Evaluation of the Effect of Topiroxostat on Renal Function in Patients with Hyperuricemia: STOP-C Study, a Retrospective Observational Cohort Study.

BACKGROUND: Serum uric acid-lowering therapy is associated with maintaining renal function. OBJECTIVE: We aimed to retrospectively evaluate renal function and serum uric acid in patients with hyperuricemia who received topiroxostat for over a year. METHODS: Medical records of patients from 1 January, 2015 to 31 October, 2019 in our hospital were used. From the medical records, data of 100 patients with hyperuricemia treated with topiroxostat were extracted (67:33 male:female). The primary endpoints were changes in serum creatinine level and estimated glomerular filtration rate at 12 months after topiroxostat administration. The secondary endpoints were changes in serum creatinine, serum uric acid, and estimated glomerular filtration rate before and after topiroxostat administration. RESULTS: The study mainly involved elderly individuals (77.2 ± 9.5 years). Forty-four patients administered uric acid-lowering drugs were switched to topiroxostat. After 12 months, the serum creatinine level and estimated glomerular filtration rate showed no significant changes from baseline; however, the serum uric acid level significantly decreased. The estimated glomerular filtration rate significantly decreased during the 6 months before topiroxostat administration (p < 0.001), but showed no significant change at 6 months after topiroxostat administration (p = 0.849). CONCLUSIONS: This study revealed that topiroxostat use not only reduced the serum uric acid level but also maintained renal function in elderly patients with hyperuricemia in daily clinical practice.

Hemoperfusion treatment in a septic shock patient with autosomal dominant polycystic kidney disease and increased HMGB1 protein levels.

This case report describes polymyxin B-immobilized fiber (PMX-F) treatment of septic shock caused by pyelonephritis in a 68-year-old woman with autosomal dominant polycystic kidney disease. She was admitted for severe lower left abdominal pain, high fever (40°C) and gross hematuria. Her endotoxin and high-mobility group box-1 protein (HMGB1) levels were extremely elevated. Her blood pressure was 68/36 mm Hg. Urinalysis revealed innumerable white blood cells (WBCs). Blood and urine cultures were positive for Klebsiella pneumoniae and Pseudomonas aeruginosa. Plain abdominal radiography showed large kidney shadows and calcium deposition. Septic shock with endotoxemia was diagnosed. Her symptoms of septic shock persisted for 3 days with antibiotics, γ-globulin and dopamine. Direct hemoperfusion was performed twice with a PMX-F column. The patient's body temperature, WBC count and C-reactive protein level decreased. Her blood endotoxin level and blood HMGB1 level also decreased to an almost normal level. She was discharged on day 23 after admission.

Massive Pericardial Effusion in a Case of Acute Pericarditis with Slight ST-Segment Elevation of Short Duration.

We present the case of a 77-year-old woman who suffered from chest pain. Her white blood cell count was 10,200/µL and C-reactive protein level was 5.5 mg/dL. There was no electrocardiogram abnormality up to 5 hours after admission. At 15 hours, slight ST-segment elevation occurred, but this disappeared on day 4. Imaging revealed slight pericardial effusion. Nonsteroidal anti-inflammatory drugs and antibiotics were administered. However, the pericardial effusion, inflammatory response, and bilateral heart failure worsened. Pericardiotomy on day 6 released 350 mL of fluid, and symptoms improved. Viral pericarditis was assumed. Massive pericardial effusion is rare in cases of acute viral pericarditis, as is slight, short-duration ST-segment elevation.

Acute Myocardial Infarction with Severe ST Segment Elevation Treated with Percutaneous Coronary Intervention More than Two Days after Onset: A Case with Remarkable Recovery.

