bluuebunny/crossref_metadata_2025 huggingface dataset:
#4489 EFFECT OF RENAL ARTERY CALCIFICATION ON THE OCCURRENCE OF ACUTE KIDNEY INJURY AND MORTALITY
Authors: Jeon Hae Eun , Kwon Soie , Hwang Jin Ho
Published: June 2023

Background and Aims

Renal artery stenosis not only causes secondary hypertension and drug-resistant hypertension by enhancing renin-angiotensin-aldosterone system (RAAS), but also causes ischemic acute/chronic kidney injury by impeding blood flow to the kidneys. Renal artery calcification (RAC) suggests chronic severe atherosclerotic changes, but the relationship between its severity and clinical prognosis has not been established.

Method

This study was conducted on subjects aged 60 years or older who had serum creatinine measured more than 3 times among patients prescribed and performed abdominal CT at Chung-Ang University Hospital from January 1, 2005 to February 28, 2020. The renal artery calcification score (RACS) was obtained by Agatston score measurement, and the incidence of AKI and mortality were compared between the groups.

Results

Of a total of 29,410 patients, 17,478 had no RAC and 11,932 was RAC (+). The median value of the group in which RACS was measured was 117.8. The prevalence and history of diabetes mellitus (DM), hypertension, dyslipidemia, and history of cardiovascular disease were significantly higher in the RAC (+) group, lower eGFR and higher proteinuria, and higher prescribing rates of ARB or ACEi, spironolactone, and statin. In the group of RAC (+), the incidence of AKI (HR 1.231, CI 1.174-1.292, P<0.001, Figure1) and all-cause mortality (HR 1.265, CI 1.182-1.355, P<0.001) was high. Regardless of DM or RACS, the risk of AKI was higher in those who were prescribed ACEi or ARB (HR 1.786, CI 1.7-1.875, P<0.001). In patients with DM, mortality risk was reduced in those taking ACEi or ARB regardless of the presence of RACS (HR 0.759, CI 0.645-0.892, P<0.001).

Conclusion

RAC(+) was associated with higher AKI and mortality risk than RAC(-). The use of RAAS blockades increased the risk of AKI regardless of the presence of RAC, but reduced mortality in patients with DM regardless of the presence or absence of RACS.
#4516 CLINICAL CHARACTERISTICS OF PATIENTS WITH LUPUS NEPHRITIS CLASS III–V: ANALYSIS OF INTERNATIONAL REAL-WORLD DATA
Authors: Anderson Seth , Delgado Ana , He Xin , Tang Zhiliu , Milligan Jack , Bracher Marguerite
Published: June 2023

Background and Aims

Lupus nephritis (LN) is a severe renal manifestation of systemic lupus erythematosus (SLE) that negatively impacts morbidity and mortality; however, real-world data for LN is scarce. This study describes: the proportion of patients with SLE managed by rheumatologists (rheum-managed) and by nephrologists (neph-managed) with LN class III–V; the proportion of patients with a Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index (SELENA-SLEDAI) score ≥8 by region; extra-renal organ systems involvement by region; flaring by region; and EQ-5D and EQ-visual analogue scale (VAS) scores by estimated glomerular filtration rate (eGFR).

Method

Data were drawn from the Adelphi Lupus Disease Specific Programme, a cross-sectional, multi-subscriber survey of physicians and their consulting patients conducted April 2021–May 2022 in China, Japan, EU5 (France, Germany, Italy, Spain and the UK) and the USA. Physicians provided demographic and clinical data for 5–6 consecutive adult patients consulting for SLE/LN. LN class III–V was assessed by the physician at data collection. SELENA-SLEDAI scores were derived by physician assessment of patients’ current clinical manifestations. Patients had the opportunity to complete an EQ-5D form. All analyses were descriptive.

Results

Overall, 9% (183/2148) of rheum- and 48% (364/766) of neph-managed patients had LN. Most patients with LN had a SELENA-SLEDAI score ≥8 (70% of rheum- and 76% of neph-managed; Table 1), compared with 48% (1032/2148) of rheum-managed patients with SLE alone. The proportion of neph-managed patients with LN with a SELENA-SLEDAI score ≥8 varied by region, from 58% in the USA to 87% in China. In total, 62% of rheum- and 43% of neph-managed patients with LN had ever flared (any organ system; Table 1). The proportion of rheum-managed patients with LN who had ever flared ranged from 52% in China + Japan to 75% in EU5. The proportion of patients with LN currently experiencing a flare was similar between rheum- (31%) and neph-managed (35%) patients, but varied by region, with the highest proportion for rheum-managed patients in China (59%) and lowest in the USA (18%). In subgroups with ≥15 patients, EQ-5D and EQ-VAS scores generally worsened as eGFR lowered (Figure 1).

Conclusion

Patients with LN class III–V had high disease burden (SELENA-SLEDAI scores ≥8) and flaring that varied by region, suggesting a need for more efficacious treatments for patients with LN.
#4589 HYPOCHLOREMIA AS A MARKER OF ALL-CAUSE MORTALITY AND UNPLANNED DIALYSIS STARTS IN A COHORT OF ACUTE KIDNEY INJURY: A 4-YEAR FOLLOW-UP STUDY
Authors: García Daniela Medina , Amado Ernesto Francisco Valga , Monzon Tania , D'orazio Yuliana Stefania Daruiz , Quintana Cristo Adonay Santana , Perez Patricia
Published: June 2023

Background and Aims

Serum chloride is an emerging marker of mortality in patients with hypertension, heart failure, sepsis, and chronic kidney disease. The relationship between hyperchloremia and acute kidney injury is well known, especially in critically ill patients. However, the role of baseline hypochloremia in the prognosis of hospitalized patients with acute kidney injury (AKI) remains poorly understood.

