Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 132
Filter
1.
Osteoporos Int ; 32(5): 865-871, 2021 May.
Article in English | MEDLINE | ID: mdl-33313993

ABSTRACT

In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin. PURPOSE: Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers. METHODS: We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n = 1005), median age 75.3 years (range 69-81 years). RESULTS: Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r = - 0.11, P = 0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r = - 0.09, P = 0.006) and total hip BMD (r = - 0.08, P = 0.010), and positively related to serum ALP (r = 0.15, P < 0.001). Hgb was positively related to total hip BMD (r = 0.16, P < 0.001), and negatively to serum osteocalcin (r = - 0.13, P < 0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin. CONCLUSIONS: Our observations support the hypothesis of an interplay between blood and bone components.


Subject(s)
Bone Density , Bone Diseases, Metabolic , Aged , Aged, 80 and over , Biomarkers , Humans , Male , Osteocalcin , Platelet Count , Sweden/epidemiology
2.
Kidney Blood Press Res ; 34(6): 396-403, 2011.
Article in English | MEDLINE | ID: mdl-21677436

ABSTRACT

AIMS: To examine biomarkers of oxidative stress (oxs), and endothelin (ET)-1, in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) and to evaluate the effect of percutaneous transluminal renal angioplasty (PTRA). METHODS: Baseline measurements were made immediately before renal angiography in patients with suspected ARAS (significant ARAS, n = 83, and non-RAS, n = 59) and in 20 healthy, matched controls. In patients with ARAS, analyses were repeated 4 weeks after PTRA. All patients were treated with statins and acetylsalicylic acid throughout. RESULTS: At baseline there were no significant differences between groups in biomarkers of oxs, whereas high-sensitivity C-reactive protein and blood leukocytes were significantly elevated in group ARAS versus both healthy controls and group non-RAS. Plasma levels of ET-1 and uric acid were significantly increased in group ARAS versus healthy controls prior to angiography and were significantly reduced compared to baseline 4 weeks after PTRA. PTRA had no significant effects on biomarkers of oxs, inflammation or serum creatinine concentrations. CONCLUSIONS: ARAS patients on treatment with antihypertensive agents, acetylsalicylic acid and statins showed elevated inflammatory indices but no increase in oxs. PTRA had no significant effects on inflammatory indices 4 weeks after intervention but reduced plasma ET-1 and uric acid.


Subject(s)
Angioplasty , Atherosclerosis/blood , Endothelin-1/blood , Oxidative Stress/physiology , Renal Artery Obstruction/blood , Aged , Angioplasty/methods , Atherosclerosis/pathology , Atherosclerosis/therapy , Biomarkers/blood , Endothelin-1/antagonists & inhibitors , Female , Humans , Hypertension/blood , Hypertension/pathology , Hypertension/therapy , Male , Middle Aged , Renal Artery Obstruction/pathology , Renal Artery Obstruction/therapy , Uric Acid/antagonists & inhibitors , Uric Acid/blood
3.
Transplant Proc ; 38(8): 2642-3, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17098025

ABSTRACT

The incidence of end-stage kidney failure (ESRF) was analyzed among the cohort of 1112 living kidney donors who underwent nephrectomy from 1965 through 2005. It was found that at least six persons had developed ESRF at 14 to 27 years (median = 20 years), following donation. Five of six were men. Five were parents and one, a sibling. The diagnoses were nephrosclerosis (n = 4), postrenal failure (n = 1), and renal carcinoma (n = 1). One donor, aged 45 years, underwent kidney transplantation.


Subject(s)
Kidney Failure, Chronic/epidemiology , Living Donors , Nephrectomy/adverse effects , Cohort Studies , Fathers , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/etiology , Kidney Neoplasms/epidemiology , Male , Mothers , Retrospective Studies , Time Factors , Tissue and Organ Harvesting
4.
J Intern Med ; 251(2): 129-35, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11905588