The patient was a 65-year-old man with marked ST-elevation myocardial infarction. Cardiac catheterization revealed an occluded middle portion of the left anterior descending artery and no collateral circulation. Percutaneous coronary intervention (PCI) was performed, and ST elevation improved 5 days after PCI. Almost all electrocardiogram (ECG) findings were normal 6 months later. Echocardiographic findings were also normal. This case was very successful and unusual in that no ventricular aneurysm formed despite ST elevation continuing for a few days and that ECG and left ventricular function were nearly normal after PCI performed days after the onset in a case without collateral circulation.

Urinary L-type fatty acid-binding protein as a new biomarker of sepsis complicated with acute kidney injury.

OBJECTIVE: This study is aimed to examine whether urinary L-type fatty acid-binding protein can detect the severity of sepsis with animal sepsis models and septic shock patients complicated with established acute kidney injury. DESIGN: Experimental animal models and a clinical, prospective observational study. SETTING: University laboratory and tertiary hospital. SUBJECTS AND PATIENTS: One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury. INTERVENTIONS: Animals were challenged by abdominal (cecal ligation and puncture) and pulmonary (intratracheal lipopolysaccharide injection) sepsis models with different severities that were confirmed by survival analysis (n = 24) and bronchoalveolar lavage fluid analysis (n = 38). MEASUREMENTS AND MAIN RESULTS: In animal experiments, significant increases of urinary L-type fatty acid-binding protein levels were induced by sepsis (severe cecal ligation and puncture 399.0 ± 226.8 µg/g creatinine [n = 12], less-severe cecal ligation and puncture 89.1 ± 25.3 [n = 11], sham 13.4 ± 3.4 [n = 10] at 6 hrs, p < .05 vs. sham; 200 µg of lipopolysaccharide 190.6 ± 77.4 µg/g creatinine [n = 6], 50 µg of lipopolysaccharide 145.4 ± 32.6 [n = 8], and saline 29.9 ± 14.9 [n = 5] at 6 hrs, p < .05 vs. saline). Urinary L-type fatty acid-binding protein predicted severity more accurately than blood urea nitrogen, serum creatinine, and urinary N-acetyl-d-glucosaminidase levels. In clinical evaluation, urinary L-type fatty acid-binding protein measured at admission was significantly higher in the nonsurvivors of septic shock with established acute kidney injury than in the survivors (4366 ± 192 µg/g creatinine [n = 68] vs. 483 ± 71 [n = 77], p < .05). Urinary L-type fatty acid-binding protein showed the higher value of area under the receiver operating characteristic curve for mortality compared with Acute Physiology and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) scores (L-type fatty acid-binding protein 0.994 [0.956-0.999], APACHE II 0.927 [0.873-0.959], and SOFA 0.813 [0.733-0.873], p < .05). CONCLUSIONS: Our results suggest that urinary L-type fatty acid-binding protein can be a useful biomarker for sepsis complicated with acute kidney injury for detecting its severity.

Effects of telmisartan and enalapril on renoprotection in patients with mild to moderate chronic kidney disease.

BACKGROUND: Blocking the renin-angiotensin system (RAS) with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors protects against renal injury in patients with chronic kidney disease (CKD). The aim of this study was to compare the chronic effects of telmisartan and enalapril on proteinuria, urinary liver-type fatty acid-binding protein (L-FABP) and endothelin (ET)-1 levels in patients with mild CKD. MATERIALS AND METHODS: Thirty CKD patients with mild to moderate renal insufficiency (20 men and 10 women; mean age, 37 years; estimated glomerular filtration rate (eGFR) > 60 mL min(-1) and blood pressure > 130/85 mmHg) were included in the study. Patients were randomly assigned to receive telmisartan at 80 mg day(-1) (n = 15) or enalapril at 10 mg day(-1) (n = 15). We measured blood pressure, serum creatinine, eGFR, urinary protein, L-FABP and ET-1 before the start of treatment and 6 and 12 months after the start of treatment. RESULTS: The blood pressure reduction rate was similar between the two groups. Urinary protein, L-FABP and ET-1 levels were significantly reduced in both groups 6 and 12 months (P < 0.001) after treatment, but the reduction rates were more pronounced in patients receiving telmisartan than in those receiving enalapril (P < 0.001). Estimated glomerular filtration rate was increased similarly in both groups at 12 months. CONCLUSIONS: The study results suggest that telmisartan results in a greater reduction of urinary markers than does enalapril and that this effect occurs by a mechanism independent of blood pressure reduction. It would be needed to investigate whether the differences may be distinct or not the same when other dosages are used.

