Severe Chronic Kidney Disease Research Articles

0719 The Risk Of Progression Of Chronic Kidney Failure In Patients With Obstructive Sleep Apnea

Abstract Introduction To describe the risks of chronic kidney disease (CKD) progression in patients with obstructive sleep apnea (OSA) Methods In this retrospective case control study; patients with CKD and OSA compared to patients with CKD without OSA who followed up at Creighton University Hospital Clinic. Data retrieved from Electronic Medical Records: demographics, time of diagnosis severity of OSA , apnea hypopnea index, severity of chronic kidney disease using serum creatinine and CKD -EPI equation for glomerular filtration rate cut offs. Patient’s kidney function was followed up for 10 years from their diagnosis of OSA. Worsening kidney function is defined on the basis of laboratory values including estimaed GFR( eGFR) and serum creatinine as well as Kidney Diseases Outcome Quality Initiative (KDOQI) 2002 definition and staging. We calculated the mean and SD when appropriate. P values less than 0.05 were considered statistically significant. Results 269 patients without OSA included in the study. 416 patients with mild OSA, 343 with moderate OSA and 225 with severe OSA mean (SD) age 46.6 (16.3), 52.9(13.5), 56.9(14.1) and 55.3(15.1) years respectively; 59.1, 56.5, 39.1 and 35.6% were females respectively. CKD stage 1 42.8, 26.9, 26.5 and 28.9% respectively. Stage 246.5, 56.3, 54.2 and 46.7% respectively. Stage 3 10.7, 16.9, 19.2 and 24.3% respectivelyPatient’s renal functions who had CKD stage 2 or 3 with mild., moderate and severe OSA got worse in 21.2,31.5 and 26.7% respectively. compared to 13.1% with no sleep apnea.(p <.001)) ,There was no significant difference on progression of CKD in late stages( CKD IV/V) Conclusion Patients with OSA and CKD are more likely to have worsening renal function compared to patients without OSA and this association may depend on severity of both CKD and OSA. Support (If Any)

Psoas muscle measurement as a marker of sarcopenia predicts risk of Grade 4 or 5 baseline chronic kidney disease and its progression

AbstractBackgroundPsoas muscle area (PMA) has recently been found to be an appropriate surrogate for whole‐body skeletal muscle mass and a measure of sarcopenia. Sarcopenia, which includes a decreased muscle mass and correlated with physical disability, morbidity, and mortality, is prevalent in and has deleterious consequences for patients with chronic kidney disease (CKD). The current study investigates the association of PMA, as a marker of sarcopenia, with baseline kidney function and CKD progression.MethodsA retrospective cohort study was conducted in a community hospital nephrology clinic setting. For this study, sarcopenia was defined as standardized PMA measured at the L3 level either as below 25th percentile or below the median. Progression of CKD was measured by estimated glomerular filtration rate (eGFR) decline rate and change in proteinuria. To assess sarcopenia as a predictor of baseline CKD Grade 4 or 5, a multivariate logistic regression model was applied using standardized PMA < 25th percentile. To assess sarcopenia as a predictor for eGFR slope, a multivariate generalized linear model was applied using PMA < median.ResultsAmong the 230 patients studied, the median age was 74 (31–92) years, 56.52% (130/230) were male patients, and the majority was Caucasian 62.61% (144/230). The body mass index classes of <18.5, 18.5–24.9, 25.0–29.9, and >29.9 kg/m2 were categorized by 4.8% (11/229), 24.89% (57/229), 33.19% (76/229), and 37.12% (85/229), respectively. Sarcopenia as a predictor of baseline CKD Grade 4 or 5 had an unadjusted odds ratio of 1.46 (0.87–2.63) and an adjusted odds ratio of 2.45 (1.13–5.31). Sarcopenia as a predictor for eGFR slope had an unadjusted odds ratio of 1.01 (1.00–1.04) and an adjusted odds ratio 1.03 (1.00–1.05).ConclusionsSarcopenia, as measured by PMA, predicts a significant risk of more severe baseline CKD grade and progression. Future studies should examine sex‐specific muscle mass tools as a predictor of renal function to create more targeted interventions.

The Impact of Moderate to Severe Chronic Kidney Disease on Outcomes of Carotid Revascularization

The goal of this study was to better understand how moderate to severe chronic kidney disease (CKD) affects the outcomes of patients undergoing carotid endarterectomy (CEA), transfemoral carotid artery stenting (TFCAS), and transcarotid artery revascularization (TCAR).

