Harold L. Moore

A Randomized Prospective Trial to Assess the Role of Saline Hydration on the Development of Contrast Nephrotoxicity

Though simple and attractive, the role of hydration for the prophylaxis of contrast nephrotoxicity has not been definitively established. We prospectively evaluated the role of deliberate saline hydration in patients undergoing nonemergency cardiac catheterization. Patients (n = 53) were randomized on the day prior to scheduled catheterization to one of two groups – group 1 (n = 27) received normal saline for 24 h (at a rate of 1 ml/kg/h) beginning 12 h prior to scheduled catheterization, and group 2 (n = 26) were allowed unrestricted oral fluids. Serum creatinine measured 24 and 48 h postcardiac catheterization was compared to the pre-randomization baseline value. The mean baseline calculated creatinine clearance was 79.6 ± 31.9 ml/min and the mean baseline creatinine was 106 ± 28 µmol/l. An increase in serum creatinine by at least 44.2 µmol/l (0.5 mg/dl), within 48 h of contrast exposure, was considered to represent clinically significant acute renal insufficiency. Ten subjects (18.9%) developed acute renal insufficiency. The incidence of acute renal insufficiency was significantly lower in group 1 (1 out of 27) as compared to group 2 (9 out of 26; p = 0.005 for comparison between groups; relative risk 0.11, 95% confidence interval 0.015 to 0.79). Twenty-four hours after contrast exposure, the mean increase in creatinine was less in group 1 vs. group 2 (8 ± 11 vs. 20 ± 21 µmol/l, p = 0.02). The increase in creatinine was not significantly different in group 1 vs. group 2 48 h after contrast exposure (12 ± 21 vs. 29 ± 40 µmol/l, p = 0.17). Deliberate saline hydration decreases the incidence of contrast-related acute renal failure and the severity of contrast-induced renal dysfunction in patients undergoing non-emergency cardiac catheterization.

Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis.

In 55 patients on continuous ambulatory peritoneal dialysis, the authors determined daily renal and dialysate clearances of urea nitrogen (CUN) and creatinine (CCr). Results are expressed as weekly CUN in liters (Kt) divided by liters of total body water determined from a nomogram (V). The authors calculated weekly CCr as the weekly dialysis clearance plus the average of renal CUN and CCr (to correct for creatinine secretion); they normalized total weekly CCr to 1.73 m2 body surface area. Mean weekly Kt/V and CCr were 2.1 and 65.2, respectively. Mean dietary protein intake by dietary survey was 0.85 g/kg body weight. Protein catabolic rate (PCR) calculated from urea kinetics was 0.94 g/kg standardized weight (V/0.58); PCR was significantly (p < 0.01) correlated with Kt/V (r = 0.53). The authors used linear regression to determine PCR, as follows: PCR = 0.80 [weekly Kt/V]/3 + 0.39. This slope is nearly 1.5 times that reported for the relationship of PCR to [weekly Kt/V]/3 in hemodialysis patients. Eighty-two percent of patients on continuous ambulatory peritoneal dialysis had more than the targeted minimum weekly Kt/V of 1.7, 71% had a weekly CCr more than the targeted minimum of 50, and 75% had a PCR > 0.8 g/kg/day. In support of the hypothesis that Kt/V requirements are related to peak concentration control rather than to time averaged blood urea nitrogen, patients on continuous ambulatory peritoneal dialysis have a higher PCR at given Kt/V values compared to hemodialysis patients. These patients are more likely to have a PCR > 0.8 if weekly Kt/V > 1.7.

Lean Body Mass Estimation by Creatinine Kinetics, Bioimpedance, and Dual Energy X-ray Absorptiometry in Patients on Continuous Ambulatory Peritoneal Dialysis

Lean body mass (LBM), which is fat free body mass, can be used as an index of nutritional status. We evaluated three techniques for LBM estimation, including dual energy x-ray absorptiometry (DEXA), creatinine kinetics (CrKin), and bioimpedance (BI) in 10 patients on continuous ambulatory peritoneal dialysis (CAPD). Two different formulae were applied for BI LBM estimation, Segal (S) and Deurenberg (D). Mean values (+/- SEM) of LBM estimated were 48.2 +/- 3.6, 46.12 +/- 2.87, 43.32 +/- 3.87, and 41.27 +/- 4.26 by DEXA, BI-S, BI-D, and CrKin, respectively. LBM by CrKin was significantly lower than that by DEXA and BI-S values. There was no statistically significant difference between DEXA and BI-S values. Statistically significant correlations were found between LBM values by all methods. Particularly strong correlations were found between DEXA versus BI-S (r = 0.976) and BI-S versus BI-D (r = 0.98). Because clinical assessment of hydration status is inaccurate, and both BI and DEXA measure excess extracellular water in LBM, falling muscle mass may be missed by these techniques. The CrKin technique for estimating LBM at normal body fluid volumes (dry weight) may be a better index of nutritional status in patients on CAPD because this may truly reflect the dry LBM and changes in muscle mass. Both DEXA and BI include excess body water in LBM and may mask malnutrition in the presence of subclinical or clinical overhydration, which is common in patients on peritoneal dialysis.

