bluuebunny/crossref_metadata_2025 huggingface dataset:
P1025HISTOLOGICAL AND CLINICAL FINDINGS IN ADULT AUTOPSIES OF TYPE 2 DIABETES MELLITUS PATIENTS WITH OR WITHOUT DIABETIC KIDNEY DISEASE
Authors: Gimenez-Civera Elena , Puchades Montesa Maria Jesãºs , Terrádez Liria , Moscardo Anais , D'Marco Luis , Pérez Ys Aurora , Moncho Francesc , Perez-Bernat Elisa , Panizo Gonzalez Nayara , Tomas Patricia , Gonzalez-Rico Miguel , Gorriz Jose Luis
Published: June 2020

Background and Aims

Few studies have analyzed early lesions of diabetic nephropathy (DN) in those patients who do not have clinical signs of this involvement, since the indication of renal biopsy is usually performed in patients with significant renal manifestations.The aim of the study was to analyze renal histological lesions from autopsies of diabetic patients with or without clinical expression of DN. Thus, we analyze their correlation according to the presence or absence of proteinuria (albumin/creatinine to ratio > 300). Autopsies from non-diabetic patients was used as a control group.

Method

Kidneys from autopsies of 21 patients with type 2 diabetes mellitus (T2DM) and 4 non-diabetic controls were analyzed by two pathologists. The histological lesions score of DN was performed according to the classification of Tervaert et al. (JASN. 2010; 21: 556–63), and a description of histological findings, clinical and analytical data were made.

Results

The mean glomeruli per sample was: 170 ±88. Patient demographics of autopsies: mean age 76 ± 11 years, mean duration of diabetes 6.08 ± 3.2 years (20%> 10 years). Last known eGFR: 51 ± 28, HbA1c: 7.3 ± 1.9%. Albuminuria and cardiovascular disease were present in 42% and 60% of patients with T2DM. Histological and clinical data are shown in Table and Graphics.

Conclusion

A high percentage of diabetics without early clinical lesions of DN (albuminuria) already express moderate to severe histological changes, especially severe mesangial expansion and severe glomerular vascular lesions. The control group showed minimal histological lesions except for mild expansion of the mesangium and inflammation associated with IFTA. Our data suggest renal involvement in T2DM is present in earlier stages (patients without albuminuria). Therefore, early metabolic control is important, as well as other risk factors that may influence in the development of DN. Large sample size studies are pending to confirm these data.
P1032CMV INFECTION & RISK OF NEW ONSET DAIBETES AFTER TRANSPLANTATION
Authors: KHAN MUHAMMAD TASSADUQ
Published: June 2020

Background and Aims

NODAT is a frequent complication among kidney transplant recipients and is considerably associated with risk of allograft rejection and allograft loss. The present research study was aimed to identify whether CMV infection acts as risk factor for NODAT development in kidney transplant recipients.

Method

This retrospective study recruited 59 kidney transplant recipients (43 males and 16 females). The diagnosis of NODAT was established if two fasting plasma glucose readings were ≥126 mg/dL after the 3rd month of post-transplantation. We carefully monitored recipients for CMV viremia (CMV DNA copies/mL) in the plasma through quantitative Polymerase Chain Reaction (qPCR). The 1 year post-transplantation allograft outcomes due to CMV viremia were also measured; eGFR (CKD-EPI method), allograft and transplant patient survival.

Results

In this study, 14 (23.7%) patients were diagnosed with NODAT. The CMV load and CMV viremia was elevated in NODAT cohort in comparison with their counterparts (4000 versus 3600 and 51.1 versus 47.6, respectively); however, no statistical relationship was observed (P = 0.79 and P = 0.84, respectively). We witnessed significantly high CMV DNA replication in first (1-6 months) half of the post-transplant period in both controls and NODAT patients; however, statistically significant CMV DNA replication was only observed for NODAT cohort (P<0.001). Majority of the NODAT diagnoses; 9 out of 14 (64.3%), in our cohort was made during the first six months of kidney transplantation (P<0.001). Overall, 7 (11.9%) of the kidney transplant recipients recruited in our study progressed to symptomatic CMV infection. We also witnessed that a greater CMV viremia load was worsening the kidney allograft function at 12 months post-transplantation. The allograft and patient survival (censored for death) was poor in the NODAT cohort; however, without any statistical significance.

Conclusion

The present study demonstrated that CMV infection is not a risk factor for NODAT development among kidney transplant recipinets.
P1036THE SHORT-TERM EFFICACY AND SAFETY OF THE APPLICATION OF SGLT2I AS A DIURETIC MEDICATION ON THE DIURETIC RESISTANCE IN PATIENTS WITH DIABETIC NEPHROPATHY ON CKD STAGE 3-4
Authors: Liang Wei
Published: June 2020

Background and Aims

At stage 3-4 of chronic renal disease, patients with diabetic-induced renal dysfunction are not sensitive to the conventional diuretic therapy based on loop diuretics and thiazide diuretics, leading to the earlier renal replacement at stage CKD 3-4. The lower sodium excretion could contribute to the development of diuretic resistance. The protective effects of SGLT2 inhibitors on cardiovascular is contributed by metabolic regulation and osmotic diuretic effect of glucose due to extra excretion of Glucose. The present study aim to investigate the efficacy and safety of SGLT2 inhibitors on the diuretic resistance of diabetic nephropathy at CKD 3-4 stage.

Method

Patients with Diabetic nephropathy at CKD3-4 stage were administrated with furosemide + hydrochlorothiazide for 3 days with urine volume <1000ml, urine sodium excretion <90mmol followed by Dapagliflozin/Canagliflozin once a day for 7 days.

