Glomerular Filtration Research Articles

Cefiderocol pharmacokinetics during acute pulmonary exacerbations in hospitalized adult persons with cystic fibrosis.

Persons with CF (pwCF) present altered pharmacokinetics (PK) and are often infected with multidrug-resistant (MDR) bacteria. Herein, we describe the PK of cefiderocol, a siderophore cephalosporin with potent activity against MDR Gram-negative rods, in hospitalized adult pwCF with acute pulmonary exacerbation (APE). PwCF received ≥3 doses of 2 g cefiderocol (3 h infusion) with frequency determined according to their estimated glomerular filtration rate (eGFR). Blood sampling collected at steady state. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. Ten pwCF were enrolled; nine completed the study with six receiving 2 g q8 h and three 2 g q6 h. A two-compartment model best fitted the data. Mean (SD) PK parameters were clearance, 5.66 (1.28) L/h; volume of central compartment, 5.81 (3.52) L, and intercompartment transfer constants, k12, 4.29 (3.46) and k21, 2.25 (2.76) h-1. Protein binding was 48% (35-57). The 2 g q8 h regimen achieved a mean free time above the MIC (fT >MIC) of 99% (94-99), 90% (69-100), and 64% (41-81) at MICs of 4 (susceptible), 8 (intermediate), and 16 (resistant) mg/L, respectively, with AUC24h of 1,191 (781-1,496) mg/L*h. In pwCF with eGFR >120 mL/min, 2 g q6 h attained 100% fT >MIC up to 8 mg/L and 87% (83-92) at 16 mg/L, with AUC24h of 1,279 (1,054-1,590) mg/L*h. Among these nine pwCF with APE with normal or augmented renal clearance, cefiderocol using label prescribed dosing regimens according to eGFR was well tolerated and achieved optimal fT >MIC exposure for pathogens up to MICs of 8 mg/L and AUC24h estimates similar to previously reported estimates in non-CF patients.

Applicability of creatinine-based glomerular filtration rate assessment equations to patients with neurogenic bladder

PurposeGlomerular filtration rate (GFR) measured by dynamic renal scintigraphy (Gates method) is used in this study as the standard to investigate the applicability of two creatinine (Cr)-based GFR estimation equations in Chinese patients of different genders, age groups, and GFR stages diagnosed with neurogenic bladder (NB).MethodsGFR values were measured using 99mTc-DTPA renal dynamic imaging, the new serum creatinine (Cr)-based chronic kidney disease epidemiology collaborative group (CKD-EPI) equation, and the equation for the estimated GFR of CKD patients in China, which were designated as sGFR, EPI-GFR, and cGFR, respectively. Pearson’s correlation and linear regression were used to compare the differences, absolute differences, precision, and accuracies of the results of the two equations with sGFR to determine the formula offering better performance for the assessment of patients with NB.ResultsMeasurements from a total of 99 patients with NB were used in the final analysis. Both cGFR and EPI-GFR were moderately correlated with sGFR in both men and women. The overall staging accuracies of EPI-GFR and sGFR were significantly higher than that of cGFR. Among the patients staged, only those with GFRs in the range of 60–89 mL/min/1.73 m2 had moderate correlations between cGFR, EPI-GFR, and sGFR, while the remaining patients had low correlations.ConclusionResearchers found that the equation developed for Chinese CKD patients performed well for patients with NB aged 20–25 years, while the race-neutral CKD-EPI equation performed better in NB patients aged 26–35 years.

Exploratory study on reference intervals of calprotectin and pentraxin 3.

