Improvement of MBD parameters in dialysis patients by a switch to, and combined use of lanthanum carbonate: Josai Dialysis Forum collaborative study.

The effects of lanthanum carbonate on MBD parameters were investigated in 59 hemodialysis patients who were taking calcium carbonate. Lanthanum carbonate (initial dosage: 750 mg/day), as a replacement for or in combination with calcium carbonate and/or sevelamer hydrochloride, was administered for 12 months with increase/decrease of dosages. Lanthanum carbonate replaced calcium carbonate for 21 cases and was co-administered in 38 cases. It replaced sevelamer hydrochloride in 20 cases and was co-administered in 10 cases. Both the number of cases to which calcium carbonate was administered and their dosages decreased to about 70-80% 12 months after the initiation, and cases administered sevelamer decreased to about 30%. In the cases for which lanthanum carbonate was co-administered, the dosages of calcium carbonate and sevelamer slightly decreased. A significant decrease in serum calcium level was observed. In the serum phosphorus levels (P levels), significant decrease compared with the initial level was observed only at six and nine months. Intact parathyroid hormone (iPTH) level remained stable at around 230 pg/mL without significant change. The dosage of vitamin D and cinacalcet remained without significant change. The results of this trial suggest that, if dosages of vitamin D and cinacalcet are adequately controlled, a switch to lanthanum carbonate and its concomitant use are effective to control the Ca and P levels without changing iPTH levels.

Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease.

BACKGROUND: We reported that urinary L-FABP reflected the progression of chronic kidney disease (CKD). This study is aimed to evaluate the clinical significance of urinary liver type fatty acid binding protein (L-FABP) as a biomarker for monitoring CKD. METHODS: Urinary L-FABP was measured using human L-FABP ELISA kit (CMIC.Co., Ltd., Tokyo, Japan). The relations between urinary L-FABP and clinical parameters were evaluated in non-diabetic CKD (n = 48) for a year. In order to evaluate the influence of serum L-FABP derived from liver upon urinary L-FABP, both serum and urinary L-FABP were simultaneously measured in patients with CKD (n = 73). RESULTS: For monitoring CKD, the cut-off value in urinary L-FABP was determined as 17.4 microg/g.cr. by using a receiver operating characteristics (ROC) curve. Renal function deteriorated significantly more in patients with 'high' urinary L-FABP (n = 36) than in those with 'low' L-FABP (n = 12). The decrease in creatinine clearance was accompanied by an increase in urinary L-FABP, but not in urinary protein. Serum L-FABP in patients with CKD was not correlated with urinary L-FABP. CONCLUSION: Urinary excretion of L-FABP increases with the deterioration of renal function. Serum L-FABP did not influence on urinary L-FABP. Urinary L-FABP may be a useful clinical biomarker for monitoring CKD.

Effects of allopurinol, a xanthine oxidase inhibitor, on renal injury in hypercholesterolemia-induced hypertensive rats.

To investigate if increased lipid peroxidation is involved in hypercholesterolemia-induced hypertension and renal injury, we examined the effects of allopurinol, a xanthine oxidase inhibitor, on these conditions. Groups of male Sprague--Dawley rats were fed for 8 weeks with a high-cholesterol diet (4% cholesterol), a high-cholesterol plus allopurinol (10 mg/kgBW/day) diet or a normal diet. Systolic blood pressure (SBP), serum lipids, uric acid (UA) and malondialdehyde (MDA) as a measure of lipid peroxides, and urinary excretion of protein (UP) were measured after 0, 4 and 8 weeks. Urinary excretion of nitrite plus nitrate (UNOx) and iron (UFe), and MDA in the kidney were measured after 8 weeks. The renal injury was evaluated by the glomerular sclerosis score (SS). The high-cholesterol diet increased SBP, serum total cholesterol and UA, MDA in the serum and kidney, UP, UNOx, UFe and SS. Allopurinol ameliorated cholesterol-induced elevation in serum UA, MDA in the serum and kidney, UP, UNOx, UFe and SS, but did not affect SBP. Hence, our results suggest that lipid peroxidation may be involved in hypercholesterolemia-induced renal injury, and that suppression of lipid peroxidation can reduce such injury.

Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: a multicenter trial.

To confirm the clinical usefulness of the measurement of urinary liver-type fatty acid-binding protein (L-FABP) in chronic kidney disease (CKD), we carried out a multicenter trial. Clinical markers were measured in patients with nondiabetic CKD (n = 48) every 1 to 2 months for a year. We divided patients retrospectively into progression (n = 32) and nonprogression (n = 16) groups on the basis of the rate of disease progression, then assessed several clinical markers. Initially creatinine clearance (Ccr) was similar in the 2 groups; however, the urinary L-FABP level was significantly higher in the former group than in the latter (111.5 vs 53 microg/g creatinine, P < .001). For the monitoring CKD, we set the cutoff values for urinary L-FABP and urinary protein at 17.4 microg/g creatinine and 1.0 g/g creatinine, respectively. Urinary L-FABP was more sensitive than urinary protein in predicting the progression of CKD (93.8% and 68.8%, respectively). However, urinary protein showed greater specificity than did urinary L-FABP (93.8% and 62.5%, respectively). Over time, the progression of CKD tended to correlate with changes in urinary L-FABP (r = - .32, P < .05), but not in urinary protein (r = .18, not significant). The dynamics of urinary protein differed from that of urinary L-FABP, which increased as Ccr declined. Urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. Urinary excretion of L-FABP increases with the deterioration of kidney function. Urinary L-FABP is therefore a useful clinical marker in the monitoring of CKD.

Effects of acute hypercholesterolemia on blood pressure and pressor response to norepinephrine in rats.

To examine if high cholesterol in blood acutely affects the blood pressure, we partly exchanged the blood of normal rats for that of hypercholesterolemic rats. Male Sprague-Dawley rats were fed for 8 weeks with a high-cholesterol diet (4% cholesterol; HC) or a normal diet (NC). The rats were catheterized; and blood of animals in NC was partly exchanged with that of HC (N-H) or other animals in NC (N-N). Systolic blood pressure (SBP) and the pressor response to norepinephrine (NE) in N-H were compared with those of N-N. Serum lipids and malondialdehyde (MDA), and urinary excretion of protein (UP) and NE (UNE) were determined. After 8 weeks, SBP, serum total cholesterol (TC), MDA, UP and UNE were higher in the HC. Blood exchange caused an increase in TC, MDA and SBP in only the N-H. Increases in SBP caused by NE injection were rather less in the N-H than in the N-N. The blood pressure increase induced by a high-cholesterol diet seemed to be caused by certain factors in the blood of hypercholesterolemic rats. Excessive lipid oxidation induced by hypercholesterolemia may be involved in the blood pressure elevation.

Thalidomide treatment for immunoglobulin D multiple myeloma in a patient on chronic hemodialysis.

A 64-year-old Japanese man suffering from IgD lambda myeloma and renal failure requiring chronic hemodialysis was treated with thalidomide. Serum IgD concentration was 4,050 mg/dl and myeloma cells constituted 95.6% of nucleated cells in bone marrow at the start of treatment. These parameters improved markedly to 1,590 mg/dl and 22.0%, respectively, in the 4 months immediately prior to his death due to pneumonia. Thalidomide caused peripheral neuropathy and constipation at a dose of 100 mg daily in the first week of treatment, but adverse effects resolved upon dose reduction. Thalidomide represents a valid therapeutic option for some myeloma patients receiving hemodialysis.

Blood sugar control reverses the increase in urinary excretion of prostaglandin D synthase in diabetic patients.

