bluuebunny/crossref_metadata_2025 huggingface dataset:
#2370 Creatinine, cystatin C, muscle mass, and mortality: findings from a primary and replication population-based cohort
Authors: Groothof Dion , Shehab Naser , Erler Nicole , Post Adrian , Kremer Daan , Polinder-Bos Harmke , Groen Henk , Pol Robert , Gans Reinold , Bakker Stephan J L
Published: May 2024

Background and Aims

Creatinine measures are used as initial test to derive eGFR and confirmatory testing with circulating cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of circulating creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making. This study aimed to disentangle these complex relationships and better inform clinical decisions on marker reliability in varying settings by investigating whether cystatin C adjustment could clarify the associations of circulating creatinine with muscle mass and mortality.

Method

We conducted a prospective, observational cohort study including 8, 437 community-dwelling adults enrolled in the Dutch PREVEND study and 5, 033 in the U.S. NHANES. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional-hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification.

Results

Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1-Q3) serum creatinine and cystatin C were 0.79 (0.69-0.90) and 0.90 (0.70-1.00) mg/dl and 0.87 (0.78-0.98) and 0.91 (0.80-1.10) mg/l, respectively. Higher serum creatinine was associated to greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1, 636 (19%) deaths were registered over a median follow-up of 12.9 (5.8-16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1-8.2%). In the NHANES, 1, 273 (25%) deaths were registered over a median follow-up of 17.9 (17.3-18.5) years with a 10-year mortality rate of 13.8% (12.8-14.7%). Both markers were associated with increased mortality (Fig. panels A and B). Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality (Fig. panel C), while the association between serum cystatin C and increased mortality strengthened (Fig. panel D). The shapes of the associations in the PREVEND study and NHANES were almost identical.

Conclusion

The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.
#83 Cardiovascular outcomes in home hemodialysis and peritoneal dialysis patients
Authors: Shah Silvi , Weinhandl Eric , Gupta Nupur , Leonard Anthony , Christianson Annette , Thakar Charuhas
Published: May 2024

Background and Aims

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Little is known about differences in cardiovascular outcomes between home hemodialysis (HHD) and peritoneal dialysis (PD).

Methods

We evaluated 68 645 patients who initiated home dialysis between 1/1/2005 and 12/31/2018 using the United States Renal Data System with linked Medicare claims. Rates for incident cardiovascular events of acute coronary syndrome, heart failure, and stroke hospitalizations were determined. Using adjusted time-to-event models, the associations of type of home dialysis modality with the outcomes of incident cardiovascular events, cardiovascular death, and all-cause death were examined.

Results

The mean age of patients in the study cohort was 64 ± 15 years, and 42.3% were women. Mean time of follow up was 1.8 ± 1.6 years. The unadjusted cardiovascular event rate was 95.1 per thousand person-years [PTPY] (95% CI, 93.6-96.8), with a higher rate in patients on HHD than on PD (127.8 PTPY; 95% CI, 118.9-137.2 vs. 93.3 PTPY; 95% CI, 91.5-95.1). However, HHD was associated with a slightly lower adjusted risk of cardiovascular events than PD (HR, 0.92; 95% CI, 0.85 to 0.997). Compared to PD patients, HHD patients had 42% lower adjusted risk of stroke (HR, 0.58; 95% CI, 0.48-0.71), 17% lower adjusted risk of acute coronary syndrome (HR, 0.83; 95% CI, 0.72-0.95), and no difference in risk of heart failure (HR, 1.05; 95% CI, 0.94-1.16). HHD was associated with 22% lower adjusted risk of cardiovascular death (HR, 0.78; 95% CI, 0.71-0.86) and 8% lower adjusted risk of all-cause death (HR, 0.92; 95% CI, 0.87-0.97) as compared to PD.

Conclusion

Relative to PD, HHD is associated with decreased risk of stroke, acute coronary syndrome, cardiovascular death, and all-cause death. Further studies are needed to better understand the factors associated with differences in cardiovascular outcomes by type of home dialysis modality in patients with kidney failure.
#2129 Tacrolimus-extended-release versus tacrolimus LCPT: preliminary data
Authors: van Schijndel Emma , Manson Nienke , van Assema Hidde , Standaar Theodora , Vogt Liffert , Mathot Ron , Marquet Pierre , Hilhorst Marc , Bemelman Frederike
Published: May 2024

Background and Aims

To prevent rejection kidney transplant recipients are treated with immunosuppressive drugs, like tacrolimus. The dosage needed to reach therapeutic trough levels of tacrolimus greatly varies between patients. Currently, there are two tacrolimus extended-release variants on the market. Tacrolimus-extended release (Tac-ER/Advagraf) and tacrolimus LCPT (Tac-LCPT/Envarsus). Tac-LCPT was developed using Meltdose technology to improve absorption. Studies suggest that with Tac-LCPT therapeutic levels can be reached with a lower total dose as compared to Tac-ER. We aim to investigate if the dose needed to reach therapeutic trough levels of tacrolimus can be reduced when using Tac-LCPT as compared to Tac-ER in patients who need a relatively high dose.

Method

A prospective open-label switch design study was performed in patients 6 months up to 5 years after receiving a kidney transplant, who received Tac-ER, with therapeutic trough levels, and a concentration/dosage ratio (CDR) <1.05 ng/mlx1/mg. Patients were switched from Tac-ER to Tac-LCPT with a dose reduction of 30% for 3 weeks. After these 3 weeks, they were switched back to their original dose of Tac-ER. Total follow-up was 6 weeks with weekly visits for adjustment of the dosage. The primary outcome was the dose of Tac-LCPT needed to reach therapeutic trough levels as compared to Tac-ER. Secondary outcomes were side effects and pill burden.

