bluuebunny/crossref_metadata_2025 huggingface dataset:
MO374: Urinary Cell Transcriptomics Provides a Non-Invasive Readout of Kidney Genes Essential to Renal Health and Disease
Authors: Eales James , Bogdanski Pawel , Wystrychowski Wojciech , Zukowska-Szczechowska Ewa , Zywiec Joanna , Woolf Adrian S , Samani Nilesh J , Keavney Bernard , Charchar Fadi , Tomaszewski Maciej
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease affects up to 15% of adults, current diagnostic methods for assessing kidney health and early detection of renal disease lack sensitivity and/or can be highly invasive. The kidney sheds cells into the urine and harvesting these cells and their transcriptomic profile could yield non-invasive insights into genes responsible for maintenance of kidney health and early detection of kidney disease.

METHOD

Cell pellets were isolated from 200 mL of fresh morning urine from 33 participants, samples were spun at 3000 g for 10 min, washed and then resuspended in PBS. Each urinary cell pellet was then profiled by standard Illumina poly-A RNA-sequencing, generating an average of 30 million paired reads per sample. These were quantified using the standard GTEx quantification pipeline and were compared against 43 different human tissues and other bodily fluids.

RESULTS

Detailed RNA-sequencing metric analysis revealed that urinary cell pellets can generate reliable data of comparable or better quality than saliva and cerebrospinal fluid at similar read coverage. The one hundred most highly expressed urinary cell genes show an enrichment for immunity (P = 1.2 × 10–7), glucose metabolism (P = 1.3 × 10–5) and renal mineral absorption (P = 9.8 × 10–4); themes shared with the renal transcriptome. Across all protein-coding genes, kidney cortex (r2 = 0.65) and kidney medulla (r2 = 0.64) showed the highest level of correlation with the urinary transcriptome in an analysis of 43 human tissues. The correlation between urinary cells and the kidney was particularly strong (r2 = 0.72) in an analysis restricted to highly specific kidney genes (including UMOD, KCNJ1 and SLC12A1 all known for their role in kidney health and disease).

CONCLUSION

Poly-A RNA-sequencing of cells harvested from human urine can yield high quality gene expression profiles that correlate with transcriptional activity of the kidney. RNA-sequencing-based profiling of urinary cells offers a completely non-invasive route to assessing the expression of kidney genes of key relevance to renal health and disease.
MO379: Collagen-Derived Peptides in CKD: A Link to Fibrosis
Authors: Mavrogeorgis Emmmanouil , Mischak Harald , Latosinska Agnieszka , Vlahou Antonia , Schanstra Joost , Siwy Justyna , Jankowski Vera , Beige Joachim , Jankowski Joachim
Published: May 2022

BACKGROUND AND AIMS

Collagen is a major component of the extracellular matrix (ECM) and has an essential role in the onset and progression of fibrosis and chronic kidney disease (CKD). Collagen alpha-1(I) (col1a1) is the most abundant collagen type in humans and the involvement of col1a1in CKD onset and progression is well established. We aimed to assess in detail the association of urinary col1a1 fragments with the progression of CKD and ageing.

METHOD

About 5000 urinary peptidomic datasets from healthy participants and CKD patients were retrieved from the ‘Human Urinary Proteome Database’. Inclusion criteria were age >18 years and eGFR being available. Urinary col1a1 fragments were identified and their abundance and correlation with eGFR and age were investigated.

RESULTS

Of 707 specific col1a1 peptides, 63 were significantly and highly positively associated with eGFR, while only six peptides showed a significant and strong negative association. A similar tendency was observed for ageing, where the abundance of most of the 244 peptides significantly associated with age, decreased with increasing age. The ten most significantly correlated peptides associated with eGFR corrected for age or age in a cohort matched for eGFR are listed in the table.

CONCLUSION

The results show a strong association between the reduced abundance of urinary collagen peptides and loss of kidney function as well as ageing. The data suggest that the col1a1 peptides indicate reduced degradation of collagen in CKD and aging. The results further suggest that fibrosis, potentially also of other organs, may be the consequence of attenuation of collagen degradation, and not increased synthesis.
MO384: Identifying Long Non-Coding RNA Biomarkers From Urinary Exosomes for Diabetic Nephropathy
Authors: Zhu Xiaoxiao , Feng Songtao , Jing Jing , Zhong Xin , Shen Anran , Liu Bicheng , LV Linli
Published: May 2022

BACKGROUND AND AIMS

Diabetic nephropathy (DN) is the common cause of end-stage renal disease. However, the early and specific diagnostic biomarkers are still lacking. Urinary exosomes are a potential source of biomarkers for kidney disease due to their renal cell origination, stability, and noninvasive collection. Long non-coding RNAs (lncRNAs) are increasingly recognized to be involved in diverse pathophysiological processes including kidney disease. Here we set to characterize the lncRNAs profiles in urinary exosomes of DN with aims to identify novel non-invasive biomarkers of DN.

METHOD

First-morning urine was collected from 11 healthy people, 9 patients with diabetes mellitus (DM), and 8 patients with biopsy-proven DN. Urinary exosomes were pelleted by ultracentrifugation and total RNA was extracted for next generation sequencing (NGS). The lncRNA profile of urinary exosomes was first characterized in terms of the detectable RNA numbers, expression levels in different groups. Then differential gene expression analysis was performed to facilitate the discovery of potential biomarkers.

