Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.

Relationship between renal function and metabolic alterations in early streptozocin-induced diabetes in rats.

To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h after streptozocin injection, and significant hyperglucagonemia and acidosis were present at 36-48 h. Glomerular filtration rate (GFR), expressed per unit of body weight, first increased at 3 days of diabetes [1.35 +/- 0.07 (SE) (N = 14)] and was 18% greater than in controls [1.14 +/- 0.03 ml X min-1 X 100 g-1 (SE) (N = 38)] (P less than .005). Renal enlargement preceded GFR changes, so that GFR per unit of kidney weight was lower at 48 h in diabetics [1.31 +/- 0.06 (SE) (N = 16)] than in controls [1.54 +/- 0.04 ml X min-1 X g-1 (SE) (N = 38)] (P less than .01). Nucleotide and RNA metabolism was studied in the renal cortex after infusion of radio-labeled orotate or adenine. Rate of RNA synthesis, total cellular RNA, and the pools of ATP, UTP, and uridine 5'-diphospho-N-acetyl glucosamine were significantly increased 13-51% in 48-h diabetics. Nucleotide precursor incorporation was significantly increased only in uracil ribonucleotides. The increase in uracil ribonucleotide pool exceeded the degree of cell hypertrophy. Our studies indicate that renal hypertrophy and specific increases in uracil ribonucleotide synthesis precede functional changes in early diabetes. Renal metabolic changes may be the critical primary factors in diabetic nephropathy.

Effect on renal function of change from high to moderate protein intake in type I diabetic patients.

The effects on renal function of moderate restriction in protein intake were studied in 14- to 20-yr-old type I diabetic patients who had no clinical renal disease or hypertension; matched normal subjects served as controls. After assessment of protein intake and renal function, studies were conducted at the completion of each of two consecutive dietary periods of 1 wk. Diets containing 3.5 and 1.5 g X kg-1 X day-1 protein were provided during the first and second periods, respectively. Baseline protein intakes were substantial in both controls (1.86 g X kg-1 X day-1) and diabetics (2.17 g X kg-1 X day-1). Baseline creatinine clearance was increased in diabetics (P = .043). At the end of the high-protein intake period, both diabetics and controls showed similar high values of glomerular filtration rate (GFR) and renal plasma flow (RPF). GFR and RPF decreased markedly (P less than .001) and to a similar degree in both groups after normal protein intake. GFR and RPF in diabetics were not higher than in controls at this point, but filtration fraction was increased in diabetics. Albumin excretion rates were similar in both groups and not influenced by renal function changes. GFR and RPF values correlated significantly with the quantity of protein intake, as estimated from the urea nitrogen appearance rate in both groups. The results suggest that the functional response to variations in protein intake is not altered in the diabetic kidney. In addition, increased renal function in diabetics may be related partly to the excessive protein content in commonly prescribed diabetic diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukopenia and hypoxemia. Unrelated effects of hemodialysis.

Hemodialysis-induced hypoxemia has been attributed to membrane-related complement activation leading to pulmonary leukostasis and to hypoventilation secondary to carbon dioxide losses via the dialyzer. We have separately assessed the role of membrane- and dialysis-related factors by using different dialyzers and sequential ultrafiltration and hemodialysis with first-use cellulose dialyzers produced both leukopenia and hypoxemia. With reused cellulose and polyacrylonitrile dialyzers, hypoxemia still occurred, but without leukopenia. Ultrafiltration produced leukopenia and no changes in Pao2; during the subsequent hemodialysis, hypoxemia developed as the leukocyte count increased by 50%. Our data indicate that leukopenia and hypoxemia are unrelated effects of hemodialysis, and favor hypoventilation as the major determinant of hypoxemia during hemodialysis.

Influence of the pretransplant hematocrit level on early graft function in primary cadaveric renal transplantation.