Method

Retrospective cohort type study. We included n=243 patients with AKI stage 3 from consultations received by the nephrology department of our hospital between January 1, 2017, to December 31, 2017. The sample was divided into two groups considering baseline serum chloride (Cl−) levels. Hypochloremia was considered if Cl−< 98 mEq/L. The primary endpoint was a composite variable for unplanned dialysis starts and all-cause mortality.

Results

The mean age was 68 years. Females accounted for 39.5%. The mean baseline sodium was 137±7.2 mEq/l, and the mean baseline chloride was 98.9±7.05 mEq/l (Table 1). The mean follow-up of the patients was 21±19.61 months. The incidence of the primary endpoint was n=166 (68.3%). 148 (60.9%) died, of whom 78 (32%) died during their hospital stay. The causes of death were: 30.6% cardiovascular, 12.9% tumor, 44.7% infectious, and 11.8% other. Kaplan-Meier estimates showed lower survival rates in patients with chloride levels below 98 mEq/l (p=0.006, log-rank test) (Figure 1).

Conclusion

Patients with AKI stage 3 with lower baseline chloride levels (<98 mEq/L) were more likely to have higher overall mortality and unplanned dialysis starts.
#4645 HISTONE LACTYLATION ENHANCES PERITONEAL FIBROSIS BY INDUCING PERITONEAL MESOTHELIAL CELL SENESCENCE
Authors: Yu Fang , Wang Xiaoyue , Cai Qingli , He Yani , Chen Kehong
Published: June 2023

Background and Aims

Peritoneal fibrosis (PF) is a serious complication limiting the application of peritoneal dialysis (PD). Histone lactylation has recently been found to increase with glycolysis and intracellular lactate levels, thereby mediating chronic organ damage. This study investigated the role and mechanism of histone lactylation in high glucose peritoneal dialysate-induced peritoneal fibrosis in mice.

Method

The PF mouse model induced by high glucose peritoneal dialysate was constructed by daily intraperitoneal injection of 4.25% glucose peritoneal dialysate combined with 40 mM Methylglyoxal for 2 weeks. We also used a lactylation enhancer (rotenone) and a lactylation inhibitor (oxamate) to validate the effects of histone lactylation in vivo and in vitro. The parietal peritoneum samples and cultured peritoneal mesothelial cells in various groups were analyzed for evidence of senescence, fibrosis, glycolysis, and histone lactylation levels. In addition, we generated DcR2 knockout mice to further verify the effects of histone lactylation on peritoneal mesothelial cell (PMCs) senescence by clearing senescent cells.

Results

In the PF group, the results of Masson staining and immunohistochemistry revealed increased peritoneal thickness and expression of fibrosis markers (α-SMA, Collagen I, and Fibronectin) and senescence markers (P16, P21, and DcR2) compared to the control group. We found that lactate and glycolysis levels were significantly higher in the PF group compared to the control group, and further immunoprecipitation results also showed enhanced levels of histone lactylation modifications in the PF group. We further found that the level of lactylation modification of H3K18la site increased significantly, suggesting that H3K18la site may play an important role in promoting PF. Similarly, in vitro, we verified that peritoneal mesothelial cells (PMCs) exhibited enhanced levels of lactate and lactylation in response to stimulation by high glucose, while we found an increasing expression of cell senescence phenotype (P16, P21, and DcR2) and senescence-associated cytokines secretion (IL-1β, IL-6, and TNF-α). By enhancing or inhibiting lactylation, we found that PMCs senescence was significantly enhanced in the lactylation-enhanced group, while the lactylation-inhibited group alleviated PMCs senescence induced by high glucose peritoneal dialysate. In the PF model of DcR2 knockout mice, compared with the wild group, there was no significant difference in the level of histone lactylation, while peritoneal thickness and the expression of markers of fibrosis markers (α-SMA, Collagen I, and Fibronectin) were significantly reduced.

Conclusion

Histone lactylation leads to peritoneal fibrosis induced by high glucose peritoneal dialysate by promoting PMSCs senescence. Histone lactylation may be a vital mechanism of peritoneal dialysis-related peritoneal fibrosis.
#4709 PERSONALISED INDUCTION THERAPY IN ANCA GLOMERULONEPHRITIS
Authors: Hamburger Laura , Leung Wing Yin , Bruce Ian , Brix Silke
Published: June 2023

Background and Aims

Patient and kidney outcome in ANCA glomerulonephritis (GN) remains unsatisfactory. Rituximab use failed to reduce the rate of infectious complications and demonstrates a significant rate of hypogammaglobulinaemia in ANCA vasculitis. Adjusting the rituximab dosage to the individual patient's need promises a reduction in treatment toxicity.

Method

Retrospective analysis of a single centre cohort of ANCA GN patients with disease flares between 2019 – 2022 using a stratified induction immunosuppression with rituximab and cyclophosphamide. Treatment intensity was adjusted to resolution of systemic inflammation and microscopic haematuria, peripheral CD19 cell count depletion and immunoglobulin G (IgG) levels.

Results

45 patients (median age 57 years, 55.7% female, median eGFR 27 mls/min) were treated with a median dose of 1.5 grams Rituximab during induction (interquartile range, IQR 1 – 2 grams). 18 patients received concomitant intravenous cyclophosphamide pulses to control the acute inflammation (median cumulative dose of 2 grams, IQR 1.65 – 3 grams). Peripheral B cell depletion was 91.4% at 3 months and 90.3% at 6 months (<3 CD19 cells/ul). During the initial 12 months treatment, IgG level fell below 7g/l in 20 patients, below 5g/l in nine patients and below 3g/l in one patient. Seven patients required renal replacement therapy at diagnosis (15.6%). Five patients recovered kidney function and three patients developed end stage kidney disease (6.7%). Twelve infections were reported requiring antibiotic treatment (26.7%), seven severe infections were documented requiring hospitalisation (13.3%) and one patient died (2.2%).