RESULTS

Similar tremendous number of lncRNAs was detected with a total number of 6439 transcripts present in urinary exosomes in each group. In terms of the expression levels, the percentage of transcripts with TPM above 1 was 31.4%, 32.8%, 33.2% in the healthy group, DM and DN patients respectively, suggesting that no significant alteration of lncRNAs numbers and distribution in DN and diabetes conditions. Next, the differential expression analysis was performed to identify the distinct differential lncRNAs. Compared with healthy people, 18 lncRNAs were upregulated and 67 lncRNAs were downregulated in DM group, while 37 unregulated and 80 downregulated lncRNAs were identified in DN group. Moreover, the profile of lncRNAs in urinary exosomes was significantly different in DN patients compared to DM group with 59 lncRNAs upregulated and 36 lncRNAs downregulated. To explore the candidate biomarkers, 12 upregulated lncRNAs and 4 downregulated lncRNAs from the two comparison sets (DN versus Healthy, DN versus Healthy) were identified, among which FLJ16779 was present with the most remarkable difference. Further analysis showed that the sensitivity and specificity of FLJ16779 for distinguishing DN from healthy people are both 87.5%, and the area under the curve (AUC) was 0.9531. Additionally, the sensitivity and specificity of FLJ16779 for distinguishing DN from DM were 75% and 87.5% respectively, and AUC was 0.9063.

CONCLUSION

Urinary exosomes contain rich lncRNAs information with differential expression profiles in DN patients compared to DM and healthy controls, suggesting the possible involvement of lncRNAs in the pathogenesis of DN. lncRNA FLJ16779 might be a promising non-invasive biomarker of DN which requires further validation.
MO389: Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney
Authors: Takenaka Tsuneo
Published: May 2022

BACKGROUND AND AIMS

Several studies demonstrate that klotho shows renoprotective actions. However, it has not been assessed whether klotho supplementation is able to reverse the renal injury.

METHOD

In the present study, the effects of klotho protein supplementation on remnant rat kidneys were assessed using three groups: renal ablation for 4 weeks, renal ablation for 12 weeks and klotho supplementation (20 μg/kg/day).

RESULTS

Klotho supplementation suppressed blood pressure, albuminuria, renal renin-angiotensin system (RAS), serum phosphate and fibroblast growth factor (FGF) 23 levels, fibrosis index, renal expression of transforming growth factor β and collagen I. Klotho protein supplementation increased glomerular filtration rate (GFR), fractional excretion of phosphate, renal expression of klotho, bone morphogenetic protein (BMP) 7 and superoxide dismutase.

CONCLUSION

Our data indicated that klotho supplementation reduced blood pressure and albuminuria with inactivation of renal RAS in the remnant kidney. In addition, exogenous klotho protein supplementation increased endogenous klotho expression, facilitating phosphate excretion with reductions in serum phosphate and FGF23. Finally, klotho protein supplementation upregulated BMP7, at least partly contributing to an increase in GFR and reversal of fibrosis in the remnant kidney.
MO412: Impact of Body Mass Index on Mortality and End–Stage Kidney Disease in Patients With Non-Dialysis Dependent Chronic Kidney Disease
Authors: Al-Chalabi Saif , Nawaz Saira , Lodge Michelle , Sinha Smeeta , A. Kalra Philip , Chinnadurai Rajkumar
Published: May 2022

BACKGROUND AND AIMS

Obesity is a major global problem affecting more than 1.9 billion adults [1]. The aetiological factors of obesity are complex and consist of genetic, social and environmental elements. Obesity can lead to chronic kidney disease (CKD) via both direct and indirect pathways. However, the effect of obesity on the progression of CKD remains unclear. This study aimed to investigate the impact of higher body mass index (BMI) on clinical outcomes in a large UK cohort of patients with non-dialysis dependent (NDD)-CKD.

METHOD

The Salford Kidney Study is a longitudinal prospective cohort of more than 3000 patients with NDD-CKD. All patients with available BMI at baseline from October 2002 to December 2016 were included in this study. Patients were grouped according to their BMI into underweight [(BMI < 18.5 kg/m2), n = 35], healthy weight [(BMI 18.5–24.9 kg/m2), n = 628], overweight [(BMI 25–29.9 kg/m2), n = 860] and obese [(BMI > 30 kg/m2), n = 897]. Cox-regression analysis was performed to study the strength of association between BMI groups and major clinical outcomes [all-cause mortality, end-stage kidney disease (ESKD) and annual rate of progression of CKD (delta eGFR)] by using the healthy weight BMI group as a reference. The outcomes were also analysed in a 1:1 propensity score-matched analysis between patients in the healthy weight and obese groups (414 in each).

RESULTS

A total of 2420 patients with a median follow-up of 44.3 months were available for analysis. The median age of the cohort was 67 years and 58% were male. The prevalence of hypertension and diabetes increased with a higher BMI (84.0% and 18.8% in healthy weight, 91.7% and 31.0% in overweight and 94.2% and 46.8% in the obese groups, respectively). There was no significant difference in the baseline eGFR between the groups with a median of 29.3 mL/min/1.73 m2. There was an inverse association between a higher BMI and all-cause mortality [obese versus healthy weight: hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.81–0.96; P = 0.004] but there was no association observed with ESKD (HR 0.96; 95% CI: 0.87–1.06; P = 0.422). The delta eGFR was not significantly different between the different BMI groups (Table 1). A similar observation with all-cause mortality being better in the obese group was noted in the propensity-matched analysis (HR:0.88; CI:0.81–0.96; P = 0.004) (Table 2).