P95 PERI–PROCEDURAL COMPLICATIONS AND LONG–TERM OUTCOMES IN ATRIAL FIBRILLATION PATIENTS STRATIFIED FOR CHRONIC KIDNEY DISEASE SEVERITY UNDERGOING LEFT ATRIAL APPENDAGE OCCLUSION: RESULTS FROM AN INTERNATIONAL, MULTICENTER REGISTRY

Abstract Background Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thromboembolic events. CKD concomitantly contributes to several pathophysiological changes predisposing towards a pro–haemorrhagic state. Objective To evaluate the impact of kidney function on peri–procedural complications and clinical outcomes in AF patients undergoing left atrial appendage occlusion (LAAO) with a Watchman device. Methods 2124 consecutive AF patients undergoing Watchman implantation at 8 different centers were categorized into CKD stage 1 + 2 (n = 1089), CKD stage 3 (n = 796), CKD stage 4 (n = 170), CKD stage 5 (n = 69) based on the estimated glomerular filtration rate at baseline. The primary efficacy endpoint included a composite of cardiovascular (CV) mortality, stroke, transient ischemic attack, peripheral thromboembolism (TE), and major bleeding. Results A non–significant higher incidence of major peri–procedural adverse events (1.7% vs. 2.3% vs. 4.1% vs. 4.3%) was observed with worsening baseline kidney function (p = 0.14). The mean follow–up period was 13 ± 7 months [2226 patient–years (PY)]. In comparison to CKD stage 1 + 2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log–rank p–value= 0.04), CKD stage 4 (log–rank p–value= 0.01), and CKD stage 5 (log–rank p–value= 0.001) (Fig. 1A). A non–significant increase in event rates for stroke/TIA and clinically relevant bleeding was observed among the four groups. LAAO led to a TE risk reduction of 72%, 66%, 62%, and 41% in each group (Fig. 1B). The relative risk reduction in the incidence of major bleeding was 58%, 44%, 51%, and 52%, respectively (Fig. 1C). Conclusion Patients with moderate–to–severe CKD had a higher incidence of the primary composite endpoint. The relative risk reduction in the incidence of TE and major bleeding was consistent across CKD groups, irrespective of the very different risk profiles at baseline.

Clinical predictors of hyponatremia in patients with heart failure according to severity of chronic kidney disease

Chronic kidney disease (CKD) has been associated with adverse clinical outcomes. Hyponatremia, amarker of illness severity and poor prognosis, is commonly exhibited in patients with CKD. This cross-sectional study included patients hospitalized due to heart failure (HF). We used stepwise logistic regression to investigate the independent association of cardiovascular drugs, markers of HF severity, and baseline clinical characteristics with hyponatremia in three subgroups; normal renal function, mild-to-moderate CKD, and severe CKD. Of the 1232patients, 38.6% were hyponatremic. Patients with severe CKD, compared to those with normal renal function and mild-to-moderate CKD, were more likely to be hyponatremic (47.1%, 34.4% and 36.6%, respectively; p ≤ 0.0001). Alcohol consumption, female sex, n-terminal pro-brain natriuretic peptide (NT-proBNP), hydrochlorothiazide (HCT), and mineralocorticoid receptor antagonist (MRA) use, or angiotensinII receptorI blocker (ARB) non-use were associated with hyponatremia in patients with normal renal function (p ≤ 0.03 in all cases). Current smoking, diabetes mellitus, NT-proBNP, loop diuretic dose, and MRA use were predictors in mild-to-moderate CKD (p ≤ 0.04 in all cases). ARB use, loop diuretic dose, and HCT use were predictors in severe CKD (p ≤ 0.03 in all cases). Non-use of dihydropyridine calcium channel blocker (CCB) was an independent predictor of hyponatremia in all CKD stages (p ≤ 0.04 in all cases). Apart from afirm favorable effect of CCBs, cardiovascular therapy should be carefully tailored to avoid hyponatremia in patients with cardiorenal syndrome.

Kynurenine pathway metabolites predict subclinical atherosclerotic disease and new cardiovascular events in chronic kidney disease.

ABSTRACTIntroductionInflammation and oxidative stress contribute to the disproportionate burden of cardiovascular disease (CVD) in chronic kidney disease (CKD). Disordered catabolism of tryptophan via the kynurenine and indole pathways is linked to CVD in both CKD and dialysis patients. However, the association between specific kynurenine and indole metabolites with subclinical CVD and time to new cardiovascular (CV) events in CKD has not been studied.MethodsWe measured kynurenine and indole pathway metabolites using targeted mass spectrometry in a cohort of 325 patients with moderate to severe CKD and a median follow-up of 2 years. Multiple linear regression and Cox regression analyses were used to assess the relationship between these tryptophan metabolites and subclinical CVD, including calcium scores, carotid intima-media thickness and time to new cardiovascular (CV) events.ResultsElevated quinolinic and anthranilic acids were independently associated with reduced time to new CVD [hazard ratio (HR) 1.28, P = .01 and HR 1.02, P = .02, respectively). Low tryptophan levels were associated with reduced time to new CV events when adjusting for demographics and CVD history (HR 0.30, P = .03). Low tryptophan levels were also associated with aortic calcification in a fully adjusted linear regression model (β = −1983, P = .006). Similarly, high levels of several kynurenine pathway metabolites predicted increased coronary, aortic and composite calcification scores.ConclusionsWe demonstrate the association of kynurenine pathway metabolites, and not indole derivatives, with subclinical and new CV events in an advanced CKD cohort. Our findings support a possible role for altered tryptophan immune metabolism in the pathogenesis of CKD-associated atherosclerosis.