ABSTRACT

OBJECTIVES: To evaluate the relationship between anti-neutrophil cytoplasmic antibody (ANCA) measured with two different methods and long-term clinical course in vasculitis. DESIGN: Retrospective determination of ANCA with two different assays for detection of PR3-ANCA, conventional direct binding ELISA and capture ELISA using monoclonal antibodies against PR3. The 245 ANCA determinations were performed from frozen blood samples collected three to four times a year in each patient. SETTING: Department of Nephrology at a Swedish University Hospital. SUBJECTS: A total of 10 ANCA-positive patients with vasculitis caused by Wegener's granulomatosis (WG) or microscopic polyarteritis (MPA) and a very long follow-up time (mean 9 years, range 5-15.5 years). RESULTS: The total number of episodes with active vasculitis was 29 and all of them (100%) were detected by the capture technique whilst the conventional technique detected 23 (79%). The mean number of episodes with active disease requiring treatment with steroids and cytotoxic drugs was three per patient (range 1-6). At the time of clinical relapse of the vasculitis disease, the ANCA titre using the capture technique was either increasing or showed a very high value in all cases. The pattern of capture ANCA response could be subdivided into three categories: a close (four patients), an intermediate (three patients), and no (three patients) relationship between capture ANCA level and long-term clinical course. CONCLUSION: Detection of PR3-ANCA by the capture ELISA showed a higher sensitivity than that obtained by the direct ELISA in diagnosing relapse during follow-up of patients with vasculitis. The specificity of the capture ANCA was, however, low, as high levels occurred in patients without clinical disease activity.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Vasculitis/immunology , Adult , Aged , Aged, 80 and over , Arteritis/diagnosis , Arteritis/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Follow-Up Studies , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/immunology , Humans , Male , Middle Aged , Myeloblastin , Retrospective Studies , Sensitivity and Specificity , Serine Endopeptidases/immunology , Vasculitis/diagnosis
5.
Nephrol Dial Transplant ; 16(11): 2158-65, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11682661

ABSTRACT

BACKGROUND: The renoprotective effect of ACE inhibition in chronic renal disease is well established but the studies on effects of calcium antagonists on progression of renal disease and on proteinuria have given varying results. METHODS: We conducted an open long-term randomized prospective multi-centre study comparing the combination of ramipril and felodipine ER (F) with either drug alone in non-diabetic renal disease. Included were patients with uncontrolled hypertension (diastolic blood pressure (DBP)) > or =95 mmHg on treatment with a diuretic and a beta-blocker. Fifty-one patients received the combination of R and F, 54 patients R, and 53 patients F. The treatment goal was a DBP <90 mmHg and a similar BP reduction in the three groups. Mean doses at the last visit were 5+5, 10 and 9 mg, respectively, after a mean treatment time of nearly 2 years. The progression of renal impairment was studied by serial measurements of serum creatinine, iohexol clearance, and albuminuria. RESULTS: The reduction in supine systolic (S) BP and DBP expressed as median values were -19.0/-14.5,-14.3/-15.0 and -13.5/-13.3 mmHg in the R+F, R, and F groups, respectively. There was no significant difference between the groups. When correction for the acute drug effect was performed the R+F group had a slower progression rate of the renal disease (loss of glomerular filtration rate (GFR) ml/min/year) compared with the F group (P<0.05) but not to the R group (P>0.20). There was a rise in albuminuria after 2 years in the F group (P<0.05), but no significant change was found in the other groups. CONCLUSIONS: In patients with non-diabetic renal disease the combination of an ACE inhibitor and a calcium antagonist in reduced doses used in addition to baseline therapy with beta-blockers and diuretics, tended to cause a better BP reduction as each drug per se. The R+F treatment also caused a slower progression of the renal disease compared with F alone. The combination treatment seems to afford better BP control and appears to be a favourable therapeutic option in patients with renal disease and hypertension.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Felodipine/therapeutic use , Kidney Diseases/drug therapy , Kidney Diseases/physiopathology , Ramipril/therapeutic use , Adult , Albuminuria/urine , Blood Pressure/drug effects , Disease Progression , Drug Combinations , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney Diseases/urine , Male , Middle Aged , Prospective Studies
6.
Clin Sci (Lond) ; 100(4): 443-9, 2001 04.
Article in English | MEDLINE | ID: mdl-11256986