CONCLUSION

In our large cohort of patients, a higher BMI was seen to be protective against all-cause mortality. Furthermore, the annual rate of decline in eGFR was similar among the BMI groups. Patients with normal BMI had significantly higher all-cause mortality compared with the obese group.
MO413: Registration of Image Modalities for Analyses of Tissue Samples Using 3D Image Modelling
Authors: Hermann Juliane , Jankowski Vera , Jankowski Joachim
Published: May 2022

BACKGROUND AND AIMS

Biopsies are a diagnostic tool for the diagnosis of histopathological, molecular biological, proteomic and imaging data, to narrow down disease patterns or identify diseases. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) provides an emerging state-of-the-art technique for molecular imaging of biological tissue. The aim of this study is the registration of MALDI MSI data sets and data acquired from different histological stainings to create a 3D model of biopsies and whole organs.

METHOD

The registration of the image modalities is achieved by using a variant of our global, deformable Schatten-q-Norm registration approach. Utilizing a connected-component segmentation for background removal followed by a principal-axis-based linear pre-registration, the images are adjusted into a homogeneous alignment. This registration approach is accompanied by the 3D reconstruction of histological and MALDI MSI data.

RESULTS

With this, a system of automatic registration for cross-process evaluation, as well as for creating 3D models, is developed and established. The registration of MALDI MSI data with different histological image data is evaluated by using the established global image registration system.

CONCLUSION

In conclusion, this multimodal image approach offers the possibility of molecular analyses of tissue specimens in clinical research and diagnosis.
MO424: Relationship Between Itch Intensity and Patient-Reported Disease Improvement in Patients With Chronic Kidney Disease-Associated Pruritus Treated With Difelikefalin
Authors: Mccafferty Kieran , Walpen Sebastian , Schaufler Thilo , Morin Isabelle , Menzaghi Frederique , Wen Warren , Fishbane Steven
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients with CKD undergoing haemodialysis (HD), leading to poor sleep quality, reduced quality of life and depression. Difelikefalin is a selective kappa opioid receptor agonist approved in the United States for the treatment of moderate-to-severe pruritus in adults undergoing HD, which significantly reduced itch intensity in HD patients with CKD-aP in the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials. The KALM trials used the Worst-Itching Numerical Rating Scale (WI-NRS) to assess itch-intensity [range from 0 (no itching) to 10 (worst itching imaginable)] and the Patient Global Impression of Change (PGIC) to assess the patient's overall perception of change in itch (range from ‘very much improved’ to ‘very much worse’) relative to the start of the study. The aim of this post hoc analysis was to establish how the WI-NRS score relates to the PGIC and to assess a clinically relevant change in WI-NRS.

METHOD

A post hoc analysis of data from KALM-1 and KALM-2 was performed. Studies enrolled maintenance HD patients with mean baseline 24-h WI-NRS score > 4 in KALM-1 or ≥ 5 in KALM-2. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo three times/week for 12 weeks. Patients completed the PGIC at the end of the 12-week, double-blind treatment period, as well as completing the WI-NRS daily. Cumulative distribution function (CDF) analyses were performed at Week 12. Results are reported for 50% CDF at week 12.

RESULTS

For the overall population, ‘very much improved’ corresponded to a 5-to-6-point WI-NRS reduction; ‘much improved’ corresponded to a 3-to-4-point WI-NRS reduction; and ‘minimally improved’ corresponded to a 1-to-2-point WI-NRS reduction (Figure 1).

CONCLUSION

There is a clear relationship between the PGIC and the WI-NRS, with greater reductions in itch severity corresponding to perceptions of better overall improvement in itch following treatment with difelikefalin. A 3-point reduction in WI-NRS can be considered clinically relevant, since it was perceived by patients as equivalent to their itch being ‘much improved’. This analysis further corroborates similar clinically meaningful changes in pruritus, previously reported in patients with CKD-aP, as ≥ 3-points [1, 2].
MO443: Accumulation of REG-1Α in Proximal Tubules of a Rat Model of Chronic Kidney Disease: A New Biomarker at the Interface Between Renal Impairment and Neurodegenerative Diseases
Authors: Cortijo Irene , Muyor Karen , Laget Jonas , Jover Bernard , Reynaud Fabrice , Duranton Flore , Fontès Pascaline , Trousse Françoise , Marcilhac Anne , Mestre-Francés Nadine , Argiles Ciscart Angel , Gayrard Nathalie
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) increases the risk of developing cognitive dysfunction and it has been identified as a modifiable risk factor for Alzheimer's disease (AD) [1]. Regenerating family member 1 alpha (Reg-1α) protein, originally identified as a 16 kDa polypeptide in the pancreas, is increased in cerebrospinal fluid (CSF) and in neurons of AD patients [2, 3]. Reg-1α is also elevated in blood in inflammatory conditions and chronic illnesses such as diabetes and interestingly, in patients with renal function impairment [4, 5]. It is not known whether Reg-1α is synthesized in the kidney or the modifications observed in CKD are merely due to a decline in the glomerular filtration rate. The aim of our study was to localize and quantify the Reg-1α protein in the kidneys of normal rats or CKD rats (5/6 nephrectomized rats) and determine, in a second time, if serum Reg-1α level is a suitable marker for assessment of renal function. As Reg-1a is able to cross the altered blood-brain barrier, it might be a new interesting biomarker at the interface between renal impairment and neurodegenerative diseases.

METHOD

A total of 16 3-month-old rats were randomly allocated to 5/6 nephrectomy (Nx) or Sham operation. Three months after surgery, serum creatinine and urea, systolic blood pressure (SBP) were measured and renal fibrosis (Sirius Red) was quantified. The expression of Reg-1α was evaluated by double-immunofluorescence using anti-Reg-1α and anti-Aquaporin-1 (Aqp-1) (as a proximal tubule marker) antibodies to determine the localization of Reg-1α in the kidney.

