Serum levels of high-density lipoprotein phospholipids correlate inversely with severity of angiographically defined coronary artery disease.

In an attempt to assess the relationship between lipid abnormalities and severity of coronary artery disease, we measured serum levels of cholesterol (SC), triglycerides (TG), phospholipids (SP), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), and high density lipoprotein phospholipids (HDL-P), in 217 men undergoing diagnostic coronary arteriography. We found significantly higher mean values of HDL-P and HDL-C in men with normal coronaries, but no significant differences in the other measured lipids. While there was no significant difference in HDL-C among patients with one, two or three-vessel disease, there was a negative correlation between HDL-P levels and the severity of the disease. These observations suggest that prospective studies would be of merit to establish the relevance of HDL-P in the development of coronary artery disease.

Factors that influence serum hyaluronan levels in hemodialysis patients.

Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.

Detection of anti-hepatitis C virus antibodies in patients undergoing dialysis by utilizing a hepatitis C virus 3.0 assay: correlation with hepatitis C virus RNA.

Hepatitis C virus (HCV) infection is endemic in long-term dialysis units. We assessed the performance of a recently developed HCV 3.0 assay for the detection of HCV antibodies in patients undergoing dialysis. The study evaluated 128 patients undergoing long-term maintenance hemodialysis. Anti-HCV was detected by 2.0 and 3.0 enzyme immunoassay (EIA). Results were confirmed with recombinant immunoblot assays (RIBA 2.0 and RIBA 3.0). HCV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR). Thirty-two patients (25%) were HCV EIA 2.0 positive. Of these, 1 was RIBA 2.0 negative (PCR positive), 3 were indeterminate (3 PCR positive), and 28 were positive (23 PCR positive). Thirty-five (27%) were HCV EIA 3.0 positive. One was RIBA 3.0 negative (PCR positive), 1 was indeterminate (c33c, PCR positive), and 33 were positive (27 PCR positive) by RIBA 3.0. Thus only 1 PCR-positive patient was negative with RIBA 2.0 and 3.0 assays. Two of the 3 RIBA 2.0 indeterminate samples were positive with RIBA 3.0. One remained indeterminate but was HCV RNA positive. In summary, HCV 3.0 EIA detected 4 additional viremic patients but was positive in 6 PCR-negative subjects. A high correlation of the presence of antibody to c33c with HCV RNA (28 of 34, 82%) was found, and it was found in all anti-HCV positive samples and in 1 indeterminate sample. We conclude that the HCV EIA 3.0 test with the supplemental confirmatory RIBA 3.0 test may improve the sensitivity for the detection of anti-HCV. Nevertheless, in potentially immunocompromised patients undergoing dialysis, PCR continues to be the only reliable test for detecting viremia.

Prevalence of hepatitis C and G virus infection in chronic hemodialysis patients.

An RNA virus designated hepatitis G virus (HGV) has been recently identified in patients with acute and chronic liver disease. HGV is transfusion transmissible, it has global distribution, and it is present in the volunteer blood donor population in the United States. One hundred sixty patients undergoing maintenance hemodialysis at the University of Miami-affiliated unit were evaluated. There were 99 men and 61 women ranging in age from 22 to 80 years. Sixty percent had a history of blood transfusion, 6% had a history of drug abuse, and 9% were infected with the human immunodeficiency virus. HGV-RNA was detected by reverse-transcriptase polymerase chain reaction with amplification of two independent regions (5'-nontranslated region and NS5a coding region). Detection of digoxigenin-labeled amplification products with specific capture probes to the coding and noncoding regions was performed with the Enzymun-test DNA on an ES-300 Immunoassay System (Boehringer-Mannheim, Mannheim, Germany). Hepatitis C antibodies were measured with anti-hepatitis C virus enzyme-linked immunosorbent third-generation assays and hepatitis C virus RNA by reverse-transcriptase polymerase chain reaction. There were 32 (20%) patients with detectable HGV RNA with both primer pairs. Because of possible mutations, the HGV virus may be detectable only with one primer pair. We considered the latter as indeterminate: 12 had detectable levels to the NS5a region only, seven to the 5'-nontranslated region, and six had borderline results. Detectable and indeterminate samples were confirmed by repeat measurements in a new blood sample. Seven of 24 (29%) patients with detectable hepatitis C virus RNA had coexisting HGV with one or both HGV primer pairs (four with both and three with one). Five patients were hepatitis B surface antigen positive and HGV negative. We conclude that HGV infection is prevalent in our dialysis patients. The clinical significance of HGV infection remains to be established.

Quantitative detection of hepatitis C virus RNA in patients undergoing hemodialysis.

