Biomedical subjects
Publications and source records attributed to R J Caruana.
Hyponatremia is a common clinical problem and can result in severe morbidity and even death. Understanding the pathophysiology of hyponatremic encephalopathy is central to accurate diagnosis and management. This article reviews the controversies surrounding the treatment of hyponatremia with special emphasis on risk to benefit ratio of different therapeutic strategies.
OBJECTIVE: To determine the effects of continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) on endothelin-1 (ET-1) levels in patients with end-stage renal disease (ESRD) and to assess the relationship between plasma ET-1 levels and selected patient parameters. DESIGN: Prospective, nonrandomized comparison study. SETTING: Outpatient CAPD and HD units of a university medical center. PARTICIPANTS: Twelve ESRD patients (6 on CAPD and 6 on HD) and 5 healthy normotensive subjects. INTERVENTIONS: CAPD patients had blood and peritoneal dialysate samples collected and measurements made following an overnight exchange. HD patients had blood collected and measurements made at 0 hours (basal) and again at 3 hours during a midweek HD session. Blood samples were also collected from normal subjects and served as ET-1 controls. MEASUREMENTS: ET-1 and patient parameters (creatinine, peritoneal dialysate volume, blood pressure, body weight, age, and treatment duration) were determined. Data are reported as the mean +/- one standard deviation. RESULTS: Plasma and dialysate ET-1 levels in the CAPD group were 19.5 +/- 4.2 pg/mL and 9.2 +/- 4.2 pg/mL, respectively. The control group plasma and unused dialysate contained no detectable ET-1 (< 3.0 pg/mL, the limit of detection). The peritoneal clearance of ET-1 was less than that of creatinine (2.29 +/- 0.69 mL/minute vs 4.22 +/- 0.66 mL/minute, p = 0.005). The basal (0 hour) plasma ET-1 level in the HD group (16.5 +/- 7.8 pg/mL) did not differ from that of the CAPD group, p = 0.423. Furthermore, no differences in patient parameters were detected between the CAPD and basal HD groups. Although the mean arterial pressure (MAP) decreased during HD, the plasma ET-1 level at 3 hours (13.5 +/- 5.4 pg/mL) remained unchanged from the basal level, p = 0.307. An analysis of pooled data from the CAPD and HD groups revealed no significant correlation between plasma ET-1 and MAP, body weight, creatinine, or treatment duration. There was, however, a positive correlation between plasma ET-1 and age (r = 0.643, p = 0.024).
In this study we measured indices of T-lymphocyte activation in normal volunteers, chronic hemodialysis patients, CAPD patients and chronic renal failure patients not yet on dialysis. Serum IL-2 levels were elevated in patients compared to controls. Soluble IL-2 receptors were elevated in all three patient groups and were highest in CAPD patients. Clearance of IL-2 and soluble interleukin receptors was negligible in dialysis and renal failure patients. Hemodialysis patients had a significantly lower percentage of CD3-positive cells than all other groups. Hemodialysis with a variety of membrane/bath combinations did not significantly affect any of the parameters measured. This study provides some support for the hypothesis that chronic T-cell activation is present in renal failure.
We performed a controlled parallel study comparing the effects of heparin sodium to epoprostenol sodium (prostacyclin sodium, Flolan) during hemodialysis in 30 dialysis patients. Mean fiber bundle volume loss and dialyzer function were similar with both anticoagulation methods. Intradialytic symptoms occurred in 100% of the epoprostenol dialyses and 88% of the heparin dialyses, but only 10/325 epoprostenol and 3/374 heparin dialysis were discontinued prematurely because of symptoms. Long-term hemodialysis with epoprostenol is safe and effective. Epoprostenol may be a suitable alternative to heparin in some dialysis settings.
A review of hospital epidemiologic data disclosed five cases of polymicrobial bacteremia on a nephrology inpatient service over a period of 30 months. All five cases occurred in patients receiving long-term hemodialysis; four of them had indwelling silicone rubber vascular access devices. Although all patients had risk factors other than uremia and dialysis predisposing to an increased likelihood of infection, no patient had either obvious skin infection at the site of the vascular access or documented visceral infection. One patient died, and the other four recovered after removal of the vascular access device and appropriate antibiotic therapy. The increased risk of polymicrobial bacteremia associated with long-term hemodialysis should be taken into account when empiric antibiotic therapy is undertaken.