RESULTS

5/6Nx rats showed increased serum creatinine levels (97.3 ± 17.6 versus Sham 26.3 ± 0.8 µmol/L; P < 0.05) and serum urea levels (23.9 ± 8.9 versus Sham 4.7 ± 0.1 mmol/L). They also had a higher SBP (158 ± 12 versus Sham 133 ± 5 mmHg) and renal fibrosis increased in the 5/6Nx group (8.1 ± 1.5 versus Sham 2.7 ± 0.2% staining). The double-immunofluorescence revealed an increased expression of Reg-1α of 5/6Nx rats compared with the Sham group. This expression seemed to be specific to the cytoplasm of the proximal tubules, with a ring-shaped distribution (preliminary results, Figure 1).

CONCLUSION

Our data show, for the first time, a proximal tubule-specific accumulation in Reg-1α in CKD suggesting an influence of impaired renal function on Reg-1α accumulation. Further assessment of Reg-1a in the blood, the blood-brain barrier and neuroinflammation status in this model is needed to better understand the potential effect of kidney accumulation of Reg-1α on brain dysfunction. Should this effect be confirmed, Reg-1α would be a new actor involved in the kidney-brain dialogue.
MO449: Polycystins are Upregulated in Fibrotic Kidneys and Promote Renal Fibrosis
Authors: Wang Yanzhe , Wu Ming , Ye Chaoyang
Published: May 2022

BACKGROUND AND AIMS

Mutations in PKD1 or PKD2 gene, which encodes polycystin-1 or polycystin-2, cause autosomal polycystic kidney disease (ADPKD). The development of ADPKD is associated with the progression of renal fibrosis. Whether renal fibrosis in ADPKD is a direct effect of PKD mutation or a consequence of cyst growth-induced tubular obstruction is currently unknown. Polycystin-2 has been identified as a direct target of triptolide and we used triptolide as a probe to study the role of polycystin-2 in renal fibrosis.

METHOD

Unilateral ureteral obstruction (UUO), unilateral ischemia-reperfusion injury (UIRI) and aristolochic acid nephropathy mouse models were established. Mice were treated with vehicle or triptolide. Western blotting and Masson's trichrome staining were performed to evaluate renal fibrosis. Moreover, human kidney 2 (HK2) cells and normal rat kidney 49F (NRK-49F) cells were used as in vitro models.

RESULTS

Here we showed that polycystin-2 is up-regulated in these three mouse models and tightly correlated with the expression of collagen-I in a time-dependent manner. Treatment with triptolide inhibited the expression of polycystin-2 and pro-fibrotic markers in UUO and UIRI models. Moreover, triptolide dose-dependently inhibited the expression of polycystin-2 and pro-fibrotic markers in rat renal fibroblasts or in TGF-β stimulated human renal epithelial (HK2) cells. Knockdown of PKD2 reduced the expression of pro-fibrotic markers in TGF-β stimulated or unstimulated HK2 cells. Moreover, we showed that knockdown of PKD2 attenuated the inhibitory effect of triptolide on the expression of pro-fibrotic markers in TGF-β stimulated HK2 cells. Finally, using Pkd2 conditional knockout mice, we showed that heterozygous or homozygous deletion of Pkd2 reduced the expression of pro-fibrotic markers in UUO kidneys. Polycystin-1 was also up-regulated in three renal fibrotic models and conditional deletion of Pkd1 reduced the expression of pro-fibrotic markers in UUO or folic acid-induced fibrotic kidneys. Furthermore, conditional knockout of the methyltransferase EZH2 attenuated the anti-fibrotic responses induced by PKD1 deletion in UUO kidneys.

CONCLUSION

Polycystins are pro-fibrotic proteins in injured kidneys suggesting that renal fibrosis in ADPKD kidneys is not a direct effect of PKD mutation.
MO485: Chronic Kidney Disease in Patients With Lung Transplant
Authors: Luisa Serrano Salazar Maria , Rubio Arboli Lucia , Sánchez-Sobrino Beatriz , De Valdenebro Recio Maria , López Paula , Aguilar Myriam , Teresa Lazaro Carrasco de la Fuente Maria , Portoles Jose' M
Published: May 2022

BACKGROUND AND AIMS

The incidence of chronic kidney disease (CKD) in patients with lung transplantation (LTx) has increased over the last decades.

Progression factors recognized in the development of CKD are: older age and comorbidity of recipients, immunosuppressive (IS) toxicity and longer survival. There is a lack of specific information about other risk factors or specific preventive management of CKD.

METHOD

Retrospective, single-centre study including all patients with LTx on Nephrology outpatient clinic among 2007 and 2020. Demographic, comorbidity and intercurrent events, renal function impairment, proteinuria and IS treatment were analyzed. We defined composite renal event (MARE) as renal replacement therapy (RRT), death or doubling serum creatinine.

RESULTS

A total of 69 LTx receptors (79.4% double LTx) were followed in a dedicated outpatient nephrology clinic. A total of 52.2% male, mean age at LTx 48.3 years (SD 16.6).

Etiology of lung disease: cystic fibrosis (30.4%), obstructive lung disease or emphysema (33.3%) and interstitial disease (30.4%). After LTx, as complications, infection was the most frequent event (89.7%) and 49.3% presented neoplasic illness.

The mean time from LTx until first nephrologist evaluation was 6.6 years (2 months–19.9 years) and main comorbidities were: hypertension (81.2%), diabetes mellitus (52.2%), dyslipidemia (50.7%), 60.3% former smokers and 26.1% had suffer from a previous CV event.

After 1 year of LTx, mean eGFR decreased to 49.8 mL/min, which means that only in the first year after LTx there is a loss of ∼50% of mean kidney function. Factor associated with impaired kidney function at the first year after LTxw was cystic fibrosis (higher percentage in the rapid progression group).