ABSTRACT

The activity of the erythrocyte transport system, sodium/lithium countertransport (SLC), has been linked to the metabolic syndrome characterized by insulin resistance and compensatory hyperinsulinaemia. We measured SLC and insulin sensitivity with the euglycaemic hyperinsulinaemic clamp method in a patient sample (n = 93) randomly selected from a large clinically healthy group of 58-year-old men (n = 818). The lipid profile, blood pressure, body mass index (BMI) and insulin were also analysed. There was a significant difference (P < 0.001) in SLC between subjects with the metabolic syndrome (n = 19) and subjects without any components of this syndrome (n = 20). There was a highly significant correlation between SLC and BMI, waist/hip ratio, total body fat mass, serum triglycerides, plasma insulin, proinsulin split products and C-peptide in a univariate analysis. There was also a significant correlation between SLC and insulin sensitivity measured as insulin-mediated glucose uptake (P < 0.01). In multiple regression analysis, only two of the variables showing univariate significance were independently correlated to SLC, i.e. serum triglycerides (P < 0.001) and BMI (P < 0.01). The subjects with a SLC value in the highest tertile had a 6-fold higher prevalence of insulin resistance (low-insulin-mediated glucose uptake) as compared with those with a SLC value in the lowest tertile. We conclude that, in clinically healthy 58-year-old men from the general population, erythrocyte SLC is closely linked to metabolic syndrome, in particular to obesity, triglycerides and insulin resistance.


Subject(s)
Albuminuria/blood , Antiporters/blood , Insulin Resistance/physiology , Body Mass Index , Erythrocytes/metabolism , Glucose Clamp Technique , Humans , Lithium/blood , Male , Middle Aged , Obesity/blood , Sodium/blood , Syndrome , Triglycerides/blood
7.
Hypertension ; 36(4): 543-8, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11040233

ABSTRACT

Hypertension with renal artery stenosis is associated with both an activated renin-angiotensin system and elevated sympathetic activity. Therefore, in this condition it may be favorable to use a therapeutic modality that does not reflexly increase heart rate, renin secretion, and sympathetic nervous activity. The purpose of the present study was to assess overall, renal, and muscle sympathetic activity after short-term administration of an angiotensin-converting enzyme inhibitor (enalaprilat) and a nonspecific vasodilator (dihydralazine) to hypertensive patients with renal artery stenosis. Forty-eight patients undergoing a clinical investigation for renovascular hypertension were included in the study. An isotope dilution technique for assessing norepinephrine spillover was used to estimate overall and bilateral renal sympathetic nerve activity. In 11 patients simultaneous intraneural recordings of efferent muscle sympathetic nerve activity were performed. Thirty minutes after dihydralazine administration, mean arterial pressure fell by 15%, whereas plasma angiotensin II, muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover increased (P<0.05 for all). In contrast, after enalaprilat administration a fall in arterial pressure similar to that for dihydralazine was followed by decreased angiotensin II levels and unchanged muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover, whereas renal norepinephrine spillover increased by 44% (P<0.05). Acute blood pressure reduction by an angiotensin-converting enzyme inhibitor provokes a differentiated sympathetic response in patients with hypertension and renal artery stenosis, inasmuch that overall and muscle sympathetic reflex activation are blunted, whereas the reflex renal sympathetic response to blood pressure reduction is preserved.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Dihydralazine/administration & dosage , Enalaprilat/administration & dosage , Hypertension, Renovascular/drug therapy , Sympathetic Nervous System/drug effects , Angiotensin II/blood , Blood Pressure/drug effects , Electrophysiology , Female , Heart Rate/drug effects , Humans , Hypertension, Renovascular/metabolism , Male , Middle Aged , Muscle, Skeletal/innervation , Norepinephrine/metabolism , Peroneal Nerve , Renal Artery Obstruction/complications , Renal Artery Obstruction/metabolism , Sympathetic Nervous System/metabolism
8.
Kidney Int ; 58(2): 774-82, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10916102

