bluuebunny/crossref_metadata_2025 huggingface dataset:
#898 Acceleration in kidney function decline after COVID-19 infection: the Stockholm CREAtinine Measurements (SCREAM) project
Authors: Mahalingasivam Viyaasan , Faucon Anne-Laure , Sjölander Arvid , Bosi Alessandro , Mansfield Kathryn , Bruchfeld Annette , Evans Marie , Nitsch Dorothea , Tomlinson Laurie , Carrero Juan-Jesus
Published: May 2024

Background and Aims

Severe COVID-19 infection, which usually presents as a viral pneumonia, has been observed to frequently be accompanied by acute kidney injury (AKI). However, possible effects of COVID-19 on long-term kidney function decline are not well quantified. We investigated whether kidney function decline is accelerated after COVID-19 infection, and whether the progression of decline differs from other respiratory tract infections.

Method

We undertook an observational study using the SCREAM project, including adults from Stockholm who survived COVID-19 infection (February 2020-December 2021), and adults who survived pneumonia caused by other pathogens (February 2018-December 2019, historical comparison cohort). We used generalized estimating equations to examine the age- and sex-adjusted slopes of estimated glomerular filtration rate (eGFR) decline in the 2 years before versus after each infection (i.e., intra-individual changes). We also compared to post-infection eGFR slopes of COVID-19 versus pneumonia (i.e., inter-individual changes) adjusting for a broad range of demographic, socioeconomic and clinical covariates (including pre-infection eGFR slope). We stratified analyses by whether the infection required hospitalization, hypothesizing more severe infection may lead to more rapid eGFR decline.

Results

We identified 59 267 COVID-19 survivors and 20 138 pneumonia survivors with repeated outpatient eGFR measurements. The pneumonia group was older, with lower income, and more comorbidities and healthcare utilization than the COVID-19 group. Both infections resulted in an accelerated decline of the observed eGFR slope, but with a greater magnitude of intraindividual slope changes after COVID-19 (Fig. 1): eGFR decline was 6.14 (95% confidence interval [95% CI] 5.88-6.41) ml/min/1.73 m2/year faster after COVID-19, and 2.52 (95% CI 2.17-2.88) ml/min/1.73 m2/year faster after pneumonia. When adjusting for pre-infection slope and other identified confounders (Fig. 2), COVID-19 survivors had an eGFR decline that was 0.47 (95% CI 0.29-0.66) ml/min/1.73 m2/year faster than that of pneumonia survivors. Observed intra- and inter-individual differences were larger in magnitude among participants whose infection required hospitalization.

Conclusion

COVID-19 infection is associated with a subsequent acceleration in eGFR decline, of a larger magnitude than other respiratory tract infections, and particularly among more severe cases that required hospitalization. We propose that survivors of severe COVID-19 receive monitoring of kidney function, and that policymakers consider implications for future healthcare planning and renal service provision.
#1205 Protein intake and mortality in older adults with chronic kidney disease: a multicohort study
Authors: Casla Adrián Carballo , Avesani Carla Maria , Beridze Giorgi , Ortola Rosario , García-Esquinas Esther , Lopez-Garcia Esther , Dunk Michelle , Stenvinkel Peter , Lindholm Bengt , Rodríguez-Artalejo Fernando , Vetrano Davide , Calderón-Larrañaga Amaia
Published: May 2024

Background and Aims

Limiting protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of its progression, but whether it can adversely impact nutritional status and overall health is not well known. We aimed to study the associations of total, animal, and plant protein intake with all-cause mortality in older adults with CKD and replicated the analyses in those without CKD for comparison.

Method

We used data from three cohorts (Seniors-ENRICA 1 and Seniors-ENRICA 2 in Spain and SNAC-K in Sweden) of community-dwelling adults ≥60 years (2 555 with CKD and 6014 without). According to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from electronic health records, 98% of participants with CKD were in stages 2 and 3. Cumulative protein intake was estimated via validated dietary histories and food frequency questionnaires. Vital status was ascertained with national death registers. Associations were estimated with Cox proportional hazards regression models, adjusted for sociodemographic, lifestyle, morbidity, and dietary variables.

Results

After a median follow-up of 10 years, 1 901 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD [hazard ratio (95% confidence interval) for 1.15 and 1.35 g/kg/day versus 1.0 g/kg/day  =  0.93 (0.88, 0.98) and 0.85 (0.76, 0.95), respectively]. Low total protein intake was more detrimental to the youngest old (<75 years) and high total protein was less beneficial. Plant protein showed a stronger protective association with mortality than animal protein [0.73 (0.59, 0.90) and 0.91 (0.85, 0.98) per 0.2 g/kg/day increment, respectively]. Among participants without CKD, most hazard ratios were lower, especially in the oldest old, but no significant interactions between protein intake, CKD, and mortality arose.

Conclusion

Higher protein intake might have a positive impact on mortality in older adults with mild or moderate CKD, particularly plant protein. Recommendations for these patients may not differ substantially from those without CKD.
#412 Influence of SGLT2I on tubulointerstitium in DKD patients with moderate renal dysfunction
Authors: Murakami Keisuke , Kato Sawako , Sugaya Takeshi , Kuwatsuka Yachiyo , Ando Masahiko , Maruyama Shoichi
Published: May 2024

Background and Aims

In the FAGOTTO study (jRCTs041200069) to evaluate changes of renal hemodynamics on initial glomerular filtration rate (GFR) dip induced by Sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients (pts) with type 2 diabetic kidney disease (DKD) and moderate renal dysfunction, we reported that SGLT2 inhibition maintained the levels of glomerular filtration fraction (FF) and renal vascular resistance (RVR) during decrease in GFR as well as renal plasma and blood flow. In this sub analysis, we evaluated if GFR dip by SGLT2i might induce tubulointerstitial disorder by measuring urinary biomarkers.