Results

For this preliminary analysis, 8 kidney transplant recipients were included. At baseline, the median age was 52.5 (IQR 44.5, 57.0) years old, 75% of patients were male, and the median number of months after transplantation was 14.2 (IQR 11.50, 16.08). The median dose of Tac-ER needed at baseline was 9.0 mg (IQR 8.0, 11.25) with a CDR of 0.89 (IQR 0.68, 0.92). The tacrolimus dosage needed to reach therapeutic trough levels was significantly lower with Tac-LCPT compared to Tac-ER (5.5 mg vs. 9.5 mg, p = 0.03). However, the patients experiencing side effects and the pill burden did not change between the formulations. The Cmax of Tac-ER and Tac-LCPT varied between patients, with no significant difference between formulations (Fig. 1). At the end of the study, two patients preferred to continue Tac-LCPT, one patient preferred Tac-ER and the remaining patients had no preference.

Conclusion

In conclusion, the total needed dosage of tacrolimus to obtain therapeutic trough levels with Tac-LCPT is smaller than with Tac-ER. However, this smaller dosage administered did not translate to fewer side effects, a smaller pill burden, or a lower peak concentration. When inclusion is completed, additional pharmacokinetics will be calculated as well as the determination of CYP3A5 polymorphisms.
#1130 Biopsy-based transcript diagnostics identify early antibody-mediated rejection phenotypes in biopsies with subclinical donor-specific antibodies
Authors: Baumgartner Annina , Schmid Nicolas , Weidmann Lukas , Bortel Nicolà , Lopez Kai Castrezana , Korach Raphael , Harmacek Dusan , Rho Elena , George Britta , Von Moos Seraina , Schachtner Thomas
Published: May 2024

Background and Aims

Biopsy based transcript diagnostics using the molecular microscope diagnostic system (MMDx) have the potential to add diagnostic clarification in the antibody mediated rejection (AMR) continuum. While de novo donor specific antibody (dnDSA) or preformed DSA accompanied by allograft function deterioration are accepted indications for allograft biopsy with therapeutic implications, management strategy for subclinical DSA lacks consensus. MMDx might show clinical utility in this controverse scenario by helping with therapeutic decisions.

Method

In this single-center cohort of 326 indication kidney transplant biopsies assessed by histology and MMDx at the University Hospital Zurich, we analyzed 58 cases with subclinical DSA as biopsy indication. Cases with (n = 44) and without (n = 14) histopathologic features of AMR according to Banff 2022 were compared for molecular AMR rejection transcripts.

Results

When biopsied for subclinical DSA, all 14 cases without histopathologic features of AMR showed absence of molecular AMR. In contrast, molecular AMR was detected in 6/19 (32%) cases with histopathologic diagnosis of AMR and 2/25 (8%) with probable AMR (p = 0.059), Fig. 1. Microvascular inflammation below threshold with C4d negativity was significantly associated with absence of molecular AMR (p < 0.0001). Higher number of calculated epitope mismatch load for HLA class II as measured by PIRCHE II Score was significantly associated with molecular AMR (p = 0.01). In cases with molecular AMR, early AMR scores predominated (R4 vs R6, 0.0002 and R4 vs R5 0.051).

Conclusion

No molecular AMR was observed in absence of histopathologic AMR. Yet, in cases with histopathologic features of AMR, only 8/44 showed molecular AMR. Predominance of early AMR rejection phenotype in cases with molecular AMR transcripts allows hope for MMDx to identify treatment amenable cases with subclinical DSA. Discrepant cases call for re-biopsy to guide therapeutic decisions.
#67 Is Sodium bicarbonate a better alternative in kidney transplantation for better early renal function? A systematic review and meta-analysis
Authors: Abdelshafi Abdelrahman , Hamdallah Aboalmagd , Kedwany Ahmed M , Barakat Ahmed , Sayad Reem , Abdelazeem Basel
Published: May 2024

Background and Aims

Kidney transplantation is a choice treatment for end-stage renal disease. It is the most cost-effective treatment and significantly improves the quality of life. However, metabolic acidosis increased following the transplantation. It can lead to several undesirable effects, such as disturbing the protein balance, resulting in a negative nitrogen equilibrium, increased protein degradation and essential amino acid oxidation, reduced physical functioning, and consequently decreased quality of life. The intraoperative crystalloid used may have significant effects on early function and acid-base balance. Also, sodium bicarbonate may enhance early graft function. This study aims to compare the effect of sodium bicarbonate in enhancing early graft function post-renal transplantation.

Method

We conducted a comprehensive search on multiple databases, including PubMed, MEDLINE, Embase, Scopus, WOS, and the Central Cochrane Registry. We included randomized controlled trials (RCTs) that compared sodium bicarbonate to normal saline during intraoperative kidney transplantation.

Results

Our search retrieved three RCTs, with 246 patients eligible for our criteria. We used either fixed- or random-effects models in the quantitative synthesis of the eligible studies accounting for clinical heterogeneity. Pooled data revealed that the sodium bicarbonate group was associated with a significantly improve in PH level (MD = 0.1; 95% CI: 0.06, 0.13; P < 0.01), Base Excess level (MD = 4.60 mEq/L; 95% CI: 3.43, 5.77; P = 0.003), and urine volume (MD = 2.59 L; 95% CI: 0.88, 4.29; P < 0.01). However, there was no significant difference between two groups in decreasing creatinine level after first day (MD = −0.46 mg/dl; 95% CI: −1.68, 0.76; P = 0.46), but the creatinine level significantly decreases after 2nd day (MD = −1.11 mg/dl; 95% CI: −1.96, −0.26; P = 0.01), and 3rd day (MD = −1 mg/dl; 95% CI: −1.17, −0.72; P < 0.01).