Results

3 male and 7 female patients with diabetic nephropathy were included, aged 51-80 years, with eGFR 60-4.6ml/min, and 3 patients presented with cardiac insufficiency. Urine volume was 800±300ml/24 hours before treatment and 2000±500ml/24 hours after treatment. Sodium excretion in urine was 80±20mmol/24 hours before treatment and 150±50mmol/24 hours before treatment. The average net weight change was -3.5±2.2kg. The Scr increased by 30%±5% before and after treatment, and the renal function in 2 patients increased by >30% after 7 days of treatment, and returned to the level of Scr before treatment after 7 days of withdrawal of Dapagliflozin/ Canagliflozin. Electrolyte levels were comparable before and after treatment.

Conclusion

The diuretic regimen based on SGLT2i could significantly improve the resistance of diabetic nephropathy patients to loop diuretics, increase urinary sodium excretion, and slightly elevate renal function in the short term without affecting blood electrolyte level. The efficacy and safety of long-term use of SGLT2i in diabetic nephropathy patients at CKD3-4 stage need further investigate in larger sample size.
P1037EFFECT OF VITAMIN D SUPPLEMENTATION ON PROTEINURIA, LIPID STATUS, GLICOREGULATION, C-REACTIVE PROTEIN, VEGF-A, TGF-BETA1 AND NEPHRIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Petroviä‡ Marijana , Petrovic Stanko , Obrencevic Katarina , Dragovic Tamara , Rancic Nemanja , Vavic Neven , Vojvodic Danilo , Petrovic Dejan , Rabrenovic Violeta , Tadic Jelena , Mijuskovic Mirjana , Terzic Brankica , Pilcevic Dejan
Published: June 2020

Background and Aims: Vitamin D insufficiency/deficiency is often present in patients with Type-2 diabetes mellitus and could present a risk factor for rapid progression of diabetic nephropathy and higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on glucoregulation, inflammation, cholesterol, triglycerides, albuminuria and biomarkers of renal injury – nephrin, VEGF-A and TGF- β1 in patients with Type-2 diabetes mellitus and vitamin D insufficiency/deficiency. Method: We included 90 patients with Type-2 diabetes mellitus and vitamin D insufficiency/deficiency in this prospective, cohort study. Patients are divided in 3 equal groups: 30 patients with normal albuminuria, 30 with microalbuminuria and 30 with macroalbuminuria. Therapy included 6 months of supplementation with cholecalciferol drops: first 2 months with 20000 IU twice weekly, than if vitamin D level remained below normal range, we procedeed with same dose next 4 months. If the level of vitamin D normalized, we proceeded with 5000 IU twice weekly. At the beginning and at the end of the study we measured levels of albumin, hemoglobin, serum iron, urea, creatinine, fasting blood glucose, hemoglobin A1c, calcium, phosphorus, total cholesterol, triglycerides, C-reactive protein, intact parathyroid hormone, and urine analysis: 24-hour urine protein, albumin/creatinine ratio and creatinine clearance. Biomarkers are measured in serum and urine. Levels of calcium, phosphorus and vitamin D are also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results are analysed according to the vitamin D level at the beginning and at the end of the study. Results: The lowest level of vitamin D, before therapy, is found in patients with macroalbuminuria, while at the end of the study we found significantly higher level of vitamin D in all three groups. After 6 months of therapy we found significant decrease of 24-hour urine protein, total cholesterol, triglycerides, hemoglobin A1c and VEGF-A in urine, in all three groups, and C-reactive protein in patients with normal albuminuria and microalbuminuria, nephrin in urine in patients with microalbuminuria and TGF- β1 in urine in patients with macroalbuminuria. Conclusion: vitamin D supplementation with high-dose cholecalciferol in patients with Type-2 diabetes mellitus (with or without albuminuria) decreases C-reactive protein, hemoglobin A1c, total cholesterol, triglycerides in serum, and albumin/creatinine ratio, 24-hour urine protein, VEGF-A, TGF- β1 and nephrin in urine.
P1040PREGNANCY IN WOMEN WITH DIABETIC NEPHROPATHY: COMPLICATIONS AND OUTCOMES
Authors: Prokopenko Elena , Vatazin Andrey , Gurieva Vera , Nikol`skaya Irina , Burumkulova Fatima , Zulkarnaev Aleksei
Published: June 2020

Background and Aims

Pregnancy in patients with diabetic nephropathy (DN) is characterized by an increased incidence of complications and adverse outcomes. The aim of the study was to determine the nature and incidence of pregnancy complications and maternal and fetal outcomes in women with DN.

Method

61 pregnant women with diabetes mellitus (DM) type 1 and CKD 1-4 stages: 1 st. –29 patients, 2 st. - 19, 3-4 st. – 13 (age 29.7±4.9 years, DM duration 18.6 ± 5,3 years) and 72 pregnant patients with pre-existing (type 1) DM without CKD (age 28.2±4.8 years, DM duration 11.4 ±3.7 years) observed in 2010-2017 were included. The incidence of chronic arterial hypertension (AH), preeclampsia (PE), fetal macrosomia, fetal growth restriction, preterm delivery, cesarean section, stillbirth and the effect of pregnancy on kidney function were evaluated.

Results

Chronic AH was detected in 19.4% of women w/o CKD, in 10.3% – CKD 1 st, 17.6% – CKD2, 61.3% – CKD 3-4 (p < 0.05 CKD3-4 vs CKD1). The incidence of PE in patients w/o CKD was 12.5% (2-3% for general population), with CKD 1 – 24.1%, CKD 2 – 41.2%, CKD 3-4 – 38.5% (p < 0.001 when comparing all groups). Macrosomia was common in pregnant diabetic women w/o CKD (30.6%), patients with CKD 1 (41.4%) and CKD 2 (52.9%), but was not observed in CKD 3-4 (0%). In contrast, the incidence of fetal growth restriction was highest with CKD 3-4 (61.5%) compared women w/o CKD (5.6%) and with CKD1(13.8%) and CKD2 (11.8%), p < 0.05.Preterm delivery was more common in women with CKD, and its frequency increased with increasing severity of CKD: w/o CKD – 18.1%, CKD 1 – 48.3%, CKD2 – 61.3%, CKD 3-4 –84.6% (p < 0.05). Incidence of cesarean section was high and did not differ significantly between groups: w/o CKD – 62.5.1%, CKD 1 – 55.2%, CKD2 – 82.4%, CKD 3-4 –92.3% (p > 0.05). Stillbirth was observed only with CKD stage 3-4 in 15.4% of cases.Four out of 13 (30.8%) patients with pre-existing CKD 3-4 and none of the patients with CKD1-2 reached stage 5 CKD and started regular hemodialysis with a median follow-up period of 43.3 months (min 29.7 - max. 81.5).

