Periodic limb movements in sleep revealed by treatment of sleep apnea with continuous positive airway pressure in the advanced chronic kidney disease population.

The chronic kidney disease (CKD) population has a high incidence of sleep disorders, including sleep apnea (SA) and periodic limb movements in sleep (PLMS). SA and PLMS often occur concurrently and may predict mortality in the end stage renal disease (ESRD) population. In this study, we investigated whether sleep fragmentation secondary to SA masks the underlying frequency or severity of PLMS in 16 patients with CKD, dialysis and not-on-dialysis patients (CKD-ND), and if successful treatment of SA with continuous positive airway pressure (CPAP) results in the increased appearance of PLMS. All subjects had polysomnography (PSG) diagnosed SA. The mean apnea-hypopnea index (AHI) at baseline and with CPAP treatment was 49.8 ± 25.6/h and 5.2 ± 9.1/h, respectively. With successful treatment of SA with CPAP, PLMS index (PLMSI) increased 237.7% from baseline of 13.8 ± 23.8/h to 32.8 ± 33.7/h with CPAP treatment (p = 0.019). Arousing PLMS index (APLMSI) also increased 191.5% from mean baseline of 8.2 ± 18.2/h to 15.7 ± 18.5/h with CPAP treatment (p = 0.026). PLMS occur during uninterrupted NREM sleep. SA may mask the underlying incidence and severity of PLMS in CKD patients by disrupting NREM sleep. PLMS more than doubled during successful treatment of SA. Therefore, despite successful treatment of SA with CPAP, sleep deprivation may persist due to clinical manifestation of underlying PLMS in patients with CKD. The actual underlying prevalence and severity of CKD-associated PLMS are likely higher than appreciated and are suppressed by SA in the CKD population.

Quantifying the role of factors that limit attainment of K/DOQI urea reduction ratio dialytic goal.

BACKGROUND: For many ESRD patients who are prescribed a certain level of hemodialysis (HD), delivered dose often does not achieve prescription. While various causes have been well-documented in the literature, there are no available data that may be used in predicting the likelihood of achieving a particular urea reduction ratios (URR) goal based on the number of these factors present. This study evaluated URRs of all patients in an outpatient HD unit for a 6-month period to identify factors significant in attaining goal in order to predict likelihood of goal attainment based on number of factors present. METHODS: The inclusion criterion in this study was any HD patient during the study period with > or = 3 monthly URR measurements. Of 203 patients, 169 qualified for 900 treatments. A database was created for each patient that included demographics, factors affecting K(urea), time and access. After grouping percentages of patients with URR > or = 70%, 65 - < 70%, and < 65%, we studied a subset of 107 patients (568 treatments) that had at least 1 URR < 70% to identify factors associated with a URR of > or = 65% vs. < 65%. To determine factors predictive of URR > or = 65%, a sum percentage across all treatments was created for each patient. Mean percentages were compared between groups created by constant characteristics (e.g. gender, DM). Variables, e.g. catheters, were summarized as a percentage for each patient, and these percentages were correlated with rate of URR > or = 65%. Time was assigned a value of 0 (prescribed), positive (longer), negative (shorter), summarized as per-patient mean. After these factors were identified, each treatment was reviewed to determine the percentage of treatments > or = 65% with the number of statistically significant factors present. RESULTS: The average, across all patients, of percentage of treatments meeting URR > or = 65% was 87.95% while a mean of 66.65% met URR > or = 70%. Factors associated with percentage of treatments per patient not meeting K/DOQI goal included catheter use (Spearman's correlation = -0.31, p = 0.001), blood flow < 90% of prescription (Spearman's correlation = -0.17, p = 0.041), younger age (> or = 61 years vs. < 61 years, p = 0.001: patients > or = 61 years had a higher percentage of URR > or = 65%), inadequate access for prescribed blood flow (Spearman's correlation = -0.32, p = 0.001), actual time vs. prescribed time (Spearman's correlation = 0.25, p = 0.009), and HD w/o heparin (Spearman's correlation = -0.21, p = 0.031). In 178 treatments, all having "good" values (no catheter, blood flow > or = 90% prescribed, age < or = 61 years, etc.), the percentage of treatments meeting URR of < or = 65 was 96.1%. With 1 bad value factor: 83.8% of 216 treatments met goal, 2 bad value factors: 71.7% of 106 met goal, 3 bad value factors: 60.5% of 43 met goal. With 4 or 5 bad value factors: only 36.1% of 25 treatments met goal. CONCLUSIONS: Significant factors in meeting adequacy defined by K/DOQI in rank order (excluding age) include inadequate access for prescribed blood flow, catheter use, time, lack of heparin and inability to achieve blood flow > or = 90% prescribed. A direct correlation exists between number of these factors present and K/DOQI goal attainment in a given treatment.

