Glomerular crescent formation in renal amyloidosis. A clinicopathological study and demonstration of upregulated cell-mediated immunity.

BACKGROUND: Several studies examined glomerular crescents associated with renal amyloidosis. However, the incidence of crescents, the association between the 2 lesions, treatment and outcome are still controversial. PATIENTS AND METHODS: We studied 107 consecutive biopsies of renal amyloidosis, and found cellular or fibrocellular crescents in 13 cases (12.1%). We investigated the clinical characteristics, pathological findings, treatment and outcome. We also performed immunohistochemical staining using T cell, macrophage and osteopontin (OPN) markers. RESULTS: Amyloid was of the AA type in 12 cases, and all patients had rheumatoid arthritis. Six cases with AA amyloidosis had crescentic glomerulonephritis (CrGN), and 5 presented with rapidly progressive glomerulonephritis (RPGN). The percentage of crescents correlated negatively with serum albumin (r = -0.83, p < 0.001), and positively with serum creatinine (r = 0.72, p < 0.01) and urinary protein excretion (r = 0.85, p < 0.001). All RPGN patients developed end-stage renal disease, and 2 patients died shortly after treatment. Microscopic examination showed inflammatory cells within the glomeruli, and immunohistochemical study revealed abundant intrarenal T cells and macrophages in CrGN cases. Strong expression of OPN was observed in tubular epithelial cells and intraglomerular macrophages. CONCLUSION: Cellular immune responses play a crucial role in glomerular crescents in renal amyloidosis. Immunosuppressive treatment is often ineffective and raises the risk of complications in CrGN with abundant glomerular sclerosis and tubulointerstitial injury.

Two cases of calciphylaxis treated by parathyroidectomy: importance of increased bone formation.

Calciphylaxis (calcific uremic arteriolopathy) is a poorly understood and highly morbid syndrome of both vascular calcification and skin necrosis. The main histopathological finding is calcium deposits within arteriolar and small vessel walls, showing endovascular fibrosis associated with fat necrosis. The therapeutic strategy is to normalize the high calcium-phosphate products (Ca x P). When calciphylaxis is complicated with advanced renal hyperparathyroidism (HPT), parathyroidectomy (PTX) should be performed promptly. However, for patients with low PTH level, calciphylaxis is unresponsive to PTX, and such an approach may worsen hyperphosphatemia and hypercalcemia. We report two patients with calciphylaxis confirmed by skin biopsy. PTX was performed in both patients based on high PTH levels. PTH and Ca x P level decreased in both patients post PTX. In Case 1, the skin ulcers gradually improved and almost disappeared after PTX. However, in Case 2, new ulcers appeared after PTX. In Case 1, alkaline phosphatase (ALP) after PTX was approximately twice its level before surgery and PTX resulted in normalization of uptake on bone scintigraphy. However, no rise in ALP was noted in Case 2, probably due to long-term use of aluminum, which prevented bone formation. These findings suggest that differences in the extent of bone formation explain the different response in post-PTX ulcer healing.

Candida glabrata fungemia in a diabetic patient with neurogenic bladder: successful treatment with micafungin.

A 69-year-old man was transferred to our hospital because of fever and acute renal failure. 5 weeks prior to admission, he was admitted to another hospital and treated with several antibiotics including vancomycin, but fever did not subside and renal dysfunction showed rapid progression. On admission, laboratory findings revealed pyuria, inflammatory changes, acute renal failure, and disseminated intravascular coagulation (DIC). Computed tomography showed left ureteral stone and hydronephrosis. Gallium scintigraphy showed avid uptake in the left kidney. Serum concentration of vancomycin was 57.4 micro/ml. Candida glabrata was isolated from blood, sputum and urine. Under the diagnosis of fungemia and left pyelonephritis, he was treated with micafungin (150 mg/day), gabexate mesilate and insertion of a double-ended pigtail catheter. The above treatment produced regression of systemic inflammation, DIC and acute renal failure. At the last follow-up 3 weeks after discharge, ureteroscopy showed that the ureter stone had already passed but a soft white-yellowish bezoar was detected in the ureter. In this case, neurogenic bladder, poorly controlled diabetes, and long-term antibiotic treatment probably enhanced the development of C. glabrata infection. Antifungal treatment with micafungin is useful in patients with non-albicans Candida infection.

