Acute tubular injury is an important component in type I acute antibody-mediated rejection.

BACKGROUND: "Acute tubular necrosis (ATN)-like" changes in type I acute antibody- mediated rejection (AAMR) have been proposed since 2005, but the presence of "ATN-like" injury in AAMR has not well been established. The aim of this study was to confirm the presence of acute tubular injury in type I AAMR, using the specific proximal tubular injury marker, kidney injury molecule-1 (KIM-1). DESIGN: The study included 3 groups of cases, namely, a negative control group (normal nontransplantation renal parenchyma as group 1, n = 11), a positive control group (transplant ATN with negative C4d staining as group 2, n = 12), and study cases (type 1 AAMR as group 3, n = 19). Biopsy specimens from all groups were stained immunohistochemically for KIM-1 (monoclonal antibody) and KIM-1 staining intensity in proximal tubules was graded from 0.5 to 3+. Clinical indices were also correlated and analyzed. RESULTS: Group 1 demonstrated significantly lower serum creatinine levels (1.02 ± 0.10 mg/dL) when compared with both group 2 and group 3. Both groups 2 and 3 showed similar serum creatinine levels (4.02 ± 0.59 mg/dL in group 2 and 3.24 ± 0.34 mg/dL in group 3). The negative control group demonstrated negative proximal tubule staining for KIM-1, whereas both groups 2 and 3 showed positive KIM-1 staining in proximal tubules (intensity ranging from 1+ to 3+ in group 2 and from 0.5 to 3+ in group 3). CONCLUSION: Our results, using KIM-1 immunohistochemistry, demonstrated that acute tubular injury is an important component of type I AAMR.

Glomerulitis during acute cellular rejection may be a surrogate marker of vasculitis in renal allografts--better index for diagnosis of vasculitis.

BACKGROUND: The Banff criteria (from 2005 to 2009) use "T cell-mediated rejection" to indicate acute cellular rejection. Vasculitis in smaller arteries is an important diagnostic criterion for moderate and severe T cell-mediated rejection. The renal allograft endothelium is a significant target of inflammatory response-mediated tissue damage. Medium-size arteries (arcuate arteries) are mostly absent in routine allograft biopsies, so identification of vasculitis relies on its identification in small arteries (arterioles to interlobar arteries). Although inflammation in terminal vessels such as the glomerular capillaries has been previously recognized, their role in grading the rejection process is not well characterized. We therefore evaluated the expression of CD3-positive T lymphocytes and CD68-positive macrophages in glomeruli, small arteries, and arcuate arteries of nephrectomy specimens obtained from transplant and renal tumor patients. METHODS: The study group included 21 renal explant subjects with nonreversible moderate to severe T cell-mediated rejection (IIa to III) and/or severe chronic changes. The control group comprised 17 individuals with nephrectomy for renal tumors. In each case, a large renal section from cortex to medulla was stained for CD3 and CD68 by immunohistochemical method. CD3-positive T lymphocytes and CD68-positive macrophages per balanced high-power field were counted in glomeruli, interlobar arteries, and arcuate arteries. RESULTS: In control kidney sections, neither CD3-positive T lymphocytes nor CD68-positive macrophages were noted in glomeruli, interlobar arteries, or arcuate arteries. In the study group, 15/21 showed diffuse C4d positivity. Also in the study group, positive CD3 and CD68 counts in glomeruli were significantly correlated to both interlobar and arcuate artery counts by linear regression analysis. CONCLUSION: We conclude that in renal allograft biopsies, T lymphocytes and macrophages in the glomeruli not only represent a separate entity, "transplant glomerulitis," but also may be a surrogate marker of vasculitis present in larger vascular beds. Comparable amounts of T cells and macrophages imply that "acute cellular rejection" may be a better terminology to reflect the true inflammatory status.

Use of bioelectrical impedance techniques for monitoring nutritional status in patients on maintenance dialysis.

Malnutrition continues to be an important correlate of survival in dialysis patients. Nutritional surveillance at the clinical level requires use of simple, reasonably accurate, and easily accessible techniques for multicompartmental body composition analysis. Unfortunately, although gold standard methodologies (body density by underwater weight, total body water by isotope dilution, bone mineral content by neutron activation, total body potassium by (40)K whole body gamma counting) provide very precise assessments, they are not applicable to routine clinical practice. Because of its availability and simplicity, bioelectrical impedance (BEI) has significant potential as a complement to standard anthropometric techniques in the nutritional monitoring of patients with chronic renal failure. Consistency of technique and standardization of BEI equipment are essential for reproducibility of results. 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 for measurement of lean body mass has been extensively evaluated in stable healthy populations, with results similar to those obtained using hydrodensitometry and total body potassium. In dialysis patients, accuracy is contingent on a stable hydration status and/or appropriate correction for changes in extracellular volume status over time. Recent publication of bioimpedance norms for the hemodialysis population allows better comparisons with the national reference population studied as part of the National Health and Nutrition Examination Survey III (US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD). BEI methodology is a practical bedside tool for assessment of body composition that provides more consistent and reproducible results than standard anthropometry alone.

