Development Of Chronic Kidney Disease Research Articles

Long-term renal outcomes of children with cancers treated with platinum-based chemotherapy: A retrospective chart analysis.

Platinum-based chemotherapy is a mainstay of treatment for many childhood cancers but is associated with acute nephrotoxicity and long-term ototoxicity. There is emerging evidence of long-term renal complications. This study aimed to assess the prevalence of chronic kidney disease (CKD) in children treated with platinum chemotherapy (cisplatin and carboplatin) and identify potential risk factors for the development of CKD. We conducted a retrospective review of children diagnosed with hepatoblastoma, osteosarcoma, neuroblastoma, or medulloblastoma who received platinum chemotherapy over a 16 year timeframe. Patients were excluded if they did not have at least 3 years follow up data, died within 3 years of platinum chemotherapy, or if they relapsed. Clinical data were collected at baseline (first dose), 1 year, and at most recent follow up. Of 328 treated patients, 147 met the inclusion criteria and were followed for a mean of 8.1 years (range 3-15.7 years). The median age at first dose was 3.7 years (IQR 1.7-9.6 years). CKD ≥grade 2 was present in 53(36%) at last follow up and 15(10%) had tubular dysfunction. A history of acute kidney injury at any time during treatment was associated with CKD (OR 3.12 CI 1.07-9.12, p =0.04). On multivariable analysis older age at platinum therapy (OR 1.2, CI 1.1-1.4, p = 0.004) and a high aminoglycoside or vancomycin trough level (OR 4.3, CI 1.9-9.7, p<0.001) were risk factors for CKD. The high rate of CKD in children treated with platinum chemotherapy warrants long-term follow-up and screening for progressive disease.

Black Garlic Supplementation and Glomerular Protection in Hyperuricemic Rats: A Study on Kidney Health Prevention

Introduction: Hyperuricemia is a significant risk factor for the development of chronic kidney disease. Excessive uric acid can deposit in the kidneys, triggering inflammatory reactions and oxidative stress, leading to structural damage in the glomeruli. Black garlic, with its antioxidant and bioactive compounds, has the potential to protect the kidneys from hyperuricemia-induced damage. Our objective is to evaluate the effect of black garlic supplementation on the histopathological features of glomeruli in a hyperuricemic rat model. Methods: This study was an analytical observational study using Biological Remnant Materials (BRM) from a previous study. The sample consisted of 30 male Sprague-Dawley rats divided into 5 groups: disease control, drug control (allopurinol), and 3 black garlic dose groups (240 mg/day, 480 mg/day, and 960 mg/day). Data were collected through histopathological examination of kidney tissue using the glomerular damage scoring method (0-3). Data analysis was performed using one-way ANOVA and post hoc LSD tests. Results: Black garlic demonstrated protective effects on the histopathological features of glomeruli in hyperuricemic rats. The 240 mg/day dose showed the most significant improvement in kidney health, reducing glomerular damage scores compared to the disease control group (p &lt; 0.05). These findings suggest that black garlic can serve as a preventive agent against kidney complications caused by hyperuricemia. Conclusion: Black garlic provides protective effects on glomerular histopathology in hyperuricemic rats, with the 240 mg/day dose being the most effective. These results suggest potential use for black garlic in preventing kidney complications in hyperuricemia.

Pathophysiology of vascular ageing and the effect of novel cardio-renal protective medications in preventing progression of chronic kidney disease in people living with diabetes.

Among people with diabetes those with chronic kidney disease (CKD) have a reduced life expectancy with increased risk of cardiovascular disease (CVD) a major contributor to morbidity and mortality. CKD related to diabetes is growing worldwide and is one of the leading causes of kidney failure globally. Diabetes is associated with accelerated vascular ageing and the related mechanisms and mediators that drive the progression of CKD and CVD disease in people with diabetes may help provide insights into the pathophysiology of cardio-renal complications and guide treatment interventions in people with diabetes. We conducted a narrative review of the literature using PubMed for English language articles that contained keywords that related to diabetes, chronic or diabetic kidney disease, ageing, cellular senescence, arterial stiffness, Klotho and sirtuins, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, renin angiotensin aldosterone system (RAAS) and glucagon-like peptide-1 (GLP-1) receptor agonists. Progressive kidney disease in diabetes is associated with accelerated ageing driven in part by multiple processes such as cellular senescence, inflammation, oxidative stress and circulating uremic toxins. This accelerated ageing phenotype contributes to increased arterial stiffness, endothelial dysfunction, cognitive decline and muscle wasting, thereby elevating morbidity and mortality in individuals with diabetes and CKD. Deficiency of the kidney-derived anti-ageing hormone Klotho and reduced sirtuin levels play pivotal roles in these ageing pathways. Dietary, lifestyle and pharmacological interventions targeting vascular ageing may help reduce the progression of CKD and associated CVD in people with diabetes. The current standard of care and pillars of treatment for kidney disease such as RAAS inhibitors, SGLT-2 inhibitors and GLP-1 receptor agonists all influence pathways involved in vascular ageing. A multifactorial intervention to prevent the development of CKD by targeting traditional risk factors as well as treatment with novel agents with cardio-renal beneficial effects can prevent accelerated ageing and extend lifespan in people with diabetes.

