Rapid Decline In Renal Function Research Articles

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = −0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Determinant and Impact of Left Ventricular Hypertrophy (LVH) in Chronic Renal Failure (CRF) Patients

Left ventricular hypertrophy is the most common cardiovascular complication in chronic renal failure. It appears to be associated with excess mortality. Objective: To determine the factors associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD), and to describe their influence on renal function. Patients and methods: This was a descriptive and analytical study conducted over 6 years (January 1, 2012 to December 31, 2017) on CKD patients who had an electrocardiogram or cardiac ultrasound. Results: A total of 329 patients were included. LVH was found in 223 patients, a prevalence of 68%. The sex ratio M/F was 2.1. Mean age was 51.05±14.17 years (range 11-95 years). Arterial hypertension predominated (97% of cases), followed by diabetes (26%).Univariate and multivariate analysis showed that LVH was associated with: age ≤51 years (p=0.0037) and with arterial hypertension (p=0.0018) and anemia (p=0.0018). Over a 5-year period, CKD patients with LVH experienced a more rapid decline in renal function than those without LVH (p<0.0001). There was also a higher rate of death in patients with LVH (83%) than in those without (46%) during a 5-year follow-up. Conclusion: LVH is an important factor in the poor prognosis of CKD. This calls for systematic screening and early management by a multidisciplinary team.

Advances in understanding of dendritic cell in the pathogenesis of acute kidney injury.

Acute kidney injury (AKI) is characterized by a rapid decline in renal function and is associated with a high morbidity and mortality rate. At present, the underlying mechanisms of AKI remain incompletely understood. Immune disorder is a prominent feature of AKI, and dendritic cells (DCs) play a pivotal role in orchestrating both innate and adaptive immune responses, including the induction of protective proinflammatory and tolerogenic immune reactions. Emerging evidence suggests that DCs play a critical role in the initiation and development of AKI. This paper aimed to conduct a comprehensive review and analysis of the role of DCs in the progression of AKI and elucidate the underlying molecular mechanism. The ultimate objective was to offer valuable insights and guidance for the treatment of AKI.

Role of Blood Cell Indexes in Progresses to ESRD

AbstractChronic kidney disease (CKD) is a complex health condition characterized by the gradual loss of renal function, often leading to end-stage renal disease (ESRD). It results from a combination of medical, environmental, and genetic factors. Predicting the rate of renal function decline and effectively managing the progression to ESRD is challenging in clinical practice. CKD assessment involves various indicators, including estimated glomerular filtration rate (eGFR), albuminuria levels, serum creatinine, and others. This study aimed to explore the predictive potential of specific blood cell indexes in forecasting further renal function decline and the transition from CKD stage 3–4 to ESRD. We assessed the following blood cell indexes in 377 CKD stage 3–4 patients: absolute neutrophil count (ANC), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), derived NLR (dNLR), mean platelet volume (MPV), aggregate index of systemic inflammation (AISI), and systemic inflammation index (SII). ANC, MPV, NLR, PLR, dNLR, and SII were found to independently predict a rapid decline in eGFR. Notably, NLR and dNLR demonstrated the highest sensitivity and specificity with cut-off values of 3.36 and 2.45, respectively (NLR: 88.6 and 81.7%; dNLR: 85.2 and 75.8%). The corresponding area under the ROC curve values were 0.877 (95% CI 0.837–0.918, p < 0.001) for NLR and 0.849 (95% CI 0.805–0.892, p < 0.001) for dNLR. However, none of the blood cell indexes independently predicted the transition to ESRD. The NLR and the dNLR exhibited the highest predictive capacity towards a rapid decline in renal function in CKD. No blood cell index, however, independently predicted the transition into ERSD.

Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice.

Acute kidney injury (AKI) is defined as a rapid decline in renal function, in which persistent kidney dysfunction gradually progresses to chronic kidney disease (CKD) due to the irreversible loss of nephrons and their maladaptive repair. In recent years, the incidence of AKI has been increasing concerning diverse etiologies, including volume depletion, sepsis, nephrotoxicity, muscle injury, and major trauma, in which ischemia-reperfusion injury (IRI)accounts for most episodes. Development of the IRI model in mice is induced by surgical clamping of the renal pedicles, which provides powerful and controllable tools for preclinical models of AKI. Importantly, the IRI model is deployed at different stages of the AKI development, especially in the processes of AKI to CKD. Despite the IRI model being widely practiced in many laboratories, a series of variables still influence the results of this model. Here, we describe the procedure of IRI model development to provide a repeatable and reliable method for researchers to explore the underlying pathogenesis in the development of AKI and the progression of AKI to CKD.

