Optimal Oral Iron Therapy for Iron Deficiency Anemia Among US Veterans.

Importance: Optimal oral iron supplementation strategy is unclear in patients with iron deficiency anemia (IDA) who have either normal kidney function (NKF) or chronic kidney disease (CKD). Objective: To investigate the association of different oral iron supplementation strategies with the change in hemoglobin and iron indices among patients with IDA with either NKF or CKD. Design, Setting, and Participants: This retrospective cohort study was conducted between 2009 and 2019 at nationwide Veterans Health Administration facilities. Eligible participants included veterans with IDA (defined as hemoglobin <12 g/dL and either iron saturation <20% or ferritin <50 ng/mL) who received their first outpatient prescription of oral iron. Patients were further divided into those with NKF (estimated glomerular filtration rate >60 mL/min/1.73 m2) and CKD (estimated glomerular filtration rate ≥15 mL/min/1.73 m2 and <60 mL/min/1.73 m2). Data analysis was conducted from February to October 2023. Exposures: Patients were classified into 3 groups based on their oral iron dosing schedule: daily (once a day), multiple doses per day (MDD; ≥2 times per day), or alternate-day dose (ADD). Main Outcomes and Measures: The primary outcomes were change of hemoglobin, ferritin, total iron binding capacity (TIBC), and iron saturation (ISAT), which were calculated with linear mixed-effects models. Results: A total of 71 677 veterans with IDA (63 202 male [88.2%] and 8475 female [11.8%]; mean [SD] age, 68.47 [13.09] years), including 47 201 with NKF and 24 476 with CKD, were identifed. In patients with NKF in the daily group, hemoglobin increased from baseline (estimated per-30-day difference [SE], 0.27 [0.00] g/dL; P < .001). In comparison with the daily group, hemoglobin increased more in the MDD group (estimated per-30-day difference [SE], 0.08 [0.03] g/dL; P < .001), but no difference was noted in the ADD group (estimated per-30-day difference [SE], -0.01 [0.01] g/dL; P = .38). Ferritin, ISAT, and TIBC results were similar, except TIBC showed less change in the ADD group compared with the daily group. Patients with CKD showed similar trends but smaller magnitudes in changes. Among patients with NKF, the adjusted mean increase in hemoglobin was 1.03 g/dL (95% CI, 1.01-1.06 g/dL) for those in the daily group, 1.38 g/dL (95% CI, 1.36-1.40 g/dL) for those in the MDD group, and 0.93 g/dL (95% CI, 0.84-1.02 g/dL) for those in the ADD group at 90 days. Among patients with CKD, the adjusted mean increase in hemoglobin was 0.71 g/dL (95% CI, 0.68-0.73 g/dL) for those in the daily group, 0.99 g/dL (95% CI, 0.97-1.01 g/dL) for those in the MDD group, and 0.62 g/dL (95% CI, 0.52-0.73 g/dL) for those in the ADD group at 90 days. Conclusions and Relevance: In this retrospective cohort study of veterans with IDA, there was no significant difference in the improvement of hemoglobin and iron indices between daily and ADD groups, but quickest improvement was observed in the MDD group. These findings suggest that the choice of oral iron therapy should depend on the rapidity of response desired and patient preference due to adverse effects.

Impact of renal function recovery utilizing left ventricular assist device support.