Renoprotective Effects of Various Angiotensin II Receptor Blockers in Patients with Early-Stage Diabetic Nephropathy.

BACKGROUND: There is increasing evidence that inhibition of the renin-angiotensin system provides renoprotection independent of blood pressure lowering. The aim of the present study was to determine whether various angiotensin II receptor blockers (ARBs) affect urinary albumin excretion (UAE), urinary liver-type fatty acid-binding protein (L-FABP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in early-stage diabetic nephropathy patients with microalbuminuria. METHODS: Sixty-eight diabetic nephropathy patients with microalbuminuria were randomly allocated to 1 of 4 treatment groups: losartan 100 mg/day (group A), candesartan 12 mg/day (group B), olmesartan 40 mg/day (group C), or telmisartan 80 mg/day (group D). Treatment was continued for 12 months. UAE, L-FABP and 8-OHdG excretion, serum creatinine, and 24-hour creatinine clearance (Ccr) were measured. RESULTS: The serum creatinine and 24-hour Ccr were not affected during the experimental period in any of the groups. Systolic and diastolic blood pressures, UAE, urinary L-FABP and 8-OHdG excretion were significantly reduced after 6 and 12 months compared with baseline in any of the groups. ΔL-FABP and Δ8-OHdG were significantly greater in group D than in the other 3 groups after 12 months. CONCLUSIONS: ARBs have renoprotection and this effect of telmisartan appears to be more potent than that of losartan, candesartan, or olmesartan in early-stage diabetic nephropathy patients.

Molecular evidence for the presence of new Babesia species in feral raccoons (Procyon lotor) in Hokkaido, Japan.

We recently reported that feral raccoons (Procyon lotor) with splenomegaly native to Japan were carriers of a Babesia microti-like parasite identical to that found in the United States, which was likely introduced to Japan from North America via raccoons imported as pets. Thus, we attempted extensive molecular survey for piroplasma infections of feral raccoon with normal spleen in Hokkaido, Japan using nested PCR that target broadly to 18S ribosomal RNA gene (SSU-rDNA) of all the parasites in the genus Babesia, Theileria, Cytauxzoon and B. microti group. Of the 348 raccoon samples analyzed, 9 gave positive signals. Cloning and phylogenetic analysis on SSU-rDNA sequences revealed that six of nine positives were found to be infected with Babesia and the remaining three with previously unreported Sarcocystis. Babesia sequences were further separated into two distantly related groups, those that reside in a novel phylogenetic group were consisted solely of four parasites found in this study, while those which included one identical sequence found in the three of our specimens were assembled together with both Babesia parasites of tick's in Japan and of raccoon's in U.S. These results may indicate that not only a B. microti-like parasite but also at least two yet undescribed Babesia species are being established in their new life cycles in the feral raccoon populations in Japan.

Comparison of renal and vascular protective effects between telmisartan and amlodipine in hypertensive patients with chronic kidney disease with mild renal insufficiency.