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.

Nutritional status assessment and body composition analysis in pre-end stage renal disease patients.

Malnutrition is a known risk factor for survival in renal failure patients. Of concern, a significant degree of malnutrition may develop in the predialysis period due to dietary restrictions and uremia. To further define this issue, we evaluated 25 predialysis patients using serum chemistries, body mass index (BMI), fat free mass (FFM), body cell mass (BCM), and protein appearance rate (PAR) as surrogates of nutritional status and compared their results to those obtained in established hemodialysis patients and recipients of living donor renal allografts during a nine-month observation period. Pre- dialysis patients had significantly (p<0.0001) higher body weight (28%), body mass index (26%), body cell mass (17%) and fat free mass (15%) than hemodialysis and transplant patients. Intracellular water content was similar in all groups. As many patients do not start dialysis until clearance values fall below 10 ml/min, it is possible that greater tissue mass losses occur in the weeks preceding initiation of dialytic therapy. Why renal transplant recipients fail to increase tissue mass may relate to the catabolic effects of immunosuppression. We conclude that the early stages of pre-end stage renal disease are associated with relatively good preservation of body cell mass.

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.

Simplified measurement of intra-access pressure.

The measurement of intra-access pressure (P[IA]) normalized by mean arterial BP (MAP) helps detect venous outlet stenosis and correlates with access blood flow. However, general use of P(IA)/MAP is limited by time and special equipment costs. Bernoulli's equation relates differences between P(IA) (recorded by an external transducer as PT) and the venous drip chamber pressure, PDC; at zero flow, the difference in height (deltaH) between the measuring sites and fluid density determines the pressure deltaPH = P(IA) - P(DC) Therefore, P(DC) and PT measurements were correlated at six different dialysis units, each using one of three different dialysis delivery systems machines. Both dynamic (i.e., with blood flow) and static pressures were measured. Changes in mean BP, zero calibration errors, and hydrostatic height between the transducer and drip chamber accounted for 90% of the variance in P(DC), with deltaPH = -1.6 + 0.74 deltaH (r = 0.88, P < 0.001). The major determinants of static P(IA)/MAP were access type and venous outflow abnormalities. In grafts, flow averaged 555 +/- 45 ml/min for P(IA)/MAP > 0.5 and 1229 +/- 112 ml/min for P(IA)/MAP < 0.5. DeltaPH varied from 9.4 to 17.4 mmHg among the six centers and was related to deltaH between the drip chamber and the armrest of the dialysis chair. Concordance between values of P(IA)/MAP calculated from PT and from P(DC) + deltaPH was excellent. It is concluded that static P(DC) measurements corrected by an appropriate deltaPH can be used to prospectively monitor hemodialysis access grafts for stenosis.

Impact of peritoneal dialysis modality and acidosis on nutritional status in peritoneal dialysis patients.

Continuous ambulatory (CAPD) and continuous cyclic peritoneal dialysis (CCPD) differ in solute transport, and variances in mass balance could impact nutritional parameters. Chronic acidosis may decrease albumin synthesis and increase catabolism. We prospectively studied 50 peritoneal dialysis patients (age: 55 +/- 16 yrs; CAPD = 33; CCPD = 17) over 24 months. Acidosis was defined by an anion gap > 18 mEq/L. Bioimpedance analysis was used to estimate body cell mass and fat-free mass. Patients on CAPD had a lower body mass index than CCPD patients (27 +/- 5 kg/m2 vs. 29 +/- 9 kg/m2 respectively; P = 0.039). However no differences were observed in body cell mass (25 +/- 8 kg vs. 26 +/- 9 kg respectively; P = 0.787) or fat-free mass (53 +/- 14 kg vs. 50 +/- 18 kg respectively; P = 0.404). Urea kinetic modeling showed no differences in Kpt/V or nPCR (0.26 +/- 0.06 vs. 0.24 +/- 0.07; P = 0.709 and 0.67 +/- 0.29 g/kg per day vs. 0.65 +/- 0.23 g/kg per day; P = 0.709 for CAPD and CCPD respectively). When categorized by the presence of acidosis no differences were observed in body cell mass (24 +/- 8 kg vs. 27 +/- 9 kg respectively; P = 0.131) or fat-free mass (54 +/- 15 kg vs. 50 +/- 16 kg respectively; P = 0.348), while body mass index was greater in acidotic than nonacidotic individuals (30 +/- 8 kg/m2 vs. 26 +/- 6 kg/m2 respectively; P = 0.005). Dietary protein intake assessed as nPCR was similar in both groups (0.64 +/- 0.26 vs. 0.71 +/- 0.28 g/kg per day; P = 0.319, for CAPD and CCPD respectively). We conclude that over a 24-month period neither peritoneal dialysis modality nor the presence of acidosis has a detrimental influence on nutritional parameters in well dialyzed patients.