The aim of our study was to determine reference intervals for serum pentraxin 3 and calprotectin, as well as for urine calprotectin according to the CLSI EP28-A3C guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory. A total of 120 serum and urine samples from either healthy volunteers or outpatients were used for reference interval establishment. The participants had CRP levels, leucocyte counts, serum urea levels, creatinine levels, and estimated glomerular filtration rates (CKD-EPI eGFRs) within the reference range and no medical history of acute/chronic inflammatory diseases/conditions or cancer. Calprotectin was measured via a commercially available turbidimetric method - the Bühhlmann fCAL® Turbo Reagent Kit - while pentraxin 3 was measured using the Human Pentraxin 3 ELISA Kit from the BioVendor Group. The serum calprotectin reference range was ≤3.6mg/L, the 90% CI for the upper reference range was 3.1-4.1mg/L, while the serum pentraxin 3 reference concentration was ≤3.0µg/L, and the 90% CI for the upper reference range being 2.7-3.2µg/L. Additionally, the urinary calprotectin concentration was ≤1.4mg/L, with a 90% CI for the upper reference range of 1.0-1.7mg/L. This study reports sample and method-specific reference intervals for the detection of various inflammatory conditions.

Diagnostic Test Characteristics of Ultrasound-Based Hydronephrosis for Chronic Kidney Disease in Children and Adolescents With Myelomeningocele: Results From the UMPIRE and NSBPR Cohort Studies.

Renal ultrasounds are performed in patients with myelomeningocele to screen for markers of kidney health, including hydronephrosis. We evaluated the diagnostic accuracy of hydronephrosis to screen for low kidney function defined by estimated glomerular filtration rate (eGFR). We performed a retrospective cross-sectional study using data from 2 cohorts of children and youth with myelomeningocele. The first cohort is the Urological Management to Preserve Initial Renal Function Protocol for Young Children With Spina Bifida (UMPIRE; 2016-2022) and the second from the National Spina Bifida Patient Registry (NSBPR; 2009-2021). We identified patients aged 1 to 18 years with available eGFR data within 6 months of an ultrasound. We excluded NSBPR patients younger than 6 years to address potential duplication across cohorts. The primary outcome was eGFR < 90 mL/min/1.73 m2, calculated using the bedside Schwartz formula. Hydronephrosis was dichotomized into any/none. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of any hydronephrosis using eGFR as the reference standard. In UMPIRE, 221 patients were included with median age 2.4 years (IQR, 1.9-3.8) and 24% having eGFR < 90. Any hydronephrosis vs none conferred a sensitivity/specificity/PPV/NPV of 25%/75%/24%/77%, respectively. In NSBPR, 2269 patients were included with median age 13 years (IQR, 9.6-16.3) and 17% having eGFR < 90. Any hydronephrosis vs none conferred a sensitivity/specificity/PPV/NPV of 24%/87%/26%/85%, respectively. In 2 cohorts of children and youth with myelomeningocele, hydronephrosis conferred a sensitivity of ∼25% for a creatinine-based eGFR < 90 mL/min/1.73 m2. This low sensitivity suggests that hydronephrosis alone is a poor screening marker of kidney health.

Sarcopenia may increase cisplatin toxicity in bladder cancer patients with borderline renal function.

To assess whether the effect of sarcopenia on neoadjuvant chemotherapy (NAC) toxicity is modified by borderline renal function (estimated glomerular filtration rate [eGFR] 40-65 mL/min) and whether sarcopenia and borderline renal function are independently associated with NAC toxicity risk. All patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC) between 2010 and 2022, with available cross-sectional imaging prior to NAC initiation, were included. Skeletal mass was measured from axial computed tomography images obtained at the level of the L3 vertebral body, using Aquarius Intuition software. Sarcopenia was assigned based on consensus definitions of skeletal mass index. NAC toxicity was graded according to Common Terminology Criteria for Adverse Events version 5.0. Binary logistic regression was used to identify the predictors of NAC-associated renal toxicity. A total of 216 patients were included. Most patients had sarcopenia (83%) and received gemcitabine/cisplatin NAC (76%). In an unadjusted model, sarcopenia was associated with a significant risk of renal-associated NAC toxicity (odds ratio [OR] 4.88, 95% confidence interval [CI] 1.65-14.44; P = 0.004). In an effect modification model evaluating the interaction between sarcopenia and renal function, the OR for renal toxicity with sarcopenia among patients with eGFR 40-65 mL/min was 8.46 (95% CI 1.06-67.72) vs 3.11 (95% CI 0.81-11.88) among patients with normal renal function (P = 0.43). Among MIBC patients who received NAC, sarcopenia was associated with higher odds of NAC-associated renal toxicity and may increase risk of renal toxicity among patients with borderline renal function.