Conclusion

DN has a negative effect on pregnancy outcomes, increasing the frequency of preeclampsia, fetal growth restriction, preterm birth and stillbirth, however, fetal macrosomia practically does not occur with CKD 3-4. The rapid achievement of CKD 5D after delivery is typical for diabetic women with advanced stages of CKD.
P1047URICOSURIA AND URINARY GLUCOSE EXCRETION ON DIABETIC KIDNEY DISEASE (DKD) PATIENTES TREATED WITH SGLT2 INHIBITORS
Authors: Marques Vidas Maria , Maroto Alba , Sanz Ignacio , López Paula , Portoles Jose' M
Published: June 2020

Background and Aims

The use of sodium glucose co-transporter 2 inhibitors (SGLT2i) is consistently associated with decrease of serum uric acid levels due to increase uricosuria coupled to glucosuria by mechanisms that are still incompletely understood. In diabetic kidney disease these drugs had shown only modest effects on HbA1c control allegedly due insufficient glucosuric effect. However, renal patients also benefit from hypouricemic effect of SGLT2 inhibitors. The aim of this study was to evaluate glucosuria and uricosuria in DKD patients treated with SGLT2i

Method

We prospectively analyzed glucose and urate fractional excretions of patients that were to initiate treatment with an SGLT2i, using fractional excretion classical formulas. Patients on GLP1ar or any uricosuric agent including losartan were excluded. All participants gave written consent.

Results

37 patients (75.7% male) diagnosed from DKD were included, median age 69.6 years IQR [65.6-73.4], median CKD-EPI eGFR 54,10 ml/min/1,72 m2 [ 41,12- 69,68 IQR] and UACR 137 [49-443] mg/g. SGLT2i used was 53.3% dapagliflozin, 24.4% empagliflozin or 22.2% canagliflozin and mean follow- up was 1.5 years.Serum uric acid levels didn’t show any significative difference along time in this group of patients (6.8 vs 6.3; p 0.4) and %HbA1C was only slightly decreased by month 12 (7.1 vs 6.7; p0.03). Urinary uric acid fractional excretion increased by month 3 and was stabilized till month 12 when this effect seemed to decrease (figure and table) Glucosuria exhibit a similar effect: Urinary glucose fractional excretion increased immediately after the addition of the drug and stabilized over time decreasing at the end of the observation period. Spearman rank correlation test indicated dependency glucosuria and uricosuria (Spearman´s rho 0,24, p 0,03). GFR estimated by CKD-EPI kept stable along the study indicating that loss of uricosuric and glucosuric effect are independent of GFR

Conclusion

We conclude that uric acid renal excretion is significantly increased in patients treated with SGLT2i even in the presence of DKD but tends to diminish over time, feature that was also observed on urinary glucose excretion and that showed no correlation with GFR. Over-expression of SGLT1 after SGLT2 inhibition has been described in animal models of DKD. Whether this extends to human tubule and explains these results need to be further investigated
P1048EMPHYSEMATOUS PYELONEPHRITIS IN TYPE 2 DIABETES -CLINICAL PROFILE AND MANAGEMENT
Authors: Bhat Dr Sanjay , Srivastava Alok , Ahmad Nisar , Rai Priyanka , Singh R P , Srivastava Rohit , ROY A K , Fatima Jalees
Published: June 2020

Background and Aims

Emphysematous pyelonephritis (EPN) is a rare but life-threatening acute suppurative infection of the kidney.60-70% are associated with uncontrolled diabetes mellitus (DM) with or without obstructive uropathy and superimposed with infection caused by gas-forming organisms. Conventional treatment of EPN is parenteral antibiotics with percutaneous or open surgical drainage and/or nephrectomy. There is no current consensus on management of EPN as to whether present day antibiotics alone good enough or is surgical intervention necessary and if surgical intervention required when should one go for nephrectomy.

Method

A prospective observational study was conducted at Tertiary care hospital, Lucknow from 2015-2018 to look for clinical, microbial profile and treatment outcome of diabetic patients with emphysematous pyelonephritis.The clinical features and laboratory data at the initial presentation, management and outcomes were analyzed .Contrast enhanced computerized tomography (CECT) was performed in case of suspected renal abscess and nonrecovering pyelonephritis

Results

A total of 76 Diabetic patients diagnosed with pyelonephritis were identified, of which 15 patients were diagnosed with EPN (26.3%) Renal papillary necrosis and renal abscess was seen in 1 and 3 patients, respectively. The mean age of the patients was 58.4 ± 6.5 years (age range 22-79 years). Pyelonephritis was more common among males. Duration of symptoms prior to hospitalization ranged from 16.34 ± 7.32 (range 8-32) days. Renal dysfunction at presentation was seen in 15 (100%) patients. Bilateral involvement was seen in 5 (33.3%) patients. Fever was the most common presenting symptom followed by dysuria. Urine and blood cultures were positive in 13 (88.3%) and 3 (20 %) patients respectively. Gram-negative bacilli were the most frequent organisms isolated, Escherichia coli in 11 (73.3%), Klebsiella sp. in 1 (6.6%), Pseudomonas in 1 (6.6%), and 1 each with polymicrobial and fungal UTI respectively. The fungus included Candida albicans managed with fluconazole. Good, moderate, and poor glycemic control was seen in 13 (12.3%), 16 (15.2%) and 76 (72.3%), respectively.Of 15 EPN patients, 13 (86.6 %) survived and 2 (13.3%) expired. 2 of them underwent Nephrectomy both survived.All patients with Stage I, II and IIIa EPN (n = 12) were managed with antibiotics with or without PCD. In EPN Stage IIIb/IV (n = 3), all the 3 (20 %) patients were managed with antibiotics and PCD and later 2 (13.3%) needed nephrectomy.Of different variable only altered sensorium and shock at presentation were associated with poor outcome in EPN patients (P < 0.05)