Gynecologic and reproductive issues in women on dialysis.

Most women on dialysis are amenorrheic and do not ovulate, but little information about menstrual patterns in women on dialysis exists, especially since the introduction and use of recombinant human erythropoietin, a therapy that may improve sexual interest and function. In this study, women who were < or = 55 years of age at the start of dialysis (n = 76) completed questionnaires and form the study group. Women older than 55 years at the start of dialysis did not complete the entire questionnaire (n = 115), but their medication records were reviewed for estrogen replacement therapy. The questionnaire asked about pregnancies, menstrual periods (regularity, frequency, duration, character of flow, menopause), and menopause before beginning dialysis and currently. Women also responded to questions about sexual activity, use of birth control, contraception counseling by physicians, yearly Papanicolaou smears, and mammograms. Demographic data (age, race, age at the time dialysis started, mode of dialysis, use of recombinant human erythropoietin, and history of renal transplant) were also obtained through the questionnaires. Fifty-nine percent of the 76 women who completed the study were white and had been on dialysis a median of 3 years (range, 0.1 to 18 years). The median age was 43 years, 68% were on hemodialysis, 90% were receiving recombinant human erythropoietin, and 70% had been pregnant (a total of 179 pregnancies; four pregnancies in four women occurred after the start of dialysis). Significantly more women were menstruating before dialysis started than currently (63% v 42%; P < 0.025), but the difference could be explained by patient age: currently menstruating women were younger (37 +/- 9 v 46 +/- 11 years; P = 0.0002). More women reported menstrual regularity before beginning dialysis (75% v 42% currently; P < 0.005), but there were no differences in number of days between or number of days of menstruation before beginning dialysis and currently. Menstrual flow was reported as heavier currently by more women (64% heavy flow with clots v 38% before dialysis started; P < 0.05). The median age at menopause was 47 years; 28% of the women were postmenopausal. Fifty percent of the women were sexually active, but only 36% used birth control. Discussions between the women and their nephrologist about possible pregnancy and contraception were reported by only 13% of women. Sixty-three percent of the women reported having yearly Papanicolaou smears and 73% had had a mammogram. Only 5% of the 113 women who were older than 55 years when they began dialysis were receiving estrogen replacement therapy. Amenorrhea was reported in this study by a smaller proportion of women than in studies conducted before the introduction of recombinant human erythropoietin. The possibility that erythropoietin may restore normal hormonal cyclic function in women with end-stage renal disease requires further study. Nephrologists as well as primary care physicians and gynecologists need to focus more on the gynecologic concerns of women on dialysis, including the potential for pregnancy. The effects of estrogen replacement on atherosclerosis and osteoporosis, and consideration of such therapy in women on dialysis warrants attention.

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.

Impact of peritoneal dialysis modality on nutritional and biochemical parameters.

Several lines of evidence suggest that continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) may differ in glucose, amino acid, and protein mass transfer. Thus, depending on modality, variances in protein and caloric balance could affect nutritional parameters. We prospectively followed 58 patients on CAPD (n = 36) or CCPD (n = 22) for 21 months (age: 54 +/- 14 years; weight: 76 +/- 16 kg; body mass index: 25.8 +/- 5.1 kg/m2). Twenty-four-hour dialysate effluent (Kpt/V) and normalized protein catabolic rate values were comparable in both CAPD and CCPD patients (0.23 +/- 0.05 vs 0.20 +/- 0.05 and 0.93 +/- 0.23 vs 0.87 +/- 0.21 g/kg/day, respectively). At the last trimester, CAPD patients had greater body weight and body mass index increases than those on CCPD (1.6 +/- 1.1 vs 0.3 +/- 1.1 kg and 0.53 +/- 0.42 vs 0.06 +/- 0.35 kg/m2, respectively), which did not reach statistical significance. No differences were noted in serum protein, albumin, or cholesterol levels (6.5 +/- 0.1 vs 6.5 +/- 0.2 g/dL; 3.5 +/- 0.1 vs 3.7 +/- 0.1 g/dL; and 211 +/- 10 vs 209 +/- 10 mg/dL for CAPD and CCPD, respectively). In summary, this study demonstrates that CAPD and CCPD, when delivered in equal amounts, result in similar weight gains and maintain comparable biochemical nutritional parameters.

