Hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess in maintenance dialysis patients: a matched case-control study.

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.

Folate status is the major determinant of fasting total plasma homocysteine levels in maintenance dialysis patients.

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.

Lack of effect of oral N-acetylcysteine on the acute dialysis-related lowering of total plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia refractory to standard B-vitamin supplementation treatment persists in > or = 75% of maintenance dialysis patients, potentially increasing their risk for atherothrombotic sequelae. We examined whether predialysis administration of oral N-acetylcysteine (NAC), which acutely increases the non-protein bound, dialyzable fraction of plasma homocysteine, might augment the homocysteine-lowering effect of dialysis therapy. Predialysis and postdialysis total plasma homocysteine levels were determined on a control day, and on a day in which oral NAC (1200 mg) was administered predialysis in n = 11 maintenance hemodialysis patients. Although NAC treatment had no significant effect on hemodialysis removal of plasma homocysteine (P = 0.594), we observed a 16% reduction (P = 0.033) in non-fasting prehemodialysis total plasma homocysteine on the NAC treatment vs. non-treatment day. Longer term, placebo-controlled confirmation of this finding will be required to evaluate the possible chronic homocysteine-lowering efficacy of NAC treatment in hemodialysis patients.

High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients.

Hyperhomocysteinemia, an arteriosclerotic risk factor, persists in 75% of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism, and normal or supernormal plasma status of these vitamins (Atherosclerosis 114:93, 1995). We conducted a placebo-controlled eight-week trial of the effect on plasma homocysteine of adding supraphysiologic dose folic acid (15 mg/day), B-6 (100 mg/day), and B-12 (1 mg/day) to the usual daily dosing of 1 mg folic acid, 10 mg B-6, and 12 micrograms B-12, in 27 hyperhomocysteinemic dialysis patients. Total plasma homocysteine was measured at baseline, and after four and eight weeks. Blinded analyses revealed no evidence of toxicity in the group randomized to supraphysiologic dose B-vitamin supplementation. Plasma homocysteine was significantly reduced after both four weeks (-29.8% vs. -2.0%; P = 0.0024) and eight weeks (-25.8% vs. +0.6%; P = 0.0009) of active versus placebo treatment. Also, 5 of 15 treated versus 0 of 12 placebo group patients had their plasma Hcy reduced to within the normative range (< 15 mumol/liter). Supraphysiologic doses of B-vitamins may be required to correct hyperhomocysteinemia in dialysis patients.

Antibiotic-induced D-lactic acidosis.

OBJECTIVE: To describe a case of oral antibiotic-induced D-lactic acidosis in a patient with enteric overgrowth of Lactobacillus acidophilus. DESIGN: Single case study. SETTING: University-affiliated community hospital. INTERVENTION: Oral carbohydrate challenge test with 4000 kcal/d. MAIN RESULTS: A patient had several episodes of D-lactic acidosis after receiving oral antibiotics. Stool cultures yielded Lactobacillus acidophilus resistant to the implicated agents. Provocative challenge with dietary carbohydrate alone, in the absence of antibiotics, failed to reproduce the syndrome. CONCLUSIONS: Oral antibiotics may induce D-lactic acidosis in patients with the short-bowel syndrome by promoting the overgrowth of resistant D-lactate-producing organisms. Interactions between carbohydrate intake and antibiotic use are likely determinants in the development of this syndrome. Periodic use of stool cultures with antimicrobial susceptibility testing may assist in the management of these patients by optimizing the selection of antimicrobial agents.

Application of the ambulatory 24-hour electrocardiogram in the prediction of cardiac death in dialysis patients.

The value of a 24-hour ambulatory electrocardiogram (AmECG) in assessing the risk of cardiac death was studied in 122 stable-condition dialysis patients followed up from two to six years after monitoring. An abnormal AmECG was defined by second-degree or greater AV block or by Lown grade 3 or greater ventricular ectopy. The incidence of cardiac mortality or an abnormal AmECG was not influenced by hypokalemia or beta-blockers. Digitalis was associated with both an abnormal AmECG and a twofold increase in mortality whether or not the AmECG was normal. Cardiac mortality accounted for 26 of 33 deaths within the first year after the AmECG. In the absence of coronary artery disease, survival at six months was 100% in patients with normal AmECG vs 90% (abnormal AmECG). In the presence of coronary artery disease, survival at six months was 83% (normal AmECG) vs 54% (abnormal AmECG).