Conclusion

EPN in diabetics needs good multidisciplinary approach with adequate antibiotics and surgical management as and well required for better patient outcomes.
P1049LOWER ACCEPTANCE RATE FOR PANCREAS OR ISLET TRANSPLANTATION AFTER INTRODUCTION OF A MULTIDISCIPLINARY APPROACH FOR TRANSPLANT ELIGIBILITY
Authors: Nordheim Espen , Lindal Jørn Petter , Nordheim Espen , Åsberg Anders , Birkeland Kåre , Horneland Rune , Boye Turid Birgitte , Jenssen Trond Geir
Published: June 2020

Background and Aims

β-cell replacement therapy, with either pancreas or islet transplantation, is a treatment option for selected patients with brittle type 1 diabetes. All patients referred to the national transplant centre for assessment of this treatment, are evaluated in the outpatient clinic before any work-up for transplantation is initiated. Before 2015, this assessment was performed by a nephrologist alone, while from 2015 the assessment has also included an endocrinologist, a transplant surgeon and a psychiatrist in a multidisciplinary team.

Method

The proportion of patients accepted for transplantation before and after the multidisciplinary approach were compared. A chi square test was used for comparing the groups in the two periods; 2010-2014 versus 2015-2019 vs. P-values are reported according to two- tailed analysis, and p- values < 0.05 were considered statistically significant.

Results

From 2010 to December 2019, 144 patients were assessed for β-cell replacement therapy eligibility. Out of all patients referred, 64 out of 79 (81%) and 22 out of 65 (34%) were listed for transplantation before and after the multidisciplinary assessment was introduced (p-value < 0.005). The main reasons for not being listed after the introduction of a multidisciplinary team were suboptimal diabetes treatment and that the patients withdrew their interest after the outpatient clinic visit with thorough information about advantages and risks.

Conclusion

The rate of patients who were accepted for islet or single pancreas transplantation declined after a multidisciplinary approach was introduced for transplant candidate eligibility. We suggest that a broader, multi-disciplinary approach revealed previously undetected medical issues and improved patient information that subsequently resulted in fewer patients listed for transplantation.
P1050THE EFFICACY AND RENAL SAFETY OF SWITCHING FROM DAPAGLIFLOZIN TO EMPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES
Authors: YANG AI-YU , Chen Hung-Chun
Published: June 2020

Background and Aims

Both dapagliflozin (DPG) and empagliflozin (EPG) are highly selective sodium-glucose cotransporter-2 (SGLT-2) inhibitors that inhibit glucose reabsorption and increase its excretion in urine. Previously, DPG was limited to patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, while EPG can be used for those with an eGFR ≥ 45 mL/min/1.73 m2. Therefore DPG was switched to EPG in many patients when eGFR decreased. However, the clinical efficacy and safety of these switches are not clear. In this study, we compared the efficacy and renal safety between patients switching from DPG to EPG and those continuing DPG in patients with type 2 diabetes mellitus (T2DM).

Method

This retrospective observational study included patients with T2DM who were treated with DPG for more than 6 months. This study included patients who switched to EPG and those who continued using DPG. All other hypoglycemic drugs were maintained at the same dosage before and after the study period. The primary outcome measure was the change in hemoglobin A1c (HbA1c) level after 6 months. The EPG group was evaluated for whether the hypoglycemic effect remain effective after drug switching. Patients with HbA1c levels at or lower than the baseline value after 6 months were defined as effective and patients with levels higher than the baseline were defined as invalid. Safety was evaluated by comparing the difference of eGFR between the baseline value and six months after treatment.

Results

This study included 169 patients. Among them, 72 patients continued DPG and 97 patients switched to EPG. HbA1c level decreased significantly only in EPG group. In EPG group, 59 patients belong to the effective group (60.8%) and 38 patients were invalid (39.2%). There was no significant change in eGFR after treatment in both groups. Ten patients in DPG group develop adverse reactions (three patients felt uncomfortable and seven patients had urinary tract symptoms), but all continued treatment. In EPG group, five patients lacked follow-up records during the study period and it was difficult to determine whether the patient’s willingness to continue treatment was affected by adverse reactions.

Conclusion

Our study showed that switching from DPG to EPG in patients with T2DM was effective for blood glucose maintenance and caused no significant changes in renal function. In addition, no severe drug-related adverse reactions were found.
P1055REMARKABLE REMOVALS OF BETA-2-MICROGLOBULIN AND PHOSPHATE WITH SHORT-DAILY HOME HEMODIALYSIS USING LOW DIALYSATE FLOW RATE
Authors: Gonzã¡lez Moya Mercedes , Molina Pablo , Vizcaíno Belén , Rodrigo María , Pascual Pilar , Beltrán Sandra , Yugueros Alejandra , Calatayud Emma , Lidón Maria Jesús , Moncho Cristela , Santaolaria Marisa , Carbonell Araceli , Sáez Guillermo , Estañ Nuria , Pallardó Luis M
Published: June 2020

Background and Aims

Short-daily hemodialysis (HD) with low-dialysate volume is an appealing portable dialysis approach for home use. Although this type of HD has proved being effective for the volume control and the clearance of low molecular-weight uremic toxins, limited data are available on the impact on the removal rates of other uremic toxins like β2-microglobulin (β2M) or phosphate (P), whose clearance is limited by sequestration into compartments, poor diffusion, high time-dependency, or protein binding. We evaluated the impact of short-daily HD with slow dialysate flow rate on the removal of solutes of different molecular weights and distribution volumes.