Conclusion

Our study suggests a potential advantage of sodium bicarbonate over the normal saline solution as an intraoperative fluid in improving metabolic acidosis during kidney transplantation.
#762 Hyperkalemia and discontinuation of RAS blockade after initiating SGLT-2i vs. DPP-4i in patients with type 2 diabetes; a population-based cohort study
Authors: Bosi Alessandro , Xu Yang , Fu Edouard L , Faucon Anne-Laure , Sjölander Arvid , Carrero Juan-Jesus
Published: May 2024

Rate of hyperkalemia and discontinuation of renin-angiotensin system blockade after initiating SGLT-2 inhibitors vs. DPP-4 inhibitors in patients with type 2 diabetes; a population-based cohort study

Background and Aims

Post-hoc analyses of clinical trials have suggested that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) lower the rate of hyperkalemia and facilitate the use of renin-angiotensin system inhibitors (RASi) in people with type 2 diabetes and CKD. Whether these effects are generalizable to patients treated in routine clinical practice is unclear. Here, we evaluated the comparative effects of SGLT-2i and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the rate of hyperkalemia and RASi discontinuation.

Method

We conducted a population-based active-comparator, new-user cohort study using data from the Stockholm CREAtinine Measurements (SCREAM) project of people with type 2 diabetes who newly initiated SGLT-2i or DPP-4i between January 2014 and December 2021. The primary outcomes were time to first outpatient hyperkalemia (plasma potassium >5.0 mmol/L) occurrence and recurrent hyperkalemia. The secondary outcomes were mild (potassium >5-≤5.5 mmol/L) and moderate-severe (potassium >5.5 mmol/L) hyperkalemias. Among RASi users, we also studied time to RASi discontinuation through evaluation of pharmacy fills. Cox regression with inverse probability of treatment weighting was used to estimate hazard ratios (HRs) and rate differences for time to first hyperkalemia. Weighted Poisson regression was used to estimate incidence rate ratios (IRRs) for hyperkalemia recurrence.

Results

We included 24 417 individuals (of which 14 470 initiated SGLT-2i and 9, 947 DPP-4i therapy), followed for median 2.0 (Q1-Q3 0.8-3.7) years. Mean age was 67 years and 37% were women. Compared with DPP-4i, initiation of SGLT-2i was associated with a lower rate of first hyperkalemia (adjusted hazard ratio [HR] 0.83; 95% CI 0.72-0.96) and recurrent hyperkalemia (incidence rate ratio [IRR] 0.75; 0.64-0.85). Similar findings were observed among people with eGFR ≥60 (HR 0.73; 95% CI 0.63-0.86) and <60 (HR 0.87; 95% CI 0.63-1.16) ml/min/1.73 m2, as well as for mild (HR 0.82; 95% CI 0.71-0.95) and moderate-severe (HR 0.67; 95% CI 0.52-0.84) hyperkalemias. Out of 15 746 participants that were prevalent RASi users, 17% discontinued RASi therapy during 2.0 (IQR 0.8-3.7) years of follow-up. Initiation of SGLT-2i vs. DPP-4i was not associated with the rate of RASi discontinuation (HR: 1.00; 0.91-1.11).

Conclusion

In patients with type 2 diabetes managed in routine clinical care, the use of SGLT-2i was associated with a lower rate of first and recurrent hyperkalemia compared with DPP-4i. However, this was not accompanied by higher persistence on RASi therapy.
#1225 Lactate aggravates mitochondrial dysfunction via ALDH2 lactylation in acute kidney injury
Authors: Li Jiaying , Shi Xiaoxiao , Hou Fangxing , Luan Xiaodong , Chen Limeng
Published: May 2024

Background and Aims

Elevated lactate levels have been recognized as an independent risk factor in acute kidney injury (AKI) contributed by mitochondrial dysfunction. We previously proved the crucial role of acetaldehyde dehydrogenase 2 (ALDH2) in AKI but not focused on the lactate and lactylation of ALDH2.

Method

We first established a maleic acid (MA) induced AKI model (MA-AKI) in C57BL/6J mice, administrating 2-DG i.p. (a glycolysis inhibitor) or oxamate (a lactate dehydrogenase A inhibitor) to suppress the lactate production. We measured the renal function, mitochondrial function, and lactate in serum and urine, then evaluated the ALDH2 lactylation by co-immunoprecipitation assays, and identified the specific lactation site by mass spectrum. The role of ALDH2 lactylation was explored through point mutation in HEK293 cells. Furthermore, an ALDH2 lactylation eraser was identified, and its function was elucidated in mice and HK-2 cells.

Results

The elevated lactate in the kidney, serum, and urine showed a significant positive correlation to the serum creatinine (Scr, R2 = 0.83, P < 0.0001) in MA-induced mice. Both 2-DG and oxamate partly abolished the Scr increasing and the proximal tubular histopathological injuries. Increased pan-lactylation in AKI mice was effectively inhibited by oxamate, parallel with increased ALDH2 lactylation in MA-stimulated HK-2 cells. Mass spectrometry identified a single lactylate lysine residue in ALDH2 (K52). The introduction of a point mutation (K52 to R) in ALDH2, mimicking the delactylated state, led to partial recovery of ALDH2 activity (1.11 ± 0.07 vs. 0.68 ± 0.15, P = 0.0029) and mitochondrial function in MA-stimulated HK-2 cells. Additionally, sirt3 was identified as an ALDH2 lactylation eraser, and Honokiol (a sirt3 activator) demonstrated enhanced renal function and mitigation of mitochondrial dysfunction in both MA-induced mice and HK-2 cells.

