Dialysis Protocol Research Articles

Kidney and Hepatic Support in Severe Septic Shock from Leptospirosis: A "Case Series" and the Adoption of a New Dialysis Protocol

Kidney and Hepatic Support in Severe Septic Shock from Leptospirosis: A "Case Series" and the Adoption of a New Dialysis Protocol

Non-mesh inguinal hernia repair with early resumption of peritoneal dialysis in patients on continuous ambulatory peritoneal dialysis.

Inguinal hernia is a common complication of peritoneal dialysis (PD). Although tension-free mesh repair is a leading option for inguinal hernia repair, concerns over serious mesh-related complications may indicate a role for non-mesh inguinal hernia repair. In addition, there is no consensus on the perioperative dialysis regimen. Early resumption of PD may avoid the additional risks associated with hemodialysis. We report on the outcomes of non-mesh inguinal hernia repair in patients on continuous ambulatory PD (CAPD) and provide a perioperative dialysis protocol that aims to guide early resumption of PD. Between May 2019 and September 2023, thirty CAPD patients with 43 inguinal hernias who underwent non-mesh inguinal hernia repair were retrospectively analyzed. Data on the patient characteristics, perioperative dialysis regimen, perioperative features, complications, and hernia recurrence were collected and assessed. Thirty patients with a total of 43 inguinal hernia repairs were included in this study. The median age was 53years. 23 patients were male and 7 were female. Non-mesh inguinal repair was performed for all patients. PD was resumed at a median of 2days after the surgery. Five patients received interim hemodialysis. There were no postoperative surgical or uremic complications and no recurrence after a median follow-up of 31.5months. Our study demonstrates the effectiveness and safety of non-mesh repair with early resumption of PD in patients on CAPD. Interim HD is unnecessary in selected patients. Choosing the optimal perioperative dialysis regimen is essential to managing inguinal hernias in CAPD patients.

Impact of Ring-Closing on the Photophysical Properties of One-Dimensional π-Conjugated Molecular Aggregate.

The self-assembled state of molecules plays a pivotal role in determining how inherent molecular properties transform and give rise to supramolecular functionalities and has long attracted attention. However, understanding the influence of morphologies spanning the nano- to mesoscopic scales of supramolecular assemblies derived from identical intermolecular interactions has been notoriously challenging due to dynamic structural change and monomer exchange of assemblies in solution. In this study, we demonstrate that curved one-dimensional molecular assemblies (supramolecular polymers) of lengths of around 70-200 nm, originating from the same luminescent molecule, exhibit distinct photoluminescent properties when they form closed circular structures (toroids) versus when they possess chain termini in solution (random coils). By exploiting the difference in kinetic stability between the toroids and random coils, we developed a dialysis protocol to selectively purify the former. It was revealed that these terminus-free closed structures manifest higher energy and more efficient luminescence compared with their mixed state with random coils. Time-resolved fluorescence measurements unveiled that random coils, due to their dynamic structural fluctuation in solution, generate local defects throughout the main chain, leading to luminescence from lower energy levels. In mixtures of the two assemblies, luminescence was exclusively observed from such a lower energy level of random coils, a result attributed to energy transfer between the assemblies. This work emphasizes that for identical supramolecular assemblies, only averaged properties have traditionally been considered, but their structures at the nano- to mesoscopic scale are important especially if they have a certain degree of shape persistency even in solution.

Recurrence Rate of Early Hepatitis C Virus Infection After Renal Transplantation Following Successful Treatment of Patients on Dialysis With Direct-Acting Antiviral Agents.

