Underutilization of aspirin in hemodialysis patients for primary and secondary prevention of cardiovascular disease.

BACKGROUND: Patients on hemodialysis are at high risk for cardiovascular disease (CVD). Aspirin is an established therapy for primary and secondary prevention of CVD that may be underutilized in hemodialysis patients. To better understand the use of aspirin in hemodialysis patients, we examined the experience of an urban hemodialysis center. Guidelines for use as well as associated risks and benefits are reviewed. METHODS: Medical records for patients receiving hemodialysis treatment at our center (New York City, USA) in May 2004 were reviewed for aspirin use, presence of CVD, and potential contraindications to aspirin therapy. CVD was defined as a history of coronary artery disease, ischemic stroke, transient ischemic attack, or peripheral vascular disease. Potential contraindications to aspirin therapy included history of clinically significant bleeding or increased risk of bleeding, aspirin allergy and routine treatment with other anticoagulants. RESULTS: 176 patients were eligible for the study and 172 (98%) were included. Although 74 patients had a history of CVD, only 38 (51 %) of these were treated with aspirin. Among patients with a history of CVD who were not treated with aspirin, 19 (53%) had no identifiable contraindications to aspirin therapy for secondary prevention of CVD. Ninetyeight patients had no history of CVD, and 18 (18%) of these were treated with aspirin. Of patients without a history of CVD who were not treated with aspirin, 57 (71%) had no identifiable contraindications to aspirin therapy for primary prevention of CVD. CONCLUSIONS: Aspirin is underutilized in hemodialysis patients for the primary and secondary prevention of CVD. Given the high risk of CVD in hemodialysis patients, therapy with aspirin may be of significant benefit and prospective studies of aspirin therapy are needed.

Increasing incidence of focal segmental glomerulosclerosis and an examination of demographic patterns.

BACKGROUND: Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of the nephrotic syndrome in adults and an important cause of end-stage renal disease. Its incidence has dramatically increased in the last two decades and it is especially prevalent among black patients. The trend of FSGS incidence has not been reported beyond 1997. METHODS: We retrospectively reviewed all renal biopsies performed at our institution between 1986 and 2002 and identified patients with diagnoses consistent with primary glomerulopathy (PG), which included: minimal-change disease (MCD), idiopathic focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN), IgA nephropathy (IgA), membrano-proliferative glomerulonephritis (MPGN) and mesangioproliferative glomerulonephritis. Patients with possible secondary causes for their renal disease were excluded. Clinical data at the time of biopsy and follow-up data were collected and analyzed. RESULTS: During the period from January 1986-December 2002, 299 renal biopsies were performed and 132 patients were diagnosed with PG. FSGS was the most common form of PG representing 37.8% of all PG followed by IgA 27.3%, MGN 16.6% and MCD 9.1%. Among FSGS patients 59% were females, 64% had nephrotic range proteinuria and 54% had the nephrotic syndrome. Mean serum creatinine was 2.0 +/- 0.2 mg/dl and mean protein excretion was 6.1 +/- 1.0 g/day. The incidence of FSGS increased from 19.3% (1986-1991) and 16.6% (1992-1997) to 58.5% in the period from 2002. The increase occurred among black and Hispanic patients (33.3-79.2%) as well as white patients (12.5-51.5%). Black and Hispanic patients with PG presented for renal biopsy at a significantly younger age than white patients (p = 0.003), with mean age 37.5 +/- 2.0 years vs. 50.3 +/- 1.8 years. White FSGS patients were significantly older than white non-FSGS patients (mean age 56.4 +/- 3.2 years vs. 48.0 +/- 2.0 years, p = 0.03). Black and Hispanic FSGS patients were also older when compared to their non-FSGS counter-parts (mean age 40.6 +/- 2.8 years vs. 32.1 +/- 2.0 years, p = 0.04). When patients were stratified by age (< 45 years and > or = 45 years), FSGS was the most common diagnosis in both age groups among black and Hispanic patients (55.1% and 88.8%) but only among older white patients (36.2%). CONCLUSIONS: The incidence of FSGS as a proportion of PG in our population has increased markedly in the most recent time period analyzed (1998-2002). The increase has occurred among both white and black and Hispanic patients. We also found that FSGS was most prevalent in patients > or = 45 years.

Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

INTRODUCTION: Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. METHODS: HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33% were enrolled. Subjects were divided as follows: Group 1: target SFer of 200 ng/ml, Group 2: target SFer of 400 ng/ml. Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target. HCT was maintained between 32.5% and 36% by adjusting rHuEPO dosage. RESULTS: Mean SFer concentration at the study conclusion in Group 1: 261 ng/ml; Group 2: 387 ng/ml. The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week (250 - 219 U/kg bw/wk) while in Group 2 it was 154 U/kg body weight/week (312 - 158 U/kg bw/wk) (p < 0.001). There was no difference in HCT between groups. Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements.

Combined converting enzyme inhibition and angiotensin receptor blockade reduce proteinuria greater than converting enzyme inhibition alone: insights into mechanism.

Patients with various renal diseases receiving an angiotensin-converting enzyme inhibitor (CEI) were enrolled in a protocol to determine whether adding an angiotensin type 1 receptor blocker (ARB) reduces urinary protein excretion (UPE). All patients had significant proteinuria (range 517-8,562 mg/24 h) despite administration of CEI for at least 4 weeks. Following baseline measurements, losartan (50 mg/d) was started and testing was repeated at 1 month. Compared with CEI alone, combined CEI plus ARB reduced UPE by 45 +/- 8% (p < 0.005). Compared with CEI alone, CEI + ARB lowered UPE in each patient independent of baseline protein excretion or renal diagnosis. Reduction in proteinuria occurred independent of changes in mean arterial blood pressure (MAP), suggesting that the mechanism involved local changes in glomerular dynamics. If renal angiotensin II (ANG II) formation occurred despite CEI, the ANG II formed would suppress plasma renin activity (PRA), and adding an ARB would cause PRA to rise. In 7 of 10 subjects, addition of ARB to CEI increased PRA (p < 0.03) suggesting that intrarenal ANG II formation occurred in CEI-treated subjects. As a second marker of ANG II tissue activity, we measured the effects adding ARB on plasma aldosterone (ALDO). In 9 of 10 subjects, ALDO was acutely lowered (p < 0.009) suggesting that ANG II levels were incompletely blocked by CEI. We conclude that: combined CEI and ARB reduces UPE greater than CEI alone; reduction in proteinuria is independent of changes in MAP or renal diagnosis; and the additive effects of CEI and ARB are due at least in part to greater inhibition ofANG II action at the tissue level in the kidneys and adrenal glomerulosa.

Assessment of sonographic venous peak systolic velocity in detecting hemodialysis arteriovenous graft stenosis.

There is no single effective means of assessing arteriovenous access function, although monitoring hemodialysis venous pressure (VP) or measuring access recirculation may be of some benefit. The present study assesses prospectively the efficacy of following the peak systolic velocity (PSV) as a single measure to detect arteriovenous graft (AVG) stenosis. PSV was measured in 12 patients after new AVG placement and at approximately 2-month intervals. Angiography was also performed after new graft placement and when PSV was elevated to greater than 200 cm/sec, hemodialysis access VP increased to greater than 150 mm Hg on three consecutive readings, or access recirculation increased to greater than 11%. PSV was then compared with results from angiography, VP monitoring, and access recirculation. The 12 patients underwent 34 PSV studies, followed by angiography on 25 occasions. Each patient underwent at least one angiogram. Each abnormal PSV value was confirmed with the finding of stenosis on angiogram, except for two patients with PSVs greater than 400 cm/sec and normal angiography results. VP and recirculation were not elevated. During this period, two patients developed thrombosis of the AVG, and two patients underwent angioplasty with improvement in PSV. We conclude that elevations in PSV measured at the venous anastomosis are an effective means of screening for AVG stenosis, AVG stenosis can occur early after AVG placement, and elevated VP and recirculation are late findings in AVG dysfunction.

Body composition assessed by neutron activation analysis in dialysis patients.