Method

The FAGOTTO study was a 12-week multicenter, open-label, randomized (1:1), parallel-group study treated with Canagliflozin (Group CA) or control groups (Group CO) in DKD pts with 30 ≤ estimated GFR (eGFR) ≤ 60 mL/min/1.73 m2. Urinary biomarkers including liver-type fatty-acid binding protein (L-FABP), N-acetyl-glucosaminidase (NAG), β2-microglobulin (β2MG) and monocyte chemoattractant protein-1 (MCP-1) were measured at baseline, 4 weeks and 12 weeks after start of the trial. The adjusted mean and SE for changes were calculated at each time point by a linear mixed model with baseline values, time point, and interaction of the treatment group as the fixed effects. We compared these changes between treatment the groups the Tukey-Kramer method to correct for multiplicity.

Results

The adjusted mean changes in L-FABP at the 4-week and 12-week time point after trial start were estimated −0.35 and −0.17 μg/gCr in Group CA and 0.06 and 1.23 μg/gCr in Group CO in a linear mixed model, respectively. Similarly, the changes were estimated 2.63 and 3.71 U/gCr in Group CA and 1.38 and −1.21 U/gCr in Group CO in NAG, 317.7 and 291.4 μg/gCr in Group CA and 416.6 and 375.1 μg/gCr in Group CO in β2MG and 19.6 and 64.6 pg/gCr in Group CA and −7.7 and −2.7 pg/gCr in Group CO in MCP-1, respectively. When compared the changes in L-FABP, NAG, β2MG and MCP-1 between Group Ca and Group Co by Tukey-Kramer multiple-comparison test, there were no significant differences in any biomarkers. (Figure).

Conclusion

In this analysis, no significant difference in any of these biomarkers was detected in Group CA compared to those in Group CO at 4 weeks and 12 weeks after administration of SGLT2i. Although further studies should be needed to conclude, transient decrease in GFR after administration of SGLT2i might not be involved with tubulointerstitial damage and our study gives one evidence as a safety information in use of SGLT2i to DKD pts with moderate renal dysfunction.
#1060 Prevalence and adverse outcomes of hypokalemia and the role of potassium supplementation in patients receiving peritoneal dialysis
Authors: Yang Changyuan , Hu Xiaoxuan , Ling Xitao , Xiao Cuixia , Duan Ruolan , Qiu Jiamei , Qin Xindong , Liu Xusheng , Lindholm Bengt , Johnson David W , Lu Fuhua , Su Guobin
Published: May 2024

Background and Aims

Hypokalemia is common and potentially life-threatening in patients undergoing peritoneal dialysis (PD). The reported prevalence of hypokalemia in PD patients varies significantly across studies, with ongoing debate about its association to adverse outcomes and the effects of potassium supplementation.

Method

We searched MEDLINE, Embase, Web of Science and references from eligible studies from database inception through September 2023 without language restriction for randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional studies on the prevalence and adverse outcomes (all-cause mortality, cardiovascular mortality, infection-related mortality, and PD-associated peritonitis) of hypokalemia or the role of potassium supplementation in patients receiving PD. Random effects meta-analysis is conducted to pool Hazard ratio (HR) and 95% confidence interval (CI) for the outcomes of interest. The certainty of findings was rated according to GRADE criteria.

Results

Out of 3 298 reports identified, 23 studies involving 59 433 participants met inclusion criteria. The prevalence of hypokalemia across all definitions was 37.9% (95% CI: 27.2-52.7%), 19.0% (95% CI: 13.0-27.6%) (Fig. 1), and 4.4% (95% CI: 1.9-10.2%) for patients with potassium level below 4.0, 3.5 and 3.0 mmol/L. Hypokalemia was associated with increased risk of all-cause mortality (HR: 1.49; 95% CI: 1.18-1.89) (Fig. 2), cardiovascular mortality (HR: 1.50; 95% CI: 1.19-1.88), and PD-associated peritonitis (HR: 1.53; 95% CI: 1.23-1.88). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for subgroup and sensitivity analyses were consistent with the primary finding. Only two studies examined the impact of correcting hypokalemia with potassium supplementation in PD patients, and the results are inconclusive.

Conclusion

Hypokalemia is common and portends poorer survival and higher risk of peritonitis among PD patients. Further research into the optimal prevention and treatment strategies for hypokalemia is warranted to improve outcomes.
#1713 Blood pressure goals in kidney transplant recipients: an analysis of the collaborative transplant study
Authors: Speer Claudius , Benning Louise , Morath Christian , Zeier Martin , Döhler Bernd , Tran Hien
Published: May 2024

Background and Aims

Hypertension is an independent risk factor for cardiovascular disease, the leading cause of death in kidney transplant recipients. Because there is no “one size fits all” approach to blood pressure targets, particularly in the heterogenous group of kidney transplant recipients, identification of subgroup-specific targets, considering factors like age and sex, may be appropriate. However, currently available studies are limited because of sample sizes, and no subgroup analyses have been performed examining the effects of different blood pressure targets on allograft and patient survival. The aim of our study was to investigate the impact of different ACC/AHA blood pressure categories on graft survival and patient mortality and to identify subgroup-specific targets.