Recurrence of hepatitis C virus after organ transplant has dreadful complications. An excellent response has been shown with direct-acting antiviral agents in transplant recipients. Although a sustained virological response is considered as the virological cure, it requires patients to be on dialysis for 3 months more before undergoing renal transplant, thus increasing the risk of hepatitis C virus reinfection and associated complications. We aimed to determine hepatitis C virus recurrence in renal transplant recipients who had achieved endof-treatment response before transplant. Per our institutional dialysis protocol, patients who do not achieve rapid virological response are treated with 6 months of direct-acting antiviral agents. All patients who achieve end-of-treatment response are then referred for renal transplant. Our study included kidney transplant recipients who were treated with directacting antiviral agents and had a hepatitis C virus polymerase chain reaction test 3 months after renal transplant. We obtained demographic and clinical data of patients and used SPSS version 20.0 for statistical analyses. Our study included 48 transplant recipients; most were males (81.1%) with mean age of 28.7 ± 9.4 years. All patients received sofosbuvir, daclatasvir, and ribavirin combination before transplant. Most patients (70%) received treatment for 3 months. The polymerase chain reaction test for hepatitis C virus was conducted after a mean of 8.3 ± 3.3 months posttransplant. Laboratory parameters showed total bilirubin of 3.6 ± 17.5 mg/day, alanine aminotransferase of 51.5 ± 80.2 IU/L, and gammaglutamyltransferase of 133.9 ± 220 IU/L. Two recipients (4.2%) had posttransplant recurrence of hepatitis C virus infection. To our knowledge, this study is the first to document excellent response of direct-acting antivirals in renal transplant recipients who had been referred early for transplant. Thus, dialysis patients can undergo transplant after achieving end-oftreatment response.

The Impact of Medical Nutrition Intervention on the Management of Hyperphosphatemia in Hemodialysis Patients with Stage 5 Chronic Kidney Disease: A Case Series

The treatment and interdisciplinary management of patients with chronic kidney disease (CKD) continue to improve long-term outcomes. The medical nutrition intervention's role is to establish a healthy diet plan for kidney protection, reach blood pressure and blood glucose goals, and prevent or delay health problems caused by kidney disease. Our study aims to report the effects of medical nutrition therapy-substituting foods rich in phosphorus-containing additives with ones low in phosphates content on phosphatemia and phosphate binders drug prescription in stage 5 CKD patients with hemodialysis. Thus, 18 adults with high phosphatemia levels (over 5.5 mg/dL) were monitored at a single center. Everyone received standard personalized diets to replace processed foods with phosphorus additives according to their comorbidities and treatment with prosphate binder drugs. Clinical laboratory data, including dialysis protocol, calcemia, and phosphatemia, were evaluated at the beginning of the study, after 30 and 60 days. A food survey was assessed at baseline and after 60 days. The results did not show significant differences between serum phosphate levels between the first and second measurements; thus, the phosphate binders' initial doses did not change. After 2 months, phosphate levels decreased considerably (from 7.322 mg/dL to 5.368 mg/dL); therefore, phosphate binder doses were diminished. In conclusion, medical nutrition intervention in patients with hemodialysis significantly reduced serum phosphate concentrations after 60 days. Restricting the intake of processed foods containing phosphorus additives-in particularized diets adapted to each patient's comorbidities-and receiving phosphate binders represented substantial steps to decrease phosphatemia levels. The best results were significantly associated with life expectancy; at the same time, they showed a negative correlation with the dialysis period and participants' age.

Dialysis-Associated Nonarteritic Anterior Ischemic Optic Neuropathy: A Case Series and Review.

