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Increased plasma adrenomedullin levels in hemodialysis patients with sustained hypotension.BackgroundSustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients.MethodsThree groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1β (IL-1β) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated.ResultsPlasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 ± 25.4 pg/mL) than normotensive (225 ± 9.9 pg/mL) and hypertensive HD patients (278.2 ± 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0.53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01).ConclusionsPlasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.

From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival1 year mean hospitalization days was 9.6 (P0.001). The median survival was 20 months and six patients survived for3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long-term survivors.

About 5% of patients with MM develop acute renal failure requiring dialysis. From Jan 1982 through Dec 1993, 20 patients (11 M, 9 F, median age 62 yr) with MM required long-term HD (> 2 months) at our institution. The M-component type was IgG in 8 cases (3k, 5A), IgA in 8 cases (7k, 1A), free light chain in 3 cases (2k, 1A) and Ig-Mre in one case. Among 17 patients evaluable for response to chemotherapy, the objective response rate was 47% (8/17). In only two patients could be discontinued. The total number of hospital admissions was 42. Mean hospitalization days per year was 19.3 ± 13.9 (SD). The subgroup of patients who survived less than one year spent a mean of 38.3 ± 21.4 (SD) days in hospital, while in the subgroup with a survival longer than one year mean hospitalization days was 9.6 ± 5.6(SD)(P

Carpal tunnel syndrome, peripheral arthropathy, erosive spondyloarthropathy and lytic bone lesions have all been associated with dialysis amyloidosis. Recent studies indicate that beta 2-microglobulin is the major constituent protein in this new form of amyloidosis. Dialysis amyloidosis was reported to have a local rather than a systemic involvement, although its full extent is yet to be determined. We investigated 3 patients on maintenance hemodialysis with bilateral carpal tunnel syndrome and amyloid arthropathy and found amyloid depositions in several organs. These findings suggest that, in contrast to what had been thought previously, dialysis amyloidosis could have systemic as well as visceral distribution. The amyloid deposits found were resistant against potassium permanganate treatment and reacted with anti-human beta 2-microglobulin antibody.

A 28-year-old patient with chronic renal failure on maintenance hemodialysis developed fever, granulomatous hepatitis, pulmonary infiltrates, sacroiliitis, and spondylitis which were unresponsive to conventional antituberculous treatment. Cultures of the sputum gave repeated growth of Mycobacterium fortuitum. This organism was resistant 'in vitro' to most antituberculous drugs and sensitive to some aminoglycosides and doxycycline. No mycobacteria were found in the water used for dialysis. The patient was successfully treated with amikacin and doxycycline. Nontuberculous mycobacterial infection should be considered in the differential diagnosis of febrile illnesses resembling tuberculosis in hemodialysis patients. Defective immune mechanisms could contribute to this complication. Since M. fortuitum is usually resistant to antituberculous drugs, precise identification and sensitivity testing are essential for optimal management.

During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.