John D. Bower

Hypertension in the hemodialysis population: Any relation to one-year survival?

Few studies have quantified the effect of hypertension on survival in the hemodialysis population. We report the effect of hypertension on 1-year survival in 649 hemodialysis patients (89% black). In univariate analysis, hypertension was associated with improved 1-year survival (relative risk [RR], 0.48; P = 0.002 compared with normotensive patients). This effect of hypertension was mostly caused by the associated antihypertensive treatment because untreated hypertensive patients had survival rates equal to normotensive patients (RR, 0.87; P = 0.70). On the other hand, treated hypertensive patients fared better than normotensive patients (RR, 0.41; P = 0.0006). This was also true in multivariate analysis, in which antihypertensive treatment was associated with reduced RR (RR, 0.55; P = 0.02) whereas the level of blood pressure per se was insignificant (RR, 0.99; P = 0.63 per 1 mm Hg increase in predialysis mean arterial pressure). Other factors of significance in multivariate analysis included age (RR, 1.03/y; P = 0.0004), serum albumin (RR, 0.38/g; P = 0.002), and diabetes mellitus (RR, 1.58; P = 0.06). Our study suggests that antihypertensive treatment has a favorable effect on survival in the hemodialysis population irrespective of the level of blood pressure control.

Reversal of endocardial endothelial dysfunction by folic acid in homocysteinemic hypertensive rats

The role of L- and D-isomers of homocysteine (Hcy) in vascular versus endocardial endothelial (EE) remodeling and function is not well understood. The hypothesis is that Hcy decreases EE cell density by activating matrix metalloproteinase (MMP) and by inducing left ventricular hypertrophy (LVH) in homocysteinemic hypertensive rats (HHR). And L- and D-isomers of Hcy have differential effects in vessel and myocardium. We used: 1) spontaneously hypertensive rats (SHR) in which endogenous total homocyst(e)ine (tHcy) levels are moderately high (18 micromol/L); 2) control age- and sex-matched normotensive Wistar rats (NWR) in which tHcy levels are normal (4 micromol/L); to create hyperhomocyst(e)inemia, 32 mg/day Hcy was administered for 12 weeks in 3) SHR (SHR-H), and in 4) NWR (NWR-H) rats; 5) endogenous tHcy levels were reduced (from 18 to 12 micromol/L) in SHR by folic acid administration (SHR-F). Plasma tHcy levels were measured by HPLC and spectrophometric methods. The MMP activity, measured by zymography, is increased by chronic Hcy administration, and folic acid treatment decreases MMP activity. The collagen and transforming growth factor-beta1 (TGF-beta1), measured by reverse transcriptase-polymerase chain reaction, are increased by Hcy. Folic acid treatment decreases collagen expression and increases TGF-beta1. In vivo LV function was measured in anesthetized rats by a catheter in the left ventricle. The partial decrease in tHcy levels and no change in arterial pressure in SHR after folic acid administration, suggested that folic acid decreases one of the L- or D-isomer of Hcy, which is not responsible for an increase in arterial pressure, but may be responsible for myocardial dysfunction. The chronic Hcy administration decreases EE function in NWR and SHR. The treatment of folic acid in SHR improves LVH and EE function. Folic acid improves cardiac remodeling and EE function by decreasing one of the D- or L-isomer of Hcy and by decreasing MMP activity in HHR. These results may suggest a differential role of L- and D-isomers in vascular versus cardiac remodeling.

Effect of insulin on renal sodium handling in hypertensive rats.

Spontaneously hypertensive rats have reduced peripheral insulin sensitivity. To determine whether hypertensive rats demonstrate reduced response to the antinatriuretic effect of insulin, urinary sodium excretion was determined in hypertensive and normotensive rats (n = 7 per group) before and during euglycemic insulin administration at two infusion rates (21 milliunits/kg load and 4 milliunits/kg/min or 85 milliunits/kg load and 8 milliunits/kg/min). Hypertensive and normotensive time controls received the vehicle for insulin administration. Mean arterial pressure was greater (p less than 0.05) and inulin clearance was less (p less than 0.05) in hypertensive than normotensive rats before insulin infusion. Baseline fractional sodium excretion was not different between groups. Low dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.81 +/- 0.43% to 0.31 +/- 0.07% in hypertensive rats and from 1.05 +/- 0.37% to 0.47 +/- 0.18% in normotensive rats. High dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.67 +/- 0.22% to 0.21 +/- 0.08% in hypertensive rats and from 0.81 +/- 0.15% to 0.30 +/- 0.09% in normotensive rats. Sodium excretion was unchanged in time controls. The reduction in sodium excretion was similar in both rat groups during low dose and high dose insulin infusions. Mean arterial pressure and inulin clearance were unchanged from baseline values during insulin infusion in all rat groups. Glucose requirement to maintain euglycemia was greater (p less than 0.05) in normotensive than hypertensive rats at both insulin infusion rates. Thus, while hypertensive rats have reduced sensitivity to the hypoglycemic effects of insulin, the antinatriuretic response to insulin is not different from that of normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The Determination of Hemodialysis Blood Recirculation Using Blood Urea Nitrogen Measurements