The present study was conducted to compare the renal and vascular protective effects of telmisartan and amlodipine in untreated hypertensive chronic kidney disease (CKD) patients with moderate renal insufficiency. Thirty hypertensive CKD patients were randomly assigned to receive telmisartan 40 mg (n = 15) or amlodipine 5 mg (n = 15) once daily for 12 months. Changes in blood pressure, serum creatinine, 24-h creatinine clearance (Ccr), proteinuria, brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT), plasma interleukin-6 (IL-6), plasma matrix metalloproteinase (MMP)-9 and lipid profiles were monitored in all patients. Before treatment, there were no significant differences in these parameters between the telmisartan and amlodipine groups. Over the 12 month observation period, blood pressure decreased equally in both groups. However, serum creatinine, proteinuria, baPWV, IMT, plasma levels of IL-6 and MMP-9 and total cholesterol decreased and 24-h Ccr increased more strikingly in the telmisartan group than the amlodipine group. These data suggest that telmisartan is more effective than amlodipine for protecting renovascular functions, and potentially for ameliorating atherosclerosis, in hypertensive CKD patients with moderate renal insufficiency.

Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy.

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is a clinical biomarker of tubulointerstitial damage, which plays an essential role in the progression of chronic kidney disease (CKD), including immunoglobin A (IgA) nephropathy. The effect of combination therapy with the angiotensin receptor blocker (ARB) and the angiotensin-converting enzyme inhibitor (ACEI) on CKD has not been elucidated. METHODS: Twenty-four normotensive patients with IgA nephropathy were randomly assigned to receive olmesartan 10 mg/day, temocapril 2 mg/day, or combination therapy with both drugs. Urinary levels of L-FABP as well as 8-hydroxydeoxyguanosine (8-OHdG) and protein excretion were measured before and after 3 months of treatment. The chronicity index and activity index were also assessed by histopathologic findings. RESULTS: Urinary levels of L-FABP and 8-OHdG were higher in patients with IgA nephropathy than in age-matched and sex-matched healthy controls (122.5 +/- 25.5 v 6.4 +/- 3.8 mug/g.creatinine, P < .001; and 22.6 +/- 4.4 v 4.8 +/- 1.4 ng/mg.creatinine, P < .01, respectively). Urinary levels of L-FABP were correlated with those of 8-OHdG (baseline, P = .0001; after 3 months, P = .008) and the severity of proteinuria (baseline, P = .0015; after 3 months, P = .0001). The percent reductions in urinary levels of L-FABP and 8-OHdG, protein excretion, and activity index after 3 months were greater in the combination therapy group, compared with each monotherapy group of olmesartan (P < .05) and temocapril (P < .05). CONCLUSIONS: The data suggest that a combination therapy of ARB plus ACEI has a greater beneficial effect on renal injury compared with monotherapy using ARB or ACEI in normotensive patients with IgA nephropathy.

Polymyxin B-immobilized fiber hemoperfusion with the PMX-05R column in elderly patients suffering from septic shock.

BACKGROUND: Direct hemoperfusion with the polymyxin B-immobilized fiber (PMX-20R) column has a positive effect on outcome in patients with sepsis or septic shock. The PMX-05R column has a low priming volume and has been used in pediatric patients with septic shock. The aim of the present study was to determine whether PMX-F treatment with the PMX-05R column is effective in elderly patients with septic shock. PATIENTS AND METHODS: We performed direct hemoperfusion twice with the PMX-05R column in 8 septic shock patients who were over 80 years of age. Five of the 8 patients survived. The 3 patients who died were undergoing hemodialysis for chronic renal failure, and methicillin-resistant Staphylococcus aureus was detected in all 3. RESULTS: PMX-F treatment significantly increased systolic and diastolic blood pressures (P = 0.0004 for both) and significantly reduced heart rate (P < 0.0001), the blood endotoxin level (P = 0.0011), blood IL-6 level (P = 0.039), C-reactive protein level (P < 0.0001), and white blood cell count (P < 0.0001). CONCLUSIONS: Direct hemoperfusion with the PMX-05R column is effective in ameliorating clinical and laboratory abnormalities in elderly septic shock patients.

Azelnidipine reduces urinary protein excretion and urinary liver-type fatty acid binding protein in patients with hypertensive chronic kidney disease.