Conclusion

Lactate played a crucial role in mitochondrial dysfunction in AKI partly via induction of ALDH2 lactylation, which shed light on the potential target for the therapy.
#1416 Extracorporeal removal of per- and polyfluoroalkyl substances (PFAS) by hemoadsorption: in vitro kinetic model
Authors: Lorenzin Anna , Perin Natascha , de Cal Massimo , Brendolan Alessandra , Zanella Monica , Ronco Claudio
Published: May 2024

Background and Aims

Per- and polyfluoroalkyl substances (PFAS) are known water pollutants leading to potential public health consequences. High blood levels of PFAS have been associated with several pathological conditions including testicular and kidney cancer. Classic extracorporeal therapies have demonstrated limited efficiency and new approaches should be explored. In this study we studied the possible role of hemoadsorption to achieve a fast, safe and effective removal of PFAS from blood in patients with high blood levels.

Method

We developed an in vitro model of hemoadsorption to test the potential of PFAS removal by extracorporeal treatment. We recirculated a highly polluted batch of water (4 liters) through HA380 sorbent cartridge (Jafron Medical, Zuhai, China) for 120 minutes at a flow of 150 mL/min in a closed loop configuration (Fig. 1). We collected samples at different time points and analyzed 39 different PFAS compounds.

Results

For the PFAS compounds with concentrations significantly above normal, we observed a removal ratio close to 90% already within the first 60 minutes of circulation leading to almost complete elimination of all pollutants at 120 minutes (Fig. 2). RR is remarkably high already in the very early moments of the adsorption process. This is likely dependent on the interaction of the different solutes with the molecular structure of the sorbent.

Conclusion

The in vitro model of hemoadsorption suggests the possible application in vivo of this technique to reduce/normalize the concentrations of PFAS in patients exposed to water or environmental pollution.
#736 The short-term and long-term impact of COVID-19 on the kidney disorders: an observational and Mendelian randomization study
Authors: Chunyang Li , Zhang Chao , Chen Jie , Zeng Xiaoxi
Published: May 2024

Background and Aims

The impact of “long COVID-19” on “short-term” or “long-term” influence on kidney function change remains unknown. We aimed to investigate the causal association between COVID-19 and subsequent kidney outcomes.

Method

10121 participants exposed to COVID-19 were matched up to 3 unexposed controls by age, sex, Townsend deprive index and severity of COVID-19 from UK Biobank. Using conditional and time-varying Cox proportional hazard regression, we first investigated the association between the SARS-CoV-2 infection and incidence of acute kidney disorder and chronic kidney disease (CKD). One-sample mendelian randomization (MR) using polygenetic risk score (PRS) of COVID-19 as instrumental variable was performed. Then, we extended the finding with two-sample MR analyses using GWAS summary statistics from UKB as outcomes, and GWAS of COVID-19 severity, hospitalization and susceptibility from the COVID-19 Host Genetics Initiative (r7) database as exposures.

Results

In observational study, we observed time-varying effects of COVID-19 on the risk of acute kidney disorder incidence, with the highest hazard effect in the second week (HR 12.77, 95% CI: 5.93-27.70) and disappearing in the fourth week (HR 2.28, 95% CI: 0.75-6.93). In subgroup analysis, this time-varying effects were only found in patients with moderate and severe COVID-19, but not mild COVID-19 patients. No association was observed between SARS-CoV-2 infection and the risk of incident CKD. Subsequent individual-level MR showed that COVID-19 severity, hospitalization and susceptibility were significantly associated with increased risk of acute kidney disorder, but not CKD. Two-sample MR indicated that none of the COVID-19 phenotypes were associated with these two diseases nor other kidney traits.

Conclusion

COVID-19 had “short-term” effects on the risk of subsequent acute kidney disorder incidence, and the hazard effects were only observed in moderate or severe but not mild COVID-19 patients.
#807 Presepsin and procalcitonin levels are associated with acute kidney injury in sepsis patients
Authors: Isaranuwatchai Suramath , Sophonphan Jiratchaya , Voharnsuchon Parima , Thong-on Kwannapa , Sri-on Jiraporn
Published: May 2024

Background and Aims

Acute kidney injury (AKI) is a leading cause of death in patients with sepsis. Presepsin is a novel biomarker which has been used to predict sepsis and the outcomes of sepsis. Presepsin was also demonstrated in a small clinical trial to be associated with AKI in sepsis patients. Procalcitonin is a biomarker which was well-studied in sepsis and AKI patients. We aimed to study the association of presepsin and procalcitonin with AKI and outcomes of AKI in sepsis patients.

Method

We conducted a multicenter prospective trial in eight tertiary-care hospitals in Thailand. We included suspected sepsis patients aged 18 years or older who entered the emergency room during January 2021 to July 2022. We excluded patients with pregnancy, previous trauma, and postcardiac arrest. We also excluded dialysis patients and patients with estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m2 from our study. We measured blood presepsin and procalcitonin at day 0, 3 and 7 along with other investigation for usual intensive care of sepsis. We calculated the level of presepsin and procalcitonin that could distinguish between sepsis patients with and without AKI. We also analyzed whether presepsin and procalcitonin were associated between severity of AKI determined by Kidney Disease: Improving Global Outcomes (KDIGO) staging of AKI.