Cholecystectomy Increases the Risk of Chronic Kidney Disease: A Nationwide Longitudinal Cohort Study.

Background/Objectives: Growing evidence suggests that cholecystectomy is associated with adverse health outcomes, including the development of metabolic diseases. However, data on the association between cholecystectomy and kidney disease are limited. The present study aimed to investigate the association between cholecystectomy and chronic kidney disease (CKD) using a nationwide longitudinal cohort. Methods: Participants aged ≥20 years with cholecystectomy between 2010 and 2014 (n = 116,748) and age- and sex-matched control participants without cholecystectomy (n = 116,748) were analyzed using the Korea National Health Insurance Service data. The adjusted hazard ratios (aHRs) were calculated for incident CKD in the cholecystectomy group compared with the nonoperative controls. Results: A total of 233,496 participants were included (mean age, 54.7 ± 12.7 years; 52.6% men). During the mean follow-up period of 4.8 ± 1.7 years, 6450 patients (5.5%) were newly diagnosed with CKD in the cholecystectomy group. Cholecystectomy was an independent risk factor for the development of CKD after adjustment for confounders, including age, sex, income, health behaviors, and comorbidities. The risk of CKD was 21% higher in the cholecystectomy group compared to the non-cholecystectomy group (aHR, 1.21; 95% CI, 1.17-1.26). The increased risk of CKD in the cholecystectomy group was consistently significant when a stratified analysis by age, sex, and presence or absence of comorbidities was conducted. Conclusions: Cholecystectomy was independently associated with an increased risk of developing CKD in a nationwide population-based study. Therefore, careful and long-term monitoring of the risk of CKD after cholecystectomy is necessary.

Investigating the cause of cardiovascular dysfunction in chronic kidney disease: capillary rarefaction and inflammation may contribute to detrimental cardiovascular outcomes.

Myocardial ischemia-reperfusion (IR) injury is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The most frequently used and representative experimental model is the rat dietary adenine-induced CKD, which leads to CKD-associated CVD. However, the continued intake of adenine is a potential confounding factor. This study investigated cardiovascular dysfunction following brief adenine exposure, CKD development and return to a normal diet. Male Wistar rats received a 0.3% adenine diet for 10weeks and normal chow for an additional 8weeks. Kidney function was assessed by urinalysis and histology. Heart function was assessed by echocardiography. Sensitivity to myocardial IR injury was assessed using the isolated perfused rat heart (Langendorff) model. The inflammation profile of rats with CKD was assessed via cytokine ELISA, tissue histology and RNA sequencing. Induction of CKD was confirmed by a significant increase in plasma creatinine and albuminuria. Histology revealed extensive glomerular and tubular damage. Diastolic dysfunction, measured by the reduction of the E/A ratio, was apparent in rats with CKD even following a normal diet. Hearts from rats with CKD had significantly larger infarcts after IR injury. The CKD rats also had statistically higher levels of markers of inflammation including myeloperoxidase, KIM-1 and interleukin-33. RNA sequencing revealed several changes including an increase in inflammatory signaling pathways. In addition, we noted that CKD induced significant cardiac capillary rarefaction. We have established a modified model of adenine-induced CKD, which leads to cardiovascular dysfunction in the absence of adenine. Our observations of capillary rarefaction and inflammation suggest that these may contribute to detrimental cardiovascular outcomes.

Serum Osmolality as a Predictor of Renal Function Decline: A Retrospective Cohort Study.