Although use of human recombinant erythropoietin has alleviated symptoms of anemia in renal failure, effects of increased hematocrit (HCT) on early post-transplant renal function are unknown. Of 244 consecutive primary cadaveric kidney recipients transplanted over 74 months, 43% had HCT > or = 30% and 57% had HCT < 30% at transplantation. The incidence of delayed graft function (DGF) was greater in recipients with HCT > or = 30% (61%) than in recipients with HCT < 30% (33%; P = 0.0001). Ten percent of recipients with HCT > or = 30% experienced primary nonfunction (PNF) of the allograft (P = 0.0001). No recipient with HCT < 30% had PNF. Absolute rises in HCT over the 3 months preceding transplantation were greatest in those with PNF (2.5 +/- 2.4) followed by those with DGF (2.0 +/- 3.1) and immediate graft function (IGF) (0.2 +/- 5.2; P = 0.0328). Logistic regression analysis identified HCT > or = 30% (P = 0.0014), cold storage > or = 24 hr (P = 0.0006) and rising HCT (P = 0.0090) as independent predictors of DGF with relative risks of 3.1-, 3.3-, and 2.7-fold, respectively. Recipients with rising pretransplant HCTs who underwent dialytic fluid removal within 24 hr before transplantation had DGF with greater frequency (67%) than nondialyzed recipients with rising HCTs (45%). Primary cadaveric kidney recipients with HCT > or = 30% at transplantation have significantly greater risk for DGF and PNF. Rising pretransplant HCT levels may predispose recipients to DGF; this risk may be heightened in those undergoing hemodialysis shortly before transplantation.

Long-term alternate day steroid therapy in renal transplantation. A controlled study.

Seventy-six adult renal allograft recipients were allocated 5 months post-transplantation to daily or alternate day maintenance methylprednisolone therapy. All 15 recipients of living related kidneys and 23 recipients of cadaver kidneys were placed on the alternate day regimen, while 38 patients with cadaveric grafts remained on daily methylprednisolone. In patients on alternate day methylprednisolone, serum creatinine concentrations, frequency of acute rejection episodes, and prevalence of chronic rejection were similar to those of patients on daily steroids. Furthermore, no differences were noted in the rate of loss of graft function between recipients of cadaver kidneys on daily versus alternate day steroids. There were no differences in body weight, blood pressure, degree of hyperglycemia, or hyperlipidemia between patients on the daily or alternate day schedules. However, the prevalence of clinical osteonecrosis and the rate of infectious complications requiring hospitalization were significantly decreased in patients on alternate day methylprednisolone. We conclude that alternate day methylprednisolone therapy is as effective as daily steroids for the maintenance of graft function in renal transplant recipients. The decreased incidence of osteonecrosis and the lower frequency of infectious complications represent a strong argument in favor of alternate day steroid therapy.

Continuous arteriovenous hemofiltration of aminoglycoside antibiotics in critically ill patients.

The effect of continuous arteriovenous hemofiltration on the clearance of either tobramycin or gentamicin (mean dose, 1.65 +/- 0.36 mg/kg) was studied in eight critically ill patients. Mean aminoglycoside clearance by hemofiltration was 3.47 +/- 1.93 mL/min and total body clearance was 11.92 +/- 3.51 mL/min. Hemofiltration clearance (HFCL) was directly correlated with hemofiltration flow rate (HFQR): HFCL (mL/min) = 1.03 HFQR (mL/min)-0.88 (R = .89). Mean volume of distribution was 0.31 +/- 0.08 L/kg, and the elimination rate constant was 0.020 +/- 0.01 hr-1. Continuous arteriovenous hemofiltration was responsible for the removal of between 3% and 36% of each aminoglycoside dose in 24 hours. In critically ill patients with changing hemofiltration flow rates, measurement of multiple serum aminoglycoside concentrations is necessary to accurately assess dosing requirements and avoid ototoxicity and nephrotoxicity.

Nabumetone-associated interstitial nephritis.

