bluuebunny/crossref_metadata_2025 huggingface dataset:
MO322: Utility of Contrast-Enhanced Ultrasound to Predict Renal Recovery in Patients With Sepsis-Associated Acute Kidney Injury Receiving Renal Replacement Therapy
Authors: Cho Heejin , Yun Lee Hyang , Shin Jungho , Ho Hwang Jin , Hyun Kim Su
Published: May 2022

BACKGROUND AND AIMS

Microcirculation plays a critical role in the development of sepsis-associated acute kidney injury (S-AKI); however, it remains uncertain whether microcirculatory dysfunction influences recovery. We investigated the association of contrast-enhanced ultrasound (CEUS)-assessed microcirculatory parameters with dialysis dependence in patients with S-AKI receiving renal replacement therapy.

METHOD

This study included 23 patients who underwent renal replacement therapy due to S-AKI, in addition to 17 healthy individuals and 18 subjects with chronic kidney disease (CKD). Parameters obtained from CEUS were compared.

RESULTS

Of the CEUS-derived parameters, patients with S-AKI had delayed rise time, time to peak and fall time, compared with healthy individuals (P = .039, .045 and .072), but they had similar values of peak enhancement, wash-in/out area under the curve (AUC), and wash-in perfusion index. Parameters did not differ between the S-AKI and CKD groups. Among patients with S-AKI, 10 (43.5%) patients did not experience renal recovery and required the lifelong dialysis treatment. They had lower values of peak enhancement, wash-in/out AUC, and wash-in perfusion index than in those with recovered renal function (P = .049, .021, .036 and .049). In addition, these values were slightly related to renal recovery after the adjustment with age, sex and disease severity (P = .096, .065, .094 and .072, respectively). We further evaluated the receiver operating characteristic curve and observed that CEUS-derived peak enhancement, wash-in/out AUC, and wash-in perfusion index predicted renal recovery (P = .047, .022, .035 and .047).

CONCLUSION

Assessment of microcirculatory alterations using CEUS may help to predict the probability of renal recovery in patients with S-AKI receiving renal replacement therapy. Further studies are needed to confirm the utility of CEUS, in consideration with baseline renal function and pathologic findings.
MO324: Serum Potassium Trajectory During AKI and Mortality Risk
Authors: Chávez-Iñiguez Jonathan S , Aranda-G de Quevedo Andres , Chávez-Alonso Gael , Oliva Ana E , Díaz-Villavicencio Bladimir , Calderón-García Clementina E , García-García Guillermo , Alcantar-Vallin Luz , Medina-González Ramón
Published: May 2022

BACKGROUND AND AIMS

Kidneys play a primary role in potassium homeostasis. The association between potassium (sK+) level and mortality or the need for kidney replacement therapy (KRT) during acute kidney injury (AKI) has not been adequately explored.

METHOD

In this prospective cohort study, AKI patients admitted to the Hospital Civil de Guadalajara were enrolled from August 2017 to June 2021 with AKI. We divided patients into eight groups based on the serum potassium level trajectories up to 10 days following hospitalization: (1) normokalemia (normoK), defined as sK + values between 3.5 and 5.5 mEq/L; (2) corrected hyperkalemia (hyperK), sK+ > 5.5 mEq/L on hospital admission and decreased to normoK; (3) corrected hypokalemia (hypoK), sK+ < 3.5 mEq/L on hospital admission and increased to normoK; (4) fluctuating potassium, sK + increased/decreased in and out of normoK parameters; (5) uncorrected hypoK, sK+ < 3.5 mEq/L; (6) normoK to hypoK, sK + that were normal on hospital admission and decreased to hypoK and never went back to normal; (7) normoK to hyperK, sK + that were normal on hospital admission and increased to hyperK and never went back to normal; and (8) uncorrected hyperK, sK+ > 5.5 mEq/L. We assessed the association of serum potassium trajectories with mortality and the need for KRT (secondary objective).

RESULTS

A total of 311 AKI patients were included. The mean age was 52.6 years, and 182 (58.6%) were male. AKI stage 3 was present in 199 (63.9%). KRT started in 112 (36%) patients, and 66 patients (21.2%) were died. After adjusting for confounders, 10-day hospital mortality was significantly higher in group 7 and 8 (OR 1.37 and 1.63; P = < .05 for both, respectively), and KRT initiation was higher only in group 8 (OR 1.40; P = < .05) compared with group 1. Mortality in different subgroups of patients in group 8 did not change the primary results.

CONCLUSION

In our prospective cohort, most patients with AKI had alterations in sK + . NormoK to hyperK and uncorrected hyperK were associated with death, while only uncorrected hyperK was correlated with the need for KRT.
MO326: Factors Influencing Death Rate in COVID-19-Associated Acute Kidney Injury
Authors: Daniela Radulescu , Cuiban Elena , Adela Vacaroiu Ileana , David Cristiana , Tuta Liliana-Ana , Liliana Turcu Flavia , Carmen Bogeanu , Onofrei Simona-Daniela
Published: May 2022

BACKGROUND AND AIMS

During a 2-year pandemic, COVID-19 proved to be a condition with a high potential to affect various organs other than the lungs. Acute kidney injury (AKI) in hospitalized COVID-19 patients is associated with a poor prognosis. The aim of this study was to identify factors influencing in-hospital mortality.

METHOD

In a retrospective analysis, we included 268 adult patients with RT-PCR-confirmed SARS-CoV-2 infection and AKI admitted to two Emergency University Hospitals during a 6-month period, between 1 November 2020 and 30 April 2021. Data were retrieved from the electronic databases of the two hospitals. We analysed kidney and patient outcomes at discharge and the potential risk factors for mortality in AKI patients. We defined and staged AKI according to KDIGO 2012 creatinine criteria.