Method

This large-scale retrospective study included 1-year blood pressure data from 62, 556 kidney transplant recipients reported to the Collaborative Transplant Study from 209 centers in 39 countries. Hypertension was categorized according to 2017 ACC/AHA guidelines. The primary outcomes were death-censored graft failure and patient mortality during post-transplant year 1 to 6. Multivariable Cox regression analysis was performed to control for immunologic and nonimmunologic confounders.

Results

One year after transplantation, 77% of kidney transplant recipients had hypertension. Hypertension stages 1 (130–139/80–89 mmHg), 2a (140–159/90–99 mmHg), and 2b (≥160/≥100 mmHg) were associated with an 8%, 34%, and 102% increased risk of death-censored graft failure, respectively, whereas elevated blood pressure levels (120–129/<80 mmHg) did not significantly increase the risk. Patient mortality was only significantly higher in those with hypertension stage 2b with a Hazard Ratio of 1.21 (95% CI, 1.08–1.36; P < .001). In addition, the impact of hypertension stages on death-censored graft failure varied in different subpopulations (Fig. 1). Female recipients, younger recipients, recipients who received kidneys from donors younger than 60 years, re-transplanted recipients, and recipients with pre-transplant HLA antibodies had a significantly increased risk of death-censored graft failure associated with higher blood pressure levels (Fig. 1). Kidney transplant recipients with hypertension stage 2 continued to have an increased risk of graft failure one year after transplantation, even when they achieved normal blood pressure in the second year.

Conclusion

This study highlights the importance of treating hypertension early after kidney transplantation to improve long-term graft and patient survival. Attention should be paid to female, younger, and sensitized recipients, who may particularly benefit from optimal blood pressure control.
#1216 Comparable outcomes for old, older and very old deceased donors in old kidney transplant recipients
Authors: Tegzess Erzsi , de Boer Silke E , Moers Cyril , Berger Stefan P , Sanders Jan-Stephan F
Published: May 2024

Background and Aims

Old patients (≥ 65 years) make up almost 1/3 of the waiting list for kidney transplantation in the Netherlands, and this proportion continues to rise. These patients have a high waitlist mortality and benefit from early transplantation, even with kidneys from older or ‘marginal’ donors. Transplanting marginal donor kidneys may help to cut the proportion of elderly patients on the waiting list and improve clinical outcomes. More epidemiological support regarding the graft outcomes of old, older and very old donor kidneys is needed to support clinicians in accepting these kidneys. We therefore studied the outcomes of these kidneys in old recipients.

Method

Retrospective cohort study of all kidney transplant recipients ≥ 65 years with a deceased donor ≥ 65 years in the Netherlands between 2005 and 2022. Discarded kidneys from deceased donors ≥ 65 years in the same time period were included as well. Donors were categorized into old (65-69 years, OD), older (70-74, OD+) and very old (75+, OD++).

Results

We included 1301 transplantations from donors ≥ 65 years, of which 435 from an OD+ and 90 from an OD++. Median recipient age was 69 years (66 - 72), 67% was male. The transplanted OD+ and OD++ kidneys were more often from DBD donors (OD 42%, OD+ 51.3%, OD++ 70%, P < 0.01) with lower nadir creatinine compared to the OD kidneys (61.0 umol/l [51.0, 74.0] vs. OD+ 59.0 [49.0, 72.0] P = .034, vs OD++ 58.0 [49.0, 64.5] P  =  .021).

Patient survival was similar for recipients of OD, OD+ and OD++ kidneys at one year (91% vs 89% vs 93%, respectively; Plog-rank = 0.3) and at five years (60% vs 60% vs 64%; Plog-rank = 0.2) after transplantation. Additionally, in multivariable Cox regression, donor age category was not associated with recipient mortality risk (Ref  =  OD. OD+: P = .7; OD++: P = .2).

Death-censored graft survival was ≥92% in all groups after 1 year, and did not differ significantly between donor age categories (PGray's  =  0.2). Results remained non-significant in multivariate Cox regression (Ref  =  OD, OD+: P  =  .942; OD++: p  =  0.403).

Kidneys offered but not accepted for transplantation (before procurement) had a higher serum nadir creatinine in comparison with transplanted kidneys (68 umol/L [56 - 84] vs 61 umol/L [51 - 78], P < .001), and were more often from DCD donors (79% vs 53%, P < .001). However, donor characteristics of many discarded kidneys resembled that of successfully transplanted kidneys.

Conclusion

Recipient and graft survival are good and similar for old patients receiving kidneys from old, older and very old deceased donors. These findings may contribute to a wider acceptance of kidneys from these donors.
#1103 Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients: a systematic review and meta-analysis
Authors: Oliveras Laia , Lopez-Vargas Pamela , Melilli Edoardo , Codina Sergi , Royuela Ana , Coloma Ana , Favà Àlex , Manonelles Anna , Lloberas Núria , Couceiro Carlos , Garrit Josep Maria Cruzado , Montero Nuria
Published: May 2024

Background and Aims

Delayed graft function (DGF) is more common in donors after cardiac death, especially expanded criteria donors and those with longer cold ischaemia time, older or with an increased serum creatinine. There is no agreement on the optimal immunosuppressive approach in patients at increased risk of DGF, with strategies including a delayed introduction of calcineurin inhibitors (CNI) or initial low dose CNI.