An 84-year-old woman was admitted to the hospital for progressive edema and decreased urine output. She had been taking nabumetone for 6 months, but had discontinued the agent 2 weeks before admission due to progressive edema. On admission she had 2-3+ pitting edema. Her serum electrolytes were sodium 122 mEq/L, potassium 5.9 mEq/L, chloride 93 mEq/L, and carbon dioxide 19 mEq/L. A urinalysis was significant for protein 3061 mg/dl, ketones 15 mg/dl, blood 2+, leukocytes 26-50/high-power field, and a protein:creatinine ratio 24.9. The serum creatinine and blood urea nitrogen concentrations were 2.7 mg/dl and 70 mg/dl, respectively. Throughout hospitalization the patient underwent aggressive diuresis. She developed congestive heart failure, and hemodialysis was initiated. A renal biopsy specimen on hospital day 9 showed tubular damage with minimal glomerular changes consistent with a diagnosis of nonsteroidal agent-induced nephropathy. On day 13, a 24-hour urine collection had a protein excretion of 3151 mg. Although the patient recovered from her renal failure (creatinine clearance 43 ml/min), the nephrotic syndrome persisted (13 g protein/day). The patient developed infectious complications and died on hospital day 32.

Relationship between values of bioelectrical impedance and creatinine clearance.

This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty-eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24-hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance-derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values.

Effect of Misoprostol on Mesangial Cell Growth and Collagen Metabolism.

Independent of etiology, progressive chronic renal failure is characterized by accumulation of mesangial matrix and collagenous materials leading to glomerular sclerosis and closure. Pharmacologic intervention aimed at ameliorating this process has significant potential for substantial clinical benefit. We, therefore, assessed the effect of misoprostol on glomerular mesangial cell growth and collagen metabolism. Studies were carried out using a rat glomerular mesangial cell line cloned in our laboratory. At the concentration tested (1 &mgr;M), neither misoprostol nor prostaglandin E(2) had any effect on glomerular mesangial cell proliferation. Misoprostol did not change the absolute synthesis rates for collagen or total protein when measured by (14)C-proline incorporation into protein-associated hydroxyproline and proline respectively. However, the amount of collagen extruded into the medium, as a percentage of protein synthesis, was decreased by 10% in misoprostol-treated cells (p = 0.042). In addition, collagen breakdown was 26% greater in misoprostol-treated cultures (p = 0.044). Misprosotol had no such effects on cell cultures subjected to mechanical stress applied as continuous stretch-relaxation cycles. These results indicate that misoprostol influences mesangial cell collagen metabolism by increasing the rate of endogenous breakdown and decreasing collagen export outside the cell. Misoprostol has no effect on mesangial cell proliferation.

Use of urea kinetics in the nutritional care of the acutely ill patient.

In acutely ill patients nitrogen balance is often assessed clinically from measurements of protein intake and urinary urea nitrogen. We have utilized urea kinetic modeling to measure urea generation rates, protein catabolic rates and nitrogen balance in 19 acutely ill patients with varying degrees of renal dysfunction and have studied the effect of varying caloric intake on protein balance during a period of fixed protein intake. In patients with measured creatinine clearances equal to or greater than 50 ml/min there was a highly significant correlation between nitrogen balance estimates derived from urea kinetic modeling and those obtained from urinary urea nitrogen (R = 0.939; p less than 0.001). When creatinine clearance measurements were between 20 to 50 ml/min the correlation between the two estimates was poorer (R = 0.337; p less than 0.001). In patients whose creatinine clearance was below 20 ml/min the correlation between measurements was worse still (R = 0.229; p less than 0.002). To determine the effects of increasing caloric intake on protein catabolic rate seven acutely ill patients were studied. When caloric intake was increased from 27.8 to 34.2 kcal/kg/day while on a fixed protein intake of 1.27 g/kg/day there was a significant fall in protein catabolic rate from 1.39 to 0.99 g/kg/day (p less than 0.002). As urea kinetic modeling takes into account changes in blood urea nitrogen, extrarenal losses of urea and the urinary urea pool, it is the preferred method for measuring protein balance in acutely ill patients particularly those with poor renal function. Serial monitoring of protein catabolic rates permits easy continuous assessment of the effect of increasing caloric intake on protein sparing during parenteral hyperalimentation.