Cyclosporin treatment for aplastic anemia: a case report demonstrating a second response to second exposure to cyclosporin.

Cyclosporin has been used in the treatment of aplastic anemia, often in combination with other drugs, making it difficult to make a clear distinction between the effects of cyclosporin and those of other treatments. This report demonstrates a clear response of a patient with aplastic anemia to single drug cyclosporin therapy.

Local steroids in dialysis-associated pericardial effusion. A single intrapericardial administration of triamcinolone.

Five patients receiving maintenance hemodialysis for end-stage renal disease underwent therapeutic pericardiocentesis for pericarditis manifested by either cardiac tamponade or effusion unresponsive to conservative therapy. Pericardiocentesis was followed by a one-time instillation of triamcinolone hexacetonide, a nonabsorbable corticosteroid, into the pericardial space with subsequent needle withdrawal. All patients had prompt hemodynamic and symptomatic improvement. Serial echocardiograms showed resolution of the pericardial effusion in all patients. Follow-up evaluation for six months to six years has shown no clinical or postmortem evidence of recurrence. This procedure appears safe and effective and potentially can obviate the need for prolonged catheter drainage or more invasive surgical procedures as therapy for these patients.

Cardiorenal failure: treatment of refractory biventricular failure by peritoneal dialysis.

Fifteen patients with New York Heart Association Class IV functional cardiac disability whose mild-to-moderately severe renal failure had produced life-threatening fluid overload underwent dialytic therapy. Ten were dialyzed by the peritoneal route initially and five were switched from hemodialysis to peritoneal dialysis because of hemodynamic instability. All patients improved, resulting in renewed responsiveness to more conservative measures (2), stabilization for cardiac surgery (4), or less-restricted lifestyle out of hospital (9). We recommend consideration of peritoneal dialysis when biventricular and renal failure are refractory to conventional therapy.

Peripheral hepatic artery embolization for primary and secondary hepatic neoplasms.

Eighteen patients underwent peripheral arterial embolization with Gelfoam powder for treatment of primary or metastatic hepatic neoplasms. Except for two cases in which the patients could not undergo long-term arterial infusion, all cases were treatment failures from intravenous chemotherapy, intra-arterial chemotherapy, or, in some cases, intra-arterial chemotherapy plus radiation therapy. Fourteen patients had good symptomatic relief from the procedure. Four of these patients are alive at 3, 5, 6, and 18 months following the procedure. Four patients died within 2 weeks following embolization, three of progression of disease and one of aspiration pneumonia. Of the patients showing symptomatic relief, 10 died of progression of cancer 2 to 14 months following embolization, with a median survival of 5 months. Based on the results in this small group of patients, it would seem that transcatheter hepatic dearterialization is often successful palliative therapy in patients who are not responsive to traditional therapies. Because of the low procedural morbidity, transcatheter embolization is superior to surgical dearterialization.

Nonoliguric acute renal failure.

Nonoliguric acute renal failure is being recognized more commonly as a frequent initial observation for azotemia. Use of automated biochemical monitoring, aminoglycoside antibiotic utilization, and administration of potent diuretics and mannitol in settings of oliguria all contribute to its increased incidence. There appears to be less morbidity and mortality in patients with nonoliguric acute renal failure, and diagnostic urinary indexes suggest less of an insult to renal function. This article reviews the available literature and explores the reasons for the increased frequency of recognition of nonoliguric acute renal failure. Another aim is to compare nonoliguric acute renal failure with the oliguric from because there are important differences to be recognized by the clinician.

Nonoliguric acute renal failure associated with a low fractional excretion of sodium.

Measurement of the fractional excretion of sodium has been recommended as a useful clinical tool in evaluating acute renal failure. Six patients with nonoliguric acute renal failure had a fractional excretion of sodium less than or equal to 1.0%; these patients had severe liver dysfunction, which suggested a sodium-avid state. A review of the literature showed that in patients with other sodium-avid states (congestive heart failure, nephrotic syndrome, and burns) the fractional excretion of sodium was frequently less than or equal to 1.0%. The fractional excretion of sodium is thus a less useful diagnostic test in patients whose clinical state makes them sodium avid.