The purpose of the current study was to detect quantitatively hepatitis C virus (HCV)-RNA among patients undergoing maintenance hemodialysis. Study subjects were 88 patients on hemodialysis at the Miami Veterans Administration Medical Center and the REN Dialysis Unit at the University of Miami School of Medicine. There were 66 men and 22 women, mean age 52 years (range, 22-87 years), and mean duration of dialysis was 2.8 years (range 0.2-12.5 years). Seventy-three percent had a history of blood transfusion. Anti-HCV was determined by enzyme linked immunosorbent assay (ELISA), confirmed by four antigen strip immunoblot assay (RIBA 2.0 SIA). HCV-RNA was quantitated directly in human sera using a branched DNA (bDNA) signal amplification assay. Twenty-seven of 88 (31%) patient samples were found to be anti-HCV reactive by ELISA. Twenty-two of 27 were confirmed reactive, 2 were indeterminate, and 3 were nonreactive by RIBA HCV. Eighteen of 22 (82%) reactive by RIBA 2.0 HVC were found to have detectable (> 3.5 X 10(5) Eq/ml) HCV-RNA levels (mean [&/- SD], 43.3 +/- 35.4 X 10(5) Eq/ml; range 4.9-123.3). No additional cases were identified with reverse transcription polymerase chain reaction (RT-PCR) using 5' untranslated region "nested" primers. HCV-RNA was not detected in four RIBA HCV 2.0 reactive, the two intermediate, or the 64 patient samples nonreactive for anti-HCV. The two epitopes most commonly associated with HCV-RNA were c22-3 and c33c. Sixteen of 18 (89%) patients with detectable levels of HCV-RNA had normal alanine aminotransferase (ALT). Three patients with the highest levels of HCV-RNA were infected with the human immunodeficiency virus. The authors conclude that HCV-RNA by bDNA assay is a sensitive, specific, and simple test that can be used in association with antibody assays and a PCR-based assay to study the prevalence and management of HCV infection in the dialysis setting.

Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis.

PURPOSE: To determine the additive renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclosporine A (CYA) in patients with rheumatoid arthritis (RA) and to determine the effects of CYA on active RA. PATIENTS AND METHODS: Eleven patients with RA refractory to other agents were treated separately for 2-week periods with an NSAID (sulindac or naproxen), CYA (5 mg/kg/d), and NSAID plus CYA in combination (NSAID/CYA). The NSAID/CYA combination was continued for an additional 20 weeks. Clinical parameters of RA, electrolytes, renal function, and the renin-aldosterone system were evaluated at each interval to determine the potential interaction of these two agents. RESULTS: Combined therapy was effective in suppressing many measures of active RA in 9 of the 11 patients. Adverse drug reactions were common, but withdrawals were limited to hirsutism (one) and peripheral neuropathy (one). In about half of the patients, CYA or NSAID resulted in a decrease in the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), with a mild reduction in the filtration fraction. With NSAID or CYA, early morning renin-aldosterone system values were mildly suppressed, and their response to ambulation/intravenous (IV) furosemide was not blunted. When combined, NSAID/CYA caused more marked reductions of GFR and ERPF at 2 weeks, and this persisted at 20 weeks. The morning renin-aldosterone system values during administration of NSAID/CYA were suppressed, with an added blunted response to ambulation/IV furosemide. CONCLUSION: As previously suspected, the impairment of renal function when CYA and NSAID are combined is greater than that obtained with either agent alone. This hemodynamic effect was reversible and appeared to be, at least in part, due to renal vasoconstriction.

Disordered breathing patterns during bicarbonate hemodialysis in COPD. Effect of cuprophane versus polysulfone membranes.

This study explored the breathing patterns and arterial blood gases before and during cuprophane (CU) bicarbonate and polysulfone (PS) bicarbonate dialysis in six chronic dialysis patients with mild chronic obstructive pulmonary disease (COPD). The studies were performed in random order during two consecutive dialyses. Breathing patterns were monitored by respiratory impedance plethysmography. Apneic episodes, defined as a decrease in tidal volume of 75% lasting 10 sec, were present before and during hemodialysis. In these patients with COPD a high number of apneic episodes (17 +/- 6 [SE]) were observed during CU bicarbonate hemodialysis. Most of these episodes were central rather than obstructive in character. There were fewer events when the same patients were dialyzed with PS membranes (10 +/- 5; p = 0.05). The decrement in PO2 (baseline to 60 min) was 17 +/- 7 during CU and 4 +/- 5 mmHg during PS dialysis (p = 0.10). Minute ventilation decreased in four of six patients on CU bicarbonate and increased in all six patients on PS bicarbonate. It was concluded that bicarbonate hemodialysis does not completely prevent hypoxemia or apnea during dialysis in patients with COPD. Apneic episodes and hypoxemia appear to be less severe during PS bicarbonate than during CU bicarbonate hemodialysis.

