Clinical outcomes associated with anti-coagulant therapy in patients with renal infarction.

Background: Patients with renal infarction are vulnerable to thromboembolic complications with poor outcomes. There is limited report concerning the effect of anti-coagulant therapy in this population. Aim: To assess the impact of anti-coagulant therapy on outcomes in patients with renal infarction. Design: A retrospective cohort study of 101 renal infarction patients was conducted. Methods: The association between anti-coagulant therapy, all-cause mortality, thromboembolic complications and renal outcome was evaluated. Demographic data and comorbidities were collected for analysis. Anti-coagulant therapy was treated as a time-dependent variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multi-variate Cox proportional hazards models. Results: Fifty-seven (56.4%) patients with renal infarction received anti-coagulant therapy during the study period. The all-cause mortality rate was 7.56 per 100 patient-years. Age (HR 1.05, 95% CI 1.02-1.08) was a risk factor for all-cause mortality and anti-coagulant therapy was associated with a 92% improved survival (HR 0.08, 95% CI 0.02-0.34). Twelve (11.9%) thromboembolic events occurred following renal infarction. Current smoking (HR 10.37, 95% CI 1.60-67.43) had an adverse effect and anti-coagulant therapy (HR 0.14, 95% CI 0.03-0.73) had a significant protective impact on thromboembolic complications. There was no significant association between anti-coagulant therapy and long-term renal outcome in renal infarction patients including the monthly change in the estimated glomerular filtration rate (eGFR), the incidence of eGFR reduction of more than 50% and end-stage renal disease. Conclusion: Anti-coagulant therapy in patients with renal infarction was associated with better survival and reduced thromboembolic complications.

Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

INTRODUCTION: Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). METHODS: In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. RESULTS: Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-ß-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. CONCLUSIONS: MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell-based therapeutic strategies for regenerative medicine in renal fibrosis.

Post-angioplasty far infrared radiation therapy improves 1-year angioplasty-free hemodialysis access patency of recurrent obstructive lesions.

OBJECTIVE: To explore the role of far infrared (FIR) radiation therapy for hemodialysis (HD) access maintenance after percutaneous transluminal angioplasties (PTA). METHODS: This was a prospective observational study. Eligible patients were those who received repeated PTA with the last PTA successfully performed within 1 week before the study enrollments. Consecutively enrolled patients undergoing successful HD treatments after PTA were randomly assigned to the FIR-radiated group or control group without radiation. FIR-radiated therapy meaning 40-minute radiation at the major lesion site or anastomosed site three times a week was continued until an end-point defined as dysfunction-driven re-PTA or the study end was reached. RESULTS: Of 216 participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR-radiated participants and 48 control participants) and 119 with arteriovenous fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the FIR-radiated therapy compared with free-radiated usual therapy significantly enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted for the overall improved patency rates (21.4% vs. 10.3%; p = .02). CONCLUSIONS: This study suggests FIR-radiated therapy improves PTA-unassisted patency in patients with AVG who have undergone previous PTA.

Beyond-limit light focusing in the intermediate zone.

We experimentally verify that a new nanolens of a designed plasmonic aperture can focus visible light to a single line with its width smaller than the limit of half the wavelength in the intermediate zone. The experimental measurement indicates that while the near field plays a role to increase the spot size in the near zone, it is negligible at the beyond-limit focused region; i.e., the focused light is dominated by the radiative fields. The image taken by the optical microscope shows that the fields focused have propagated to the far zone. Besides being of academic interest, the nanolens capable in achieving a lower diffraction limit in the intermediate zone is important for application possibilities.

High prevalence of latent tuberculosis infection in patients in end-stage renal disease on hemodialysis: Comparison of QuantiFERON-TB GOLD, ELISPOT, and tuberculin skin test.