RESULTS

In our cohort the mean age was 72.28 years, 169 (63%) patients were men, and 111 (41.4%) had previously known chronic kidney disease. 81 patients were classified as having stage 1 AKI, 79 patients had stage 2 AKI and 108 had stage 3 AKI. A total of 135 (50.37%) patients died during hospitalization.

Statistic analysis using the Mann–Whitney U-test revealed significant differences (P < .01) between survivors and non-survivors regarding peak values of serum urea (137.9 versus 190.9 mg/dL), creatinine (2.88 versus 3.94 mg/dL), procalcitonin (3.56 versus 15.86 ng/mL), C-reactive protein (92.32 versus 176.09 mg/L), interleukin-6 (243 versus 9552 pg/mL), ferritin (1331 versus 5189 ng/ml) and d-dimers (3.68 versus 6.88 mcg/ml). No significant differences were found between survivors and non-survivors regarding peak values of erythrocyte sedimentation rate (69 versus 71 mm/1 h; P = .35) and fibrinogen (629 versus 645 mg/dL; P = .24) and also regarding the lowest lymphocyte count during hospitalization (519 versus 649/mmc; P = .80).

The analysis using Fisher’s exact test showed that deceased patients were significantly more associated with AKI KDIGO stage 2 or 3 (51.9%/63% versus 32.1%), with higher need for renal replacement theraphy (RRT) (68.8% versus 47.9%), with ICU (intensive care unit) admission (90.1% versus 22.3%) (Table 1). Moreover, death was associated more frequently with partial or absent renal function recovery (20%/50% versus 6.4%) (P < .05) (Table 1).

In a logistic regression model (using KDIGO stages, serum urea and need for RRT), it was proved that only serum urea had a significant prediction power (P = .001): every increase of serum urea with 1 unit increases the risk of death by 1.007 times (95% confidence interval 1.003–1.011).

CONCLUSION

Mortality of COVID-19 patients associating AKI is proportionally augmented by both markers of severity of SarS-CoV-2 and also by severity of AKI. In our study, the peak value of serum urea during hospitalization was the best predictor for death in COVID-19.
MO341: Clinical Significance of Post-Operative Acute Kidney Disease After Non-Cardiac Surgery
Authors: Kwon Soie , Yang Sunah , Lee Hajeong
Published: May 2022

BACKGROUND AND AIMS

Acute kidney disease (AKD), the condition of which acute kidney injury (AKI) has not recovered, is being emphasized because it increases the risk of progression to chronic kidney disease (CKD). Post-operative AKI (PO-AKI) is a common clinical setting prone to develop AKI although information on post-operative AKD (PO-AKD) is lacking. We investigated characteristics of PO-AKD events after non-cardiac surgery.

METHOD

We performed a retrospective cohort study from a tertiary referral center in South Korea. The patients who underwent non-cardiac surgery (five departments: general surgery, gynaecology, urology, neurosurgery and orthopedic surgery) >1 h from 2014 to 2020 were enrolled. Patients having advanced CKD patients and those receiving nephrectomy were excluded. PO-AKI was defined as whether the KDIGO AKI criteria were satisfied within 7 days after surgery. PO-AKD was defined as a case of not recovering to <1.5× from baseline within 7 days of peak creatinine measurement after surgery among PO-AKI patients. The information of death event and initiation of renal replacement therapy were collected.

RESULTS

A total of 83 361 patients were enrolled and 4824 (5.8%) cases of AKI and 852 cases of critical AKI (1.0%) were occurred. Among PO-AKI patients, 321 (6.7%) patients were progressed to PO-AKD. Patients with PO-AKD had a higher blood pressure, a lower body mass index, more coronary artery disease, higher inflammatory markers and a higher proportion of hematuria compared with those with PO-AKI but recovered. They were younger and more women. Moreover, they had fewer comorbidities such as lower SPARK scores, lower proportions of diabetes mellitus, hypertension and malignancy, and better kidney function immediately before receiving surgery than the recovered group (Table 1). However, they tended to experience more critical AKI (critical AKI event among PO-AKI 157 patients, 48.9%; recovery 695 patients, 15.4%) and consequently showed a higher incidence of all-cause mortality (post-operative 1 year: PO-AKD 56 patients, 17.4%; recovery 606 patients, 13.5%; p = .055; post-operative 3 year: PO-AKD 126 patients, 39.3%; recovery 1496 patients, 33.2%; p = .032) and newly started of renal replacement therapy after surgery (PO-AKD 49 patients, 15.3%; recovery 136 patients, 3.0%, p <.001).

CONCLUSION

In this large-scale study, we found that 6.7% of PO-AKI patients progressed to PO-AKD. PO-AKD patients tended to experience more severe AKI and also be associated with worse patients and kidney outcomes compared with their pre-existing condition.
MO375: The Health Economic Impact of Accurately Diagnosing CKD With and Without a UACR Test at Different Points in the Pathway of Disease Progression
Authors: Mernagh Paul , Folkerts Kerstin , Garreta Rufas Antonio , Meredith Kimberley , Harris James , Wanner Christoph , Rossing Peter , Hobbs Richard
Published: May 2022

BACKGROUND AND AIMS

In the Kidney Disease Improving Global (KDIGO) guidelines, it is recommended that an accurate chronic kidney disease (CKD) diagnosis is based on repeated positive test results for estimated glomerular filtration rate (eGFR) and urine albumin-to-creatine ratio (UACR). While eGFR indicates kidney function decline, UACR identifies kidney damage, predicts CKD progression, and indicates risk for cardiovascular events. UACR testing is, therefore, a critical component of identifying CKD patients early. There is a lack of evidence that demonstrates the economic impact of early CKD diagnosis; hence, a cost-effectiveness model was built to demonstrate the potential clinical and economic benefit of undertaking UACR tests in those with early-stage CKD.

