Niacin deficiency in rats increases the severity of ethylnitrosourea-induced anemia and leukopenia.

Many chemotherapeutic agents function by damaging the DNA of rapidly dividing cells, leading to side effects in the bone marrow, including anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We have created an animal model of alkylation-based chemotherapy, in nontumor-bearing rats, to investigate the effect of niacin deficiency on the side effects of chemotherapy [2 x 2 design, niacin-deficient (ND) vs. pair-fed (PF) control, and ethylnitrosourea (ENU) vs. vehicle control (C)]. Weanling Long-Evans rats were fed ND diet or PF niacin replete diet for 4 wk. ENU or C treatment started after 1 wk of feeding and consisted of 12 doses delivered by gavage, every other day. At 4 wk postweaning, niacin deficiency and ENU treatment ended, the rats were fed a high-quality control diet (AIN-93M) and the recovery of blood variables was monitored. ND alone decreased growth rate and caused anemia and neutrophilia. ENU treatment alone caused anemia, lymphopenia, neutropenia and an increase in circulating reticulocytes. In combination, ND and ENU treatment synergistically decreased hematocrit. ND prevented the ENU-induced increase in reticulocyte numbers observed in control rats. ND also increased the severity of ENU-induced lymphopenia. A combination of ND and ENU abolished the neutrophilia caused by ND alone. In summary, ND significantly increased the susceptibility of young Long-Evans rats to ENU-induced bone marrow suppression, suggesting that niacin-deficient cancer patients may benefit from supplementation.

Effects of ascorbic acid and pyridoxine supplementation on oxalate metabolism in peritoneal dialysis patients.

We studied the effect of vitamin C and B6 supplementation on oxalate metabolism in seven patients receiving chronic peritoneal dialysis therapy. The study was divided into three phases, each lasting 4 weeks. Plasma oxalate, total ascorbic acid, and pyridoxal-5'-phosphate (PLP) were measured at the end of each phase. Twenty-four-hour urinary excretion and dialysate removal rates of oxalate were also obtained. At the end of phase I (supplement-free period), plasma oxalate levels were markedly elevated at 47.6 +/- 7.1 mumol/L (437 +/- 66 micrograms/dL) (normal, 3.4 +/- 0.4 mumol/L [30.3 +/- 1.6 micrograms/dL]). Plasma total ascorbic acid levels were 62 +/- 6 mumol/L (1.0 +/- 0.1 mg/dL) (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]), while plasma PLP levels were markedly reduced to 24 +/- 5 nmol/L (normal, 40 to 80 nmol/L). Daily supplements of 0.57 mmol (100 mg) ascorbic acid orally (phase II) resulted in a 19% increase in the plasma oxalate levels to 57.8 +/- 6.1 mumol/L (520 +/- 55 micrograms/dL) (P less than 0.03), with a concomitant 60% increase in the plasma ascorbate levels (91 +/- 6 mumol/L [1.6 +/- 0.1 mg/dL], P less than 0.01). Plasma PLP values remained low. Finally, during phase III (0.57 mmol or 100 mg ascorbic acid plus 59.6 mumol or 10 mg pyridoxine HCI orally daily), plasma oxalate levels declined by 17% to 47.9 +/- 5.2 mumol/L (431 +/- 47 micrograms/dL) (P greater than 0.05 v phase II).(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic acid supplements in patients receiving chronic peritoneal dialysis.