BACKGROUND: Individuals with end-stage renal disease (ESRD) are 10- to 25-fold more likely than immunocompetent people to develop active tuberculosis (TB) and are candidates for being treated for latent TB infection (LTBI). However, diagnosis using the tuberculin skin test (TST) is doubly difficult due to cutaneous anergy and cross-reactions with Bacille-Calmette-Guérin (BCG) vaccination. MATERIALS AND METHODS: This was a prospective, doublematched, cohort study in which 32 ESRD patients and 32 age-matched, healthy controls were enrolled. The TST and two new interferon-gamma blood tests, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (ELISPOT), were performed. The subjects were followed up 2 years for active TB disease. ELISPOT was done in ESRD patients only. RESULTS: Compared to the healthy controls, a high prevalence of LTBI was found in the ESRD patients by TST (62.5%, 95% confidence interval [CI] 43.7-78.9), QFT-G (40.0%, 95% CI 22.7-59.4), and ELISPOT (46.9%, 95% CI 29.1-65.3). Agreement was moderate (kappa [kappa] = 0.53) for QFT-G and ELISPOT but only slight between TST and QFT-G (kappa = 0.25) and fair between TST and ELISPOT (kappa = 0.32). ESRD (p = 0.03) and diabetes mellitus (p = 0.04) were significant risk factors for QFT-G positivity on the multivariable analysis. The overall rate of active TB was 1.66 cases per 100 person-years (pys), with the rate higher in patients with ESRD (3.53 per 100 pys) and those with positive (3.40 per 100 pys) and indeterminate QFT results (30.16 per 100 pys), although the difference was not statistically significant. Sensitivity, specificity, and positive and negative predictive values of QFT-G for active TB was 100%, 62.1%, 8.3% and 100%. CONCLUSION: This pilot study is the first to compare QFT-G, ELISPOT, and TST in ESRD patients on hemodialysis and demonstrates a high prevalence of LTBI in this population. In our study, the QFT-G was the more accurate method for identifying those truly infected with Mycobacterium tuberculosis, even in BCG-vaccinated individuals.

A preliminary report of brain edema in patients with uremia at first hemodialysis: evaluation by diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with hemodialysis in patients with severe azotemia remains obscure. To investigate whether either interstitial or cytotoxic edema is responsible for dialysis disequilibrium syndrome (DDS), we used diffusion-weighted MR imaging (DWI) to measure the apparent diffusion coefficient (ADC), which is sensitive for detecting tissue water dynamics. METHODS: Eight consecutive patients with end stage renal disease (ESRD) and blood urea nitrogen level of more than 100 mg/dL (160.9 +/- 53.1 mg/dL) were recruited. Conventional MR images, DWI, and clinical manifestations were obtained before and after the 1st hemodialysis. The ADC values were determined for regions of normal-appearing gray and white matter and for regions of hyperintensity of white matter on T2-weighted MR imaging. RESULTS: Foci of bright areas of white matter were found in all patients on T2-weighted images. The ADC values of the patients with ESRD, in white matter and gray matter before and after hemodialysis, were greater than those of the healthy controls (P < .005). Regarding the impact of hemodialysis, the ADC of frontal lobe white matter increased significantly after hemodialysis (1.09 +/- 0.11 versus 1.03 +/- 0.11, P = .036). We did not find the specific area of brain edema reported in posterior leukoencephalopathy and the osmotic demyelination syndrome. CONCLUSIONS: These results suggest that severe azotemia in end stage renal disease leads to interstitial brain edema reflected as increased ADC, and the further increased ADC reflects that edema associated with 1st hemodialysis is interstitial rather than cytotoxic in nature.

Physiological changes during hemodialysis in patients with intradialysis hypertension.

Intradialysis hypertension is a frustrating complication among hemodialysis (HD) patients. This study was conducted to investigate the physiological changes during intradialytic hypertension. The beat-to-beat continuous heart rate, hematocrit (Hct) changes during HD, serum levels of nitric oxide, plasma levels of catecholamine, renin, endothelin (ET-1), cardiac output (CO), and peripheral vascular resistance (PVR) were measured before and after HD in patients prone to develop intradialysis hypertension (n = 30) and from age, sex-matched control HD subjects (n = 30). It was found that the baseline values of Hct, serum levels of nitric oxide, plasma levels of catecholamine, renin, and ET-1, CO, PVR, and power index (low frequency/high frequency ratios) of heart rate variability were not significantly different between the patients and control subjects. In the hypertension-prone group, the plasma levels of catecholamine, renin, and the serial measurements of power index, did not show significant changes. However, the patients showed a significant elevation of systemic vascular resistance (56.8 +/- 9.2% vs 17.7 +/- 9.5; P < 0.05), ET-1 (510.9 +/- 43.3 vs 276.7 +/- 30.1 pg/ml; P < 0.05) and a significant decrease of nitric oxide (NO)/ET-1 balance (0.018 +/- 0.003 vs 0.034 +/- 0.005; P < 0.05) at the end of HD compared with the control patients. It was found that the physiological changes in intradialysis hypertension patients were characterized by inappropriately increased PVR through mechanisms that did not involve sympathetic stimulation or renin activation but might be related with altered NO/ET-1 balance.