METHOD

The KDIGO heatmap quadrants were organised into a Markov model with three levels of severity (moderate, high, and very high CKD risk) over a lifetime horizon, for a cohort of 60-year-old patients in the base-case. Costs, life-years (LYs), quality adjusted life-years (QALYs), and the associated incremental cost-utility ratios (ICURs) were calculated (discounted at 3.5%). Costs consisted of testing, general practitioner (GP) visit, nephrologist visit, and treatment costs. Data inputs were based on published data from the literature and validated by clinicians.

RESULTS

Hypothetical comparisons between a 1000-patient cohort who had UACR tests undertaken in the early stages of CKD, predicted higher LYs and QALYS for patients in the KDIGO heatmap quadrants of G3aA1, G1A2, G2A2, G3aA2, G1A3, G2A3 and G3aA3 compared with a 1000-patient cohort who did not have UACR tests. By identifying individuals in the early stages of CKD, treatment can be initiated earlier, reducing the number of patients progressing to late-stage CKD and ultimately offsetting the more expensive treatment costs associated with late-stage CKD. Overall, ICURs for all quadrants were less than the UK's willingness to pay threshold of £20 000 per QALY.

CONCLUSION

Preliminary results suggest that undertaking regular UACR tests early in patients with CKD is a cost-effective strategy, as this allows an individual to initiate the appropriate treatment, resulting in slower disease progression. This is an important consideration for clinicians and policymakers due to the suboptimal UACR testing rates globally.

Funding: Bayer AG
MO381: Estimating GFR in Renal Transplanted Patients With Equations Based on Creatinine (With or Without Race Variable) and/or Cystatin C
Authors: Delanaye Pierre , Masson Ingrid , Maillard Nicolas , Pottel Hans , Mariat Christophe
Published: May 2022

BACKGROUND AND AIMS

Current Glomerular filtration rate (GFR) estimating equations based on serum creatinine are facing increased criticism due to the inclusion of a race correction in black Americans with the CKD-EPI equation (CKD-EPIASR, A = Age, S = Sex, R = Race). New equations without race (CKD-EPIAS) has been proposed with creatinine and/or cystatin C. These equations were developed mainly from US cohorts with few renal transplanted patients. In the current analysis, we compared these new equations, notably with the new European Kidney Function Consortium (EKFC) equation.

METHOD

In this retrospective analysis, 489 transplanted patients from the University Hospital of Saint-Etienne were included. All subjects were white. GFR was measured with inulin or iohexol clearances. IDMS creatinine and standardized cystatin C results were available. Median bias (eGFR—mGFR), imprecision (interquartile range: IQR), and P30 accuracy (percentage of eGFR-values within ± 30% of mGFR) were calculated.

RESULTS

Among creatinine-based equations, the bias were 2.3, 5.5 and 2.2 mL/min/1.73 m² for the CKD-EPIASR, CKD-EPIAS and EKFC, respectively. IQRs were 16.1, 16.2 and 15.3 mL/min/1.73 m², respectively. P30 were 74.2, 68.3 and 75.3%, respectively. Among cystatin C-based equations, the bias were −3.1 and 0.8 mL/min/1.73 m² for the CKD-EPICC and the EKFCCC, respectively. IQRs were 13.7 and 13.4 mL/min/1.73 m², respectively. P30 were 78.5 and 81.4%, respectively. Among equations combining creatinine and CC, the bias were −1.3, 0.5 and 1.6 mL/min/1.73 m² for the CKD-EPIASR-CC, CKD-EPIAS-CC and EKFCcreatCC, respectively. IQRs were 12.7, 12.4 and 12.1 mL/min/1.73 m², respectively. P30 were 84.5, 82.6 and 80.6%, respectively.

CONCLUSION

In our cohort of European transplanted patients, both the EKFCcreat and CKD-EPIASR equations performed better than the new CKD_EPIAS. Compared with creatinine-based equations, the new EKFCCC equation and all combined equations performed better. Cystatin C-based equations have the advantage to be accurate without any race variable.
MO390: Prognosis of Kidney Damage Associated With Tobacco Consumption in Former Smokers
Authors: Tascón Javier , G. Casanova Alfredo , Vicente-Vicente Laura , Pescador Moisés , Prieto Marta , Isabel Morales Martín Ana
Published: May 2022

BACKGROUND AND AIMS

Tobacco is a risk factor for some cardiovascular and respiratory diseases, as well as for the development of some tumours. Furthermore, new research has shown evidence of the risk that smokers have of developing kidney disease [1]. On the other hand, biomarkers used in the clinical setting, such as plasma creatinine, are not useful to detect that injury. Considering this problem, the need to use biomarkers that provide a faster, more reliable and efficient diagnosis is clear. It is the case of biomarkers of subclinical kidney damage [2, 3]. In fact, studies from our laboratory have shown that smoking patients suffer subclinical kidney damage evidenced by the excretion of these novel urinary biomarkers [4]. The aim of this study was to evaluate the prognosis of kidney damage associated with tobacco in former smokers using these biomarkers. That is, to study the role that smoking cessation plays in the evolution of kidney injury.

METHOD

A clinical study was designed where three groups of patients, without previous kidney damage and risk factors for kidney disease, were included: i) non-smokers (control group), ii) smokers and iii) former smokers (according to the World Health Organization, a person who has not used tobacco in the last 6–12 months). They were recruited from a Salamanca Health Centre (Spain). Urine samples were collected and the biomarkers of subclinical kidney damage N-acetyl-β-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injure molecule 1 (KIM-1) and total proteins, were quantified by ELISA and colorimetric techniques. The data obtained were analysed with the statistical software SPSS®.

RESULTS

The results showed a higher excretion of NAG, NGAL, KIM-1 and total proteins in smokers with respect to non-smoker ones. Rather, this excretion was significantly lower in the groups of former smokers and non-smokers.