Prevalence, phenotypic characteristics and prognostic role of apparent treatment resistant hypertension in the German Chronic Kidney Disease (GCKD) study.

Treatment resistant hypertension (TRH) appears of particular relevance in patients with chronic kidney disease (CKD). However, causes and consequences of TRH in CKD patients remain incompletely understood. Therefore, we analyzed the prevalence of apparent TRH (aTRH), and phenotypic characteristics and prognosis associated with aTRH among participants of the German Chronic Kidney Disease (GCKD) study. As insufficient medication adherence has been shown to be a frequent cause of pseudoresistance, we also assessed treatment adherence. Study participants were classified as having aTRH, controlled hypertension and uncontrolled hypertension based on study visit blood pressure and self-reported medication intake. Drug adherence was assessed by comparing self-reported antihypertensive medication with detectable urinary drug metabolites measured by mass spectroscopy. Out of 4901 individuals included in this study, 38% were classified as having aTRH. Male sex, older age, lower estimated glomerular filtration rate (eGFR), higher body mass index (BMI), higher urine albumin-to-creatinine ratio (UACR) and presence of diabetes mellitus were independently associated with higher prevalence of aTRH in a multivariable adjusted regression model. Patients classified as aTRH had higher risk for major adverse cardiovascular events and worsening of kidney disease compared to patients with no aTRH after multivariate adjustment for potential confounders. There was a high agreement between self-reported medication and detectable urinary drug metabolites. In conclusion, in a cohort of Caucasian patients with moderately severe CKD, aTRH was highly prevalent and, in most cases, likely not caused by low medication adherence. Furthermore, aTRH was linked to cardio-renal endpoints, emphasizing the need for improved management.

MO540: Are the Haematological Markers of Inflammation Predictors of Fibroblast Growth Factor-23 in Non-Dialysis Chronic Kidney Disease?

Abstract BACKGROUND AND AIMS Recently, a growing body of evidence point to the relationships between inflammation and fibroblast growth factor 23 (FGF23) in adults with and without chronic kidney disease (CKD). On the other hand, some haematological indices derived from the complete blood count appear as simple and inexpensive biomarkers of systemic inflammation. Therefore, this study aimed to evaluate the association between the haematological markers of inflammation and FGF23 in non-dialysis CKD. METHOD This single centre, cross-sectional study prospectively enrolled 90 subjects with moderate to severe stable CKD [median estimated glomerular filtration rate (eGFR) 25 (95% confidence interval 95% CI 24.9–30.5) mL/min, 46% in stage G3, urinary albumin-to-creatinine ratio (ACR) 221 (95% CI 498–954) mg/g], mostly males (61%), aged 62 (95% CI 57–64) years. Patients on renal replacement therapy (RRT) and those with active malignancies, infectious and inflammatory diseases were excluded. Demographic, past medical history (CKD vintage and etiology, comorbidities, chronic medications) and laboratory data were collected. Haematological markers of systemic inflammation [red blood cell distribution width (RDW), platelet distribution width (PDW), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)] were obtained from the complete blood count. Other measured lab parameters were: c-terminal FGF23 (cFGF23), intact parathyroid hormone (iPTH), serum calcidiol (25OHD), total calcium (tCa), phosphate (PO4), alkaline phosphatase, C-reactive protein, albumin, transferrin, ferritin and transferrin saturation, as markers of mineral metabolism, inflammatory, nutritional and iron status, respectively. Associations among studied parameters were assessed by Spearman rank test, multivariate linear regression and logistic regression models. Non-parametric variables were log-transformed. RESULTS The median cFGF23 was 4.65 (95% CI 7.57–14.4) pg/mL. Subjects in the highest cFGF23 quartile [n = 22, cFGF23 20.8 (95% CI 20.8–40.8) pg/mL] had higher RDW (P = 0.02), iPTH (P < 0.001), PO4 (P = 0.005) and ACR (P = 0.004), but lower tCa (P = 0.04), haemoglobin (P = 0.01) and eGFR (P < 0.001) as compared to those in the lowest quartile [n = 23, cFGF23 0.84 (95% CI 0.71–1.10) pg/mL]. Moreover, they had higher proportions of arterial hypertension (P = 0.01) and previous treatment with intravenous iron (P = 0.03). A trend to higher PLR (P = 0.052), NLR (P = 0.064), and ferritin (P = 0.076) was also observed. However, beside the expected bivariate correlations with eGFR, ACR, iPTH, tCa and PO4, cFGF23 was further correlated solely with haemoglobin (rs = –0.33, P = 0.002). In a multivariate linear regression model which explained 34% of the log(cFGF23) variance, log(PLR) (B 1.59, 95% CI 0.14–3.03, P = 0.03) and log(eGFR) (B –1.65, 95% CI –2.51 to –0.80, P < 0.001) were independent predictors. After adjustment for history of arterial hypertension and previous intravenous iron treatment, in a model of logistic regression (Nagelkerke R2 0.57, Chi2 16.7, P = 0.03), log(eGFR) was found as independent predictor of the log(FGF23) [odds ratio (OR) 0.07, 95% CI 0.01–0.36, P = 0.002]. However, RDW was retained in the last step of this model with a borderline significance (OR 4.3, 95% CI 0.98–19.02, P = 0.052). CONCLUSION Taken together, our findings suggest that, in addition to the kidney function, RDW and PLR seem to predict cFGF23 in non-inflammed, stable, non-dialysis CKD adults. Thus, one might speculate in favour of the association between chronic inflammatory state and FGF23 metabolism and in support of the revelatory role of some haematological markers of inflammation, a hypothesis that needs further research.