BACKGROUND: In heart failure (HF) patients with renal insufficiency (RI), we hypothesize that mechanical circulatory support (MCS) with the left ventricular assist device (LVAD) will promote renal function recovery (RR). We sought to quantify RR with LVAD support over 6 months of follow-up. METHODS: RR data at 30, 90, and 180 days were analyzed for all LVAD patients with RI at the time of surgery. RI was defined as either the use of hemodialysis (HD) or a glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 . RESULTS: Between January 2008 and December 2013, 47 of 127 (37%) LVAD recipients had RI at the time of surgery. The mean preoperative GFR was 48 ± 7. We observed RR at each follow-up, with 30-, 90-, and 180-day mean GFRs of 79 ± 33, 71 ± 31, and 63 ± 21, respectively. The absolute increase in GFR at 30, 90, and 180 days was 34 ± 31, 26 ± 29, and 19 ± 20, respectively (All with P < .001). Four patients (8.5%) with RI required HD preoperatively. Of these, three recovered renal function, the fourth patient died. An additional 13 patients (30.2%) that were previously non-HD-dependent required HD postoperatively. Six of these 13 (46%) recovered renal function during the study period, four (30.7%) remain on HD and three (23%) died. CONCLUSIONS: RI improves significantly with LVAD support. Improvements in GFR are marked in the first 30 days. Among those patients requiring either pre- or post-operative HD, a majority recovered renal function.

Human salt taste and the lingual surface potential correlate.

We have demonstrated in humans that Na(+) evokes changes in the lingual surface potential (LSP) using a custom chamber. To assess whether a relationship exists between the Na(+)-evoked changes in the LSP and the intensity of salt taste, we measured the LSP and the intensity of salt taste simultaneously in 7 subjects using test solutions (50, 100, 300, and 1000 mM NaCl) presented in random order. The evoked LSPs and intensity scores correlated with one another well (r(2) = 0.992, P < 0.01). We then screened 14 subjects for their ability to discriminate between 100 and 300 mM NaCl using the chamber. Three subjects were consistently capable of distinguishing the salt concentrations. In these 3 subjects, an inhibitor of the epithelial sodium channel, amiloride (10 muM), blocked the ability to distinguish salt concentrations and affected the LSP. These data suggest that the LSP may be a component of the signal transduction system involved in human salt taste. In adept salt tasters, an amiloride-sensitive mechanism appears to have a role in distinguishing salt concentrations.

Evaluation of an in vitro dialysis system to predict drug removal.

BACKGROUND: Variation in the extent of drug removal under different dialysis conditions presents a challenge for prediction of drug elimination and dosage regimen adjustment during haemodialysis (HD). Dependence on clinical pharmacokinetic studies in HD patients for dosing guidelines is problematic given the increasing number of dialysers with variable rates of drug removal. Thus, the purpose of this study was to characterize drug removal using an in vitro system and to evaluate its reliability to predict in vivo elimination by HD using vancomycin (VANC) as a model drug. METHODS: In vitro dialysis was performed for 2 h (volume 4.0 l normal saline, initial VANC concentration 30 mg/l, flow rate 300 ml/min, dialysate flow 800 ml/min) using four different dialysers: polymethylmethacrylate (BK-2.1 U), polysulfone (F-80), AN69 (Filtral-20) and hemophan (COBE 700HE). The in vitro dialysis clearance for VANC (CL(D)) for the polysulfone dialyser was compared with values determined in eight HD patients. In vitro VANC CL(D) for all dialysers was compared with the clearance and KoA for B12 reported for each dialyser. RESULTS: In vitro VANC CL(D) values were 93+/-11 ml/min for the polymethylmethacrylate BK-2.1, 136+/-7 ml/min for the AN69, 65+/-9 ml/min for the hemophan COBE 700HE and 143+/-10 ml/min for the polysulfone F80. The CL(D) for the polysulfone F80 was not statistically different from the in vivo CL(D) of 135+/-18 ml/min (P = 0.48). In vitro VANC CL(D) correlated with the B12 CL(D) (r(2) = 0.77) and the B12 KoA (r(2) = 0.63) reported for each dialyser. CONCLUSION: VANC CL(D) in HD patients for the polysulfone dialyser was correctly predicted using the in vitro dialysis system. Use of this system may be superior to estimations of drug CL(D) based on dialyser information provided by the manufacturer for compounds of similar molecular weight.