CONCLUSION

Our research suggests that subclinical kidney damage associated with tobacco consumption would improve its prognosis when patients quit smoking, being able to recover kidney function to similar levels to non-smokers. This finding supports that smoking cessation carries an important benefit for the health of smoking patients.
MO392: Mildly Impaired Kidney Function May Be Associated With the Risk of Hippocampal Atrophy in Young and Midlife Adults
Authors: Gadalean Florica , Virdol Malina , Schiller Adalbert , Bob Flaviu , Anca Gluhovschi Cristina , Oana Milas Livia , Suteanu - Simulescu Anca , Patruica Mihaela , Chisavu Lazar , Dana Grosu Iulia , Iova Iasmina , Florina Parv , Petrica Ligia
Published: May 2022

BACKGROUND AND AIMS

To date, associations between kidney function and brain structural abnormalities have been described in several studies [1]. Reports of renal function in relation to hippocampal atrophy have been scarce and the majority of studies have been focussed on older end-stage renal disease populations [2]. Particularly, with the ageing process, the hippocampus has a greater propensity to atrophy than other cerebral structures.The purpose of this study was to evaluate the relationship between kidney function assessed by estimated glomerular filtration rate (eGFR) and the degrees of hippocampal atrophy among young and midlife adults.

METHOD

In this cross-sectional study, the risk factors for hippocampal atrophy were evaluated in a cohort of 219 non-diabetic chronic kidney disease (CKD) patients, age ≤ 55 years, who had undergone magnetic resonance imaging (MRI) of the brain. The eGFR was calculated using the CKD-EPI formula. Hippocampal volume (HV) was assessed in brain MRIs with the Scheltens’ Medial Temporal Atrophy score, including a 5-stage escalation—0: no atrophy, 1: only widening of choroid fissure, 2: also widening of the temporal horn of lateral ventricle, 3: moderate loss of HV (decrease in height) and 4: severe loss of HV [3].

RESULTS

In our group, the median and interquartile ranges (IQR) of age was 45 (14) years, 57.53% (126 patients) being males. The median eGFR was 100.6 (34.7) mL/min/1.73m2 and 46.75% (102 patients) presented with mild reduction in eGFR (eGFR between 60 to 89 mL/min/1.73m2). In univariable regression analysis, eGFR (R2 = 0.207, P < 0.001), arterial hypertension (R2 = 0.018, P = 0.045), dyslipidaemia (R2 = 0.044, P = 0.002), haematocrit (R2 = 0.021, P = 0.032), natrium levels (R2 = 0.018, P = 0.047), and potassium levels ( R2 = 0.019, P = 0.042) were associated with smaller HV. In multivariable regression analysis, eGFR [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.94–0.97; P < 0.001) and serum natrium (OR, 0.91; 95% CI, 0.83–0.98; P = 0.027) were significantly associated with hippocampal atrophy.

CONCLUSION

This cross-sectional study shows that mild decrease in eGFR is independently associated with hippocampal atrophy. Our results suggest that brain imaging tests should be routinely performed in patients with mild reduction of eGFR, as the hippocampal atrophy process appears to be due, in part, to the mild renal dysfunction itself.
MO396: Development, Establishment and Validation of in Vitro and EX Vivo Assays of Vascular Calcification
Authors: Orth-Alampour Setareh , Holmar Jana , Jankowski Joachim
Published: May 2022

BACKGROUND AND AIMS

Vascular calcification is one major complication in patients with chronic kidney disease (CKD), with a misbalance in calcium and phosphate metabolism playing a crucial role. The mechanisms underlying vascular calcification have not been entirely revealed to date. As studies aiming at the identification and characterization of the involved mediators are highly relevant, standardized operating protocols (SOP) for reliable assays to make different studies comparable, are needed.

METHOD

We are dealing with the following in vitro and ex vivo experimental conditions to study vascular calcifications: induction of calcification by phosphate and CaCl2, incubation time, as well as foetal calve serum concentration and ageing. Furthermore, the location and inhibition of vascular calcifications are studied. Human aortic smooth muscle cells are used for in vitro experiments and rat aorta for ex vivo experiments. The degree of calcification is estimated by quantification of calcium concentrations and by von Kossa staining.

RESULTS

As a result, a step-by-step protocol for performing experiments on vascular calcification was created.

CONCLUSION

Through the established protocol and examination of decent modifications nuances, we aim to promote standardized research on vascular calcification.
MO401: Low Glomerular Density, a Risk Factor for Progression of Extra-Membranous Nephropathy
Authors: Ajimi Khawla , Ben Salem Meriem , Hammouda Mouna , Ben Salah Manel , Ben Mahmoud Nouha , Jafar Ines , Letaief Ahmed , Sabra Aloui , Skhiri Habib
Published: May 2022

BACKGROUND AND AIMS

Before the onset of renal failure in idiopathic membranous nephropathy (MN), the role of certain histological factors in the progressive loss of renal function are still poorly understood. The present study examined the relationship between glomerular density (GD: non-sclera glomerular number/renal cortical biopsy area) and renal prognosis in patients with idiopathic MN, particularly in those without apparent renal dysfunction at diagnosis.

METHOD

The predictive value of GD on renal outcome was analyzed retrospectively in 40 patients with idiopathic MN with estimated glomerular filtration rate (eGFR) ˃60 mL/min/1.73 m2 (mean, 80 mL/min/1.73 m2) at the time of the biopsy.

RESULTS

Individual GD values ​​ranged from 1.3 to 5.5/mm2 with a 3-fold variation. Lower GD was associated with progression based on ≥ 50% reduction in GFR or onset of end-stage renal disease (ESRD). An association between decreased GD and progression of renal failure was observed, particularly in patients with persistent proteinuria ≥ 1 g/day at follow-up. In contrast, no patient who achieved proteinuria < 1 g/day at follow-up showed progression regardless of their GD level. In addition, among the various clinicopathologic factors studied, we found that GD was the only histologic factor that independently predicted the deterioration of renal function during the observation periods.

