Effect of time-dependent dialysate bicarbonate concentrations on acid-base and uremic solute kinetics during hemodialysis treatments.

Recent studies have suggested benefits for time-dependent dialysate bicarbonate concentrations (Dbic) during hemodialysis (HD). In this clinical trial, we compared for the first time in the same HD patients the effects of time-dependent changes with constant Dbic on acid-base and uremic solute kinetics. Blood acid-base and uremic solute concentration were measured in twenty chronic HD patients during 4-h treatments with A) constant Dbic of 35 mmol/L; B) Dbic of 35 mmol/L then 30 mmol/L; and C) Dbic of 30 mmol/L then 35 mmol/L (change of Dbic after two hours during Treatments B and C). Arterial blood samples were obtained predialysis, every hour during HD and one hour after HD, during second and third treatments of the week with each Dbic concentration profile. Blood bicarbonate concentration (blood [HCO3]) during Treatment C was lower only during the first three HD hours than in Treatment A. Overall blood [HCO3] was reduced during Treatment B in comparison to Treatment A at each time points. We conclude that a single change Dbic in the middle of HD can alter the rate of change in blood [HCO3] and pH during HD; time-dependent Dbic had no influence on uremic solute kinetics.

Intraoperative dialysis with the use of a mobile dialysis system during liver transplantation.

PURPOSE: Over the last few years, transplant centers have started to use various intraoperative renal replacement therapy (ioRRT) modalities during liver transplantation (LT) in patients with pre-existing renal impairment. Here, we present a study on the safety and clinical outcomes of intraoperative hemodialysis (ioHD) performed using a mobile dialysis system during LT. PATIENTS AND METHODS: We retrospectively analyzed 102 adult patients undergoing LT with ioHD; pre-existing renal failure and/or intraoperative metabolic derangement were ioHD treatment indications. RESULTS: Our study cohort consisted of three groups: LT with preoperative serum creatinine (sCr) â€‹< â€‹2 â€‹mg/dL (Group 1:n â€‹= â€‹22), LT with preoperative sCr ≥2 â€‹mg/dL (Group 2:n â€‹= â€‹73), and simultaneous liver-kidney transplantation (Group 3:n â€‹= â€‹7). Among the procedures, 30% were re-transplantations. The mean calculated Model for End-stage Liver Disease score in Group 2 was 39.2, and 67% of patients were hospitalized in the intensive care unit. Patients in Group 1 were less acutely ill but developed severe intraoperative derangements and, therefore, underwent urgent ioHD intraoperatively. However, it was delayed when compared to Group 2. All groups achieved post-reperfusion potassium levels <4 â€‹mmol/L and a decrease in central venous pressure. No serious procedural complications occurred. Post-reperfusion syndrome occurred in 12.7% of patients. Elevated mortality was likely due to the high illness severity in the cohort. CONCLUSIONS: Performing ioHD with a mobile dialysis system during LT was safe and effective, while being easier to perform than continuous techniques. Its effect on intra- and postoperative outcomes should be addressed in a study with a control group.

Simultaneous Liver-Kidney Transplantation and the Use of Intraoperative Dialysis: A Monocenter Study.

BACKGROUND: Simultaneous liver and kidney transplants (SLKT) represent 1.1% of all liver transplants in Poland. Patients undergoing SLKT experience a longer operation time and concurrent kidney dysfunction may aggravate metabolic derangement associated with the procedure. The benefits of intraoperative dialysis (ioHD) in these patients have not been determined. METHODS: A retrospective observational study of all adult patients undergoing SLKT in our center from January 2009 till December 2016. RESULTS: Study group consisted of 10 patients with End-Stage Kidney Disease (0.9% of all liver transplants): 6 patients treated with ioHD during SLKT (group 1) and 4 patients managed conservatively (group 2). All recipients were on chronic dialysis. The mean calculated Model for End-Stage Liver Disease score was 21 ± 0.9 in group 1 and 30 ± 9.5 in group 2 (P = .009). The mean preoperative serum potassium was 4.7 ± 0,6 mmol/L in group 1 and 3.97 ± 1,02 in group 2. Intraoperative serum potassium levels were comparable between the groups, but the maximum lactate and minimum bicarbonate levels were significantly worse in group 2. Postreperfusion syndrome occurred in no patient. Dialysis circuit clotting occurred in 50% of ioHD. Six patients (2 in group 1) required renal replacement therapy after SLKT; no patient was on dialysis on discharge. Three patients died within 1 year after surgery (2 in group 2). CONCLUSIONS: No patient developed intraoperative hyperkalemia or postreperfusion syndrome. We observed a high frequency of circuit system clotting during ioHD. Clinical benefits of intraoperative hemodialysis during SLKT need to be determined in a larger study.