Conclusion

An early assessment of treatment response assists adjusting vasculitis therapy. Adjusting management to the patient's individual immunological and treatment response may result in better outcome with less treatment toxicity.
#4740 DIFFERENT ORAL IRON PREPARATIONS IN CHRONIC KIDNEY DISEASE: A COMPARATIVE ANALYSIS
Authors: Sharma Sourabh , Sharma Neha , Varma Prem
Published: June 2023

Background and Aims

Anaemia is common and undertreated morbidity in chronic kidney disease (CKD). Optimal approach to treatment of renal anemia is matter of ongoing debate. This is the first comparative analysis between different oral iron preparations in CKD patients.

Method

This prospective observational multicentre study was performed from March 2019 to May 2021. In total, 214 non-dialysis dependent CKD stage3-5 patients with 3 months follow-up were included. Inclusion & exclusion criteria are mentioned in Table 1. Primary outcome was rise in Haemoglobin at 1 month/3 months & rise in Transferrin saturation (TSAT) at 3 months. Treatment adherence was also evaluated. Figure 1 depicts the study model.

Results

Table 2 depicts demographic data while Table 3 depicts correlation between baseline haemoglobin & different modifiable/non-modifiable variables. Rise in haemoglobin & TSAT with different oral iron preparations has been shown in Table 4 while the ANOVA tables for clinical significance of this rise has been shown in Figures 2 & 3. Rise in haemoglobin and TSAT% was highest with Ferric Pyrophosphate > Ferric Fumarate > Ferric Saccharate. Treatment adherence was highest with Ferric Pyrophosphate (100%) > Heme Iron Polypeptide (91.4%) > Ferrous Ascorbate (88.9%).

Conclusion

Ferric Pyrophosphate is most effective among available oral iron preparations in rising haemoglobin level. It effectively repletes iron stores & has highest treatment adherence.
#4762 PREGNANCY-RELATED ACUTE KIDNEY INJURY: 10-YEAR SERIES OF A NEPHRO-OBSTETRIC CLINIC
Authors: Nogueira Estela , Peres Nadiesda , Godinho Iolanda , Centeno Mónica , Pinto Luísa , Lopes José António
Published: June 2023

Background and Aims

Pregnancy-related acute kidney injury (P-AKI) is a rare complication of pregnancy associated with significant maternal and fetal morbidity and mortality. Its incidence has progressively decreased worldwide with the improvement of obstetric care, but recently some developed countries have noticed an increase in its incidence. Adjusted definition of AKI in pregnancy is lacking, making its incidence difficult to ascertain. Herein, the authors retrospectively evaluated the causes and outcomes of P-AKI patients surveilled by the nephro-obstetric clinical team.

Method

Retrospective analysis of maternal, obstetric and perinatal outcomes of P-AKI patients, that were followed by the Nephro-obstetric clinical team between 2011 and 2022.

Results

We evaluated 29 patients, with mean age of 32 ± 6 years [17 – 42], 19 Caucasian and 9 Black, 17 nulliparous, 16 hypertensive, 7 diabetic, 1 with HIV, and 1 with systemic lupus erythematosus. Only 12 patients had CKD and 3 were renal transplant patients. In 2/29 patients P-AKI occurred before 20 weeks [15-17] due to obstructive uropathy and pregnancy hyperfiltration in a CKD G3 patient. After 20 weeks of gestation, P-AKI occurred in 27/29 patients (mean 32 weeks; range 21-41weeks), with mean SCr of 3,1 mg/dl [1,8-4,5] in previously CKD patients and mean SCr of 2.4mg/dl (1,2-58mg/dl) in the patients with normal renal function. Regarding the severity of P-AKI, 16/7/6 patients developed AKI stage 1/2/3 (KDIGO), respectively. Causes of P-AKI after 20 weeks in patients with normal renal function were preeclampsia (PE; 8/14), HELLP syndrome (1/14), hemolytic uremic syndrome (1/14), sepsis (3/14), renal obstruction (1/14), severe hypercalcemia (1/14), cortical necrosis due to hemorrhagic shock (2/14), hypovolemia and nephrotoxic agents (1/14). All patients had full renal recovery. In renal transplant patient P-AKI was related to PE (2/3), sepsis (1/3) and probable calcineurin inhibitor toxicity (1/3). Regarding CKD patients, P-AKI was caused by PE (6/10), hyperfiltration of pregnancy (3/10) and allergic interstitial nephritis (1/10). The need for renal replacement therapy occurred in 7/29, and only 2/7 became dialysis dependent (both with previous CKD diagnosis). De novo or worsening proteinuria occurred in 15/29 (3975 g/day; 431-14000 g/day) and 10/29 patients (mean 6227 mg/day; 681-14937 mg/day), respectively. Regarding fetal outcomes, there were 2 stillbirths, mean gestation duration was 33 weeks (25-41weeks), mean birth weight 1947 g (550-3950 g) and mean Apgar 1/5/10 was 8/9/10, respectively. Cesarean was performed in 19/27 patients and 7 newborns were admitted to the neonate care unit due to prematurity.

Conclusion

In a tertiary referral center, P-AKI was associated to a wide range of causes, frequently required a multidisciplinary approach and was associated to significant worse maternal, obstetric and perinatal outcomes.
#4778 THE NATURAL HISTORY OF IGA NEPHROPATHY IN THE GERMAN CHRONIC KIDNEY DISEASE (GCKD) COHORT
Authors: Stamellou Eleni , Nadal Jennifer , Seikrit Claudia , Hendry Bruce , Mercer Alex , Möller Marcus Johannes , Schmidt Matthias , Schiffer Mario , Eckardt Kai-Uwe , Floege Jürgen
Published: June 2023

Background and Aims

Primary IgA nephropathy (IgAN) is the most common form of glomerulonephritis and a major cause of kidney failure. Here we describe the natural history of individuals with IgAN in the German Chronic Kidney Disease (GCKD) cohort.