Thrombotic thrombocytopenic purpura associated with polyarteritis nodosa.

We present a case of classical polyarteritis nodosa (PN) overlapping thrombotic thrombocytopenic purpura (TTP). A 70-year-old woman was transferred to our hospital because of general fatigue and fever. On admission, laboratory findings revealed leukocytosis, normochromic normocytic anemia and renal dysfunction. About one week later, she developed disturbance of consciousness, and laboratory findings revealed rapidly progressive thrombocytopenia and renal dysfunction. We suspected the presence of microscopic polyangiitis (MPA), based on mild elevation of myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA). On post-admission Day 11, renal biopsy was performed but the diagnosis of MPA could not be confirmed because of the absence of glomerular crescent formation or vasculitis. However, the biopsy specimen showed many collapsed glomeruli and interstitial inflammation, indicating the presence of occlusive lesions, such as vasculitis in larger arteries. We instituted methylprednisolone pulse therapy, cyclophosphamide and plasma exchange, because the clinical symptoms also satisfied the criteria of TTP. Despite the intensive treatment, the patient died on 43rd day of hospitalization due to thalamic hemorrhage. Autopsy showed typical findings of classical PN including disruption of arterial walls and fibrinoid necrosis in the medium-sized arteries of the kidneys and colon. We detected reduced activity of von Willebrand factor-cleaving protease (VWF-CP) and the presence of plasma inhibitory IgG against VWF-CP. A better understanding of the mechanisms would be useful.

Blood concentration and urinary excretion of captopril (SQ 14,225) in patients with chronic renal failure.

Blood concentration and urinary excretion of captopril following 50 mg oral administration were determined by high-performance liquid chromatography in normal subjects and patients with chronic renal failure. In normal subjects, the maximum blood concentration of the free form of captopril was obtained within 1 hour and was not detectable after 6 hours; 41% of administered captopril was excreted into the urine as free form and metabolites within 2 hours, and 58% within 6 hours. In chronic renal failure patients with an average serum creatinine of 5.1 mg/dl, the absorption constant (Ka), maximum concentration (Cmax), and area under the blood concentration curve (AUC) were not significantly different from those in the normal subjects, but the elimination constant (Ke) and biological half-life (T1/2) showed a significant delay in the disappearance of captopril from the blood (p less than 0.01 respectively). The cumulative amount of urinary excretion of either free-form captopril or its' metabolites was significantly decreased at 2, 4, and 6 hours in chronic renal failure patients (p less than 0.01 or less, respectively). Impairment of kidney function is suggested to be an important factor in the promotion of blood retention of captopril.

Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (alacepril) after oral dosing in fasting or fed states.

The plasma concentration and urinary excretion of a newly developed angiotensin I converting enzyme inhibitor, alacepril (which is converted to captopril after absorption), were investigated in seven normal healthy subjects. Fifty milligrams of the drug was administered orally either in the fasting or in the fed state. In the fasting state, the time of maximal plasma concentration (tmax) was 1 hour for free captopril, 1.7 hours for protein-conjugated captopril, and 1.6 hours for total captopril. The biologic t1/2 of free, protein-conjugated, and total captopril was 1.9, 4.2, and 5 hours, respectively. In the fed state, neither tmax nor t1/2 changed, except that the tmax of free captopril was prolonged to 1.9 hours (P less than 0.01). Cumulative urinary excretion of free captopril at 8 hours was 35% of the drug administered in the fasting state and that of total captopril at 24 hours was 59%. These data did not differ significantly from those obtained after food intake. The biologic t1/2 of free captopril after alacepril dosing was longer than in previous studies of captopril per se. Because biologic or clinical effects have not been studied, it should be left conjectural whether alacepril is a longer-acting angiotensin I converting enzyme inhibitor. A prolonged effect of the drug can be expected by its administration after a meal.

Disadvantage of long-term CAPD for preserving cardiac performance: an echocardiographic study.