Our aim was to evaluate the benefits and harms of delayed initiation of CNI or reduced CNI dose as initial immunosuppression therapy for kidney transplant (KT) recipients at high risk of DGF.

Method

We searched the Cochrane Kidney and Transplant Register of Studies up to 07 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomized controlled trials (RCTs) and quasi-RCTs evaluating early vs delayed initiation of CNI or reduced vs standard initial dose of CNI in kidney transplant (KT) recipients at high risk of DGF. Three authors independently assessed study eligibility, and two assessed the risk of bias, certainty of evidence, extracted the data, and performed the analysis. Results were reported as risk ratios with 95% confidence intervals for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. Statistical analysis was performed using the random-effects model. Risk of bias was assessed with RoB2 and the certainty of the evidence according to GRADE methods.

Results

Thirteen studies were included (2386 randomized participants). Incidence of DGF (RR 1.09, 95% CI 0.89 to 1.32; I2 =  18%) and acute rejection (RR 0.98, 95% CI 0.72 to 1.33; I2 =  54%) were similar between early and delayed introduction of CNI, as well as between low vs standard dose of CNI (DGF: RR 1.16, 95% CI 0.90 to 1.50; I2 =  9%; acute rejection: RR 0.70, 95% CI 0.43 to 1.14; I2 =  58%). There were also no differences in secondary outcomes such as graft function, graft loss, risk of death, or infection.

Conclusion

In patients at high risk of DGF, the strategy of delaying CNI introduction or starting at a lower dose does not reduce the risk of DGF.
#2578 Safety profile of dapagliflozin therapy in the kidney peritransplant period
Authors: Coca Armando , Ardura Paula , Manrique María Martínez , Fernández Beatriz , Núñez Pilar Pascual , Martín María Fernández , Serrat Teresa Ronda , Moultamis Aya , Acosta-Ochoa Isabel , Mendiluce Alicia
Published: May 2024

Background and Aims

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of glucose-lowering drugs that have demonstrated important cardio- and nephroprotective effects. These effects, according to preclinical data, may include attenuation of ischemia/reperfusion injury due to downregulation of pro-inflammatory cytokines and necroptosis mediators. This effect could be critical in the peritransplant period, protecting the allograft and potentially reducing delayed graft function (DGF). However, administration of SGLT2i immediately after deceased-donor kidney transplantation (KTx) could potentially be associated with adverse outcomes, such as urinary tract infections (UTI). We report the results of the first 10 patients of an ongoing study aimed at describing the safety profile of dapagliflozin in the peri-KTx period.

Method

Prospective, uncontrolled pilot study of consecutive, incident KTx patients that received a daily dose of dapagliflozin 10 mg, starting immediately before surgery and continuing until completing the first week post-transplant. All subjects provided informed consent for the study. Those with liver dysfunction, known allergy to SGLT2i, programmed for live-donor or multiorgan kidney transplantation or unable to provide informed consent were excluded. The primary outcome was the development of UTI during index hospitalization, defined either as a positive urine culture and/or symptoms suggestive of UTI. For comparison purposes, a retrospective sample of age- and sex-matched patients that received a KTx prior to the start of this study was included in this analysis. Two controls were selected for each case.

Results

Demographics and clinical characteristics of both patients in the study and retrospective controls are summarized in Fig. 1. Recipients that received dapagliflozin had similar rates of UTI when compared to controls, and were prescribed less frequently antibiotic therapy for UTI, although none of these differences reached statistical significance. Most cases of both groups consisted in asymptomatic bacteriuria. Of all four cases of documented UTI among treated patients, only one subject developed UTI during the days of dapagliflozin administration (the first 7 days after surgery). This patient did not require antibiotic therapy. The other three cases developed UTI after dapagliflozin discontinuation.

Conclusion

Results of this preliminary and limited experience lead us to believe that dapagliflozin in the peritransplant period may be a safe and feasible therapy that could help protect the renal allograft from ischemia/reperfusion injury.
#2362 Clinical utility Anti-human T-lymphocyte Immunoglobulin (ATLG) as an induction agent in a living donor kidney transplantation: 5-year follow-up data
Authors: Sinha Vijay Kumar
Published: May 2024

Background and Aims

The usage of induction agents for living donor kidney transplants in India is varied. Polyclonal antibodies currently in use are anti-thymocyte globulin (ATG) and anti-T-lymphocyte globulin (ATLG). The role and dose of ATLG need to be defined. This study is focused on ATLG usage and the outcome with long-term follow-up.

Method

This is an analysis of 206 patients who received ATLG as an induction agent from 2017 to 2023. Patients received triple immunosuppression therapy: Tacrolimus, Mycophenolate Mofetil (MMF), and prednisolone for maintenance immunosuppression.