Circadian syndrome is associated with the development of chronic kidney disease and rapid decline in kidney function in middle-aged and elder adults: a China nationwide cohort study.

The correlation between circadian syndrome (CircS) and kidney outcomes is currently supported by limited empirical evidence. Thus, the objective of this study was to determine the potential relationship between CircS and the development of chronic kidney disease (CKD), as well as the rapid decline in renal function. We utilized data from the 2011 China Health and Retirement Longitudinal Study (CHARLS), which involved 6002 Chinese adults ≥40 years of age. Among these participants, 3670 subsequently had follow-up evaluations in the 2015 survey. The primary outcome was the development of CKD, as defined by an estimated glomerular filtration rates decrease to a level <60ml/min/1.73m2, while the secondary outcome was rapid decline in renal function, as defined by an estimated glomerular filtration rates decrease of >5ml/min/1.73m2 per year. Multivariable logistic regression analysis was utilized to determine the association between CircS and kidney outcomes. Compared to participants without CircS, those with CircS had a higher risk of CKD in the cross-sectional studies conducted in 2011 (OR, 1.292; 95% CI, 1.053-1.585) and 2015 (OR, 1.860; 95% CI, 1.469-2.355). Participants with CircS in the longitudinal cohort study had a higher risk of progressing to CKD (OR, 3.050; 95% CI, 2.052-4.534) and a rapid decline in renal function (OR, 1.959; 95% CI, 1.433-2.677) after 4 years of follow-up evaluations and adjustment for covariates. Moreover, participants who had CircS with ≥6 CirS components had the highest risk of a rapid decline in renal function (OR, 1.703; 95% CI, 1.054-2.753). CirS significantly increased the risk of CKD progression and rapid decline in renal function among middle-aged and elder individuals. Our study findings highlights the importance of recognizing and managing CirC as a preventative strategy for CKD.

Determinant and Impact of Left Ventricular Hypertrophy (LVH) in Chronic Renal Failure (CRF) Patients

Left ventricular hypertrophy is the most common cardiovascular complication in chronic renal failure. It appears to be associated with excess mortality. Objective: To determine the factors associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD), and to describe their influence on renal function. Patients and methods: This was a descriptive and analytical study conducted over 6 years (January 1, 2012 to December 31, 2017) on CKD patients who had an electrocardiogram or cardiac ultrasound. Results: A total of 329 patients were included. LVH was found in 223 patients, a prevalence of 68%. The sex ratio M/F was 2.1. Mean age was 51.05±14.17 years (range 11-95 years). Arterial hypertension predominated (97% of cases), followed by diabetes (26%).Univariate and multivariate analysis showed that LVH was associated with: age ≤51 years (p=0.0037) and with arterial hypertension (p=0.0018) and anemia (p=0.0018). Over a 5-year period, CKD patients with LVH experienced a more rapid decline in renal function than those without LVH (p&lt;0.0001). There was also a higher rate of death in patients with LVH (83%) than in those without (46%) during a 5-year follow-up. Conclusion: LVH is an important factor in the poor prognosis of CKD. This calls for systematic screening and early management by a multidisciplinary team.

Identification of ferroptosis-related genes in acute kidney injury by bioinformatic analysis

ABSTRACT Background: Acute kidney injury (AKI) is a rapid decline in renal function characterized by a decrease in glomerular filtration rate in a short period. Ferroptosis affects the development of various kidney diseases. Therefore, searching for genes related to ferroptosis is crucial for understanding the occurrence and development of AKI. Methods: We obtained data from 18 samples (8 with acute kidney injury and 10 non-pathological tissue) in GSE53769 and 48 samples (39 with acute kidney injury and 9 non-pathological tissue) in GSE139061. We obtained differentially expressed genes (DEGs) of AKI/Control samples from both two datasets and intersected them with known ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FRDEGs). GO annotation, KEGG pathway analysis, and GSEA analysis were conducted on the FRDEGs to understand their enriched biological functions and pathways. Next, we constructed the protein-protein interaction (PPI) network. Results: A total of 312 genes were obtained, which were abnormally expressed in both two datasets. After intersecting with known FRGs, 14 FRDEGs were obtained, namely ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1. The results of the immune infiltration analysis showed that multiple gene expressions among 14 genes are correlated with immune cell infiltration. Conclusion: Fourteen ferroptosis genes (ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1) are involved in the occurrence and development of AKI, among which NDRG1 might be the core functional gene, and PPARA is expected to become the most effective therapeutic target gene.