18F scintigraphy in the early diagnosis of osteonecrosis of the femoral head in chronic hemodialysis and transplantation.

Osteonecrosis of the femoral head results in an increased uptake of 18F due to a reparative reaction in the necrotic area and its surroundings. Twenty hemodialysis and twenty-seven post-transplant patients were studied serially. In the hemodialysis group, nine patients had positive scintigraphs and eleven had negative studies. All were asymptomatic. In the transplant group, twelve were positive and fifteen were negative. Four patients with positive scans later developed unequivocal clinical and radiographic evidence of osteonecrosis. Patients with negative scans have been asymptomatic and without radiological abnormalities. Age, sex, duration of dialysis, bone mineral densitometry, total steroid dose, duration of hospitalization after transplantation, and serum chemistries were not different in positive and negative patients. All patients on alternate-day steroids have negative scans. A positive 18F scintigraph antedates the occurrence of clinical and radiological findings of osteonecrosis.

Indirect measures of total body water may confound precise assessment of peritoneal dialysis adequacy.

Urea kinetic modeling (UKM) has yet to be optimized as a practical tool for assessing adequacy of therapy in continuous ambulatory peritoneal dialysis (CAPD) patients. Watson equation (WV) and 58% body weight (58%WT) estimates of total body water (TBW) are indirect measures likely to yield imprecise estimates of Kt/V. Bioelectrical impedance (BEI) measures body composition as a function of electrical conductance, minimizing fat contribution to TBW. TBW values were highest when measured as 58% WT and lowest when calculated from WV. These differences were most striking in patients with overweight body habitus. BEI-derived TBW correlated best with UKM values. The relationship between BEI-derived and anthropometrically derived TBW was best in patients of normal habitus. Kt/V values were highest when calculated from WV-derived volumes and significantly differed from Kt/V values calculated from BEI-derived and 58%WT volumes. When segregated by habitus, however, only in overweight patients was this pattern of clinical significance. Serial body weight, lean body mass, and TBW remained stable in patients of normal habitus. Overweight patients increased weight by 5%, lean mass by 2%, and TBW by 5%, 3%, and 2% when measured by 58%WT, WV, and BEI respectively. BEI measures of TBW exclude fat mass and thus strengthen the use of Kt/V for assessing dialysis adequacy in CAPD patients of all body weights.

Abbreviated method for urea kinetic modeling in continuous ambulatory peritoneal dialysis patients.

Urea kinetic modeling (UKM) is an established method for quantitating hemodialysis, with target values clearly defined. Precise methods for measuring continuous ambulatory peritoneal dialysis (CAPD) prescriptions are less well-defined, and 24-hour collections of dialysate effluent are logistically impractical. UKM parameters derived from an abbreviated (4-hour) collection period were compared with simultaneously obtained 24-hour collections of urine and dialysate effluent in 22 CAPD patients. Daily Kt/V was calculated from total (residual renal and peritoneal) urea clearance and an anthropometric-derived total body water volume. Results yielded from the 24-hour collection included a mean Kt/V of 0.29 +/- 0.09, and mean protein catabolic rate (PCR) of 0.84 +/- 0.24 g/kg/day. Daily Kt/V values were calculated from each individual dialysate cycle. The first morning cycle after an overnight dwell correlated best with results obtained using 24-hour collections (r = 0.921; p < 0.0001) with no significant differences in Kt/V found (p = 0.454) between the short and 24-hour methods. Daily Kt/V values converted by exponential transformation to a thrice-weekly hemodialysis value yielded a Kt/V equivalent of 1.02 +/- 0.40. UKM using an abbreviated collection period is an accurate and practical tool for quantitating CAPD adequacy in a routine clinical setting.