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We measured tumor necrosis factor (TNF alpha), interleukin-1 (IL1-B), and beta-2 microglobulin (B2M) levels in 10 chronic hemodialysis patients before and during dialysis with six different dialysate/dialyzer combinations. The mean pre-dialysis serum level of B2M was 23.4 +/- 11.1 mg/L (nl less than 3 mg/L). There was no significant effect of hemodialysis with any dialysate/dialyzer combination on intradialytic serum B2M levels. Five patients had detectable pre-dialysis serum levels of TNF alpha (greater than 40 pg/ml) at least once and 2 had detectable levels prior to all dialyses. Six patients had detectable pre-dialysis serum levels of IL1-B (greater than 20 pg/ml) at least once, and 2 had detectable levels prior to all dialyses. Serum TNF alpha, IL1-B and B2M levels were not significantly correlated with one another. Our data do not support the hypothesis that blood-membrane interactions significantly affect circulating levels of TNF alpha, IL1-B or B2M. Chronic high level elevations of plasma IL1-B and TNF alpha are not uniformly observed in hemodialysis patients, arguing against a role for these substances as systemic uremic toxins.
To define normal limits for serum creatinine levels, as well as to explore the relationship between age and the prevalence and severity of renal disease in patients with sickle cell anemia (SCA), we retrospectively analyzed renal function parameters in 368 patients followed in our SCA clinic. Dipstick proteinuria was present in 78 patients (20.6%). Chronic renal insufficiency (CRI) was present in 17 patients (4.6%) and showed a high degree of association with proteinuria and increased age. In patients with CRI, the severity of renal dysfunction was also age-related. In the 284 patients without proteinuria or CRI, mean serum creatinine levels were lower than predicted. We conclude that in patients with SCA, serum creatinine levels at the upper limit of normal should be regarded with suspicion, and that the prevalence and severity of proteinuria and CRI in SCA is high and increases with age.
We performed a case-control study of acute renal failure (ARF) in patients hospitalized with sickle cell anemia (SCA). Twelve of the 116 patients (10.3%) whose records were suitable for analysis were diagnosed as having ARF based on a minimum of doubling of their serum creatinine levels (mean rise was 205 +/- 49%). ARF patients were more likely to have been admitted with infection and had a lower mean hemoglobin level than the control group. Volume depletion was the most common identifiable cause for ARF. Two of 3 patients with severe ARF received dialytic support. Ten of 12 ARF patients survived and subsequently had recovery of renal function.
Cisplatin-associated hemolytic-uremic syndrome (HUS), an under-reported form of HUS induced by chemotherapy, typically pursues a fulminant and lethal course. We report the cases of two patients with squamous cell carcinoma of the head and neck who developed massive hemolysis, profound thrombocytopenia, and dialysis-dependent renal failure after therapy with cisplatin. Plasma exchange was ineffective in both patients, but plasma perfusion with a staphylococcal protein A column produced a dramatic and permanent response in the second patient. These cases show the importance of considering HUS as a cause of renal failure in such patients who receive cisplatin-based chemotherapy, and support the role of staphylococcal protein A plasma perfusion as treatment for this condition.
Inadequate control of serum chemistries and extracellular fluid volume may result in patients being changed from continuous ambulatory peritoneal dialysis (CAPD) to another form of dialysis. We report 2 patients in whom apparent inadequacy of CAPD resulted from dialysate dumping. The first patient could not control her fluid intake and required frequent hypertonic exchanges. She felt too full with these exchanges and drained a substantial portion of each exchange 30 to 60 min after infusion. Patient 2 had similar complaints but simply drained a large portion of each fresh bag directly into the drain bag at the start of the flush-before-fill step. Both patients had improved results from CAPD once they stopped their dialysate dumping. Partial wasting of each exchange because of abdominal discomfort should be added to the causes of inadequate dialysis in CAPD.
The purpose of this study was to evaluate the effects of oral base therapy on selected chemical parameters in chronic hemodialysis patients. Oral base supplements were administered to 20 acidotic chronic hemodialysis patients for one month. Serum bicarbonate levels rose from 18.6 +/- 2.9 to 22.5 +/- 4.0 mEq/L (p less than 0.0005) and pH rose from 7.35 +/- 0.03 to 7.39 +/- 0.04 (p less than 0.0005). Serum ionized calcium levels fell from 5.03 +/- 0.37 to 4.83 +/- 0.34 mg/dL (1.25 +/- 0.09 to 1.21 +/- 0.08 mmol/L) (p less than 0.01), while intact parathyroid hormone (PTH) levels rose from 547 +/- 697 to 619 +/- 776 pg/mL (p less than 0.05). Base therapy did not result in significant changes in serum levels of total calcium, phosphorus, alkaline phosphatase, urea nitrogen, creatinine, total protein, albumin or potassium. If empiric therapy with exogenous base is given to dialysis patients, ionized calcium levels should be closely monitored since changes in calcium supplement or vitamin D therapy may be required to maintain ionized calcium and parathyroid hormone values at the pre-treatment levels.