Influence of formalized Predialysis Education Program (fPEP) on the chosen and definitive renal replacement therapy option.

BACKGROUND: It is widely accepted that patients with chronic kidney disease (CKD) should play an active role in the selection of renal replacement therapy (RRT) option. However, patients' knowledge about CKD and treatment options is limited. The implementation of structured education program and shared decision-making may result in a better preparation to RRT, more balanced choice of dialysis modalities and better access to kidney transplantation (TX). OBJECTIVES: The aim of this long-term study was to assess the impact of formalized Predialysis Education Program (fPEP) on knowlege on RRT options, as well as on selected and definitive therapy. MATERIAL AND METHODS: The study included 435 patients (53% men, mean age 60 years) with CKD stage 4 and 5, participating in fPEP at our center. The program included at least 3 visits, during which balanced information about all RRT options was presented and self-care and informed decision-making were encouraged. The knowledge about RRT options before and after fPEP attendance, and selected and definitive RRT options were assessed. RESULTS: Ninety-two percent of patients received prior nephrology care. After fPEP completion, in most patients, the knowledge about CKD and RRT options and selected preferred modality improved - 40% of participants chose hemodialysis (HD), 32% peritoneal dialysis (PD) and 18% TX. During the observation period, 4% of patients died before commencement of dialysis, 2.7% received preemptive kidney transplant, 8.6% were placed on transplant waiting list, and 94% started dialysis (30% PD and 70% HD). Among those who chose PD, 69% started PD and 24% started HD; the leading causes of the discrepancy between choosing and receiving PD was the deterioration in clinical condition (50%) and change of decision (32%). CONCLUSIONS: The fPEP increases CKD patients' knowledge on RRT methods. The implementation of a decision-making process based on fPEP leads to a satisfying distribution between modalities, with a good concordance between chosen and definitive modality.

Haematological disorders following kidney transplantation.

Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management.

Cholecalciferol vs. Small Doses of Alfacalcidol vs. Placebo in Chronic Kidney Disease Patients on Hemodialysis: A Randomized Parallel Group Study.