Shenshuaifu Granule Attenuates Acute Kidney Injury by Inhibiting Ferroptosis Mediated by p53/SLC7A11/GPX4 Pathway.

Acute kidney injury (AKI) is a common clinical condition resulting in a rapid decline in renal function, and requires improvement in effective preventive measures. Ferroptosis, a novel form of cell death, is closely related to AKI. Shenshuaifu granule (SSF) has been demonstrated to prevent AKI through suppressing inflammation and apoptosis. This study aimed to explore whether SSF can inhibit ferroptosis in AKI. Active ingredients in SSF were detected through HPLC-MS/MS, and their binding abilities with ferroptosis were evaluated by molecular docking. Then, male C57/BL/6J mice were randomly divided into control, cisplatin, and cisplatin+SSF groups. In the latter two groups, mice were intraperitoneally injected with 20 mg/kg of cisplatin. For five consecutive days prior to cisplatin injection, mice in the cisplatin+SSF group were gavaged with 5.2 g/kg of SSF per day.72 h after cisplatin injection, the mice were sacrificed. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to evaluate renal function. H&E and PAS staining were used to observe pathological damage of kidney. Cell death was observed by TUNEL staining, and iron accumulation in kidneys of mice was detected by Prussian blue staining. Western blotting, immunohistochemistry, and immunofluorescence were used to investigate the presence of inflammation, oxidative stress, mitochondrial dysfunction, iron deposition, and lipid peroxidation in mouse kidneys. Active ingredients in SSF had strong affinities with ferroptosis. SSF reduced SCr (p<0.01) and BUN (p<0.0001) levels, pathological damage (p<0.0001), dead cells in the tubular epithelium (p<0.0001) and iron deposition (p<0.01) in mice with cisplatin induced AKI. And SSF downregulated macrophage infiltration (p<0.01), the expressions of high mobility group box 1 (HMGB1, p<0.05) and interleukin (IL)-17 (p<0.05), upregulated superoxide dismutase (SOD) 1 and 2 (p<0.01), and catalase (CAT, p<0.05), and alleviated mitochondrial dysfunction (p<0.05). More importantly, SSF regulated iron transport and intracellular iron overload and reduced the expression of ferritin (p<0.05). Moreover, it downregulated the expressions of cyclo-oxygenase-2 (Cox-2, p<0.001), acid CoA ligase 4 (ACSL4, p<0.05), and solute carrier family 7, member 11 (SLC7A11, p<001), upregulated glutathione peroxidase 4 (GPX4, p<0.01) and p53 (p<0.01), and decreased 4-hydroxynonenal (4-HNE) level (p<0.001). SSF attenuates AKI by inhibiting ferroptosis mediated by p53/SLC7A11/GPX4 pathway.

Overexpression of long noncoding RNA 4933425B07Rik leads to renal hypoplasia by inactivating Wnt/β-catenin signaling pathway.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a general term for a class of diseases that are mostly caused by intrauterine genetic development limitation. Without timely intervention, certain children with CAKUT may experience progressive decompensation and a rapid decline in renal function, which will ultimately result in end-stage renal disease. At present, a comprehensive understanding of the pathogenic signaling events of CAKUT is lacking. The role of long noncoding RNAs (lncRNAs) in renal development and disease have recently received much interest. In previous research, we discovered that mice overexpressing the lncRNA 4933425B07Rik (Rik) showed a range of CAKUT phenotypes, primarily renal hypoplasia. The current study investigated the molecular basis of renal hypoplasia caused by Rik overexpression. We first used Rapid Amplification of cDNA ends (RACE) to obtain the full-length sequence of Rik in Rik +/+;Hoxb7 mice. Mouse proximal renal tubule epithelial cells (MPTCs) line with Rik overexpression was constructed using lentiviral methods, and mouse metanephric mesenchyme cell line (MK3) with Rik knockout was then constructed by the CRISPR‒Cas9 method. We performed RNA-seq on the Rik-overexpressing cell line to explore possible differentially expressed molecules and pathways. mRNA expression was confirmed by qRT‒PCR. Reduced levels of Wnt10b, Fzd8, and β-catenin were observed when Rik was expressed robustly. On the other hand, these genes were more highly expressed when Rik was knocked out. These results imply that overabundance of Rik might inhibit the Wnt/β-catenin signaling pathway, which may result in renal hypoplasia. In general, such research might help shed light on CAKUT causes and processes and offer guidance for creating new prophylactic and therapeutic strategies.