The indices of cardiac performances were compared between 31 continuous ambulatory peritoneal dialysis (CAPD) and 20 long-term hemodialysis (HD) patients. They were subdivided into three groups according to dialysis duration: L-CAPD (n = 16, mean age and CAPD duration were, respectively, 53 +/- 8 [SD] years and 77 +/- 13 months); S-CAPD (n = 15; 52 +/- 12 years, 28 +/- 12 months); HD (n = 20; 51 +/- 10 years, 162 +/- 52 months). The diabetic HD patients (DM-HD; n = 13; 60 +/- 13 years of age, 22 +/- 11 months) were chosen separately. Thirteen normotensive subjects with normal kidney function (mean age, 57 +/- 9 years) were selected as an age-matched control group. There were no significant differences between groups in age, gender, incidence of original kidney disease, or serum biochemical data. The blood pressure and the cardiothoracic ratio in L-CAPD were highest among groups. The indices of left ventricular (LV) hypertrophy as well as LV performance by means of echocardiography or pulsed Doppler were compared. Among nondiabetic dialysis patients, the calculated LV mass index (LVMI) of 166.4 +/- 84.3 g/m2 and the ratio of the peak atrial filling velocity to the peak diastolic flow velocity of 1.25 +/- 0.4 in L-CAPD were greatest, and the left ventricular fractional shortening (%FS) of 34.2 +/- 10.8% in L-CAPD was smallest. LVMI or %FS of L-CAPD was the same as DM-HD of 161.0 +/- 40.7 g/m2 or 31.6 +/- 8.2%. Possibly, poor control of hypervolemia, which is caused by peritoneal problems induced by either peritonitis or chronic exposure to high-glucose dialysate, causes a substantial cardiac preload leading to incipient cardiac failure in L-CAPD. According to the similar results of L-CAPD and DM-HD, it may be that hypertension, hyperlipidemia, or long-term constant glucose loading of CAPD fluids in addition to impaired glucose tolerance by chronic renal failure is more or less related to the progression of LV hypertrophy and latent cardiac dysfunction in long-term CAPD patients. In this context, CAPD of more than 5 years' duration is disadvantageous for preserving cardiac function as compared with HD.

Hemodialysis causes severe orthostatic reduction in cerebral blood flow velocity in diabetic patients.

Orthostatic hypotension is a serious problem in patients with diabetes mellitus (DM) undergoing hemodialysis (HD). To evaluate cerebral circulation during orthostasis in patients with DM, we examined changes in mean blood flow velocity in the middle cerebral artery (VMCA) during 60 degrees head-up tilt for 5 minutes in patients with DM (six men, two women; age, 57 +/- 3 years [mean +/- SEM]; HD duration, 47 +/- 27 months) before and after bicarbonate HD by using transcranial Doppler sonography. The findings were compared with those in HD patients without diabetes (non-DM; 12 men, 5 women; age, 47 +/- 3 years; HD duration, 82 +/- 23 months). Mean blood pressure (MBP) in the supine position, hematocrit (Hct), plasma fibrinogen, and volume of fluid removed by HD were not significantly different between the two groups (MBP, 106 +/- 6 versus 103 +/- 4 mm Hg; Hct, 26% +/- 1% versus 28% +/- 1%; fibrinogen, 355 +/- 37 versus 357 +/- 27 mg/dL; fluid, 2.5 +/- 0.2 versus 2.3 +/- 0.2 L). Percentage of change in VMCA (% VMCA) during tilt was compared between the groups before and after HD. Before HD, MBP decreased significantly to 93 +/- 5 mm Hg during tilt only in patients with DM. The degree of MBP reduction was -13 +/- 2 mm Hg in DM and -2 +/- 2 mm Hg in non-DM patients (P < 0.01). % VMCA equally decreased during tilt; DM, -12% +/- 3%, and non-DM, -12% +/- 2%. After HD; MBP decreased by 36 +/- 7 mm Hg in patients with DM, which was significantly greater than before HD. VMCA also decreased in both groups after HD, and % VMCA in DM (-32% +/- 5%) was significantly greater than before HD (P < 0.01) and in non-DM patients (-13% +/- 2%; P < 0.01). % VMCA positively correlated with the percentage of change ratio of MBP during tilt in both groups after HD (DM, r = 0. 87, P < 0.01; non-DM, r = 0.61, P < 0.01). Our results showed a significant decrease in cerebral blood flow velocity during tilt of equal magnitude in both groups before HD despite differences in the level of hypotension, whereas reduction in cerebral blood flow velocity and decrease in MBP were more marked in DM after HD. Orthostasis could thus cause hemodynamically mediated brain damage after HD, especially in patients with DM.