Identifying subgroups benefiting from intensive glycaemic treatment to improve renal outcomes in type 2 diabetes: Insights from the ACCORD trial.

The ACCORD trial showed that intensive glucose-lowering therapy has a limited impact on renal function decline. We aimed to identify subgroups in the ACCORD population that might derive renal benefits from intensive glucose-lowering therapy. The primary renal outcome included a ≥50% decline in baseline estimated glomerular filtration rate or end-stage renal disease (ESRD). Using the causal tree model, we employed internal cross-validation to identify five pivotal variables influencing the renal efficacy of intensive glycaemic control. These variables were integrated into the model-based recursive partitioning approach, yielding a visualizable tree model that depicted benefitting subgroups. Node 4, characterized by no cardiovascular history, systolic blood pressure (SBP) ≤142.67 mm Hg, and triglycerides ≤172 mg/dL, showed significantly reduced hazards of the composite renal outcome (fully adjusted hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.49-0.89; p = 0.006) and doubling of serum creatinine (fully adjusted HR 0.59, 95% CI 0.36-0.98; p = 0.041). Node 7 (no cardiovascular history and SBP 142.67-154 mm Hg) showed reduced hazards of the primary renal outcome (fully adjusted HR 0.67, 95% CI 0.49-0.93; p = 0.016) and ESRD (fully adjusted HR 0.35, 95% CI 0.17-0.74; p = 0.0057). Encouragingly, neither node 4 nor node 7 displayed elevated cardiovascular risk or hypoglycaemic events. Through innovative machine learning, we identified ACCORD subgroups benefitting significantly from intensive glycaemic therapy for renal outcomes, without increased cardiovascular or hypoglycaemic risks.

Assessing Chronic Heavy Metal Exposure by Analysis of Human Cataract Specimens and the Relationship to Metabolic Profiles

Purpose With age, the mammalian lens forms successive layers of crystallin protein fibers which infoliate with lens growth and development. As heavy metals generally bind to tissue protein, heavy metals are posited to sequester within the lens with age. Therefore, this study aims to compare heavy metals in human crystalline lens of older adults to known physiologic blood and urine levels and assess the association between concentrations in the lens and metabolic biomarkers. Methods Consecutive lens specimens obtained during cataract surgery by phacoemulsification were subjected to atomic spectrometry for heavy metal content. A one-sample t-test compared heavy metals in lens to known physiologic blood and urine concentrations. Linear regression models assessed the association between heavy metals and biomarkers of metabolic function. Linear discriminant analysis assessed the classification of gender and smoking status based on multiple and individual heavy metals. Results All heavy metal levels were elevated in lens specimens compared to blood and urine with the exception of iron (p < 0.0001). Lens titanium and copper were positively associated with blood-urea nitrogen (Titanium: β ̂ = 1.14, p = 0.04, Copper: β ̂ = 1.12, p = 0.03. Lens copper was positively associated with creatinine ( β ̂ = 1.10; p = 0.02), but negatively associated with glomerular filtration rate ( β ̂ = 0.89; p = 0.02). Lens chromium and lead were positively associated with albumin (Chromium: β ̂ = 1.03, p = 0.03; Lead: β ̂ = 1.02, p = 0.04). Lens nickel was positively associated with bilirubin ( β ̂ = 1.14; p = 0.03). Classification based on multiple or individual heavy metals for gender and smoking status was not statistically significant. Conclusions Our results suggest the human crystalline lens accumulates heavy metals with age and demonstrate the correlation between abnormality of metabolic function and heavy metal deposition in older adult lens.

Vanadium exposure and kidney markers in a pediatric population: a cross-sectional study.

Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed. A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin-creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders. Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile. Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.