Method

From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the GCKD study, a prospective observational cohort study (N = 5217). Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. The adjudicated composite renal endpoint (Major Adverse Kidney Events; MAKE) was defined as eGFR decline>40%, eGFR< 15 ml/min or initiation of kidney replacement therapy. The associations between the incidence of MAKE and baseline risk factors were analyzed using the Cox proportional hazards regression model. Data relating to baseline demographics, laboratory, comorbidity, and mortality were used.

Results

The mean age at baseline of IgAN patients was 51.6 years (±13.6) and 67% were male. Duration of disease at baseline was 5.9 ± 8.1 years. Baseline median UACR was 0.4 g/g (0.1-0.8) and mean eGFR was 52.5 ± 22.4 mL/min/1.73m2. Over a follow-up of 6.5 years, 53 (12.6%) initiated kidney replacement therapy, 64 (15.2%) experienced >40% eGFR decline and additional 3 (0.7%) reached eGFR< 15 ml/min, i.e. 28% of the patients experienced a MAKE. Albuminuria, with reference to < 0.1 g/g was most associated with MAKE. Hazard ratios at UACR 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 (1.02-4.05), 3.8 (1.92-7.5), 5.64 (2.58-12.33) and 5.02 (2.29-11-03), respectively. Relapse, defined as UACR >2.2g/g, after partial remission (defined as UACR ≥0.1 g/g to <0.6 g/g) or complete (defined as UACR < 0.1 g/g) remission developed in only 13 (3.1%) patients.

Conclusion

The GCKD study reflects a large cohort with long follow up allowing for a thorough analysis of the natural history of IgAN. More than every fourth patient experienced a MAKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate for poor kidney outcomes.
#4791 TREATMENT WITH PCSK9 INHIBITORS IN PATIENTS WITH CHRONIC KIDNEY DISEASE AT VERY HIGH CARDIOVASCULAR RISK
Authors: Amaro Jose Manuel , Fernández Florentino Villanego , Muñoz Javier Naranjo , Orellana Cristhian , Sánchez Luis Alberto Vigara , López Juan Manuel Cazorla , Mejía Carlos Narváez , Alonso Marta , Aguilera Aurora , Blanca María Auxiliadora Mazuecos
Published: June 2023

Background and Aims

Proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitors may be an option in the treatment of dyslipidaemia in patients with chronic kidney disease (CKD) who do not reach therapeutic targets or who do not tolerate statins at maximal doses. However, studies in this population are scarce. The aim of our study is to analyse the efficacy and safety of iPCSK9 in patients with CKD.

Method

Retrospective cohort study of patients with CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, who started treatment with iPCSK9 in our centre between 2016 and 2020. All patients had at least 2 years of follow-up. We compared total cholesterol, LDL cholesterol (c-LDL), triglycerides and eGFR at baseline, 6, 12 and 24 months after iPCSK9 prescription. Adverse effects were collected.

Results

During the study period, 278 patients started treatment with iPCSK9 in our centre, of whom 41 had CKD and a follow-up of more than 2 years. Of these, 21 were on treatment with Alirocumab and 20 with Evolocumab. Of these, 51.2% were men with a mean age of 70.6 ± 9.4 years and 87.8% had G3a or G3b stage. One patient was on peritoneal dialysis. Acquired dyslipidaemia was present in 82.9% and 87.8% had suffered from coronary events. 53.7% of iPCSK9 prescriptions were for failure to achieve c-LDL targets, while in the remaining patients the reason was non-tolerance of maximum statin doses.

After 6 months of treatment, a significant reduction in total cholesterol (226.7 ± 52.9 mg/dL vs. 142.1 ± 46.17 mg/dL; p<0.001), c-LDL (147.8 ± 48.8 mg/dL vs. 62.9 ± 37.1 mg/dL; p<0.001) and triglycerides (229.8 ± 112.4 mg/dL vs. 192.4 ± 119.2 mg/dL; p = 0.025) was observed, and these differences were maintained at 2 years of treatment (p = 0.016, p<0.001, p = 0.004). 48.8% of patients achieved c-LDL targets (≤ 55 mg/dL) at 6 months of treatment

and 48.8% at 12 months of treatment. Renal function remained stable during follow-up.

No side effects or cardiovascular events were documented.

Conclusion

iPCSK9 reduce cholesterol, c-LDL and triglycerides in patients with CKD, allowing therapeutic targets to be achieved while maintaining stable renal function. Due to the apparent advantages of this drug in CKD patients, we believe that conducted clinical trials should be designed for this population.
#4792 SECOND, THIRD, AND MORE HITS: IMPACT OF SUCCESSIVE AKI EPISODES ON CKD PROGRESSION AND AKI TO CKD TRANSITION
Authors: Acosta-Ochoa Isabel , Coca Armando , Ardura Paula , Manrique María Martínez , Merizalde Carlos , Cobo Kenia , Mendiluce Alicia
Published: June 2023

Background and Aims

The second hit theory refers to the link between two or more deleterious events that cause AKI simultaneously (e.g., triple whammy) or successively (e.g., cardiac surgery after coronary angiography). We investigated the effect of 3 or more consecutive AKI episodes on baseline serum creatinine (SCr) and if these changes leaded to AKI to CKD transition (Transition), CKD progression (Progression) or stable SCr.

Method

Retrospective study of patients with AKI attended by nephrology during a 3-year period. AKI severity was categorized by KDIGO criteria. We searched for patient's successive admissions and if suffered a new AKI episode and included all patients with ≥3 AKI episodes during the study period. We analyzed the baseline SCr for every episode and investigated if serial AKI episodes leaded to incident CKD, Progression, or no changes in SCr.

Results

144 individuals that suffered 525 AKI episodes were included. We observed 36 patients in the Transition, 70 in the Progression group, and 38 didn't vary their SCr. We found no statistically significant differences in hypertension, DM, Charlson's Index, admission to ICU, severity of AKI or length of stay between groups. See Table 1A. We found that progressors had shorter time to nephrology consultation, they were more prone to receive acute HD and to be dialysis dependent at discharge. With no difference in the mortality rate between groups. See Table 1B. Figure 1 plots baseline SCr of every episode that shows a trend to incremental cyphers.