BACKGROUND: The ability of extrarenal tissues to convert 25(OH)D (calcidiol) into 1,25(OH)2D (calcitriol) and dependence of the conversion on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both: 25(OH)D and 1,25(OH)2D. The primary aim of the study was to compare effects of small doses of cholecalciferol (12,000 IU/week) with frequently used in Europe, small doses of alfacalcidol (1.5 µg/week) or placebo, given for 12 weeks, on serum 1,25(OH)2D in hemodialysis patients with 25(OH)D deficiency. Secondary outcomes were changes in serum calcium, phosphate, 25(OH)D, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and sclerostin during the treatment. METHODS: This was a prospective, randomized, partly double-blind (cholecalciferol vs. placebo) study. Out of 522 patients dialyzed in 5 centers in the Mazovian Province, 93 gave informed consent and met the inclusion criteria: any vitamin D metabolites and calcimimetics naïve; no history of liver or intestinal disease; serum 25(OH)D <20 ng/ml, iPTH <1,000 ->110 pg/ml, calcium <10.2, and phosphate <6.8 mg/dl. The subjects were stratified by serum iPTH, then randomized into 3 groups according to the treatment. RESULTS: To our knowledge, this is the first study comparing head-to-head these drugs in the hemodialysis population. There were no significant differences between the groups at baseline. 81 patients completed the study. Cholecalciferol normalized serum 25(OH)D, with a mean rise from 12.9 ± 6.7 to 31.3 ± 10.1 ng/ml (p < 0.0001). This was accompanied by a marked increase of 1,25(OH)2D from 13.8 ± 9.3 to 25.1 ± 14.2 pmol/l (p < 0.0001). A rise in serum 1,25(OH)2D was also observed in alfacalcidol treated patients, however much smaller (from 13.5 ± 10.1 to 18.5 ± 11.0 pmol/l; p = 0.02). Neither cholecalciferol nor alfacalcidol treatment resulted in significant changes in serum PTH and the remaining parameters. CONCLUSIONS: In most patients, treatment with cholecalciferol in a 12,000 IU/week dose permits safe correction of 25(OH)D deficiency and is more effective than 1.5 µg/week dose of alfacalcidol in rising serum 1,25(OH)2D. This, together with a lack of influence on circulating iPTH the usefulness of such small alfacalcidol doses in hemodialysis patients is debatable.

Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress.

BACKGROUND: Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS. SUMMARY: Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and - in high-risk cases - considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted.

Renal Involvement in Systemic Sclerosis: An Update.

BACKGROUND: Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. SUMMARY: Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and life-threatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients' outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.

Acute kidney injury, its definition, and treatment in adults: guidelines and reality.

In the last decades, a lot of research has been done to improve our understanding of acute kidney injury (AKI) as well to standardize its diagnostic criteria. As a result of many years of work of intensivists and nephrologists, consensus definitions were established, finally unified in 2012 by the Kidney Disease: Improving Global Outcomes (KDIGO) group. These criteria refer to the time of AKI development and are based on serum creatinine level increase and / or urine output decrease. Acute kidney injury is defined as an increase in serum creatinine levels by at least 0.3 mg/dl within 48 hours or 1.5­fold the baseline, which is known or presumed to have occurred within the preceding 7 days, or-according to the urine output criterion-urine volume less than 0.5 ml/kg/hour for at least 6 hours. The present review covers issues discussed during the KDIGO controversy conference, devoted to AKI. Here, we attempted to answer 3 main questions: Is the KDIGO definition of AKI valuable in clinical research and global epidemiology? Is it helpful in everyday clinical practice? Is it useful in the treatment of critically ill patients with AKI?

Intraoperative Dialysis During Liver Transplantation.

BACKGROUND: Orthotopic liver transplantation (LT) is a technically complex surgical procedure associated with a major risk of hemodynamic instability and metabolic derangement, especially in patients with coexisting renal dysfunction. Some centers have applied intraoperative renal replacement therapy (ioRRT) to support patients with preoperative renal failure and prevent critical complications. Although there is a strong theoretical rationale for this treatment, there remains a paucity of definite data demonstrating its benefits. METHODS: This was a retrospective observational study of all adult patients undergoing intraoperative dialysis in our center from January 2010 till December 2016. RESULTS: The study group consisted of 88 patients with a mean MELD score of 31.4. Six patients underwent simultaneous liver and kidney transplantation. Forty-four (50%) recipients were admitted to the intensive care unit before transplantation, and 19 (21.6%) needed mechanical ventilation. Twenty-eight (31.8%) of the procedures were retransplantations, and 40 (45.4%) patients had been undergoing renal replacement therapy before LT. The mean preoperative serum creatinine was 2.82 ± 1.13 mg/dL. The majority of patients (54.5%) was operated on using the veno-venous bypass technique. The mean arterial blood pH and potassium levels after reperfusion were 7.2 ± 0.12 and 4.04 ± 0.95 mmol/L, respectively. Postreperfusion syndrome (PRS) occurred in 11 (13.9%) patients in whom dialysis started at least 15 minutes before reperfusion. Dialysis circuit clotting occurred in 9.1% of cases. There were no other adverse events of ioRRT. CONCLUSION: Our data suggests that intraoperative dialysis in severely ill patients with a high MELD score is safe and effective. Lower than expected PRS occurrence needs to be confirmed in a study with a control group.