Effective continuous ambulatory peritoneal dialysis following abdominal aortic aneurysm repair.

OBJECTIVE: To review a single center's experience with the initiation and maintenance of continuous ambulatory peritoneal dialysis (CAPD) in 8 patients with a history of abdominal aortic aneurysm repair (AAAR). DESIGN: Retrospective case review with long-term follow-up. PATIENTS (OR PARTICIPANTS): Eight patients with multiple medical problems including a history of abdominal aortic aneurysm repair and end-stage renal failure who received peritoneal dialysis catheters between December 1986 and July 1991. MAIN OUTCOME MEASURES: Success of catheter implantation and maintenance of continuous ambulatory peritoneal dialysis; incidence of peritoneal infection and long-term complications; overall clinical course. RESULTS: Over five years 8 patients with a history of reconstructed abdominal aortic aneurysm received peritoneal dialysis catheters without complication and dialyzed successfully for 88 patient-months in total. Three patients had a total of five episodes of peritonitis, at an incidence of 0.68 episodes per patient per year, a rate not significantly different from that of our overall CAPD patient population (1.09) and that reported by other groups. CONCLUSION: Our experience suggests that historical AAAR poses no significant risk to and should not preclude the implementation of continuous ambulatory peritoneal dialysis. Indeed, CAPD offers a safe and optimal dialytic alternative for patients with historical abdominal aortic aneurysm repair in whom compromised cardiovascular hemodynamics may significantly influence morbidity and survival.

Use of bioelectric impedance analysis and dual-energy X-ray absorptiometry for monitoring the nutritional status of dialysis patients.

Despite recent technological advances, inadequate nutrition has been clearly identified as a significant risk factor to survival of patients undergoing chronic maintenance dialysis therapy. Although body density by underwater weight and residual lung volume, total body water by isotope dilution, bone mineral content, and total body potassium measurements will provide a very accurate multicompartmental analysis of body composition, they are not applicable to routine clinical or field work. Because of availability and simplicity, in addition to anthropometry, bioelectrical impedance and dual energy X-ray absorptiometry have received the most attention from the renal community. Several studies have validated the use of total body water by BEI as a surrogate for isotope dilution methods in dialysis patients, whereas others have established an excellent correlation with the volume of distribution of urea as measured by urea kinetic volume. Bioimpedance analysis has been extensively validated in stable healthy populations for measurement of lean body mass. Results are similar to those obtained with hydrodensitometry and total body potassium. Several studies in dialysis patients have compared lean body mass measurements by BEI and DEXA. Although the number of patients studied is relatively small, there is a high degree of correlation and concordance between the two methods. Nevertheless, selective equations for specific patient populations may be required with both methodologies for individual clinical applications. Longitudinal follow-up of body composition using BEI and DEXA in dialysis patients is contingent on a stable hydration status and/or accurate estimation of extracellular volume status for appropriate corrections. Consistency of technique and standardization of BEI and DEXA equipment is essential for reproducibility of results. Equations used in calculations must be age, sex, race, body habitus, and population specific whenever possible. Multiple compartment models including BEI, DEXA and isotopic dilution provide the best current "gold standard" for body composition analysis. BEI methodology is a practical bedside tool for assessment of total body water, and provides more consistent and reproducible results than anthropometry.

Abbreviated two sample, single pool, variable volume urea kinetic modeling.