BACKGROUND: Hypoxia plays a significant role in the pathogenesis and progression of chronic renal disease. Urinary liver-type fatty acid binding protein (L-FABP) levels reflect the clinical prognosis of chronic renal disease. The calcium channel blocker azelnidipine has anti-oxidative properties and these may contribute to the beneficial effects of this drug. The aim of the present study was to determine whether azelnidipine and/or amlodipine affected urinary protein excretion or the urinary levels of 8-OHdG and L-FABP in hypertensive patients with mild chronic kidney disease (CKD). METHODS: Thirty moderately hypertensive chronic kidney disease patients were randomly assigned to 2 treatment groups: azelnidipine 16 mg once daily or amlodipine 5 mg once daily. Treatment was continued for 6 months. Urinary protein excretion and urinary levels of 8-OHdG and urinary L-FABP were measured before 3 and 6 months after the treatment period. RESULTS: Both drugs exhibited comparable and significant effects on the systolic and diastolic blood pressure. Azelnidipine decreased heart rate significantly after 3 and 6 months whereas amlodipine increased it significantly after 3 and 6 months. Urinary protein excretion, urinary 8-OHdG and urinary L-FABP levels decreased significantly after 3 months (p < 0.05) and 6 months (p < 0.05) in the azelnidipine group. In contrast, amlodipine showed little effect on urinary protein excretion or the urinary levels of 8-OHdG and L-FABP throughout the experimental period. CONCLUSIONS: Azelnidipine is renoprotective in hypertensive patients with mild CKD and this action is, at least in part, due to the anti-oxidative effect.

Evaluation of the heart and great vessel calcification by conventional computed tomography in hemodialysis patients.

Heart diseases are responsible for death in hemodialysis patients. The aim of this study was to determine whether we can assess the degree of calcification of the heart and great vessels in hemodialysis patients by non-gated conventional computed tomography (CT) without contrast media. Thirty patients were included in the present study. The hemodialysis group comprised 15 patients and the age-matched control group comprised 15 patients without hemodialysis or cardiac diseases who underwent CT scanning. Axial cross-sectional images were taken from the aortic arch to the diaphragm to detect calcification of the aorta and coronary arteries. Eleven patients in the hemodialysis group showed calcification in 1.9 +/- 1.4 coronary vessels, a frequency significantly greater than that of the 0.3 +/- 0.2 coronary vessels in the control group (p < 0.01). Fourteen patients in the hemodialysis group showed calcification of the aorta with a mean score 9.7 +/- 7.2, significantly greater than mean score in the control group (3.5 +/- 2.2; p < 0.01). These results suggest that we can assess an increase in the incidence of calcification of the coronary arteries and the aorta by conventional CT scanning without contrast media in patients undergoing hemodialysis.

Urinary excretion of liver-type fatty acid-binding protein in contrast medium-induced nephropathy.