Dialysis-associated nonarteritic ischemic optic neuropathy (DA-NAION) occurs secondary to intradialytic hypotension often with catastrophic consequences and is one of the rare situations where NAION can recur in the same eye. We describe 3 cases of DA-NAION associated with hypotension, review the current literature on DA-NAION, and provide recommendations for decreasing the risk of intradialytic hypotension. In addition to describing 3 cases of DA-NAION, PubMed was searched for all reports of DA-NAION in adults with documented episodes of hypotension preceding the onset of NAION. A total of 50 eyes of 31 patients were included. Age, visual acuity at presentation, rate of bilateral involvement at presentation, sequential involvement of the fellow eye, and recurrence of NAION in the same eye were analyzed. We found that most cases of DA-NAION occur in relatively young patients (47.7 ± 14.7 years) with a high rate of bilateral involvement at presentation (23%) and bilateral sequential involvement (39%). Vision loss is severe with 64% of patients presenting with 20/200 acuity or worse in the involved eye and 19% of patients with final visual acuity of 20/200 or worse in both eyes. 3 patients (9.7%) had recurrence of NAION in the previously affected eye. Neuro-ophthalmologists have an important role in identifying patients who have suffered DA-NAION and communicating their findings to nephrologists to minimize the chance of involvement of the fellow eye and recurrence in the same eye. Intradialytic blood pressure must be closely monitored, and fluid balance, dialysate composition, and dialysis protocol must be optimized to prevent occurrence of intradialytic hypotension, which is the culprit for DA-NAION.

Dissolution of citrate-stabilized, polyethylene glycol–coated carboxyl and amine-functionalized gold nanoparticles in simulated biological fluids and environmental media

Dissolution is an important property utilized to elucidate both short- and long-term effects of nanoparticles for their potential to cause harm to humans and the environment. Nanoparticles may therefore be classified based on their (bio)durability between those that are amenable and those that are resistant to dissolution, biodegradation and/or disintegration. The dissolution kinetics of uncoated citrate-stabilized, polyethylene glycol–coated (PEGylated) gold nanoparticles functionalized with carboxyl and amine functional groups in simulated biological and environmental fluids at physiological and room temperature, respectively, were studied using the static dialysis protocol to predict their (bio)durability. Citrate-stabilized gold nanoparticles showed high degrees of resistance to dissolution in the simulated media unlike those which were coated with polyethylene glycol and functionalized with carboxyl and amine functional groups. Generally, the extent of AuNP dissolution in acidic media (phagolysosomal fluid and gastric fluid) was greater than that in neutral or alkaline media such as Gamble’s fluid, blood plasma and intestinal fluids, freshwater and seawater. However, in all these experimental conditions, the particles did not completely dissolve. In the case of amine-functionalized AuNPs, the nanoparticles released a maximum of only 15% of their original concentration whereas carboxyl-functionalized and citrate-stabilized gold nanoparticles released 9% and 8.5% of gold ions, respectively. The rate and degree of dissolution depended on the surface functionalization, pH, ionic strength of the simulated fluid and particle aggregation. Therefore, the results indicate that gold nanoparticles with low dissolution rates are expected to be (bio)durable in biological and environmental surroundings; thus, they might impose long-term effects on humans and the environment. In contrast, those with high dissolution rate are not (bio)durable and hence may cause short-term effects.

Separate and combined effects of cold dialysis and intradialytic exercise on the thermoregulatory responses of hemodialysis patients: a randomized-cross-over study

BackgroundThe separate and combined effects of intradialytic exercise training (IET) and cold dialysis (CD) on patient thermoregulation remain unknown. This study assessed the thermoregulatory responses of hemodialysis patients under four different hemodialysis protocols: a) one typical dialysis (TD) protocol (dialysate temperature at 37 °C), b) one cold dialysis (CD) protocol (dialysate temperature at 35 °C), c) one typical dialysis protocol which included a single exercise bout (TD + E), d) one cold dialysis protocol which included a single exercise bout (CD + E).MethodsTen hemodialysis patients (57.2 ± 14.9 years) participated in this randomized, cross-over study. Core and skin temperatures were measured using an ingestible telemetric pill and by four wireless iButtons attached on the skin, respectively. Body heat storage (S) calculated using the thermometric method proposed by Burton.ResultsThe TD and TD + E protocols were associated with increased S leading to moderate effect size increases in core body temperature (as high as 0.4 °C). The low temperature of the dialysate during the CD and the CD + E protocols prevented the rise in S and core temperature (p > 0.05), even during the period that IET took place.ConclusionsTD and IET are accompanied by a moderate level of hyperthermia, which can be offset by CD. We recommended that CD or with IET can prevent the excessive rise of S.Trial registrationClinical Trial Registry number: NCT03905551 (clinicaltrials.gov), DOR: 05/04/2019,

Inguinal hernias in patients on continuous ambulatory peritoneal dialysis: is tension-free mesh repair feasible?