THU280 Acute Interstitial Nephritis- A Complication Of Semaglutide Use

Abstract Disclosure: M. Alsayed Hasan: None. J. Doroshow: None. Background: With the widespread use of glucagon-like peptide 1 (GLP-1) agonists in diabetes, several cases have been reported of GLP-1 induced acute interstitial nephritis (AIN) with variable recovery in kidney function (1). Although it is a rare side effect, the primary management requires early identification and removal of the offending agent. Clinical Case: A 75-year-old male presented with a week of nausea, vomiting, abdominal pain, and reduced urine output. He was started on semaglutide 4 months prior to admission when his creatinine was 1.16 mg/dL. Initial lab abnormalities included an elevated blood urea nitrogen 119 mg/dL (n 8-20 mg/dL), elevated creatinine 13.8 mg/dL (n 0.7-1.3 mg/dL), anion gap acidosis with a CO2 of 15 mEq/L (n 22-32 mEq/L) and an anion gap of 18 (n&amp;lt;12), lipase 659 U/L (n 20-51 U/L). His urinalysis demonstrated too numerous to count red blood cells, 4-10 white blood cells, rare eosinophils and no casts or crystals. Urine culture was negative. The fractional excretion of sodium and urea were 5.56% and 56% respectively, consistent with intrinsic renal disease. CT of the abdomen and pelvis demonstrated peri-pancreatic inflammation. A follow up renal ultrasound showed normal echotexture with no hydronephrosis or renal calculi. His picture was concerning for pancreatitis and pre-renal/acute tubular necrosis from diuretic use and vomiting. Despite aggressive fluid resuscitation, there was minimal improvement in his creatinine. Further work up for his renal injury was negative for monoclonal antibodies on protein electrophoresis and immunofixation. An autoimmune work up was negative for antinuclear antibody, anti-double stranded DNA, antineutrophil cytoplasmic (ANCA) myeloperoxidase IgG, anti-proteinase 3 ANCA IgG, glomerular basement membrane antibody, hepatitis B and C antibodies, and HIV. Complements and immunoglobin G subclasses were normal. A renal biopsy was performed which showed active interstitial inflammation with eosinophils consistent with allergic interstitial nephritis without an immune complex mediated glomerular lesion. He was started on intravenous methyl prednisone for 3 days followed by a prednisone taper. His home metformin, ramipril and hydrochlorothiazide were discontinued on discharge. He was eventually started on mycophenolate as the creatinine did not return to baseline with steroids. Conclusion: AIN is a rare, yet serious complication of GLP-1 use that requires early identification and discontinuation of the medication. A rapid or unexplained decline in renal function after starting a GLP-1 should be evaluated early on with concern for AIN once volume depletion is ruled out (1). Reference: (1) Chaudhury N., Liarakos A., Gopalakrishnan K., Ayub W., Murthy N., Rao R. Antidiabetic medication-induced acute interstitial nephritis: case report and literature search. British Journal of Diabetes. 2021;21(2);228-32. Presentation: Thursday, June 15, 2023

Exploring the connection between types of acute kidney injury and chronic kidney disease

Acute kidney injury (AKI) is a common clinical condition characterized by a rapid decline in renal function. AKI is associated with significant morbidity and mortality, and many patients with AKI develop chronic kidney disease (CKD). Previous studies have examined the association between AKI and CKD; however, the relationship between AKI types and CKD development has not been thoroughly investigated. Therefore, a multi-center prospective observational study is required to investigate this relationship thoroughly. These findings may have significant implications for the early identification, prevention, and management of CKD in patients with a history of AKI.