Background and Aims: Dehydration is a prevalent and costly healthcare concern, linked to heightened risks of acute kidney injury and in-hospital mortality. Despite its significance, limited evidence exists regarding its prevalence and correlation with renal function decline in apparently healthy individuals. This retrospective cohort study aimed to investigate the prevalence and association of dehydration with renal function decline and the development or progression of chronic kidney disease (CKD) in the general population. Methods: The medical records of subjects undergoing annual health check-ups from 2016 to 2019 at a single center in Taiwan were analyzed, and those with CKD stage V, insufficient data, or an increased estimated glomerular filtration rate (eGFR) were excluded. Serum osmolality, eGFR, and relevant parameters were measured. Logistic regression and Kaplan-Meier analyses were used to assess associations between osmolality and CKD-related outcomes. Results: Among the 4449 eligible subjects, those in the higher osmolality quartiles had an elevated risk of CKD or CKD progression. Multivariate analyses identified age, systolic blood pressure, serum osmolality, uric acid, proteinuria, and a history of diabetes as independent risk factors, with high-density lipoprotein being protective. Cumulative incidence curves demonstrated a significant increase in the risk of CKD with increasing osmolality levels. Restricted cubic spline analyses confirmed a nonlinear relationship between osmolality and CKD risk. Conclusions: Elevated serum osmolality independently predicted renal function decline and CKD development in apparently healthy individuals, and this effect persisted after adjusting for established risk factors. Our findings underscore the importance of addressing dehydration as a modifiable risk factor for CKD.

Longitudinal and cross-sectional associations of NT-proBNP with kidney function and chronic kidney disease: results from KORA cohort studies

Abstract Background Chronic kidney disease (CKD) and cardiovascular disease (CVD) exhibit a bidirectional and complex relationship, and share common risk factors and mechanisms of disease development. Thus, important CVD-related biomarkers, such as N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), may serve as a biomarker for CKD development. Purpose We aimed to investigate the cross-sectional and longitudinal associations of NT-proBNP with kidney function and CKD in data from two population-based cohort studies. Methods We included 5854 men and women, aged 25-74 years, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort studies S3 and S4, and their 1-2 subsequent follow-up surveys, with a median follow-up time of 9.4 and 13.4 years, respectively. Kidney function was assessed by 3 estimated glomerular filtration rate (eGFR) assessments, calculated using creatinine (eGFRcr), cystatin C, and combined creatinine and cystatin C. Serum NT-proBNP was logarithmically transformed followed by Z-score standardization and categorized into 4 groups (G1-4), &amp;lt;48.6, 48.6-125, 125-300, and ≥300 pg/ml. In cross-sectional analysis, linear regression and logistic regression were used to estimate β/odds ratio (OR) and their 95% confidence intervals (CIs) of continuous eGFR or prevalent CKD. For longitudinal analysis of repeated eGFR measurements during follow-up (5854 participants, 11870 observations), linear mixed-effects models were used. For incident CKD associations, interval-censored Cox regression models were performed in participants free of CKD at baseline. Results In cross-sectional analyses, higher NT-proBNP levels were associated with lower eGFR and higher prevalence of CKD across all 3 eGFR assessments. For example, results based on eGFRcr showed that the fully-adjusted β (95% CIs) for per 1 SD increase in log-transformed NT-proBNP were -1.03 (-1.42, -0.64) and -7.01 (-8.93, -5.09) 60 ml/min/1.73m2 for G4 compared to G1, respectively. Corresponding OR (95% CIs) were 2.22 (1.81, 2.74) and 13.8 (5.76, 36.4), respectively. In longitudinal analyses, participants with higher baseline NT-proBNP had a faster decline in eGFR during follow-up. The fully-adjusted β (95% CIs) for 5-year eGFRcr decline were -0.67 (-0.87, -0.47) per 1 SD increase, and -0.37 (-0.79, 0.05), -1.53 (-2.18, -0.88), -4.24 (-5.57, -2.90) 60 ml/min/1.73m2/year for G2-4. Higher NT-proBNP levels were associated with higher incident CKD risks. For associations with incident creatinine-based CKD, hazard ratio (95% CIs) were 1.16 (1.00, 1.33) per 1 SD increase and 1.03 (0.77, 1.38), 1.07 (0.75, 1.52), and 1.81 (1.07, 3.04) for G2-4. Conclusions We found associations of higher NT-proBNP with lower kidney function and higher CKD prevalence. Moreover, higher baseline NT-proBNP levels were associated with faster kidney function decline and higher incident CKD risks. Our findings indicate the potential utility of NT-proBNP as a biomarker of kidney health.Figure 1.Cross-sectional associationsFigure 2.Longitudinal associations

