George Eisele

Serum Potassium and Outcomes in CKD: Insights from the RRI-CKD Cohort Study

BACKGROUND AND OBJECTIVES The relationship between serum potassium (S(K)) and mortality in chronic kidney disease (CKD) has not been systematically investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the predictors and mortality association of S(K) in the Renal Research Institute CKD Study cohort, wherein 820 patients with CKD were prospectively followed at four US centers for an average of 2.6 years. Predictors of S(K) were investigated using linear and repeated measures regression models. Associations between S(K) and mortality, the outcomes of ESRD, and cardiovascular events in time-dependent Cox models were examined. RESULTS The mean age was 60.5 years, 80% were white, 90% had hypertension, 36% had diabetes, the average estimated GFR was 25.4 ml/min per 1.73 m(2), and mean baseline S(K) was 4.6 mmol/L. Higher S(K) was associated with male gender, lower estimated GFR and serum bicarbonate, absence of diuretic and calcium channel blocker use, diabetes, and use of angiotensin-converting enzyme inhibitors and/or statins. A U-shaped relationship between S(K) and mortality was observed, with mortality risk significantly greater at S(K) < or = 4.0 mmol/L compared with 4.0 to 5.5 mmol/L. Risk for ESRD was elevated at S(K) < or = 4 mmol/L in S(K) categorical models. Only the composite of cardiovascular events or death as an outcome was associated with higher S(K) (> or = 5.5). CONCLUSIONS Although clinical practice usually emphasizes greater attention to elevated S(K) in the setting of CKD, our results suggest that patients who have CKD and low or even low-normal S(K) are at higher risk for dying than those with mild to moderate hyperkalemia.

Controlled evaluation of thermal biofeedback in treatment of elevated blood pressure in unmedicated mild hypertension

In the first of two studies, 42 unmedicated mild hypertensives completed either 16 sessions of thermal biofeedback (TBF) training for hand (7 sessions) and foot (9 sessions) warming or 8 weeks of monitoring BPs at home. There was a trend (p<.10) for more of those treated (57.1%) to have DBPs lower than 90 mm Hg than for those only monitoring BPs at home (33%). Analyses of clinic BP values from random zero sphygmomanometer measurements, from 24-hour ambulatory BP monitoring, and from home BP measurements made by the patient showed no advantage for treatment versus BP monitoring. Sixteen of the 21 patients in BP monitoring were later treated. Analyses of treatment effects across all treated subjects by gender revealed a significant (p=.02) decrease in DBP for treated female subjects (n=13) but not for males (n=24). In the second study the 22 initial treatment successes, that is, those whose DBP was below 90 mm Hg at posttreatment (59.4% of those who completed treatment), were randomized to an intensive follow-up (monthly visits for 6 months, then visits every two months) emphasizing regular home practice with an electronic TBF device or regular follow-up (visits every 3 months). Twelve of the 22 were still normotensive at 12 months. There were no differences at any point during the follow-up between the two conditions in success rate or BPs despite a numerical advantage in reported frequency of home practice by those in the intensive follow-up condition.

Combined Furosemide and Human Albumin Treatment for Diuretic-Resistant Edema

OBJECTIVE: To evaluate the clinical usefulness of combined furosemide and human albumin for the treatment of diuretic-resistant edema in patients with nephrotic syndrome and cirrhosis. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966–May 2002). Key search terms included furosemide, albumin, human albumin solution, nephrotic syndrome, and cirrhosis. DATA SYNTHESIS: Hypoalbuminemia, edema, and ascites are often manifestations of nephrotic syndrome and cirrhosis of the liver. Many patients with these conditions are resistant to the effects of diuretics. The combination of furosemide and human albumin solution is occasionally used in these patients. An evaluation of published studies focusing on combined furosemide and albumin in the management of nephrotic syndrome and cirrhosis was conducted. CONCLUSIONS: Published studies report conflicting results regarding the efficacy of combined furosemide and albumin. Although it is difficult to generate firm conclusions, it appears the combination may provide clinical benefits for select patients. Given these findings, we believe that the addition of albumin to enhance diuretic efficacy should be reserved for patients with recalcitrant edema or ascites in whom diuretic doses have been maximized and those with severe hypoalbuminemia.