Association of cumulative resting heart rate exposure with rapid renal function decline: a prospective cohort study with 27,564 older adults.

To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Dipeptidyl peptidase-4 inhibitor-related renal disease

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors are widely used to treat type 2 diabetes (T2D). Lowering blood glucose is expected also to reduce the progression of diabetic nephropathy. We experienced a patient with T2D who achieved good glycemic control with a DPP-4 inhibitor but experienced rapid deterioration of renal function. Therefore, we performed a retrospective study of similar patients treated at our hospital. MethodsOut of 56 patients with biopsy-proven diabetic nephropathy who underwent native kidney biopsy at Toranomon Hospital from January 2018 through December 2022, we selected 22 patients who had been receiving DPP-4 inhibitors for at least 9 months at the time of kidney biopsy. Of these patients, we evaluated 16 diagnosed with class IIa diabetic nephropathy according to Tervaert's pathologic classification. The yearly estimated glomerular filtration rate (eGFR) slope in the 16 patients was arranged from the highest to the lowest slope. Ten patients with a large eGFR slope had thrombotic microangiopathy (TMA)-like lesions characterized by glomerular endothelial cell proliferation and GBM duplication on kidney biopsy (group A), whereas the remaining 6 patients did not have TMA-like lesions (group B). ResultsGroup A had a median (interquartile range [IQR]) eGFR of 18.2 (16.2, 26.2) and a yearly median (IQR) eGFR slope of −11.2 (−17.6, −9.2) mL/min/1.73 m2 after of DPP-4 administration, whereas group B had a median (IQR) eGFR of 31.5 (21.9, 34.8) mL/min/1.73 m2 and a yearly median (IQR) eGFR slope of −1.6 (−3.1, −0.3). Renal function declined significantly more rapidly in group A than in group B, and proteinuria was higher in group A than in group B (median [IQR], 3.4 [2.6, 4.4] g/day vs 0.8 [0.4, 1.3] g/day, respectively). Five patients in group A progressed to dialysis during follow-up, but none of the patients in group B did. Median (IQR) hemoglobin A1c was 6.2 % (6.0 %, 6.6 %) in group A and 5.8 % (5.7 %, 6.6 %) in group B. ConclusionDPP-4 inhibitors promote vascular endothelial regeneration, but when this effect occurs in the glomerulus, glomerular endothelial cell proliferation leads to TMA-like lesions, which may cause an increase in proteinuria and rapid decline in renal function.

Engineered nanodrug targeting oxidative stress for treatment of acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function, and is associated with a high risk of death. Many pathological changes happen in the process of AKI, including crucial alterations to oxidative stress levels. Numerous efforts have thus been made to develop effective medicines to scavenge excess reactive oxygen species (ROS). However, researchers have encountered several significant challenges, including unspecific biodistribution, high biotoxicity, and in vivo instability. To address these problems, engineered nanoparticles have been developed to target oxidative stress and treat AKI. This review thoroughly discusses the methods that empower nanodrugs to specifically target the glomerular filtration barrier and presents the latest achievements in engineering novel ROS-scavenging nanodrugs in clustered sections. The analysis of each study's breakthroughs and imperfections visualizes the progress made in developing effective nanodrugs with specific biodistribution and oxidative stress-targeting capabilities. This review fills the blank of a comprehensive outline over current progress in applying nanotechnology to treat AKI, providing potential insights for further research.

A 5-Year Follow-Up Study to Explore Factors Associated with Rapid Kidney Function Decline Among Bus Drivers.