Results

We recruited 621 patients who was diagnosed sepsis at emergency department. AKI was diagnosed in 246 patients (39.6%). Of these AKI patients, maximal KDIGO stage of AKI were stage 1, 2 and 3 in 140 (56.9%), 64 (26.0%) and 42 (17.1%) patients, respectively. The median age was 70.1 years with 54.6% was male patients. The median BMI was 21.9 kg/m2. The median Charlson comorbidity index (CCI) was 5 (IQR 4-7). The median presepsin level in AKI patients was 1012 pg/mL (IQR 528-1719 pg/mL), which was significantly higher (P < 0.001) than the median presepsin level in non-AKI patients, which was 594 pg/mL (IQR 337-1138 pg/mL). The median procalcitonin level in AKI patients was 1.24 ng/mL (IQR 0.22-6.06 ng/mL), which was significantly higher (P < 0.001) than the median presepsin level in non-AKI patients, which was 0.50 ng/mL (IQR 0.09-2.34 ng/mL). The cut-point of presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively. The higher level of presepsin and procalcitonin also significantly associated with higher KGIDO staging of AKI as shown in Fig. 1. However, the mortality rate in both groups were not significantly different (24.0% in AKI group vs. 21.1% in non-AKI group, P = 0.39)

Conclusion

To date, this is one of the largest studies to evaluate the association between presepsin level, procalcitonin level and AKI in sepsis patients. The presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively.
#1052 Associations of new-onset proteinuria during hospitalization with all-cause mortality and kidney outcome
Authors: Zhou Shiyu , Chen Ruixuan , Xu Xin , Nie Sheng
Published: May 2024

Background and Aims

Proteinuria has been routinely screened in hospitalized patients at admission, but the changes in urinary protein during hospitalization is usually neglected. The epidemiology and clinical implication of new-onset proteinuria during hospitalization remains unclear. We aim to examine the associations between new-onset proteinuria during hospitalization with all-cause mortality, cardiovascular mortality, and composite kidney outcomes after discharge.

Method

We conducted a multicenter cohort of hospitalized adults without proteinuria at admission and with at least one repeated urinary protein test before discharge from the China Renal Data System. New-onset proteinuria was defined as a change in the urine dipstick protein test from negative to 1+ or more during hospitalization. The primary outcome was all-cause mortality after discharge. Secondary outcomes included cardiovascular mortality and composite kidney outcomes of sustained new-onset eGFR<60 ml/min/1.73 m2, >40% decline in eGFR, maintain dialysis, kidney transplant, or end stage renal disease. The associations between new-onset proteinuria and study outcomes were assessed by Cox proportional hazard models.

Results

Among 219,669 inpatients with mean age of 54 years, new-onset proteinuria occurred in 7.3% of the study population during hospitalization. After a mean follow-up of 4.9 years, patients with new-onset proteinuria during hospitalization was significantly associated with increased risk of all-cause mortality (hazard ratio [HR] 1.16; 95% confidence interval [CI], 1.07-1.25), cardiovascular deaths (HR 1.25; 95% CI, 1.07-1.46), and adverse kidney outcomes (HR 1.51; 95% CI, 1.14-2.01), compared to those without proteinuria. These associations were independent of the occurrence of AKI and remained consistent across subgroups and multiple sensitivity analyses, regardless of the severity and recovery status of new-onset proteinuria.

Conclusion

The presence of new-onset proteinuria during hospitalization demonstrated significant prognostic value and should be carefully monitored to improve patient care.
#2053 The third-day blood lactate levels and APACHE III are important for predicting mortality in intensive care unit patients: Physionet data
Authors: Son Min Kook , An Won Suk , Yang Dong Eun
Published: May 2024

Background and Aims

Intensive care patients had higher mortality and SOFA score is used for mortality prediction. The SOFA score was developed more than 25 years ago to monitor organ dysfunction. Nowadays, blood lactate levels indicate septic shock and work as a new vital sign. This study aimed to evaluate the blood lactate levels for prediction mortality and search for the best predictors for mortality.

Method

Physionet data (MIMIC3) were used for this retrospective analysis. A total of 13,357 intensive care unit patients were enrolled, they were admitted to the intensive care unit over 24 hours and aged 20 years old, were initially checked for blood lactate levels. We also analyzed 2,748 patients who were checked for blood lactate levels at baseline, the second day, and the third day. We classified patients into three groups according to initial blood lactate levels (group 0: <4 mmol/L, group 1: 4-7.99 mmol/L, group 2: >8 mmol/L).

Results

The total mortality rate (60.3% vs. 24.4%), 7-day mortality rate, and 30-day mortality rate were the highest in group 2 compared to group 0 among 13,357 intensive care patients. Charlson-comorbidity index, SOFA score, and APACHE III score were the highest in group 2 compared to group 0 among 13357 intensive care patients. The arterial pH, pC02, systolic blood pressure, and GFR were the lowest in group 2 compared to group 0 among 13357 intensive care patients. These findings were similarly found in 2,748 intensive care patients. The third-day blood lactate levels and APACHE III score showed a higher area under the ROC curves predicting total mortality, 7-day mortality, and 30-day mortality than initial blood lactate levels and SOFA score. The third-day blood lactate levels, third-day/initial blood lactate ratio, and APACHE III score were independently associated with total mortality, seven-day and 30-day mortality in 2,748 intensive care patients, but GFR, ventilator care and SOFA score were not.

