The possibility of using effluent ionized calcium to assess regional citrate anticoagulation in continuous renal replacement therapy.

AIM: This study aimed to investigate whether effluent ionized calcium was an appropriate indicator to assess anticoagulant effect in continuous renal replacement therapy with regional citrate anticoagulation instead of post-filter ionized calcium. METHODS: In total, 48 paired samples of effluent fluid and post-filter blood were obtained from critically ill patients who required continuous renal replacement therapy. All samples were taken for ionized calcium measurements and were assessed by point-of-care analyzer. Correlations and agreements between two methods were performed by Pearson linear analysis and Bland-Altman analysis accordingly. RESULTS: The mean post-filter ionized calcium was 0.42 ± 0.12 mmol/L, and mean ionized calcium level of effluent fluid was 0.39 ± 0.11 mmol/L. The ionized calcium level of effluent fluid was significantly correlated with post-filter ionized calcium in all continuous renal replacement therapy patients. Bland-Altman analysis showed that the mean difference of ionized calcium between two sampling sites in all continuous renal replacement therapy patients was -0.02 mmol/L with 95% confidence interval ranging from -0.09 to 0.04 mmol/L. The significant correlations and agreements were also demonstrated in continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, and continuous veno-venous hemodiafiltration modalities separately. CONCLUSION: The effluent ionized calcium could be a considerable substitute for post-filter ionized calcium to monitor the validity of regional citrate anticoagulation in continuous renal replacement therapy with less blood loss.

Calcium supplementation in CVVH using regional citrate anticoagulation.

INTRODUCTION: Calcium supplementation is one of the most important factors in maintaining the safety and efficacy of regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). The aims of this study were to assess the determinants of calcium requirements in RCA-CVVH and to simplify the calcium supplementation approach. METHODS: Our study consisted of two parts. The first part was a discovery phase to determine the key factors of calcium supplementation. Twenty critically ill patients who required RCA-CVVH were enrolled in this part. Systemic citrate, total calcium, protein-bound calcium, and ionized calcium concentrations were serially measured using the traditional RCA protocol. A two-phase calcium supplementation protocol was then proposed, and algorithms were developed for calcium supplementation. The second part of the study was the validation phase. Another 97 critically ill patients were enrolled and were treated with RCA-CVVH using the new version of the calcium supplementation protocol. FINDINGS: The loss of calcium flux in the extracorporeal circuit and the increase in citrate-calcium complexes in vivo were the main determinants of the required calcium supplementation. In the CVVH mode, the rate of calcium infusion had to be reduced after systemic citrate level reached a steady state. With the aid of mathematical models, systemic calcium levels could be stably maintained in the normal range, and the frequencies of calcium monitoring were reduced. DISCUSSION: Calcium supplementation during RCA-CVVH undergoes two phases. We propose mathematical models to quantify the need for calcium supplementation, which enable individualization of the RCA prescription and simplify the management of RCA in the CVVH mode.

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy.

BACKGROUND/AIMS: Clinical manifestation and renal histology serve as the current "gold standard" for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. METHODS: Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal -miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-ß1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. RESULTS: Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-ß1 was inversely correlated (r = -0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. CONCLUSIONS: Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-ß and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.

Optimized Calcium Supplementation Approach for Regional Citrate Anticoagulation.

BACKGROUND: It has been confirmed that regional citrate anticoagulation (RCA) plays an effective role in extracorporeal anticoagulation. The current trial-and-error calcium supplementation approach, with intensive monitoring of calcium levels, restricts the widespread use of RCA. Therefore, this study aimed to optimize the calcium supplementation approach for RCA. METHODS: Patients requiring RCA treatment for various reasons were included. Citrate was infused into the arterial port, and the ionized calcium levels in the extracorporeal circulation tubes and body were monitored to maintain them within the target range. Linear regression equations between the clearance of non-protein bound calcium (n-Ca) and prescribed effluent rate were determined; the ratio of the n-Ca concentration to total calcium concentration (fa) after the infusion of citrate was also calculated. Then, we estimated a simplified calcium supplementation approach. RESULTS: Positive correlations were found between the clearance of n-Ca and effluent rate both during continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemofiltration (CVVH; R2: 0.66 and 0.65, respectively, p < 0.01). The fa values at the pre-filter point and after infusion of citrate were constants, but the values differed from CVVHD to CVVH. For CVVHD, fa was 0.93, and for CVVH, fa was 0.80. Using the extracorporeal removal characteristics of n-Ca, the amount of extracorporeally removed calcium per mmol per hour can be quantified with a simplified equation. CONCLUSION: The optimized calcium supplementation approach could provide a more precise and practical method to estimate the amount of extracorporeal calcium removal with regard to different modalities and dosages of RCA.

Involvement of HDAC6 in ischaemia and reperfusion-induced rat retinal injury.

BACKGROUND: The role of histone deacetylases 6 (HDAC6) has been elucidated in various neurodegenerative diseases. However, the effect of HDAC6 on retinal degenerative processes remains unknown. The aim of this study was to elucidate the potential role of HDAC6 in the retinal ischaemia and reperfusion (I/R) injury model. METHODS: The retinal pathological lesion was evaluated by haematoxylin and eosin (H&E) staining. HDAC expression or activity was detected by immunohistochemistry, Western blotting assays or colorimetric assays. The expression of apoptotic- and autophagic- related proteins were quantified by Western blotting and RT-PCR. The expression of peroxiredoxin 2 (Prx2) was determined by RT-PCR and ELISA. The levels of acetylated α-tubulin and acetylated histone 3 in the retina were assayed by Western blotting. RESULTS: We found that I/R-induced reduction of the retinal thickness was ameliorated, and the survival of RGCs was increased by the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) as well as by tubacin (an HDAC6 selective inhibitor). The decreased expression of THY (thymus cell antigen) in the I/R-induced retinas was also reversed by TSA and tubacin. Elevated HDAC6 expression and activity in the retina from I/R injury were significantly inhibited by tubacin, which also attenuated I/R-mediated apoptosis by decreasing TUNEL-positive RGCs and Bax expression and increasing Bcl-2 expression. Additionally, tubacin increased the expression of autophagy-related gene Beclin 1 and microtubule-associated protein 1 light chain 3B (LC3B) and the levels of Prx2. Furthermore, the protective effect of tubacin was associated with acetylated α-tubulin and was independent of acetylated histone 3. CONCLUSIONS: Our findings suggest that tubacin exhibits neuroprotective effects after I/R retinal injury, and HDAC6 may be a potential therapeutic target for the retinal neurodegenerative disease of glaucoma.

Prognostic Value of the Delivery Dialysis Dose on Twice-Weekly Hemodialysis Patients.

BACKGROUND: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. METHODS: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). RESULTS: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). CONCLUSIONS: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.