A two-point model has been developed that uses actual predialysis (C0) and postdialysis (C1) blood urea nitrogen (BUN) values, and calculates the third value (C2) by forcing a solution for urea generation (Gurea) and urea volume of distribution (Vurea) that results in a predialysis BUN value a week later (C7) similar to C0. This two-point model was evaluated in 64 patients (mean age: 59 +/- 17 years) undergoing thrice weekly chronic hemodialysis, with mean predialysis (C0) and postdialysis (C1) midweek BUN values of 70 +/- 16 and 28 +/- 10 mg/dl, respectively. Compared to the standard three-point, single pool, variable volume standard, the two-point model accurately predicted Kt/V (1.08 +/- 0.22 versus 1.08 +/- 0.23, respectively) and Vurea (48.1 +/- 14.1 versus 48.1 +/- 13.9 L, respectively). The model also approximated C2 concentrations within an 11% range (66 +/- 20 versus 69 +/- 16 mg/dl for modeled and actual, respectively; p = 0.007) that allowed useful estimates of Gurea (6.64 +/- 1.87 versus 6.71 +/- 2.47 g/min for model and actual, respectively) and normalized protein catabolic rate (0.94 +/- 0.19 versus 0.94 +/- 0.26 for modeled and actual, respectively; p = ns). It is concluded that the two-point model described may be used for calculation of Kt/V and normalized protein catabolic rate in the clinical setting when a third BUN value is not available.

Intermittent intraperitoneal ceftazidime dosing in end-stage renal disease.

Infections are a common problem in dialysis patients. As hospital stay shortens, many require outpatient antibiotic therapy. Parenteral administration may pose considerable logistic and financial burdens, whereas daily intraperitoneal dosing increases the risk of contamination. Ceftazidime, with its long half-life, may provide adequate dosing when administered intraperitoneally thrice weekly. The authors therefore studied the kinetics of a 2 g loading dose followed by a 1.5 g dose every 48 hr in seven stable chronic peritoneal dialysis patients. In vitro stability at 4 degrees C (measured by high performance liquid chromatography) was 91% at 120 hr. Peak serum concentration (60 +/- 22 microg/ml) was reached at 4.9 +/- 2.2 hr. Serum values were 25 +/- 9 and 8 +/- 3 microg/ml at 24 and 48 hr, respectively. However, median trough levels at 48 hr in dialysate were significantly lower than in serum (2.8 vs 8.5 microg/ml, respectively; p = 0.0425). Pharmacokinetic parameters were as follows: bioavailability (F), 88% +/- 8%; volume of distribution at steady state (VDss), 20 +/- 8 L; absorption half-life (T1/2(abs)), 1.8 +/- 1.3 hr; elimination half-life (T1/2(el)), 11.4 +/- 4.5 hr; and clearance (CL), 22 +/- 10 ml/min. Intraperitoneal ceftazidime every 48 hr is a practical alternative to parenteral therapy of nonperitoneal infections. In peritonitis, whether increased permeability results in improved dialysate levels remains to be defined.

Impact of dialysis modality and acidosis on nutritional status.

Experimental evidence suggests that acidosis may have a deleterious effect on protein metabolism. We evaluated 124 chronic dialysis patients (59 +/- 17 years) and defined acidosis as an anion gap >18 meq/L. A direct correlation (p < 0.0001 was found between anion gap and serum albumin (R = 0.402), BUN (R = 0.488), and serum creatinine (R = 0.473) concentrations. Acidotic patients (43%), when compared with nonacidotic patients, had greater serum albumin concentrations (3.95 +/- 0.50 vs. 3.60 +/- 0.48 g/dl, p = 0.0001, respectively), higher normalized protein catabolic rates (1.12 +/- 0.27 vs. 0.96 +/- 0.26 g/kg/d, respectively; p = 0.0004), and higher BUN (70 +/- 19 vs. 55 +/- 17 mg/dl, p = 0.0001) and serum creatinine (11.1 +/- 3.4 vs. 8.3 +/- 3.2, p = 0.0001 mg/dl) concentrations. However, no differences in midarm muscle circumference, fat free mass, or body cell mass were noted between groups when assessed by dialysis modality or acidosis status. In conclusion, mild chronic metabolic acidosis, likely caused by increased dietary protein intake, does not independently and adversely impact nutritional status in chronic dialysis patients.

Filtration of dialysate using an on-line dialysate filter.

UNLABELLED: Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.