Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients

BACKGROUND: Secondary hyperparathyroidism is a common complication among long-term dialysis patients. The method of predicting future parathyroid function has not yet been established. Fibroblast growth factor-23 (FGF-23) is a newly found humoral phosphaturic factor. METHODS: One hundred and three nondiabetic dialysis patients whose plasma intact parathyroid hormone (PTH) levels were below 300 pg/mL were included in the study. Blood samples were stored at -80 degrees C for 2 years. Meanwhile, each physician in charge decided upon the strategy of medical therapy for maintaining intact PTH levels between 150 and 300 pg/mL. Patients were judged 2 years after the sample collection with regard to whether the hyperparathyroidism responded to the medical therapy. The definition of refractory secondary hyperparathyroidism was either (1) retaining intact PTH levels greater than 300 pg/mL 2 years after sample collection, or (2) having received the parathyroid intervention therapy during the observation period. Serum FGF-23 levels were determined with a sandwich enzyme-linked immunosorbent assay system that detects biologically active human FGF-23. RESULTS: Seventeen patients with intact PTH levels greater than 300 pg/mL were judged as having secondary hyperparathyroidism refractory to medical therapy. A stepwise regression analysis revealed that only serum levels of FGF-23 were significantly related to the prognosis of parathyroid function. A receiver-operated characteristic analysis demonstrated that the area under the curves obtained from FGF-23 (7099.9) was significantly greater than that obtained from intact PTH (6306.4, P < .01) and Ca x Pi (5670.3, P <.0001). Although the plasma intact PTH levels at the beginning of the observation period were comparable to each other, the intact PTH levels at 2 years after the sample collection were significantly higher in the patients with FGF-23 >/=7500 ng/L than in those with FGF-23 <7500 ng/L (P < .0001). CONCLUSION: Serum FGF-23 level was found to be the most useful factor in predicting future development of refractory secondary hyperparathyroidism in long-term dialysis patients with mild secondary hyperparathyroidism. The measurement of serum FGF-23 levels is a promising laboratory examination that can be applied in the clinical practice of uremic secondary hyperparathyroidism.     

Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy

BACKGROUND: The slit diaphragm plays a critical role in maintaining the barrier function of the glomerular capillary wall. The pathogenic mechanism of proteinuria in membranous nephropathy remains uncertain. This study was undertaken to analyze the pathogenic role of slit diaphragm in proteinuria in experimental membranous nephropathy. METHODS: The expression and the localization of slit diaphragm-associated molecules (nephrin, podocin, and CD2AP) and other podocyte-associated molecules (podocalyxin and alpha(3) integrin) in passive and active Heymann nephritis were analyzed by immunofluorescence and Western blot analysis. The interaction of slit diaphragm-associated molecules was investigated by the dual-labeling immunofluorescence method. The mRNA expression of these molecules was also analyzed. RESULTS: Shifts in nephrin and podocin staining patterns, from linear to granular, were detected in the early stages of passive Heymann nephritis. These shifts were not parallel, and the dissociation of these molecules was detected by the dual-labeling immunofluorescence method in passive and active Heymann nephritis. Western blot analyses with sequentially solubilized materials indicated that the nephrin-rich fraction changed from being partly detergent-resistant to being predominantly detergent-soluble. This change did not occur with podocin. Nephrin excreted into urine was already detected in the early stages of passive Heymann nephritis. Decreased mRNA expression of nephrin and podocin was observed before the onset of proteinuria. By contrast, no extensive change in the expression of alpha(3) integrin was observed in this study. CONCLUSION: Nephrin is dissociated from podocin and excreted into urine in the early stages of Heymann nephritis. The reduced expression of nephrin and podocin, along with their dissociation, may contribute to the development of proteinuria in Heymann nephritis.     

