain between these two groups. Plasma nitrite and nitrate levels did not correlate with either predialysis serum creatinine or blood urea nitrogen. The mean arterial pressure (MAP) was significantly lower and plasma nitrite and nitrate levels were significantly higher in chronic hypotensive patients than in normotensive patients (MAP: 68.30 +/- 3.24 mmHg vs 95.20 +/- 2.44 mmHg, p < 0.001; plasma nitrite and nitrate: 72.49 +/- 14.41 mumol/L vs 36.42 +/- 5.45 mumol/L, p < 0.05). In addition, MAP from hypotensive and normotensive patients on hemodialysis was inversely correlated with plasma levels of nitrite and nitrate (r = -0.54, p < 0.01). It was concluded that enhanced NO production in this subset of patients on hemodialysis may contribute to their chronic hypotension.

Infective endocarditis complicated with rapidly progressive glomerulonephritis: a case report.

A 26-year-old man who had suffered from intermittent chills and fever over a two month period was quite clear of heart or kidney involved developed acute deterioration of renal function. A new pansystolic murmur over the apex of the heart was heard on auscultation, and echocardiography clearly showed a vegetation about 0.7-0.9 cm in size on the atrial site of the mitral value. Laboratory investigation displayed normochromic anemia with negative Coombs' test. Immunological studies were positive for rheumatoid factor and circulating immune complex. High serum levels of erythrocyte sedimentation rate and C-reactive protein, nephritic sediment of urinalysis and negative blood cultures for bacteria, tuberculosis or fungus were also noted. Abdominal sonography showed normal kidney size, bilaterally. Renal biopsy revealed typical crescentic glomerulonephritis. After intravenous penicillin therapy for two weeks, the serum creatinine level recovered from 6.7 mg/dl to 2.0 mg/dl and circulating immune complex disappeared. In consideration of cardiac insufficiency and the potential risk for complications of the vegetation, the patient underwent mitral valve replacement. Four weeks after operation, all the abnormal data had resolved completely. These data suggested that infective endocarditis with rapidly progressive glomerulonephritis is curable by antibiotic therapy and surgical intervention.

Effects of intravenous calcitriol on lipid profiles and glucose tolerance in uraemic patients with secondary hyperparathyroidism.

1. Secondary hyperparathyroidism in chronic renal failure may contribute to abnormalities of lipid metabolism and glucose tolerance. Amelioration of secondary hyperparathyroidism has been reported to mitigate the hyperlipidaemia and improve glucose tolerance experimentally. 2. The effect of the partial suppression of hyperparathyroidism by intravenous calcitriol on lipid levels and glucose tolerance was studied in 15 haemodialysis patients with secondary hyperparathyroidism. All received intravenous calcitriol 1 microgram at the end of haemodialysis thrice weekly for eight weeks. Oral glucose tolerance test and plasma lipid profiles including triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoprotein A-I and apoprotein B were determined simultaneously before and after eight weeks of therapy. 3. Before calcitriol treatment, uraemic patients with secondary hyperparathyroidism displayed a significant higher triglyceride and a significant lower HDL-C and apoprotein A-I as well as marked glucose intolerance with an increment of the area below the glucose curve when compared with healthy control subjects. 4. After eight weeks of calcitriol treatment, there was a significant decrement in serum intact parathyroid hormone (476.45 +/- 48.33 versus 191.37 +/- 30.17 ng/l, P < 0.001) and plasma triglyceride (2.24 +/- 0.34 versus 1.80 +/- 0.29 mmol/l, P < 0.05) as well as a significant increment of plasma apoprotein A-I (38.13 +/- 2.14 versus 44.19 +/- 2.18 mumol/l, P < 0.05), whereas there was no significant change in serum total cholesterol, LDL-C, HDL-C, and apoprotein B.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous calcitriol on platelet intracellular calcium in uremic hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: To investigate the effect of the reversal of hyperparathyroidism on platelet intracellular free calcium ([Ca2+]i) by pharmacological parathyroidectomy with intravenous calcitriol in uremic patients with secondary hyperparathyroidism (2 degrees HPT). METHODS: Serum concentrations of intact parathyroid hormone (I-PTH) were measured by two-site immunometric assay, and platelet [Ca2+]i was assessed using the fluorescent indicator fura-2. Fifteen hemodialysis patients with 2 degrees HPT and serum I-PTH 4 times greater than the normal upper limits, were selected for treatment with intravenous calcitriol 1 microgram thrice weekly for one month. RESULTS: An increase of serum I-PTH (449.17 +/- 52.35 vs 32.52 +/- 1.95 pg/ml) and elevated platelet [Ca2+]i (139.49 +/- 8.78 vs 74.70 +/- 6.48 nM/L) was observed in uremic patients with 2 degrees HPT. Serum I-PTH levels were significantly correlated with platelet [Ca2+]i in uremic patients with 2 degrees HPT (r = 0.736, p = 0.002). The serum I-PTH levels decreased from 449.17 +/- 52.35 to 221.27 +/- 35.66 pg/ml (p < 0.001) and platelet [Ca2+]i fell from 139.49 +/- 8.78 to 97.86 +/- 7.25 nM/L (p < 0.001) after treatment. Fall in platelet [Ca2+]i was related to concomitant reduction in PTH levels (r = 0.572, p = 0.026). CONCLUSIONS: It was concluded that an increase in cytosolic calcium in uremia may be at least in part induced by PTH. Besides, intravenous calcitriol can provide an effective way to suppress elevated serum I-PTH and attenuate platelet free calcium in uremia with 2 degrees HPT.