BackgroundContinuous ambulatory peritoneal dialysis (CAPD), which often causes a common complication such as abdominal wall hernia, is a prevalent alternative therapy for end-stage renal failure patients. However, relevant studies are somewhat rare, and the peritoneal dialysis (PD) protocol during the perioperative period is still controversial. The aim of this study was to evaluate the effectiveness and perioperative management of tension-free mesh repair for inguinal hernias in CAPD patients.MethodsBetween January 2013 and December 2019, 18 CAPD patients with 20 inguinal hernias who underwent tension-free mesh repair were retrospectively analyzed. Data on demographics, perioperative features, the perioperative dialysis protocol and surgical complications were collected and assessed.ResultsAll hernias were diagnosed after the start of CAPD, and the median duration from PD onset to hernia formation was 16 months (2–61 months). All patients underwent successful tension-free mesh repair, including 17 Lichtenstein and 3 anterior Kugel procedures. The median operation time was 62.5 min, and the median postoperative hospital stay was 3 days. Fifteen patients received low-exchange volumes and high-frequency exchanges from 1 to 3 days after surgery for 2 weeks with gradual resumption of the original CAPD regimen within 4 weeks. Complications included seroma (n = 2) and hematoma (n = 1). No wound or mesh infection or recurrence occurred during the follow-up period.ConclusionsTension-free mesh repair is safe and feasible for inguinal hernias in CAPD patients, The Lichtenstein mesh repair should be the first choice, and anterior Kugel repair may be considered an effective procedure. Bridging hemodialysis seems unnecessary except for emergency surgery.

Safely reducing haemodialysis frequency during the COVID-19 pandemic

BackgroundPatients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients.MethodsDialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice.ResultsThere were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project.ConclusionsShort term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

New insights into the altered binding capacity of pharmaceutical-grade human serum albumin: site-specific binding studies by induced circular dichroism spectroscopy

The ADMET profile of drugs is strongly affected by human serum albumin (HSA), due to its leading role as carrier of poorly soluble compounds in plasma; a critical assessment of the binding capacity of HSA and the evaluation of binding competition between drugs are therefore pivotal for a reliable pharmacokinetic and pharmacodynamic characterization. In clinical practice, a potential source of impairment in the binding properties of HSA is the use of octanoate and N-acetyltryptophan as stabilizers during the production of pharmaceutical-grade HSA for infusion (i-HSA), which is currently administered in the treatment of a growing range of pathological conditions. The peculiar sensitivity of circular dichroism (CD) spectroscopy towards the stereochemical features of high-affinity binding events is herein exploited to achieve a site-specific assessment of the effect of stabilizers on the binding properties of i-HSA. The binding affinity and capacity of fatty-acid-free HSA towards site-selective induced circular dichroism (ICD) markers for the three high-affinity binding sites of HSA was compared to that of i-HSA submitted to ultrafiltration and dialysis to remove both stabilizers. Results showed a considerable impairment of the binding capacity of i-HSA at site II and a relatively lower influence on the binding properties of site I. Ultrafiltration proved to be ineffective in depleting octanoate, while the proposed dialysis protocol, which involves a pH-induced reversible unfolding of the protein, resulted in a total clearance of both stabilizers, confirmed by the full restoration of the binding properties of HSA at all binding sites. The outcomes of this study proved that CD spectroscopy is a suitable technique to evaluate the binding properties of i-HSA, ensuring an assessment of the availability of the binding sites and the possibility of monitoring the clearance of stabilizers. Eventually, the proposed method for their depletion might constitute a connection bridge between albumin in vitro studies and its clinical applications.