The determination of blood recirculation using blood urea nitrogen (BUN) measurements in hemodialysis patients is a standard technique. The accuracy and reproducibility of these calculations have never been determined. Two pairs of recirculation studies (study A and study B) were performed in 13 patients during a single dialysis treatment. Blood samples were analyzed for BUN and recirculation was calculated. The first recirculation study (study A) was performed within 1 hour of the initiation of dialysis, with a duplicate test of recirculation performed within 15 minutes. In study B, the dialyzer blood lines were reversed in an attempt to enhance blood recirculation. After 15 minutes, duplicate tests of recirculation were again performed. Calculated recirculations before the line reversal (study A) ranged from -3.3% to 11.9% in the first test and -2.9% to 12.2% in the second test. In study A, there was no correlation (P > 0.05, r = 0.09) between the first and second calculated recirculations. In study B, an increase in recirculation was observed. Calculated recirculations ranged from 16.3% to 53.5% for the first test and 5.4% to 58.1% for the second test. A significant relationship was observed in the calculated recirculation in study B (P < 0.05, r = 0.81). The results from the present study show that the use of BUN measurements may not provide a consistent indicator of access recirculation in a patient with a low recirculation. This lack of consistency should be considered when determining further clinical treatment.

Peritoneal Abnormalities during Infectious Episodes of Continuous Ambulatory Peritoneal Dialysis

Exchanges were performed in 1-hour and 3- to 5-hour cycles when patients were noninfected and during episodes of peritonitis. The hourly exchange dialysate effluent volume decreased with the occurrence of peritonitis. These exchanges were associated with increased glucose absorption from dialysate, diminished sodium removal and augmented clearances of urea and creatinine. Protein losses were increased in the dialysate effluent of patients during an episode of peritonitis during the hourly exchanges. In the long-dwell exchanges obtained after clinical improvements of peritonitis, only protein losses were increased over control. Clearances, sodium loss in dialysate and glucose absorption were not altered from control.

Fungal Peritonitis During Continuous Ambulatory Peritoneal Dialysis: A Report of 17 Cases

Seventeen cases of fungal peritonitis and one case of Nocardia asteroides peritonitis were observed in 141 patients during the first 5 years of our continuous ambulatory peritoneal dialysis program (CAPD). Fungal peritonitis accounted for 7% of the episodes of peritonitis observed in this interval. There were eight deaths associated with fungal peritonitis. In only three instances could factors predisposing to fungal peritonitis be identified. We were unable to predict who would develop fungal peritonitis by analysis of nutritional, demographic, or technical factors associated with the dialysis procedure. The diagnosis of fungal peritonitis was easily established using routine blood agar culture techniques. Successful management of these patients included prompt removal of the Tenckhoff catheter and intravenous (IV) administration of amphotericin.

Non-invasive determination of recirculation in the patient on dialysis.

Recirculation of blood flow occurs when the fistula flow rate is inadequate to support the desired dialyzer blood flow. The percentage recirculation is normally calculated using the blood urea nitrogen of blood samples from the two dialyzer blood lines and a peripheral blood sample. However, this method is time consuming, costly, and may not always give accurate measurements. A technique was developed to measure recirculation using the injection of saline into the venous dialysis line. For this technique, an optical detector is placed across the arterial dialysis tubing, and the light intensity, which is proportional to the hematocrit, is continually measured using a computerized data collection system. After a baseline data collection period, 10 ml of saline is injected into the venous dialysis line using the sampling port. The saline that appears in the arterial dialysis line as a result of recirculation will cause a dilution of the blood and an increase in light intensity. In vitro testing showed an excellent correlation between the area under the dilution curve and percentage recirculation. This technique will provide a quick, inexpensive, and reliable measurement of recirculation.

The Tenckhoff Catheter for Peritoneal Dialysis – An Appraisal

We prospectively evaluated early (within 40 days) catheter complications in all patients receiving a dialysis catheter between 1/8/80 and 1/8/81. 50% of patients achieved a functioning catheter at the first insertion and 24% required replacement of the catheter because of poor dialysate flow. Leaking from the catheter exit site occurred in 20%, infection at the exit site in 9% and peritonitis in 19% of patients. In patients who maintain a catheter over 40 days and undergo treatment by long-term peritoneal dialysis median catheter survival was 400 days with delayed cytheter failure primarily due to failure to resolve a clinical episode of peritonitis. Although the Tenckhoff catheter is readily inserted frequent complications occur.

Attenuation of ischemic renal injury with fructose 1,6-diphosphate

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.

Peritonitis in Continuous Ambulatory Peritoneal Dialysis Patients

Peritonitis is the most important complication of continuous ambulatory peritoneal dialysis (CAPD). We reviewed our experience with peritonitis over a 2 1/2-year period. Our patients spent 4% of their total time on dialysis in hospital due to peritonitis. Thirty-eight percent of the episodes of peritonitis were treated without hospitalization. We evaluated the dialysate bag change technique as commonly performed with currently available devices (extension tubing and titanium Luerlock Tenckhoff catheter adapter). The aseptic techniques described for dialysis extension tubing changes appear adequate (with no increased incidence of peritonitis demonstrated shortly after an extension tubing set change). Long-term sterility is maintained at the dialysate bag puncture port and at the orifice of the dialysis catheter adapter (no positive cultures from the bag port and orifice of the titanium adapter). Etiologic diagnosis of uremia was not a risk factor predisposing to peritonitis. The incidence of peritonitis was greater among patients with less formal education and lower income. Out data suggest that patients with less formal education and of lower economic status be carefully evaluated before commencing CAPD.