Malnutrition is prevalent in end-stage renal disease (ESRD) patients treated with hemodialysis (HD) and peritoneal dialysis (PD). In addition, there is increased incidence of morbidity in this group. Evaluation of nutritional status is important. Application of body composition in the ESRD population to evaluate body compartments and to assess nutritional health has become more common in clinical practice. Neutron activation analysis (NAA) may provide data on metabolically active tissue by quantification of total body potassium (TBK) for body cell mass and assessment of protein by total body nitrogen (TBN). This method may be able to detect changes in body composition before clinical signs of malnutrition are apparent. Ten HD (5 male and 5 female) and 10 PD patients (7 male and 3 female) were evaluated by NAA, TBK, and isotope dilution. Female PD patients had an increased total body water (TBW) and increased intracellular water compared to HD females. Albumin was lower in PD women. There was no significant difference between PD men and laboratory controls in TBW, extracellular water, and TBN. The clinical application of body composition methods for evaluation of dialysis patients by serial assessment and for development of a bedside tool needs further study.

Dual-energy X-ray absorptiometry: a review.

Dual-energy X-ray absorptiometry (DXA) has been recently used for body composition analysis in dialysis patients. It is based on the principle that X-rays passed through various body tissues have different attenuation and, therefore, can be differentiated. By using X-rays at two different energy levels, better tissue differentiation is possible compared with single energy systems. This article will review the evolution of DXA scanners and the role DXA has in assessing body composition in dialysis patients. Overall, this technique has excellent precision and holds promise for use in the serial evaluation of body composition and nutritional evaluation of dialysis patients.

Long-term follow-up after subtotal parathyroidectomy in patients with renal failure.

OBJECTIVES/HYPOTHESIS: The most appropriate type of surgery for hyperparathyroidism secondary to renal failure remains controversial. We report a 5-year experience of patients with hyperparathyroidism secondary to end-stage renal disease who underwent subtotal parathyroidectomy. We believe that this is the procedure of choice, offering several advantages over total parathyroidectomy with and without reimplantation. STUDY DESIGN: Retrospective review. METHODS: Review of 14 consecutive renal failure patients who underwent subtotal parathyroidectomy by one surgeon (A.K.) was performed. Follow-up ranged from 4 to 54 months. All patients were receiving chronic maintenance dialysis. All patients came to surgery with clinical symptoms of parathyroid bone disease, elevated serum calcium levels (10.1-12.4 mg/dL), and intact parathyroid hormone levels (619-4160 pg/mL), despite maximal medical therapy. At exploration four glands were identified in all patients and three and a half were removed. RESULTS: All patients experienced symptomatic relief postoperatively with normalization or near-normalization of serum calcium concentration and intact parathyroid hormone concentrations. One patient developed recurrent disease 4 months after surgery, and on re-exploration a supernumerary substernal gland was identified. A second patient developed recurrent symptoms 4 years after surgery and at the time of this writing was awaiting re-exploration. CONCLUSIONS: All patients had either resolution of or marked improvement in their subjective complaints. There have been no cases of permanent hypoparathyroidism. We believe that subtotal parathyroidectomy is the best procedure for patients with refractory symptoms of secondary hyperparathyroidism.

Renin-aldosterone system can respond to furosemide in patients with hyperkalemic hyporeninism.

Thirty-four patients (65.3+/-3.3 years of age, mean+/-SEM) with hyperkalemia (serum potassium >5.0 mEq/L) had measurement of their renin-aldosterone system. Nineteen patients (56%) had plasma renin activity (PRA) >1.5 ng/mL/h, which was not low, while 15 (44%) had PRA <1.5. Twelve of the 15 hyporeninemic hyperkalemic patients were studied to determine whether their renin-aldosterone system responded to 2 weeks of furosemide, 20 mg daily. Four were nonresponders: PRA averaged 0.3+/-0.1 ng/mL/h, and it did not increase with furosemide or respond to captopril before or after furosemide. Eight patients were responders: PRA averaged 0.6+/-0.2 ng/mL/h and increased with furosemide to 5.5+/-3.4 ng/mL/h. Captopril failed to increase PRA before furosemide, but PRA increased to 15.3+/-8.4 ng/mL/h after furosemide. Plasma aldosterone was low in both nonresponders and responders (3.5+/-1.2 ng/dL vs 5.8+/-2.5 ng/dL) and did not increase significantly with furosemide (4.3+/-1.7 ng/dL vs 8.7+/-2.5 ng/dL). Serum potassium did not fall and therefore did not limit the rise in aldosterone. Renin responders had greater body weight, were predominantly female (6/8 vs 2/4) and were more likely to have diabetes mellitus (7/8 vs 0/4). Plasma atrial natriuretic peptide (ANP) fell with furosemide in 8 of 8 responders and in 1 of the 2 nonresponders in whom it was measured. Neither group had suppressed plasma prorenin levels, indicating no suppression of renin gene expression. These results indicate that many hyperkalemic patients do not have suppressed PRA. Further, a majority of patients with suppressed PRA have high levels of ANP and can respond to diuretic therapy with a rise in PRA and a fall in ANP, suggesting physiologic suppression of the renin system by volume expansion. A minority of hyperkalemic patients with suppressed PRA had PRA that did not increase under these study conditions.