Contribution of ECT2 to Tubulointerstitial Fibrosis in the Progression of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a complex disorder resulting from a combination of various environmental and genetic factors. Considerable efforts have been dedicated to elucidating its etiological mechanisms. Nevertheless, the pathogenic mechanism of CKD remains poorly understood, which hinders the development of effective therapeutic strategies. In this study, we aimed to identify novel mediators that could contribute to the development of CKD. The ClinVar, STRING, MEME Suite, TRRUST, bedtools, GEO, and R Studio databases and software were used to analyze their common features and investigate potential CKD disease genes. Transcriptomic analysis, immunohistochemistry, qRT-PCR, and Western blotting were utilized to further validate the role of ECT2 in kidney fibrosis. In total, 26 CKD disease genes were obtained from the ClinVar database, and the STRING, MEME Suite, TRRUST, bedtools, and GEO databases and software were used to analyze their common properties and explore potential CKD disease genes. Epithelial cell transforming sequence 2 (ECT2), cyclin B 1, caspase 7 and collagen alpha-1 (IV) were identified as potential candidates for CKD progression. Weighted correlation network analysis (WGCNA) subsequently revealed the relationships between potential genes and CKD. The results of the transcriptomic analysis further confirmed that ECT2 expression was greater in the kidney tissue of CKD patients than in that of healthy controls. Next, immunohistochemistry and Western blotting demonstrated that ECT2 was predominantly expressed in the renal tubules of a unilateral ureteral obstruction (UUO) mouse model. Consistently, in vitro experiments revealed that ECT2 was upregulated in TGF-β1-treated HK-2 cells. Moreover, ECT2 overexpression or knockdown in HK-2 cells altered the intensity of fibrosis markers. ECT2 significantly affects the development and progression of CKD, particularly in association with tubulointerstitial fibrosis.

Stenosis of the glomerulotubular neck in progressive chronic kidney disease.

Morphology and morphometric evaluation of lesions beyond conventional parameters can inform the pathophysiology of chronic kidney disease (CKD). We sought to determine whether the occurrence of glomerulotubular neck stenoses associates with progressive CKD. We evaluated the normal parenchyma from radical nephrectomies removed for tumor between 2000 and 2021 and analyzed cortex for stenoses of the glomerulotubular neck. Stenosis of the glomerulotubular neck is defined a focal narrowing for which the draining tubule has a greater diameter than at the neck. Progressive CKD was defined as dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73m2 or sustained 40% decline from the post-nephrectomy eGFR. Each case of progressive CKD was age-sex-matched to 2 controls without progressive CKD. Logistic regression models assessed the risk of progressive CKD with stenotic necks adjusting for other histological features, kidney function, and CKD risk factors. There were 65 cases with a mean of 255 glomeruli and 130 controls with a mean of 329 glomeruli. Among both cases and controls, 5% of glomeruli showed visible glomerulotubular necks. The proportion of necks that were stenotic was higher in cases than controls (35% vs. 11%, p<0.0001). Stenotic necks associated with progressive CKD independent of other histologic and clinical characteristics. Glomerulotubular neck stenosis is associated with development of progressive CKD.