Method

Single-session and weekly balances of β2M, P, urea, and creatinine were prospectively assessed with total dialysate collection and serum measurements before and after 341 dialysis sessions (mean dialysate volume: 30963 ± 862 mL; mean length of dialysis session: 153 ± 8 min) in 31 stable patients (female; 9, 29 %; mean age: 55.6 ± 13.6 y; dry weight: 74.9 ± 13.3 kg) undergoing short-daily home HD with NxStage cycler, between July 2014 and October 2019. The mean blood flow rate was 365 ± 17 mL/min, whereas the mean dialysate flow rate was 194 ± 12 mL/min.

Results

Single-session β2M, P, urea, and creatinine removals were 0.138 ± 0.050 g, 0.610 ± 0.161 g, 18.89 ± 6.07 g and 1.07 ± 0.31 g, respectively, whereas the reduction rates (%) were 38.0 ± 13.0, 46.8 ± 8.6, 48.2 ± 7.0 and 46.6 ± 6.6, for β2M, P, urea and creatinine, respectively. The estimated weekly β2M, P, urea and creatinine removals in HDD patients dialyzing 5-6 days per week were comparable with 4-h in-center thrice-weekly on-line hemodiafiltration according to previous studies (Table 1).

Conclusion

Treating patients with short-daily HD with low-dialysate volume at a 5-6 days per week prescription may achieve an efficient weekly β2M and P removal.
P1059REMOVAL OF LOW MOLECULAR WEIGHT AND PROTEIN-BOUND UREMIC RETENTION SOLUTES WITH ALLO-HEMODIALYSIS: RESULTS FROM EX VIVO STUDY
Authors: Maheshwari Vaibhav , Grobe Nadja , Chao Joshua , Tao Xia , Thijssen Stephan , Kotanko Peter
Published: June 2020

Background and Aims

It is projected that in 2030, 14.5 million people will have end stage kidney disease and need kidney replacement therapy, yet only 5.4 million will receive it due to economic, social, and political factors. We have proposed allo-hemodialysis (alloHD) as a simple and low-cost HD alternative (https://www.kidneynews.org/kidney-news/features/buddy-dialysis-probed-hemodialysis-alternative). In alloHD, the patient’s blood is dialyzed against the blood of a healthy subject (‘buddy’), who receives the excess fluid and uremic solutes and excretes them via his/her healthy kidneys.

Method

We conducted ex vivo experiment with bovine whole blood, 4L in a patient and buddy bucket, respectively. In this setup, buddy blood flows through the dialyzer fiber lumen, while patient blood flows in the dialysate space (Nipro Cellentia 17H dialyzer). The patient blood was spiked with urea, creatinine, potassium chloride, indoxyl sulfate (IS), and p-cresyl sulfate (pCS); solute levels on the buddy side were not altered. The alloHD session lasted for 3 hours, the ultrafiltration (UF) volume was 750 mL. The blood flow rates were kept constant at 150 and 200 mL/min on the patient and buddy side, respectively. Heparin (5000 IU/L) was added to either bucket. The alloHD machine prototype comprises 2 pumps on the buddy side and one on patient side (Figure 1A). UF is controlled by the blood flow rate differential between the buddy-sided arterial and venous pumps, respectively.

Results

The levels of small unbound solutes (urea, creatinine, potassium) equilibrate quickly between patient and buddy buckets (Fig. 1B, top panel). Of note, the buddy-sided potassium equilibrium concentration is lower, because ongoing UF dilutes albumin in the buddy bucket and concentrates it in the patient bucket, resulting in a Gibbs-Donnan potential. The protein-bound uremic solutes IS and pCS equilibrate towards lower total concentrations on the buddy side due to the earlier mentioned UF-induced albumin dilution. Of note, the levels of free IS and pCS, respectively, converge on both sides of the dialyzer membrane (Fig 1B, bottom panel).

Conclusion

Our ex vivo data suggest that alloHD can be used to treat hyperkalemia, a major cause of death in acute and chronic kidney failure. Both unbound and protein-bound low molecular weight uremic solutes are also removed. With elimination of “classical” dialysate, we simplify the HD procedure and reduce machine size and costs significantly, making it an affordable HD alternative. Feasibility and efficacy studies in animal models are the next step.
P1063PERFORMANCE OF MEDIUM CUT-OFF DIALYZERS IN EXPANDED HEMODIALYSIS PATIENTS IN COLOMBIA
Authors: D'Achiardi Roberto , Zuñiga Eduardo , Molano Alejandra , Tran Ha , Parreno Rhea , Vesga Jasmin , Rivera Angela
Published: June 2020

Background and Aims

Uremic toxins which are retained in ESRD include small solutes to large middle molecules. Large middle molecules play significant roles in immune modulation and cardiovascular morbidity and mortality. Expanded hemodialysis (HDx) enabled by innovative medium cut-off (MCO) membrane more effectively removes large uremic toxins vs current dialytic therapies.

Aims: To evaluate the efficacy of MCO dialyzer in large middle molecules removal and pre-dialysis albumin levels after 24 weeks of treatment.

Method

This was an exploratory, prospective observational, multicenter cohort study. Prevalent patients on HD therapy for at least 90 days at the Renal Care Services (RCS) were included between June 6, 2018, to June 14, 2018. Uremic toxins removal was evaluated by measuring the reduction ratio (RR) of free light chains (FLC) κ, λ, Interleukin (IL) 6, IL-10, β2 Microglobulin (β2 M) and fibroblastic factor 23 (FGF-23) at 12 weeks ( w) of treatment, as well as the change in predialysis midweek serum level of β2M, FGF-23, factor XIV activity, and VII at baseline, 12 w and 24 w of treatment. A mixed-model repeated measures analysis (MMRM) was performed to identify statistical differences over time

Results

The RR of κ-FLC, λ-FLC, β2 M, and FGF-23 at week 12 showed a reduction between 46-72%; while in IL-6 RR was not significantly changed (Table 2). Predialysis serum levels decreased for β2m, FLCs and IL-6 and FGF 23 (Table 3). The decrease in albumin was within 5% from baseline.