The Influence of Physical Activity on Serum Phosphate Levels in a Group of Hemodialysis Patients

The prevalence of mineral bone disorders in chronic kidney disease (MBD-CKD) and the cardiovascular risk are increased in hemodialysis (HD) patients. Hyperphosphatemia is one of the complications often associated with increased cardiovascular risk, and in CKD patients, the reduced renal excretion of phosphate is an important cause of elevated serum of this microelement. Physical activity represents another contributing factor in evaluating the risk of cardiovascular disease. The aim of our study was to determine the influence of physical activity on serum phosphate levels in HD patients. The inclusion criteria of this 3-months study were: age ] 18 years old, dialysis vintage ] 6-months, diuresis ] 500 mL/day, PTH values between 100-500 pg/mL, similar dialysis protocol, phosphate daily intake and MBD-CKD therapy. The following parameters were monitored: dry weight, diuresis, associated comorbidities, hemoglobin, serum calcium, phosphate, sodium, potassium, serum albumin, intact parathormon, bicarbonate. The physical activity was assessed during 4 days (3 week-days and 1 during the week-end) for 3 months, and the patients had to complete a questionnaire, too. 49 patients were included and divided in 5 groups, depending on their physical activity. Analyzing the parameters influence on serum phosphate levels, we observed that physical activity, serum calcium and albumin were the only parameters statistically significant (p = 0.001, p = 0.033, and p = 0.47, respectively). The nutritional recommendations of chronic HD patients should be adapted to their individual level of physical activity, in order to avoid an abnormal increase of serum phosphate level, and to improve to over-all outcome.

“ALTERATIONS IN PARATHORMONE, CALCIUM AND PHOSPHORUS LEVELS IN CKD PATIENTS ON MAINTENANCE HAEMODIALYSIS IN A HOSPITAL SETTING IN PUNJAB.”

Objective: Many people who have severe chronic kidney disease (CKD) will eventually develop kidney failure and will require dialysis. The controlof parathormone (PTH), phosphorus, and calcium metabolism is one of the objectives in an adequate dialysis protocol. Therefore, we conductedthis study to describe alterations in PTH, calcium, and phosphorous homeostasis in patients with CKD on hemodialysis in our center. Our study alsoaimed to find an association between hormonal and biochemical abnormalities in CKD patients, who have been on hemodialysis for ≥5 months andcomparing the results obtained with that recommended by Kidney Disease Improving Global Outcomes (KDIGO) guidelines.Methods: This was a hospital-based cross-sectional observational study. The study population of 330 patients (>18 years) on maintenancehemodialysis coming to dialysis Unit of Department of Medicine of Gian Sagar Hospital, Ramnagar (Patiala), over a period of 3 years (2012-2015),were enrolled in the study. Each patient was considered only once for the study. In addition, biochemical analysis of serum intact PTH (iPTH), correctedcalcium, phosphorus, total alkaline phosphatase (tALP), serum creatinine, blood urea, serum albumin, and hemoglobin of all cases was done usingfully automated equipment. All statistical analyses were performed using SPSS statistical software, version 17.Results: The study population of 330 patients comprised adults, mainly illiterate (54.5%) predominantly belonging to the rural (66.4%) strata witha mean age of 52.67±15.05 (range: 25-98 years). The abnormality in the laboratory profile of the patients was found to be hyperparathyroidism in40.3% as compared to hypoparathyroidism in 33.5% and normal iPTH levels in 26.2%. Hypocalcaemia was detected in 50.6% and hyperphosphatemiain 62.1% of the patients. There was statistically significant association of serum iPTH, with corrected calcium and phosphorus (P=0.032 and P=0.035,respectively). Corrected calcium was also significantly associated with phosphorus (P=0.001) and tALP (P=0.007).Conclusion: We showed in the present study that disorders of mineral metabolism are common in hemodialysis patients and that only a smallproportion adheres to the targets as advised in the KDIGO guidelines for bone metabolism and disease in CKD. We demonstrated that these disordersare associated with important negative clinical outcomes, such as increased all-cause lack survival, more muscle and bone problems. Our findings,therefore, support a strict control of mineral metabolism in dialysis patients. Further research and progress in this area are required to establish amore rational approach with a view toward improving patient outcomes.Keywords: Parathormone, Calcium, Phosphorus, Hemodialysis.