Use of antibacterial agents in renal failure.

This article reviews the pharmacokinetics of antibacterial agents in patients with normal and decreased renal function. The concepts of volume and distribution, rate of elimination, loading and maintenance doses, and therapeutic drug monitoring are delineated. Special reference is made to the intermittent dosing of cefazolin with hemodialysis. Newer, as well as traditional methods of extracorporeal circulation and the resultant changes in antibacterial agent pharmacodynamics are discussed.

Potential novel predictors of mortality in end-stage renal disease patients with sleep disorders.

Patients with end-stage renal disease (ESRD) have an annual mortality rate exceeding 20%, although some survive many years. The ESRD population has a high incidence of sleep disorders, including sleep apnea and periodic limb movements in sleep (PLMS). Sleep disorders result in sleep deprivation, which can negatively affect immune function and cardiovascular-related outcomes, common causes of death in patients with ESRD. This study examined predictors of mortality in patients with ESRD with sleep problems. Twenty-nine consecutive patients with ESRD reporting disrupted sleep or daytime sleepiness were studied by all-night polysomnography. All patients were followed up until death, transplantation, or study termination. Among the variables studied, including such previously reported predictors as serum albumin level, urea reduction ratio, and hematocrit, only the PLMS index (PLMSI), arousing PLMSI (APLMSI), and total number of arousals per hour of sleep significantly predicted mortality. The 20-month survival rate with a PLMSI less than 20 was greater than 90% versus 50% for a PLMSI of 20 or greater (exact log-rank, P = 0.007). For the deceased versus survivor groups, mean PLMSI was 119.1 versus 19.8 (P = 0.01) and APLMSI was 48.1 versus 7.8 (P = 0.00006), with a mean survival of 10.3 versus greater than 25.5 months, respectively (P = 0.001). Median survival of patients with a PLMSI greater than 80 was only 6 months. PLMSI, APLMSI, and total arousals per hour of sleep were strongly associated with mortality in patients with ESRD with sleep disorders independent of other factors and may be novel predictors of near-term mortality.

Use of antibacterial agents in renal failure.

This article provides information on the pharmacokinetics of antibacterial agents in patients with normal renal function and those with impaired renal function. Specific discussion includes the use of serum levels, dosage adjustments in dialysis, new strategies for cefazolin dosages in dialysis patients, and antibiotic toxicity in renal failure, and tabular data is presented for determining appropriate dosages for varying degrees of renal failure.

A preliminary study of the effects of correction of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (The SLEEPO study).