Impact of acidosis on nutritional status in chronic peritoneal dialysis patients.

Malnutrition is a well-recognized risk factor for survival in chronic dialysis patients. Experimental evidence links acidosis to decreases in albumin synthesis and increased breakdown. We studied serum bicarbonate, albumin, and total protein concentrations in 79 peritoneal dialysis patients (mean age 53 +/- 14 years) during a 21-month observation period. No changes were observed in blood urea nitrogen (66 +/- 19 vs 61 +/- 18 mg/dL), serum creatinine (9.8 +/- 4.5 vs 10.7 +/- 4.5 mg/dL), serum bicarbonate (25 +/- 3 vs 25 +/- 3 mEq/L), anion gap (16 +/- 3 vs 17 +/- 3 mEq/L), and serum albumin (3.6 +/- 0.6 vs 3.6 +/- 0.6 g/dL) concentrations between the first and last trimester of follow-up. A poor correlation was also found between serum albumin concentration and anion gap (R = -0.373) and bicarbonate (R = -0.172) concentrations. Finally, when grouped by acid-base status, serum protein (6.5 +/- 0.7 vs 6.5 +/- 0.8 g/dL) and albumin (4.0 +/- 0.4 vs 3.9 +/- 0.4 g/dL), concentrations were similar in patients with serum bicarbonate levels < or > or = 22 mEq/L, respectively. In conclusion, a mild to moderate degree of acidosis is not associated with decreases in serum albumin concentrations in stable chronic peritoneal dialysis patients.

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.

Electrolyte disturbances in elderly patients with severe diarrhea due to cholera.

The purpose of this clinical study was to evaluate prospectively electrolyte disturbances in elderly patients with severe diarrhea due to cholera. A total of 20 adult (Group I; < 60 yr) and 22 elderly (Group II; > or = 60 yr) patients were studied. In all patients, extracellular fluid (ECF) volume reexpansion was achieved with normal saline at 50 mL/kg per hour. Once a diuresis of 40 mL/h was achieved, intravenous therapy was discontinued and patients' ECF volumes were reexpanded orally with a polyelectrolyte solution. Blood and urine samples were obtained on admission, at the time when adequate diuresis ensued, and after 12 h of oral ECF volume reexpansion. On admission, both groups had severe ECF volume contraction but only mild increases in osmolality (308 +/- 12 and 310 +/- 13 mosmol/kg for Groups I and II respectively; P = NS). Acidemia (pH) was equally severe in both (Group I: 7.13 +/- 0.11; Group II: 7.11 +/- 0.09; P = NS), and the anion gap was comparably increased in both groups (30 +/- 8 and 26 +/- 7 mmol/L for Groups I and II, respectively; P = NS). None of the patients was hypokalemic at the time of admission (Group I: 4.3 +/- 0.5 mmol/L; Group II: 4.5 +/- 0.5 mmol/L; P = NS). Adequate diuresis was achieved at 2.0 +/- 0.7 h in both groups. At the end of the rapid ECF volume reexpansion phase, the anion gap normalized in both groups (Group I: 15.6 +/- 3.7 mmol/L; Group II: 14.4 +/- 2.8 mmol/L; P = NS), and serum potassium concentrations remained normal (Group I: 4.4 +/- 0.4 mmol/L; Group II: 4.1 +/- 0.4 mmol/L; P = NS). We conclude that use of aggressive intravenous hydration with normal saline followed by oral ECF volume reexpansion allows prompt correction of electrolyte abnormalities in adult and elderly patients with severe diarrhea as a result of cholera.

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.

Vancomycin removal by high-flux polysulfone hemodialysis membranes in critically ill patients with end-stage renal disease.