MO469: GPR124—A Driver of Fibrotic Kidney Diseases

Abstract BACKGROUND AND AIMS Renal fibrosis is a central feature of chronic kidney disease (CKD), and the severity of CKD correlates with the magnitude of renal fibrosis. Despite the causative role attributed to fibrosis in CKD progression, there is still no treatment available that directly targets renal fibrosis. Upon kidney injury, embryonic signalling pathways are activated, promoting the repair and regeneration of injured tissue. Maladaptive repair mechanisms have been associated with the development of renal fibrosis and sustained activation of Wnt/β-catenin signalling contributes to CKD progression. GPR124 (ADGRA2 gene), has been identified as a potential fibrotic mediator through its upregulation in pericytes during pericyte to myofibroblast transition. GPR124 has been identified to function as a co-receptor for Wnt7 mediating canonical Wnt signaling in endothelial cells. We observed elevated GPR124 expression in mouse kidneys after chronic ischaemia reperfusion injury (cIRI). To further explore the role of GPR124 in CKD progression, we have studied its correlation with disease severity in human NURTuRE kidney biopsies [1]. We have also looked at GPR124 therapeutic potential in mouse cIRI. Given its potential disease relevance, we set out to develop inhibitory GPR124 antibodies as novel therapeutics to treat renal fibrosis. METHOD Diagnostic FFPE kidney cortex biopsy samples from 497 NURTuRE patients were subjected to bulk RNA-Seq. Library preparation with Illumina Enrichment Tagmentation technology was followed by sequencing and alignment of paired-end reads to the reference genome GRCh38/ENSEMBL 97 and quantification. Monoclonal Anti-GPR124 antibodies were generated against the extracellular domain of human GPR124. Top candidates were selected by FACS binding and further characterized in a TCF/LEF luciferase assay for the inhibition of Wnt7 signaling. One hu/ms cross-reactive candidate was studied in a 14-day IRI mouse model to assess its anti-fibrotic effect in vivo. Mice were exposed to 30-min unilateral renal ischaemia, followed by 14 days recovery. Kidneys were studied for gene expression by RT-PCR. Animals were divided into sham (n = 5), control IRI (no antibody, n = 12) and treated groups (each n = 12). The antibody was administered before ischemia and during the recovery phase in two doses [50 mg/kg and 150 mg/kg]. RESULTS CONCLUSION NURTuRE provides us with a unique opportunity to assess relevance of a potential target candidate gene in kidney disease patients. The potential of GPR124 as a therapeutic target was highlighted by the upregulation of expression levels along disease severity and biological pathway analysis, where our data supports a potential role in extracellular matrix reorganization. The administration of GPR124 antibodies and inhibition of the GPR124-mediated Wnt signaling in vivo inhibited the development of ischaemia-induced fibrosis in the mouse kidney. The results strongly support a role for GPR124 in human kidney disease progression, through inhibition of fibrosis, and its potential as a future clinical target.

MO456: Renal and Major Clinical Outcomes After Nephrectomy in Patients With Pre-Existing Chronic Kidney Disease (ON-CKD Study)