Conclusion

The third-day blood lactate levels and APACHE III score were the best predictors for mortality in intensive care unit patients. Therefore, intensive care for reducing blood lactate levels is important to increase survival.
#2262 Renal outcomes of postpartum atypical hemolytic uremic syndrome treated with plasma exchange
Authors: Khedr Lamis , Zaki Shaimaa , Elsharabasy Reem
Published: May 2024

Background and Aims

Postpartum acute kidney injury (AKI) with features of thrombotic microangiopathy (TMA) are particularly challenging and complex cases. Causes include Preeclampsia (PE), hemolysis, elevated liver enzymes and low platelet count syndrome (HELLP) and atypical hemolytic uremic syndrome (aHUS). In a limited resource setting, it is difficult to diagnose such cases with more than standard blood tests. Therapeutic Plasma exchange (TPE) is the only available option for treatment in the absence of complement inhibitors. This study evaluates renal outcomes in patients with aHUS treated with plasma exchange.

Method

This is a single centre observational study conducted in a Tertiary Obstetric Intensive Care unit. The data of women who were admitted with postpartum AKI from January 2021 to October 2023 was retrospectively collected and analyzed. We used the following criteria to diagnose postpartum atypical HUS (Serum creatinine ≥1.9 mg/dL, Lactate dehydrogenase (LDH) ≥1832 U/L, or serum creatinine ≥1.9 mg/dL in combination with LDH ≥600 U/L) [1]. Inclusion criteria include women older than 18 yrs with microangiopathic hemolytic anaemia, schistocytes on peripheral blood film, negative direct antiglobulin test (DAT) and platelet count <100 /mm3.Lack of improvement of kidney functions and hemolysis 72 hours after delivery. Patients with sepsis, disseminated intravascular coagulopathy (DIC), postpartum hemorrhage (PPH) and chronic kidney disease were excluded. We identified 10 patients with postpartum aHUS. Peak creatinine, LDH, AST and Nadir platelet count and hemoglobin were recorded. Patients were followed up in the nephrology outpatient clinic.

Results

Fifty-two patients developed postpartum AKI in the study period. Ten patients (19%) were diagnosed with aHUS according to the above-mentioned criteria. Mean age was 24.5 ± 6.9 yrs. Median peak creatinine 5.1 (2.6-7) mg/dl, LDH 1950 (612-4000) U/L, AST 246 (150-699) U/L. Median nadir hemoglobin 7.25 (6-8.2) g/dl and platelets 57 (41-95)/mm3. All 10 patients received 3 to 6 sessions of TPE guided by platelets and LDH levels. All patients required at least 3 sessions of hemodialysis. Eight patients received TPE with plasma filter and 2 had centrifugal TPE (due to lack of plasma filters). Two patients died during ICU admission. Two months after discharge 4 (50%) patients had partial recovery of kidney functions average creatinine (3.5 ± 0.8) mg/dl and four (50%) remained dialysis dependent. Six of these patients had kidney biopsies, three biopsies showed a picture of thrombotic microangiopathy and two showed thrombotic microangiopathy with renal cortical necrosis. The other patient was lost to follow up.

Conclusion

It is difficult to diagnose and treat aHUS in a resource limited setting. The available treatment with therapeutic plasma exchange has poor renal outcomes.
#1934 Association between transient AKI and all-cause mortality in critically ill patients according to baseline BUN/SCr ratio and diuretics use
Authors: Nie Sheng , Mingzhen Pang
Published: May 2024

Background and Aims

Previous studies have yielded inconsistent results regarding the prognosis of transient acute kidney injury (AKI). We aimed to assess the risk of mortality and kidney outcomes in critically ill patients with transient AKI according to BUN/SCr ratio (BCR) level and diuretics treatment at baseline.

Method

We conducted a multicentre retrospective cohort study of critically ill patients, including 131,034 patients from China (CRDS) and 9,778 patients from US (MIMIC-IV) spanning from 2012 to 2021. Transient AKI was defined as AKI that recovered within two days. Study outcomes included one-year all-cause mortality and the occurrence of major adverse kidney events (MAKE). The associations between transient AKI and study outcomes were compared in patients stratified by BCR level and diuretics use at baseline.

Results

Of 140,812 eligible patients, 3,863 were diagnosed with AKI according to KDIGO criteria and classified as having transient AKI. In patients with a baseline BCR level ≤ 20 (N = 79,883), transient AKI was associated with 42% and 58% increased risk of mortality and MAKE, respectively, compared to those without AKI. However, these associations were not significant in those with a BCR level > 20 (N = 60,929) (P for interaction < 0.05). Similar modified effects of diuretics on the outcomes of transient AKI were also observed. The associations of transient AKI with mortality and MAKE were both significantly different in patients with (N = 26,140) or without (N = 114,672) diuretics treatment before AKI (P for interaction < 0.05).

Conclusion

The effects of transient AKI on mortality and kidney outcomes in critically ill patients were modified by the BCR level and diuretics use before AKI.
#2679 Prediction of acute eGFR decline after first initiation of RASI inhibitors and its impact on clinical outcomes
Authors: Zhang Yuping
Published: May 2024

Background and Aims

The objective of this study is to investigate the correlation between acute eGFR (estimated glomerular filtration rate) decline after initiation of ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin receptor blocker) medications and clinical outcomes in a real-world setting. Additionally, we aim to establish a risk prediction model to identify high-risk individuals who are more likely to experience a rapid decline in eGFR after drug initiation.