Conclusion

In our study the clinical characteristics between Transition and Progression groups were similar. We observed more individuals in the Progression group and their time to nephrology consultation was significantly shorter, maybe because no nephrology specialists are afraid of managing CKD patients. Patients that progressed needed acute HD more frequently and were more dialysis dependent at discharge, this finding could be explained by their diminished renal reserve, with no differences in the rate of in-hospital mortality. Successive AKI episodes portend a higher risk of adverse clinical outcomes, with excessive burden for patients with previous CKD. New AKI therapies could change the course of these ominous outcomes? This issue is under intense investigation, but it is very difficult to translate bench to bedside. Therefore, now we can only count on prevention and timely nephrological attention.
#4815 COMPARISON OF DIFFERENT ANTIVIRALS REGARDING THEIR ASSOCIATION WITH HOSPITAL-ACQUIRED ACUTE KIDNEY INJURY AMONG ADULTS WITH HERPES ZOSTER
Authors: Xu Ruqi , Xin Xu , Nie Sheng
Published: June 2023

Background and Aims

Antiviral therapy is commonly used to treat herpes zoster. Though antivirals are generally considered nephrotoxic, few studies compared the relative risk of acute kidney injury in patients with herpes zoster that is attributable to different antivirals. We aim to examine the association of use of different antivirals with hospital-acquired acute kidney injury (HA-AKI) among Chinese adults with herpes zoster.

Method

The study population was derived from the China Renal disease System (CRDS), a retrospective cohort of hospitalized patients from 19 medical centers throughout China. We selected from CRDS 3,847 adults who received antiviral therapy for herpes zoster during hospitalization. We identify and stage AKI using patient-level serum creatinine data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We compared the relative risks of HA-AKI among patients treated with different antivirals using Cox proportional hazards model, and explored the non-linear association between the accumulative dose of antivirals and the risk of HA-AKI using a penalized smoothing spline.

Results

Among 3,847 patients, 1,585 (41.2%), 699 (18.2%), 599 (15.6%) and 964 (25.1%) were treated with acyclovir/valacyclovir, ganciclovir, penciclovir/famciclovir, and foscarnet, respectively. The incidence of HA-AKI was 4.9%, 2.9%, 2.8% and 0.8%, respectively, in the patients treated with acyclovir/valacyclovir, ganciclovir, penciclovir/famciclovir, and foscarnet. Compared with acyclovir/valacyclovir therapy, use of foscarnet was associated with a 69% reduction in the risk of HA-AKI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.14-0.66), while use of other nucleoside analogues was associated with a marginally lower risk of HA-AKI, with a HR (95% CI) of 0.62 (0.36-1.09) for penciclovir/famciclovir and 0.67 (0.41-1.11) for ganciclovir. When compared with foscarnet, nucleoside analogues (HR, 2.72; 95% CI, 1.28-5.75) showed a higher risk of HA-AKI. The associations were consistent across various subgroups and sensitivity analysis.

Conclusion

Among antiviral therapies for herpes zoster, acyclovir/valacyclovir was associated with the highest relative risk of HA-AKI, and the association appears to be dose dependent. Clinicians should exercise rational drug use according to the different renal toxicity associated with a particular antiviral drug.
#4818 IMPACT OF COMBINED PHYSICAL FRAILTY AND DEPRESSIVE SYMPTOMS ON MORTALITY IN PATIENTS ON HEMODIALYSIS
Authors: Tobita Asumi , Imamura Keigo , Yoshikoshi Shun , Uchida Juri , Nakajima Takuya , Fukuzaki Narumi , Nikkawa Sayaka , Harada Manae , Matsunaga Atsuhiko
Published: June 2023

Background and Aims

Patients receiving hemodialysis [HD] are getting older, with 38.8% of patients in Japan being 75 years or older. HD patients also have multiple comorbidities, which are known to be associated with poor clinical outcomes, especially in the older patients. Moreover, physical frailty and depressive symptoms are common in HD patients and these are known to be risk factors for poor prognosis. However, it is unclear whether the coexistence of physical frailty and depressive symptoms contributes to an increased risk of mortality in older patients with multiple comorbidities. As a result, the goal of this study was to look at the relationship between physical frailty and depressive symptoms and mortality in HD patients of different ages.

Method

This study included 409 Japanese outpatients with HD (mean age 65.9 years, 62.6% male, and 2.0 years of hemodialysis history). Slow walking speed and/or weak hand grip strength were used to define physical frailty. The Center for Epidemiological Studies-Depression scale was used to assess depressive symptoms. Patients were divided into four groups: (1) no depressive symptoms, no physical frailty; (2) depressive symptoms, no physical frailty; (3) no depressive symptoms, physical frailty; and (4) depressive symptoms, physical frailty. All-cause mortality was the outcome; Cox regression analysis was performed, with analysis stratified by age group (<75 years, ≥75 years) to examine differences by age.

Results

Physical frailty and depressive symptoms were prevalent in 268 (65.5%) and 143 (35.0%) of the population, respectively. Physical frailty and depressive were present in 103 people (25.2%). 129 (31.5%) people died during the follow-up period (median 49 months). In all patients, Cox regression analysis revealed that physical frailty and no depressive symptoms (hazard ratio [HR], 1.86, 95% confidence interval [CI], 1.01–3.44) and coexistence of physical frailty and depressive symptoms (HR, 2.30, 95% CI, 1.23–4.28) were significantly associated with an increased risk of death. In the <75-year-old group, a combination of physical frailty and depressive symptoms was significantly associated with an increased risk of death (HR, 2.45; 95% CI, 1.23–4.88). In the ≥75-year-old group, however combined physical frailty and depressive symptoms were not significantly associated with mortality (HR, 2.06; 95% CI, 0.34–12.55), whereas C-reactive protein was (HR, 1.59; 95% CI, 1.10–2.28).