Owing to the stressful occupational characteristics, bus drivers have been reported to have a higher risk of renal dysfunction. However, the related factors associated with rapid kidney function decline among bus drivers have not been explored in the existing literature. Therefore, our research aimed to investigate factors related with rapid kidney function decline, and to explore the correlation of baseline SUA (serum uric acid), longitudinal changes in SUA, and rapid eGFR (estimated glomerular filtration rate) decline for bus drivers. This was a five-year cohort study in Shenzhen, China, between 2017 and 2021. We included 832 bus drivers with normal kidney function at baseline. Study subjects were stratified into four quartiles of change in eGFR, and rapid eGFR decline was regarded as the highest (4th) quartile of ΔeGFR (eGFR in 2017-eGFR in 2021). Univariable and multivariable logistic regressions were conducted to explore factors affecting rapid eGFR decline. The incidence of hyperuricemia among bus drivers was 37.7% in 2017 and 40.5% in 2021. The overall subjects had a median 5-year decrease in eGFR of 6.72 mL/min/1.73 m2, and individuals with increased SUA from normal to hyperuricemia group had the greatest decline of eGFR. Multivariate analysis showed bus drivers' age (Odds radio: OR, 1.04), elevated baseline eGFR (OR, 1.08), and SUA increase (OR, 1.38) were significantly associated with rapid eGFR changes. The high prevalence of hyperuricemia among bus drivers should warrant more attention from health professionals. Subjects' age, elevated baseline eGFR, and SUA increase were risk factors for rapid eGFR decline over 5-year. The findings can provide significant evidence for timely prevention and intervention to decrease the incidence of rapid renal function decline among bus drivers.

#4381 INCIDENCE AND FREQUENCIES OF HYPERKALEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE DATABASE STUDY FROM US CLINICAL CARE

Abstract Background and Aims Hyperkalemia (HK) is associated with significant risks for premature mortality, adverse clinical outcomes, and with a potentially more rapid decline of renal function. Reported numbers on the epidemiology of HK in patients diagnosed with chronic kidney disease (CKD) vary significantly and are unclear in real-world patients across different CKD stages, eGFR and UACR strata. We aimed to evaluate the occurrence of moderate to severe hyperkalemia episodes among a large, representative sample of patients with CKD from the US between 2009 and 2020. Method Using Optum Electronic Health Records data, we included patients with CKD between January 2009 and December 2020, who had at least two qualifying estimated glomerular filtration rate (eGFR) (15-60 ml/min/1.73 m2) and/or UACR values (≥30 mg/g) between 90 and 365 days apart. The second qualifying value was considered confirmatory and set as the index date. Patients had to have 365 days of baseline activity prior to index, be ≥18 years of age, and not show any diagnoses, procedures, or lab values of kidney failure or hemodialysis or kidney transplant during baseline. A HK episode was defined in two ways, (1.) as either a combination of two elevated inpatient or outpatient serum potassium values (sK+) ≥5.5 mmol/l, not longer than 7 days apart, or (2.) a combination of one elevated sK+ and the initiation of pharmacotherapy (e.g., i.v. calcium or insulin-glucose, nebulized albuterol, potassium binders) or a diagnostic code for HK, not longer than 3 days apart. We calculated relative frequencies and incidences of HK in the overall CKD study population and specific subgroups of interest. Results 1,771,900 patients met our selection criteria for CKD, with advanced stages 3 and 4 predominantly represented (85.7% and 10.2%, respectively). The cohort consisted of 57.7% females, 83.8% Caucasian and 9.8% African American. Most common baseline comorbidities were hypertension (68.5%), hyperlipidemia (55.1%) and T2D (34.2%). 69.3% of patients were prescribed antihypertensives, 45.7% statins and 45.6% antiarrhythmics. 99.1% of patients had at least one baseline potassium measurement with values averaging 4.3 mmol/L (median, 4.3; IQR, 4.0-4.55). During an average follow up 3.9 years, 220,339 (12.4%) patients experienced at least one episode of hyperkalemia. Of those, 69.3%, 17.5%, and 13.2% showed one, two, and three or more HK episodes, respectively. Across all patients with CKD, the mean incidence rate was 3.37 (95% CI, 3.36-3.38) cases per 100 patient years (PYs). HK incidence correlated with lower eGFR and increased UACR values, with rates of 1.32 (1.25-1.39), 2.48 (2.40-2.55), 3.00 (2.99-3.01) and 8.80 (8.71-8.88) cases/100 PYs for patients with CKD stage 1, stage 2, stage 3 and stage 4, respectively. Highest incidence rates (13.81; 12.96-14.70) were found in patients with UACR values ≥3500, irrespective of their eGFR value. In addition, across disease-related subgroups, significantly higher incidence rates were found in patients co-diagnosed with T2D (5.43; 95% CI, 5.40-5.47) and HF (8.70; 8.62-8.77), and sMRA users (7.66; 7.57-7.76) at baseline. Conclusion Our contemporary findings demonstrate that HK is common in patients with CKD undergoing routine clinical care in the US, and it is notable in patients with reduced eGFR and elevated UACR. In addition, HK was more predominant in patients with T2D, heart failure or sMRA use, emphasizing a need for more routine sK+ monitoring in patients with these risk factors. Further research is needed to assess additional intrinsic risks, clinical consequences and management approaches of HK in patients with CKD to further inform clinical practice.