ABSTRACT

BACKGROUND: Renovascular hypertension is the most common form of curable secondary hypertension and, if untreated, may lead to end-stage kidney disease. Given that renal function and hypertension may improve after renal angioplasty, it is pertinent to identify patients with renal artery stenosis. The aim of the present study was to evaluate both duplex ultrasound and captopril renography for detection of renal artery stenosis among hypertensive patients. METHODS: To avoid selection bias, all patients referred to our center for evaluation of renovascular hypertension were asked to participate in the study. Patients were examined by intra-renal duplex ultrasound (N = 121), measuring pulsatility index and acceleration of the blood flow during early systole. In 98 patients, 99mTc-DTPA captopril renography was performed in conjunction with duplex ultrasound. Renal angiography was performed in all patients regardless of the results of the noninvasive tests. RESULTS: The prevalence of renal artery stenosis was 19%. In the 98 patients examined by both duplex ultrasound and captopril renography, sensitivity and positive predictive values for detection of a renal artery stenosis of 50% degree or more were 84 and 76%, respectively, for duplex ultrasound, whereas captopril renography was associated with a sensitivity and positive predictive value of 68% for both (P = NS). Specificity and negative predictive values were 94 and 96%, respectively, for duplex ultrasound, whereas the corresponding values for captopril renography were 92% for both (P = NS). Specificity and negative predictive values were 94 and 96%, respectively, for duplex ultrasound, whereas the corresponding values for captopril renography were 92% for both (P = NS). CONCLUSIONS: Both duplex ultrasound and captopril renography are associated with high specificity and negative predictive values for detection of renal artery stenosis. Sensitivity and positive predictive values are at least as good for duplex ultrasound compared with captopril renography. Given that duplex ultrasound is easier to perform and more cost effective, we propose that it should be the method of first choice when screening for renal artery stenosis in a hypertensive population.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Captopril , Hypertension, Renal/diagnostic imaging , Radioisotope Renography , Ultrasonography, Doppler, Duplex , Blood Flow Velocity , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Male , Middle Aged , Predictive Value of Tests , Radiopharmaceuticals , Renal Artery Obstruction/diagnostic imaging , Renal Circulation , Sensitivity and Specificity , Technetium Tc 99m Pentetate
9.
J Hypertens ; 18(7): 945-53, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10930193

ABSTRACT

Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.


Subject(s)
Autoantibodies/immunology , Hypertension, Malignant/immunology , Hypertension, Renal/immunology , Immunoglobulin G/immunology , Receptors, Angiotensin/immunology , Animals , Biomarkers/blood , Cells, Cultured , Cricetinae , Enzyme-Linked Immunosorbent Assay , Female , Heart Ventricles/embryology , Heart Ventricles/immunology , Heart Ventricles/metabolism , Humans , Hypertension, Malignant/blood , Hypertension, Renal/blood , Kidney Cortex/cytology , Kidney Cortex/immunology , Kidney Cortex/metabolism , Male , Middle Aged , Ovary/cytology , Ovary/immunology , Ovary/metabolism , Rats , Receptor, Angiotensin, Type 1 , Receptors, Angiotensin/blood
10.
Blood Press ; 9(2-3): 104-9, 2000.
Article in English | MEDLINE | ID: mdl-10855732

ABSTRACT

BACKGROUND: The mechanism of the rapid transition of a stable benign hypertensive disease to a severe and devastating malignant hypertension is not fully understood. However, the renin angiotensin system, which is highly activated in malignant hypertension, is established as an important pathogenetic factor in different cardiovascular and renal diseases. Over the last decade, a polymorphism in genes regulating this system has been found. This includes the 287 bp sequence deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme (ACE) gene and the methionine (M) to threonine (T) point mutation polymorphism in the angiotensinogen (AGT) gene. These gene polymorphisms have been associated with various cardiovascular and renal diseases and the aim of this study was to investigate whether they were linked to malignant hypertension. METHODS: Forty-two patients with malignant hypertension (mean age 55 years), 42 patients with non-malignant hypertension (mean age 57 years) and 85 normotensive control subjects (mean age 42 years) were investigated with respect to ACE I/D and AGT M/T genotypes. DNA was prepared by standard methods from isolated white blood cells and analysed by the PCR technique. The PCR reaction used in the detection of the ACE I/D polymorphism was optimized for an equal amplification of the I and D alleles. RESULTS: The frequency of the DD genotype was significantly increased in patients with malignant hypertension (43%) compared with patients with non-malignant hypertension (14%) and normotensive control subjects (18%) (p <0.01) for both. The frequency distribution of AGT M/T genotype did not differ between patients with malignant and non-malignant hypertension. CONCLUSION: The DD genotype of the ACE gene occurred more than twice as often in malignant hypertension than in non-malignant hypertension and indicates that ACE gene polymorphism is a significant risk factor for initiation of malignant hypertension.