Renal function at the time of renal biopsy as a predictor of prognosis in patients with primary AL-type amyloidosis

Background Amyloid light-chain (AL)-type amyloidosis is a plasma cell disorder with a poor prognosis for survival. Although prognostic factors, such as the number of organs involved and heart function or failure in respond to therapy have been clarified based on studies including a large series of patients, there are large interindividual differences in the prognosis of patients with primary AL-type renal amyloidosis.Methods To clarify the prognostic factors of AL-type renal amyloidosis, we retrospectively investigated the clinical manifestations, histopathological data, and prognosis of 21 patients with amyloidosis, who had been diagnosed by renal biopsy.Results Eleven patients died, at a mean observational time of 21.7 months after renal biopsy, whereas the mean observational time was 51.0 months for the 10 patients who survived. The creatinine clearance rate was significantly higher, and the serum creatinine concentration and the grade of interstitial damage were significantly lower in surviving patients (P < 0.05). The presence of amyloid fibrils in organs other than the kidney did not influence prognosis for survival. However, the intraventricular septum was thinner in surviving patients (P < 0.1). Thirteen patients had undergone melphalan-prednisolone therapy, but it did not affect prognosis for survival. Cox proportional hazard regression analysis revealed that the renal function at the time of diagnosis was a significant and independent prognostic factor for survival.Conclusions Our study demonstrated that renal function at the time of biopsy and renal interstitial damage are the best predictors of survival in AL-type renal amyloidosis.     

Interference of (1 --> 3)-beta-D-glucan administration in the measurement of plasma (1 --> 3)-beta-D-glucan

OBJECTIVE: Blood (1 --> 3)-beta-D-glucan (betaG) measurement is widely used as an effective sero-diagnostic method for deep-seated mycosis. Antitumor betaG (lentinan, schizophyllan) administration is known as one of the false-positive factors of blood betaG measurement. To understand the influence of administered betaG preparation to betaG measurement in blood, we compared the interfering effect of betaG administration in different betaG measuring methods. METHODS: betaG concentration in plasma was measured by three different methods. MATERIALS: betaG concentration was measured in plasma of 18 samples of 7 cases with betaG administration and 86 samples without betaG administration. The period after last betaG administration was three days to three years. RESULTS: In the cases for which betaG was administered, blood betaG level drastically increased using the method which employs alkaline pretreatment. Even in the cases for which betaG was administered three years previously; betaG value measured by alkaline pretreatment was significantly high. Thus, interference of betaG administration in blood betaG measurement continued for years after the last administration. CONCLUSION: Disparity in betaG values measured by different methods for betaG administered cases is due to differences among sample pretreatment methods. Conformation of administered betaG seemed to be transformed into a sensitive form to factor G by alkaline pretreatment. Especially in the case of the alkaline pretreatment method, betaG administration disturbance was much stronger than for dilution-heating pretreatment. Therefore, in suspected cases, it is important to pay attention to betaG administration during the previous few years.     

Angiotensinogen gene variation and renoprotective efficacy of renin-angiotensin system blockade in IgA nephropathy

BACKGROUND: Blockade of the renin-angiotensin system (RAS) is well documented to be renoprotective; however, not all patients with glomerulonephritis respond well to this therapy. The interindividual variation in response to the RAS blockade may be in part genetically determined, whereas the results have been controversial. METHODS: We investigated whether the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blocker on renal prognosis is modified by the angiotensinogen gene (AGT) polymorphism in immunoglobulin A nephropathy (IgAN). In total, 259 patients with histologically proven IgAN were analyzed for clinical manifestations, renal survival, and their associations with AGT A(-20)C and M235T. RESULTS: The renal prognosis of 110 patients, who received ACE inhibitors/angiotensin receptor blocker during their clinical course, was significantly better than those without ACE inhibitors/angiotensin receptor blockers despite higher blood pressures and heavier proteinuria. The Cox proportional hazards regression model showed an increased hazard ratio (HR) for urinary protein (more than 1.0 g/day) of 3.346 (P = 0.0001), hypertension of 1.949 (P = 0.01), deteriorated renal function of 3.040 (P < 0.0001), no ACE inhibitor/angiotensin receptor blocker administration of 2.725 (P = 0.0004), and the T235 and C(-20) haplotype of 1.608 (P = 0.0322). Only in patients carrying at least one M235 and A(-20) haplotype did the administration of ACE inhibitors/angiotensin receptor blockers have no significant effect on the prognosis of renal function (Kaplan-Meier, log rank test, chi2 = 0.700; P = 0.4028), whereas it was significant in patients who had other haplotypes of AGT (chi2 = 11.805; P = 0.0006). CONCLUSION: This study provides evidence that the M235T and A(-20)C genotype of AGT can influence the therapeutic efficacy of a RAS blockade on the renal survival in IgAN.     