End-stage renal disease (ESRD) is commonly associated with complaints of disturbed sleep and sleep disorders, frequently related to periodic limb movements in sleep (PLMS) or sleep apnea that may result in daytime sleepiness and other sequelae. Improvements in quality of life, including subjective sleep quality, have been reported in ESRD patients treated with recombinant human erythropoietin (rHuEPO). We investigated the objective effects of normalizing hematocrit on sleep disorders, sleep patterns, and daytime ability to remain awake in ESRD patients. Ten hemodialysis patients with sleep complaints while on rHuEPO therapy were studied by polysomnography while moderately anemic (mean hematocrit, 32.3%) and again when hematocrit was normalized (mean hematocrit, 42.3%) by increased rHuEPO dosing. Sleep patterns and associated parameters were monitored. Delivered dialysis dose and iron storage factors were monitored. Maintenance of Wakefulness Testing (MWT) was performed to assess daytime alertness/sleepiness. All 10 subjects experienced highly statistically significant reductions in the total number of arousing PLMS (P = 0.002). Nine of 10 subjects showed reductions in both the Arousing PLMS Index (P < 0.01) and the PLMS Index (P = 0.03) when hematocrit was normalized. Measures of sleep quality showed trends to improved quality of sleep. MWT demonstrated significant improvement in the length of time patients were able to remain awake (9.7 versus 17.1 minutes; P = 0.04). RHuEPO therapy with full correction of anemia reduces PLMS, arousals from sleep, and sleep fragmentation while allowing for more restorative sleep and improved daytime alertness. These findings may explain one mechanism for the improved quality-of-life parameters reported in ESRD patients treated with rHuEPO.

Antibacterial agents in renal failure.

This article provides background information on the pharmacokinetics of antimicrobial agents in patients with normal and impaired renal function. Tables are provided to allow quick determination of appropriate dosages for varying degrees of renal failure. Specific mention is made of aminoglycoside dosing, dosage adjustment in dialysis, and antibiotic toxicity in renal failure.

Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients.

The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.

Renal papillary necrosis in a hemodialysis patient.

We present the first case report of bilateral renal papillary necrosis developing in a patient on hemodialysis. A 37-year-old hypertensive male with chronic glomerulonephritis had a normal retrograde pyelogram one year prior to initiation of hemodialysis. After two years of maintenance dialysis, he presented with gross hematuria and was found to have extensive bilateral renal papillary necrosis. His only predisposing factor was hepatic cirrhosis. It is postulated that recurrent hypotensive episodes associated with hemodialysis may lead to renal papillary necrosis in predisposed individuals. This diagnosis should be considered in hemodialysis patients who develop hematuria.

Sleep disordered breathing in ESRD: acute beneficial effects of treatment with nasal continuous positive airway pressure.

Complaints about sleep and daytime alertness are common in ESRD patients. Eight consecutive ESRD patients with a sleep complaint were studied with all-night polysomnography. All were found to have significant sleep apnea with a mean apnea/hypopnea index (AHI) of 64 +/- 41.6 episodes per hour of sleep (range 7.5 to 140/hr of sleep). The majority of apneas were of the central or mixed variety causing severe fragmentation of sleep and frequent awakenings. Treatment was attempted with nasal continuous positive airway pressure (NCPAP). NCPAP was highly successful in six of the eight patients, reducing the mean AHI to normal or near normal levels (6.0 +/- 3.8/hr of sleep, P < 0.02 vs. baseline). The quality of sleep was significantly improved with statistically significant decreases in light stage 1 sleep, and nocturnal oxygenation improved with statistically significant increases in low SaO2 values. Five of six responders reported that they awoke feeling more alert and fewer times from sleep. The etiology of sleep apnea in ESRD is unknown although the frequent central apneas suggest a dysfunction of central respiratory control resulting from the effects of renal failure. Sleep-related complaints in patients with ESRD are likely to result from sleep apnea, a sleep disorder that can be diagnosed with polysomnography and treated with NCPAP.

Suppression of renal vein renin profiles by mannitol prophylaxis: implications in the evaluation of renovascular hypertension.