FUNCTIONAL STATE OF RENAL PARENCHYMA IN CHILDREN WITH DYSMETABOLIC NEPHROPATHY

Abstract. Metabolic nephropathy in children is a relevant issue in our time, as the prevalence of this disease is increasing. Negative consequences of metabolic nephropathy include a gradual deterioration of kidney function. A significant aspect is the fact that metabolic nephropathy can lead to the development of chronic kidney disease in children. Chronicity requires continuous medical monitoring and treatment to support kidney function and prevent further complications, such as renal insufficiency and other metabolic disorders. There is no doubt that one of the leading pathogenetic factors in kidney dysfunction is hypoxia. It can be caused by both hemodynamic disturbances associated with renal pathology and tissue respiration disorders in congenital dysplasia of the kidney's connective tissue, which arises in the embryo under the influence of epigenetic factors in utero and is further exacerbated by various epigenetic factors in postnatal life. Purpose of the work to investigate the functional state of kidney parenchyma in children with dysmetabolic nephropathy. Materials and methods. Two groups of children were examined: those with a complicated course of dysmetabolic nephropathy, a history of inflammatory episodes of the urinary system organs (Group I - UN, 52 children), and dysmetabolic nephropathy with persistent crystalluria (Group II - DN, 56 children). A control group consisted of 65 healthy children. Tubular reabsorption, as a partial function of the proximal segment of the nephrons, was assessed based on urinolysis test data, specifically the levels of excretion of inorganic phosphates, proteinuria, amino acids, reduced sugars (maltose, sucrose, fructose by Benedict's test), glucose (by Gaines's test), and calcium (by Sulcovitch's test). The level of creatinine and glycosaminoglycan (GAG) excretion in daily urine in children with dysmetabolic nephropathy was determined and compared with data from healthy children in the control group. Research results. In children from both observation groups, a significantly high frequency of hyperphosphaturia (94.23% and 96.42%), calciuria (94.23% and 89.28%), glucosuria (78.85% and 73.21%), increased excretion of amino acids in the urine (40.38% and 37.5%), microproteinuria (32.69% and 28.57%), and increased excretion of reduced sugars (28.85% and 26.79%) were observed. The daily excretion of creatinine, glycosaminoglycans, and oxypyrrolidine in the urine of children with dysmetabolic nephropathy indicates a significantly reduced level of creatinine in the daily urine in the majority of children in Group I (0.56±0.19 g/L, 80.77% of those examined) and more than half of the children in Group II (0.83±0.08 g/L, 57.14% of those examined), compared to the data from healthy children in the control group (1.25±0.75 g/L, 0.0%). Conclusions. The analysis of the functional state of the kidney tissue in oxalate dysmetabolic nephropathy in children allows us to testify to the presence of tubular and glomerular partial renal tissue failure. Significant decreases in creatinine excretion and increased excretion of glycosoaminoglycans in the urine and significantly higher levels of oxyproline in the urine indicate the presence of glomerular type partial renal failure in oxalate dysmetabolic nephropathy in children and the presence of undifferentiated dysplasia of the renal connective tissue with the onset of its sclerosis with subsequent transition to interstitial nephritis. The presence of these changes in the vast majority of children with complicated course of oxalate dysmetabolic nephropathy in the period of clinical and laboratory remission of the inflammatory process indicates the priority of renal connective tissue dysplasia and paucity of renal failure in the pathogenesis of dysmetabolic nephropathy and its severity in children. Indicators of oxyproline creatinine, glycosoaminoglycans and oxyproline excretion can be used as epigenetic markers of susceptibility to dysmetabolic nephropathy in general and its more severe course in particular. Keywords: dysmetabolic nephropathy, functional state, kidney parenchyma, nephron.

Slowing the progression of diabetic and non-diabetic kidney disease: A summary of the current evidence base for sodium-glucose co-transporter-2 inhibitors.

The global prevalence of chronic kidney disease (CKD) is approximately 9%. CKD is predicted to become the fifth largest global cause of death by 2040. Moreover, CKD causes disability, diminished quality of life and poses a high cost to healthcare systems. Delaying the development and progression of CKD is therefore of the utmost importance. Several kidney-specific outcome trials on sodium-glucose co-transporter-2 inhibitors (SGLT-2s) have recently provided a paradigm shift in the treatment of people with CKD, with or without diabetes, as these agents have been shown to reduce the progression of CKD on top of maximally tolerated renin-angiotensin-aldosterone system (RAAS) blockade. The relative benefit and safety of SGLT-2is seems to be consistent across ethnicities, ages and frailty categories; however, this needs to be tested in dedicated clinical trials. Guidelines make clear recommendations for the prescription of SGLT-2is and RAAS inhibitors as standard of care for people with CKD. Their combination with other newer antidiabetic agents may provide further benefits by targeting different components of CKD mechanisms. Dedicated randomized controlled trials are needed to test whether combination with other agents could extend the use of SGLT2is and identify people in whom a combination of drugs may be most effective. Increased efforts to implement the guidelines on treatment with SGLT-2is for people with CKD are needed, particularly in those at the highest risk of adverse outcomes and without type 2 diabetes. Moreover, strategies to target the equitable use of SGLT-2is are needed.

Relationship of body mass index and kidney outcomes in patients with primary glomerulonephritis: A systematic review and meta-analysis.