At first evaluation by Nephrology, the mean eGFR was 30.9 mL/min (SD 15.3), with a CKD distribution: 39.4% CKD 3; 45.5% CKD 4 and 12.1% CKD 5 (<15).

Clinical study and biopsy define CKD etiologies: CNI toxicity (68.1%) thrombotic microangiopathy (11.6%), tubular (10.1%), vascular (7.3%) and glomerulopathies (2.9%).

A total of 88.4% patients reached MARE at the end of the study. A total of 24 patients required RRT (mean time since LTx 9.2 years) and thereafter, 10 received a kidney transplantation (KTx).

In Dyalisis group, a higher mortality was observed versus no dialysis group (24 versus 2.2%), a higher percentage of vascular origin disease with a further deterioration of eGFR at the time of referral to Nephrology.

At the end of follow-up, 15 patients died (14 were in RRT), 5 continued on HD and 5 with a functional KTx, and 44 patients were still without RRT.

CONCLUSION
MO487: Rates of Hyperkal a EMIA and Management Patterns in a Tertiary Outpatient Renal Clinic
Authors: Rosati Erica , D'ambrosio Viola , Baccaro Rocco , Bargagli Matteo , Manuel Ferraro Pietro
Published: May 2022

BACKGROUND AND AIMS

The optimal ambulatory management of hyperkalaemia (HK) in patients with chronic kidney disease (CKD) is still an important unmet challenge. Common strategies include dose reduction or discontinuation of nephroprotective medications (e.g. renin-angiotensin-aldosterone system inhibitors [RAASi]), dietary restriction of potassium (K), loop diuretics, bicarbonate and sodium polystyrene sulfonate; all the above interventions are characterized by specific pitfalls and limitations. However, new potassium binders are available that might improve the management of chronic hyperkalaemia. In the light of their widespread use, it will be important to increase our knowledge of the incidence, characteristics and current real-life management patterns of hyperkalaemia in CKD patients.

METHOD

We performed a retrospective analysis of patients followed at our tertiary outpatient renal clinic from 1 April 2016 to 31 December 2021. HK was defined as serum K > 5.0 mmol/L and stratified according to severity. eGFR was estimated with the CKD-EPI equation and stratified according to the KDIGO criteria. The time span between each episode of HK was assessed with Poisson regression models. A sample of 100 HK events was selected at random for manual chart review of the management strategies performed: Information was abstracted using a standardized form.

RESULTS

The final analysis included 1844 patients, contributing 4480 occasions. Baseline characteristics by hyperkalaemia status are reported in Table 1. Patients with HK were older, with lower eGFR and a higher prevalence of diabetes.

At least one episode of HK was documented in 525 patients (28.5%) and among them, 166 patients (31.6%) had at least two HK episodes (on average, 1.55 episodes/patient). HK events were more frequent among patients with more advanced stages of CKD. The time span between episodes decreased significantly (Fig. 1): on average, each episode was 17% [95% confidence interval (95% CI), 3%–29%) closer to the subsequent (P = .016). Of the 100 HK episodes randomly reviewed, 79% received no intervention, whereas 21% triggered at least one intervention. The probability of intervention increased with increasing severity of HK: 8.6%, 35.9%, 50.0% and 100% for K-values 5.0–5.4, 5.5–5.9, 6.0–6.4 and ≥6.5 mmol/L, respectively. Most interventions included dose reduction or discontinuation of RAASi. One patient was sent to the emergency department for urgent examination and treatment (K 7.0 mmol/L).

CONCLUSION

Hyperkalaemia is a common and recurring problem for patients with renal impairment: It occurs in almost one-third of the overall population of this study, and many hyperkalaemic patients experience recurring events. As expected, the prevalence rates of hyperkalaemia increase with worsening CKD severity. Furthermore, the decreased time span between consecutive episodes highlights an accelerated recurrence pattern of hyperkalaemia despite interventions.
MO488: Serum P-CRESYL Sulfate Level is an Independent Marker of Peripheral Arterial Stiffness as Assessed Using Brachial-Ankle Pulse Wave Velocity in Patients With Non-Dialysis Chronic Kidney Disease Stage 3–5
Authors: Chang Yu-Chi , Tang Chi-Chong , Hsu Bang-Gee
Published: May 2022

BACKGROUND AND AIMS

p-cresyl sulfate (PCS) is associated with inflammation and its contribution to cardiovascular damage in patients with chronic kidney disease (CKD). The brachial-ankle pulse wave velocity (baPWV) is a simple marker to assess the peripheral artery stiffness (PAS) and is a useful marker to predict future cardiovascular events. The aim of this study was to determine the relationship between serum PCS levels and PAS measured by baPWV values in patients with CKD stage 3–5.

METHOD

Fasting blood samples and baseline characteristics were obtained from 160 CKD stage 3–5 patients. Automatic pulse wave analyzer (VaSera VS-1000) to measure baPWV values, and both sides of baPWV value that was >18.0 m/s were determined as PAS. Serum total PCS levels were determined by high-performance liquid chromatography–mass spectrometry.

RESULTS

In the study cohort, 54 patients (33.8%) were in the PAS group. When compared with those in the control group, the PAS group had a high prevalence of hypertension (P = .021), older age (P < .001), lower height (P = .033) and body weight (P = .012), higher systolic blood pressure (P < .001), diastolic blood pressure (P = .008), serum calcium–phosphorus product levels (P = .030) and PCS levels (P = .008). The multivariable logistic regression analysis revealed that serum levels of PCS {odds ratio (OR): 1.098, [95% confidence interval (95% CI): 1.029–1.171]; P = .005}, advanced age (OR: 1.105, 95% CI: 1.055–1.159; P < .001) and diastolic blood pressure (OR: 1.058, 95% CI: 1.002–1.118; P = .043) were independently associated with PAS in patients with CKD stage 3–5.