血液透析導入期に非典型的なヘパリン起因性血小板減少症を発症し, 腹膜透析導入を余儀なくされた1例

89歳女性. 201X年12月, 急性腎盂腎炎, 敗血症性ショックのため当院紹介. 同日より心房細動の合併に対しヘパリンを開始. 腎不全急性増悪のため右大腿静脈に透析用カテーテルを留置し翌日から血液透析を開始した. 第3病日, カテーテル脱血不良のため右内頸静脈に再留置. 第4病日, カテーテル閉塞. 第11病日, 下肢血栓症のため下大静脈フィルターを留置. 血小板は13.4万/μLから6.1万/μLへ低下した. 経過よりⅡ型ヘパリン起因性血小板減少症 (HIT) を疑い, ヘパリンを中止しアルガトロバンを開始した. しかし, バスキュラーアクセスの確保が困難となり, 第25病日, 腹膜透析へ移行した. 抗血小板第4因子/ヘパリン複合体抗体は1.3U/mLで陽性. ヘパリン開始後4日以内の血栓傾向や血小板減少は, 非典型的であり, 急速発症型または特発性の可能性について検討する必要がある.

Cloning, expression and characterization of the recombinant cold-active type-I pullulanase from Shewanella arctica

An activity-based screening approach led to the identification of a novel glycoside hydrolase family-13 pullulanase gene (pul13A) from a psychrophilic bacterium. The recombinant enzyme exhibited a deduced peptide sequence of 1440 amino acid residues and was produced in a heterologous host in Escherichia coli. Purification from inclusion bodies was achieved by a six-step dialysis protocol enabling mild refolding of the urea-denaturated protein followed by affinity- and size-exclusion chromatography under native conditions. Pul13A is a type-I pullulanase, which is capable of hydrolysing α-1,6-glycosidic bonds in pullulan to produce maltotriose, while maltose and intermediate oligosaccharides are produced from soluble starch and amylopectin. The recombinant enzyme exhibited typical properties of cold-adapted proteins including low thermostability at elevated temperatures. It showed a temperature optimum at 35°C, while at 10°C residual activity (25%) remained. The optimal pH was in the range of 6.0–7.0, with Pul13A being stable at neutral and basic pH, but not in the acidic range. Catalytic activity was increased in the presence of divalent cations calcium and cobalt and both metal ions were also able to restore catalytic activity of EDTA-chelated enzyme samples. Pul13A represents the first type-I pullulanase from a psychrophile that has been produced in recombinant form. Moreover, its favourable enzymatic properties make this enzyme a potential candidate for industrial applications such as starch degradation for ethanol based biofuel production.

Dialysis: a characterization method of aggregation tendency.

All researchers immersed in the world of recombinant protein production are in agreement that often the production and purification process of a protein can become a nightmare due to an unexpected behavior of the protein at different protocol stages. Once the protein is purified, scientists know that they still cannot relax. There is a decisive last step missing: performing a protein dialysis in a suitable buffer for subsequent experimental trials. Here is when we can find proteins that precipitate during dialysis by buffer-related factors (ionic strength, pH, etc.), which are intrinsic to each protein and are difficult to predict. How can we find the buffer in which a protein is more stable and with less tendency to precipitate? In this chapter we go over possible factors affecting the protein precipitation tendency during the dialysis process and describe a general dialysis protocol with tricks to reduce protein aggregation. Furthermore, we propose a fast method to detect the most appropriate buffer for the stability of a particular protein, performing microdialysis on a battery of different buffers to measure afterwards precipitation by a colorimetric method, and thus being able to choose the most suitable buffer for the dialysis of a given protein.