Atrial natriuretic peptide (ANP) is a hormone liberated from the heart during atrial stretch (volume overload). In order to determine if ANP levels are altered in patients on continuous ambulatory peritoneal dialysis (CAPD) or affected by the dialysis procedure itself, we measured plasma ANP in patients before and after peritoneal infusion of two liters of 1.5% Dianeal dialysate and in dialysate subsequently drained from these patients. Plasma ANP is elevated in CAPD patients, but is not affected by infusion of dialysate. ANP is cleared from plasma by peritoneal dialysis.
First-use reactions comprise a spectrum of adverse clinical signs and symptoms occurring in end-stage renal failure patients during hemodialysis treatments. This report describes four patients experiencing first-use reactions in the context of being referred to or from a tertiary care inpatient dialysis facility. Theories on the pathogenesis of first-use reactions are reviewed and recommendations for identifying patients at increased risk for this problem are proposed.
The clinical and laboratory findings in 14 infants, 2 children and 42 adults with RTA-1 have been retrospectively analyzed and the patients classified as having the hereditary (14%), acquired (31%), or idiopathic (55%) form. In 7 of the 8 hereditary cases, RTA-1 appeared to be a complication of hereditary hypercalciuria. The majority of acquired cases (61%) were secondary to immune-mediated diseases. All of the 14 infants with RTA-1 were classified as idiopathic. All of the idiopathic cases in children and adults were associated with nephrolithiasis and/or nephrocalcinosis, 33% of which had a family history of nephrolithiasis. The 14 infants presented with failure to thrive. Seventy-seven percent of children and adults with RTA-1 had nephrolithiasis and/or nephrocalcinosis and usually presented with symptoms related to this problem. Adults without nephrolithiasis or nephrocalcinosis usually presented with electrolyte disturbances or acidosis. Hypokalemia, the most common electrolyte disturbance, was present in 28% of the entire series. Acidosis was present in all infants and in 70% of children and adults. Clinically apparent bone disease was observed in 3 infants, and in 1 adult with nephrolithiasis. Glomerular function was normal in infants and in the 2 children, but depressed in 40% of adults. Recurrent urinary tract infection was a contributing factor but was not the sole cause of renal failure. Surprisingly, kidney stone number, the number of surgical procedures, and the presence of nephrocalcinosis had no apparent effect on the development of renal failure. Glomerular filtration rate was significantly higher in patients with incomplete RTA-1, and serum total CO2 was significantly correlated with creatinine clearance and minimum urinary pH. Hypercalciuria was present in 32% of patients with nephrolithiasis and/or nephrocalcinosis, and urinary citrate excretion was low in all of 16 patients in whom it was measured. Hypocitraturia appeared to be due in most cases to potassium depletion and renal failure, but may have occurred as a primary defect in 1 patient with hereditary RTA. Urinary uric acid excretion was elevated in 23% of patients with stones in whom it was measured. The mean number of stone-forming events was 51 +/- 14. Although a weak correlation between urinary calcium excretion and stone number was observed, the cause for prodigious stone formation could not be explained. This series emphasizes the variable degree to which the common clinical manifestations of RTA-1 (metabolic acidosis, hypercalciuria, nephrolithiasis, nephrocalcinosis, and potassium depletion) are expressed.(ABSTRACT TRUNCATED AT 400 WORDS)
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The human immunodeficiency virus (HIV) was transmitted to a patient who received a cadaveric renal transplant from a donor who had received massive blood component replacement. A negative HIV antibody test was obtained on serum drawn immediately after transfusion. After transplantation, pretransfusion sera and sera obtained several hours after transfusion tested positive for HIV antibody, suggesting that transfusions had transiently diluted the patient's serum and resulted in a false-negative HIV antibody test. Immediately after transplantation, the recipient showed a transient increase in HIV antigen levels followed by a more sustained increase representing de-novo antigen synthesis. Antibodies to HIV were detected 51 days after transplant. The recipient has shown no signs or symptoms of HIV infection after 1 year. In potential cadaveric organ donors, HIV antibody testing should be performed on pretransfusion sera or on sera obtained several hours after massive transfusion of blood products.