Depressed cerebral oxygen metabolism in patients with chronic renal failure: a positron emission tomography study.

To elucidate brain oxygen metabolism in uremic patients, regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and oxygen metabolism (rCMRO(2)) were measured by positron emission tomography (PET) in 10 hemodialysis (HD) patients and 13 predialysis patients with chronic renal failure (CRF). Data were compared with 20 nonuremic patients (controls) without neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. In the hemisphere, rCMRO(2) in both HD (1.82 +/- 0.10 mL/min/100 g) and CRF patients (1.95 +/- 0.09 mL/min/100 g) showed significantly lower values compared with controls (2.23 +/- 0.05 mL/min/100 g; P < 0.01). Hemispheric rCBF in HD (35.6 +/- 2.1 mL/100 g/min) and CRF patients (36.1 +/- 2.1 mL/100 g/min) was not different from controls (31.8 +/- 1.4 mL/100 g/min). Hemispheric rOEF in CRF patients (45.7% +/- 1.6%) was significantly greater than that in controls (40.5% +/- 1.2%; P < 0.02), but rOEF in HD patients (43.7% +/- 1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially cerebral cortices. All PET parameters in frontal cortices tended to show the lowest values in patients with renal failure. For all HD patients, rCBF in both the frontal cortex and white matter correlated inversely with HD therapy duration (P < 0.05). In conclusion, brain oxygen metabolism is depressed in patients with renal failure on or before the start of HD therapy. The cause for depressed brain oxygen metabolism is considered to be either dysregulation of cerebral circulation or lower brain cell activity.

Association of a T-cell receptor constant alpha chain gene polymorphism with progression of IgA nephropathy in Japanese patients.

Immunogenetic studies have suggested the role of the T-cell receptor (TCR) in the development of immune-mediated diseases. We investigated whether a genetic polymorphism in the TCR constant alpha (Calpha) chain region might modify the susceptibility or progression of immunoglobulin A (IgA) nephropathy. The TCR Calpha chain genotype was studied in 213 Japanese patients with IgA nephropathy and 73 individuals from the general population. A polymerase chain reaction-based TaqI restriction fragment length polymorphism assay (TaqI RFLP) was applied on the 5' flanking region of the TCR Calpha first exon. The TaqI-undigested (t) and TaqI-digested (T) alleles showed similar genotype distributions between the patients with IgA nephropathy and controls (tt:Tt:TT = 16.9%:46.5%:36.6% in IgA nephropathy v 9.6%:58.9%:31.5% in controls; chi(2) = 1.9; P = not significant). To further investigate the role of TCR Calpha chain gene polymorphism in renal prognosis, we analyzed those patients with IgA nephropathy in whom renal status had been monitored for a period of more than 3 years (n = 182). According to outcome, two groups were formed. The stable (S) group included 98 patients with renal function that remained unchanged during an average follow-up of 10.7 +/- 0.4 (SE) years. The progressive (P) group (n = 84) included patients with progressively declining renal function, with an average follow-up of 11.9 +/- 0.5 years. The genotype distributions of the TCR Calpha chain gene polymorphisms between these two groups differed significantly (tt:Tt:TT = 25.5%:40.8%:33.7% in S v 10.7%:44.1%:45.2% in P; chi(2) = 7.0; P < 0.05). The frequency of the T allele was greater in the P group (67.3% in P v 54.1% in S; chi(2) = 6.6; P = 0.01). The TT or Tt genotypes were more commonly observed in patients from the P group (89.3% of T allele carriers in P v 74.5% in S; chi(2) = 6.5; P = 0.01). It appeared the T allele might foreshadow a poor renal prognosis, conferring a potential risk for developing renal failure with time (odds ratio, 2.7; confidence interval, 1.2 to 6.0; P < 0.05). In summary, TCR Calpha chain genetic variability was associated with loss of renal function over time in patients with IgA nephropathy. In conclusion, the TCR Calpha chain polymorphism might prove helpful to predict progression to chronic renal failure in Japanese patients with IgA nephropathy.