Low anion gap resulting from unexplained exposure to bromide in a patient with renal amyloidosis.

A patient with nephrotic syndrome secondary to renal amyloidosis was consistently observed to have serum anion gap levels as low as -1 mEq/L and averaging approximately 2 mEq/L. Neither multiple myeloma nor extreme hypertriglyceridemia was present, and the patient's serum albumin concentrations were not low enough to depress the anion gap to this degree. An increased serum bromide level (below the range expected to produce clinical toxicity) was the apparent cause of the low anion gap. The patient's parents, who live in the same apartment, also manifested low anion gaps and inexplicably elevated serum bromide levels. Despite detailed investigation, no environmental or pharmacologic source of bromide was uncovered. Although the source of the bromide in the present instance remains elusive, this report illustrates the necessity to measure serum bromide when a low anion gap cannot be explained by other factors, even when there is no history to suggest bromide exposure.

Severe cerebral edema in a patient with anasarca and hypernatremia.

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure.

Fatal destructive cervical spondyloarthropathy in two patients on long-term dialysis.

Two patients with fatal cervical cord compressive myelopathy are described, both of whom had been on dialysis for more than 15 years. Destructive changes were noted in mid and upper cervical regions, with soft tissue mass in the atlanto-occipital region in one patient. Clinical and radiographic findings suggest both amyloid and hyperparathyroidism as possible etiologies for these destructive spinal changes. Clinicians should be aware that the full picture of quadriparesis may be associated with destructive spondyloarthropathy (DSA) in long-term dialysis patients.

Serum sulfate concentration and the anion gap in hemodialysis patients.

First-of-the-month predialysis serum sulfate (SO4) and other blood chemistry values were measured prospectively for 5 to 7 months in 14 patients undergoing single pass chronic tri-weekly maintenance hemodialysis with bicarbonate dialysate. Blood was also obtained predialysis and again immediately postdialysis from seven patients (five of whom also participated in the chronic study). As expected, the patients manifested a high anion gap (AG) metabolic acidosis. Serum SO4 was only moderately stable from month to month (the average coefficient of variation was 0.30; correlation between the serum SO4 value of month one and months two and five were r = 0.59, p = 0.026; and r = 0.38, p = 0.182, respectively). The ratio of mean serum SO4 to mean AG (5.0 +/- 0.4 [SE] mEq/L divided by 19.1 +/- 0.5 mEq/L) was 0.26. Although there was a statistically significant correlation between the serum SO4 and the blood urea nitrogen (BUN), there was no such correlation between SO4 and AG. A single hemodialysis reduced serum SO4 by 54% (from 3.5 +/- 0.5 mEq/L to 1.6 +/- 0.1 mEq/L), but there was no correlation between the change in SO4 and the change in AG. The authors concluded that SO4 contributes importantly to the elevated AG in patients receiving chronic hemodialysis. Single pass bicarbonate hemodialysis temporarily reduces, but does not normalize, both the serum SO4 and the AG of such patients.

Effect of hyperkalemia on insulin secretion.

The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68 +/- 0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p less than 0.05). We concluded that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.

Tetany induced on separate occasions by administration of potassium and magnesium in a patient with hungry-bone syndrome.

The case is described of a 68-year-old man whose therapy induced tetany during each of two consecutive hospital admissions. On each occasion the patient had marked hypocalcemia and hypomagnesemia, presumably as a result of the hungry-bone syndrome associated with diffuse prostatic osteoblastic metastases. During the February 1991 admission, marked hypokalemia was the principal initial concern. It seems likely that the tetany associated with the administration of KCl, without sufficient calcium, resulted from attenuation of the protection against hypocalcemia-enhanced neuromuscular excitability conferred by coexisting hypokalemia. The admission in March 1991 was prompted by the finding (without symptoms) of very low levels of both serum Mg and serum Ca. Tetany occurred during the infusion of MgSO4, without calcium. An acute decrement in plasma ionized Ca resulting from complexing of Ca with sulfate ions together with augmented urinary excretion of Ca were likely pathogenic factors.

Effect of hypertonic versus isotonic sodium bicarbonate on plasma potassium concentration in patients with end-stage renal disease.

