Early response to erythropoiesis-stimulating agents in non-dialysis chronic kidney disease patients

Background

Renal anemia complicated with chronic kidney disease is usually treated with erythropoiesis-stimulating agents (ESAs). However, few studies have compared the early response of hemoglobin (Hb) to different kinds of ESAs.

Methods

The effects of three types of ESAs—epoetin alfa or beta (EPO), darbepoetin alfa (DPO), and epoetin beta pegol (EPObp)—on renal anemia were followed in 416 pre-dialysis chronic kidney disease (CKD) patients. After the initial 12-week administration of ESAs, ΔHb/ESA dose/kg was calculated as an index of efficacy of each ESA. Furthermore, independent variables associated with ΔHb/ESA dose/kg (dependent variable) were determined using multiple linear regression analysis. The ten independent variables selected for analysis were: presence of diabetic nephropathy, estimated glomerular filtration rate (eGFR), Hb, albumin, iron (Fe), transferrin saturation (TSAT), ferritin, phosphate (P), intact parathyroid hormone (iPTH), and C-reactive protein.

Results

The efficacy of DPO and EPObp were similar and higher than EPO. TSAT was most strongly correlated with ΔHb/EPO dose/kg in all three types of ESAs. Other significant independent factors were Hb, albumin, P, iPTH, and diabetic nephropathy in the EPO group, eGFR in the DPO group, and Fe in the EPObp group. The adjusted coefficient of determination (R ²) ranged from 0.415 to 0.520 in the three ESA groups.

Conclusions

The study results suggest that TSAT is the best predictor of the initial 12-week responsiveness to ESA, irrespective of the type. Variables not investigated in this study also affect responsiveness to ESA in Japanese pre-dialysis CKD patients.

     

Risk factors associated with relapse or infectious complications in Japanese patients with microscopic polyangiitis

Background

The prevention of relapse and infection complications during remission maintenance therapy is required to improve the prognosis of patients with microscopic polyangiitis (MPA) showing rapidly progressive glomerulonephritis (RPGN). The clinicopathological characteristics of patients with ANCA-positive MPA were examined to determine the risk factors for relapse or infectious complications after remission induction therapy.

Patients and methods

The study population consisted of 52 patients diagnosed as ANCA-positive MPA showing RPGN from 2002 to 2012, after publication of the Japanese guideline for RPGN. The clinicopathological findings were examined between the presence and absence of relapse or infectious complications.

Results

The value of vasculitis damage index (VDI) was high for the relapse group and VDI value was identified as the leading factor associated with relapse [hazard ratio (HR) 3.36, 95 % confidence interval (CI) 1.58–7.12, P < 0.01]. On the other hand, the values of Birmingham Vasculitis Activity Score, clinical grade category of RPGN at diagnosis, and VDI at remission were high in the infectious group. Furthermore, clinical grade category of RPGN was the leading factor associated with infectious complications (HR 5.30, 95 % CI 1.41–19.9, P = 0.01).

Conclusion

The disease activity at diagnosis and severity of organ damage at remission were associated with relapse and infectious complications during remission maintenance therapy and infectious complication affected kidney survival and all-cause mortality in patients with ANCA-positive MPA exhibiting RPGN.

     

Relationships between insulin release and taste

Tasting sweet food elicits insulin release prior to increasing plasma glucose levels, known as cephalic phase insulin release (CPIR). The characteristic of CPIR is that plasma insulin secretion occurs before the rise of the plasma glucose level. In this experiment, we examined whether taste stimuli placed on the tongue could induce CPIR. We used female Wistar rats and five basic taste stimuli: sucrose (sweet), sodium chloride (salty), HCl (sour), quinine (bitter) or monosodium glutamate (umami). Rats reliably exhibited CPIR to sucrose. Sodium chloride, HCl, quinine, or monosodium glutamate did not elicit CPIR. The non-nutritive sweetener saccharine elicited CPIR. However, starch, which is nutritive but non-sweet, did not elicit CPIR although rats showed a strong preference for starch which is a source of glucose. In addition, we studied whether CPIR was related to taste receptor cell activity. We carried out the experiment in rats with bilaterally cut chorda tympani nerves, one of the gustatory nerves. After sectioning, CPIR was not observed for sweet stimulation. From these results, we conclude that sweetness information conducted by thistaste nerve provides essential information for eliciting CPIR.     

Stabilization Mechanism of Roxithromycin Tablets Under Gastric pH Conditions

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of 3 widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A, and azithromycin. The results indicated that not only CAM but also RXM gelated under acidic conditions. Erythromycin A and azithromycin did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that 2 of the 4 macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides.     

In situ localization of gelatinolytic activity during development and resorption of Meckel's cartilage in mice

Degradation of Meckel's cartilage in the middle portion is accompanied by hypertrophy and death of chondrocytes, calcification of the cartilaginous matrix, and chondroclastic resorption. We hypothesize that the gelatinolytic activity of matrix metalloproteinases (MMPs) largely contributes to the degradation of extracellular matrix (ECM) in the process. The activity in Meckel's cartilage of mouse mandibular arches at embryonic days 14-16 (E14-E16) was examined by a combination of in situ zymography (ISZ), using quenched fluorescent dye-labeled gelatin as a substrate, with CTT (a selective inhibitor of MMP-2 and -9) or with EDTA (a general MMP inhibitor). On E14 and E15, ISZ showed fluorescence in the perichondrium, in the intercellular septa between chondrocytes, and in the nucleus of chondrocytes. CTT attenuated fluorescence, and EDTA eliminated it. On E16, calcified cartilaginous matrix showed intense fluorescence, and dot-like fluorescence was observed in as-yet uncalcified intercellular septa, even after CTT treatment. EDTA inhibited fluorescence, but unexpectedly intense fluorescence was found in the cytoplasm of hypertrophic chondrocytes facing the resorption front. MMP-2, -9, and -13 immunoreactivity was detected in the perichondrium and chondrocytes of Meckel's cartilage. These findings suggest that MMPs and other proteinases capable of degrading gelatin play an integral role in the development, calcification, and resorption of Meckel's cartilage through ECM reconstitution.     

Laparoscopic trans-peritoneal hernioplasty (TAPP) is useful for obturator hernias: report of a Case

A 71-year-old female presented to our hospital due to pain from the right hip joint to the lower abdomen. The pain had suddenly appeared and spontaneously disappeared more than 10 times during the past 2 years. She had visited many hospitals, but remained undiagnosed. The patient underwent a computed tomography (CT) scan of the pelvis, and a soft tissue shadow was seen between the external obturator and pectineal muscles. She was diagnosed with a right obturator hernia and underwent elective repair by laparoscopic trans-peritoneal hernioplasty (TAPP). 1 year has passed since the surgery, without any recurrence of the abdominal pain. Obturator hernias are rare, and most cases are found as incarcerated hernias. It is rare to find an obturator hernia without intestinal obstruction, or with the recurrent pain as in our case. We herein report a case in which an obturator hernia was undiagnosed and intermittent pain was experienced for 2 years prior to TAPP, which appears to have successfully treated the hernia.