BACKGROUND: Administration of contrast agents can cause a decrease in renal function and, occasionally, end-stage renal disease. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of free fatty acids that is expressed in proximal tubules of the human kidney. Whether urinary excretion of L-FABP can predict the occurrence of contrast medium-induced nephropathy was studied. METHODS: Sixty-six patients (46 men, 20 women; mean age, 60.0 years) undergoing nonemergency coronary angiography or intervention at 1 of our institutions who had a serum creatinine (Cr) level greater than 1.2 mg/dL (> 106 micromol/L) and less than 2.5 mg/dL (< 221 micromol/L) and 30 healthy volunteers (21 men, 9 women; mean age, 56.5 years) were included. Urinary L-FABP levels were measured before and after coronary angiography with the use of monoclonal antibodies. Contrast medium-induced nephropathy is defined as an increase in serum Cr level of greater than 0.5 mg/dL (> 44 micromol/L) or a relative increase of more than 25% at 2 to 5 days after the procedure. RESULTS: Contrast medium-induced nephropathy occurred in 13 of 66 patients (19.7%). Before angiography, urinary L-FABP levels were significantly greater in these 13 patients (contrast medium-induced nephropathy group; 18.5 +/- 12.8 microg/g Cr; range, 5.8 to 33.6 microg/g Cr) than in the remaining 53 patients (non-contrast medium-induced nephropathy group; 7.4 +/- 4.4 microg/g Cr; range, 2.8 to 13.8 microg/g Cr; P < 0.01) or healthy volunteers (5.4 +/- 4.4 microg/g Cr; range, 1.0 to 10.0 microg/g Cr; P < 0.01). The next day and 2 days after angiography, urinary L-FABP levels increased significantly to 46.8 +/- 30.5 microg/g Cr (range, 12.0 to 84.5 microg/g Cr; P < 0.01) and 38.5 +/- 28.5 microg/g Cr (range, 9.5 to 70.5 microg/g Cr; P < 0.01) in the contrast medium-induced nephropathy group, respectively. After 14 days, serum Cr returned to the baseline level, but urinary L-FABP level remained high (34.5 +/- 30.0 microg/g Cr; range, 4.0 to 68.0 microg/g Cr). However, urinary L-FABP levels in the non-contrast medium-induced nephropathy group changed little throughout the experimental period. CONCLUSION: Urinary L-FABP level can serve clinically as a predictive marker for contrast medium-induced nephropathy.

Effect of pitavastatin on urinary liver-type fatty acid-binding protein levels in patients with early diabetic nephropathy.

OBJECTIVE: Liver-type fatty acid-binding protein (l-FABP) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis. The aim of this study was to determine whether urinary l-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary l-FABP levels in early diabetic nephropathy. RESEARCH DESIGN AND METHODS: Fifty-eight patients with type 2 diabetes (34 men and 24 women, median age 52 years) and 20 healthy, age-matched subjects (group E) were recruited for the study. The diabetic patients included 12 patients without nephropathy (group A), 20 patients with microalbuminuria (group B), 14 patients with macroalbuminuria and normal renal function (group C), and 12 patients with chronic renal failure but not undergoing hemodialysis (blood creatinine >1.2 mg/dl; mean 2.5 mg/dl, group D). Twenty group B patients were randomly assigned to receive 1 mg/day pitavastatin (10 patients, group B1) or placebo (10 patients, group B2). Treatment was continued for 12 months. Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay. Urinary 8-hydroxydeoxyguanosine and serum free fatty acids (FFAs) were also measured in group B. RESULTS: Urinary l-FABP levels in groups A-D were 6.2 +/- 4.6 microg/g creatinine, 19.6 +/- 13.5 microg/g creatinine, 26.8 +/- 20.4 microg/g creatinine, and 52.4 +/- 46.8 microg/g creatinine, respectively. Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects (group E, 5.8 +/- 4.0 microg/g creatinine) (group B, P < 0.05; group C, P < 0.01; group D, P < 0.01). In group B1, urinary albumin excretion (UAE) and urinary l-FABP levels were decreased after pitavastatin treatment (UAE before, 110 +/- 74 microg/min; 6 months, 88 +/- 60 microg/min, P < 0.05; 12 months, 58 +/- 32 microg/min, P < 0.01; l-FABP before, 18.6 +/- 12.5 microg/g creatinine; 6 months, 12.2 +/- 8.8 microg/g creatinine, P < 0.05; 12 months, 8.8 +/- 6.4 microg/g creatinine, P < 0.01). In group B2, UAE and l-FABP levels showed little change during the experimental period. In group B1, urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment (before 32.5 +/- 19.5 ng/mg creatinine, after 18.8 +/- 14.5 ng/mg creatinine, P < 0.01), but in group B2, these showed little difference during the experimental period. In both groups B1 and B2, serum FFAs showed little difference during the experimental period. CONCLUSIONS: Urinary l-FABP levels appear to be associated with the progression of diabetic nephropathy, and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy.