Twenty-two adverse events (AEs) occurred during the follow-up period; No AEs during HDx were deemed related to MCO membrane use.

Conclusion

MCO dialyzers are safe and effective in removing large MMs and decrease in the uremic toxins levels.
P1066OBJECTIVIZATION OF “DRY WEIGHT” CLINICAL ASSESSMENT IN HEMODIALYSIS PATIENTS BY MULTI-FREQUENCY BIOIMPEDANCE SPECTROSCOPY WITH VECTOR ANALYSIS
Authors: Vishnevskii Konstantin , Dudash Ekaterina , Domashenko Olga , Volkova Olga , Turbasova Elena , Frolova Ekaterina
Published: June 2020

Background and Aims

Hydration status is an important prognostic factor in patients receiving hemodialysis (HD). An accurate hydration status assessment and determination of the euvolemia (“dry weight”, DW) target value is a difficult task and need to be objectified by instrumental methods. One of these methods is the vector analysis of multi-frequency bio-impedance spectroscopy (MBIS). The aim of the study was to assess the effect of DW correction according to the results of a vector analysis of MBIS on the blood pressure dynamics and the frequency of intra-dialysis complications.

Method

Total 104 patients were included in the study. The mean age was 63±11 years, mean duration of renal replacement therapy was 91±68 months. Patients were randomly (block randomization) divided into the study (SG, N=52) or control (CG, N=52) groups. In the SG, the correction of DW performed according to the results of the MBIS vector analysis using the Bodystat MultiScan 5000 analyzer (Bodystat Ltd) with specially developed correction algorithm (figure). In the CG the correction of DW was carried out only according to clinical indicators. Within 3 months before and 3 months after the initial assessment of DW the blood pressure during HD and the number of intradialytic complications were recorded in all patients.

Results

In the SG, DW was increased in 13 patients by an average of 1.0±0.9 kg, decreased in 26 patients (-1.1±0.7 kg) and did not change in 13 patients. In the CG, DW increased on average by 1.3±0.9 kg in 19 patients, in 27 decreased (-1.2±0.8 kg) and in 2 did not change. In patients who had a history of increased blood pressure during dialysis, in SG the frequency of hypertension episodes decreased from 3.8 to 1.1 episodes per month (p=0.02), in contrast to CG (from 2.4 up to 2.3 episodes per month, p=0.87). Also, among patients initially prone to hypertension in SG, in contrast to CG, a decrease in systolic blood pressure was observed both before the HD (from 163±16 to 143±10 mm Hg, p=0.004) and after the HD (from 151±23 to 130±15 mmHg, p=0.02). No changes in the frequency of episodes of hypotension and diastolic blood pressure during HD were observed either in the study or in the control group

Conclusion

Objectification of the dry weight clinical assessment of in HD patients using multifrequency bioimpedance spectroscopy with vector analysis can help to reduce the complications rate and arterial hypertension severity.
P1069COMPARISON OF BIOCOMPATIBILITY OF REGULAR AND INCREASED DOSE OF CITRATE IN CHRONIC HEMODIALYSIS - PRELIMINARY RESULTS OF A RANDOMIZED TRIAL
Authors: Orsag Alesa , Bozic-Mijovski Mojca , Simcic Sasa , Gubensek Jakob
Published: June 2020

Background and Aims

The dose of citrate that is needed in regional citrate anticoagulation (RCA) to achieve optimal biocompatibility of the extracorporeal circuit is not known. Insufficient biocompatibility is related with increased inflammation and oxidative stress and therefore higher risk for cardiovascular events, as well as decreased dialysis dose. Biocompatibility is multifaceted and includes activation of coagulation and complement cascades, as well as degranulation of leukocyte and platelets. We performed a randomized control trial (ACTRN12613001340729) to compare regular and increased dose of citrate in RCA.

Method

30 chronic hemodialysis patients were randomly assigned to a single hemodialysis session with RCA using either regular (2.7 mmol/l) or increased dose of citrate (4.0 mmol/l). Markers of activation of complement system (C5a), activation of hemostasis (thrombin – antitrombin complex (TAT)), activation of platelets (platelet factor 4 (PF4)) and activation of leukocyte (myeloperoxidase (MPO)) were taken at the beginning (time 0), after 30 minutes (arterial line) and after 4 hours (arterial and venous line) of dialysis. Results were corrected for changes in hematocrit, and compared between groups using T test.

Results

There was no significant difference in any of the measured biocompatibility parameters between the two citrate dose groups at any of the time points. We have observed a significant, but transient increase in PF4 after 30 minutes (28 +/- 17 to 47 +/-29 IU/mL vs. 30 +/-17 to 54 +/- 33 IU/mL, p<0.05 for both groups), which was parallel in both groups (p=0.76 for between group comparison). No significant changes in TAT, MPO or C5a were observed during dialysis. There were no clotting problems or significant hypocalcemia observed in either group.

Conclusion

Given the absence of significant increase in the majority of biocompatibility parameters at the standard dose of citrate and absence of blunting of PF4 increase by the higher dose of citrate, the standard dose of citrate (2.7 mmol/l) seems sufficient in RCA for chronic hemodialysis.
P1070ONLINE HIGH-VOLUME HEMODIAFILTRATION REDUCES PRE-DIALYSIS LEVELS OF INDOXYL SULFATE COMPARED TO HIGH-FLUX HEMODIALYSIS: RESULTS FROM HDFIT MULTICENTRIC RANDOMIZED CONTROLLED TRIAL
Authors: Lima Jordana , Guedes Murilo , Rodrigues Silvia , Flórido Ana Clara , Barra Ana Beatriz , Canziani Maria Eugênia , Cuvello Américo , Poli De Figueiredo Carlos Eduardo , Pecoits-Filho Roberto , Nakao Lia
Published: June 2020

Background and Aims

Online High-Volume Hemodiafiltration (OL-HDF) combines convective and diffusive clearances and is associated with better outcomes compared to standard hemodialysis (HD). Although HDF has been shown to improve the clearance and pre-dialysis concentration of middle size uremic toxins, little is known about its effect on concentration of protein-bound uremic toxins (PBUT), particularly in comparison to high-flux HD. Here, we investigated whether high-volume post-dilution OL-HDF impacts pre-dialysis plasma levels of PBUT indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole 3-acetic acid (IAA) compared to high-flux HD over time, since accumulation of these PBUT has been associated with increased overall mortality of CKD patients.