Abstract BACKGROUND AND AIMS Partial nephrectomy (PN) has progressively replaced radical nephrectomy (RN) whenever feasible for renal tumors. However, its effects on renal outcomes are less known in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We aimed to assess renal and major clinical outcomes after PN or RN in patients with moderate to severe CKD or SK. METHOD We included all surgical procedures conducted between 2013 and 2018 in the Hospices Civils de Lyon, in patients with last pre-operative estimated glomerular filtration rate (eGFR) <60mL/min/1.73m², or with SK. Exclusion criteria were eGFR < 15mL/min/1.73m² or dialysis, RN on SK, ablative therapy. Demographic, tumors and surgeries characteristics were collected, as well as eGFR 1 month and 1 year after surgery. Main outcome was a composite criterion including CKD progression or major cardio-vascular events or death, assessed 1 year after surgery. Predictors of the main outcome were determined using multivariate analyses. RESULTS We included 173 procedures (67 RN and 79 PN on CKD patients, 27 PN on SK patients). Patients undergoing RN were older, had bigger tumors and higher T stages on TNM classification. Preoperative estimated glomerular filtration rate (eGFR) and CKD stages were not different between the groups. One year after surgery, PN was associated with less occurrence of the main composite outcome compared to RN (42.9% versus 70.7%, P < 0.01). On multivariate analysis, independent risk factors for the main outcome were postoperative AKI (no AKI as reference; AKI stage 1 odds ratio (OR) = 8.68, 95% confidence interval (CI) 3.23–23.33; AKI stage 2 OR = 23.50, 95% CI 2.33–236.51; AKI stage 3 OR = 28.87, 95% CI 4.77–167.61) and bigger tumor size (OR = 1.21/cm, 95% CI 1.02–1.45), while preoperative eGFR was not (Table 1). Compared to pre-operative values, eGFR significantly decreased both after RN or PN 1 month after surgery (eGFR loss -12mL/min 1.73m² after RN P < 0.001, −3mL/min/1.73m² after PN, P < 0.05) and this decrease remained stable 1 year after surgery (eGFR loss -11mL/min/1.73m² after RN, P < 0.001, −3mL/min/1.73m² after PN, P < 0.05), but renal function was better preserved after PN than after RN at 1 month (P < 0.05) or 1 year (P < 0.01) (Figure 1). CONCLUSION In moderate to severe CKD patients, PN was associated with less risk of CKD progression or major cardio-vascular event or death 1 year after surgery, compared to RN. Postoperative AKI was the major determinant of clinical and renal outcomes.

FC006: Sex Differences in the Recognition, Monitoring and Management of Chronic Kidney Disease in Health Care

Abstract BACKGROUND AND AIMS Sex-specific differences exist in the population prevalence of chronic kidney disease (CKD), progression rates and health outcomes. Recognition, diagnosis and monitoring are central processes in the management of patients with CKD, but it is unknown whether these processes differ between men and women. METHOD This is an observational cohort study of all adult individuals (n = 227 847) with at least one eGFR (from serum creatinine) <60 mL/min/1.73 m2 during outpatient routine care in Stockholm, Sweden, 2009–2017. Through logistic regression, we evaluated differences by sex in carrying an ICD-10 code for CKD and provision of recommended medications (renin–angiotensin system inhibitors [RASi] and statins) at inclusion. Through Cox regression, we evaluated potential sex differences in receiving a CKD diagnosis, referral to nephrology care and performance of laboratory monitoring (creatinine and albuminuria) in the next 18 months from inclusion. We also explored time-trends, comparing the above-mentioned nephrology care indicators among 70–80 000 unique eligible individuals per calendar year (in total 695 632 observations), thus allowing participants to contribute to different calendar year-cohorts. RESULTS We identified more women (55%) than men (45%) with probable CKD (eGFR < 60 mL/min/1.73 m2). Women were generally older than men (median 77 versus 74 years), but eGFR was similar between sexes (51 mL/min/1.73 m2). More men than women had diabetes or myocardial infarction, but there was similar prevalence of hypertension. At inclusion and compared with men, women had lower risk of carrying an ICD-10 code for CKD (odds ratio [OR]: 0.47, 95% CI: 0.45–0.49) and were less likely to receive RASi (OR: 0.55; 0.50–0.61, among patient with albuminuria A3) or statins (OR: 0.64; 0.63–0.66, among patients ≥ 50 years), despite the presence of clear indications. In subsequent time-to-event analyses, women were less likely to receive a CKD diagnosis (hazard ratio [HR]: 0.43; 0.42–0.45) and visit a nephrologist (HR: 0.46; 0.43–0.48) regardless of CKD severity, presence of albuminuria or criteria for referral. Women were also less likely to undergo monitoring of creatinine or albuminuria, even among participants with diabetes (HR: 0.75; 0.74–0.76) or hypertension (HR: 0.76; 0.75–0.78). Multivariable adjustment including comorbidities, eGFR and indication for referral showed some attenuation of the effect, but a sex difference remained. Although in absolute terms there has been a gradual improvement in all nephrology care indicators over time, the observed sex gap persisted throughout. CONCLUSION We found profound sex differences in the detection, recognition, monitoring and management (including referrals) of CKD in healthcare, also across high-risk groups and indications.

MO487: Rates of Hyperkal a EMIA and Management Patterns in a Tertiary Outpatient Renal Clinic

Abstract 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.

The rationale for the need to study sodium-glucose co-transport 2 inhibitor usage in peritoneal dialysis patients.