Ascorbic acid supplements are commonly prescribed to patients with end-stage renal disease receiving peritoneal dialysis. To establish the need for ascorbic acid supplements, we evaluated seven chronic peritoneal dialysis patients during a supplement-free (phase I) period, and while receiving oral ascorbic acid (0.57 mmol/d [100 mg/d]) (phase II). Because of a proposed interaction with vitamin B6, patients were additionally supplemented with pyridoxine HCl (59.6 mumol/d [10 mg/d]) (phase III). Plasma levels and dialysate removal rates of total ascorbic acid and plasma pyridoxal-5-phosphate (PLP) were measured at the end of each phase. During phase I, plasma ascorbic acid levels (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]) declined slightly from 74 +/- 11 mumol/L (1.3 +/- 0.2 mg/dL) to 62 +/- 11 mumol/L (1.1 +/- 0.2 mg/dL) (P less than 0.02) at the end of the third week, and then remained stable to the end of the fourth week. Plasma ascorbic acid levels were no different in patients with or without residual renal function. With the addition of vitamin C supplements, plasma ascorbic acid levels increased by 45% of the baseline value at the end of phases II (P less than 0.001). The dialysate removal rate of ascorbic acid was 0.28 +/- 0.03 mmol/d (50 +/- 6 mg/d) at the end of phase I, and increased by 57% of the baseline value at the end of phases II (P less than 0.001). However, the peritoneal clearance of ascorbic acid remained unchanged during all phases the study. Pyridoxine depletion or repletion had no effect on plasma ascorbic acid levels (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin B6 requirements of patients on chronic peritoneal dialysis.

Patients with chronic renal failure often develop vitamin B6 deficiency, which is of clinical concern because the multiorgan system manifestations are similar to those of uremia. Vitamin B6 deficiency in hemodialysis patients has been previously studied, but the need for daily pyridoxine supplementation in patients on chronic peritoneal dialysis (CPD) remains unclear. Therefore, we studied a group of 11 stable patients, nine on CAPD and two CCPD, to test for vitamin B6 deficiency and to establish daily requirements. Adequacy of vitamin B6 nutrition was assessed by measurement of plasma and dialysate effluent total vitamin B6 and pyridoxal 5'-phosphate (PLP), the latter using a very sensitive modification of the tyrosine apodecarboxylase enzyme assay. After four weeks without vitamin B6 supplements on a diet containing 1.3 +/- 0.2 mg vitamin B6/day (7.7 +/- 1.2 mumol/day), all patients had subnormal plasma PLP levels, 16 +/- 3 nmol/liter (nml 40 to 60), seven having a severe deficiency (less than or equal to 20 nmol/liter). Plasma total vitamin B6 levels (which includes non-PLP forms of the vitamin) were normal in all patients at baseline, 116 +/- 29 nmol/liter. Peritoneal losses were small, 8 +/- 2 nmol PLP/day and 545 +/- 61 nmol total vitamin B6/day. Supplementation with 5 mg/day oral pyrodoxine HCl for up to 16 weeks adequately repleted eight patients (65 +/- 7 nmol PLP/L), while three patients required 10 mg/day to achieve normal plasma PLP levels. During three episodes of peritonitis, dialysate losses of PLP did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a magnesium-free dialysate on magnesium metabolism during continuous ambulatory peritoneal dialysis.

While the use of magnesium-containing compounds is usually contraindicated in dialysis patients, the risk of toxicity from hypermagnesemia can be reduced by lowering the magnesium concentration in dialysate. We examined the effects of a magnesium-free dialysate on both serum magnesium level and the peritoneal removal rate of magnesium over 12 weeks in 25 stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). After 2 weeks, the serum magnesium level decreased from 2.2 to 1.9 mg/dL (0.9 to 0.8 mmol/L) (P less than .02) and the peritoneal removal rate increased from 66 to 83 mg/d (2.8 to 3.5 mmol/d) (P less than .05), with both values remaining stable thereafter. There was a strong association between these parameters (r = -0.62, P less than .05), suggesting that the serum magnesium level decreased as a result of the initial increased peritoneal removal rate. For an additional 4-week period, a subgroup of nine patients received magnesium-containing, phosphate binding agents instead of those containing only aluminum. During this phase, serum inorganic phosphorus was well controlled. The serum magnesium level increased only from 1.8 to 2.5 mg/dL (0.7 to 1.0 mmol/L) (P less than .05), due in great part to the concomitant 41% rise in peritoneal magnesium removal from 91 to 128 mg/d (3.8 to 5.3 mmol/d) (P less than .05). No toxicity was noted during the entire 16-week study period, nor did serum calcium change. Thus, serum magnesium levels remained within an acceptable range as magnesium-containing phosphate binders were given through the use of magnesium-free peritoneal dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)