CONCLUSION

These results suggest that low GD is a plausible risk factor for progression to ESRD in patients with idiopathic MN, particularly in those who did not achieve remission during the follow-up.
MO402: Symmetric Dimethylarginine Inhibits Renal Fibrosis in Obstructive Kidneys
Authors: Wang Yanzhe , Wu Ming , Ye Chaoyang
Published: May 2022

BACKGROUND AND AIMS

Symmetric dimethylarginine (SDMA) is regarded as an independent cardiovascular risk factor in patients with chronic kidney diseases. Renal interstitial fibrosis is a common pathway of all kinds of chronic kidney diseases progressing to the end-stage of renal diseases. In this study, we investigated the role of SDMA in renal fibrosis and its underlining mechanisms.

METHOD

Normal saline (NS) and SDMA (2.50 µmol/kg) were administered to the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested on day 7. Western blotting and Masson's trichrome staining were performed to evaluate renal fibrosis. Moreover, human kidney 2 (HK2) cells were treated with various concentrations of SDMA (0.01 µM–10 µM) in the presence of 2.5 ng/mL TGF-β. Protein samples were collected from cells to measure the expression of fibrotic markers.

RESULTS

We observed that intrarenal administration of SDMA attenuated renal fibrosis as shown by Masson staining and Western blotting analysis of the expression of fibronectin, collagen-I and α smooth muscle actin (αSMA). In parallel, SDMA dose-dependently reduced the expression of pro-fibrotic proteins in TGF-β stimulated HK2 cells. Phosphorylation of Smad3 protein was analyzed in vivo and in vitro, which showed that SDMA inhibited phosphorylation of Smad3 in UUO kidneys and TGF-β stimulated HK2 cells.

CONCLUSION

Thus, our data suggest that renal SDMA exerts direct anti-fibrotic effects in fibrotic kidneys probably through inhibition of the Smad3 signalling pathway.
MO417: Obesity Associated With Vitamin D Deficiency Impairs Renal Function, Haemodynamics, Metabolic Parameters And Aggravates the Renal Morphological Damage in Rats Submitted To Ischaemia-Reperfusion Injury
Authors: Bernardo Desiree , Carolina de Braganca Ana , Heloisa Massola Shimizu Maria , Carlos Seguro Antonio , Moura Nascimento Mariana , Canale Daniele , Aparecido Volpini Rildo
Published: May 2022

BACKGROUND AND AIMS

Acute kidney injury (AKI) alters renal haemodynamics, leads to tubular injury, activates pathways of inflammation, proliferation and cell death. The initial damage caused by ischaemia/reperfusion injury (IRI) plays an important role in the pathogenesis of the AKI and predisposition to chronic kidney disease (CKD). Vitamin D deficiency has been considered a risk factor for kidney disease and is associated with haemodynamic changes and tubulointerstitial damage. Obesity is directly related to diabetes mellitus (DM) and hypertension, the main metabolic disorders responsible for the progression to end-stage kidney disease. In addition, studies have been showing that adipose tissue expansion can increase the secretion of pro-inflammatory cytokines and its possible influence on the course of CKD. Thus, we evaluated the influence of both obesity and vitamin D deficiency risk factors on renal disease progression in a murine model of renal IRI.

METHOD

We followed Male wistar rats during a 90-day protocol. On day 45, we submitted all rats to bilateral 45 min IRI surgery. We shared the animals into four groups: i) Standard (S)—fed a standard diet for 90 days; ii) Vitamin D Deficient (VDD)—fed a vitamin D-free diet for 90 days; iii) High-fat (H)—fed a high-fat diet for 90 days; and iv) High-fat vitamin D deficient (H + VDD)—fed a high-fat vitamin D-free diet for 90 days. We evaluated insulin clearance (Cin); mean arterial pressure (MAP); anthropometrical parameters such as body mass index (BMI) and abdominal circumference (AC); plasma levels of 25(OH)D, aldosterone, leptin, glucose, triglycerides and cholesterol as well as renal tissue levels of collagen type 3 (COL-3) and MCP-1 by ELISA. Moreover, we performed qPCR and immunoblotting for vitamin D receptor (VDR) in adipose and renal tissues, respectively. We also analysed α-actin expression by immunohistochemistry and evaluated the fractional interstitial area (FIA). All the results are described in Table 1.

RESULTS

H + VDD animals presented a lower glomerular filtration rate, higher MAP and increased anthropometrical and metabolic parameters compared to the other groups. In addition, we observed severe morphological damage, characterized by an increase in the fractional interstitial area and renal expression of α-actin, MCP-1 and COL-3.

CONCLUSION

Our study suggests that the association between vitamin D deficiency and obesity impairs the haemodynamics, renal function and metabolic parameters in the H + VDD rats. In addition, obesity-associated to vitamin D deficiency aggravated the renal inflammation and morphological alterations associated to renal disease progression.

FUNDING: CAPES and FAPESP (2019/20840–0, 2018/12297–1, 2018/04930–6).
MO430: Octogenarians Referred to the Nephrologist: Evolution and Progression Risk Factors
Authors: Frías González Aida , Vargas Francisco , Berzal Rico Raquel , Rivero Martínez Marta , Cordero García-Galán Lucía , Hernández Paúl , González García Celia , Pascual Julio , Morales Enrique
Published: May 2022

BACKGROUND AND AIMS

The actual definition of chronic kidney disease (CKD) applied to patients ˃80 years has generated an increase in the number of referrals to Nephrology for consultation. Nowadays there is a debate about the evolution of kidney function in elderly patients, from physiological evolution of kidney function to identifying which factors are associated with a real progression of CKD.

The aim of this study is to analyse the evolution of kidney function in patients ˃80 years referred to Nephrology for consultation for the first time.