The wave of kidney and heart outcome trials, showing multiple potential benefits for sodium-glucose co-transport 2 (SGLT2) inhibitors, have excluded patients with an estimated glomerular filtration rate below 25 ml/min/1.73 m2. However, dialysis patients are at the highest risk of cardiovascular disease and would benefit most from effective cardioprotective therapies. There is emerging evidence from experimental studies and post hoc analyses of randomised clinical trials that SGLT2 inhibitors are well tolerated and may also be effective in preventing cardiovascular and mortality outcomes in patients with severe chronic kidney disease, including patients receiving dialysis. As such, extending the usage of SGLT2 inhibitors to dialysis patients could provide a major advancement in their care. Peritoneal dialysis (PD) patients have an additional unmet need for effective pharmacotherapy to preserve their residual kidney function (RKF), with its associated mortality benefits, and for treatment options that help reduce the risk of transfer to haemodialysis. Experimental data suggest that SGLT2 inhibitors, via various mechanisms, may preserve RKF and protect the peritoneal membrane. There is sound physiological rationale and an urgent clinical need to execute robust randomised control trials to study the use of SGLT2 inhibitors in PD patients to answer important questions of relevance to patients and healthcare systems.

Modeling the Progression of Hypertensive Kidney Disease in African Americans

Chronic kidney disease (CKD) is associated with the progressive functional loss of nephrons and hypertension (HTN). Several clinical studies demonstrate calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN, but there are few long‐term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. African Americans (AA) have a faster progression to end stage renal disease as compared to the white population which may be partially explained by factors such as salt‐sensitive blood pressure (BP) and greater prevalence of uncontrolled HTN. Observational studies demonstrate BP to be a strong independent risk factor for CKD progression, yet intense BP lowering in AA does not diminish the renal function decline any more than standard therapy. The African American Study of Kidney Disease and Hypertension (AASK) trial suggests AA with proteinuric CKD may have detrimental responses to CCB as compared to an angiotensin converting enzyme (ACE) inhibitor. Therefore, using a large physiological model, we set out to replicate the AASK trial findings and predict the roles of the renin‐angiotensin system, salt intake, and intensive antihypertensive therapy in a virtual population during CCB therapy. Our current mathematical model, HumMod, is a large physiological simulator that is comprised of key systems that play an integral role in BP control such as neural, endocrine, circulatory, and renal systems. All of the parameters (n=335) that control these systems were randomly varied and resulted in over 3,000 unique models that we define as a virtual population. We calibrated this virtual population to patient level data from the AASK trial (BP and glomerular filtration rate [GFR] before and after 3 years of amlodipine). After matching the virtual population to individual level data, the virtual population (n=140) was associated with statistically similar BP and GFR before and after CCB therapy (Figure) as well as similar increases in glomerular damage. Baseline factors such as elevated single nephron GFR and increased tubuloglomerular feedback were correlated with greater declines in renal function and increased glomerulosclerosis after 3 years of CCB. Interestingly, when looking at the models with severe CKD (<35 mL/min), glomerulosclerosis and angiotensin II significantly increased with CCB despite significant falls in mean BP (‐7 ± 7 mmHg). Adding an ACE inhibitor decreased angiotensin II levels and abrogated the increase in glomerulosclerosis while further decreasing BP (‐12 ± 9 mmHg). Decreasing salt intake in addition to the CCB+ACE inhibitor therapy further benefited systemic and glomerular pressures but significantly decreased overall GFR independent of any glomerular damage. Finally, all antihypertensive therapies were associated with significant decreases in left ventricular mass. These data suggest the current clinical markers of renal function such as eGFR may not fully reflect the actual progression of CKD, especially with intensive antihypertensive treatment. Our simulation also supports that angiotensin system inhibitors are renoprotective and cardioprotective when combined with CCB therapy in African American CKD patients.

Spatial transcriptomics and single cell sequencing identifies a unique injury associated resident macrophage subpopulation and reveals differential response to injury

Abstract Acute kidney injury (AKI) is a growing concern in the U.S. and globally. Despite recovery of kidney function, patients remain at increased risk for developing chronic kidney disease (CKD). The cause of this increased risk is unknown and biomarkers to determine kidney injury are severely lacking. A potential candidate is the network of kidney resident macrophages interwoven throughout the tissue, and specifically a subpopulation of kidney injury associated macrophages (KIA) we first identified to appear after AKI and lack MHC II expression. KIA cells were localized within the tissue using Visium Spatial Transcriptomics and flow cytometry. Comparison of KIA cell kinetics between AKI and CKD indicated a correlation between the presence of KIA cells and the persistence of injury. Additionally, KIA cells have localized to the sight of greatest injury following an ischemic event. As kidney function recovers, KIA cells decrease in number and return to quiescent levels by 14 days post injury. In contrast, in the severe CKD model, KIA cells persist for up to six weeks, composing approximately 20% of the total kidney resident macrophage population. A less severe version of CKD results in fewer KIA cells but similar persistence, indicating appearance of KIA cells directly correlates with injury severity. Targeting KIA cells to either enhance or negate their function is a possible therapeutic target to reduce the risk of developing CKD following AKI. As we have identified KIA cells in multiple models of kidney injury, in the future they should be investigated as a potential injury biomarker. We hypothesize that KIA cells are uniquely involved in the pathogenesis of injury and may be a key to an AKI to CKD transition. Supported by grants from the American Heart Association: (AHA 827257)