BACKGROUND/AIMS: We investigated basal levels of serum and urinary lipocalin-type prostaglandin D synthase/beta-trace (L-PGDS) in type-2 diabetic patients and explored whether glycemic control affects L-PGDS status in another 55 diabetic inpatients with normoalbuminuria. METHODS: Fifty-five type-2 diabetic outpatients (HbA1c, 9.14 +/- 0.20%; creatinine (Cr), 85.1 +/- 2.4 micromol/l), and 55 age-matched healthy control subjects were recruited. Serum and urinary levels of L-PGDS were determined with respect to the stage of diabetic nephropathy. The L-PGDS was localized by immunohistochemistry. RESULTS: The urinary L-PGDS index increased in diabetic patients, compared with the controls (234.8 +/- 27.4 vs. 73.8 +/- 7.8 microg/mmol Cr, p < 0.001). Even in normoalbuminuric patients as well as in microalbuminuric patients, urinary L-PGDS indexes were higher than the controls (166.0 +/- 21.1, p < 0.0001 and 338.6 +/- 62.5 microg/mmol Cr, p < 0.0001, respectively), although the serum L-PGDS level was equal to that in the control subjects. Multiple regression analysis revealed that the urinary L-PGDS index was predicted solely by glucose levels and type-IV collagen index, whereas the serum L-PGDS was determined mainly by age and serum Cr. Glycemic control reduced the urinary L-PGDS index towards the normal range in diabetic patients with normoalbuminuria (172.3 +/- 6.6 vs. 118.1 +/- 2.6 (SE) microg/mmol Cr, p < 0.0001). Immunohistochemistry showed that L-PGDS was uniquely present in the renal tubules in diabetes while in nondiabetics, L-PGDS occurred solely in the peritubular interstitium, not in the tubular cells. CONCLUSION: Inadequate glycemic control is responsible for urinary L-PGDS excretion in the diabetic patients. Urinary L-PGDS is useful to predict subclinical renal injury associated with type-2 diabetes.

Lipocalin-type prostaglandin d synthase in essential hypertension.

Lipocalin-type prostaglandin D synthase (L-PGDS) reportedly well predicts cardiovascular injuries in humans. However, little is known about the implications of L-PGDS in hypertension. In the present study, we investigated the alterations of serum and urinary L-PGDS in hypertensive patients with or without renal dysfunction. A total of 111 patients with hypertension (EHT; 65 with normoalbuminuria, 23 with microalbuminuria, 12 with macroalbuminuria, 11 with renal failure) and 102 normotensive, nomoalbuminuric subjects (NT) were studied. L-PGDS was measured by enzyme-linked immunosorbent assay, and L-PGDS in the kidney was localized using immunohistochemical methods. Blood pressure was higher in EHT groups than in the NT group (P<0.0001). There were no differences in age, gender, BMI, TC, TG, and HbA1c levels among the groups. Serum creatinine and urinary albumin levels were higher in the group with renal failure. Serum levels of L-PGDS were increased in EHT with normoalbuminuria, as compared with NT (0.88 +/- 0.05 versus 0.65 +/- 0.02 microg/mL; P<0.001). Serum levels of L-PGDS increased with the renal function worsened and positively correlated with serum creatinine, particularly in patients with renal impairments (r=0.76, P<0.0001). Similarly, the urinary L-PGDS excretions in EHT with normoalbuminuria were higher than that in NT (2.31 +/- 0.29 versus 1.16 +/- 0.14 mg/gCr, P<0.001), whereas there were no differences in urinary albumin excretion between the 2 groups. Moreover, urinary L-PGDS excretion increased dramatically with an increase in albuminuria or proteinuria. L-PGDS was stained in the tubules and the interstitium of the kidney in nephrosclerosis. In conclusion, patients with hypertension exhibited a higher level of L-PGDS in serum and urine, and this became increasingly obvious along with advance in renal dysfunction. These data suggest that L-PGDS metabolism is related to blood pressure and kidney injuries associated with hypertension.