Method

A total of 2026 adult new users of ACEI/ARB were selected from the China Renal Data System (CRDS). Patients in acute clinical states and those using nephrotoxic drugs were excluded, and it was required that patients had at least one creatinine measurement during the baseline period and one week to four weeks after drug initiation. Cox proportional hazards models were used to compare the relative risks of adverse long-term outcomes in patients with different degrees of acute eGFR decline. A multivariable logistic regression model was employed to analyze the factors influencing acute eGFR decline. Lasso regression was used to select predictive factors, resulting in a logistic regression model with 18 predictive factors.

Results

Among the 2026 patients, 1148 (57%), 473 (23%), and 405 (20%) experienced eGFR decline <5% or increase, 5-20% decline, and ≥20% decline, respectively, after initiation of RASI (renin-angiotensin system inhibitor). Following adjustment for multiple variables, an eGFR decline ≥20% was found to be associated with a higher risk of long-term renal disease progression, with a hazard ratio of 1.84 (95% confidence interval 1.19-2.85), but not significantly associated with an increased risk of all-cause mortality and cardiovascular events. Factors associated with an eGFR decline ≥20% after RASI initiation included higher BMI and Charlson index, more severe proteinuria, lower hemoglobin levels, presence of hypertension, diabetic nephropathy, arrhythmias, and concomitant use of thiazide diuretics or loop diuretics. The predictive model had a C-statistic of 0.75.

Conclusion

This study demonstrates that a short-term eGFR decline after RASI initiation is associated with a higher risk of long-term renal disease progression but not significantly associated with increased risks of all-cause mortality and cardiovascular events. We have developed a prediction model to estimate the risk of eGFR decline ≥20% after the initial use of RASI, which can aid clinicians in identifying patients with poorer renal outcomes following RASI initiation and facilitate timely intervention.
#959 Developing and validating a risk score model for prediction of AKI in non-ICU hospitalized patients
Authors: Elrewihby Walid
Published: May 2024

Background and aim

: Acute kidney injury (AKI) is an increasingly common and potentially catastrophic complication in hospitalized patients. Several risk score models have been designed for intensive care unit (ICU) patients. Aim in this work was to establish a new risk prediction score for AKI patients in general wards.

Methods

All hospitalized ward patients from the first of July 2019 to 31st of December 2019 who developed AKI 24 hours after admission were included. To create a new prediction score model of AKI in hospitalized patients we used the data collected from 107 patients who developed AKI. We used our prospective cohort to develop and validate this prediction score model of AKI in patients admitted to general wards.

Results

Only 107 patients of 10,243 (1%) developed AKI 24 hours after admission to the general wards. Mortality rate was 26.2%. A score model of 15 points, based on a combination of clinical and laboratory data, was developed for prediction of AKI. We demonstrated that a cutoff value ≥ 4 out of 15 was a predictor of Acute Kidney Injury in non-ICU hospitalized patients. The area under the receiver operating characteristic (AUC ROC) value of the score model was 0.950, 95% CI (confidence interval) 0.922–0.978 and the P-value <0.001 with sensitivity of 94.39 and specificity of 81.43. Applying the score model in another group of patients (validation group n = 122) showed that the AUC ROC value in the validation group was 0.826.

Conclusion

We developed and validated a new risk score model with a cutoff value ≥ 4 out of 15 for prediction of Acute Kidney Injury in non-ICU hospitalized patients with a good sensitivity and specificity. It will help the early prediction of Acute Kidney Injury in non-ICU patients.
#862 Prevalence and surrogate predictors of acute kidney injury in tropical infections in eastern India
Authors: Mukhopadhyay Pinaki
Published: May 2024

Background and Aims

Acute kidney injury (AKI) in tropical countries is strikingly different from the other countries with a temperate climate. The epidemiology of AKI is largely influenced by environmental factors and climatic conditions and differ significantly its outcome and the surrogate predictors are not much studied.

1. To observe the spectrum and estimate the prevalence of AKI in tropical infections. 2. To evaluate the outcome and surrogate predictor of tropical AKI.

Method

This was a tertiary level single centre prospective observational study. All patients admitted with tropical infections associated AKI (KDIGO) were enrolled in two years and underwent complete history taking, clinical examinations and necessary laboratory investigations according to situations.. All patients were followed up more than 6 month. All data recorded were analysed in suitable statistical tool. Univariate analysis is followed by multivariate analysis was done for predictors followed by hazards ratio and Neglekers test.

Results

Out of 132 patients with Tropical AKI M:F was 1.5:1. Mean age was 42.3 ± 14.4 year, About 35.6% had Malaria,31.1% Dengue, 17% Scrub typhus, 10.4% Leptospira, and 5.9% patients had Typhoid fever. Malaria was the most common causative factor followed by Dengue. study reflecting the high dengue incidence occurring in the months of August, September, October & November. Among Malaria AKI (MAKI) 43.75% (21) had Falciparum malaria, 50% (24) had Vivax malaria and 6.25% (3) had dual infection. Out of 132 patients with Tropical AKI about 60% totally recovered at the time of discharge. 40% patients had Shock. Among them 60% Dengue AKI, 33.3% Malarial AKI 5 (21.7%) Scrub typhus, 4 (28.6%) Leptospira AKI & 3 (37%) Typhoid AKI patients had Shock. About 23% patients required RRT. Among them 8 (25%) patients died, 5 (15.6%) patients had CKD progression compared to non-RRT group where only 3 (2.9%) patients died, and 2 (1.94%) patients had progression to CKD.