Trends in the pathophysiological characteristics of malignant hypertension.

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.

The differential effects of alpha 2-adrenergic stimulation on the myocardium and coronary vessels in the isolated rat heart.

The differential effects of alpha 2-adrenoceptor stimulation on myocardial contractility and coronary circulation were examined in the isolated perfused rat heart. We studied 20 Sprague-Dawley rats of similar age (26-28 weeks) and body weight (500-550 gm). Myocardial contractility (LV +dp/dt and developed pressure, LVP) and coronary flow resistance (CFR) were tested in the isolated isovolumic hearts using Langendorff preparation at a constant perfusion rate (2.5 ml/min/100 g BW) of Krebs-Henseleit bicarbonate solution. Group I (N-7) received B-HT 920 (specific alpha 2-adrenergic agonist, 0.6 to 58 micrograms/min), Group II (N-7) received B-HT 920+Yohimbine (300 nM in the perfusate). Group III (N-6) received vehicle only. Baseline LVP, LV +dP/dt and CFR were not significantly different among the 3 groups. During drug or vehicle administration, LVP and LV +dP/dt remained unchanged in all the groups. Coronary flow resistance increased in a dose-response fashion with a maximum increase of 22.7 +/- 3.6 (SE) mmHg/ml/min/g LV in Group I, and 10.5 +/- 2.0 mmHg/ml/min/g LV in Group II (p less than 0.02). We conclude that in the Sprague-Dawley rat heart, the physiologic effects of alpha 2-adrenoceptors are predominant in the coronary circulation but not in the myocardium itself possibly because of absence of post-synaptic alpha 2-adrenergic receptors in the rat myocardium.

The effect of azelastin hydrochloride on pruritus and leukotriene B4 in hemodialysis patients.

Pruritus is a very common complication in chronic hemodialysis (HD) patients, however the exact mechanism for this affliction is still not known. Anti-histaminics usually failed to alleviate uremic pruritus. In others, an anti-allergic drug, which inhibits the release of chemical mediators, such as leukotrienes or histamine from mast cells, was reported to be effective. We evaluated the values of leukotriene B4 and interleukin 6 in HD patients with pruritus and the effect of an anti-allergic drug on these factors. Leukotriene B4, interleukin-6, C3a, C5a, the number of eosinophil and IgE at 0, 15 and 180 minutes after the start of regular HD in 11 HD patients suffering from pruritus and as well as in 11 HD patients without pruritus were examined. These HD patients in both groups showed significantly higher (p < 0.001) values of leukotriene B4 and C3a compared to healthy non-HD subjects. There was no difference in the leukotriene B4, interleukin-6, IgE, C3a and C5a levels between the patients with and without pruritus. Two mg/day of azelastin hydrochloride, an anti-allergic drug was orally given to the pruritus group for 3 weeks. In 5 of 11 patients, the pruritus symptoms disappeared, while in 4 of 11 they improved. Independent of the effect of the drug on pruritus, leukotriene B4 levels significantly decreased compared with those before the administration of this drug in the pruritus group (p < 0.01). Interleukin 6, C3a, C5a and the number of eosinophils demonstrated no significant change. In conclusion, although azelastin hydrochloride was effective in treating pruritus and also suppressed leukotriene B4 levels in hemodialysis patients, the high leukotriene B4 activity itself did not seem to be related to the development of pruritus in these patients.

Participation of the renin-angiotensin system in the captopril-induced worsening of anemia in chronic hemodialysis patients.