Tuberculosis in patients with end-stage renal disease.

OBJECTIVE: To elucidate the clinical manifestations and risk factors of the mortality rate in uraemic patients with tuberculosis (TB) infection. DESIGN: We retrospectively analysed 62 patients with uraemia and active tuberculosis who were admitted to our hospital from 1990 through 2000. The patients were followed up for 2 years after discharge or until death. RESULTS: There were 43 men and 19 women, with a mean age of 63 +/- 13 years. Extra-pulmonary TB was noted in 51.6%. The peritoneum and pleura were the two most common organs involved. Fever of unknown origin was the most common manifestation (77.4%). The corrected serum Ca2+ level of the patients was >10.5 mg/dl in 46.8%. C-reactive protein >6 mg/dl and leukocytosis (white blood cell count >10,000/mm3) at presentation were noted in more than half of the patients. A reversed serum albumin/globulin ratio and leukocytosis were found to be associated with mortality rate. CONCLUSION: More than half of the TB infections in patients with end-stage renal disease presented with extra-pulmonary involvement. Fever of unknown origin, reversed serum albumin/globulin ratio, and unexplained hypercalcaemia in maintenance dialysis patients suggested the possibility of tuberculosis.

Acute oxalate nephropathy induced by star fruit in rats.

In this study, we intend to establish a connection between star fruit and acute oxalate nephropathy and also investigate predisposing factors for its development. Male Sprague-Dawley rats of 180 to 200 g were assigned to four groups; namely, control, experimental, fasting, and water-deprivation groups. The former two groups were subjected to both fasting and water deprivation, whereas the latter two groups were subjected to either fasting or water deprivation, respectively. Except for tap water for controls, the remaining groups were administered 4 mL/100 g of body weight of sour star fruit juice with an oxalate concentration of 2.46 g/dL. After these procedures, serial measurement of serum creatinine levels and kidney pathological examination were performed. Peak serum creatinine levels in the control, experimental, fasting, and water-deprivation groups were 0.50 +/- 0.04, 1.46 +/- 0.26, 0.68 +/- 0.20, and 0.52 +/- 0.08 mg/dL, respectively. The experimental group had a greater peak serum creatinine level (P < 0.05). Mean serum creatinine levels of the experimental group days 0, 1, 2, 3, 4, and 5 were 0.43 +/- 0.03, 1.11 +/- 0.18, 1.31 +/- 0.27, 1.16 +/- 0.28, 0.8 +/- 0.26, and 0.82 +/- 0.28 mg/dL, respectively. Mean serum creatinine levels days 1 to 3 were greater than that day 0 (P < 0.05). Pearson's correlation analysis of peak serum creatinine level and kidney weight for the experimental group showed a significant correlation (R = 0.75; P < 0.05; n = 9). In addition to typical changes of oxalate nephropathy, kidney pathological examination showed many refractile oxalate crystals with all rainbow colors under polarized light microscopy in the experimental group. In conclusion, sour star fruit with abundant oxalate contents could cause acute oxalate nephropathy in rats under the conditions of fasting and water deprivation.

CP55,940 increases intracellular Ca2+ levels in Madin-Darby canine kidney cells.

