Circadian rhythm and day to day variability of serum potassium concentration: a pilot study.

BACKGROUND: Hyperkalemia is a common and life-threatening complication frequently seen in patients with acute kidney injury, end-stage renal disease and chronic heart failure. Cardiac arrest and ventricular fibrillation are possible consequences. Biosensors are currently being developed to measure serum potassium under ambulatory conditions and trigger an alarm if the potassium concentration exceeds normal limits. Only few studies exist on the circadian rhythm of potassium; and its dependence on age and kidney function is less clear. METHODS: Our observational monocentric exploratory study included 30 subjects of which 15 had impaired renal function (RF) (GFR <60 ml/min/1.73 m(2)). Subjects were further categorized into three age groups: 18-39 years (N normal RF = 5, N impaired RF = 4), 40-59 years (N normal RF = 5, N impaired RF = 6), 60-80 years (N normal RF = 5, N impaired RF = 5). Serum potassium levels were measured every 2 h during a 24 h period and repeated once after 2, 4, or 6 days. RESULTS: In the 15 subjects with normal RF, the lowest mean potassium level (3.96 ± 0.14 mmol/l) was observed at 9 p.m. and the greatest (4.23 ± 0.23 mmol/l) at 1 p.m. In patients with impaired RF the lowest mean potassium level (4.20 ± 0.32 mmol/l) was observed at 9 p.m. and the highest (4.57 ± 0.46 mmol/l) at 3 p.m. The range between the mean of minimum and maximum was greater in patients with impaired RF (0.71 ± 0.45 mmol/l) than in subjects with normal RF (0.53 ± 0.14 mmol/l) [p < 0.001]. No difference in the circadian rhythm was found between the first and second examination. CONCLUSION: Our results indicate that patients with normal and impaired RF have comparable circadian patterns of serum potassium concentrations, but higher fluctuations in patients with impaired RF. These results have clinical relevance for developing an automatic biosensor to measure the potassium concentration in blood under ambulatory conditions in patients at high risk for potassium fluctuations.

Pathologic alterations of the heart and the kidney in patients with ankylosing spondylitis.

BACKGROUND: The occurrence of a variety of pathological lesions of the heart and kidneys have been described in patients with ankylosing spondylitis (AS). The frequency of these alterations and whether they are specific for AS has been discussed controversially. - METHODS: Outpatients with AS were studied to determine the frequency of cardiac and renal alterations and to assess the associated clinical and demographic factors. - RESULTS: A total of 77 patients with AS participated in the study (male 84.4%, mean age 48.3 +/- 1.5 years, mean duration of disease 15.4 +/- 1.2 years). Hypertension was present in 36.4% and diabetes mellitus in 13.0%. Impaired renal function (defined by a decrease in GFR) combined with markers of kidney damage suspective for chronic kidney disease were present in 3 patients (3.9%). Pathologic alterations of the heart were found in 25 patients (37.3%). Echocardiographic abnormalities were present in 20 patients (e.g. aortic and mitral insufficiency). Electrocardiographic abnormalities were present in 12 patients (e.g. atrioventricular, left and right branch block). Patients with cardiac abnormalities were older (54.2 +/- 2.9 vs. 44.9 +/- 1.7 years) and had a longer duration of disease (20.6 +/- 2.1 vs. 13.9 +/- 1.6 years) as compared to non-affected patients. - CONCLUSION: In our study, cardiac abnormalities were frequently seen in patients with AS, while renal disease was more rare and might be due to diseases not related to AS in most of patients. In contrast to cardiac involvement, it therefore appears questionable, that chronic kidney disease is part of the extraskeletal manifestations, or at least that AS has a high impact on renal integrity.

Influence of short-term versus prolonged cardiopulmonary receptor stimulation on renal and preganglionic adrenal sympathetic nerve activity in rats.

Renal and preganglionic adrenal sympathetic nerve activities (RSNA, ASNA) are regulated differentially. Various cardiopulmonary receptor (CPR) stimulation procedures were performed to distinguish short-term and prolonged as well as mechanical and chemical stimulatory effects on RSNA and ASNA. In anesthetized male Sprague-Dawley rats blood pressure, heart rate, left ventricular end-diastolic pressure (LVEDP), RSNA and ASNA were recorded. CPRs were stimulated as follows: Short-term mechanical: LVEDP changes (+/-4, +/-6, +/-8 mmHg) via aortic and caval vein occlusion; Short-term chemical: phenylbiguanide (PBG-bolus, 0.1, 1, 10 microg IV); Prolonged mechanical (15 min): volume expansion (0.9% NaCl, 5% body weight) and hemorrhage, to modulate LVEDP; Prolonged chemical: PBG infusion (32 microg/min IV, for 15 min); Stimulations were done with 1) all afferents intact, 2) bilateral cervical vagotomy (VX), 3) VX + SAD (sino-aortic denervation; short-term protocols and hemorrhage).1) Short-term mechanical stimuli decreased RSNA (-52 +/- 12%) and ASNA (-37 +/- 13%). 2) PBG-bolus decreased RSNA (-54 +/- 12%) but increased ASNA (+40 +/- 13%). 3) Volume expansion decreased RSNA (-55 +/- 7%), ASNA was unaffected. 4) PBG infusion persistently decreased RSNA (-60 +/- 6%) but just shortly increased ASNA (+120 +/- 15%); VX abolished all responses. 5) Hypotensive hemorrhage decreased RSNA (-39 +/- 9%) but increased ASNA (+42 +/- 9%). VX abolished RSNA response; ASNA response only disappeared with VX + SAD.Short-term mechanical CPR stimulation uniformly decreased sympathetic activities, whereas chemical stimulation had opposing effects on renal and adrenal sympathetic responses. All prolonged stimuli decreased RSNA, whereas ASNA was virtually unaffected: Sympathetic out.ow is differentially controlled not only with regard to target organs or afferent receptors but also stimulus time pattern.