METHOD

A single-centre retrospective study in which we included patients ˃80 years with an estimated glomerular filtration rate (eGFR) <60 mL/min/1,73m2 who were referred to Nephrology consultation from 2015 to 2018.

We collected clinical and analytical parameters at the following points in time: 12 months before the visit, baseline and 12 months after the initial visit. We divided patients into two groups based on annual eGFR loss: Group 1 progressors (>5 mL/min/1.73m2) and group 2 non-progressors (≤5 mL/min/1.73m2).

RESULTS

A total of 348 patients were included in the study, 55.2% were women and the mean age was 84 years (80–97). At the time of first medical visit, the mean creatinine value was 1.6 ± 0.6 mg/dL, median eGRF was 38 mL/min/1.73m2 (29–44) and median albumin/creatinine ratio was 55 mg/g (6–419), with 12% of the patients, presenting albuminuria over 1000 mg/g. The most frequent referral criteria were worsening of renal function (85.6%). Comorbidities were very common, and hypertension, dyslipidaemia and diabetes mellitus were present in 89.4%, 42.8% and 42.2% respectively. A total of 51% of the patients met the definition of progressor at baseline (initial-progressors) and 29.4% were progressors after a 12-month follow-up. Interestingly, only 21.6% of initial-progressors kept meeting this definition 12 months after (Figure 1). The main risk factors for progression were a higher baseline eGFR (P < 0.001) and albuminuria (P < 0.002). No association with comorbidities was found in the multivariate analysis.

CONCLUSION

The majority of patients ˃80 years evaluated by a Nephrologist were non-progressors at 12 months according to our definition (70.6%). It is more important to estimate the progression of CKD patients and request albuminuria and/or proteinuria than an isolated GFR value. It is likely that non-progressors do not need to be followed by a Nephrologist and may remain under primary care control.
MO431: Estimation of the Risk of Progression and Renal Substitution Treatment in Patients With Chronic Kidney Disease Using an Artificial Intelligence Model
Authors: Isaza Ruget Mario A , Yomayusa Nancy , Gonzalez Camilo , Alvarado H Catherine , De Oro V Fabio A , Gonzalez-Velez Abel , Colmenares-Mejía Claudia C
Published: May 2022

BACKGROUND AND AIMS

The use of tools that allow to estimate the probability of progression of chronic kidney disease (CKD) to advanced stages, has not yet gained a notable space in our clinical practice. The aim of this study was to develop and validate a model to predict disease progression, and the need for renal replacement therapy, based on machine learning, for patients with CKD grades 3 to 5. This is the first model of its kind to be implemented in Colombia.

METHOD

This is an observational retrospective closed cohort study. We included patients with CKD from a primary care program and followed them for 5 years. Demographic, clinical and laboratory predictors were included. The outcomes were CKD stage progression, >25% reduction in baseline glomerular filtration rate (eGFR) and the need for renal replacement therapy (RRT), dialysis, or kidney transplantation. We designed two prediction models, one time-independent, based on logistic regression, neural networks and random forest; and a second model, a survival analysis (time to event), by Cox regression, random forest and gradient boosting. Finally, we conducted an internal validation with bootstrapping for the first model, and external validation for the second model in a second real cohort. As a result, we designed a risk calculator.

RESULTS

Time-independent model included 2619 patients, 62.7% female, 92.6% with hypertension, 23.5% diabetics, with a baseline eGFR 51.06 mL/min/1.73m2 (40–61.9). An estimated performance for predicting RRT risk of F1: 0.61 and Kappa: 0.60 (113 events) was detected; stage progression of F1: 0.4 and Kappa: 0.25; reduction in eGFR F1: 0.29 and Kappa: 0.21. For this first model, the most relevant predictors were: initial eGFR, hemoglobin, sex, central region, total cholesterol and socioeconomic status.

The second, a 5-year Time-to-Event prediction model, included data from 1803 patients, had good accuracy with a C-Index assessed performance for RRT risk of 0.96, grade progression of 0.71 and eGFR reduction of 0.69 respectively. The most relevant predictors were initial eGFR, mean heart rate, hemoglobin, hospitalizations, sex, hypertension, diabetes, total cholesterol and central region. The validation cohort, with 658 patients with CKD, 63.9% male, 39% diabetics, with a mean eGFR of 34.9 mL/min/1.73m2, showed good accuracy with a C-Index for RRT risk of 0.935, grade progression of 0.69 and eGFR reduction of 0.0.62 respectively.

CONCLUSION

Our study demonstrated the utility of novel tools to predict renal outcomes in a CKD population in Colombia. This is the first study conducted with our local population. The resulted risk calculator is intended to be part of the electronic medical history in our hospitals.
MO437: Decreased Urinary Citrate Levels as a Marker of Progressive Deterioration of Glomerular Filtration in Patients With Autosomic Dominant Polycystic Kidney Disease (ADPKD)
Authors: Borrego-Utiel Francisco-Jose , Merino Garcia Enoc , Herrera Isidoro , Camacho Reina Victoria , Luisa Garnica Alvarez Maria , Ocaña Perez Esther
Published: May 2022

BACKGROUND AND AIMS

In a previous work we have found that there is a reduction in urinary citrate levels in autosomic dominant polycystic kidney disease (ADPKD) patients. Their levels are related to GFR but not serum bicarbonate levels. Our aim was to analyse whether there is any relationship between rate of GFR deterioration and citraturia in ADPKD patients.

METHOD

We collected routinary determinations of urine citrate in 24-h urine samples and analysed its predictive role for GFR deterioration with general linear modelling.

RESULTS

We included 94 patients, 42 ± 14 years old, 59.6% men and 40.4% women. Follow-up from citrate determination 55 ± 28 months (range 16–119).

Baseline data: urea 40.2 ± 12.3, Cr 1.15 ± 0.38 mg/dL, GFR 78 ± 26 mL/min/1.73 m2. Bicarbonate 25.1 ± 2.5 (18.2–29.2) mEq/L.

