Effect of daily hemodialysis on monocytes apoptosis.

Uremia is associated with a state of immune dysfunction with increased susceptibility to infection and malignancy possibly related to dysregulation of immune system cell apoptosis. Peritoneal dialysis can restore plasma apoptosis activity on monocytes compared to intermittent hemodialysis. Whether the continuous modality or diverse clearance mechanisms involved are responsible is unknown. Apoptosis rates correlate with phagocytic function highlighting the benefit of efficient toxin clearance. The plasma of 16 patients on daily hemodialysis (D-HD) was incubated with U937 monocytes and compared to 18 hemodialysis (HD) patients, 5 chronic renal failure (CRF) subjects and 5 healthy volunteers (controls). Apoptosis was evaluated by immunofluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V cytoflowmetry at 96 h. Plasma-induced U937 apoptosis (mean values) was significantly enhanced in D-HD (18.8 +/- 4.1), HD (19.67 +/- 5.5) and CRF patients (20.8 +/- 4.7) compared to controls (9.6 +/- 3.6; p < 0.05 for CRF vs. controls, HD vs. controls and D-HD vs. controls). No significant differences were observed between D-HD, HD and CRF sera on apoptosis rate, caspase-3 activity and phagocytic capacity of U937 monocytes. This study demonstrates that the plasma of various HD schedules was unable to reduce monocyte apoptosis induced by uremia.

Phosphate kinetics during different dialysis modalities.

BACKGROUND: An abnormal serum phosphate concentration is common in acute renal failure patients, with a reported incidence of 65-80%. Phosphate removal and kinetics during intermittent hemodialysis (IHD) have been investigated, but there is no information on its kinetics during slow low-efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT). METHODS: Eight IHD, 8 SLED, and 10 continuous venovenous hemofiltration (CVVH) patients with a residual renal clearance of <4.0 ml/min were studied during a single treatment to evaluate phosphate removal and kinetics. CVVH was studied the first 24 h after initiation. Dialysis/replacement fluid contained no phosphate. Kt/V, clearance of urea (Ku), inorganic phosphate (Kp) and solute removal was determined by direct dialysate quantification (DDQ). RESULTS: Kp recorded with the three techniques were: IHD, 126.9 +/- 18.4 ml/min; SLED, 58.0 +/- 15.8 ml/min, and CVVH, 31.5 +/- 6.0 ml/min. However, in shorter dialysis treatment the total removal of phosphate was significantly lower than in longer dialysis (IHD, 29.9 +/- 7.7 mmol; SLED, 37.6 +/- 9.6 mmol; CVVH, 66.7 +/- 18.9 mmol, p = 0.001). The duration of treatment is the only factor determining phosphate removal (r = 0.7, p < 0.0001 by linear correlation model). Like IHD, phosphate kinetics during SLED could not be explained by the two-pool kinetic model, and the rebound of phosphate extended beyond 1 h after dialysis. Rebound, however, is less marked than in short dialysis. CONCLUSION: These results are reliable evidence about amount of phosphate removal and behavior of intradialytic phosphate kinetics in renal failure patients undergoing different dialysis modalities. These data will help clinicians plan phosphate supplementation and treatment intensity.

Uremic toxins: a new focus on an old subject.

The uremic syndrome is characterized by an accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin (EUTox) Work Group has listed 90 compounds considered to be uremic toxins. Sixty-eight have a molecular weight less than 500 Da, 12 exceed 12,000 Da, and 10 have a molecular weight between 500 and 12,000 Da. Twenty-five solutes (28%) are protein bound. The kinetics of urea removal is not representative of other molecules such as protein-bound solutes or the middle molecules, making Kt/V misleading. Clearances of urea, even in well-dialyzed patients, amount to only one-sixth of physiological clearance. In contrast to native kidney function, the removal of uremic toxins in dialysis is achieved by a one-step membrane-based process and is intermittent. The resulting sawtooth plasma concentrations of uremic toxins contrast with the continuous function of native kidneys, which provides constant solute clearances and mass removal rates. Our increasing knowledge of uremic toxins will help guide future treatment strategies to remove them.