Operational characteristics of continuous renal replacement modalities used for critically ill patients with acute kidney injury.

Renal replacement therapy (RRT) is required in a significant percentage of patients developing acute kidney injury (AKI) in an intensive care unit (ICU) setting. One of the foremost objectives of continuous renal replacement therapy (CRRT) is the removal of excess fluid and blood solutes that are retained as a consequence of decreased or absent glomerular filtration. Because prescription of CRRT requires goals to be set with regard to the rate and extent of both solute and fluid removal, a thorough understanding of the mechanisms by which solute and fluid removal occurs during CRRT is necessary. The following provides an overview of solute and water transfer during CRRT and this information is placed in the appropriate clinical context with a discussion of recent clinical trials assessing the relationship between CRRT dose and patient survival. Moreover, the differences between solute removal in CRRT and other dialysis modalities, especially sustained low-efficiency dialysis (SLED) and extended daily dialysis (EDD), along with the potential clinical implications are discussed.

Ultrafiltration rate as a dose surrogate in pre-dilution hemofiltration.

For critically ill patients treated with continuous hemofiltration (HF), doses recently shown to improve survival can usually be achieved only in the pre-dilution mode. However, use of the pre-dilution mode results in reduced treatment efficiency, relative to post-dilution at the same ultrafiltration rate (Qf ) and blood flow rate (Qb ). The objective of this study is to determine the effect of Qf on removal parameters for solutes over a wide molecular weight spectrum in pre-dilution HF. Experiments were performed in an isovolemic, plasma-based pre-dilution system with Qb=200 ml/min. Removal parameters were measured for a 1.2 m2 polysulfone hemofilter (HF1200, Minntech) at Qf values of 20, 40, and 60 ml/min, corresponding to 17, 34 and 51 ml/h/kg for a 70 kg patient (N=3 hemofilters for each Qf ). Clearance of urea and creatinine (small solute surrogates) was derived from plasma and ultrafiltrate concentrations at 30, 60, 120, 180, and 240 min while clearance of vancomycin and inulin (middle molecule surrogates) was estimated from changes in plasma concentrations over time. In addition, the sieving coefficient (SC) of vancomycin and inulin was measured at the same time points and at baseline (T=0 min). Our findings indicate pre-dilution had a predictable effect on clearance for each solute, as clearance increased linearly with Qf. Sieving coefficient values were not significantly influenced by either Qf or time and the equivalence of SC values in the middle molecule range suggest attenuation of secondary membrane effects. These data indicate filter performance can largely be preserved despite high Qf values by use of predilution. Moreover, Qf appears to be a reasonable dose surrogate in pre-dilution HF.

Current status of renal replacement therapy for acute renal failure. A survey of US nephrologists. The National Kidney Foundation Council on Dialysis.

Although the management of acute renal failure (ARF) constitutes a major component of the activities of practicing nephrologists, minimal information is available on the dialysis techniques utilized to treat ARF in the USA. It is evident from several recent publications that there are wide variations in the dialytic and nondialytic management of ARF. In order to obtain a better understanding of the current practice for dialytic management of ARF, the National Kidney Foundation (NKF) Council on Dialysis commissioned a survey of NKF members. This article describes the results of this survey and provides a snapshot of the current management practices for ARF. It is our hope that this information will provide a baseline for further research in this area.

Serial measurements of body composition and total body mineral content in dialysis and nondialysis patients with renal failure.

Thirty-two patients with chronic renal failure, and 68 patients on maintenance hemodialysis underwent serial total body neutron activation over periods of time ranging from 23 to 159 months. Measurements of total body potassium (TBK), total body sodium (TBNa), total body calcium (TBCa), total body phosphorus (TBPhos), and total body chloride (TBC1) were performed. The results were normalized by lean body mass (LBM) or kilogram body weight (BW). The TBNa/LBM and TBC1/BW decreased during the first 36 months of measurements in the dialysis males, while there was no change in the nondialysis males. The TBNa/LBM, TBC1/LBM and TBC1/BW decreased during the first 36 months of monitoring the dialysis females, while a decrease in the LBM was the only change in the nondialysis females. In patients with an increasing K ratio (observed/predicted TBK), the TBNa/LBM and TBCa/LBM decreased and the LBM/BW increased. Similarly, in patients with an increasing Ca ratio (observed/predicted TBCa), the TBCa/LBM and TBPhos increased. The increasing K ratio in dialysis patients with a decreasing TBNa/LBM probably represents an improvement in nutritional status. The increasing TBPhos in dialysis patients with an increasing Ca ratio may represent an increase in skeletal tissue and/or soft tissue calcification. In dialysis females, the total body nitrogen is not different from controls. The total body fat, as a percentage of body weight, is greater in dialysis patients than in controls.

Plasma calcium fraction dynamics in uremic patients undergoing hemodialysis.

22 patients with chronic renal failure, maintained on chronic maintenance dialysis with a dialysate calcium of 1.5 mmol/l, were randomly selected for measurement of pre- and postdialysis plasma calcium fractions. Total, ionized and protein-bound calcium fractions in plasma showed significant increases following dialysis, but with correction for hemoconcentration due to ultrafiltration from dialysis, only protein-bound calcium showed a significant increase. Change of in vitro pH from 7.35 to 7.44 did not influence calcium binding. Similarly, in vitro addition of calcium to pre- and postdialysis blood samples did not result in significant differences for protein-bound calcium fractions. Comparison of dissociation constants for protein-bound calcium between pre- and postdialysis samples showed a significant change. Our results indicate that dialysis alters the affinity of serum protein by some unexplained mechanism and may contribute to the genesis of dialysis-bone disease.