Subject(s)
DNA Transposable Elements , Gene Deletion , Hypertension, Malignant/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic/genetics , Adult , Female , Gene Frequency , Genotype , Humans , Hypertension/genetics , Male , Middle Aged , Reference Values
11.
Lakartidningen ; 97(11): 1263-6, 2000 Mar 15.
Article in Swedish | MEDLINE | ID: mdl-10771545

ABSTRACT

The syndrome of cholesterol embolism is a multiorgan disorder caused by peripheral embolization of cholesterol crystals from an ulcerated aorta plaque. The kidney is the organ most often affected (approx 50%). Prognosis is poor, with a mortality of about 70%. We describe two of four cases of cholesterol embolism diagnosed during the autumn of 1997. All were elderly men with advanced generalized atherosclerosis. Positive diagnosis upon renal biopsy required demonstrating cholesterol crystals in renal interlobar and arcuate arteries. Workups for progressive renal failure were performed due to suspected vasculitis in three cases and radiologically induced renal damage subsequent to coronary angiography in another. None of the patients showed renal vasculitis upon biopsy, but one who was ANCA positive developed vasculitis after a few months. Three patients died within a couple of months of onset. The patient with renal vasculitis was treated with cyclophosphamide and steroids, and survives one and a half years after onset. It is vital to consider the diagnosis cholesterol embolism whenever an elderly patient with pronounced atherosclerosis develops progressive renal failure and multi-organ failure. Angiography, aorto-iliaco-femoral surgery and thrombolytic therapy increase the risk of cholesterol embolism in this group. There is no effective therapy. The key is prophylaxis, which means identifying patients at risk prior to invasive vascular procedures.


Subject(s)
Angiography/adverse effects , Embolism, Cholesterol/etiology , Vascular Surgical Procedures/adverse effects , Aged , Cardiac Surgical Procedures/adverse effects , Coronary Angiography/adverse effects , Diagnosis, Differential , Embolism, Cholesterol/diagnosis , Fatal Outcome , Humans , Kidney/pathology , Male , Middle Aged , Prognosis , Risk Factors , Thrombolytic Therapy/adverse effects , Vasculitis/complications , Vasculitis/etiology , Vasculitis/pathology
13.
Lakartidningen ; 96(47): 5209-14, 1999 Nov 24.
Article in Swedish | MEDLINE | ID: mdl-10608112

ABSTRACT

One hundred years ago, in 1898, Professor Robert Tigerstedt, Karolinska institutet, Sweden, discovered renin. The subsequent elaboration in 1960 of the renin-angiotensin-aldosterone system signalled the start of modern hypertension research. The kidney takes part in blood pressure regulation in a number of ways. Indications are that increased renovascular resistance due to increased renin-angiotensin activity is of importance for the barostatic function of the kidneys and for the pathogenesis of human hypertension. Several commonly used, efficacious and well tolerated antihypertensive agents act by blocking the renin-angiotensin system, thus normalising kidney function. A number of current large-scale trials--utilising ACE inhibitors and angiotensin receptor antagonists--will, it is hoped, elucidate the proper role of 'anti-renin therapy' in the treatment of hypertension. Thanks to effective modern management of hypertension, renal failure due to hypertensive kidney disease is rare in Sweden today.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Hypertension, Renal/drug therapy , Renin-Angiotensin System/drug effects , Renin/history , Acute Kidney Injury/physiopathology , Angiotensin II/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/history , History, 19th Century , History, 20th Century , Humans , Hypertension, Renal/epidemiology , Hypertension, Renal/etiology , Hypertension, Renal/physiopathology , Kidney Failure, Chronic/physiopathology , Renin/physiology , Risk Factors , Sweden/epidemiology
14.
Kidney Int ; 56(5): 1838-45, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10571792