Results

A total of 206 patients received ATLG as an induction agent for living donor kidney transplants. The mean age of the patients was 39.13 ± 12.56 years. There were 87.3% (n = 180) males and 12.6% (n = 26) females. The majority of transplants in our study were ABO-compatible (94.6%, n = 195) and ABO-incompatible (5.2%, n = 11). The mean age of donors was 41 ± 13.7 years. Males were 38.3% (n = 79), and females were 61.6% (n = 127). Overall survival observed in the current study was 98% (n = 202), Post-transplant, 4 patients died (n = 2 died due to COVID-19, 1 due to Heart failure and 1 was infectious mortality.) The mean cumulative dose of ATLG in the current study was 305.1 ± 61.8 mg, and the mean dose was 5.4 ± 1.4 mg/kg. The baseline etiologies of patients who underwent transplant were chronic glomerulonephritis (47.5% n = 98), diabetic nephropathy (16.9% n = 35), hypertension (29.1% n = 60), CIN, and other GMB diseases. In the current study, the figure shows overall 11.6% (n = 24) rejections and 5-year follow-up data of Serum creatinine within a normal range. Post-transplant BK Virus Nephropathy was observed in 3.39% (n = 7) cases, CMV infection in two cases, TB was observed in three cases and fungal pneumonia in one case.

Conclusion

Long-term 5 year follow-up of Living donor kidney transplant shows that ATLG is an effective and safe induction agent. Good compliance with Oral immunosuppressant can improve graft survival as per the current study.
#1038 Progressive multifocal leukoencephalopathy in kidney transplant recipients: a retrospective multicenter nationwide cohort study
Authors: Sanson Adelaide , Lombardi Yannis , Francois Helene
Published: May 2024

Background and Aims

Progressive multifocal leukoencephalopathy (PML) is a serious opportunistic infectious disease affecting the central nervous system caused by JC virus. While extensively studied in patients with HIV infection, haematological malignancies, or undergoing immunotherapies, there is a lack of data concerning kidney transplant recipients (KTRs).

Method

We performed a retrospective, multicentric, nationwide study. We contacted all kidney transplantation centres in France to gather all cases of PML. We obtained the count of patients with a functional kidney allograft using the registry of the French regulatory agency.

Results

We collected 24 cases of PML. Between 2012 and 2021, the estimated minimal nationwide incidence of PML was 4.7/100 000 patient-years. The median duration from kidney transplantation to PML was 88 months (interquartile range: 9 to 355). Eight patients (33%) had been exposed to belatacept (median exposure: 18.5 months). Almost all patients underwent reduction or withdrawal of immunosuppressive drug doses and 13 (54%) received a specific treatment. Fifteen patients (65%) died within one year after diagnosis.

Conclusion

In this nationwide study, PML incidence rate in KTRs was at least 4.7/100 000 patient-years resulting in an alarming 65% mortality rate within a year despite immunosuppressants doses decrease or withdrawal. Further investigations are warranted to demonstrate the efficacy of specific treatments and confirm a potential association between belatacept exposure and PML occurrence, as suggested by our study.
#1718 Infectious complications among early versus late pulse steroid therapy among renal transplant recipients
Authors: Kaul Anupma , Prasad Narayan , Roy Shuvam
Published: May 2024

Background and Aims

Renal transplant recipients are at risk for infectious complications, with opportunistic infections predominating early after transplant and community acquired infections occurring in late transplant period. Pulse steroid is a form of heightened immunosuppression given to a transplant recipient, usually for treatment of rejection. This study aimed to investigate the effects of early and late pulse steroid therapy on the development of infectious complications in renal transplant recipients.

Method

Study population was drawn from patients undergoing kidney transplantation in the period between 1st January, 2016 and 31st December, 2020 in the study centre. Early and late pulse steroid therapy was defined based on whether pulse steroid was received within or after 90 days from date of transplant respectively. Patients receiving either early or late (but not both) pulse steroids who were more than or equal to 18 years of age and had at least 90 days of follow up were included in the study. Patients were followed up till 31st December, 2021 or till their death (whichever came earlier).

Results

Total of 516 patients underwent renal transplantation in the study centre in the specified period, out of whom 128 patients (24.8%) fulfilled the inclusion criteria without fulfilling the exclusion criteria. Out of these 128 patients, 83 (64.8%) and 45 (35.2%) patients received early and late pulse steroids respectively. The 2 groups were similar with respect to respect to baseline characteristics and use of other immunosuppressive agents. The mean values (95% confidence interval) for overall infections in early and late pulse steroid categories were 0.46 (0.31-0.61) and 1.16 (0.55-1.78) episodes per year respectively (p = 0.28). Sepsis occurred at higher rate in patients receiving late pulse steroids, with mean values (95% confidence interval) for sepsis in early and late pulse steroid categories being 0.02 (0.00-0.06) and 0.30 (0.04- 0.57) episodes per year respectively (p = 0.01). Viral infections also occurred at higher rate in patients receiving late pulse steroids, with mean values (95% confidence interval) for viral infections in early and late pulse steroid categories being 0.04 (0.02- 0.09) and 0.23 (0.03-0.43) episodes per year respectively (p = 0.01). Rates of other types of infection did not significantly differ between the 2 categories. A greater proportion of patients receiving late pulse steroids died (4.8% and 17.8% in early and late pulse steroid categories respectively, p = 0.02).