To define the pharmacokinetics of vancomycin in patients undergoing maintenance hemodialysis in an acute care setting and to characterize the rebound phenomenon occurring after hemodialysis, vancomycin t1/2 during the interdialytic and intradialytic phases and intradialytic clearance were measured in eight critically ill patients undergoing high-flux hemodialysis using F-80 or F-60 polysulfone dialyzers. Intradialytic clearance was determined using the recovery method. In patients dialyzed with F-80 dialyzers, interdialytic and intradialytic t1/2 for vancomycin were 162 +/- 69.8 hours and 4.7 +/- 1.3 hours, respectively. Intradialytic clearance was 108.5 +/- 16.3 mL/min, and 238 +/- 55 mg of vancomycin was recovered in the dialysate. In patients dialyzed with F-60 dialyzers, interdialytic and intradialytic t1/2 were 211.0 +/- 166.8 and 4.6 +/- 0.4 hours, respectively. Intradialytic clearance was 100.6 +/- 18.3 mL/min and the amount of vancomycin recovered was 252 +/- 79 mg. Vancomycin concentrations rebounded by 16% to 37% between 3 and 6 hours in patients dialyzed with the F-80 dialyzer and 15% to 38% between 2 and 3 hours in patient dialyzed with F-60 dialyzers. Hemodialysis with high-flux polysulfone dialyzers removes significant amounts of vancomycin in patients dialyzed in an acute care setting. A suggested scheme for vancomycin dosage adjustments in these patients is presented.

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.

Thyroid function surveillance in CAPD patients.

We monitored thyroid function in 75 peritoneal dialysis patients (55 +/- 15 years). A total of 20 (27%) were hypothyroid; 9 were diagnosed about the time of initiation of dialysis, and 11 prior to onset of renal failure. Thyroid function surveillance found an increase in serum thyrotropin (TSH) concentration to hypothyroid values in only one patient. On replacement therapy serum thyroxine was similar in euthyroid and hypothyroid patients (6.94 +/- 1.69 vs 6.52 +/- 1.65 micrograms/dL, respectively; p = 0.380), but TSH was higher in hypothyroid patients (5.61 +/- 5.67 vs 2.59 +/- 1.49 microU/mL, respectively; p = 0.001). Serum creatinine (8.6 +/- 3.1 vs 11.4 +/- 5.1 mg/dL, respectively; p = 0.049) and albumin concentrations (3.76 +/- 0.47 vs 3.33 +/- 0.71 g/dL, respectively; p = 0.006) were lower in hypothyroid than euthyroid patients. Hyperthyroid patients had higher serum triglyceride concentrations than euthyroid patients (306 +/- 176 vs 189 +/- 122 mg/dL, respectively; p = 0.013). Parathyroid hormone (PTH) was lower in hypothyroid than normothyroid patients (108 +/- 80 vs 261 +/- 265 pg/mL, respectively; p = 0.032). No differences were observed in serum calcium, phosphorus, and alkaline phosphatase. We conclude that hypothyroidism is common in peritoneal dialysis patients, usually antedates dialysis therapy, results in lower serum albumin and creatinine concentrations and higher serum triglyceride concentrations, is associated with lower serum PTH concentrations, and that thyroid function surveillance is not necessary in the absence of symptoms suggestive of hypothyroidism.

The method used for volume estimation significantly influences KprT/V results in peritoneal dialysis patients.

We studied 51 patients (age 50 +/- 15 years; weight 75 +/- 17 kg; blood urea nitrogen 62 +/- 20 mg/dL), 61% of whom were obese. The volume of distribution of urea was estimated by anthropometric formulas (Watson and Hume) and as 58% of actual and ideal body weight. Volumes derived from use of 58% of actual body weight were highest (43.4 +/- 10.0 kg; p = 0.0005); no differences were noted between Watson and Hume volumes and those obtained using 58% of ideal body weight (38.5 +/- 8.0, 39.4 +/- 7.5, and 37.0 +/- 5.6 kg, respectively). Normalized daily urea clearance (KprT/V) was lowest and highest when using 58% of actual and ideal body weight, respectively (0.251 +/- 0.081 and 0.290 +/- 0.091; p < 0.0001). KprT/V values derived using the Watson and Hume methods were similar (0.279 +/- 0.081 and 0.274 +/- 0.083, respectively), but significantly lower than those obtained using actual body weight (p < 0.0001). Differences were magnified in obese patients. A subset of patients underwent hemodialysis for urea volume measurement by urea kinetic modeling. Volume estimates using bioelectrical impedance showed the least bias when compared to values calculated during a hemodialysis treatment. We conclude that KprT/V is very dependent on body habitus and the method used for volume determination. Standardization of the volume parameter is essential to defining therapeutic guidelines and for meaningful comparisons between centers.