Effect of low-density lipoprotein apheresis on urinary protein and podocyte excretion in patients with nephrotic syndrome due to diabetic nephropathy.

BACKGROUND: The aim of the present study is to determine whether low-density lipoprotein (LDL) apheresis affects proteinuria and urinary podocyte excretion in patients with type 2 diabetes and nephrotic syndrome. METHODS: LDL apheresis was performed on patients with diabetes with long-standing nephrotic syndrome, and urinary protein level and number of urinary podocytes were compared between these patients (5 men, 3 women; mean age, 54.6 years) and 10 nephrotic patients with diabetes not treated with LDL apheresis (6 men, 4 women; mean age, 56.5 years). RESULTS: LDL apheresis reduced total cholesterol (P < 0.001), LDL cholesterol ( P < 0.001), lipoprotein(a) (P < 0.001), creatinine (P < 0.05), and blood urea nitrogen (P < 0.05) levels and increased creatinine clearance (P < 0.05). The LDL apheresis group showed a significant decrease in urinary protein excretion (from 10.8 +/- 3.2 to 1.8 +/- 1.1 g/d; P < 0.001) and number of urinary podocytes (from 4.8 +/- 2.2 to 0.9 +/- 0.4 cells/mL; P < 0.01). CONCLUSION: These data suggest that LDL apheresis effectively reduces proteinuria and podocyte excretion, ameliorating renal dysfunction in patients with nephrotic syndrome caused by diabetic nephropathy.

Candesartan reduces urinary fatty acid-binding protein excretion in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Free fatty acids (FFAs) bound to albumin are overloaded in renal proximal tubules and exacerbate tubulointerstitial damage. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of FFAs that is expressed in renal proximal tubules in humans. Urinary L-FABP reflects the clinical prognosis of chronic glomerulonephritis. The aim of the present study was to determine whether urinary L-FABP excretion is altered in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether candesartan cilexetil, an angiotensin II receptor antagonist, affects these levels. METHODS: Subjects comprised 20 normotensive ADPKD patients (8 men and 12 women, mean age 42.6 years) and 20 age-matched healthy volunteers (8 men and 12 women, mean age 44.0 years). The 20 ADPKD patients participated in a randomized double-blind placebo-controlled study of candesartan cilexetil for 6 months. Urinary L-FABP levels were measured by a newly established ELISA method. RESULTS: Urinary L-FABP levels were significantly higher in ADPKD patients (154.5 +/- 110.6 microg/g Cr) than in healthy subjects (5.5 +/- 3.8 microg/g Cr) (P < 0.001). Candesartan cilexetil reduced urinary L-FABP levels from 168.5 +/- 104.5 microg/g Cr to 98.5 +/- 68.5 microg/g Cr after 3 months (P < 0.01) and to 44.6 +/- 30.8 microg/g Cr after 6 months (P < 0.001). Placebo had no effect on L-FABP levels (before, 140.5 +/- 100.5 microg/g Cr; at 3 months, 148.5 +/- 108.5 microg/g Cr; at 6 months, 150.5 +/- 110.8 microg/g Cr). During the 6 months, serum creatinine, blood urea nitrogen, 24-hour creatinine clearance and blood pressure showed little change in either group. CONCLUSIONS: Increased urinary L-FABP levels may be associated with the development of ADPKD, and candesartan cilexetil has a beneficial effect on reducing these levels.

Polymyxin B-immobilized fiber hemoperfusion with low priming volume in an elderly septic shock patient with marked endotoxemia.

