Correcting low magnesia levels in hemodialysis by higher dialysate magnesium ABOUT THE AUTHORS

Abstract: Albeit low magnesium levels are a known mortality factor in dialysis patients, low (0.5 mmol/l Mg) dialysate magnesium is routinely used. The apprehension that hypermagnesemia will be induced by higher dialysate magnesium prevents its use. How high patients′ magnesium levels actually are is mostly unknown, since magnesium levels are not even routinely measured. Thus, we determined the predialytic magnesium levels in 205 outpatients, dialysed with a magnesium concentration of 0.5 mmol/l and found them lower compared to age matched non dialysis patients. In another group of 54 patients we demonstrated that dialysis itself causes a significant loss of magnesium. We tested different magnesium substitutions and found higher dialysate magnesium levels of 0.75 mmol/l convenient to handle. To study the safety of such dialysate magnesium levels, we utilized a dialysate magnesium of 0.75 mmol/l in 34 patients over 30 months and heeded for complications due to hypermagnesemia. Before substitution, magnesium levels were in the low range of 0.53 mmol/l. The elevated magnesium dialysate increased serum levels to 0.63 mmol/l and was not associated to any apparent side effects or significant changes in calcium, phosphate or iPTH levels. In summary, a higher dialysate magnesium concentration is safe and averts the loss of magnesium during dialysis

Correcting low magnesia levels in hemodialysis by higher dialysate magnesium

Albeit low magnesium levels are a known mortality factor in dialysis patients, low (0.5 mmol/l Mg) dialysate magnesium is routinely used. The apprehension that hypermagnesemia will be induced by higher dialysate magnesium prevents its use. How high patients′ magnesium levels actually are is mostly unknown, since magnesium levels are not even routinely measured. Thus, we determined the predialytic magnesium levels in 205 outpatients, dialysed with a magnesium concentration of 0.5 mmol/l and found them lower compared to age matched non dialysis patients. In another group of 54 patients we demonstrated that dialysis itself causes a significant loss of magnesium. We tested different magnesium substitutions and found higher dialysate magnesium levels of 0.75 mmol/l convenient to handle. To study the safety of such dialysate magnesium levels, we utilized a dialysate magnesium of 0.75 mmol/l in 34 patients over 30 months and heeded for complications due to hypermagnesemia. Before substitution, magnesium levels were in the low range of 0.53 mmol/l. The elevated magnesium dialysate increased serum levels to 0.63 mmol/l and was not associated to any apparent side effects or significant changes in calcium, phosphate or iPTH levels. In summary, a higher dialysate magnesium concentration is safe and averts the loss of magnesium during dialysis

Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal agrin fragment levels in end-stage renal disease patients

C-terminal agrin fragment (CAF, 22 kDa) has been shown to be a promising new rapid biomarker for kidney function. This study evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF concentrations in patients with end-stage renal disease (ESRD). A total of 36 patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high-flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H membrane). On a midweek session, blood samples were obtained before, at halftime, and post-treatment. Dialysate samples were obtained 4 times during treatment. Serum and dialysate CAF, cystatin C, urea, and creatinine concentrations were measured. Reduction ratios (RRs), total solute removal, overall dialytic clearance, and instantaneous dialytic clearance at halftime were calculated and compared. Although HD/Elisio19H and HDF/Elisio19H treatments significantly reduced CAF concentrations (RR 46.6 ± 9.1% and 57.6 ± 11.7%, respectively, P = 0.018 and P = 0.001), HD/Fx60 treatment did not remove CAF from serum (RR 2.4 ± 15.4%, P = 0.25), there was no relevant CAF detection in dialysate. In the HD/Fx60 group, the RR of CAF was significantly lower compared with cystatin C, urea, and creatinine, in which significant removal was detected (37.9 ± 14.8%, 65.0 ± 10.7%, and 56.0 ± 9.8%, respectively, P < 0.001). CAF is a new biomarker for kidney function whose serum concentration is not influenced by conventional high-flux HD using Fx60 membrane. It might therefore represent a promising dialysis-independent biomarker for evaluation of kidney function, for example, in acute kidney failure

Transpulmonary thermodilution (TPTD) before, during and after Sustained Low Efficiency Dialysis (SLED). A Prospective Study on Feasibility of TPTD and Prediction of Successful Fluid Removal.