Renal arteriography with concomitant renal vein renin profiling remains the diagnostic standard for evaluating the anatomic and physiologic significance of stenotic renal artery lesions in hypertensive patients. False-negative renal vein renin profiles with failure of lateralization in patients with anatomically apparent high-grade stenosis complicate the diagnostic process. Mannitol is frequently administered prophylactically to minimize the risk of dye nephropathy in these patients. Yet, the potential effects of mannitol on renal vein renin profiling in man have not been previously reported. Seven patients with renovascular hypertension were studied prospectively to determine changes in renal vein renin profiles before and after mannitol prophylaxis. Despite captopril stimulation, all patients demonstrated significant renin suppression leading to the loss of renin lateralization in patients with unilateral renovascular hypertension. In 60% of the patients, renal vein renin ratios fell to below the standard 1.5 to 1 ratio after mannitol infusion. In patients with bilateral renovascular disease, the least stenotic side suppressed completely, while the more stenotic side suppressed partially. Percent suppression analysis showed a mean suppression of 56.8% on the stenotic side versus 8.2% on the noninvolved side (P less than 0.002). In every study, suppression equaled or exceeded 32% on the involved side and was less than this on the noninvolved side. Thus, the degree of renin suppression following mannitol infusion may prove to be an important tool in the diagnosis of clinically significant stenotic lesions. The mechanism of mannitol-induced suppression remains undefined, but appears independent of volume expansions or dilutional effects. The inhibitory effects of mannitol on renin profiles can obscure the diagnosis of underlying renovascular hypertension.

Successful treatment of postparathyroidectomy hypocalcemia using continuous ambulatory intraperitoneal calcium (CAIC) therapy.

Severe, recalcitrant hypocalcemia and hungry bone syndrome can complicate parathyroidectomy in end-stage renal disease patients. Treatment with prolonged and massive doses of intravenous calcium, with calcitriol supplementation, is often necessary, but potentially dangerous and may prolong hospitalization. Three CAPD patients (including 1 with malabsorption) were safely treated by adding 1 to 3 ampules (10-30 mL) of 10% calcium gluconate solution to each bag of dialysate for up to 29 months. Continuous ambulatory intraperitoneal calcium (CAIC) therapy was initiated postoperatively and continued on an outpatient basis until the patients' hungry bone syndrome resolved and serum calcium normalized. Complications such as visible dialysate precipitation or an increased rate of peritonitis were not observed. Mean total calcium uptake was approximately 137 to 226 mg/exchange. We conclude that CAIC therapy is a safe, effective treatment both for CAPD patients with postparathyroidectomy hypocalcemia with hungry bone syndrome, as well as in patients with hypocalcemia secondary to malabsorption.

Carpal tunnel syndrome in dialysis patients: comparison between continuous ambulatory peritoneal dialysis and hemodialysis populations.

Carpal tunnel syndrome (CTS) has been reported with increased frequency in hemodialysis (HD) patients. A comparative study of patients on continuous ambulatory peritoneal dialysis (CAPD) has not been previously reported. To delineate the significance of dialytic modality and access-related risk factors, this study investigated the incidence and patient characteristics of CTS in CAPD v HD populations. One hundred and fifty one patients (HD n = 90, CAPD n = 61) were evaluated by questionnaire, physical examination, and nerve conduction studies. Age, gender, renal diagnosis, access, diabetic history, and duration of dialysis were determined. Eight of 57 CAPD and 15/83 HD patients had CTS. chi 2 testing revealed no significant difference in incidence (P = 0.7). It is concluded that CTS occurs with similar incidence in CAPD and HD populations. Dialytic modality and access are not likely to be factors in the development of CTS. Rather, CTS is a metabolic complication of end-stage renal failure.

Hydrothorax in continuous ambulatory peritoneal dialysis: successful treatment with intrapleural tetracycline and a review of the literature.

Recurrent hydrothorax complicating peritoneal dialysis has been considered a contraindication to continuing peritoneal dialysis. In the continuous ambulatory peritoneal dialysis (CAPD) population this problem has generally required a change of dialytic modality. Talc poudrage has been attempted to ameliorate the problem but has met with limited success. We report a successful case of intrapleural instillation of tetracycline to induce a pleural symphysis and prevent recurrence of peritoneal dialysis-related hydrothorax in a patient who refused any alternative mode of dialysis. We also review the literature, pathophysiology, epidemiology, diagnosis, and management of this compromising problem.