The effect of CP55,940, a presumed CB1/CB2 cannabinoid receptor agonist, on intracellular free Ca2+ levels ([Ca2+]i) in Madin-Darby canine kidney cells was examined by using the fluorescent dye fura-2 as a Ca2+ indicator. CP55,940 (2-50 microM) increased [Ca2+]i concentration-dependently with an EC50 of 8 microM. The [Ca2+]i signal comprised an initial rise and a sustained phase. Extracellular Ca2+ removal decreased the maximum [Ca2+]i signals by 32+/-12%. CP55,940 (20 microM)-induced [Ca2+]i signal was not altered by 5 microM of two cannabinoid receptor antagonists, AM-251 and AM-281. CP55,940 (20 microM)-induced [Ca2+]i increase in Ca2+-free medium was inhibited by 86+/-3% by pretreatment with 1 microM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor. Conversely, pretreatment with 20 microM CP55,940 in Ca2+-free medium for 6 min abolished thapsigargin-induced [Ca2+]i increases. CP55,940 (20 microM)-induced intracellular Ca2+ release was not inhibited when inositol 1,4,5-trisphosphate formation was abolished by suppressing phospholipase C with 2 microM U73122. Collectively, this study shows that CP,55940 induced significant [Ca2+]i increases in canine renal tubular cells by releasing stored Ca2+ from the thapsigargin-sensitive pools in an inositol 1,4,5-trisphosphate-independent manner, and also by causing extracellular Ca2+ entry. The CP55,940's action appears to be dissociated from stimulation of cannabinoid receptors.

Tuberculosis in maintenance dialysis patients.

In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in dialysis patients previously found only in a small number of cases. We collected the cases of newly diagnosed TB patients in Taiwan during 1997. Simultaneously, all dialysis patients were collected and matched with the TB cases to identify the dialysis patients who had also contracted TB. The annual incidence of the dialysis population was 493.4/100,000, 6.9 times that of the general population (71.1/100,000). The annual incidence for the male dialysis population was 573.3, the incidence was 479.2 for the female dialysis population. The incidence for the general population was 97.1 and 43.7/100,000, respectively. Although the 1-year mortality rate due to TB (1.7 vs. 1.9%, p > 0.05) was similar in both populations, the non-TB mortality was much higher in the dialysis population than that in the general population (25.6 vs. 11.1%, p < 0.05). Finally, the 1-year mortality rate of dialysis patients with TB is 3.3 times higher than that in dialysis patients without TB (27.3 vs. 8.3%, p < 0.05). The findings suggest that uremia modifies the behavior of TB, jeopardizes female and younger dialysis patients, poses a higher risk of extrapulmonary dissemination, and predicts a higher overall mortality.

Acute oxalate nephropathy after ingestion of star fruit.

Acute oxalate nephropathy associated with ingestion of star fruit (carambola) has not been reported before. We report the first two cases. These patients developed nausea, vomiting, abdominal pain, and backache within hours of ingesting large quantities of sour carambola juice; then acute renal failure followed. Both patients needed hemodialysis for oliguric acute renal failure, and pathologic examinations showed typical changes of acute oxalate nephropathy. The renal function recovered 4 weeks later without specific treatment. Sour carambola juice is a popular beverage in Taiwan. The popularity of star fruit juice is not compatible with the rare discovery of star fruit-associated acute oxalate nephropathy. Commercial carambola juice usually is prepared by pickling and dilution processes that reduce oxalate content markedly, whereas pure fresh juice or mild diluted postpickled juice for traditional remedies, as used in our cases, contain high quantities of oxalate. An empty stomach and dehydrated state may pose an additional risk for development of renal injury. To avoid acute oxalate nephropathy, pure sour carambola juice or mild diluted postpickled juice should not be consumed in large amounts, especially on an empty stomach or in a dehydrated state.

Mechanism of bifonazole-induced [Ca2+]i increases in MDCK renal tubular cells.