Continuous ambulatory peritoneal dialysis with a high flux membrane

The standard peritoneal equilibration test (PET) was performed in 66 patients on CAPD. Patients were classified as low (n=5), low average (n=22), high average (n=27), and high (n=12) transporters based on the dialysate/plasma creatinine (D/P Cr) after 4 hour dwells. After an average time interval of 14 months on CAPD, indices of dialysis adequacy and nutrition were assessed. Based on monitoring of patient chemistries and drain volumes, peritoneal transport was considered stable during the interval. Instilled volumes and exchange tonicity were individualized in each patient to achieve combined renal and dialysis weekly creatinine clearance and KT/V urea that were not significantly different between groups. Overall, there were significant positive correlations of PET D/P Cr with dialysate albumin concentrations (r=0.30, p<0.02) and dialysate albumin losses (g/wk, r=0.27, p<0.04). There were significant inverse correlations with lean body mass (r=—0.26, p<0.03), drain volumes (r=—0.025, p<0.04), and KT urea by dialysis (L/wk, r=-0.24,p<0.05). High transporters had significantly (p<0.05) lower mean serum albumin, net protein catabolic rate (nPCR), lean body mass calculated from creatinine kinetics, and daily creatinine production (and presumably lower muscle mass) compared with one or more lower transport groups. In conclusion, we hypothesize that, in high transporters, use of more hypertonic exchanges with greater glucose absorption may inhibit appetite and nPCR; also, protein losses in drain volumes are increased. High transporters may require increased clearance and protein intake targets compared with other groups to maintain nutrition. Also, high transporters may be better suited for nightly intermittent peritoneal dialysis where short cycles provide more ultrafiltration with less glucose absorption.

The Relationship between Urine Osmolality and Specific Gravity

Background: In general, there is a good correlation between the specific gravity and osmolality of a urine sample. In certain clinical conditions, such as uncontrolled diabetes mellitus, nephrotic syndrome, after the administration of intravenous radiocontrast material or saline diuresis, dependence upon specific gravity for determining the concentrating ability will result in over‐ or underestimation. Methods: We studied the relationship between specific gravity and osmolality in vitro with simulated urines of varying composition. Urine samples from patients with different clinical conditions were also analyzed. Results: The in vitro curves for sodium chloride, urea, creatinine, glucose, contrast dye, and albumin were plotted (specific gravity versus osmolality). We found a linear correlation between the specific gravity and osmolality of the 6 substances that were studied and for their combinations. The urine samples obtained from patients with different clinical conditions documented that reliance on specific gravity could over‐ or underestimate the urine osmolality. Conclusions: We concluded that in those clinical conditions, urine osmolality should always be determined and it should not be estimated based on specific gravity.

Protein Losses in Continuous Ambulatory Peritoneal Dialysis

Protein losses in peritoneal dialysate were determined in 220 exchanges from 19 patients undergoing continuous ambulatory peritoneal dialysis. With four exchanges per day, mean protein losses in 79 di

Weight Limitations for Adequate Therapy Using Commonly Performed CAPD and NIPD Regimens

This paper delineates standard weights in anephric patients above which recommended targets cannot be achieved on standard continuous ambulatory peritoneal dialysis (CAPD) and nightly intermittent peritoneal dialysis (NIPD). Based on the relationship of net protein catabolic rate (PCR), (gkg standard weighuday) to urea clearances in our CAPD population, we have recommended minimum weekly clearances of urea by dialysis and the kidney (Kt, Uwk) normalized to total body water (V,1) of 1.7 or greater (1). This is the weekly KtIV urea value that predicts a net PCR of 0.8 glkgfday in our average CAPD patient. In stable patients, this net PCR provides a reasonable estimate of dietary protein intake (1, 2). Although not all agree that weekly Kr/V urea is a precise predictor of long-term outcome (3), recently published longitudinal studies suggest that weekly KrIV urea values below 1.7 in CAPD are associated with decreased patient survival and poorer nutritional status (4). Clinical experience suggests that weekly KtIV urea targets in CAPD are well below those of hemodialysis (5). The peak-concentration hypothesis proposes that, at comparable urea appearance rates, an intermittent therapy such as hemodialysis requires higher weekly urea clearances to maintain peak serum urea nitrogen concentrations at or below those of the essentially steady state values seen with CAPD (5). This hypothesis assumes that peak urea concentrations correlate better with uremic toxicity than time-averaged concentrations, Clinical experiences continue to support this hypothesis (69). A recent editorial reviewed compelling reasons (in our opinion) why peritoneal dialysis should be quantitated with delivery of at least the minimum target level (10). NIPD is an intermittent dialysis therapy with small peak and trough serum urea nitrogen concentration fluctuations. We believe it is essential to increase the weekly KrIV urea in NIPD in order to maintain weekly dialysis-creatinine clearances at levels comparable to those on CAPD and to com-