Conclusion

Physical frailty and depressive symptoms were common in HD patients. In terms of prognosis, the coexistence of physical frailty and depressive symptoms were linked to mortality in the <75-year-old group, whereas in the <75-year-old group, the coexistence of physical frailty and depressive symptoms was not associated with death, but higher inflammation was associated.
#4834 THE PROPORTION OF UNAFFECTED GLOMERULI IS A ROBUST PROGNOSTIC FACTOR OF KIDNEY OUTCOME IN PATIENTS WITH ANCA-ASSOCIATED GLOMERULONEPHRITIS
Authors: Song Seung Min , Lee Hyun Suk , Kim Minhyung , Jang Min Young , Jeon Jeunseok , Jang Hye Ryoun , Kwon Gee-Young , Huh Wooseong , Kim Yoon-Goo , Lee Jung Eun
Published: June 2023

Background and Aims

Anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN), the most common form of secondary GN in elderly (>60 years), requires immunosuppressive treatment that may increase risk of opportunistic infections. This study evaluated the prognostic value of clinical factors and histopathologic findings affecting kidney outcome in ANCA-associated GN patients.

Method

From 2000 to 2018, we identified 106 adults (≥18 years old) who were pathologically confirmed as ANCA-associated GN. The number of normal, crescent, and sclerotic glomeruli was recorded for each biopsy by slide review. The primary outcome was incident end stage kidney disease (ESKD).

Results

The age was 67 (57-73) years, the estimated glomerular filtration rate (eGFR) was 19 (11-36) mL/min/1.73 m2, and % of normal glomeruli in kidney specimen was 25 (11-47) %. Overall kidney survival was 85% and 76% at 1 and 5 years, respectively. Among clinical variables, lower eGFR (adjusted hazard ratio [aHR], 0.339; 95% confidence interval [CI], 0.180-0.638; p<0.001) was independently associated with increased risk of incident of ESKD. Multivariate Cox proportional hazard model including both clinical and histological variables demonstrated that % of normal glomeruli (aHR, 0.960; 95% CI, 0.935-0.986; p<0.001) was a sole risk factor of incident ESKD, independently of eGFR and other pathological findings. When the % of normal glomeruli was divided by quartiles, the risk of incident ESKD in the lowest quartile was significantly increased compared to the highest quartile (<11%; HR, 5.986; 95% CI, 2.114-16.950 vs. >46%; p<0.001).

Conclusion

The proportion of unaffected glomeruli was independent predictor of kidney outcome in patients with ANCA-associated GN.
#4935 TYG INDEX CORRELATED WITH PPROGRESSION OF CHRONIC KIDNEY DISEASE IN METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE
Authors: Choi Hoon Young , Lee Jung Eun , Jhee Jong Hyun , Park Hyeong Cheon
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is an established major risk factor for cardiovascular disease. Moreover, progression of CKD results in end-stage kidney disease, and an increased risk of death. The recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) has been suggested to better reflect risk of developing CKD. This study aimed to evaluate the association between the triglyceride-glucose (TyG) index and CKD progression in patients with MAFLD.

Method

In the data from the medical records database in Gangnam Severance Hospital from 2006 through 2020, a longitudinal analysis included participants with CKD. MAFLD was diagnosed in patients with was diagnosed in individuals with hepatic steatosis and at least one of the conditions as follows: 1) overweight or obese (defined as body mass index [BMI] ≥ 23 kg/m2), 2) type 2 diabetes mellitus, or 3) two or more metabolic abnormalities. Progression of CKD was defined by a reduction in the GFR ≥30% of baseline. Logistic regression analyses were used to determine the association between TyG index and progression of CKD by adjusting for the influence of confounders.

Results

The study included 4,286 patients, of whom 582 had MAFLD. Mean age was 51.49 ± 11.451 years. After adjusting for age, sex, systolic blood pressure, fasting plasma glucose, CRP, LDL-cholesterol and smoking status, TyG index was associated with progression of CKD [OR 1.760 (1.089-2.844), P = 0.021].

Conclusion

This study demonstrated that TyG index was significantly associated with progression of CKD in patients with MAFLD.
#4953 IMPACT OF IMMUNOSUPPRESSIVE REGIMEN ON ANTIBODY RESPONSE AFTER CHADOX1 NCOV-19 VACCINATION IN THAI KIDNEY TRANSPLANT RECIPIENTS
Authors: Larpparisuth Nuttasith , Pongsakornkullachart Kritsada , Vongwiwatana Attapong , Skulratanasak Peenida
Published: June 2023

Background and Aims

The lower humoral immunity response after COVID-19 vaccine in kidney transplant recipients (KTRs) has been reported in several studies. However, the study regarding efficacy of ChAdOx1 nCoV-19 (AstraZeneca) vaccine among various immunosuppressive treatments in Asian population is scarce.

Method

We conducted a cross-sectional study in Siriraj Hospital, Bangkok, Thailand. Adult KTRs who received two doses of the ChAdOx1 nCoV-19 vaccine at intervals of 3 months were enrolled. Anti-SARS-COV-2 S-RBD-IgG antibody (anti-RBD) was assessed at the one month after the second vaccine dose and considered positive if the level ≥ 50 AU/ml. Primary outcome was seropositivity of anti-RBD. Association between type, dose and level of immunosuppressive regimen, and seropositivity of anti-RBD were analyzed. The statistical analysis was performed using SPSS version 23.0.