Conclusion

Late pulse steroid therapy is associated with more episodes of sepsis and viral infections compared to early pulse steroid therapy, although rate of overall infections do not significantly differ between the two groups. This study highlights the importance of surveillance for infections after pulse steroid therapy in renal allograft recipients.
#2287 Impact of renal reserve before donation in post-transplant renal function of donors and recipients
Authors: González-Rinne Ana , Sorensen Cristian Acosta , Luis-Lima Sergio , Cruz Coriolano , Martin Laura Díaz , Rivero Yaiza , Tirado Marian Rincón , Gallego Eduardo , Tamajon Maria Lourdes Perez , Cabrera Beatriz Escamilla , Hernández Domingo , Porrini Esteban
Published: May 2024

Background and Aims

The influence of Renal Reserve (RR), i.e. its presence or absence, in post-transplant renal function both in living kidney donors and recipients is unknown. The presence of RR in donors may be beneficial in terms of better renal function both for the donor and recipient after transplantation. In the other hand, the absence of RR in donors might indicate a lower renal endowment and so predispose to lower GFR post-transplantation in donors and recipients. However, little evidence is available in this field.

Method

In a previous study (ERA Abstract 2023, #3737) we described in a group of 52 potential living kidney donors, the presence (24-46%), absence (13-25%) or use (15-29%) of RR before donation. The latter was defined as the lack of increase in GFR after stimulation in patients with basal GFR > 100 mL/min. GFR was measured before and after transplantation by the clearance of iohexol with dried blood spots. Presence of RR was defined as an increase >10% of basal GFR after IV amino acid infusion. GFR was unadjusted to body surface area (BSA). In this follow-up study we investigated the impact of the presence, absence or use of RR before donation in GFR 12 months after transplantation, both in donors and recipients.

Results

Of the 52 pairs of donors and recipients, renal transplantation was performed in 21 who also had 12 months of follow-up. Before transplantation 9 donors had RR, 4 did not and 8 had RR in use. Pre-transplant GFR was 95 ± 15 ml/min, 89 ± 6 ml/min and 127 ± 16 ml/min in donors with RR, without RR and with RR in use, respectively. At 12 months after kidney donation, GFR was higher in donors who had RR in use before donation: 79 ± 12 ml/min, compared with those with RR: 65 ± 9 ml/min (p = 0.048) and those without RR 59 ± 10 (p = 0.03). In recipients, GFR was comparable between those who had a donor with RR or RR in use: 72 ± 19 ml/min vs 68 ± 12 ml/min (p = ns), whereas both groups had higher GFR than those recipients whose donors had no RR before donation 53 ± 5 ml/min, although of borderline signification (p = 0.07). Non parametric tests were used. No major complications after transplantations such as rejections or surgical complications, etc, that could alter GFR were observed.

Conclusion

The presence or use of RR may determine a better renal function 12 months after donation both for donors and recipients. This is a preliminary study and we acknowledge that the low number of cases is a limitation and so, these results require further studies.
#2573 Effect of pre-transplant dialysis modalities on delayed graft function
Authors: Panuccio Vincenzo Antonio , Cosentino Sonia , Tripepi Rocco , Cambareri Francesco , Parlongo Giovanna , Versace Maria Carmela , Tripepi Giovanni Luigi
Published: May 2024

Background and Aims

Kidney transplantation represents the optimal treatment for end-stage renal disease patients. Benefits and disadvantages of different pre-transplant dialysis modalities and the effects on post-transplant outcomes remain unclear, but many authors identify peritoneal dialysis (PD) such a “bridge” versus renal transplantation.

Method

We analyze a consecutive series of 249 renal transplanted patients (mean age 48 ± 11 years, 67% males) between June 1998 and February 2016 with a low prevalence of comorbidities (diabetes 2%, hypertension 31%, previous cardiovascular events 2%). The median follow-up was 136 months [interquartile range (IR) 91-197 months]. The pre-transplant treatment was hemodialysis (HD) in 215 patients (86%) and peritoneal dialysis (PD) in the remaining 34 patients (14%). The majority of patients received a cadaveric donor organ (219 patients, 88%).

Results

Delayed Graft Function (DGF) was registered in 151 patients (61%). Analyzing pre-transplant dialysis treatment, 15 patients about 34 (44%) on pre-transplant PD had DGF vs 136/215 (63%) on pre-transplant HD treatment (P = 0.03). Remarkable PD patients were older (48 ± 12 years) than HD patients (44 ± 11 years), but this difference did not rise statistical significance (P = 0.09); similarly the prevalence of living donors were higher (13%) in the group of HD patients respect the group of PD patients (9%, P = 0.53).

In a longitudinal analysis the last estimated Glomerular Filtration Rate (eGFR) was lower in patients with DGF (44, IR 19-66 ml/min/1,73 m2) vs patients without DGF (48, IR 35-73 ml/min/1,73 m2, P = 0.04), but no substantial differences was noted at the end of observation in eGFR between the two groups of patients (HD, eGFR 45, IR 25-68 ml/min/1,73 m2 vs PD eGFR 46, IR 24-67 ml/min/1,73 m2).

Conclusion

Results of this study confirm that PD treatment can be considered an optimal “bridge” for renal transplantation probably because peculiar characteristic of this dialysis modality (such us long term preserved diuresis and residual renal function respect HD patients) impacts positively on recovery of renal function. Further study need to clarify these controversial points.
#1207 Post transplant diabetes mellitus in kidney transplanted patients: factors related and impact on long-term outcome
Authors: Alfieri Carlo , Regalia Anna , Campise Maria Rosaria , Verdesca Simona , Delfrate Nicholas Walter , Favi Evaldo , Molinari Paolo , Pisacreta Anna , Castellano Giuseppe
Published: May 2024

Background

Alterations in glucose metabolism are one of the most important complications of renal transplant recipients. The aim of this study was to analyze their prevalence and determinants and assess their influence on the main long-term clinical outcomes in a cohort of kidney transplant recipients.