Percentage body fat determination in hemodialysis and peritoneal dialysis patients: a comparison.

OBJECTIVE: To evaluate percentage body fat in hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: A prospective study of 20 HD patients and 20 PD patients. SETTING: Sol Goldman Renal Therapy Center, Lenox Hill Hospital, New York, NY; Baumritter Kidney Center Albert Einstein College of Medicine, Bronx, NY; Body Composition Unit, St Luke's Roosevelt Hospital, Columbia University, New York, NY. PATIENTS: Twenty HD (10 men, 10 women) patients, mean age 41.8 +/- 2.4 years and 20 PD (12 men, 8 women) patients, mean age 48.6 years +/- 3.0 years. INTERVENTION: This is a noninterventional study. PATIENTS signed consent to undergo dual-energy x-ray absorptiometry, total body potassium counting bioelectrical impedance analysis, total body water determination, and anthropmetric evaluation. MAIN OUTCOME MEASURES: Present and compare percentage body fat between HD and PD patients as determined by the methods used. RESULTS: Percentage fat is not different between HD and PD patients. Differences in absolute values of percent fat between techniques exist. CONCLUSION: HD patients and PD patients may be evaluated by the methods of body composition used. Percentage body fat will vary among techniques; therefore the same method should be used to follow a patient over time.

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.

Comparison of five body-composition methods in peritoneal dialysis patients.

Body-composition assessment is an important method of evaluating nutritional status in peritoneal dialysis patients. Because body-composition measurement estimates have not been fully validated in this population, we assessed five body-composition methods in 30 well-dialyzed peritoneal dialysis patients. The techniques studied included bioelectrical impedance analysis, dual-energy X-ray absorptiometry, total-body potassium counting, and anthropometry by two techniques. The dialysis patients were matched for age, race, sex, height, weight, and body mass index with 29 healthy control subjects in our laboratory database. By 5 x 2 x 2 analysis of variance, significant differences were found between results by modality (P < 0.0001) as well as by sex, with women having an increased percentage of fat (P < 0.0001). However, there was no significant intermethod difference by condition (peritoneal dialysis or control). That is, although significantly different percentage fat values were found between the body-composition techniques, this variability was independent of whether the measurement was made on control or peritoneal dialysis patients. Despite the differences between modalities, all techniques were found to correlate significantly with each other (P < 0.01 or better for men and P < 0.001 or better for women). Our experience shows that these routine techniques for measuring body composition can be readily applied to stable peritoneal dialysis patients.

Perturbations in sodium balance. Hyponatremia and hypernatremia.

Perturbations of serum sodium concentration are the most common electrolyte abnormalities seen in clinical medicine. Patients may exhibit profound alterations in mental status or be asymptomatic. Appropriate diagnosis and treatment is essential to reducing morbidity from serum sodium abnormalities. This article reviews the etiology, symptoms, and treatment of hyponatremic and hypernatremic syndromes.

Laboratory investigation of renal stone disease.

Renal stone disease is a chronic disease associated with a high rate of recurrences and hospitalizations. Over the past three decades, the incidence of nephrolithiasis has increased by 60% to 75%. Because there is a significant amount of morbidity associated with development of stone disease, a comprehensive yet simple evaluation to determine the cause of the problem is warranted.