Results

Between October 2021 and January 2022, 153 KTRs with median follow up time of 59 (30 – 125) months, were enrolled. Mean age was 49.3 ± 11 years and 61.4% were male. Regimen of tacrolimus (TAC)/mycophenolate (MPA)/prednisolone (CS), everolimus (EVR)/MPA/CS and TAC/EVR/CS were prescribed for 92 (60.1%), 23 (15%) and 24 (15.7%) patients, respectively. The anti-RBD ≥ 50 AU/ml after vaccination was observed in 82 patients (53.6%) with median level of 476.7 (129 – 1253.2) AU/ml. Patients received TAC/EVR/CS had significantly higher proportion of seropositivity than EVR/MPA/CS (95.8% vs 65.2%; p = 0.008) and TAC/MPA/CS regimen (95.8% vs 37%; p < 0.001). Among the seropositive KTRs, the median level of anti-S is significantly highest in TAC/EVR/CS treatment when compared to EVR/MPA/CS and TAC/MPA/CS group, respectively (1,204 vs 260.7 vs 315.4; p < 0.001). Among KTRs who received tacrolimus, the seropositivity was significantly higher in patients who had tacrolimus trough level < 3 ng/mL (83.3% vs 45.7%; p = 0.014).

Conclusion

The seropositivity of anti-S after vaccination with ChAdOx1 nCoV-19 in KTRs was 53.6% which was lower than general population. KTRs who received TAC/EVR/CS regimen had highest immune response after vaccination, which is relatively comparable to healthy control in Thailand. Immunosuppressive regimen should be considered for vaccine dose and schedule in the future.
#4971 IMPACT OF RAMADAN FASTING ON NUTRITION, INFLAMMATION AND DIALYSIS ADEQUACY AMONG HEMODIALYSIS PATIENTS
Authors: Taher Eman , Sobh Mohamed , Nassar Mohammed Kamal , El Wasif Salwa
Published: June 2023

Background and Aims

There is a paucity of data concerning safety of fasting in Ramadan in End stage kidney disease patients (ESKD) on haemodialysis (HD). The aim of the present study was to assess the possible effect of fasting on nutritional status (clinical, biochemical variables), inflammatory status and adequacy of haemodialysis. This observational study was carried out during 2022 when fasting duration was around 14 hours.

Method

Sixty-five patients suffered from ESKD who received regular HD for more than six months in dialysis unit, urology and nephrology center Mansoura university were included in this prospective observational study. Patients were categorized into three groups. 21 patients fasted all days of Ramadan,25 patients fasted days other than session days and 19 patients never. We did not oblige our patient to fast. nutritional status was assessed clinically by Anthropometric measurements including body weight, BMI, triceps skin fold thickness (TSF) and estimation of protein catabolic rate (PCR) were measured, and laboratory by serum Albumin, cholesterol and fasting blood glucose. Neutrophils to lymphocytes ratio (NLR), Soluble receptor of advanced glycation end product(SRAGE) and human B-cell lymphoma/leukemia2 (BCL2) was measured as inflammatory markers, also dialysis adequacy was determined with urea reduction ratio (URR) and KT/V. Assessment of all patients were carried out before and after Ramadan month and was repeated 3 months after Ramadan in all patients.

Results

In 30 days fasting group: there was significant reductions (all P < .02), serum albumin, triceps skin fold thickness, Subjective global assessment score (SGA) for nutritional assessment also in inflammatory markers as neutrophils to lymphocytes ratio (NLR) and human Bcell lymphoma/leukemia2 (BCL2). But these were not accompanied by any significant change (all P >0.05) in body mass index, serum cholesterol, fasting blood sugar (FBS), urea reduction ratio (URR), intradialytic weight gains (IDWG), Kt/V and human soluble receptor for advanced glycation end products (sRAGEs). In the group Who was reported fasting in days other than HD session days: fasting led to significant reductions (all P < .02) only in serum albumin and triceps skin fold thickness. There were no significant changes in BMI, URR, Cholesterol, FBS, KT/V, IDWG, SGA score, NLR, sRAGEs and BCL2. In patients Who never fast at all: there was significant reduction (all P<0.02) in triceps skin fold thickness, significant change in SGA score and also in sRAGEs and BCL2.

Conclusion

There was no harmful effect for Muslim patients receiving regular HD who want to fast Ramadan in days other than HD session days. In the current study the fasting group has the benefit of both being fasting and non-significant changes in mostly all nutritional assessment points, inflammatory markers and the adequacy of HD.
#5001 AKI AND AKD AFTER RADICAL CYSTECTOMY FOR MUSCLE INVASIVE BLADDER CANCER: AN UNEXPECTED NEPHROLOGICAL AFFAIR
Authors: Trevisani Francesco , Longoni Mattia , Cinque Alessandra , Rosiello Giuseppe , Malvestiti Marco , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Moschini Marco , Floris Matteo
Published: June 2023

Background and Aims

Radical cystectomy (RC) represents the first line surgical treatment for muscle-invasive bladder cancer (MIBC). RC is a complex surgical procedure characterized by significant morbidity and mortality. The incidence of significant complications following RC is a well-recognized issue however still paucity of data exists regarding postoperative renal function. Aim of the study was to evaluate the incidence of acute kidney injury (AKI) and Acute kidney disease (AKD) after RC, evaluating the impact of surgery (open or robotic one), comorbidities (hypertension, diabetes, CAD) and previous oncological treatments (chemotherapy, immunotherapy and radiotherapy).

Method

We collected a consecutive cohort of 839 patients who underwent RC for MIBC in a single tertiary institution between 2010 and 2022. All clinical variables and comorbidities were reported pre and after surgery. Serum creatinine with subsequently eGFR using CKD-EPI formula were collected at baseline pre-operative and in the acute setting at 24h, 48, 72h, 6 days for the AKI onset, and after 9,12,15,18,21,24,27,30,45, 60, 75, 90 days for the AKD establishment. We compared the incidence of AKI and AKD upon the two different surgical approaches for RC :the open and robotic one. Fisher's exact test; Wilcoxon rank sum test; Pearson's Chi-squared test were used for the statistical analysys.

Results

General characteristics of patients included in the study are summarized in Table 1. Surprisingly, a very high rate of both AKI (30%) and AKD (50%) was reported in the total cohort of patients, with an augmented incidence in the robotic surgery (p < 0.001). Moreover, stage II and III of both AKI and AKD affected a non-negligible percentage of patients, requiring advanced nephrological medical treatments and prolonged hospitalization (Table 1). The multivariate analysis showed that age, blood hypertension and BMI represent the major risk factors to develop both AKI and AKD (Table 3 and Figure 1).