Methods

we retrospectively analyzed the data of 832 kidney transplant recipients between 2004 and 2020 in our center. Patients were studied at 1 (T1), 6 (T6), and 12 (T12) months after transplantation and followed clinically for a follow-up time of 103 ± 60 months. At T6, an oral glucose tolerance test (OGTT) was performed in 484 patients.

Results

The mean age of the cohort studied was 49 ± 13 years, with a mean dialysis vintage of 54 ± 52 months. Hemodialysis was the therapy before KTx in 70.6% of patients, whereas 20.9% had been treated with peritoneal dialysis. The 8.5% of patients received a pre-emptive KTx. Fifty-seven percent of the patients were male and 83.5% had a KTx from a deceased donor. Both at T1 and T12, immunosuppressive therapy was mainly composed of steroids (average cumulative dose at T12: 2914 ± 962 mg), calcineurin inhibitors and mycophenolate. In our cohort at T12, diabetic patients were 237 (28.6%), of which 51 (6.2%) were already affected by diabetes before KTx. Of note, we diagnosed diabetes by OGTT in 23 KTxps, while in 90 KTxps, OGTT showed prediabetic alterations. Patients with glucose metabolism abnormalities were significantly older, had an altered lipid profile associated with higher BMI values and a significantly higher inflammatory index. Interestingly, our data showed that graft loss was not affected by any type of alteration of glucose metabolism. On the contrary, we found that mortality was significantly higher in patients with pre-transplant diabetes and in those with alterations in glucose metabolism detected with OGTT (both including diabetes and considering only IGT and IFG).

Conclusions

Our data showed that age at transplantation, lipid profile, and the inflammatory state were the variables that most influenced the development of PTDM. Interestingly, mortality was significantly associated with pre-transplant diabetes and alteration in glucose metabolism. This allowed us to highlight the impact of prediabetes status and the importance of OGTT as a screening test in post-transplant and potentially pre-transplant. Future randomized controlled trials will be able to resume the topic, including the analysis of the effects of new antidiabetic drugs.
#2219 Glycemic control and adverse outcomes in patients with diabetes and CKD stage 4-5: a nationwide cohort study
Authors: Faucon Anne-Laure , Caldinelli Aurora , Regland Minnie , Carrero Juan-Jesus , Evans Marie
Published: May 2024

Background and Aims

Although poor glycemic control is strongly associated with adverse clinical outcomes, few studies have evaluated their risk across the full glycemic spectrum in patients with moderate to advanced chronic kidney disease (CKD). Guidelines for HbA1c targets are mainly derived from extrapolation of trials conducted in people with normal or mildly reduced kidney function. In non-dialysis CKD individualized targets are recommended, often aiming for less strict glycemic control, due to lack of evidence for the efficacy of lower HbA1c, and potentially greater harm. In this study, we analyzed long-term outcomes across the full spectrum of HbA1c in CKD stage 4-5.

Method

Using data from the Swedish Renal Registry, we included patients with diabetes and CKD stages 4-5. Adjusted cause-specific Cox models were used to analyze associations between the one-year baseline mean HbA1c level (<43, 43-52 [reference], 53-64, 65-74, 75-89, ≥90 mmol/mol) and the occurrence of major adverse cardiovascular events (MACE, a composite of cardiovascular death, hospitalization for myocardial infarction or stroke), kidney replacement therapy (KRT), all-cause mortality, and hospitalization/death due to hypoglycemia.

Results

We included 2571 patients (71 years, 64% men, eGFR 20 mL/min per 1.73m², HbA1c 59.7 mmol/mol [7.6%], 75% insulin users). At baseline, patients with a higher HbA1c level were younger, had a higher prevalence of cardiovascular disease and were more likely prescribed insulin. Kidney function and malnutrition-inflammation markers were, however, not different between groups.

Over a median follow-up of 4.9 [4.6;5.2] years, 939 (37%) KRT, 1078 (42%) MACE, and 1523 (59%) deaths occurred. Increasing HbA1c was gradually associated with the risk of MACE (adjusted HR from 0.76 [95% CI: 0.60-0.96] for HbA1c <43 mmol/mol to 1.39 [1.01-1.92] for HbA1c ≥ 90 mmol/mol) (Fig.). In contrast, a J-shaped relationship was observed for the risk of all-cause mortality. Compared to the reference group (43-52 mmol/mol; 5-year absolute risk 52% [48-56]), a HbA1c <43 mmol/mol was not associated with a higher mortality (adjusted HR 1.03 [0.86-1.23], 5-year absolute risk 57% [51-63]), while any HbA1c above 75 mmol/mol was associated with a higher risk of death. The risks of KRT and severe hypoglycemia were not different across HbA1c levels.