Method

This is post hoc analysis of the multicentric randomized controlled trial (RCT) studying the impact of post-dilution high-volume OL-HDF versus high-flux HD on measured physical activity (HDFit - clinicalTrials.gov: NCT02787161), which included clinically stable HD patients with a vintage >3 to <24 months. Total plasma levels of IxS, pCS and IAA were determined by high performance liquid chromatography (HPLC) with fluorescence detection at baseline, 3 and 6 months. The difference between HDF and HD in respect to changes in the PBUT concentrations during the follow up, analyzed using linear mixed effect models, was compared. Results are presented as mean differences between groups in the change from baseline along with 95% confidence intervals (CI).

Results

193 patients (mean age 53 years old, 70% males and 60% white – no differences between groups) were analyzed. There were no differences between HD and OL-HDF groups regarding clinical and biochemical characteristics at the baseline. In the OL-HDF group, 99% of patients achieved a convective volume higher than 22 L and both groups had similar dialysis session duration and blood flows throughout the follow up. The mean differences (95% CI) in concentrations over time for PBUTs among HDF and HD groups are shown in Figure 1. HDF group presented a significantly lower trajectory of IxS levels and a lower trajectory of pCS levels than HD group. Trajectories of IAA levels were not different between groups.

Conclusion

OL-HDF reduced the pre-dialysis concentration of IxS and pCS through 6 months-period compared to high-flux HD.
P1074SIMPLIED REGIONAL CITRATE ANTICOULATION USING A CALCIUM-CONTAINING REPLACEMENT SOLUTION FOR RENAL REPLACEMENT THERAPY: A RANDOMIZED CONTROLLED CLINICAL TRIAL
Authors: Wei Tiantian , Fu Ping , Zhang Ling
Published: June 2020

Background and Aims

A simplified protocol for Regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without a continuous calcium infusion, is more efficient to be used in continuous renal replacement therapy (CRRT). We aim to design a randomized prospective pilot trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solution in CRRT with RCA.

Method

Of the 59 patients who requiring CRRT and being treated with RCA-based continuous venovenous hemodiafiltration (CVVHDF) enrolled, 31 patients were randomized to calcium-containing group and 28 to calcium-free replacement solution group. Primary endpoints were filters lifespan. Secondary endpoints were mortality, kidney function recovery and severe complications rates. Time spent on fluids preparation before CRRT and the amount of 4% trisodium citrate solution pumped during CRRT were recorded. Serum and effluent citrate and calcium concentration during CVVHDF were measured during CRRT.

Results

Filters lifespan were superior for calcium-containing group (mean 58.06 versus 47.12 hours, P=0.05). Mortality and renal outcome were comparable between groups during hospitalization: 10/31 (33.26%) of calcium-containing group patients died versus 13/28 (46.43%) of calcium-free group patients, and 16/31 (51.61%) of calcium-containing group patients had kidney function recovery versus 15/28 (53.57%) of calcium-containing group (P = 0.265). Only 5 patients showed the symptoms and signs of hypocalcemia or citrate toxicity in this study. The mean CRRT preparation time in calcium-containing group: 25.5 minutes, was significantly shorter than calcium-free group: 43.7 minutes (p<0.001). The serum and effluent calcium concentration was slightly lower in calcium-containing group during CRRT. While, the mean 4% trisodium citrate solution infusion rate was similar between groups (161.5 mL/h versus 157.4 mL/h, P=0.376).

Conclusion

Patients treated with calcium-containing or calcium-free replacement solution have similar clinical outcomes. Since the calcium-containing replacement solution based RCA has longer filter lifespan and obviates the need for a separate venous catheter and intravenous calcium preparation for continuous intravenous calcium infusion, it is more efficient to be used in clinical practice and superior to the calcium-free replacement solution.
P1075CONTROL AND MONITORING OF DIAGNOSTIC AND TREATMENT PROCESS IN HEMODIALYSIS CLINIC USING TELEMEDICINE TOOLS
Authors: Zinovev Dmitriy , Novitskiy Vladimir , Malkoch Andrey
Published: June 2020

Background and Aims

Quality of life of hemodialysis patients and adequacy of hemodialysis therapy in general, is defined by the number and duration of incidents during hemodialysis procedures. In this study we examined the effect of telemedical system for control and monitoring of hemodialysis procedures on patients’ condition and their quality of life.

Method

The system described in this work included: doctor/patient video call functionality initiated from both ends; functionality of hemodialysis procedure parameters and patient’s condition parameters monitoring and registration; functionality of alerting medical staff about registered incidents, functionality of visual control of hemodialysis procedure. The effect of control and monitoring system usage was studied on population of 2300 hemodialysis patients (at the start of the study) with median follow-up of 2 years. The primary end-point was doctor’s reaction time on patient’s complaint, medical staff reaction time on intradialysis hypertension incidents. Secondary end-points were: number of patients who left the clinic due to reasons besides lethality, patients’ satisfaction by hemodialysis therapy (according to survey), number of incidents of intradialysis and interdialysis hypertension.

Results

During the study we observed that as a result of system deployment average doctor’s reaction time on patient’s complaint (defined as the time from emergence of the complaint to start of patient/doctor communication) reduced from 8 to 1.5 minutes, average staff reaction time on intradialysis hypertension incidents (defined as time from registration of hypertension incident to start of blood pressure normalization actions) reduced from 5 to 2 minutes. Number of patients who left the clinic due to reasons besides lethality reduced from 2.5 per 100 patients before system deployment to 1.7 per 100 patients at the end of the study. Average value of patient’s satisfaction by dialysis therapy increased from 7.2 to 9.1 points on 10-point scale (according to survey conducted at the beginning and at the end of the study). By the end of the study, average number (across population) of hypertension incidents per month reduced from 8.3 to 6.2 and from 20.7 to 16.5 episodes for intradialysis and interdialysis hypertension correspondingly.