#5438 SERUM TUMOUR NECROSIS FACTOR RECEPTOR 1 PROTEIN ACCURATELY PREDICTS RAPID DISEASE PROGRESSION IN DIABETIC KIDNEY DISEASE

Abstract Background and Aims Diabetic kidney disease (DKD) has an enormous disease burden globally. In the area of personalised medicine, biomarker is set to play an important role in the management of DKD. Prior studies have reported the possible association of Tumour Necrosis Factor Receptor 1 (TNFR1), Dickkopf-3 (DKK3) and B cell lymphoma 3 (BCL-3) with the pathogenesis of DKD. However, there had been no prior studies that investigate the association of these biomarkers as prognostic markers for DKD disease progression. Hence, we aim to investigate the correlation of these biomarkers with renal progression among the diabetic population with and without kidney disease. Method A total of 156 subjects were recruited, which consisted of 64 control vs 92 patients with DKD. The principal outcomes of this study were rapid renal decline (doubling of serum creatinine, renal decline &amp;gt; 5ml/min/year and &amp;gt; 10 ml/min/year) and their association with serum TNFR1, BCL-3 and urine DKK3. A bivariate analysis was used to test the association of rapid renal decline, and sensitivity and specificity were used to test the validity of the level of the biomarkers with outcomes. Results The baseline parameters for both case and control: age 50.19±9.22 vs 60.35±13.73, serum albumin 38.97±2.07 vs 33.01±8.98g/l (p&amp;lt; 0.001), eGFR 117.96±31.94 vs 38.00±22.04 ml/min/ 1.73 m2 (p&amp;lt;0.001), serum creatinine 77.34±14.15 vs 247.45±148.09 µmol/L (p&amp;lt; 0.00), uPCI g/day 0.001±0.0 vs 4.268±5.29 (p&amp;lt; 0.001), HbA1c 7.83±1.88 vs 7.86±1.78 mmol/L (p = 0.942), sTNFR 11781.91±337.46 vs 4394.03±1960.06 pg/mL (p&amp;lt;0.001), uDKK3/creatinine 132.84±37.61 and 1243.63±495.27 pg/mg (p&amp;lt; 0.001), and sBCL3 194.60±32.81 vs 490.17±259.02 pg/mL(p&amp;lt;0.001). During the follow-up, there was a significant association of sTNFR1 with rapid renal decline &amp;gt; 5ml/min/year, &amp;gt; 10 ml/min/year and doubling of serum creatinine [p &amp;lt; 0.003 [IQR = 2891.50-4885.75], p&amp;lt; 0.009 [2891.50-4885.75], p&amp;lt; 0.001 [2891.50-4885.75] but not with uDKK3 and sBCL-3 (Table 1). Specificity and sensitivity analyses on the performance of the biomarkers versus outcomes were highly significant (Figure 1). Conclusion Despite TNFR1, BCL-3 and urine DKK3 were all elevated in our DKD patients, there was a strong association between incident serum TNFR1 level and the subsequent deterioration of renal function which has not been reported in the literature before. In addition, TNFR1 level had consistently picked up cases of DKD that would experience rapid renal progression, be it &amp;gt; 5ml/min/year, &amp;gt; 10 ml/min/year or doubling of serum creatinine. The correlation studies have shown TNFR1 level high sensitivity, and specificity of TNFR1 on the rapid renal function decline. Thus, we believe in our DKD population, targeting TNFR1 pathway could be a promising tool in monitoring and treating our DKD population.

Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients.

Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients. We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%. During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 (p value = 0.17), FEP/FGF23 (p value = 0.78), TRP (p value = 0.62) and Klotho (p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 (p = 0.048) and remained significant in multivariable analysis. T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.

Risk stratification for worsening renal function and renal decline in heart failure patients with reduced ejection fraction after sacubitril/valsartan treatment

BackgroundIn the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. MethodsBetween 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. ResultsAmong the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71–0.78 and 0.69–0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. ConclusionsThis study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.