Na+-H+ exchange activity in taste receptor cells.

mRNA for two Na(+)-H(+)-exchanger isoforms 1 and 3 (NHE-1 and NHE-3) was detected by RT-PCR in fungiform and circumvallate taste receptor cells (TRCs). Anti-NHE-1 antibody binding was localized to the basolateral membranes, and the anti-NHE-3 antibody was localized in the apical membranes of fungiform and circumvallate TRCs. In a subset of TRCs, NHE-3 immunoreactivity was also detected in the intracellular compartment. For functional studies, an isolated lingual epithelium containing a single fungiform papilla was mounted with apical and basolateral sides isolated and perfused with nominally CO(2)/HCO(3)(-)-free physiological media (pH 7.4). The TRCs were monitored for changes in intracellular pH (pH(i)) and Na(+) ([Na(+)](i)) using fluorescence ratio imaging. At constant external pH, 1) removal of basolateral Na(+) reversibly decreased pH(i) and [Na(+)](i); 2) HOE642, a specific blocker, and amiloride, a nonspecific blocker of basolateral NHE-1, attenuated the decrease in pH(i) and [Na(+)](i); 3) exposure of TRCs to basolateral NH(4)Cl or sodium acetate pulses induced transient decreases in pH(i) that recovered spontaneously to baseline; 4) pH(i) recovery was inhibited by basolateral amiloride, 5-(N-methyl-N-isobutyl)-amiloride (MIA), 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), HOE642, and by Na(+) removal; 5) HOE642, MIA, EIPA, and amiloride inhibited pH(i) recovery with K(i) values of 0.23, 0.46, 0.84, and 29 microM, respectively; and 6) a decrease in apical or basolateral pH acidified TRC pH(i) and inhibited spontaneous pH(i) recovery. The results indicate the presence of a functional NHE-1 in the basolateral membranes of TRCs. We hypothesize that NHE-1 is involved in sour taste transduction since its activity is modulated during acid stimulation.

Salt-evoked lingual surface potential in humans.

Salt sensing in animals involves the epithelial sodium channel (ENaC). If ENaC were involved in human salt sensing, then the lingual surface potential (LSP) would hyperpolarize when exposed to sodium. We developed a chamber to measure the LSP while different solutions superfused the surface of the tongue and a technique to adjust for the junction potentials induced by varying salt concentrations. Changing the superfusion solution from rinse solution (30 mM KCl) to 300 mM NaCl (+30 mM KCl) caused the LSP to hyperpolarize by 10.1 +/- 0.7 mV (n = 13, P < 0.001). With repeated challenge the LSP response was reproducible. Increasing the Na concentration from 100 to 600 mM increased hyperpolarization by 35 +/- 4.8% (n = 9, P < 0.001). To examine whether amiloride affects the LSP, 0.1 mM amiloride was added to 300 mM NaCl; it reduced the hyperpolarization by 18.5 +/- 4.3% (P < 0.005, n = 11). However, the amiloride effect was not uniform: in six volunteers, amiloride inhibited the LSP by as much as 42%, while in five subjects, amiloride inhibited <5% of the LSP. In an amiloride sensitive volunteer, amiloride exerted 50% of its effect at 1 microM. In conclusion, we have demonstrated that the LSP can be measured in humans, that Na hyperpolarizes the LSP, that increasing the Na concentration increases LSP hyperpolarization, and that amiloride inhibits the Na evoked LSP in some humans. While ENaC is involved in sensing salt, its role appears to vary among individuals.

Successful treatment of steroid-resistant minimal change disease with mycophenolate mofetil.

Mycophenolate mofetil has been reported to be effective in the treatment of steroid-responsive minimal change disease. We report a case of steroid- and cyclosporin-resistant minimal change disease with severe nephrotic syndrome that responded to mycophenolate mofetil with complete remission. The patient remains in complete remission 1 year after the discontinuation of mycophenolate mofetil. The presented case argues for the need of a prospective controlled study with the goal of evaluating the efficacy of mycophenolate mofetil in the therapy of steroid-resistant minimal change disease.