Conclusion

The use of telemedical tools of hemodialysis procedures control and monitoring has positive impact on patients’ satisfaction level by the dialysis procedure and on duration/frequency of incidents registered by these tools, which, in return may improve the quality of patient’s life.
P1078IMPACT OF A MEDIUM CUT-OFF DIALYZER ON SKIN AUTOFLUORESCENCE IN HAEMODIALYSIS PATIENTS
Authors: Viramontes Horner Daniela , Kolhe Nitin , Leung Janson , Fluck Richard , Selby Nicholas , Taal Maarten
Published: June 2020

Background and Aims

Advanced glycation end-products (AGEs) are middle-sized uraemic toxins that accumulate in haemodialysis (HD) patients due to increased production, impaired excretion and insufficient removal. Previous studies have reported that the use of a medium cut-off (MCO) dialyzer promotes a greater removal of larger middle molecules (such as AGEs) than conventional high-flux HD and haemodiafiltration. However, to our knowledge, there is no published evidence regarding the effect of an MCO dialyzer on skin autofluorescence (SAF), a measure of long-term tissue AGE accumulation and independent risk factor for mortality in the HD population. We aimed to investigate the impact of using an MCO dialyzer on change in SAF over time in HD patients.

Method

HD patients were enrolled in a prospective observational study. SAF was measured using a validated Autofluorescence Reader at baseline, 12 and 24 months. During the initial 12 months patients dialysed using high-flux polysulphone, polyarylethersulfone or polyvinylpyrrolidone dialyzers. At a variable time after 12 months patients were switched to an MCO dialyzer (Theranova; Baxter®). Forty patients who had been using the MCO dialyzer for at least 3 months were included in this analysis.

Results

Mean age, baseline SAF levels and time on MCO dialyzer were 63±13 years, 3.5±0.9 arbitrary units (AU) and 124±49 days, respectively. SAF increased significantly from baseline to 12 months (3.5±0.9 vs. 3.9±1.1 AU; p<0.0001) but tended to decrease between 12 and 24 months, after conversion to an MCO dialyzer (3.9±1.1 vs. 3.7±0.7 AU; p=0.06). Additionally, mean ΔSAF from baseline to 12 months was positive (0.41±0.68 AU) whereas ΔSAF from 12 to 24 months was negative (-0.18±0.76 AU; p=0.002 for comparison). Furthermore, SAF at 24 months correlated negatively and significantly with time on MCO dialyzer (r= -0.384; p=0.01) though second year ΔSAF (delta from 12 to 24 months) did not (r= 0.061; p=0.7).

Conclusion

We found in this observational study that SAF levels decreased/stabilised in HD patients after switching to an MCO dialyzer compared to the time when patients were using conventional high-flux HD and haemodiafiltration, during which SAF levels increased. Future prospective and interventional studies with larger sample sizes and longer follow-up are needed to confirm these findings and to evaluate the impact of using an MCO dialyzer on long-term outcomes, including survival.
P1088BRAND NEW METHOD TO CALCULATE THE VOLUME OF EXTRA CELLULAR FLUID IN HEMODIALYSIS PATIENT ONLY FROM REGULAR BLOOD TEST
Authors: Shibata Kazuhiko , Nakai Shigeru , Masakane Ikuto , Ito Takahito , Ozawa Kiyoshi , Maeda Kanenori , Matusuoka Teppei , Shinzato Takahiro
Published: June 2020

Background and Aims

Uric acid is a small molecule with molecular weight 168, but has an electrical pole which enables pass through the phospholipid bilayers of cell membranes by simple diffusion. Urate transport proteins of cell membranes (URAT1, GLUT9, OAT, MRP4, MCT9, NPT4, ABCG2) are expressed only in uric acid-excreting tissues. These findings suggest that uric acid does not pass through the cell membrane, either by diffusion or active transport. Since uric acid does not pass through cell membranes, the uric acid distribution volume (UDiV) would reflect the extracellular volume (ECV). At ASN 2018, we reported that UDiV significantly correlated with ECV predicted by the bio-impedance method measured by InBody, S 20 (Biospace Co., Ltd, Korea). However, both data were correlated, there was a large fixed error. This time, we examined the correlation with the UDiV again using the Fresenius BCM (Fresenius Medical Care, Bad Homberg, Germany), which is trusted worldwide.

Method

We calculated UDiV from regular blood test results by uric acid kinetic modeling.

This study was performed in Yokohama Minami Clinic. One hundred nine patient under hemodialysis was consented and enrolled in this study. The HD patients were 59males and 50females. 68.0±10.9years old.

We performed UDiV calculation from blood samples obtained before and after hemodialysis. Then, after the hemodialysis session, 30minutes interval was made to measure the BIA-ECV using BCM. Then, we compared UDiV with BIA-ECV .

We used least squares regression analysis and Bland–Altman analysis to compare the UDiV method and the BIA-ECV method, and the Steel test for multiple comparisons of UDiV and symptoms. All analyses were performed using JMP 9.0.2 (SAS Institute, Inc., Cary, NC, USA).

Results

There was a significant correlation between UDiV(x) and BIA-ECFV (y): (y = 0.70x +3.02, r-square = 0.61, p < 0.0001, Figure 1a). The regression line closely coincided with the line of identity. Bland–Altman analysis showed a systematic error for UDiVvs. BIA-ECV (Figure 1b). There was a significant difference between UDiVand BIA-ECV (mean difference 1.32 L, 95% CI -2.6 to 5.2 L).

Conclusion

UdiV could be a viable alternative marker of BIA-ECV for the assessment of hydration status of patients with HD.