An 84-year-old woman with septic shock caused by pyelonephritis is described herein. She was admitted for severe back pain and high fever. Her white blood cell (WBC) count and C-reactive protein (CRP) and endotoxin levels were elevated at 38,000/microl, 40.0 mg/dl, and 8,400 pg/ml, respectively. Her blood pressure was 80/34 mm Hg. Urinalysis revealed occult blood with innumerable WBCs. Plain abdominal radiography showed calcium stones in both kidneys. Septic shock with endotoxemia was diagnosed, and the patient was treated with antibiotics, gamma-globulin, and dopamine. However, her plasma endotoxin level remained high for 3 days. We performed direct hemoperfusion twice using a polymyxin B-immobilized fiber (PMX-F) column with a low priming volume. After PMX-F treatment, the patient's temperature decreased to 36.8 degrees C; her WBC count and CRP level decreased to 9,200/microl and 3.8 mg/dl, respectively. Her plasma endotoxin level decreased to 840 pg/ml after the first treatment and to 188 pg/ml after the second treatment. The next day, her blood endotoxin level further decreased to 32 pg/ml. Her blood pressure increased to 92/60 mm Hg after the first treatment and to 118/76 mm Hg after the second treatment. The patient was discharged on day 26 after admission. Our experience in this case suggests that PMX-F treatment with a low priming volume may be beneficial in elderly patients with septic shock and marked endotoxemia.

Polymyxin B-immobilized fiber hemoperfusion in a patient with active ulcerative colitis.

A case involving a 31-year-old woman with active ulcerative colitis is described. She suffered symptoms of infraumbilical abdominal pain, severe diarrhea, and low-grade fever that did not improve with conventional treatment, including antidiarrheal drugs and antibiotics. Ulcerative colitis was diagnosed according to endoscopic and histologic findings. She was treated with prednisolone and sulfasalazine, and her symptoms disappeared after 1 month. Sulfasalazine therapy was continued for 3 months, and the patient's condition remained stable for 4 years. Recently, she was admitted with abdominal pain, severe diarrhea, and melena. She was again treated with prednisolone and intravenous hyperalimentation, but her symptoms did not improve. Colonoscopy showed multiple ulcers with bleeding and polyposis and severe edema in the colon. In addition, she had a high blood endotoxin concentration (38.0 pg/ml; normal < 9.8 pg/ml). She underwent polymyxin B-immobilized fiber (PMX-F) hemoperfusion therapy twice. After 2 weeks, her symptoms resolved completely, colonoscopy showed disappearance of the edema, revascularization of the mucosa, and improvement of the ulcers, and blood endotoxin concentration decreased to 5.0 pg/ml. These results suggest that PMX-F treatment may be beneficial for the management of ulcerative colitis with endotoxemia.

Effect of polymyxin B-immobilized fiber on bone resorption in patients with sepsis.

OBJECTIVE: To analyze the effects of polymyxin B-immobilized fiber (PMX-F) on bone resorption in septic patients. DESIGN AND SETTING: Observational prospective study in intensive care units of a general hospital. PATIENTS AND PARTICIPANTS: 25 patients with severe sepsis and 20 healthy controls. MEASUREMENTS AND RESULTS: Septic patients were randomly assigned to two groups: PMX-F treatment group (n=15) and conventional treatment group (n=10). Total pyridinium crosslink pyridinoline (PYD) and deoxypyridinoline (DPD) in urine were determined by modified high-performance liquid chromatography. Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products to urinary creatinine (NOx/Cr). Plasma endotoxin levels were determined by endospecy test. The blood albumin, ionized calcium, and parathyroid hormone were also measured. PMX-F treatment was performed twice separated by 24 h. Urinary NOx/Cr, PYD/Cr, and DPD/Cr were significantly increased in septic patients compared with those in healthy controls. Blood ionized calcium in septic patients was lower than in healthy controls, while parathyroid hormone levels in septic patients were higher than in healthy controls (P<0.01). PMX-F treatment reduced plasma endotoxin, urinary NOx/Cr, PYD/Cr, DPD/Cr, and serum parathyroid hormone levels and increased blood ionized calcium significantly; however, conventional treatment did not affect these levels. CONCLUSIONS: Septic patients increased nitric oxide production and bone resorption, and PMX-F treatment is effective in reducing nitric oxide levels and bone resorption markers.