Determinants of oxygenation during hemodialysis and related procedures. A report of data acquired under varying conditions and a review of the literature.

A decrease in arterial oxygen tension during hemodialysis has been attributed to a number of factors. In order to more completely define these factors, we studied respiratory gas exchange, arterial blood gases and pH, and dialyzer flux of CO2 during pure ultrafiltration, three types of acetate dialysis, and sorbent regenerated bicarbonate dialysis in which the dialysate concentration of bicarbonate varies. Changes due to position and extracorporeal circulation of a 300-ml volume of blood (sham dialysis) were studied for any effect contributing to the hypoxemia noted with circulation through the membrane and variation in dialysate. Alveolar oxygen tension (PAO2) is calculated by the equation PAO2 = PIO2-PaCO2 (FIO2 + 1-FIO2/RE). RE is the ratio of CO2 excretion by the lung (VCO2) to oxygen consumption (VO2). RE equals RQ (metabolic quotient) when no extrapulmonary CO2 losses occur. Normals in a lounge chair had no change in RE and PAO2. RE decreased to 0.75 during sham dialysis and PAO2 decreased. During pure ultrafiltration RE decreased due to a decrease in VO2 and VCO2 with proportionately greater decrease in VCO2. PAO2 decreased accordingly. Acetate dialysis produced an increase in oxygen consumption without a proportional increase in CO2 excretion and both RQ and RE decreased. When PAO2 decreased during any of these procedures, arterial oxygen tension (PaO2) decreased without a change in A-aO2 gradient. No changes in PaCO2 were noted. RQ did not change during bicarbonate dialysis. At high bicarbonate dialysate concentrations, however, PaCO2 increased and PAO2 decreased. The major reason for hypoxemia during acetate dialysis is a decrease in alveolar oxygen tension due to changes in metabolism and a decrease in pulmonary CO2 excretion when CO2 is lost from the dialyzer. The increasing pH may contribute to the metabolic change during acetate dialysis and the hypoventilation during bicarbonate dialysis. There is little evidence to support an effect of pulmonary capillary obstruction or changes in oxyhemoglobin association on the decrease in arterial oxygen tension observed.

Glutamine metabolism in bone.

Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.

Total body electrolyte composition and distribution of body water in uremia.

Total body sodium and chloride were measured by neutron activation analysis, and total body potassium was measured by whole body counting in ten male patients with endstage renal disease requiring chronic maintenance hemodialysis. The extracellular fluid volume was estimated from the simultaneously measured volume of distribution of bromine 77 and sodium 24. Total body water was estimated from the volume of distribution of triated water. Total body sodium and chloride were significantly increased above normal measured values, but total body potassium was not significantly different from normal. The increase in total body sodium could be attributed to an increase in exchangeable sodium because no significant change in the nonexchangeable portion of total body sodium could be detected. Extracellular fluid volume, estimated fro three different techniques (total body chloride, sodium 24, and bromine 77), and total body water were increased significantly above normal values. Extracellular fluid volume was correlated with exchangeable sodium, and total body water was closely correlated with total cation content (exchangeable sodium and total body potassium). The calculated intracellular fluid volume was decreased and was closely correlated with total body potassium. Despite adequate control of uremia by chronic maintenance hemodijalysis, body electrolyte composition and the distribution of body water remain significantly different from normal.

Effect of uremic sera on parathyroid hormone (PTH) mediated release of calcium from normal rat embryonal bone maintained in tissue culture.

1. 45Ca released from embryonal fetal rat bone into a tissue culture system containing uremic serum was lower than 45Ca measured in culture media containing normal sera. 2. With stimulation of bone calcium mobilization by the addition of PTH, 1,25(OH)2D3, 24,25(OH)2D3 and 25 (OH)2D3, the 45Ca released into media containing uremic serum was significantly lower than measured in cultures containing normal serum. 3. Addition of PTH in combination with 24,25(OH)2D3 or with 24,25(OH)2D3 and 1,25(OH)2D3 to bone cultures containing uremic serum increased the 45Ca released into the media when compared to cultures containing uremic serum and PTH.

Changes in total body calcium on prolonged maintenance hemodialysis with high and low dialysate calcium.

In vivo neutron activation analysis was used to measure sequential changes in total body calcium in 25 unselected patients with end-stage renal disease on dialysis for a period as long as 5 years. In 7 unselected patients (group 1), dialysis with a calcium solution of 5.0 mg/100 ml resulted in significant calculated daily loss of calcium (-321 +/- SEM 76 mg/day) while dialysis with 6.5 mg/100 ml resulted in a significant calculated calcium gain (182 +/- SEM 103 mg/day; p less than 0.0025). The remaining 18 patients (group 2) were dialyzed with a dialysate calcium of 6.5 mg/100 ml and sequential total body calcium measurements showed no significant calcium losses (-12 +/- SEM 68 mg/day) for a period as long as 2 years.