Conclusion

In CKD stage 4-5, HbA1c above the general recommendation for non-CKD patients (43-52 mmol/mol) is associated with a higher risk of MACE and all-cause mortality, but not KRT, without increased risk of severe hypoglycemia. This suggests that targeting a lower HbA1c, together with other cardio-reno-metabolic prevention strategies, might contribute to improve health outcomes in this very high-risk population.
#1405 Salt sensitivity and hypertensive nephropathy: a link to be discovered
Authors: Tunesi Francesca , Simonini Marco , D'urbano Luca , Citterio Lorena , Zagato Laura , Manunta Paolo , Lanzani Chiara Livia
Published: May 2024

Background and Aims

Sodium sensitivity (SS) is a change in blood pressure (BP) depending on Na+ intake, 30% of population has it. Either a salt load test or a sodium dietary protocol can be used to stratify the population into 3 groups based on BP variation: sodium sensitive (SS), sodium resistant (SR), inverse sodium sensitivity (ISS), based on an increase, a non-significant variation or a decrease in BP following the administration of Na+. SNPs located in genes related with Na+ metabolism, aldosterone synthesis and kidney tubular Na+ reabsorption are related to this phenotype.

Method

We analyzed data collected from the follow-up (FUP) of 127 subjects with a new diagnosis of hypertension, categorized by their profile through acute salt load test. We analyzed the kidney damage by annual decline of eGFR and development of microalbuminuria. Genetic polymorphism analysis has been executed.

Results

No differences in the decline of eGFR are observed among the groups (−1.3084 ml/min ± 0.16 p-Value 0.372). SR subjects seem to be more prone to develop earlier microalbuminuria (χ 2 10.682, p = 0.005) even with an adequate BP control (P-Anova SBP 0.766; P-Anova DBP 0.856). An inverse correlation exists between pressure-natriuresis ratio and decline in eGFR (R −0.194 p = 0.016). Polymorphism in CYP11B2 (0.72 OR p = 0.045) and NEDD4L (0.74 OR p = 0.027) are protective against eGFR decline. ADD3 polymorphism (3.73 OR p = 0.049) is a risk factor for development of microalbuminuria. KL (0.15 OR p = 0.034), PKD and TRPC6 (p-Value 0.037, p-Value 0.009) polymorphism are protective factor against microalbuminuria.

Conclusion

SR patients are more at risk of developing hypertensive nephropathy earlier than other groups; steeper pressure natriuresis ratio is involved in quicker decline in renal function possibly accelerating development of hypertensive nephropathy. Further studies with larger sample and standardization in salt sensitivity test are needed to translate this knowledges into clinical setting.
#2183 Does thrombotic microangiopathy drive the occurrence and pattern of cerebrovascular disease in malignant hypertension?
Authors: Chen Peter , Delorme Stephen , Alamowitch Sonia , Koumako Cedi , Doreille Alice , Mousseaux Cyril , Paques Michel , Lombardi Yannis , Rafat Cédric
Published: May 2024

Background and Aims

Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused by severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute and chronic forms, stands as a hallmark of the disease, being identified in up to half of patients. Thrombotic microangiopathy (TMA), defined as the association of mechanical hemolytic anemia with thrombocytopenia, also emerges as a frequent complication in MHT patients. However, the potential contribution of TMA to cerebrovascular disease remains unexplored. The secondary objective of this study was to provide a comprehensive description of the patterns of cerebrovascular injury occurring in MHT, with a focus on acute ischemic strokes (AIS).

Method

We retrospectively assessed the brain MRI of patients admitted to the kidney intensive care unit at Tenon hospital for malignant hypertension during the 2017-2023 period. Brain MRIs were performed on a systematic basis regardless of neurological symptoms and were independently reviewed by two trained specialists in a blinded fashion. Patterns of acute cerebrovascular disease, defined as AIS, intracerebral hematoma (ICH) or posterior reversible encephalopathy syndrome (PRES), were systematically assessed. Number of AIS lesions, their size and localization were recorded. Underlying chronic cerebral small vessel disease (CSVD) was defined as presence of lacunes, white matter hyperintensities, cerebral microbleeds or perivascular spaces. Severity of the chronic cerebrovascular disease was measured using a validated CSVD score.

Results

A total of 60 patients were admitted for malignant hypertension, with a mean age of 42.9 years. 40 patients (66.7%) presented with severe acute kidney injury. Cerebrovascular disease, either acute or chronic, was found in 42 patients (70.0%). Underlying chronic CSVD was present in 33 patients (55.0%). Acute patterns of injury occurred in 27 patients (45.0%). AIS was the most frequent (33.3%), followed by PRES (21.7%). Only one patient presented with ICH. Among patients with AIS, 14 (70%) presented with multiple simultaneous lesions. Of note, most patients with AIS exhibited diffuse encephalopathy syndrome (60.0%) rather than focal deficit (40.0%). Systemic TMA was present at admission in 34 patients (56.7%). In an exploratory data analysis, presence of AIS on brain MRI was associated with the presence of underlying CVSD (p = 0.013), but not with the presence of TMA at admission (p = 0.79). No association was found between TMA and PRES (p = 0.22).

Conclusion

Our study confirmed the high incidence of cerebrovascular disease during MHT. Most notably, 1 in 3 patients presented with AIS. TMA did not appear to increase the incidence nor to influence the pattern of brain injury.
#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD
Authors: Han Seung Hyeok , Joo Young Su , Koh Hee Byung , Park Jung Tak , Yoo Tae-Hyun , Oh Kook-Hwan , Kang Shin-Wook
Published: May 2024

Background and Aims

Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD.

Method

We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP < 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score >0; Uncontrolled BP, SBP >140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT.

Results

During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P < 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66).

Conclusion

Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.