Effect of individualized exercise during maintenance haemodialysis on exercise capacity and health-related quality of life in patients with uraemia.

To investigate the effect of individualized exercise on exercise capacity and health-related quality of life (HRQoL) in uraemic patients during maintenance haemodialysis (MHD). Patients receiving MHD were divided randomly into a test group, who underwent recumbent cycling exercise during dialysis, and a control group, who performed simple stretching exercises. The same dialysis protocol was used for all study participants. At study start and after 12 weeks, exercise capacity was measured using tests of physical ability; HRQoL was measured using the kidney disease quality of life score (KDQOL-SF™). A total of 65 patients were included in the study: 33 in the control group and 32 in the test group. There were no significant differences in patient characteristics between the two groups at baseline. After 12 weeks, there were significant improvements in exercise capacity and in many of the items of the KDQOL-SF™ in the test group compared with the control group. Individualized exercise during MHD significantly improved the exercise capacity and HRQoL for uraemic patients within a short time period, and could therefore be used as a simple, cost-effective therapeutic approach.

High-Cut Off Dialysis In Multiple Myeloma Patients With Dialysis Dependent Acute Renal Failure Shows Durable Renal Recovery: A Long-Term Follow Up Analysis

Acute kidney injury (AKI) either in primary diagnosis or at relapse is one of the frequent complications in multiple myeloma (MM). Myeloma cast nephropathy is induced by mechanical occlusion of the distal tubule by casts consisting of free light chains (FLC) and Tamm Horsfall protein. Impairment of renal function affects prognosis, with particularly poor outcomes in patients requiring hemodialysis with a historically reported median survival of 3-4 months. Introduction of novel therapeutic agents in MM therapy has improved MM response as well as renal outcome mainly due to a short time to initial response and consecutively reduction of the toxic FLC component. Extracorporeal light chain elimination in addition to chemotherapeutic treatment has been discussed controversially so far. We and others introduced the high-cut off (HCO) dialysis which allows effective elimination of FLC in an extended standard dialysis protocol. Recently, we demonstrated the efficacy of combined systemic and extracorporeal therapy regarding time to FLC reduction and renal recovery in a first case series of MM patients with dialysis-dependent AKI (Heyne et al., Ann Haematol 2012). Here, we report long-term renal outcome and overall survival data.19 MM patients with dialysis dependent AKI were treated between November 2006 and October 2009 with HCO dialysis in parallel to systemic chemotherapy. The applied chemotherapy was chosen by the treating haematologist. All data was calculated by intent-to-treat (ITT) analysis. Progression-free survival (PFS) was analysed from the first day of HCO dialysis to progression or death, whichever occurred first. Overall survival was calculated from the first day of HCO dialysis to death. For statistical analysis GraphPad Prism (GraphPad Software Inc., La Jolla/CA, USA) and R (R Foundation for Statistical Computing, Vienna) biostatistical software was used.The ITT cohort consisted of 19 patients. Median age was 69 (range 50-83) years. 10 patients had newly diagnosed, 9 relapsed or refractory MM. All patients had ISS stage III disease. Median serum FLC concentration at baseline was 8,580 (1 590-66 100) mg/L. Median serum creatinine was 6.8 (4.4-11.6) mg/dL, median eGFR 7.0 (3.3-10.9) mL/min/1.73m². Four (21%) early deaths occurred in the first three months of treatment, 2 patients with newly diagnosed and 2 patients with relapsed disease. Chemotherapy consisted mainly of bortezomib based regimens. As we reported previously, sustained renal recovery was achieved in 73.7% or 14/19 patients with a median time to independence of hemodialysis of 15 (4-64) days. In the long-term follow up analysis with a median follow-up of 62 months, 11/14 dialysis independent patients remained free of dialysis during further disease course. 3 patients again requiring dialysis all showed terminally refractory disease. Median PFS of the IIT population was 7.8 months for primary diagnosed and 4.8 months for relapsed and refractory patients, median OS of the whole population was 9.5 (range 2.8-not reached) months for primary diagnosed patients and 4.8 (range 1.0-19.8) months for the relapsed and refractory group.Combination of systemic treatment and HCO dialysis in patients with myeloma cast nephropathy and dialysis dependent renal failure results in durable renal remissions in the majority of patients. Close monitoring of patients and early treatment intervention can prevent recurrent severe AKI in myeloma relapse. Survival data reflect the critically ill patient population with high tumor burden and high-risk of early death, but also show encouraging long-term myeloma and renal remissions. The benefit of the additional HCO dialysis in addition to conventional chemotherapy is currently investigated in a randomised multicenter trial (EuLITE study). Disclosures:Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding.