ABSTRACT

BACKGROUND: Experimental studies have shown that nitric oxide (NO) generation in the kidney from L-arginine participates in the regulation of renal function. Our purpose was to study the effect of infusion of L-arginine (1, 5, and 10 mg/kg/min) on blood pressure (BP), renal hemodynamics, and urinary excretion of sodium and albumin in normotensive subjects with a family history of either severe hypertension (FHSH, N = 17) or mild hypertension (FHMH, N = 20) and in control subjects (N = 18) without a hereditary predisposition for hypertension. METHODS: The glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by renal clearances of Cr51 ethylenediaminetetraacetic acid and paramino-hippurate. Renal tubular reabsorption of sodium was estimated by lithium clearance. To evaluate the effect of L-arginine infusion on the L-arginine/NO pathway, we measured the NO-metabolite nitrate in plasma, and urinary excretion of cGMP, the second messenger of NO. The derivative at an L-arginine dose of 7.5 mg/kg/min was used as a measure of sensitivity to L-arginine. RESULTS: There was no difference in baseline systolic BP between the groups, but diastolic BP was significantly higher in FHSH compared with control subjects (P < 0.05). L-arginine caused a significant increase in urine flow, urinary excretion of albumin and sodium, and lithium clearance in all groups. FHSH showed a significantly decreased sensitivity to L-arginine with respect to urine flow rate (P = 0029) compared with FHMH and control subjects. L-arginine caused a significant decrease in the GFR in FHSH (P < 0.02) and control subjects (P < 0.001), but in FHMH, the decrease did not reach statistical significance (P = 0.097). There was no difference in sensitivity to L-arginine with respect to BP, RPF, or GFR between the three groups. In all patients, there was a significant positive relationship between Delta urine flow rate or Delta urinary sodium excretion and Delta GFR during infusion of L-arginine (P = 0.003 and P = 0.03, respectively). Plasma nitrate and urinary cGMP decreased in all groups during the L-arginine infusion. CONCLUSION: L-Arginine infusion in normotensive subjects caused an enhanced urine flow rate and urinary sodium and albumin excretion and a slight reduction in GFR. The effect of L-arginine on the urine flow rate was significantly less pronounced in subjects with a family history of severe hypertension, which may indicate a tubular disturbance in hypertension.


Subject(s)
Arginine/pharmacology , Hypertension/genetics , Kidney/drug effects , Adult , Glomerular Filtration Rate/drug effects , Humans , Hypertension/physiopathology , Kidney/physiology , Male , Nitric Oxide/physiology , Renal Circulation/drug effects , Renin/blood , Sodium/metabolism
15.
Scand J Urol Nephrol ; 33(5): 312-6, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10572994

ABSTRACT

The purpose of the present study was to determine the change in bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) in patients with Kock reservoirs for urinary diversion who were examined with the same technique 3 years earlier, and relate the changes to kidney function and variables reflecting bone metabolism. A total of 28 patients with Kock ileal reservoirs to the skin (23) or urethra (5) were reinvestigated 3 years after the first measurement. BMD was measured in the lumbar spine, femur and whole body with DXA. Bone specific alkaline phosphatase, osteocalcin, parathyroid hormone (PTH), calcitonin and chloride were also determined in serum. GFR was determined from the plasma clearance of 51Cr-EDTA. The mean values for BMD expressed in percentage of corresponding mean values for age-matched controls (BMD%) were almost identical after 3 years. Only osteocalcin levels correlated with the BMD% values. However, significant positive correlations were found between GFR and the observed individual changes in BMD% over the 3 years in spite of the fact that most GFR values were fairly normal. Enhanced bone loss was associated with high concentrations of osteocalcin and bone specific alkaline phosphatase. Comparisons with blood gas analyses and determination of 1,25 dihydroxyvitamin D performed in the previous study indicate to us that the relation between reduced GFR and low mineral content might, in part, be related to a low-grade metabolic acidosis and reduced availability of the biologically active vitamin D hormone. The conclusion to be drawn is that urinary diversion with a Kock reservoir does not regularly cause bone demineralization. However, patients with even moderately reduced GFR appear to be at risk for developing osteoporosis in the long-time run.