Primary glomerulonephritis, is a major contributor to the development of chronic kidney disease and end-stage renal disease. Previous studies on the relationship between overweight/obesity with primary glomerulonephritis in the chronic kidney disease was inconsistent. This study aimed to systematically review and meta-analyze the relationship between body mass index and adverse kidney outcomes in patients with primary glomerulonephritis. PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure were searched. Patients were divided into an overweight/obesity group (group O) and a non-overweight/obesity group (group N) according to their body mass index values. Twenty-six studies with 11,038 patients were selected. Patients in group O had deteriorated baseline characteristics, including worse baseline estimated glomerular filtration rate (weighted mean differences [WMD] = -5.99), higher Scr (WMD = 7.34), uric acid (WMD = 47.53), 24-hour proteinuria (WMD = 0.40), and a higher prevalence rate of hypertension (odds ratio, OR = 2.70) and diabetes mellitus (OR = 2.644). On the histopathologic level, patients in group O had a significantly lower total glomerular number (WMD = -2.30); however, no difference was observed in mesangial cell proliferation, endocapillary hypercellularity, crescents, sclerosis, and tubular atrophy/interstitial fibrosis between the 2 groups. The incidence of adverse renal outcomes in the 2 groups was similar (OR = 0.96). The meta-analysis of hazard ratios from Cox regressions indicated a strong association between overweight/obesity and poor renal outcomes in glomerulonephritis (HR = 1.17). Overweight/obesity glomerulonephritis patients had remarkably poor baseline clinicopathological characteristics. Being overweight or obesity would likely impact the progression of primary glomerulonephritis but not serious enough to contribute to significant poor renal outcomes, which could be prevented by aggressive therapy.

Evaluation of urinary podocin and nephrin as markers of podocyturia in dogs with leishmaniosis

BackgroundRenal disease is the main cause of death in canine leishmaniosis. Detection of an active glomerular injury is important to identify early renal damage and to prevent the development of chronic kidney disease. Podocyturia can indicate renal injury, and podocyte-associated molecules such as podocin and nephrin can be used to identify podocyturia. The purpose of the study was to evaluate urinary podocin and nephrin concentrations in dogs with leishmaniosis as markers of podocyturia.MethodsA total of 35 healthy dogs and 37 dogs with leishmaniosis were enrolled in the study. Dogs with leishmaniosis were classified according to the staging of the International Renal Interest Society (IRIS). Urinary podocin and nephrin concentrations were measured in all dogs with a validated enzyme-linked immunosorbent assay test and normalized to creatinine (uPoC and uNeC, respectively). The demographic, clinical, and laboratory data from both groups were analyzed and compared. Subsequently, the laboratory results were analyzed and compared according to IRIS staging in dogs in IRIS stage I and dogs in IRIS stage II + III + IV. The Pearson’s correlation test evaluated the relationship between urinary markers of podocyturia.ResultsCompared with healthy dogs, lower urinary podocin [median values (IQR): 15.10 (11.75–17.87) ng/ml versus 8.63 (7.08–13.56) ng/ml; P < 0.01] and nephrin [median values (IQR): 3.2 (3.62–5.43) ng/ml versus 2.67 (2.06–3.44) ng/ml; P < 0.01] were found in infected sick dogs. No significant differences were observed in the uPoC and uNeC between the two groups. Urinary nephrin and podocin concentrations were higher in healthy dogs and in dogs in IRIS stage I (both P < 0.05) compared with dogs in IRIS stages II + III + IV. No significant differences were found for uPoC and uNeC between healthy dogs and dogs with leishmaniosis in different IRIS clinical stages.ConclusionsDogs with leishmaniosis had a low concentration of podocin and nephrin in more advanced IRIS clinical stages, when kidney disease was more severe compared with healthy dogs and dogs in IRIS stage I with mild disease. Urinary nephrin was detectable for the first time in healthy non-infected dogs.Graphical

New Markers of Early Kidney Damage in Children and Adolescents with Simple Obesity

The impact of obesity on kidney injury and the development of chronic kidney disease (CKD) is well documented. Unfortunately, the early stages of CKD are asymptomatic, leading to a delayed diagnosis and a worse prognosis. There is a need for more sensitive indicators of kidney damage than those currently used. We aimed to assess the usefulness of serum t-CAF, urinary netrin-1, α-GST, π-GST, calbindin, and calprotectin as biomarkers of early kidney damage in obese children and to investigate the relationship between these indicators and the degree of obesity. A total of 125 simple obese, normoalbuminuric children and 33 non-obese children as controls were selected. Patients were divided into 2 subgroups according to SDS BMI (I: 2 ≤ 4, II: &gt;4). Serum t-CAF was significantly higher in the obese group compared to the controls, as were urinary α-GST, netrin-1, π-GST, and calprotectin. No difference was found between the two obese groups. In normoalbuminuric obese children and adolescents without significant metabolic disorders, serum t-CAF may be a new biomarker for the early detection of renal dysfunction, and urinary netrin-1, α-GST, π-GST, and calprotectin may be better indicators for the detection of early tubular damage, independent of the severity of obesity.

Association of Urinary Sodium, Potassium, and the Sodium-to-Potassium Ratio with Impaired Kidney Function Assessed with 24-H Urine Analysis.