CONCLUSION

Higher serum PCS levels, diastolic blood pressure and advanced age were associated with PAS in patients with CKD stage 3–5.
MO491: Low Income is Associated With Late Nephrology Referral in Portugal: A Retrospective Study
Authors: Duarte Rui , Trigo Ana , Luz Ivan , Santos Paulo , Lopes Karina , Gonçalves Hernâni , Sofia Flora , Vila Lobos Ana
Published: May 2022

BACKGROUND AND AIMS

Social disparities in chronic kidney disease (CKD) are a reality. Low socioeconomic status is associated with an increased incidence of CKD and overall worse outcomes. In Portugal, similarly to many European countries, a National Health System (NHS) was established to provide equity in healthcare access, but its impact in specialized CKD care is unclear. This study aims to compare the effects of economic insufficiency in referral and overall specialized kidney care in a Portuguese centre.

METHOD

Retrospective cohort study evaluating maintenance haemodialysis patients of a Public Portuguese Nephrology Centre from 2017 through 2021. Medical records were compared for the presence of Low-Income status (LIs), with primary outcome as baseline estimated glomerular filtration rate (eGFR) at nephrology referral and secondary outcomes as presence of kidney replacement therapy options appointment (KRTOa), timely vascular access assessment and time to dialysis from referral.

RESULTS

A total of 212 participants were evaluated, 96 with LIs. This group presented higher sCr and lower eGFR at referral (2.35 versus 3.29 mg/dL, P < .001; 27.63 versus 18.47 mL/min/1.73 m2 P <.001, respectively). LIs associated with absence of KRTOa {OR: 2.7, [95% confidence interval (95% CI): 1.44–5.08]; P = .003} and late vascular access evaluation (OR: 2.77, 95% CI: 1.55–4.98; P = .001). Dialysis-free survival analysis revealed shorter time to dialysis in the LIs group (15.77 versus 20.71 months; P < .001) with a higher cumulative incidence in dialysis at 24 months (HR: 2.11, 95% CI: 1.39–3.21; P < .001), a difference that was not verified after adjusting for eGFR at referral (HR: 1.16, 95% CI: 0.74–1.80; P = .53).

CONCLUSION

Low-Income CKD Portuguese patients are at risk of late nephrology referral, an established factor for adverse outcomes. Shorter time to dialysis appears significative in reducing adequate kidney care access, which can be attenuated through education of primary care providers and general population for CKD.
MO501: A Nomogram Based on Heart Rate Variability Parameters for Predicting All-Cause Mortality in Stage 5 CKD Patients
Authors: Gao Xueyan , Wang Jing , Huang Hui , Gao Zhanhui , Wang Ningning
Published: May 2022

BACKGROUND AND AIMS

Heart rate variability (HRV), reflecting the circadian rhythm of heart rate, is associated with clinical outcomes in stage 5 chronic kidney disease 5 (CKD5) patients. Whether CKD-related factors combined with HRV can improve the predictive ability for their death remains uncertain. Here we evaluated the prognosis value of nomogram models based on HRV for all-cause mortality in CKD5 patients.

METHOD

Multicenter CKD5 patients were enrolled from 2011 to 2019 in China. The multivariate Cox regression analysis screened HRV parameters, which associated with all-cause mortality. Their relationships were displayed by restricted cubic spline graphs. The predictive abilities of nomogram models were evaluated for survival rate.

RESULTS

CKD5 patients included survival group (n = 155) and the all-cause mortality group (n = 45), with a median follow-up time of 48 months. Logarithm of standard deviation of all sinus R–R intervals (lnSDNN) {HR: 0.35, [95% confidence interval (95% CI): 0.17–0.73]; P = .01} and logarithm of standard deviation of average NN intervals for each 5 min (lnSDANN) (HR: 0.36, 95% CI: 0.17–0.77; P = .01) were associated with all-cause mortality, their relationships were negative linear. The area under the curve (AUC) values based on lnSDNN nomogram model for predicting 3-year and 5-year survival rates were 79.44% and 81.27%, respectively. The AUC values based on lnSDANN nomogram model for predicting 3-year and 5-year survival rates were 78.73% and 80.61%, respectively.

CONCLUSION

As clinical indicators of heart rate circadian rhythm, SDNN and SDANN are highly correlated with the prognosis of CKD5 patients. Nomogram models that integrate HRV and multiple CKD-related risk factors are promising for evaluating their all-cause mortality.
MO510: CKD Progression in a Cohort of Older Community-Dwelling Adults– Results From the Berlin Initiative Study (BIS)
Authors: Bothe Tim , Schaeffner Elke , Mielke Nina , Barghouth Muhammad , K. Kuhlmann Martin , Martus Peter , Schneider Alice , Van der Giet Markus , Ebert Natalie
Published: May 2022

BACKGROUND AND AIMS

Data on the estimated glomerular filtration rate (eGFR) over time in older populations are scarce. Identifying patterns of eGFR progression is essential for a better understanding of chronic kidney disease (CKD) in older adults.

METHOD

We used data from the BIS, a community-dwelling cohort of 2069 people aged 70 or older. Participants were recruited between 2009 and 2011. After baseline assessment, four follow-up visits were conducted biennially over a total observation period of 8 years. During all study visits, eGFR and CKD stages based on KIDGO guidelines were assessed using the creatinine and cystatin C-based BIS2 equation (eGFRBIS2). Additionally, we used the creatinine-based EKFC equation (eGFREKFC). In a sub-analysis, we included only non-deceased participants with complete attendance at all study visits and valid eGFR values at all measurements.