Determining peritoneal dialysis prescriptions by employing a patient-specific protocol.

OBJECTIVE: To develop a formula that would permit a rapid and simple calculation of required dialysate volume needed to provide a predetermined daily creatinine clearance. DESIGN: Prospective study of peritoneal dialysis patients followed for 6 months. SETTING: A primary care teaching hospital in New York. PATIENTS: Twenty-six patients beginning peritoneal dialysis entered and completed the study. INTERVENTION: By employing each patient's measured peritoneal equilibration test (PET) and a standard clearance formula, a patient-specific treatment protocol (PSP) was calculated. The PET 2-hour D/Pcreat was used for continuous cycling peritoneal dialysis (CCPD) and the 4-hour D/Pcreat was used for patients on continuous ambulatory peritoneal dialysis (CAPD) to determine a PSP that would provide a minimum of 6 L of creatinine clearance daily. MAIN OUTCOME MEASURES: Patients were followed for 6 months to assess the ability of this approach of maintaining acceptable levels of blood urea nitrogen, creatinine, albumin, and hematocrit over the 6-month period of observation. RESULTS: Our study of 26 patients revealed that only 6 patients (23%) could be treated with the standard prescription of 8 L/day on CAPD. The remaining 77% of our patients required 9-13 L/day for CAPD and 12-21 L/day for CCPD. All patients were free of uremic symptoms and demonstrated acceptable biochemical parameters over a 3-6 month period of observation. CONCLUSIONS: A patient-specific protocol utilizing individually derived PET data provides an acceptable and easy to calculate initial treatment prescription for each patient that avoids the necessity for trial and error that has heretofore been employed.

Assessment of renal osteodystrophy in hemodialysis patients.

We performed a prospective study of 30 patients undergoing chronic hemodialysis to determine which of 6 generally available diagnostic procedures provided the most useful information for the assessment of bone disease in hemodialysis patients. The 6 procedures were: routine biochemical measurements, N-terminal parathyroid hormone (N-PTH), radiographic analysis of hands and clavicles, bone density determination by dual photon absorptiometry (DPA), deferoxamine stimulation test, and iliac crest bone biopsy. Serum N-PTH was elevated in 83% of patients but was not significantly associated with abnormalities of other biochemical parameters. No significant relationship was demonstrated between biochemical data and radiographic findings or between biochemical data and bone density by DPA. All patients with abnormal DPA had an elevation of N-PTH; therefore, DPA did not reveal any unsuspected disease. Bone biopsies were done in 20 patients and findings in each were consistent with uremic osteodystrophy, including osteitis fibrosa cystica in 11 patients and aluminum-associated bone disease in 2 patients. Six patients had mixed disease, and 1 patient had osteoporosis. Despite 11 positive deferoxamine tests, bone biopsy revealed aluminum deposition in only 7 of these patients, suggesting extraosseous aluminum accumulation in the remaining 4. Evaluation of the positive and negative predictive accuracies of DPA, x-ray analysis, N-PTH levels, and aluminum bone deposition revealed that normal DPA or x-ray findings do not exclude bone disease, that N-PTH level is a good marker for secondary hyperparathyroidism, and that a negative deferoxamine test excludes aluminum-associated bone disease. Discriminant analysis also reinforced these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and etiology of hyponatremia in an intensive care unit.

To evaluate the incidence and causes of hyponatremia in intensive care unit (ICU) patients, retrospective and prospective studies were done. Hyponatremia was defined as a serum sodium concentration equal to or less than 134 mmol/l (134 mEq/l). Prospectively, 29.6% of patients displayed hyponatremia. Relevant data were obtained in twelve patients. Two patients did not have serum hypoosmolality. In the ten patients with serum hypoosmolality, urine osmolality was not maximally dilute and urine sodium concentration was greater than 30 mmol/l (30 mEq/l) suggesting inappropriate antidiuretic hormone secretion (SIADH). However, three patients exhibited suppressed ADH levels despite absence of maximal urinary dilution. The data suggest that hyponatremia is common in ICU patients and that renal diluting defects are frequent. Therefore, hypotonic fluid should be administered cautiously.