Background: Albuminuria and albumin excretion rate (AER) are important risk factors for chronic kidney disease (CKD) development. Despite the extensive evidence of the influence of sodium and potassium on cardiovascular health, the existing evidence regarding their impact on albuminuria and kidney disease is limited and inconsistent. Our study aimed to assess the correlation between urinary sodium and potassium excretion, and the sodium-to-potassium ratio (Na/K ratio) with impaired kidney function, particularly the AER and albuminuria. Materials and Methods: Data were collected from the Lithuanian NATRIJOD study. A total of 826 single 24-h urine samples from individuals aged 18 to 69 were collected and analyzed for their sodium and potassium levels, Na/K ratio, and AER. Albuminuria was defined as an AER exceeding 30 mg/24 h. Results: The participant mean age was 47.2 ± 12.1 years; 48.5% of the participants were male. The prevalence of albuminuria was 3%. Correlation analysis revealed a positive correlation between AER and urinary sodium excretion (rs = 0.21; p < 0.001) and urinary potassium excretion (rs = 0.28; p < 0.001). In univariate linear regression analysis, sodium and potassium excretion and the Na/K ratio were significant AER predictors with β coefficients of 0.028 (95% CI: 0.015; 0.041; p < 0.001), 0.040 (95% CI: 0.003; 0.077; p = 0.035), and 1.234 (95% CI: 0.210; 2.259; p = 0.018), respectively. In the multivariable model, only urinary sodium excretion remained significant, with a β coefficient of 0.028 (95% CI: 0.016; 0.041). Potential albuminuria predictive factors identified via univariate logistic regression included urinary sodium excretion (OR 1.00; 95% CI: 1:00; 1.01) and the Na/K ratio (OR 1.53; 95% CI: 1.11; 2.05). However, these factors became statistically insignificant in the multivariate model. Conclusions: Urinary sodium and potassium excretion and the Na/K ratio are significantly associated with kidney damage, considering the assessed 24-h albumin excretion rate and presence of albuminuria content.

8327 Risk Of Chronic Kidney Disease In Subjects With Metabolic Dysfunction-Associated Fatty Liver Disease Or Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Study

Abstract Disclosure: E. Rhee: None. H. Kwon: None. S. Park: None. W. Lee: None. Background: Recently, the term non-alcoholic fatty liver disease (NAFLD) is replaced by a new term, metabolic dysfunction-associated liver disease (MASLD), with a new definition made by a modified Delphi process led by three large pan-national liver associations. In this study, we aimed to analyze the risk for chronic kidney disease (CKD) development in those with MASLD defined by the new definition and metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Among 52,606 participants (mean age 35.4 years) in the health checkup program from 2002 to 2019, in whom at least 10 health checkups were performed, after strict exclusion, 48,751 participants were enrolled and analyzed the development of CKD defined by estimated glomeruls filtration lower than 60 mL/min/1.73m2) during a median of 14.7 years of follow-up. The presence of MAFLD was defined by presence of hepatic steatosis plus one of the three criteria of overweight or obese, type 2 diabetes or presence of ≥2 metabolic risk abnormalities. MASLD was defined by presence of hepatic steatosis plus at least 1 of 5 cardiometabolic risk factors. Results: At baseline, 12,773(26.2%) participants had MAFLD and 35,359(74.58%) had MASLD. During the follow-up period, 849(1.7%) participants developed CKD. In participants with MAFLD, 345(2.7%) participants developed CKD, and in participants with MASLD, 609(1.7%) developed CKD. After adjustment for age and sex, the hazard ratio(HR) of CKD was 1.44 (95% confidence interval [CI] 1.25-1.66) for MAFLD, and 1.25(95% CI 1.07-1.47) for MASLD. Both definition predicted development of CKD nicely (Harrell’s C-index: 0.79(0.77-0.81) for MAFL and MASLD) Conclusions: The participants with MAFLD and MASLD showed significantly increased risk for CKD during a median of 15 years of follow-up. Both criteria showed nice predictability for CKD. Presentation: 6/1/2024

Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation.