RESULTS

At baseline, the mean age was 80.4 years (SD = 6.7), and 52.6 % were females. Prevalence was highest for CKD stage 2 (45.4%) and 3 (49.3%). After 8 years, the prevalence for CKD stages 1 and 2 decreased, whereas stages 3 and 4 showed a consistent upward trend resulting in 18.4%,  72.4% and 8.9% of participants in stages 2, 3 and 4, respectively. Mean eGFRBIS2 decreased from 58.1 (SD = 15.2) to 48.3 (SD = 13.3) mL/min/1.73 m² after 8 years. Mean eGFREKFC showed a similar trend with estimates being slightly higher (60.4 versus 54.2 mL/min/1.73 m2 after 8 years).

Same trends applied to the subgroup with complete attendance (mean age: 77.4 years). However, compared with the total population they showed a higher mean eGFRBIS2 (63.3 versus 58.1 mL/min/1.73 m²) and lower prevalence of CKD stages 3 and 4 (stage 2: 59.4 versus 45.4%; stage 3: 37.1 versus 49.3% stage 4: 1.2 versus 3.6%) at baseline.

CONCLUSION

We found that over the observation period of 8 years, mean eGFRBIS2 decreased by 9.8 mL/min/1.73 m2 resulting in an increasing prevalence of CKD stages 3 and 4 by 23.1 and 5.3%, respectively. This was observed in the total population as well as in the subgroup with complete study attendance.
MO537: Effects of COVID-19 on Mineral and Bone Disease Outcomes in Hemodialysis Patients: A Retrospective Study From Qatar
Authors: Hamad Abdullah , Fouda Tarek , Alkadi Mohamad , Abdellatif Tarek , Al Omari Anees , Alakhras Alaa , Amood Abeer , Ibrahim Rania , Aly Sahar , Farooqi Farrukh , Almalki Hassan
Published: May 2022

BACKGROUND AND AIMS

Management of end-stage renal disease (ESRD) on dialysis has been challenging during the COVID19 epidemic. Staff illness led to a shortage of manpower that affected patient care. We established a specialty nursing management for mineral and bone disease (MBD) in the ambulatory dialysis service in Qatar in 2016. We are presenting a retrospective study about the effects of the COVID-19 epidemic on MBD outcomes in ambulatory dialysis patients in the State of Qatar.

METHOD

A retrospective cohort study in all adult patients with ESRD on chronic hemodialysis therapy (>1 month) in ambulatory dialysis clinics in the State of Qatar. Data collected were patient's characteristics, laboratory and diagnostic investigations for each patient through our electronic data system (nationwide). We focused on parathyroid hormone (PTH), calcium and phosphorus levels done routinely on monthly basis. The study duration was 31 months (January 2019–September 2021).

RESULTS

We included 623 patients. Age was 56 ± 11 years old and 61% were male. The main comorbidities were diabetes mellitus (63%), hypertension (92%) and cardiovascular disease (22%). The percentage of patients with PTH levels within targets ranged from 63 to 74%. It was stable before and during the first wave of COVID-19 in Qatar (March–June 2020) then dropped afterward briefly for 3 months (October–December 2020) (74% versus 63% respectively P = 0.0003). PTH level in target improved afterward and also during the second wave of COVID-19 (February–May 2021) but then dropped again for 3 months (July–September 2021) [72% versus 66% respectively P = 0.02 (graph below with details)]. Patients with phosphorus and calcium in the target were mostly stable [79% (77–83%) and 76% (74–79%), respectively].

CONCLUSION

Our retrospective study regarding the effect of the COVID-19 epidemic on MBD outcomes in hemodialysis (HD) showed a temporary drop in PTH level in the target without affecting calcium and phosphorus targets. The delayed drop after COVID-19 waves in PTH in target could be related to the routine quarterly measurement of PTH. We think that establishing a solid management system for MBD led to reasonably stable outcomes despite all challenges during the COVID-19 epidemic.
MO551: Targeted Ablation of PTEN in Osteocytes Induces Severe Anemia and Increases FGF23 Production in Renal Insufficiency
Authors: Miguel Diaz-Tocados Juan , Pérez-Gomez Aurora , Diego Dominguez Coral Juan , Ángel Rodríguez Martín Miguel , García-Carrasco Alicia , Martinez Bardaji Ana , Eritja Sanjuan Auria , Caus Enriquez Maite , Bozic Milica , M. Valdivielso Jose
Published: May 2022

BACKGROUND AND AIMS

Renal disease patients present bone alterations due to an imbalance of mineral metabolism. Previous studies have demonstrated that mice with conditional ablation of the phosphatase and tensin homolog (PTEN) in osteoblasts show increases in bone volume. The aim of this study was to investigate whether PTEN ablation in osteocytes has potential benefits on bone and mineral metabolism in the context of renal insufficiency.

METHOD

A few 2-month-old mice with constitutive ablation of PTEN in osteocytes (Ocy-PTEN-cKO) underwent 5/6 nephrectomy (5/6Nx) and were fed a 0.9% phosphate diet. After 2 weeks, 24-h urine samples were collected and animals were sacrificed to obtain blood samples for biochemical studies and organs for histological and biochemical analyses. Bone histomorphometry and microcomputed tomography analyses were performed in femurs. Fibroblast growth factor 23 (FGF23) expression was quantified in bone lysates and intact and c-terminal FGF23 concentrations were measured in plasma samples. Animals with normal renal function and Cre-negative littermates were used as controls. In addition, the effects of PTEN silencing were assessed in vitro in osteocyte-like bone marrow mesenchymal stem cells and in the osteosarcoma cell line SAOS-2.