How to assess kidney function in oncology patients.

Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.

FRAX prognostic and intervention thresholds in the management of major bone fractures in hemodialysis patients: A two-year prospective multicenter cohort study.

PURPOSE: The usefulness of FRAX in predicting major bone fractures in patients with end-stage kidney disease on maintenance hemodialysis treatment has been confirmed in previous studies. For meaningful clinical use, the prognostic and intervention FRAX thresholds need to be established. METHODS: The primary aim of our study was to calculate the optimal cut-off point of FRAX for the best prediction of an increased bone fracture risk in dialysis patients and additionally, to propose its intervention threshold, indicating the need for antifracture pharmacological treatment. The study included 718 hemodialysis patients, who were followed up for two years. Thirty low-energy major bone fractures were diagnosed during the study period. We used the Polish version of FRAX (without the DXA examination) and some particular variables of the FRAX calculator. The optimal cut-off point for prediction of an increased major bone fracture risk was based on the analysis of the sensitivity and specificity curves of FRAX. RESULTS: The analysis revealed FRAX >5% (sensitivity of 70.0%, specificity of 69.8%) as the prognostic threshold for major bone fractures. Its sensitivity for bone fracture prediction was significantly higher, but specificity lower than those of FRAX ≥10%, used in general Polish population. The reason for this can be an underestimation of bone fracture risk with FRAX in dialysis patients. CONCLUSIONS: We conclude that the FRAX prognostic threshold for identification of an increased risk of major bone fractures in hemodialysis patients is >5%. We propose to use this specific value of FRAX as an intervention threshold for pharmacological antifracture treatment in hemodialysis patients.

[Circulating bone turnover markers and their relationships in hemodialysis patients with vitamin D deficiency].

OBJECTIVE: Introduction: Mineral homeostasis is achieved through a complex interplay of several feedback processes involving primarily the bone, intestine and kidney, regulated by different proteins acting on endocrine, paracrine or autocrine levels. The dysregulation of these processes in chronic renal failure, called kidney disease (CKD) - mineral and bone disorder (CKD-MBD), although apparent, is still poorly understood. The aim: The aim of the study was an analysis of potential relationships between selected biomarkers of CKD-MBD in maintenance hemodialysis (HD) patients. PATIENTS AND METHODS: Material and Methods: In the first part of this cross-sectional study, the 25(OH)D serum concentrations were measured in 115 HD vitamin D naïve patients from 5 dialysis units located in central Poland. Thereafter in 81 patients (49 men, 32 women, aged 67 ± 13 years) with vitamin deficiency (25(OH)D <20 ng/ml) serum concentrations of 25(OH)D, 1,25(OH)2D, intact parathyroid hormone (iPTH), intact FGF23, sclerostin (SCL), osteocalcin (OC), and C-terminal telopeptide of type I collagen (CTX1) were determined. RESULTS: Results: Serum levels of both 25(OH)D and 1,25(OH)2D were low (mean values 13.4±6.72 ng/ml and 12.9 ± 9.08 pmol/l, respectively). While serum 25(OH)D correlated only with a declared time spent outside (r= 0.411; p=0.000139), serum 1,25(OH)2D was related to diuresis (r= 0.289; p=0.009), and negatively to time on dialysis (r= -0.272; p=0.014) , serum phosphate (r= -0.393; p=0.000289), FGF23(r= -0.295; p=0.008), and SCL (r= -0.260; p=0.019). There was a marked dispersion of FGF-23 serum levels across the group (mean 823±5647, median 379 pg/ml) , and - as expected - they correlated highly with phosphate (r= 0.549, p=0.000), calcium (r= 0,328, p=0,003), OC (r=0.479; p=0.000), and negatively with z 1,25(OH)2D (r= -0.295, p=0.008). Mean serum SCL levels (89.2±46.7, median 81.9 pmol/l) were 3x higher than in general population, and correlated highly positively with dialysis vintage (r=0.402; p<0.001), age (r=0.356; p=0.001), as well as negatively with 1,25(OH)2D (r= -0.260; p=0.019) and CTX1 (r= -0.293; p=0.008). CONCLUSION: Conclusions: In our hemodialysis population, in addition to profoundly impaired 1,25(OH)2D synthesis, there is also a widespread prevalence of 25(OH)D deficiency. The patients have also markedly increased serum bone-secreted proteins, FGF23, and SCL, which regulate mineral and bone metabolism and are associated with the systemic side effects of uremia. All these hormones interact one with the other, creating a sophisticated cross-talk between the bone, intestine, and the kidney.