Subject(s)
Bone Demineralization, Pathologic/etiology , Proctocolectomy, Restorative/adverse effects , Adult , Aged , Alkaline Phosphatase/blood , Bone Density , Female , Humans , Kidney/physiology , Male , Middle Aged , Osteocalcin/blood , Osteoporosis/etiology , Osteoporosis/prevention & control
16.
Scand J Urol Nephrol ; 33(4): 260-4, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10515090

ABSTRACT

Two patients with rhabdomyolysis-induced acute renal failure due to influenza A virus infection are presented. Both had influenza symptoms, with high fever and severe muscular pain leading to walking problems. In addition, they were dehydrated due to vomiting and diarrhoea. Both had evidence of an ongoing influenza infection according to serological tests. Muscle injury due to the viral infection gave rise to rhabdomyolysis with efflux of myoglobin from the muscles, causing renal failure. In conclusion, influenza A virus infection can cause rhabdomyolysis accompanied by reversible acute renal failure.


Subject(s)
Acute Kidney Injury/virology , Influenza A virus/isolation & purification , Influenza, Human/complications , Rhabdomyolysis/virology , Acute Kidney Injury/complications , Acute Kidney Injury/pathology , Adult , Aged , Antibodies, Viral/blood , Biopsy , Encephalitis/diagnosis , Humans , Immunohistochemistry , Influenza, Human/blood , Influenza, Human/diagnosis , Kidney/pathology , Male , Muscle, Skeletal/pathology , Rhabdomyolysis/complications , Rhabdomyolysis/pathology
17.
Circulation ; 99(19): 2537-42, 1999 May 18.
Article in English | MEDLINE | ID: mdl-10330385

ABSTRACT

BACKGROUND: Increased sympathetic nerve activity may contribute to the progression of renovascular hypertension. Because previous results have been inconclusive, we investigated whether renovascular hypertensives show increased total and regional sympathetic nerve activity. METHODS AND RESULTS: Sixty-five patients underwent renal angiography and measurements of plasma renin activity and angiotensin II in conjunction with estimation of sympathetic nerve activity by means of radiotracer dilution and intraneural recordings of muscle sympathetic nerve activity (MSNA). Age-matched healthy subjects (n=15) were examined for comparison. Total body norepinephrine (NE) spillover, an index of overall sympathetic nerve activity, was increased by 100% and MSNA by 60% in the hypertensive patients compared with healthy subjects (P<0.01 for both). A subgroup of 24 patients with well-defined renovascular hypertension (cured or improved hypertension after renal angioplasty) showed similar increases in total body NE spillover compared with the group at large. Patients with arterial plasma renin activity and angiotensin II levels above median had higher values for total body NE spillover than patients below median (P<0.01). CONCLUSIONS: This study unequivocally demonstrates elevated sympathetic nerve activity in patients with renovascular hypertension. The adrenergic overactivity may contribute to the blood pressure elevation and perhaps also to the high cardiovascular mortality in renovascular hypertension.


Subject(s)
Hypertension, Renovascular/physiopathology , Sympathetic Nervous System/physiopathology , Angiography , Angiotensin II/blood , Female , Humans , Hypertension, Renovascular/blood , Kidney/blood supply , Kidney/innervation , Kidney/physiopathology , Male , Middle Aged , Renin/blood
18.
Blood Press ; 8(5-6): 317-24, 1999.
Article in English | MEDLINE | ID: mdl-10803493

ABSTRACT

In the present study, rats were immunized with angiotensin II receptor subtype 1 (AT1) receptor peptides for 3 months to see if the immunization produced specific anti-AT1 receptor antibodies and if continuous stimulation for 3 months affected blood pressure or induced morphological changes in the organs containing AT1 receptors. Our results showed that there were constant high levels of circulating antibodies throughout the study period in all rats of the immunized group, but not in the control rats, and that there were almost no significant cross-reactions of antisera with AT2 receptor peptide and alpha1 adrenoceptor peptide, except in four rats, which showed low cross-reactions with alpha1 adrenoceptor and AT2 receptor peptides. When an affinity-purified anti-AT1 receptor antibody was used, it specifically displayed the AT1-stimulatory positive chronotropic effect and also localized AT1 receptors. However, in the immunized group, saturation binding of AT1 in homogenates from kidneys showed no difference either in maximal binding sites (Bmax) or in antagonist affinity (Kd). No difference in mRNA of AT1a was found in either kidney or heart, and no morphological changes in the organs were observed, as compared with the control group. Furthermore, immunization did not cause hypertension. In conclusion, the synthetic peptide corresponding to the second extra-cellular loop of the human AT1 receptor was able to produce highly specific and functionally active anti-AT1 receptor antibodies, but unable to induce pathological structural changes or hypertension.