Sonographic Comparison Between Echogenicity and Renal Length Among Patients Suffering with Or Without Chronic Kidney Disease

Chronic kidney disease (CKD) is defined as any abnormality and impaired kidney functions for more than three months. Most common causes of CKD is diabetes and hypertension. Objective: To determine the association between renal length and echogenicity in patients with or without chronic kidney disease. Methods: In Gilani Ultrasound Centre ,Lahore a descriptive study was conducted on Ultrasound Machine, Nemio 17 Toshiba.70 patients with or without chronic kidney disease were included. Patients with no previous clinical record of diabetes, high blood pressure and age below than 15 were excluded. Results: Data analysis demonstrated that total of 70 patients, (35 normal and 35 with CKD ) were selected in our study.Out of 70, 46(65.7%) were male and 24(34.3%) were female. Our results shows that (out of 70 patients) in right kidney echogenicity, 36(51.0%) no; of patients shows normal echogenicity with grade 0, 18(25.7%) with grade I, 10(14.3%) with grade II, 6(8.6%) with grade III , and in left kidney echogenicity ,37(52.9%) no;of patients shows normal echogenicity with grade 0,16(22.9%) with grade I, 10(14.3%) with grade II, 7(10.0%) with grade III. respectively a significant correlation of CKD with right and left renal were found as ,in right renal length with CKD mean length was 8.914 ±1.43 and without CKD ,10.4 ± 1.2 similarly in left renal length with CKD mean length was 9.49 ± 1.48 and without CKD,10.28 ±1.14.There is also a significant correlation was found between CKD ,right and left renal echogenicity ( significant P value is .000 for right and .000 for left renal length). Conclusion: Study concluded that echogenicity and renal length can help us to estimate the severity of CKD. It also states that there is a significant association, that was found between renal echogenicity, renal length and CKD.

Coronary Artery Bypass Grafting in Patients with Chronic Kidney Disease: Chronic Kidney Disease Has an Independent Adverse Effect on the Long-Term Outcome of Coronary Artery Bypass Grafting.

We examined short- and long-term outcomes of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and the effect of renal function on these outcomes. We included 2783 patients who underwent primary elective CABG at a single institution between 2002 and 2020 (age: 67.6 ± 10.2 years; male: 2281 male). They were stratified based on their preoperative estimated glomerular filtration rate and underwent off-pump CABG (completion rate, 98.1%); 57.6% cases used bilateral internal thoracic arteries (BITA). In-hospital mortality rate was 1.0%. Logistic regression analysis revealed that low left ventricular function (<40%), but not chronic kidney disease (CKD) severity, was an independent predictive risk factor for postoperative hospital mortality. Significant differences existed in respiratory complications, infections, and hospitalization duration according to CKD severity. Deep sternal wound infection rate was 0.5%. The mean follow-up period was 7.1 (0–18.5) years. Estimated 10-year survival rates were negatively correlated with CKD severity; in the Cox hazard model, severe CKD was an independent predictor of long-term survival. We examined the relationship between preoperative and intraoperative factors and their effects on long-term survival using propensity score matching by dividing the renal function severity into G1–2 and G3–5. Renal function severity, age, and operative time were independent risk factors. No prognostic improvement was observed with BITA grafts; graft patency was superior in the right internal thoracic artery (52/52; 100%) than in the great saphenous vein (48/59; 81.4%) in G5. Post-CABG in-hospital mortality was unrelated to renal function, but CKD severity strongly influenced long-term survival. Operation time was an important predictor of long-term prognosis in patients with impaired renal function. Treatment plans, including graft and anastomosis-site selections, should be designed to shorten the operation time. In conclusion, using the right internal thoracic artery in CABG is more beneficial in patients with CKD and cardiovascular comorbidities.