Urinary and Serum Biomarkers for Prediction of Acute Kidney Injury in Patients Undergoing Liver Transplantation.

Acute kidney injury (AKI) is a frequent and serious complication of orthotopic liver transplantation (OLT), with a significant impact on mortality, graft survival, and chronic kidney disease. Currently, the diagnosis of AKI is based on changes in serum creatinine, which is a late marker, usually rising when there is already significant damage to the renal parenchyma. During the last 2 decades, various biomarkers have been studied in many clinical situations, mostly after cardiac surgery, in drug-induced AKI, or in sepsis. The present article summarizes the data on those biomarkers that have been evaluated for the prediction of AKI in patients undergoing OLT.

Peritoneal Ultrafiltration in the Long-Term Treatment of Chronic Heart Failure Refractory to Pharmacological Therapy.

INTRODUCTION: Despite continuous improvement in the treatment, heart failure (HF) is a growing health problem and a major cause of mortality and morbidity in the world. There is some positive experience with the removal of the fluid excess via peritoneum in those patients, regardless of their renal function. The aim of this single center pilot study was to assess the efficacy of peritoneal ultra filtration (PUF) with a nightly 12-h exchange in the long-term treatment of refractory HF. METHODS: The study included patients with chronic HF resistant to updated HF therapy (pharmacological and devices if applicable), who had experienced at least three hospitalizations due to HF during the preceding year and were disqualified from heart transplantation. All of them were treated with nightly 12-h 7.5% icodextrin exchange. RESULTS: There were 15 patients (13 men), aged 72 ± 9 years, with charlson comorbidity index (CCI) 9 ± 1.2, NYHA class IV (11 patients) or III (4 patients), and eGFR 32 ± 11 ml/min/1.73m2. They were followed up for 24 ± 8 months (range 12-43, median 26 months). During the 1st year, all patients improved their NYHA functional class from 3.7 ± 0.5 to 2.6 ± 0.5; P = 0.0005, with stable (34.3 ± 12.4, and 35.6 ± 16.5%, respectively) left ventricular ejection fraction (LVEF), and inferior vena cava (IVC) diameter decreased from 27.8 ± 2.7 to 24.4 ± 3.4 mm; P = 0.09. Daily diuresis increased from 867 ± 413 to 1221 ± 680 ml; P = 0.25, while the dose of furosemide could be reduced from 620 ± 256 to 360 ± 110 mg/d; P = 0.0005, however, the kidney function deteriorated, with eGFR drop from 32 ± 11 to 25.6 ± 13 ml/min/1.73m2; P = 0.01). HF-related hospitalizations decreased from 8.9 ± 2.8 days/month to 1.5 ± 1.2 days/month (P = 0.003). Mechanical peritoneal dialysis complications occurred in five patients and infectious complications in four (peritonitis rate 1 per 72 patient-month). Patient survival was 93% at 1 year and 73% at 2 year. Technique survival was 100%. CONCLUSION: In patients with refractory HF, PUF with one overnight icodextrin exchange appears to be a promising therapeutic option as an adjunct to pharmacological management of those who are not transplant candidates. It should be emphasized that the treatment can have a great impact on the quality of life and the total costs of treating these patients.