N. K. Man

Kinetic modeling of plasma leucine levels during continuous venovenous extracorporeal removal therapy in neonates with maple syrup urine disease

A kinetic modeling of leucine plasma concentration changes is proposed to describe the plasma leucine reduction rate during continuous extracorporeal removal therapy (CECRT) in neonates with maple syrup urine disease. Data were obtained from seven neonates using a bicompartmental model for the best fitted curve of plasma leucine decrease during CECRT. During the first 3 h, leucine plasma levels decreased according to an exponential curve: [Leu]t = [Leu]i × 0.95 × 10-0.09t where [Leu]t is the leucine plasma level (μmol/L) at time t (h) during CECRT and [Leu]I is the initial plasma level. From h 4 to the end of CECRT, a second exponential curve was observed: [Leu]t = [Leu]i × 0.74 × 10-0.05t. Plasma leucine levels obtained from three other neonates were similar to those predicted by the model. The apparent distribution volumes for leucine that correspond to the two exponential equations obtained were calculated from the leucine mass removal collected in the spent dialysate and ultrafiltrate. The distribution volume was 34 ± 3% of body weight during the first 3 h of CECRT and 72 ± 7% from h 4 to the end of CECRT. These figures are similar to known values for the extracellular water compartment and for total body water in the newborn. The findings suggest that leucine handling during CECRT is similar to that of nonprotein-bound small-molecular-weight solutes such as urea.

Continuous venovenous hemodialysis in a neonate model : A two-pump system

OBJECTIVE To evaluate the efficiency and tolerance of venovenous hemofiltration, hemodiafiltration, and hemodialysis with a two-pump system in a neonatal animal model of acute renal failure. DESIGN Prospective trial. SETTING Animal laboratory at a large university-affiliated medical center. SUBJECTS New Zealand white rabbits, weighing 3325 +/- 380 g. INTERVENTIONS Venovenous hemofiltration, hemodiafiltration, and hemodialysis were performed in anesthetized rabbits with previous bilateral ureteral ligation. MEASUREMENTS AND MAIN RESULTS At a blood flow rate of 19 +/- 0.5 mL/min, we determined hematocrit, urea, creatinine, and electrolyte values in blood, at the inlet and outlet of the hemofilter, and in ultrafiltrate at the start and after 15, 30, 60, 90, 120, and 180 mins of hemofiltration (ultrafiltrate flow rate of 1.9 +/- 0.2 mL/min), hemodiafiltration (dialysate plus ultrafiltrate flow rate of 16.9 +/- 0.8 mL/min), and hemodialysis (dialysate flow rate of 15.7 +/- 1.1 mL/min). Arterial blood pressure, heart rate, and body temperature were monitored during the procedures. Urea and creatinine instantaneous clearances were higher with hemodiafiltration (8.0 +/- 0.7 and 6.2 +/- 0.7, respectively, n = 29) and hemodialysis (6.8 +/- 1.1 and 4.8 +/- 0.9, respectively, n = 31) than with hemofiltration (1.8 +/- 0.6 and 1.9 +/- 0.4, respectively, n = 16). Initial and final weights, temperatures, and hematocrit, sodium, and protein blood concentrations of each 180-min procedure were similar. CONCLUSIONS Hemodiafiltration had a higher urea removal rate than hemodialysis but the management of hemodiafiltration was more cumbersome and time consuming in the absence of a flow equalizer device. As a result, we recommend continuous venovenous hemodialysis as the therapy of choice.

Management of the Dialysis Patient

Managing patients on regular hemodialysis treatment comprises monitoring of the dialysis sessions to prevent intradialytic hazards, and regular long-term surveillance of the patient to prevent, or limit, clinical complications associated with uremia and/or bioincompatibility.

Evaluation of 3 hemo(dia)filtration methods in a neonatal acute renal failure animal model. 123

Evaluation of 3 hemo(dia)filtration methods in a neonatal acute renal failure animal model. 123

Causes and Consequences of End-Stage Renal Failure

The term “uremia” encompasses the sum of clinical and biochemichal disorders resulting from a severe reduction in kidney functions.Blood chemistry alterations develop early in the course of chronic renal failure and progressively increase in parallel to the reduction in active nephron mass. By contrast, overt clinical manifestations of uremic toxicity develop much later, at the very advanced stage of renal failure, usually when glomerular filtration rate (GFR) falls below 10 ml/min, i.e., ten times lower than normal.

Adequacy of Hemodialysis, Nutrition, and Dialysis Prescription

On a clinical basis, regular hemodialysis treatment may be considered adequate if the patient is in good general and nutritional condition, devoid of manifestations of uremic toxicity, and is fully rehabilitated. The main clinical criteria defining adequate dialysis are listed in Table 6-1. In the past decade, attempts have been made to define parameters predictive of dialysis adequacy, based on urea kinetic modeling, with mortality and morbidity as the main parameters to assess the therapeutic efficacy of longterm dialysis.

Outcome and Economics

Long survival and optimal quality of life afforded to the dialysis patient are the main concerns in maintenance hemodialysis.

Other Clinical Problems

Circulating levels of total T4 and T3 are usually low, but free T4 and T3 concentrations are normal, as are reverse T3 and TSH basal levels. Significant hypothyroidism is not a frequent event in uremic patients.

Cardiovascular and Neurological Problems

Cardiac and vascular disease is the major cause of morbidity and mortality in dialysis patients. Hypertension, lipid disturbances and uremic toxicity play a key role in the pathogenesis of cardiovascular disorders. Overall, cardiac complications account for 40% of deaths in dialysis patients and up to 50% when adding cerebrovascular accidents (Figure 8-1).

Bone and Joint Problems

Bone involvement, historically called renal osteodystrophy, develops to some extent in all patients with end-stage renal failure and persists or even worsens during hemodialysis therapy. Uremia-related disorders of calcium, phosphate and vitamin D metabolism result in secondary hyper parathyroidism characterized by osteitis fibrosa, a high turnover bone disease. Aluminum overload, a frequent hazard during the seventies, inhibits mineralization of the bone matrix at the origin of osteomalacia. In some cases aluminum seems able to suppress parathyroid gland activity and a low turnover bone disease may ensue of such condition. Today, however, adynamic bone disease is increasingly observed in the absence of aluminum intoxication (Table 10-1). Another late, still incompletely elucidated complication is amyloid-related arthropathy.