Current kidney function parameters overestimate kidney tissue repair in reversible experimental kidney disease

Although underlying mechanisms and the clinical course of kidney disease progression are well described, less is known about potential disease reversibility. Therefore, to analyze kidney recovery, we adapted a commonly used murine chronic kidney disease (CKD) model of 2,8- dihydroxyadenine (2,8-DHA) crystal-induced nephropathy to study disease recovery and efficacy of disease-modifying interventions. The recovery phase after CKD was characterized by improved kidney function after two weeks which remained stable thereafter. By contrast, even after eight weeks recovery, tubular injury and inflammation were only partially reduced, and fibrosis persisted. Deep-learning-based histologic analysis of 8,604 glomeruli and 596,614 tubular cross sections revealed numerous tubules had undergone either prominent dilation or complete atrophy, leading to atubular glomeruli and irreversible nephron loss. We confirmed these findings in a second CKD model, reversible unilateral ureteral obstruction, in which a rapid improvement of glomerular filtration rate during recovery also did not reflect the permanent histologic kidney injury. In 2,8-DHA nephropathy, increased drinking volume was highly effective in disease prevention. However, in therapeutic approaches, high fluid intake was only effective in moderate but not severe CKD and established tissue injury was again poorly reflective of kidney function parameters. The injury was particularly localized in the medulla, which is often not analyzed. Thus, recovery after crystal- or obstruction-induced CKD is characterized by ongoing tissue injury, fibrosis, and nephron loss, but not reflected by standard measures of kidney function. Hence, our data might aid in designing kidney recovery studies and suggest the need for biomarkers specifically monitoring intra-kidney tissue injury.

C3-Epimer of 25-Hydroxyvitamin D3 as a Superior Marker for Predicting the Severity of Chronic Kidney Disease in Rheumatoid Arthritis Patients.

Objective 25-hydroxyvitamin D3 (25[OH]D3) is involved in oxidative stress regulation by upregulating the expression of antioxidant genes except for mineral homeostasis physiological role. C3-epimer of 25(OH)D3 (C3-epi-25[OH]D3) is a form of vitamin D metabolite with low bioaffinity in vivo, but little is known about the relationship between C3-epi-25(OH)D3 and diseases. This study was aimed at investigating the relationship between C3-epi-25(OH)D3 and the severity of chronic kidney disease (CKD) in patients with rheumatoid arthritis (RA). Method A total of 318 RA inpatients were enrolled and divided into mild (n = 247), moderate (n = 46), and severe (n = 25) CKD groups according to the CKD prognosis criterion of the Kidney Disease Improving Global Outcomes guidelines. Serum levels of 25(OH)D2, 25(OH)D3, C3-epi-25(OH)D3, and free 25(OH)D (F25[OH]D) were measured, and the value of 25(OH)D was calculated. The relationship and changing trend of the indexes based on CKD severity were analyzed. Results The serum levels of 25(OH)D, 25(OH)D3, and F25(OH)D showed a decreasing trend (z = −2.781–−3.996, P < 0.01) in RA patients with CKD progression from mild to severe, while C3-epi-25(OH)D3 showed an increasing trend (z = 6.741, P < 0.001) and 25(OH)D2 showed no significant difference among the groups (z = 0.976, P = 0.329). Only levels of C3-epi-25(OH)D3 presented significant differences between adjacent CKD severity groups in RA patients (mild to moderate: z = 3.963, Padj < 0.001; moderate to severe: z = 3.269, Padj = 0.002). Multiple logistic regression analysis showed that 25(OH)D3 and C3-epi-25(OH)D3 were significant predictors for CKD progression in RA patients, and C3-epi-25(OH)D3 had a better predictive advantage (moderate vs. mild: OR = 4.79, P < 0.001; severe vs. mild: OR = 17.85, P < 0.001). Conclusions To the best of our knowledge, this is the first study to reveal that C3-epi-25(OH)D3 is a dominant predictor of CKD severity in RA patients. Further studies are needed to explore the relationship between C3-epi-25(OH)D3 and other diseases.

Association between Use of Nutrition Labels and Risk of Chronic Kidney Disease: The Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2019.

Nutrition labeling on food packages is increasingly found to promote healthier food choices associated with lower risk of chronic kidney disease (CKD). To examine associations between nutrition labels use and CKD risk, we conducted a nationally representative cross-sectional study of 32,080 adults from the 2008–2019 Korean National Health and Nutrition Examination Survey. Nutrition labels use was collected via self-reported questionnaires. Ascertainment and severity of CKD was determined by estimated glomerular filtration rate or proteinuria. In multivariable-adjusted (MV) logistic regression models, increasing awareness and use of nutrition labels was significantly associated with lower CKD risk (MV-adjusted OR “nutrition labels aware and use” group vs. “nutrition labels unaware” group [95% CIs]: 0.75 [0.59–0.95], Ptrend:0.03). This inverse association varied with CKD’s risk of progression, with 21% and 42% reduced risk observed for CKD subtypes with “moderate” and “high” risk of progression, respectively (all Ptrend ≤ 0.04). Furthermore, the nutrition labels use and CKD risk association significantly differed by age, with 35% reduced risk observed in the older group aged 49 years or older, but not in the younger group (Pinteraction < 0.001). Our results suggest increasing perception and use of nutrition labels may contribute to CKD prevention and its early asymptomatic progression, especially in older adults.