Pharmacokinetics of intermittent intraperitoneal ceftazidime

Ceftazidime is currently recommended as an alternative first-line agent in the treatment of peritonitis and for Pseudomonas peritonitis. The pharmacokinetics of intermittent intraperitoneal (i.p.) ceftazidime have been poorly characterized. This study was designed to characterize the pharmacokinetic disposition of a single dose of ceftazidime in anuric and non-anuric CAPD patients, over 48 hours. This was a prospective, open label, pharmacokinetic study. The study was conducted in an independent, outpatient dialysis center. Ten volunteer continuous ambulatory peritoneal dialysis (CAPD) patients with and without residual renal function, no peritonitis or antibiotics in the previous 4 weeks, and on CAPD for at least 2 months were recruited. Patients received a single dose of i.p. ceftazidime (15 mg/kg) in the first daytime exchange over a 6-hour dwell, after an overnight dwell. Serum, urine, and dialysate were collected over a 48-hour period. A high-pressure liquid chromatography (HPLC) assay was used to analyze ceftazidime in these samples. Pharmacokinetic parameters were calculated. Six of the 10 patients were non-anuric with a mean residual renal creatinine clearance of 2.9 +/- 1.6 mL/min. The mean +/- SD bioavailability was 72% +/- 14%, and the volume of distribution was 0.34 +/- 0.08 L/kg. The mean serum elimination half-life of 22 +/- 5 hours. The peritoneal clearance was 5.74 +/- 1.6 mL/min. No difference was detected between anuric and nonanuric patients. Mean plasma and dialysate concentrations at 24 hours were 24 +/- 6 microg/mL and 18 +/- 7 microg/mL, respectively, and were 12.0 +/- 3.6 microg/mL and 7.4 +/- 3.1 microg/mL at 48 hours, respectively. Once-daily i.p. dosing of ceftazidime achieves serum and dialysate levels greater than the MIC of sensitive organisms over 48 hours.

The Longitudinal Chronic Kidney Disease Study: A Prospective Cohort Study of Predialysis Renal Failure

Chronic kidney disease (CKD) is a significant public health problem: every year the number of Americans living with CKD and requiring renal replacement therapy increases. In addition, individuals with CKD have substantially increased morbidity and mortality compared to the general population. The Longitudinal Chronic Kidney Dialysis (LCKD) Study is a multicenter, prospective, observational study of patients with moderate to severe CKD that was designed to better describe the course of the disease and the determinants of patient outcomes. Patients with moderate to severe CKD (glomerular filtration rate [GFR] < 60 ml/min/m2) from four academic nephrology clinics were enrolled between 2000 and 2002. Special cardiac and vascular testing has recently commenced as phase II of this study. Areas that have been or are currently being studied include anemia management, health‐related quality of life (HRQOL), medication use, and markers of cardiovascular disease. This article describes the LCKD Study in the context of current knowledge of CKD.

Continuous Ambulatory Peritoneal Dialysis: A Review of its Mechanics, Advantages, Complications, and Areas of Controversy

OBJECTIVE: The primary objective of this article is to review the mechanics, advantages, complications, pharmacokinetics, and future trends of continuous ambulatory peritoneal dialysis (CAPD) as they pertain to pharmacotherapy. DATA SOURCES: Pertinent articles were obtained from an English-language literature search using MEDLINE (1980–1991), Index Medicus (1987–1990), and bibliographic reviews of review articles. Indexing terms included peritoneal dialysis, pharmacokinetics, peritonitis, vancomycin, and fluoroquinolones. DATA SYNTHESIS: All clinical studies comparing organism recovery methods and treatment of peritonitis have methodologic limitations (e.g., comparison of disparate patient groups, different definitions of peritonitis, lack of follow-up, lack of control for sterile cultures) that may affect the reported results. CONCLUSIONS: CAPD is an alternative to hemodialysis for the treatment of endstage renal disease and has many complications, leading to significant morbidity. This indicates that CAPD is not appropriate for all patients. Using blood-culturing techniques to culture for dialysate is most productive, but also the most costly. There are few data to indicate exactly the drugs, doses, and durations of choice for peritonitis. Both intraperitoneal and oral administration appear to be appropriate.