Conclusion

AKI and AKD are very frequent and insidious side effects in the RC for MIBC. Therefore, a personalized nephrological counseling both in the pre and post -surgery asset is mandatory to reduce morbidity and mortality.
#5006 RELATIONSHIP BETWEEN EXTRACELLULAR WATER PERCENTAGE AND MORTALITY IN PATIENTS UNDERGOING CHRONIC HEMODIALYSIS
Authors: Rotondi Silverio , Tartaglione Lida , Perrotta Adolfo , Moscatelli Miriana , Paoloni Emanuela , Pasquali Marzia , Lai Silvia , Mazzaferro Sandro
Published: June 2023

Background and Aims

Chronic hemodialysis (HD) patients have a high cardiovascular and mortality risk. This is secondary to numerous risk factors specific to the HD population. Relevant on cardiovascular disease and mortality in HD, is the sodium intake and the extent of the sodium pool of patients. An increase in the total sodium pool may have a negative action on cardio vascular system directly and mediated by the increase in total body water associated with an increase in the sodium pool. However, the assessment of the sodium pool in patients is clinically complex. Some evidence has suggested that the assessment of the extracellular water percentage (ECW%) in the HD patient may be a marker of the sodium pool. In fact, the increase in extracellular sodium is followed by a shift of water from the intracellular compartment to the extracellular compartment. The assessment of ECW% could therefore identify patients with greater ECW increase secondary to the greater sodium pool and therefore with high clinical risk. Primary aim: to evaluate the relationship between extracellular water percentage and mortality in patients on chronic hemodialysis.

Method

This is an observational prospective cohort study. The inclusion criteria were chronic HD for at least three months, minimum follow-up of six months, age greater than 18 years. In all of the included patients we performed the bioimpedance examination with a dedicated instrument after hemodialysis session, after the long interdialytic interval, for the evaluation of ECW (L), ECW (%), TBW (L / m), ICW (L). The protocol involved dividing the population into two groups based on normal or pathological ECW%, according to values calculated by gender and age and then evaluating the incidence of death in a 36-month follow-up.

Results

We enrolled 101 patients with an average age of 71± 14 years in HD for 51 ±15 months. During the average follow-up of 19 months we observed 31 deaths (30% of the population) with an annual mortality of 15%. ECW % correlated positively with age (R: 0.498 P:0.01) and differential post-dialysis pressure (R: 0.260; P:0.01). 41 patients (aged 64 ± 13 years) had a normal ECW % (ECW-N) and 60 patients (75±13 years) had pathological ECW% (ECW-P). ECW-P patients had an increased mortality respect to ECW-N patients (60% vs 20% p: 0.01). The survival curve confirmed higher mortality in the ECW-P group (log-rank test P 0.02). These results were confirmed in a sub-analysis of two age-matched ECW-N (n. 20 age 64±10 years) vs ECW-P (n. 20 age 65±12 years) subgroups (log-rank test P:0.05).

Conclusion

Our data showed that ECW% identifies HD patients at increased mortality risk in 36- month follow-up. These data are also confirmed in age-related subgroups, suggesting the ECW % assessment can be a simple and useful parameter to evaluate for targeted treatment choices in patients with chronic HD.
#5165 STING CONTRIBUTES TO LPS-INDUCED TUBULAR INFLAMMATION BY ACTIVATING IRE1/XBP1 PATHWAY IN ACUTE KIDNEY INJURY
Authors: Cao Yun
Published: June 2023

Background and Aims

Innate immunity and inflammation were recognized as the key factors for the progression of acute kidney injury (AKI) induced by lipopolysaccharide (LPS). Stimulator of interferon genes (STING) has emerged as a critical component of innate immune and inflammatory responses. This study aimed to explore the role of STING in LPS-induced tubular inflammation in AKI.

Method

1. The AKI mice models were induced by intraperitoneal injection of LPS. Mice were randomly divided into CTL group, LPS 24 h group and LPS 48 h group:

(1) STING protein expression in tubules was detected by IHC staining;

(2) STING protein expression in kidney cortices was detected by WB.

2. The tubule-specific STING knockout (STING-cKO) mice were generated. Then WT mice and STING-cKO mice were randomly divided into WT group, WT+LPS group, STING-cKO group and STING-cKO+LPS group:

(1) Blood samples and urine samples were collected for Scr, BUN and ACR measurement;

(2) Tubular pathological changes were detected by PAS staining;

(3) Inflammatory cell infiltration in kidney cortices was detected by IHC and IF staining;

(4) Pro-inflammatory cytokines’ mRNA level in kidney cortices was detected by QPCR;

(5) IRE1, XBP1, IL-1β and IL-18 protein expression in kidney cortices was detected by WB.

3. HK2 cells were randomly divided into CTL group, si-STING (STING siRNA) group, LPS group, LPS+si-STING group, Ad-IRE1 (IRE1 overexpression plasmid) group, si-STING+ Ad-IRE1 group, LPS+ Ad-IRE1 group and LPS+ si-STING+ Ad-IRE1 group:

(1) Pro-inflammatory cytokines’ mRNA level was detected by QPCR;

(2) IL-1β, IL-18 protein expression was detected by WB.

Results

1. STING was activated in tubules from LPS-induced AKI mice.

2. STING-cKO significantly suppressed LPS-induced renal dysfunction, tubular pathological changes, tubular inflammation and IRE1/XBP1 pathway activation.

3.IRE1 overexpression significantly promoted LPS-activated HK2 cells’ inflammation, even though STING was silenced.

Conclusion

STING contributes to LPS-induced tubular inflammation by activating IRE1/XBP1 pathway. Targeting STING may be a promising therapeutic strategy for preventing septic AKI.