Final GFR: 69 ± 32 mL/min/1.73 m2. GFR variation: −2.23 ± 4.14 mL/min/year (range −13.7 to 10).

We classified patients according to urinary citrate tertiles (≤117, 117 to ≤ 303, >303 mg/gCr). GFR was different at baseline (67.5 ± 27.9, 74.3 ± 24.3, 92.4 ± 19.7, respectively, P < 0.001) and at final observation (51.1 ± 31.8; 71.4 ± 30.1; 85.3 ± 24.9, respectively P < 0.001). There were no differences in albuminuria or proteinuria at baseline, but there were differences in uric acid serum levels and urine output. There were no differences in follow-up time.

We observed that GFR rate was different according to tertiles: −4.62 ± 3.66, −0.58 ± 2.78 and −1.53 ​​± 4.74 mL/min/year, respectively (P < 0.001).

When comparing CKD by stages, we found that patients with citrate ≤ 117 mg/gCr showed higher GFR rates than when they had higher levels: CKD1 −7.74 ± 3.37, CKD2 −4.5 ± 4.4, CKD3 −3.04 ± 1.79 versus citrate patients > 117 mg/gCr with deterioration < 2 mL/min/year (P < 0.05).

With multivariate analysis, we found that final GFR was positively associated with baseline GFR and negatively with age, follow-up time and citrate levels ˂ 117 mg/gCr.

CONCLUSION

Urinary citrate levels decrease as GFR reduction is observed in ADPKD. The reduction of urinary citrate to values ≤ 117 mg/gCr is associated with faster deterioration of renal function in patients with ADPKD.
MO438: Excessive Mitochondrial Copper Load Driven by Upregulated Copper Transporter 1 Contributes to Mitochondrial Dysfunction and Renal Fibrosis
Authors: Zhu Saiya , Yu Chen
Published: May 2022

BACKGROUND AND AIMS

Copper is an essential trace element for eukaryotes and a vital cofactor for various enzymes for a multiplicity of functions. Our previous study indicated that intracellular copper overload plays an important role in renal fibrosis. However, the underlying mechanism invoked by copper overload in renal fibrosis remains largely unknown. In this study, we found copper ions in cells were mainly accumulated in mitochondria, which damage the structure and function of mitochondria. Furthermore, copper transporter 1 (CTR1), the major transporter for the copper influx, was significantly increased in fibrotic kidneys. The activity of cytochrome C oxidase (COX), a copper coenzyme mediating the final step in the electron transport chain, was decreased. Therefore, we proposed that CTR1 might be involved in mitochondrial copper overload and renal fibrosis.

METHOD

The expression of CTR1 was examined in ischemia-reperfusion injury (IRI 28d) mice model. The regulatory mechanisms of CTR1 in vitro were investigated by treating renal tubule epithelium cell line (NRK-52E) with TGF-β1 or copper ions with or without copper chelator tetrathiomolybdate (TM) and in vivo, we use CTR1 transgenic mice subjected to IRI operation.

ICP-MS, mitoSOX Red, electron microscopy, realtime-PCR and western blot analysis were applied in the current study.

RESULTS

We found that stimulated by TGF-β1, COX activity was declined. Mitochondria and cytosol, especially mitochondria, accumulated a large amount of copper in fibrotic kidney tissues. Furthermore, we found Copper transporter 1 (CTR1) expression was increased in fibrotic kidneys from chronic kidney disease patients, experimental fibrosis model mice and in vitro. More importantly, compared with WT mice, CTR1+/- mice subjected to an ischemia-reperfusion injury (IRI) had reduced mitochondrial copper level and ameliorated mitochondrial function and renal fibrosis, as evidenced by improving mitochondrial structure, inhibiting mtROS production and reducing expression of α-smooth muscle actin (α-SMA), collagen I and fibronectin. In addition, after treatment with the copper chelator tetrathiomolybdate (TM), mitochondrial function and kidney fibrosis were improved.

CONCLUSION

Collectively, our study showed that copper overload in mitochondria could damage the mitochondrial function and lead to renal fibrosis and CTR1 is involved in the mitochondrial copper overload. Copper overload inhibits the activity of COX and impairs mitochondria, subsequently leading to renal fibrosis.
MO445: Implications of Cardiac Biomarkers in Patients With Renal Insufficiency on Probability of Coronary Angiography and Subsequent Cardiovascular Outcomes
Authors: Illum Emilie , Baumbach Zille , Linnea Freese Ballegaard Ellen , Haagensen Kofod Dea , Nelveg-Kristensen Karl-Emil , Hornum Mads , Schou Morten , Torp Christian , Gislason Gunnar , Flensted Lassen Jens , Carlson Nicholas
Published: May 2022

BACKGROUND AND AIMS

Renal insufficiency is associated with an increased risk of cardiovascular morbidity and mortality. Although cardiac troponin remains essential marker for the diagnosis of myocardial injury in the general population, the diagnostic utility remains uncertain in patients with renal insufficiency. We examined the likelihood of coronary angiography and the risk of myocardial infarction after hospitalization with elevated troponin levels in patients with renal insufficiency.

METHOD

Based on data from multiple Danish nationwide healthcare registries, all hospitalized patients with elevated troponin I or T were identified between 2000 and 2021. Patients with age < 18 years, estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 and patients hospitalized with myocardial infarction < 30 days prior to the index were excluded. Renal function was calculated based on preceding plasma creatinine using the CKD-EPI equation. The probability of being referred for coronary angiography was computed across strata of renal insufficiency [eGFR (mL/min/1.73m2) 59–45, 44–30, 29–15 and < 15, respectively] based on multiple Cox regression calculating hazard ratios for 30-day likelihood of coronary angiography, with subsequent comparison of cumulative risk and hazard ratios for myocardial infarction using the Aalen-Johansen estimator and multiple Cox regression, respectively.