The purpose of the study was to evaluate the potassium-lowering effect of hypertonic versus isotonic sodium bicarbonate (NaHCO3) in patients with end-stage renal disease (ESRD) receiving chronic maintenance hemodialysis. Immediately prior to dialysis, we infused isotonic (1.4%, 150 mEq/l) NaHCO3 in H2O (1 mEq/kg body weight over 2 h) to 10 patients with ESRD. Blood was drawn in heparinized tubes, without the use of a tourniquet, from the angioaccess for Na, K, pH, PCO2, HCO3, and osmolality at baseline (x 3) and after 10, 20, 40, 60, 90, 120, and 180 min of infusion. All patients were acidotic (HCO3 13-21 mEq/l, pH 7.25-7.38) prior to the study. In these patients, plasma HCO3 increased by an average of 3 mEq/l, and plasma K decreased by 0.35 mEq/l at 180 min. Plasma osmolality did not change. In 8 patients, a bolus of hypertonic (8.4%, 1,000 mEq/l) NaHCO3 (1 mEq/kg body weight over 5 min) tended to cause a transient increase in plasma HCO3, an increase in plasma osmolality, and minor changes in the K levels (an initial small and transient albeit significant decrease, followed by a tendency to increase). Finally, plasma K tended to increase in patients receiving infusions of either isotonic (n = 6) or hypertonic (n = 6) sodium chloride. Our data do not support the efficacy of the common practice of administering NaHCO3 for the emergency treatment of hyperkalemia in patients with ESRD receiving maintenance dialysis.

Recurrence and clearance of hepatitis B surface antigenemia in a dialysis patient infected with the human immunodeficiency virus.

Hepatitis B vaccination programs have prevented infection in many dialysis patients, although the antibody response to vaccination is still insufficient in approximately 50%. Reinfection or reactivation of latent hepatitis B infection (HBV) has been reported in certain groups of immunosuppressed patients, including those infected with the human immunodeficiency virus (HIV-1). We report the reactivation or reinfection of HBV with resurgence of hepatitis B surface antigen in a dialysis patient coinfected with HIV-1. Thus, in dialysis patients with latent HBV infection, with undetectable hepatitis B surface antigen (HBsAg) levels, the potential exists to reactivate during immunosuppression associated with HIV-1 infection and/or end-stage renal disease. Reinfection with a different subtype is also possible. The development of hepatitis B surface antigenemia in this patient population creates a potential for transmission in the dialysis setting. This is of special concern since the number of patients infected with HIV-1 and with evidence of prior hepatitis B infection is increasing in urban units.

Hepatitis C infection in two urban hemodialysis units.

We determined the prevalence of antibodies to the hepatitis C virus (anti-HCV) in 90 patients and 37 staff members of two hemodialysis units utilizing a recently developed anti-HCV recombinant based assay. Eleven patients (12%) were anti-HCV(+). Of these, eight (73%) had antibodies to the hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection; one patient was hepatitis B surface antigen (HBsAg)(+). All staff members were anti-HCV(-), although seven (19%) of them were anti-HBc(+). Alanine aminotransferase elevations were present at the time of the study in four anti-HCV(-) patients and in only one anti-HCV(+) patient. All anti-HCV(+) (mean 59 +/- 74; range 3 to 269 units) and 85% of anti-HCV(-) patients (mean 16 +/- 27; range 0 to 204 units) had received multiple blood transfusions (P = 0.348). Among 50 patients tested for human immunodeficiency virus (HIV), 43% of anti-HCV(+) as compared to only 7% anti-HCV(-) were positive (P = 0.003). There was a history of intravenous drug abuse (IVDA) in eight (72%) of the anti-HCV(+) patients and in only seven (9%) of the anti-HCV(-) group (P = 0.00001). The results of this serologic survey suggests that anti-HCV positivity is prevalent, although much less than anti-HBc, among our dialysis patients, whereas it was not detected among staff members. The prevalence rate of anti-HCV was statistically significantly higher among anti-HIV(+) and IVDA patients but not in multi-transfused patients.

Correlates of atherosclerosis in coronary arteries of patients undergoing angiographic evaluation.

The correlations between lipid and lipoprotein measurements and other risk factors of coronary artery disease were evaluated in 101 men undergoing coronary angiography. Clinically significant disease was present in 75 patients, whereas 24 had no observable lesions and 2 had minimal lesions. Comparisons of individual lipid and lipoprotein levels were nearly all significantly different between patients with and patients without clinically significant disease; however, no single variable could predict the presence of disease among patients. Logistic regression analysis identified five factors: apolipoprotein A-I, apolipoprotein B, diabetes, age, and family history of heart disease, which account for most of the differences between the two patient groups. These results could have important implications for the evaluation and management of patients suspected of having coronary atherosclerosis.