Influence of rapid correction of metabolic acidosis on serum osteocalcin level in chronic renal failure.

Metabolic acidosis induces a combination of inhibited osteoblastic and stimulated osteoclastic activity. To determine the role of alkali therapy in osteoblast function in chronic renal failure, serum bone isoenzyme of alkaline phosphatase (BAP) and osteocalcin were assessed before and after bicarbonate infusion. Eighteen patients with mild to moderate metabolic acidosis, none of whom had received dialysis therapy, were enrolled in this study. Metabolic acidosis was corrected by continuous bicarbonate infusion while plasma ionized calcium was monitored at 5 min intervals and held at the preinfusion level by calcium solution infusion during the entire procedure. The end-point of the study was reached when the plasma bicarbonate was approximately 24 mmol/l or pH was approximately 7.4 and plasma ionized calcium was clamped at the preinfusion level with only a 0.01 mmol/l fluctuation. The plasma pH (7.31 +/- 0.04 vs. 7.40 +/- 0.03, P < 0.001), bicarbonate (18.46 +/- 2.49 vs. 23.66 +/- 2.72 mmol/l, P < 0.001), serum total calcium, and osteocalcin (15.61 +/- 6.45 vs. 18.79 +/- 6.71 mg/l, P < 0.05) levels were significantly increased, whereas serum concentrations of alkaline phosphatase and albumin levels were significantly decreased after bicarbonate infusion. The serum BAP (1.85 +/- 1.29 vs. 1.79 +/- 1.18 mukat/l, P = 0.252), and inorganic phosphorus levels showed no significant differences before and after bicarbonate infusion. These results demonstrate that rapid correction of metabolic acidosis improves osteoblast function and may underline the importance of maintaining normal acid-base homeostasis in chronic renal failure.

Hyperparathyroidism, glucose tolerance and platelet intracellular free calcium in chronic renal failure.

Disturbance in the vitamin D/parathyroid hormone (PTH) axis may be important in the pathogenesis of glucose intolerance and insulin resistance in uraemia. To investigate possible relationships between hyperparathyroidism, intracellular free calcium ([Ca2+]i), and glucose tolerance in chronic renal failure, we measured serum intact PTH (I-PTH) by two-site immunometric assay, platelet [Ca2+]i using the fluorescent indicator fura-2, and plasma glucose and insulin after 14 h overnight fast and at 30, 60 and 120 min following a 75 g oral glucose load, in 18 chronic haemodialysis patients with elevated serum I-PTH. Calcitriol (1 microgram) was administered parenterally at the end of each dialysis session for four weeks. This significantly decreased serum I-PTH (p < 0.001) and platelet [Ca2+]i (p < 0.01). Uraemic patients initially showed marked glucose intolerance, with increased area below the glucose curve compared to healthy controls, but after 4 weeks of calcitriol treatment, this effect was significantly decreased, and there was a significant rise in the area under the insulin curve after glucose load. The insulinogenic index also increased significantly after calcitriol treatment. These data suggest that calcitriol treatment of haemodialysis patient with secondary hyperparathyroidism is associated with increased insulin secretion in response to glucose challenge, and that this change is linked to the decrease in intracellular free calcium.

Role of plasma catecholamines, autonomic, and left ventricular function in normotensive and hypotension prone dialysis patients.

