Effect of ferric citrate hydrate on FGF23 and PTH levels in patients with non-dialysis-dependent chronic kidney disease with normophosphatemia and iron deficiency.

BACKGROUND: In patients with normophosphatemia with chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) increase urinary phosphate excretion while maintaining serum phosphate within the normal range. Recent reports have shown that, in this stage, phosphate binders do not decrease serum FGF23 and PTH levels. Iron deficiency promotes transcription of FGF23 and iron-supplementation for iron deficiency decreases serum FGF23 levels. We hypothesized that ferric citrate hydrate, an iron-based phosphate binder, will decrease serum FGF23 levels in patients with non-dialysis-dependent CKD with normophosphatemia and iron deficiency. METHODS: This was a single-center, randomized, open-label interventional study. The inclusion criteria were as follows: (1) eGFR < 45 mL/min/1.73 m2, (2) normophosphatemia, (3) iron deficiency. Patients were assigned to the following groups: ferric citrate hydrate (FCH)-group, sodium ferrous citrate (SFC)-group, and control-group. After 12 weeks of intervention, we evaluated serum FGF23 levels and CKD-mineral bone disorder markers. RESULTS: There were 17 patients in the FCH-group, 14 in the SFC-group, and 9 in the control-group. The serum ferritin levels increased in the FCH-group and SFC-group compared with baseline. Serum FGF23 levels were unchanged; the change in the FCH-group was from 52.91 RU/mL (42.48-72.91) to 40.00 RU/mL (30.30-58.13) (P = 0.1764). However, in the FCH-group, serum PTH levels significantly decreased compared with baseline, from 68.00 pg/mL (49.00-141.00) to 60.00 pg/mL (44.00-144.00) (P = 0.0101). CONCLUSION: Iron-based phosphate binder did not decrease serum FGF23 levels, but decreased serum PTH levels.

A case of xanthinuria type I with a novel mutation in xanthine dehydrogenase.

Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal recessive disorder that is characterized by impaired renal tubular uric acid transport, or by xanthinuria, a rare autosomal recessive disorder caused by a deficiency of xanthine dehydrogenase (XDH; xanthinuria type I) or by a deficiency of both XDH and aldehyde oxidase (xanthinuria type II). In contrast to renal hypouricemia, which sometimes leads to exercise-induced acute kidney injury (EIAKI), xanthinuria has not been associated with this disorder. We report here a case of xanthinuria type I due to a compound heterozygous mutation. A 46-year-old woman was found to have undetectable plasma and urinary levels of uric acid. She had no symptoms and no history of EIAKI. Xanthinuria type I was diagnosed following the allopurinol loading test. Mutation analysis revealed a compound heterozygous mutation [c.305A>G (p.Gln102Arg) and c.2567delC (p.Thr856Lysfs*73)] in the XDH gene. Of these two mutations, the former is novel. The patient did not exhibit EIAKI. However, because xanthinuria is a rare disease, the identification of additional cases is necessary to determine whether this disease is complicated with EIAKI.

Prediction of a sustained viral response in chronic hepatitis C patients who undergo induction therapy with double filtration plasmapheresis plus interferon-ß/ribavirin.

The aim of the present study was to determine predictors of a sustained virological response (SVR) with a regimen of double filtration plasmapheresis (DFPP) combined with interferon-ß plus ribavirin (IFN-ß/RBV) induction therapy prior to pegylated (PEG-IFN/RBV) standard of care (SOC) therapy for patients with chronic hepatitis C who had experienced SOC treatment failure. Predictors of a SVR were analyzed in chronic hepatitis C patients with genotype 1b hepatitis C virus (HCV), who had a high viral load. The patients had been unresponsive to previous IFN therapy and underwent induction therapy with IFN-ß/RBV plus DFPP, which was performed five times during the same period, followed by PEG-IFN/RBV. In total, 10 patients received the combination DFPP plus IFN-ß/RBV induction therapy prior to PEG-IFN/RBV therapy for the treatment of chronic hepatitis C. Two weeks after treatment initiation, a decrease in the HCV RNA levels of ≥2 log IU/ml occurred in 9/10 patients (90%), while a decrease of ≥4 log IU/ml was observed in 4/10 patients (40%). The HCV RNA levels at week 2 after treatment initiation in the SVR and non-SVR patients decreased by 5.0±0.8 and 2.9±1.1 log IU/ml, respectively. Despite no response to previous IFN therapy, three of the 10 patients (30%) experienced a SVR. The results indicated that a rapid virological response ensued following IFN-ß/RBV induction and DFPP supplementary therapy. Although the level of interleukin-28B is an important predictor of a SVR, a decrease in the HCV RNA volume of ≥4 log IU/ml at week 2 after the initial treatment is also an important predictor. Therefore, rapid virological reduction using DFPP, in addition to IFN-ß/RBV induction therapy, is an important predictor of a SVR.

Marked elevation of serum hyaluronan levels in collagenofibrotic glomerulopathy.