Acute kidney injury (AKI) is common in critically ill patients. AKI requires renal replacement therapy (RRT) in up to 10% of patients. Particularly during connection and fluid removal, RRT frequently impairs haemodyamics which impedes recovery from AKI. Therefore, "acute" connection with prefilled tubing and prolonged periods of RRT including sustained low efficiency dialysis (SLED) has been suggested. Furthermore, advanced haemodynamic monitoring using trans-pulmonary thermodilution (TPTD) and pulse contour analysis (PCA) might help to define appropriate fluid removal goals.Since data on TPTD to guide RRT are scarce, we investigated the capabilities of TPTD- and PCA-derived parameters to predict feasibility of fluid removal in 51 SLED-sessions (Genius; Fresenius, Germany; blood-flow 150 mL/min) in 32 patients with PiCCO-monitoring (Pulsion Medical Systems, Germany). Furthermore, we sought to validate the reliability of TPTD during RRT and investigated the impact of "acute" connection and of disconnection with re-transfusion on haemodynamics. TPTDs were performed immediately before and after connection as well as disconnection.Comparison of cardiac index derived from TPTD (CItd) and PCA (CIpc) before, during and after RRT did not give hints for confounding of TPTD by ongoing RRT. Connection to RRT did not result in relevant changes in haemodynamic parameters including CItd. However, disconnection with re-transfusion of the tubing volume resulted in significant increases in CItd, CIpc, CVP, global end-diastolic volume index GEDVI and cardiac power index CPI. Feasibility of the pre-defined ultrafiltration goal without increasing catecholamines by >10% (primary endpoint) was significantly predicted by baseline CPI (ROC-AUC 0.712; p = 0.010) and CItd (ROC-AUC 0.662; p = 0.049).TPTD is feasible during SLED. "Acute" connection does not substantially impair haemodynamics. Disconnection with re-transfusion increases preload, CI and CPI. The extent of these changes might be used as a "post-RRT volume change" to guide fluid removal during subsequent RRTs. CPI is the most useful marker to guide fluid removal by SLED

Reduced Mortality in Maintenance Haemodialysis Patients on High versus Low Dialysate Magnesium: A Pilot Study

Background: Although low magnesium levels have been associated with an increased mortality in dialysis patients, they are kept low by routinely-used dialysates containing 0.50 mmol/L magnesium. Thus, we investigated the impact of a higher dialysate magnesium concentration on mortality. Methods: 25 patients on high dialysate magnesium (HDM) of 0.75 mmol/L were 1:2 matched to 50 patients on low dialysate magnesium (LDM) of 0.50 mmol/L and followed up for 3 years with regards to all-cause and cardiovascular mortality. Patients were matched according to age, gender, a modified version of the Charlson Comorbidity Index (CCI), and smoking status. Results: During the follow-up period, five patients died in the HDM and 18 patients in the LDM group. Patients in the HDM group had significantly higher ionized serum magnesium levels than matched controls (0.64 ± 0.12 mmol/L vs. 0.57 ± 0.10 mmol/L, p = 0.034). Log rank test showed no difference between treatment groups for all-cause mortality. After adjustment for age and CCI, Cox proportional hazards regression showed that HDM independently predicted a 65% risk reduction for all-cause mortality (hazard ratio 0.35, 95% confidence interval [CI]: 0.13, 0.97). Estimated 3-year probability of death from a cardiovascular event was 14.5% (95% CI: 7.9, 25.8) in the LDM group vs. 0% in the HDM group. Log rank test found a significant group difference for cardiovascular mortality (χ2 = 4.15, p = 0.042). Conclusions: Our data suggests that there might be a beneficial effect of an increased dialysate magnesium on cardiovascular mortality in chronic dialysis patients