RESULTS

Ocy-PTEN-cKO mice showed increased bone volume, mainly in the cortical compartment which showed higher cortical thickness and lower porosity. Of interest, we observed lower haematocrit in the Ocy-PTEN-cKO mice that was much lower in those with 5/6Nx. Anaemia was not associated with a lower renal EPO expression. Bone mRNA and protein expression of FGF23 were increased in Ocy-PTEN-cKO mice with normal and reduced renal function. 5/6Nx resulted in higher plasma intact FGF23, which remained similar between both, Ocy-PTEN-cKO and control groups, due to increased FGF23 cleavage as indicated by the higher plasma c-terminal FGF23 levels in the Ocy-PTEN-cKO groups, resulting in increased plasma phosphate. In vitro, PTEN silencing in bone marrow mesenchymal stem cells differentiated into osteoblasts or in the osteoblastic cell line SAOS-2 did not show significant changes regarding FGF23 levels, indicating that the effects must be indirect.

CONCLUSION

PTEN ablation in osteocytes increases cortical bone volume and exacerbates anemia in mice with reduced renal function. Moreover, bone FGF23 production was increased but subsequent proteolysis resulted in higher plasma phosphate. These results demonstrate a major role of the osteocyte in the development of anaemia in renal disease, which could be associated with FGF23 metabolism.
MO565: Evaluation of Bach1 Mrna Expression (Repressor of NRF2) in Patients With Chronic Kidney Disease
Authors: Mafra Denise , Alvarenga Livia , G. Baptista Beatriz , Fanton Susane , M. Ribeiro Marcia , R. Paiva Bruna , Trugilho Liana , Cardozo Ludmila
Published: May 2022

BACKGROUND AND AIMS

BTB and CNC homology 1 (Bach1) is a protein into the cells that antagonizes the actions of nuclear factor erythroid 2-related factor-2 (Nrf2), a master regulator of cytoprotective responses. Bach1 binds to genomic DNA and can inhibit the synthesis of antioxidant enzymes, increasing inflammation. Bach1 may be a therapeutic target to mitigate inflammation in patients with chronic kidney disease (CKD). However, no clinical study has been reported on Bach1 in patients with CKD. This study aimed to evaluate Bach1 mRNA expression in different treatments of CKD, including patients on conservative treatment (non-dialysis), hemodialysis (HD) and peritoneal dialysis (PD).

METHODS

Twenty patients on HD (54.3 ± 13.7 years old, nine men), fifteen on PD (51.4 ± 14.9 years old, eight men) and thirteen non-dialysis patients (61.0 ± 6.9 years old, seven men, estimated glomerular filtration rate of 39.2 ± 9.6 mL/min/1.73 m2) were enrolled in the study. The peripheral blood mononuclear cells were isolated and processed to evaluate the expression of nuclear factor-kB (NF-kB), Nrf2 and Bach1 by quantitative real-time polymerase chain reaction. Malondialdehyde (MDA), a lipid peroxidation marker, and C-reactive protein (CRP) plasma levels were also measured.

RESULTS

Bach1 mRNA expression was significantly higher in patients on hemodialysis (P < 0.02) when compared with PD and non-dialysis patients (Table 1 and Fig. 1). Also, as expected, CRP plasma levels were higher in HD patients when compared with non-dialysis patients (P = 0.05). Bach1 mRNA expression was positively correlated with MDA plasma levels (r = 0.37, P = 0.01) in all patients.

CONCLUSION

Patients with CKD on HD patients seem to have upregulation of Bach1 mRNA expression compared to patients on conservative and DP treatment. The associations among Nrf2 and Bach1 expressions in these patients deserve further investigation.
MO604: Determinants of an Aerobic Threshold in Chronic Kidney Disease
Authors: Chinnappa Shanmugakumar , Mooney Andrew
Published: May 2022

BACKGROUND AND AIMS

Anaerobic threshold (AT) is a widely used cardiopulmonary exercise test (CPX) parameter in the field of preoperative assessment in general population where it is used as a surrogate marker of cardiovascular fitness. There is growing interest in the application of AT in the evaluation of fitness for kidney transplantation. However, the determinants of anaerobic threshold in CKD have not been well studied. In the present study, we evaluated the hemodynamic, biochemical and anthropometric determinants of AT in CKD. Furthermore, we evaluated the association between AT and objectively measured index of cardiac functional reserve in CKD.

METHOD

In this cross-sectional study, 70 male CKD patients (stages 2–5) without any cardiac diseases or diabetes underwent a specialised CPX to measure exercise capacity, AT, peak cardiac hemodynamics and cardiac power output (CPO).1 Cardiac functional reserve was calculated as ∆CPOpeak—CPOrest. Blood samples were assayed for standard renal biochemistry. Univariate and multivariate regression were employed. Results were presented as mean ± SD. P < 0.05 is considered significant.

RESULTS

The study subjects had a mean age of 48.4 ± 12.6 years and a mean eGFR of 33.9 ± 23.5 mL/min. All subjects performed high intensity CPX to volitional exhaustion with a mean RER of 1.16 ± 0.09 and a mean peak aerobic capacity (VO2peak) of 2.51 ± 0.53 L/min. Table 1 shows the univariate and multivariate predictors of AT in CKD. Figure 1 shows the association between AT and objectively measured cardiac functional reserve.

CONCLUSION

The results demonstrate that AT only has a modest association with cardiac functional reserve in CKD. Noncardiac factors such as haemoglobin and peripheral O2 extraction are also significant determinants of AT in addition to cardiac factors. Therefore, AT should be interpreted with caution if employed as a surrogate marker of cardiovascular fitness in CKD. 1Chinnappa S et al. JASN July 2021,  32 (7): 1813–1822