RESULTS

In total 57 044 patients were included in the study. Patients were predominantly male (53%, n = 30 222), with a median age of 81 years (IQR 74–87 years). eGFR strata (%): 59–45: 46.8%; 44–30: 30.6%; 29–15; 15.6%; <15: 7.%. Cardiovascular comorbidity was substantial; 47.1% of patients had a history of hypertension, 20.5%% of patients had a history of heart failure, 26.6% of patients had a history of diabetes and 25.3% of patients had a history of ischemic heart disease. Hazard ratios for 30-day likelihood of coronary angiography were 1.26 [95% confidence interval (CI) 1.10–1.44] for eGFR 15–29 mL/min/1.73m2, 2.00 (95% CI 1.77–2.25) for eGFR 30–44 mL/min/1.73m2 and 2.95 (95% CI 2.63–3.31) for eGFR 45–59 mL/min/1.73m2, using eGFR < 15 as reference. Subsequent cumulative risk of myocardial infarction is shown in Figure 1. Hazard ratios for risk of myocardial infarction were 0.86 (95% CI 0.71–1.03) for eGFR 15–29 mL/min/1.73m2, 0.58 (95% CI 0.49–0.69) for eGFR 30–44 mL/min/1.73m2 and 0.49 (95% CI 0.42–0.58) for eGFR 45–59 mL/min/1.73m2, using eGFR < 15 as reference.

CONCLUSION

In patients with elevated troponin levels, renal insufficiency is associated with an incrementally decreased probability of coronary angiography despite a graded proportional increase in the risk of subsequent myocardial infarction.
MO460: The Association of Beta-Hydroxybutyrate and Kidney Function Decline in the General Population—Results From the Prevend Study
Authors: Knol Martine , van der Vaart Amarens , Vart Priya , Kieneker Lyanne , Connelly Margery A , Garcia Erwin , Bakker Stephan J L , Gansevoort Ronald , Van Gastel Maatje
Published: May 2022

BACKGROUND AND AIMS

Beta-hydroxybutyrate (BHB), a ketone body, has shown to be renoprotective in various disease-specific preclinical studies. The underlying mechanism of this renoprotective effect might be via the reduction of inflammation, apoptosis, oxidative stress, and fibrosis. Interest in the effects of this metabolite is rising because supplementation is possible as an intervention. We hypothesized that endogenous BHB is associated with better kidney function outcomes in the general population. The aim of this study is to assess the association between BHB and kidney function.

METHOD

We included 6127 participants with available plasma BHB data from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women. BHB was measured in fasting participants using nuclear magnetic resonance (NMR) spectroscopy. The association of BHB with estimated glomerular filtration rate (eGFR), calculated with the CKD-EPI creatinine cystatin C equation, was tested using multivariable linear regression for cross-sectional analyses and linear mixed modeling for longitudinal analyses. The analyses were adjusted for sex, age, BMI, smoking, diabetes type 2, hypertension and hyperlipidemia.

RESULTS

Overall, 50.6% of the included subjects were female, mean age was 53.6 ± 12.1 years. At baseline, the median BHB concentration was 121.5 μmol/L [inter quartile range (IQR) 92.8–169.2] and the mean eGFR was 92 ± 17 mL/min/1.73m2. In cross-sectional analyses, a higher BHB was associated with a lower eGFR, after adjustment for covariates (st.β= −0.041, P < 0.001). During a median follow-up of 7.5 years (IQR 7.2–8.0), the mean annual change in eGFR was −0.96 ± 0.52 mL/min/1.73m2/year. In longitudinal analyses, a higher BHB was associated with less eGFR decline in the fully adjusted model [0.17 (95% confidence interval, CI 0.01–0.33); P = 0.04]. After exclusion of participants with diabetes type 2, the association of BHB and eGFR decline became stronger [0.22 (95% CI 0.06–0.38); P = 0.01].

CONCLUSION

Higher BHB levels were associated with less eGFR decline in this general population cohort. In combination with previous preclinical data, this data supports the hypothesis that BHB is renoprotective and forms a rationale to study whether supplementation with BHB attenuates kidney function decline in patients with chronic kidney disease.
MO471: Adverse Drug Reactions and Drug–Drug Interaction in Chronic Kidney Disease With Tuberculosis
Authors: Datta Divya , Attur Prabhu Ravindra , Abdul Khader Nisha , Prasad Nagaraju Shankar , Ramachandra Rao Indu , Vinayak Shenoy Srinivas , Rangaswamy Dharshan , Bhojaraja Mohan V , Thunga Girish , Magazine Rahul , Shetty Raghavendra
Published: May 2022

BACKGROUND AND AIMS

The risk of developing tuberculosis (TB) is 10–25% in chronic kidney disease (CKD) patients. TB in CKD patients may have a mortality of 16–37%. Standard treatment with four drugs (Isoniazid, Rifampin, Pyrazinamide and Ethambutol) predisposes to side effects, drug interactions and incomplete adherence in this population. We studied adverse drug reactions and potential drug–drug interactions in CKD patients with TB.

METHOD

Consecutive patients with CKD and TB attending tertiary care hospitals in South India were included over a period of 12 months. CKD was diagnosed based on estimated GFR using CKD EPI and TB using standard methodology. Data on demographic details and adverse drug reactions were collected from case records. Potential drug–drug interactions were checked using Micromedex Drug-Reax® (Truven Health Analytics, Greenwood Village, Colorado, USA). Statistical analysis was done using SPSS version 20.

RESULTS

Of 1300 TB patients, 59 had CKD. The demographic details are as per Table 1.

CONCLUSION

In CKD with TB, adverse drug reactions were seen in 45.5% and potential drug–drug interactions were seen mostly with rifampin (28.81% in CKD).