Laparoscopic‐Assisted Placement of a Peritoneal Dialysis Catheter With Partial Omentectomy and Omentopexy in Dogs: An Experimental Study

To describe a technique of laparoscopic-assisted placement of a peritoneal dialysis (PD) catheter with simultaneously performed partial omentectomy and omentopexy. Pilot experimental study. Beagle dogs (n = 6). After placement of 1 sub-umbilical laparoscope portal and 1 instrument portal in the left cranial abdominal quadrant, laparoscopic-assisted partial omentectomy, and omentopexy were performed, and a modified Tenckhoff PD catheter was placed under laparoscopic guidance. A modified dialysis protocol was used twice daily for 4 days. The feasibility of the procedure, surgical duration, operative complications, and dialysis efficacy were evaluated. Postoperative pain and inflammation were graded (0-3). The procedure was successfully performed in all dogs with a median operating time of 25 minutes. No operative complications occurred. Procedure-related postoperative pain and inflammation were minimal. Eight consecutive PD procedures were successfully performed, and no leakage or obstruction was observed. Laparoscopic-assisted partial omentectomy and omentopexy can be performed at the same time as PD catheter placement with minimal morbidity.

Not all G-quadruplexes are created equally: an investigation of the structural polymorphism of the c-Myc G-quadruplex-forming sequence and its interaction with the porphyrin TMPyP4.

G-quadruplexes, DNA tertiary structures highly localized to functionally important sites within the human genome, have emerged as important new drug targets. The putative G-quadruplex-forming sequence (Pu27) in the NHE-III(1) promoter region of the c-Myc gene is of particular interest as stabilization of this G-quadruplex with TMPyP4 has been shown to repress c-Myc transcription. In this study, we examine the Pu27 G-quadruplex-forming sequence and its interaction with TMPyP4. We report that the Pu27 sequence exists as a heterogeneous mixture of monomeric and higher-order G-quadruplex species in vitro and that this mixture can be partially resolved by size exclusion chromatography (SEC) separation. Within this ensemble of configurations, the equilibrium can be altered by modifying the buffer composition, annealing procedure, and dialysis protocol thereby affecting the distribution of G-quadruplex species formed. TMPyP4 was found to bind preferentially to higher-order G-quadruplex species suggesting the possibility of stabilization of the junctions of the c-Myc G-quadruplex multimers by porphyrin end-stacking. We also examined four modified c-Myc sequences that have been previously reported and found a narrower distribution of G-quadruplex configurations compared to the parent Pu27 sequence. We could not definitively conclude whether these G-quadruplex structures were selected from the original ensemble or if they are new G-quadruplex structures. Since these sequences differ considerably from the wild-type promoter sequence, it is unclear whether their structures have any actual biological relevance. Additional studies are needed to examine how the polymorphic nature of G-quadruplexes affects the interpretation of in vitro data for c-Myc and other G-quadruplexes. The findings reported here demonstrate that experimental conditions contribute significantly to G-quadruplex formation and should be carefully considered, controlled, and reported in detail.