Infection-associated hemophagocytic syndrome in a diabetic patient undergoing chronic hemodialysis

Hemophagocytic syndrome (HPS) is an uncommon but severe illness associated with a variety of infections, malignant tumors, and autoimmune diseases. We report a case of infection-associated HPS in a patient receiving chronic hemodialysis. Peptostreptococcus-induced sepsis and abscess formation in the left iliopsoas muscle led to the onset of infection-associated HPS in this patient. The patient had diabetes mellitus and end-stage renal disease, and it is likely that immunological dysfunctions from these disorders played a part in the onset of both severe bacterial infections and HPS.     

The effect of antihistamines on seizures induced by increasing-current electroshocks: ketotifen, but not olopatadine, promotes the seizures in infant rats

Clinical reports have shown that some antihistamines, such as ketotifen, occasionally produced seizures, especially in pre-school age children or young patients with epilepsy. The purpose of this study was to investigate whether olopatadine, one of the most efficacious antihistamines, promotes seizures induced by electroshocks in young rats. We investigated the seizures induced by electroshock using increasing-current delivery in 3- or 4-week-old rats, and found that the threshold-current of tonic extensor seizures was elevated with age in weeks in the vehicle-treatment groups. While caffeine decreased the threshold-current in every age group of rats, pentylenetetrazole, a γ-aminobutyric acid (GABA)(A) receptor antagonist, significantly decreased them only in 4-week-old rats. On the other hand, ketotifen decreased them only in 3-weeks-old rats. In the 3-week-old rats, neither olopatadine nor fexofenadine had any effect on the threshold-currents of tonic extensor seizures. These results showed that histaminergic neuro-transmission in the brain plays a crucial role in inhibiting seizures in rats soon after weaning, but is no longer effective in rats as they approach sexual maturation. In addition, unlike ketotifen, olopatadine, as well as fexofenadine, do not promote the occurrence of seizures in infant rats.     

Association of ambient air pollution and meteorological factors with primary care visits at night due to asthma attack

Aim

The association of outdoor air pollution and meteorological elements with primary care visits at night due to asthma attack was studied.

Methods

A case–crossover study was conducted in a primary care clinic in Himeji City, Japan. The subjects were 956 children aged 0–14 years who visited the clinic with an asthma attack between the hours of 9 p.m. and 6 a.m. Daily concentrations of particulate matter, ozone, nitrogen dioxide, and a number of meteorological elements were measured, and a conditional logistic regression model was used to estimate odds ratios (ORs) of primary care visits per unit increment of air pollutants or meteorological elements. The analyses took into consideration the effects of seasonality.

Results

Of the 956 children, 73 (7.6 %) were aged <2 years and 417 (43.6 %) were aged 2–5 years. No association between daily ozone levels and primary care visits due to asthma attack at night in the spring or summer was found. An inverse relation between suspended particulate matter and primary care visits due to asthma attack was detected in the winter. ORs in the summer per degree increment in daily mean temperature was 1.31 [95 % confidential interval (CI) 1.09–1.56], and ORs in the autumn per hourly increment in daily hours of sunshine was 0.94 (95 % CI 0.90–0.99).

Conclusion

The findings of our study fail to support any association between daily mean concentration of air pollutant and primary care visits at night. However, we did find evidence indicating that certain meteorological elements may be associated with primary care visits