The study was aimed to show whether the renin-angiotensin system acts on erythropoiesis in chronic renal failure patients with hemodialysis, since captopril leads to the worsening of anemia in such patients. The average dose of captopril in 13 cases studied was 19.3 mg per day and duration of the administration was 48 days. Blood-pressure fall by captopril was accompanied with the worsening of anemia. There were significant decreases in hemoglobin (8.3%), hematocrit (7.3%), red blood cell count (7.6%) and reticulocyte count (43.7%). Angiotensin II was significantly decreased (15.7%) with significant reductions of plasma aldosterone concentration (15.2%) and angiotensin-I converting enzyme (45.7%), and with significant increases in plasma renin activity (158.6%) and in angiotensin I (238.3%). However, plasma erythropoietin concentration remained unchanged. Serum iron concentration was slightly but significantly increased after captopril. Reticulocyte count was significantly correlated with AII either before (r = 0.716, p less than 0.01) or after captopril (r = 0.658, p less than 0.05). There was significant correlation between angiotensin II and red blood cell count before captopril (r = 0.710, p less than 0.01). It is concluded from the present study that the reduction of angiotensin II by captopril might contribute to the worsening of anemia seen in chronic hemodialysis patients.

The hemodynamic and humoral responses to tilting in diabetic patients on chronic hemodialysis treatment.

Hemodynamic and humoral responses to tilting were examined in order to elucidate the autonomic nervous function in diabetic hemodialysis patients. Eleven diabetic (DM) and eleven non-diabetic (non-DM) patients on maintenance hemodialysis treatment were involved in the experimentation, matching the age and the duration of hemodialysis. Cardiac output, blood pressure, plasma renin activity (PRA), norepinephrine (NE) and epinephrine (EP) were measured before and 5 minutes after the 45 degree tilting. By the tilting the blood pressure significantly fell in DM, whereas it rose slightly but significantly in non-DM. In both groups, however, the heart rate remained unchanged, and either cardiac index or stroke volume index decreased equally. The percentile increase in total peripheral resistance index (TPRI) was significantly smaller in DM (14.6%) than in non-DM (27.9%). There was a significant correlation between the changes in TPRI and diastolic blood pressure (r = 0.730, p less than 0.01). NE and EP increased significantly in non-DM but not in DM. Blood pressure reduced by the tilting in DM was associated with a small or equivocal response in either TPRI or plasma NE. The heart rate did not respond to the tilting in both groups. These results indicate that both sympathetic and parasympathetic nervous systems are deranged in diabetic hemodialysis patients but parasympathetic dysfunction is evident even in non-diabetic hemodialysis patients.

Minimal daily variations of plasma and urinary endothelin-1 in healthy subjects.

The daily profiles of both the plasma level and the urinary excretion rate of endothelin-1 were examined in 13 healthy volunteers (9 males and 4 females, aged 22 +/- 1 [SEM]). Plasma endothelin-1 (PET) was measured after a one-hour recumbency every 6 hours at 8 a.m., 2 p.m., 8 p.m. and 2 a.m. and the urinary excretion rate of endothelin-1 (UET) was determined in the urine collected every 6 hours. PET was found to be quite stable throughout the day, being 1.57 +/- 0.25 pg/ml at 8 a.m., 1.88 +/- 0.21 at 2 p.m., 2.2 +/- 0.24 at 8 p.m. and 1.90 +/- 0.20 at 2 a.m. After a one-hour ambulation, PET showed no statistical difference. UET also remained unchanged for each 6-hour collecting period, measuring 4.61 +/- 0.69, 3.98 +/- 0.46, 4.63 +/- 0.73 and 3.42 +/- 0.49 ng/hr, respectively. The absence of any daily variations in either PET or UET thus suggests that apparently no specific considerations need be applied regarding the time of taking samples to measure the plasma and urinary endothelin-1.

Immediate hemodialysis after percutaneous transvenous angioplasty increases patency rates of arterio-venous fistula.

BACKGROUND: It was reported that pathogenesis of access failure of hemodialysis patients through progressive stenosis was followed by thrombosis. Nonionic contrast media increase platelet degranulation within an angioplasty-damaged vessel by releasing procoagulant molecules, which might contribute to acute thrombosis and restenosis. An adequate level of heparin provides satisfactory thrombin inhibition during routine angioplasty. This study was performed to evaluate the effect of immediate hemodialysis after percutaneous transvenous angioplasty (PTA) to remove nonionic contrast media or other factors while injecting heparin continuously. METHODS: From September 9, 1998 - May 15, 2002, successful PTAs were performed in 66 patients with arteriovenous fistula who were not given any inhibitors of platelet aggregation. Hemodialysis was performed in 31 cases immediately after PTA, and in the remainder, hemodialysis was performed the next day. Patients were randomized and fistula patency rates were compared in these 2 groups on March 20, 2004. RESULTS: The patency rates after PTA in patients who were dialyzed immediately, were significantly higher than those who were dialyzed the next day (p = 0.0120). CONCLUSIONS: Immediate hemodialysis after PTA is an effective way of increasing the patency of arteriovenous fistula for reasons which are not clear. This observation will need to be corroborated in subsequent studies using a larger sample size.