Total 11 (8.1%) patients died during hospital stay and only 7 (6.2%) patients had progressed to CKD. The mean Hospital stay was 5.51 ± 3.8 days. S hock at presentation, requirement of ICU support ( in form of ionotropic and ventilatory support), Need of RRT, prolong hospital stay, late referral was the bad prognostic predictor in terms of death. Though not statistically significant, presence of anaemia, hyponatraemia, deranged liver function & hypoalbuminemia were more in patients who died compared to survival group.

Limitations: Small enrolments. non inclusion of all cause including snake bite, less biopsy in this study.

Conclusion

There are wide spectrum of tropical AKI with high mortality and morbidity. A greater awareness and early intervention is necessary for prompt diagnosis, treatment and favourable outcome.
#604 Oral administration of UNI-494 ameliorates acute kidney injury in a rat model of delayed graft function
Authors: Medicherla Satya , Reddy Guru , Gupta Shalabh
Published: May 2024

Background and Aims

There are no FDA approved drugs for the treatment of acute kidney injury (AKI), which affects 10-15% of hospitalized patients and often results in renal transplantation or lifelong dialysis. UNI-494 is a novel nicotinamide ester derivative and selective mitochondrial ATP-sensitive potassium channel activator that may be beneficial for several disease states, including AKI. We present results from a study evaluating the in vivo efficacy of oral (PO) UNI-494 in the unilateral renal ischemia-reperfusion (I/R) rat model of AKI, which is a well-established model of delayed graft function (DGF) (Cavaille-Coll, 2013).

Method

Rats were anesthetized, the right kidney was removed, and I/R was induced in three groups of rats by clamping the renal vessels in the left kidney for 30 minutes; a fourth group had no surgery (sham group) without clamping the renal vessels. 50 mg/kg or 100 mg/kg UNI-494 were administered PO 30 minutes prior to I/R. One I/R group and the sham group were not treated. After 24 hours of reperfusion in metabolic cages, blood samples were collected for serum creatinine (sCr), and urinary samples were collected for albumin-creatinine ratio (ACR) and the tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL). The clamped left kidney was collected and processed for histology for tubular injury scores.

Results

In this study, I/R induced significant increases of sCr, ACR, NGAL, and proximal convoluted tubular injury scores in the vehicle treated I/R group vs No I/R sham group. A single PO dose of UNI-494 at 50 mg/kg/PO or 100 mg/kg/PO reduced the kidney functional markers sCr and ACR, the tubular injury marker (NGAL), and proximal tubular injury scores (all p < 0.001, Fig. 1).

Conclusion

The results indicate that UNI-494 dose dependently prevented AKI markers and proximal tubular injury in a rat model of AKI and therefore is a potential candidate for the prevention of DGF and other AKI clinical conditions.
#242 Incidence of postoperative acute kidney injury is twice as high in men than women following radical colorectal surgery—key findings from PROSACC
Authors: Franzén Stephanie Therése , Enlund Mats , Frithiof Robert
Published: May 2024

Background and Aims

Acute kidney injury (AKI) affects approximately 8% of the general surgical population. Additionally, AKI increases the risk for morbidity and mortality by 8- and 3-fold respectively. It was earlier believed that women had a greater risk for postoperative AKI. However, recent literature indicates that the incidence of AKI is actually higher in hospitalized men than women (2.2 odds ratio). Hence the male sex is currently discussed to be a risk factor for AKI. We therefore hypothesized that the incidence of postoperative AKI will be higher amongst men than women after radical colorectal surgery.

Method

We conducted a post hoc analysis (PROSACC: Propofol or Sevoflurane Anesthesia in Colon Cancer, NCT05585866) on the database from the CAN-study (Cancer and Anesthesia: Survival After Radical Surgery, NCT01975064). The CAN-study included cancer patients undergoing radical surgery at several sites in China, Croatia, Poland, and Sweden. Patients included in PROSACC were those undergoing colorectal surgery at any predefined site. Primary outcome was incidence of AKI by changes in plasma creatinine, secondary outcome was AKI in association to gender (women/men). The KDIGO criteria was used for classifying AKI on postoperative days 1-3 and 4-10. Database management and statistical analysis was performed by Uppsala Research Centre. Men vs women AKI outcome at day 1-3 and 4-10 was statistically compared with the Pearson's chi-square test.

Results

A total of 3254 patients (n = 1900 men; n = 1354 women) were included in the analysis with their preoperative plasma creatinine. Demographics showed that of the women, 39% had hypertension, 12% had diabetes and 2% had pre-existing kidney disease. In comparison, amongst the men, 24% had hypertension, 9% had diabetes and 1% pre-existing kidney disease. Postoperative plasma creatinine values were obtainable from the database in 2741 patients (n = 1578 men; n = 1163 women) on postoperative day 1-3. One hundred and ninety patients (7%) of this group had developed AKI. Separated by gender, 6% of the women (n = 72) and 8% of the men (n = 118) had established AKI according to KDIGO (p = 0.190). Plasma creatinine values were obtainable in 986 patients (n = 582 men; n = 404 women) on postoperative day 4-10 whereas 87 patients (9%) in this group had developed AKI. Separated by gender, 6% of the women (n = 23) but 11% of the men (n = 64) had established AKI at this timepoint (p = 0.004).

Conclusion

With this post hoc analysis of a global, multicentre, randomized controlled trial we conclude that the incidence of postoperative AKI is twice as high in men compared with women after 4-10 postoperative days following radical colorectal surgery. Since the women had higher rate of pronounced preoperative risk factors yet still had lower incidence of AKI, this study aligns with the conclusion that the male sex is a risk factor for postoperative AKI.