The current study looked at plasma catecholamines, clinical autonomic function tests, and hemodynamic parameters in 10 ESRD patients (five men and five woman, aged 56.4 +/- 3.6) with dialysis hypotension and 10 patients (five men and five women, aged 58.6 +/- 4.2) without dialysis hypotension. Catecholamines were measured using high performance liquid chromatography--electrochemical detection (HPLC-ECD). Dialysis led to a significant decrease in mean arterial pressure (MAP) in the hypotensive group as compared with the normotensive group. Significantly higher basal (predialysis) plasma norepinephrine (NE) and dopamine levels (DA) were found in the hypotensive uremic group as compared with the normotensive group. Levels of plasma epinephrine (EP) were not significantly different between the normotensive and hypotensive groups. In response to postural stimulation, blood pressure fell in both groups, but the fall in the hypotensive group was significantly greater. Percentage increments of plasma catecholamines in response to postural stimulation in both groups were similar, however. Among the measured hemodynamic parameters, including total peripheral vascular resistance and left ventricular function (cardiac index and fractional shortening), only the cardiac index showed significantly lower values in the hypotensive group after dialysis, as compared with the normotensive group. Results of four tests of autonomic function indicated that although both groups responded similarly to hand-grip and cold-pressor tests, impaired responses to orthostasis and Valsalva maneuver after dialysis were observed in the hypotensive group. The MAP changes in dialysis in the hypotension prone group correlated inversely with predialysis plasma NE, but not with EP and DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum osteocalcin and vitamin D in postmenopausal diabetic azotemics.

To clarify the role of serum vitamin D and bone remodeling markers in postmenopausal diabetic azotemics, we designed a study involving 3 different postmenopausal patient groups. Group I consisted of 20 diabetic women with renal insufficiency who were not yet on dialysis therapy. Group II consisted of 15 age-matched nondiabetic women with comparable degrees of renal insufficiency. Group III consisted of 20 age-matched women with normal renal function. We investigated the overnight fasting serum 25 (OH) vit-D, 1,25(OH)2 vit-D3, osteocalcin (OC), bone isoenzyme of alkaline phosphatase (ALK-PB) and intact parathyroid hormone (I-PTH) levels in these cases. The serum I-PTH and OC levels were statistically significantly higher, whereas 1,25(OH)2vit-D3 were significantly lower in Group I and Group II patients than in Group III patients. We found no significant correlation between elevation of I-PTH and reduced 1,25(OH)2 vit-D3 levels in Group I and Group II patients. I-PTH levels correlated positively with OC in Group I and Group II patients. There was no significant difference in serum 25(OH) vit-D among these 3 groups of patients. We conclude that (1) serum OC level may serve as a good parameter in evaluating secondary hyperparathyroidism in postmenopausal azotemics with or without diabetes, (2) even in the presence of menopause, renal failure per se is the main factor in determining serum 1,25(OH)2 vit-D3 levels in diabetic azotemics.

Role of creatine phosphokinase in predicting acute renal failure in hypocalcemic exertional heat stroke.

Recruits frequently develop hypocalcemia in exertional heat stroke (ExHS) with rhabdomyolysis and acute renal failure (ARF) from intensive training. It usually indicated severe skeletal muscle damage. However, the relative risk of ARF in ExHS patients complicated with hypocalcemia was unknown. The present study was undertaken to evaluate the value of peak serum creatine phosphokinase (CPK) level in predicting ARF in ExHS patients with hypocalcemia. Sixty-eight army recruits with ExHS were hospitalized at the Tri-Service General Hospital, Taiwan: 17 with ARF and hypocalcemia (group A); 7 with ARF but without hypocalcemia (group B); 20 without ARF but with hypocalcemia (group C); and 24 without ARF or hypocalcemia (group D). In the 24 patients with ARF (groups A and B) the serum phosphate and peak CPK levels were significantly higher than in patients without ARF (groups C and D; p < 0.001), serum calcium levels were also significantly lower in the former (p < 0.001). In the 37 patients with hypocalcemia (groups A and C), the peak serum CPK levels were significantly higher than in those without hypocalcemia (groups B and D; p < 0.001). There was a higher proportion of hypocalcemic patients with peak serum CPK levels greater than 10,000 U/l among ARF compared with patients without ARF (chi 2 = 12.48, p < 0.001). In 24 patients with ARF, there was a negative correlation between serum Ca and peak CPK levels (t = 3.37, r = -0.58, p < 0.01). However, a positive correlation was found between serum creatinine and peak serum CPK levels in 37 patients with hypocalcemia (t = 2.47, r = 0.39, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)