Steroid-resistant nephrotic syndrome associated with malignant thymoma.

Two patients with malignant thymoma of lymphoepithelial cell type developed nephrotic syndrome and irreversible acute renal failure 18 months after the radiation therapy. Repeated renal biopsies revealed focal segmental glomerulosclerosis (FSGS) in both cases (a 66-year-old female and a 82-year-old female). Several immunological disorders were found, being a presence of autoantibodies such as antinuclear antibody, anti-acetylcholine receptor antibody, antistriatal antibody and an elevation of serum IgM. In both cases the nephrotic syndrome was resistant to corticosteroid as well as cyclophosphamide. Renal dysfunction eventually progressed to end-stage renal failure requiring regular hemodialysis treatment. A sustained immunological impairment related to the residual malignant thymoma was considered to be of pathogenic importance for the delayed occurrence of nephrotic syndrome. Fifteen thymoma cases with nephrotic syndrome from the previous reports are also reviewed.

Long-term hemodynamic response to captopril (SQ 14,225) in hypertensive hemodialysis patients.

The long-term effect of treatment with captopril was observed in 7 hypertensive patients on maintenance hemodialysis who had been refractory to combined antihypertensive therapy with propranolol and hydralazine. Captopril showed a potent hypotensive effect in all the subjects throughout the study period of 6 months. The blood-pressure reduction during treatment with captopril was associated with a decrease in total peripheral resistance. Cardiac index increased significantly due to a significant increment in heart rate at the 6th month. Plasma renin activity increased significantly at the 3rd month, whereas it decreased at the 6th month. No significant correlation was observed between the blood-pressure response and the pre-treatment level of plasma renin activity.

Combination therapy using prednisolone and cyclophosphamide slows the progression of moderately advanced IgA nephropathy.

AIM: We retrospectively examined the effect of combination therapy using prednisolone (PSL) and cyclophosphamide (CPA) on the progression of IgA nephropathy (IgAN) in 45 patients with moderate to severe histological changes. PATIENTS AND METHODS: Patients were recruited from 129 consecutive patients with IgAN seen over 10 years based on semiquantitative histological grading. They were divided into two groups: PSL+CPA group (n = 26, male/female = 11/15, age 40+/-3 years (SEM)) or control group undergone conventional therapy with or without antiplatelet agents (n = 19, male/female = 10/9, age 41+/-3). In PSL+CPA group, PSL and CPA treatment commenced using a dose of 30 and 50 mg/day, respectively. PSL was reduced by 5 mg every month. RESULTS: The clinical parameters at the start of treatment such as age, gender, histological score, blood pressure, urinary protein excretion and serum creatinine concentration (SCr) were not different between the groups. The mean observation period in PSL+CPA group (3.3+/-0.3 years) was not different from the control group (4.0+/-0.7 years). In PSL+CPA group, urinary protein excretion, defined as the ratio of urinary protein to creatinine concentration (UP/UCr), significantly decreased from 3.9+/-0.4 to 1.3 +/-0.2 (p<0.01), whereas it remained high in the control group (3.8+/-0.7 to 2.7+/-0.8). The progression rate (PR), which was determined by the slope of the correlation between time after renal biopsy and reciprocal SCr, was significantly lower in PSL+CPA (0.054+/-0.014) than in the control group (0.172+/-0.032 dl/mg/year, p<0.001). Our results indicated that PSL+CPA combination therapy was effective in slowing the progression of moderately advanced IgAN. CONCLUSION: We suggest that the immunosuppressive treatment with CPA is sometimes necessary to preserve renal function in patients with histologically advanced IgAN.