Management of renal complications in patients with advanced multiple myeloma.

Although the kidney is frequently involved in malignant monoclonal gammopathy, the clinical outcome of the patients varies considerably. We retrospectively assessed the clinical course in seventeen patients with acute and chronic renal failure suffering from multiple myeloma, and analyzed their case history focusing on the therapeutic management, the possible clinical improvement as well as the patients' outcome. Treatment included chemotherapy (n = 17), forced diuresis (n = 3), hemodialysis (n = 11, 7 chronic, 4 intermittent) and plasmapheresis (n = 3). Renal function improved in five patients, and was stabilized compensated in four. Seven patients developed end-stage renal disease, one refused further treatment and was lost for follow up. In addition to renal failure, the most frequent complications included local bone destruction (all), anemia (n = 12), low platelet count (n = 11), and bacterial infections (n = 9). One year survival rate after admission to the nephrology department was 76 percent. Chemotherapy in combination with renal replacement therapy may improve the clinical course even in MM patients with serum creatinine levels above 3.0 mg/dL or end-stage renal disease.

An unusual case of Aspergillus endocarditis in a kidney transplant recipient.

The incidence of aspergillosis in kidney transplant recipients is low and most commonly occurs in the early posttransplantation period. We report an unusual case of a 52-year-old female patient with Aspergillus endocarditis as a late complication after kidney transplantation, presumably spread from a necrosis in the gut, associated with previous cytomegalovirus colitis. As complications, the patient experienced septic embolization into the coronary and pulmonary arteries, and an infarction of the right parietal cortex and insula. The patient died as a result of global heart failure after a 10-day course of antimycotic therapy with amphotericin B plus 5-flucytosine during surgical valve replacement.

Subthreshold stimulation of a serotonin 5-HT3 reflex attenuates cardiovascular reflexes.

Volume-sensitive and chemosensitive cardiopulmonary reflexes modulate volume homeostasis via renal sympathetic nerve activity (RSNA). Blunting of volume-sensitive cardiopulmonary reflexes is associated with volume retention, e.g., in hypertension, whereas the role of chemosensitive cardiopulmonary reflexes is largely unknown. To elucidate the possible role of chemosensitive cardiopulmonary reflexes in control of volume homeostasis, we investigated whether subthreshold stimulation of 5-HT3 receptors modulates the control of RSNA by volume-sensitive cardiopulmonary reflexes or the arterial baroreceptor reflex in rats. Phenyl biguanide (PBG) was infused intravenously to stimulate 5-HT3 receptors. Higher doses of PBG lowered RSNA, but a dose of 6 micrograms/min, given as a background infusion throughout the experiment, did not change arterial pressure, heart rate (HR), or RSNA. Ten minutes after beginning the 6 micrograms/min PBG infusion, a 15-min volume expansion (0.9% saline, 5 or 10% body weight) was started to stimulate volume-sensitive cardiopulmonary reflexes. In separate experiments, 5-min ramp infusions of methoxamine and nitroglycerin to stimulate the arterial baroreceptor reflex (evaluated by a 4-parameter logistic regression) were performed 15 min after beginning the PBG background infusion (6 micrograms/min). During PBG infusion, the RSNA responses to volume expansions were significantly impaired (5% body weight: PBG -6 +/- 6%, n = 7 vs. control -39 +/- 9%, n = 6, P < 0.001; 10% body weight: PBG -33 +/- 6%, n = 8 vs. control -52 +/- 5%, n = 7, P < 0.05). The 5-HT3 receptor antagonist odansetron (GR-38032F) abolished these effects of PBG. The maximum HR gain of the arterial baroreceptor reflex was impaired but the arterial baroreceptor control of RSNA was unaffected by PBG background infusion. We conclude that 5-HT3-serotonergic cardiopulmonary chemoreceptors blunt the RSNA decrease to volume loading. This mechanism may facilitate volume retention when cardiac serotonin is increased.

Impaired cardiovascular reflexes precede deoxycorticosterone acetate-salt hypertension.

We hypothesized that impaired cardiopulmonary reflexes but not altered baroreceptor reflexes precede deoxycorticosterone acetate (DOCA)-salt hypertension. Uninephrectomized rats were given either DOCA and 0.9% NaCl as drinking water, 0.9% NaCl alone, or tap water. We measured mean blood pressure, heart rate, and renal sympathetic nerve activity. After 8 days, mean blood pressure was not different in DOCA-salt and control rats. Volume-sensitive cardiopulmonary reflexes were tested by intravenous volume loading with saline (10% body weight in 15 minutes), which decreased renal sympathetic nerve activity without changing mean blood pressure or heart rate. This response was blunted in DOCA-salt rats. Chemosensitive cardiopulmonary reflexes were tested by 15-minute infusions of the serotonin 5-HT3 agonist phenylbiguanide, which decreased renal sympathetic nerve activity without changing mean blood pressure or heart rate. Sustained decreases in renal sympathetic nerve activity occurred during phenylbiguanide infusion in controls but were blunted over time in DOCA-salt rats. The arterial baroreflex responses to graded infusions of methoxamine and nitroprusside were analyzed by sigmoidal curve fitting. There were no differences in gain of renal sympathetic nerve activity or heart rate between the groups. Thus, DOCA-salt rats exhibit impaired cardiopulmonary reflexes before the onset of hypertension; the volume-sensitive reflexes are more severely affected than chemosensitive reflexes. The arterial baroreceptor reflex is unaltered. The decreased sensitivity of cardiopulmonary reflexes may contribute to DOCA-salt hypertension.