A novel citrate-based protocol versus heparin anticoagulation for sustained low-efficiency dialysis in the ICU: safety, efficacy, and cost

Abstract Background The high cost, complexity of the available protocols, and metabolic complications are the major barriers that impede the clinical utilization of regional citrate anticoagulation (RCA) for sustained low efficiency dialysis (SLED) in critically ill patients. By comparing a novel protocol for SLED using 30% citrate solution with common protocol using unfractionated heparin, this study aimed to provide new insights for clinical applications of RCA. Methods In this retrospective study, a total of 282 critically ill patients who underwent SLED with citrate and/or heparin anticoagulation in six adult ICUs were enrolled. These patients were divided into three groups based on the anticoagulation regimens they had received during the treatment in ICU: Group 1 (Citrate) had only received treatment with citrate anticoagulation (n=75); Group 2 (Heparin) only with heparin anticoagulation (n=79); and Group 3 (Both) with both citrate and heparin anticoagulation (n=128). We compared the mortality, metabolic complications as well as cost among these groups using different anticoagulation regimens. Results The in-hospital mortality did not significantly differ among groups (p> 0.1). However, three patients in heparin group suffered from severe bleeding which led to death, while none in citrate group. Overall, 976 SLED sessions with heparin anticoagulation and 808 with citrate were analyzed. The incidence of extracorporeal circuit clotting was significantly less in citrate (5%), as compared to that in heparin (10%) (p< 0.001). Metabolic complications and hypotension which led to interruption of SLED occurred more frequently, though not significantly, in citrate (p= 0.06, p= 0.23). Furthermore, with 30% citrate solution, the cost of anticoagulant was reduced by 70% in comparison to previously reported protocol using Acid Citrate Dextrose solution A (ACD-A). Conclusions Our results indicated that anticoagulation regimens for SLED did not significantly affect the mortality of patients. Citrate anticoagulation was superior to heparin in preventing severe bleeding and circuit clotting. The protocol adopted in this study using 30% citrate solution was safe as well as efficacious. In the meantime, it was much more cost-efficient than other citrate-based protocol

Heterozygous COL4A3 Variants in Histologically Diagnosed Focal Segmental Glomerulosclerosis

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is one of the most frequent causes for chronic kidney disease in childhood. In ~30% of these cases a genetic cause can be identified. The histological finding in SRNS is often focal segmental glomerulosclerosis (FSGS). In rare cases, however, pathogenic variants in genes associated with Alport syndrome can be identified in patients with the histological finding of FSGS. Materials and Methods: Clinical information was collected out of clinical reports and medical history. Focused molecular genetic analysis included sequencing of COL4A5 and COL4A3 in the index patient. Segregation analysis of identified variants was performed in the parents and children of the index patient. Results: The female index patient developed mild proteinuria and microscopic hematuria in childhood (12 years of age). The histological examination of the kidney biopsies performed at the age of 21, 28, and 32 years showed findings partly compatible with FSGS. However, immunosuppressive treatment of the index patient did not lead to a sufficient reduction of in part nephrotic-range proteinuria. After the patient developed hearing impairment at the age of 34 years and her daughter was diagnosed with microscopic hematuria at the age of 6 years, re-examination of the index's kidney biopsies by electron microscopy revealed textural changes of glomerular basement membrane compatible with Alport syndrome. Molecular genetic analysis identified two missense variants in COL4A3 in a compound heterozygous state with maternal and paternal inheritance. One of them is a novel variant that was also found in the 6 year old daughter of the index patient who presented with microscopic hematuria. Discussion: We were able to show that a novel variant combined with a previously described variant in compound heterozygous state resulted in a phenotype that was histologically associated with FSGS. Molecular genetic analysis therefore can be essential to solve difficult cases that show an unusual appearance and therefore improve diagnostic accuracy. Additionally, unnecessary and inefficient treatment with multiple side effects can be avoided