Collagenofibrotic glomerulopathy is a rare glomerular disease characterized by the massive deposition of type III collagen in mesangial and subendothelial spaces. We observed markedly increased serum hyaluronan levels in patients with collagenofibrotic glomerulopathy; levels in three patients were more than 1,000-times greater than the normal upper limit. However, one kidney transplant patient had normal serum hyaluronan levels. We found that serum levels and activities of the enzyme hyaluronidase were normal, and hyaluronan was not markedly deposited in the mesangial or subendothelial spaces. Our findings suggest that serum hyaluronan levels may be a specific diagnostic marker of collagenofibrotic glomerulopathy, and kidney transplantation may alleviate marked increases in serum hyaluronan.

Complete early virological response was highly achieved by double filtration plasmapheresis plus IFN-beta induction therapy for HCV-1b patients with relapse or no response after previous IFN therapy.

The efficacy of double filtration plasmapheresis (DFPP) plus interferon (IFN)-ß induction therapy was preliminarily investigated in re-treated patients with chronic genotype 1b hepatitis C and high viral load (patients with relapse or non-response to previous IFN therapies). In eight patients with chronic hepatitis C, DFPP was performed five times over 2 weeks during IFN-ß therapy, and 3 MU of IFN-ß was administered twice a day for 2 weeks. Combination therapies with ribavirin and pegylated IFN-α2b (PEG-IFN-α2b) or pegylated IFN-α2a (PEG-IFN-α2a) were subsequently used. After 4 weeks, hepatitis C virus (HCV)-RNA tended to be more greatly decreased with DFPP combination therapy than with previous IFN therapy (4.5 ± 2.0 log(10) IU/mL vs. 2.9 ± 1.2 log(10) IU/mL). Rates of both rapid virological response and complete early virological response were significantly higher with DFPP and IFN-ß induction therapy than with previous IFN therapy. DFPP plus IFN-ß induction therapy produced a great reduction of viral load during the early stage of treatment and achieved a high early virological response, suggesting that this combination therapy may be useful as a new treatment modality for chronic hepatitis C patients in difficult-to-treat states. This combination may contribute to sustained virological response (SVR). The effects of DFPP on SVR and its significance remain to be clarified.

Human glomerulonephritis accompanied by active cellular infiltrates shows effector T cells in urine.

Leukocyturia is associated with postinfectious glomerulonephritis (GN), interstitial nephritis, and renal allograft rejection. In addition, prominent infiltration of T cells and macrophages is commonly observed in the renal tissues of patients with GN, accompanied by cellular crescent formation and/or interstitial cell infiltration. Because these infiltrating T cells were thought to participate in the development of the diseases and to appear in the urinary space while functioning as effector cells in the renal inflammatory lesion, the study focused on the characterization of T cells that appeared in urine. Freshly voided urine cells were analyzed by flow cytometry to determine their phenotype and by reverse transcriptase-PCR to detect cytokine mRNA. In urine from patients with different forms of GN, including IgA nephropathy, Henoch-Schönlein purpura nephritis, and anti-neutrophil cytoplasmic antibody-associated GN, T cells appeared together with macrophages. The urine T cells were mainly CD45RA(-), CD45RO(+), and CD62L (L-selectin)(-), which are the phenotypic features of effector T cells. In agreement with this finding, T cells infiltrating glomeruli, crescents, and tubulointerstitial lesions were also effector type. Moreover, these urine cells expressed mRNA of the T helper lymphocyte 1 cytokines, interleukin-2, and/or interferon-gamma. These findings suggest that the appearance of effector T cells in urine may reflect the cellular immune reaction that occurs in the kidneys of patients with GN accompanied by active cell infiltration.

LCAT-dependent conversion of prebeta1-HDL into alpha-migrating HDL is severely delayed in hemodialysis patients.

Prebeta1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37 degrees C incubation, plasma prebeta1-HDL decreases over time due to its conversion to alpha-migrating HDL by lecithin:cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is delayed in hemodialysis patients, prebeta1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37 degrees C incubation with and without the LCAT inhibitor. It was found that the baseline prebeta1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 +/- 21.4 versus 19.8 +/- 6.7 mg/L apoAI; P < 0.001). After 2-h incubation, the LCAT-dependent decrease in prebeta1-HDL in hemodialysis patients was about one-third of that in the controls (30 +/- 27 versus 97 +/- 17% of baseline; P < 0.01). The LCAT-dependent rate of decrease in prebeta1-HDL levels (DR(prebeta1)) was the same for samples from hemodialysis patients exhibiting normal (> or =1.03 mmol/L) and low HDL-cholesterol levels (32 +/- 32 versus 28 +/- 23% of baseline; NS). DR(prebeta1) was positively correlated with LCAT activity (r = 0.617; P < 0.001). In conclusion, the LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of prebeta1-HDL may accelerate atherosclerosis in hemodialysis patients.