This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury (AKI) group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (P<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (P<0.05). This study elucidated the optimal tacrolimus through level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Characteristics of risk factors and molecular genetic parameters in children with chronic kidney disease

Introduction. Information about the health status of children with nephrological pathology includes many manifestations of functional system disorders. However, early diagnosis of chronic kidney disease (CKD) is rarely carried out due to the lack of reliable predictors of this process.The aim: To analyze the association of anamnestic signs, laboratory and genetic research results with chronic kidney disease in children to identify potential predictors of the disease.Material and Methods. The data were obtained from a single-center retrospective catamnestic cohort study (2011–2022). The main group included 128 children with chronic kidney disease aged 1 to 17 years. The comparison group consisted of 30 children without diagnosed kidney pathology aged from 1 to 17 years. There were no statistically significant differences in sex and age between the two groups. The informative value of more than 150 features, including anamnestic ones, the state of the mother’s health during pregnancy, antenatal and perinatal factors, features of the child’s development and manifestation of the disease, the results of clinical, laboratory, and genetic research methods were evaluated. An integrated approach to the study included methods for hypotheses testing on statistical significance of indicators differences, regression analysis, and ROC analysis.Results. Hereditary burden of nephrological pathology in the family, unfavorable course of pregnancy (anemia, toxicosis of the first half), obstetric and somatic pathology in the mother, the serial number of childbirth are associated with the subsequent development of CKD. Erythrocytes in the urine and daily protein loss were detected only in the group of children with CKD. In this group, a decrease in the number of red blood cells, increased erythrocyte sedimentation rate (ESR), allergies at an early age, otitis media, persistent viral and bacterial infections, and a number of signs of connective tissue dysplasia were more common. The main group statistically significantly differed from the comparison group by a number of polymorphic genetic markers. It can be assumed that the polymorphisms AGT1 Thr174Thr, AGT2 Thr235Thr, NO3 C786T are associated with a predisposition to CKD, and the products of polymorphisms AGT1 Thr174Met, AGT2 Met235Met, R1 AGT2 C1166C, NO3 T786T may have a protective effect according to development of CKD.Conclusion. The risk factors for CKD identified in this study can be used to develop software to support medical decision making for early detection of children at high risk of disease progression.

Association of depressive symptoms and incident chronic kidney disease in middle-aged and older adults

BackgroundEmerging evidence suggests that depressive symptoms may be a risk factor for the development of Chronic kidney disease (CKD). This study aimed to investigate the association between depressive symptoms and the incidence of CKD in middle-aged and older Chinese adults. MethodsWe utilized data from the 2011–2020 China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D). Incident CKD was defined based on the estimated glomerular filtration rate ≤ 60 mL/min/m2 or self-reported. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence intervals (95 % CI) for incident CKD, adjusting for potential confounders. ResultsAmong the 10,996 participants without baseline CKD, 890 developed CKD during a median follow-up of 9.0 years. After adjusting for potential covariates, participants with depressive symptoms had a significantly higher risk of developing CKD compared to those without depressive symptoms (HR: 1.450; 95 % CI: 1.249–1.682). The association remained statistically significant when the CES-D was scored according to the severity of depressive symptoms, i.e., quintiles. A linear positive association between total CES-D score and risk of incident CKD was also found using restricted cubic spline regression (Pfor non-linearity = 0.114). ConclusionsDepressive symptoms are significantly associated with an increased risk of incident CKD in middle-aged and older Chinese adults. These findings underscore the importance of mental health screening and interventions in preventing CKD in this population.

Suppression of aldehyde dehydrogenase 2 in kidney proximal tubules contributes to kidney fibrosis through Transforming Growth Factor-β signaling

Chronic kidney disease (CKD) is an increasingly prevalent disorder that poses a significant global health and socioeconomic burden. East Asian countries such as China, Taiwan, Japan, and South Korea have a higher incidence and prevalence of kidney failure when compared to Western nations, and the reasons for this discrepancy remain unclear. Aldehyde dehydrogenase 2 (ALDH2) is an essential detoxifying enzyme for exogenous and endogenous aldehyde metabolism in mitochondria. Inactivating mutations at E504K and E487K are found in 35-45% of East Asian populations and has been linked to a higher risk of various disorders, including cardiovascular diseases and cancer. However, little is known about the role of ALDH2 in CKD. Here, we characterized the expression pattern of ALDH2 in normal and CKD human and mouse kidneys and demonstrated that ALDH2 expression was significantly reduced, and that the protein level was inversely correlated with the degree of CKD and fibrosis. Further, we treated ALDH2*2 knock-in mice, a loss of ALDH2 function model, with aristolochic acid and found that these mice showed enhanced fibrosis. Moreover, ALDH2 deficiency was associated with kidney fibrosis involving epithelial cell differentiation process in vivo and in vitro. However, ALDH2 overexpression protected proximal tubule epithelial cells from transforming growth factor-β-induced dedifferentiation or partial epithelial-mesenchymal transdifferentiation in vitro. Thus, our findings yield important clinical information regarding the development and progression of CKD involving ALDH2, especially among East Asian populations.