Nutrition in Renal Transplantation

This study was conducted to determine whether a high-nitrogen, low-carbohydrate diet in the immediate post-operative renal transplant period could result in a positive nitrogen balance and fewer cushingoid side effects. Twelve consecutive nondiabetic renal transplant recipients were randomly assigned to the isocaloric control or experimental diet group. The six patients ingesting the experimental diet achieved positive nitrogen balance whereas five of the six patients on the control diet had a negative nitrogen balance. The nitrogen balance varied directly and proportionately with the protein intake. Potassium balance mirrored the nitrogen balance data. Cushingoid side effects did not develop in any of the six experimental diet patients whereas four of the six control diet patients had evidence of severe cushingoid appearance and two had moderate cushingoid appearance (P = .01). Based upon the findings of this study, we suggest that the renal transplant recipients diet could be altered to provide more protein and less carbohydrate to improve nitrogen balance and prevent cushingoid features. It is possible that a high-protein, low-carbohydrate diet may be used by additional patients taking steroids for other disease states to prevent cushingoid side effects and improve nitrogen balance.

Pharmacological reduction of lymphatic absorption from the peritoneal cavity increases net ultrafiltration and solute clearances in peritoneal dialysis

Lymphatic drainage from the peritoneal cavity occurs mainly via the subdiaphragmatic stomata and significantly reduces net ultrafiltration and solute clearances during long-dwell peritoneal dialysis. Intraperitoneal cholinergic drugs constrict these stomata and may reduce peritoneal cavity lymphatic absorption. We evaluated ultrafiltration kinetics, solute transport, and lymphatic drainage during single hypertonic exchanges in rats using 2.5% dextrose dialysis solution with and without added neostigmine. Net ultrafiltration was enhanced in the neostigmine group (p less than 0.01) by a reduction in cumulative lymphatic absorption (p less than 0.01) and without an increase in total transcapillary ultrafiltration during the dwell time. Likewise solute clearances were significantly augmented with neostigmine primarily due to the increase in dialysate drain volume (p less than 0.01) since dialysate/serum solute ratios were unchanged. Pharmacological manipulation of peritoneal lymphatic absorption provides an alternative means of increasing the efficiency of long-dwell peritoneal dialysis without altering peritoneal transport of solutes and water.

Actuarial Analysis of Patient Survival and Dropout With Various End-Stage Renal Disease Therapies

Life table analyses were applied to experiences at the University of Missouri over a 5-year period with center hemodialysis, home hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), living related donor transplantation, and cadaveric transplantation. Patient survival, graft survival, and persistence on therapy were analyzed. Mean ages and the percentage of insulin-treated diabetics were not similar in all groups; many factors influenced the choice of therapy by patient and physician. Nevertheless, the results show the net outcomes of these different therapies at an institution that has offered them all over the 5-year period analyzed. Patient survival and persistence on therapy for CAPD fell within the range of the other forms of therapy. Based on predictions of patient survival from published experiences with end-stage renal disease (ESRD) populations, observed survivals in CAPD were close to those predicted for the age of the population. At 2 years, persistence on therapy (technique survival) was similar for center hemodialysis and CAPD. However, 88% of the nondeath dropouts from center hemodialysis were for kidney transplantation, while 12% were related to technique problems. In contrast, in CAPD only 14% of the nondeath dropouts were for a kidney transplantation, 10% were based on recovery of renal function, and 76% were related to dialysis therapy problems. Nondeath dropouts from home hemodialysis were more similar to those in CAPD, with only 33% for kidney transplantation and 67% for therapy problems. These results cannot be assumed to indicate that the choice of therapy influences outcome. They show net outcomes in a single program are most likely based on multiple factors (age, diabetes mellitus, cardiac status, patient selection bias, physician selection bias, and perhaps the therapy per se) that influence these indices of success. To our knowledge these are the first comparisons of the net outcomes of all these forms of therapy at a single institution over the same period of time.