Parathyroidectomy Improves the Consumption of Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease (ESRD) patients, and it can suppress erythropoiesis. We aimed to investigate the relationship between the consumption of erythropoiesis-stimulating agents (ESAs) and parathyroidectomy (PTX) in ESRD patients with SHPT and to determine the predictors for anemia improvement. The current standard of chronic kidney disease anemia therapy relies on the prescription of iron supplementation, and ESA. We retrospectively analyzed 81 ESRD patients with PTX at Ditmanson Medical Foundation Chiayi Christian Hospital from July 2004 to Dec 2018. The requirement of ESA therapy markedly declined from a dose of 41.6 (interquartile range [IQR], 0−91.2) to 10.3 (IQR, 0−59.5, p = 0.001) unit/kg/week. In addition, 63.7% of patients required iron replacement therapy preoperatively and the proportion reduced to 52.5% after PTX (p < 0.001). The hemoglobin (Hb) level showed an insignificant change from a median value of 10.7 g/dL (9.5−11.6 g/dL) before PTX to 10.5 g/dL (9.6−11.2 g/dL) at 6 months after PTX. A preoperative Hb level ≤ 10 mg/dL (odds ratio [OR], 20.1; 95% confidence interval [CI], 4.71−125, p < 0.001) and transferrin saturation (TSAT) < 25% (OR, 12.8; 95% CI, 2.51−129, p < 0.001) were predictors for anemia improvement. Our study demonstrated that PTX markedly decreased the requirement of ESA. Patients with a low preoperative Hb level or low TSAT showed an increase in the Hb level after PTX. PTX may be considered not only for SHPT with refractory anemia but also for high ESA-dependent patients.

Older Age and High Serum Ferritin Levels Associated With the Risk of Chronic Cytopenia in Hemodialysis Patients.

Leukopenia or thrombocytopenia is sometimes observed in end-stage renal disease (ESRD) patients, but the association between chronic leukopenia or thrombocytopenia and hemodialysis (HD) is still unclear. We aimed to investigate the incidence of chronic leukopenia or thrombocytopenia in patients with ESRD who received HD and to determine the risk factors of this complication. We retrospectively analyzed ESRD patients treated with HD at Ditmanson Medical Foundation Chia-Yi Christian Hospital in 2018. The risk factors for the occurrence of chronic leukopenia and thrombocytopenia were analyzed by Cox regression models. Of the 473 patients in our study cohort, 46 (9.7%) patients had a hematologic abnormality, including 18 patients with chronic leukopenia, 18 with chronic thrombocytopenia, and 10 with pancytopenia. Multivariate analysis revealed that patient age ≥60 years at the initiation of dialysis was a significant predictor for both chronic leukopenia [adjusted hazard ratio (aHR), 2.71; 95% confidence interval (CI), 1.06-6.89] and chronic thrombocytopenia (aHR, 2.83; 95% CI, 1.08-7.35). Chronic liver disease (aHR, 3.31; 95% CI, 1.27-8.61) and serum ferritin levels >800 mg/dl (aHR, 3.29; 95% CI, 1.29-8.39) were risk factors for chronic thrombocytopenia. A trend showed that vitamin D from intravenous supplementation (aHR, 0.13; 95% CI, 0.01-1.16, P = 0.066) and serum phosphorous level (aHR, 0.73; 95% CI, 0.53-1.02, P = 0.068) may be associated with chronic thrombocytopenia. Our study demonstrated that hematological abnormality was a long-term complication of HD. These results reveal that older patients with HD and high serum ferritin levels are at an elevated risk for chronic cytopenia. Healthcare professionals should be aware of this risk when treating HD patients in order to improve their prognosis.

Commercial AHAS-inhibiting herbicides are promising drug leads for the treatment of human fungal pathogenic infections.

The increased prevalence of drug-resistant human pathogenic fungal diseases poses a major threat to global human health. Thus, new drugs are urgently required to combat these infections. Here, we demonstrate that acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway, is a promising new target for antifungal drug discovery. First, we show that several AHAS inhibitors developed as commercial herbicides are powerful accumulative inhibitors of Candida albicans AHAS (Ki values as low as 800 pM) and have determined high-resolution crystal structures of this enzyme in complex with several of these herbicides. In addition, we have demonstrated that chlorimuron ethyl (CE), a member of the sulfonylurea herbicide family, has potent antifungal activity against five different Candida species and Cryptococcus neoformans (with minimum inhibitory concentration, 50% values as low as 7 nM). Furthermore, in these assays, we have shown CE and itraconazole (a P450 inhibitor) can act synergistically to further improve potency. Finally, we show in Candida albicans-infected mice that CE is highly effective in clearing pathogenic fungal burden in the lungs, liver, and spleen, thus reducing overall mortality rates. Therefore, in view of their low toxicity to human cells, AHAS inhibitors represent a new class of antifungal drug candidates.