Subject(s)
Receptors, Angiotensin/agonists , Receptors, Angiotensin/immunology , Amino Acid Sequence , Animals , Antibody Formation , Gene Expression , Humans , Immunization , Kidney/immunology , Kidney/pathology , Liver/immunology , Liver/pathology , Male , Molecular Sequence Data , Myocardium/immunology , Myocardium/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Receptors, Angiotensin/genetics
19.
J Hypertens ; 17(12 Pt 1): 1743-50, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10658941

ABSTRACT

BACKGROUND: Previous studies in hypertensive patients with renovascular disease have shown both elevated sympathetic nerve activity and increased cardiovascular mortality. OBJECTIVE: The aim of the present study was to assess long-term survival in hypertensive patients with renal artery stenosis in relation to sympathetic activation, renal function and treatment regimens. SUBJECTS AND METHODS: A total of 169 consecutive patients aged 54 +/- 1 years with hypertension underwent a clinical investigation for renovascular hypertension including renal angiography and measurement of bilateral renal renin secretion. In 107 of these patients, arterial plasma concentrations of noradrenaline were measured. The mean follow-up time was 7.1 +/- 0.3 years and survival data were available in all patients up to May 1997. For comparison, healthy age-matched normotensive controls were examined. RESULTS: Arterial noradrenaline concentrations were threefold elevated in hypertensive patients with renal artery stenosis compared to healthy controls (P < 0.01). During the follow-up time, 44 patients died. Cardiovascular mortality accounted for 75% of all deaths. The risk ratio for overall mortality in hypertensive patients with renal artery stenosis compared to the normal population of Sweden, matched for age, was 3.3 (2.4-4.4), whereas the risk ratio for cardiovascular mortality was 5.7 (3.9-8.0). The arterial plasma concentration of noradrenaline was 3.11 +/- 0.30 pmol/ml in patients who died compared to 3.84 +/- 0.26 pmol/ml in survivors. Reduced renal function and age were independent predictors of death. Survival did not differ between patients undergoing intervention with either renal angioplasty or surgical reconstruction for renal artery stenosis and patients not undergoing intervention. CONCLUSIONS: Although sympathetic nerve activity is elevated in hypertensive patients with renal artery stenosis, our results do not suggest that this adrenergic over-activity is directly linked to the observed high cardiovascular mortality. Mortality in hypertensive patients with renovascular disease remains high whether an interventional treatment is performed or not, possibly due to the concomitant coronary disease.


Subject(s)
Hypertension, Renal/mortality , Renal Artery Obstruction/mortality , Sympathetic Nervous System/physiopathology , Angiography , Epinephrine/blood , Female , Follow-Up Studies , Humans , Hypertension, Renal/physiopathology , Hypertension, Renal/surgery , Kidney/physiology , Male , Middle Aged , Nephrectomy , Norepinephrine/blood , Renal Artery/innervation , Renal Artery/pathology , Renal Artery Obstruction/physiopathology , Renal Artery Obstruction/surgery , Survival Analysis , Treatment Outcome
20.
Scand J Urol Nephrol ; 32(5): 341-4, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9825397

ABSTRACT

The effect in vivo of the angiotensin converting enzyme (ACE) inhibitors captopril and enalapril and the calcium antagonist verapamil was studied in an experimental model using rat heart allografts. Daily post-transplant treatment of recipient rats (DA strain) with verapamil (75 mg kg-1 day-1) or captopril (40 mg kg-1 day-1) significantly prolonged survival of allografts from donors (PVG/c strain) when compared with an untreated control group (p < 0.05). No synergistic effect was observed when the two drugs were used for combined treatment. An equipotent does of enalapril (12.5 mg kg-1 day-1) caused no change in allograft survival of statistical significance. The results support the hypothesis that verapamil and captopril have effects on the immune reactivity in vivo, and that this is not a characteristic shared by all ACE inhibitors.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Graft Survival/drug effects , Heart Transplantation , Animals , Captopril/therapeutic use , Drug Therapy, Combination , Enalapril/therapeutic use , Female , Immunosuppression Therapy , Male , Rats , Rats, Inbred Strains , Time Factors , Transplantation, Homologous , Verapamil/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...