The effect of the antifungal drug bifonazole on Ca2+ homeostasis in Madin Darby canine kidney (MDCK) cells was investigated. Cell suspensions were loaded with the Ca2+-sensitive dye fura-2, and the fluorescence changes were measured with a spectrofluorophotometer. At concentrations between 10-80 microM bifonazole increased cytosolic free Ca2+ levels ([Ca2+]i) in a concentration-dependent manner. The Ca2+ signals were partly inhibited by removing extracellular Ca2+. Bifonazole (40 microM) released Ca2+ from the store sensitive to 1 microM thapsigargin, an endopolasmic reticulum Ca2+ pump inhibitor. Bifonazole (40 microM) per se induced capacitative Ca2+ entry while reduced 1 microM thapsigargin-induced capacitative Ca2+ entry. Inositol 1,4,5-trisphosphate may be involved in bifonazole-induced Ca2+ release because inhibiting phospholipase C with 2 microM U73122 partly reduced the bifonazole response. Together, bifonazole increased [Ca2+]i in renal tubular cells by inducing intracellular Ca2+ release and extracellular Ca2+ influx.

Effect of betulinic acid on intracellular-free Ca(2+) levels in Madin Darby canine kidney cells.

The effect of betulinic acid, an anti-tumor and apoptosis-inducing natural product, on intracellular-free levels of Ca(2+) ([Ca(2+)](i)) in Madin Darby canine kidney (MDCK) cells was examined by using fura-2 as a Ca(2+) dye. Betulinic acid caused significant increases in [Ca(2+)](i) concentration dependently between 25 and 500 nM with an EC(50) of 100 nM. The [Ca(2+)](i) signal was composed of an initial gradual rise and a plateau. The response was decreased by removal of extracellular Ca(2+) by 45+/-10%. In Ca(2+)-free medium, pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) abolished 250 microM betulinic acid-induced [Ca(2+)](i) increases. Conversely, pretreatment with betulinic acid only partly inhibited thapsigargin-induced [Ca(2+)](i) increases. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) increase after pretreatment with 250 nM betulinic acid in Ca(2+)-free medium for 5 min. This [Ca(2+)](i) increase was not altered by the addition of 20 microM SKF96365 and 10 microM econazole. Inhibiting inositol 1,4,5-trisphosphate formation with the phospholipase C inhibitor U73122 (2 microM) abolished 250 nM betulinic acid-induced Ca(2+) release. Pretreatment with 10 microM La(3+) inhibited 250 nM betulinic acid-induced [Ca(2+)](i) increases by 85+/-3%; whereas 10 microM of verapamil, nifedipine and diltiazem had no effect. In Ca(2+) medium, pretreatment with 2.5 nM betulinic aid for 260 s potentiated 10 microM ATP and 1 microM thapsigargin-induced [Ca(2+)](i) increases by 33+/-3% and 45+/-3%, respectively. Trypan blue exclusion revealed that acute exposure of 250 nM betulinic acid for 2-30 min decreased cell viability by 6+/-2%, which could be prevented by pretreatment with 2 microM U731222. Together, the results suggest that betulinic acid induced significant [Ca(2+)](i) increases in MDCK cells in a concentration-dependent manner, and also induced mild cell death. The [Ca(2+)](i) signal was contributed by an inositol 1,4, 5-trisphosphate-dependent release of intracellular Ca(2+) from thapsigargin-sensitive stores, and by inducing Ca(2+) entry from extracellular medium in a La(3+)-sensitive manner.

Cerebral CT findings in drug abuse: clinical and experimental observations.

Computed tomographic changes compatible with cerebral atrophy have been observed clinically and in experimental drug abuse animals. Most of the patients were thought to be polydrug users, but amphetamines and alcohol were two of the more commonly misused drugs. In the experimental animals, the effects of amphetamine, secobarbital, and marijuana were studied. Brain damage was present in the animals that received intravenous amphetamine.

Cerebral microvascular injury in experimental drug abuse.

An experimental drug abuse research project is reported, in which monkeys and rats were placed on various I.V. amphetamine (Desoxyn) and I.V. barbiturate (Seconal) regimes. The monkeys were studied by serial cerebral angiography. At the end of the study all animals were sacrificed for histological examination. I.V. methamphetamine produced relatively severe cerebral vascular injury and brain damage in most animals. At least part of the damage seemed to be the result of direct vascular injury, arterial and venous. The misuse of Seconal and Ritalin also appeared to be hazardous, but these studies are incomplete, and the degree of hazard has not been fully evaluated.