Association between markers of collagen turnover, arterial stiffness and left ventricular hypertrophy in chronic kidney disease (CKD): the Renal Research Institute (RRI)-CKD Study

BACKGROUND Markers of collagen turnover have not been well studied in the context of cardiovascular disease in patients with chronic kidney disease (CKD). We investigated the associations between serum markers of collagen turnover [N-terminal procollagen type 3 propeptide (PIIINP) and carboxy-terminal telopeptide (C1TP)] and both pulse wave velocity (PWV) and left ventricular mass index (LVMI) in a CKD cohort. METHODS The study included 242 patients (mean age 60 ± 15 years, 53% males, 80% Caucasian, CKD Stages 3-5) from the Renal Research Institute (RRI)-CKD Study. Serum PIIINP and C1TP levels were analyzed by radioimmunoassay. PWV was obtained by applanation tonometry from carotid and femoral pressure wave contours. LVMI was measured by echocardiography. Statistical analyses included Pearsons correlations and multiple linear regression. RESULTS Both PIIINP and C1TP values were significantly higher in more advanced stages of CKD (P < 0.05). A positive correlation was demonstrated between PWV and LVMI (r = 0.25, P = 0.0018), persisting after adjustment for potential confounders (partial r = 0.27, P = 0.0009). PIIINP correlated with PWV (r = 0.16, p = 0.029) and LVMI (r = 0.16, P = 0.0018), while C1TP correlated with LVMI (r = 0.18, P = 0.013) but not with PWV (r = 0.12, P = 0.09). In multivariable analysis adjusting for race, diabetes, estimated glomerular filtration rate (eGFR) and renin-angiotensin-aldosterone system inhibitors, only PWV (β = 0.45, P = 0.0017) but not LVMI (P = 0.09) remained significantly associated with serum PIIINP. CONCLUSIONS Our results demonstrate the association of PIIINP (but not C1TP), a circulating biomarker of collagen synthesis with arterial stiffness (but not with LVMI) in a CKD cohort, independent of eGFR. This suggests that altered collagen turnover may play a role in the pathogenesis of arterial stiffness in CKD.

Thermal biofeedback as an effective substitute for sympatholytic medication in moderate hypertension: A failure to replicate

Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level. They then completed one of three conditions over an 8-week interval: (I) 16 sessions of TBF (hand and foot warming); (II) 16 sessions of frontal EMG-BF; (III) regular home monitoring of BP. Attempts were then made to withdraw the patients from the sympatholytic medication. Those successfully withdrawn were followed up for one year. There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up. Only 27% of treated patients (including Condition III failures who were remedicated and treated with TBF) were successfully off of the sympatholytic at a one-year follow-up. The generally poor results on clinical outcome were confirmed by clinic BPs, home BPs by patients, and 24-hour ambulatory BPs.

Prediction of serum vancomycin concentrations following intraperitoneal loading doses in continuous ambulatory peritoneal dialysis patients with peritonitis

SummaryThe pharmacokinetics of vancomycin were studied in continuous ambulatory peritoneal dialysis patients with peritonitis. Six patients received an intraperitoneal loading dose of 15 mg/kg and 4 received an intraperitoneal dose of 25 mg/L. The ability of 2 methods to predict serum concentrations during the loading dose exchange was determined. The mean serum concentration after the exchange was 17.8 ± 2.2 mg/L in patients receiving the loading dose. The mean dialysis clearance in all patients was 0.94 ± 0.34 L/h. 66.6 ± 13.4% of a dose was absorbed into the circulation in 4h. The volume of distribution was 0.61 ± 0.46 L/kg, and the half-life for equilibration of vancomycin into the circulation from dialysate was 2.76 ± 0.94h. Two methods of predicting serum vancomycin concentrations were tested, with 1 method predicting values significantly different from measured concentrations while the other did not. Serum vancomycin concentrations can be accurately predicted during a loading dose exchange.

Effects of 24-hour ambulatory blood pressure monitoring on daily activities.

Compared the self-monitored activities, locations, and postural positions of 28 hypertensives while they wore an alarm watch and then while they wore a 24-hr ambulatory blood pressure monitor (ABPM) to see if wearing the ABPM led to alterations in behavior. Within the limitations of the study (no counterbalancing of order and twice as many ABPM measures as watch measures), we found significant differences in frequency of being at home or in miscellaneous settings, in standing and reclining positions, and in mental, physical and miscellaneous activities between the two occasions.