Serum symmetric dimethylarginine concentrations in enalapril- or telmisartan-treated dogs with proteinuric chronic kidney disease

IntroductionRenin-angiotensin-aldosterone system inhibition (RAASi) reduces intraglomerular pressure and is a standard therapy for dogs with proteinuric chronic kidney disease (CKD). RAASi can acutely decrease glomerular filtration rate (GFR); however, its effects on the marker of GFR serum symmetric dimethylarginine (SDMA) concentration in dogs have not been specifically evaluated. The objective of this study was to evaluate changes, relative to pretreatment values, in serum SDMA concentrations in dogs with proteinuric CKD receiving RAASi therapy.MethodsThis retrospective study used banked samples from 29 dogs with proteinuric CKD treated with enalapril (0.5 mg/kg PO q12h; n = 16) or telmisartan (1 mg/kg PO q24h; n = 13) alone (n = 22) or in combination with amlodipine if severely hypertensive (n = 7). Serum SDMA, creatinine, and urea nitrogen (SUN) concentrations were measured before and 7 and 30 days after starting RAASi. Percentage and absolute changes in these biomarkers were calculated for each dog and time point. A linear mixed model was used to test whether changes significantly differed from zero (α &amp;lt; 0.05).ResultsOverall, mean ± SEM Day 7 and 30 percentage change in SDMA were − 4.8 ± 3.6% and − 3.2 ± 3.4%, respectively; in creatinine were 7.4 ± 3.3% and 3.0 ± 3.1%, respectively; and in SUN were 22.1 ± 6.8% and 16.7 ± 6.2%, respectively. Mean changes varied according to whether all dogs, those on RAASi alone, or those co-treated with amlodipine were evaluated. In dogs receiving RAASi alone, at day 7, there were significant mean percentual increases in creatinine (9%; p = 0.023) and SUN (23%; p = 0.005), but SDMA was unchanged. In dogs co-treated with amlodipine, a significant absolute decrease in mean SDMA (−2.29 μg/dL; p = 0.026) occurred at days 7 and 30, while mean creatinine was unchanged and mean SUN increased.DiscussionProteinuric dogs receiving RAASi had low-magnitude changes in serum SDMA and creatinine, and moderate-magnitude changes in SUN concentrations. The direction of change in SDMA did not consistently match that of creatinine and SUN.

Endothelin receptor antagonists in chronic kidney disease.

Endothelin-1 is a potent vasoconstrictor that has diverse physiological functions in the kidney, including in the regulation of blood flow and glomerular filtration, electrolyte homeostasis and endothelial function. Overexpression of endothelin-1 contributes to the pathophysiology of both diabetic and non-diabetic chronic kidney disease (CKD). Selective endothelin receptor antagonists (ERAs) that target the endothelin A (ETA) receptor have demonstrated benefits in animal models of kidney disease and in clinical trials. In patients with type 2 diabetes and CKD, the selective ETA ERA, atrasentan, reduced albuminuria and kidney function decline. Concerns about the increased risks of fluid retention and heart failure with ERA use have led to the design of further trials to optimize dosing and patient selection. More recent studies have shown that the dual ETAreceptor andangiotensin receptor blocker, sparsentan, preserved kidney function with minimal fluid retention in patients with IgA nephropathy. Moreover, combined administration of a low dose of the ETA-selective ERA, zibotentan, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, enhanced albuminuria reduction and mitigated fluid retention in patients with CKD. Notably, sparsentan and aprocitentan have received FDA approval for the treatment of IgA nephropathy and treatment-resistant hypertension, respectively. This Review describes our current understanding of the use of ERAs in patients with CKD to guide their optimal safe and effective use in clinical practice.

Crosstalk between glomeruli and tubules.

Models of kidney injury have classically concentrated on glomeruli as the primary site of injury leading to glomerulosclerosis or on tubules as the primary site of injury leading to tubulointerstitial fibrosis. However, current evidence on the mechanisms of progression of chronic kidney disease indicates that a complex interplay between glomeruli and tubules underlies progressive kidney injury. Primary glomerular injury can clearly lead to subsequent tubule injury. For example, damage to the glomerular filtration barrier can expose tubular cells to serum proteins, including complement and cytokines, that would not be present in physiological conditions and can promote the development of tubulointerstitial fibrosis and progressive decline in kidney function. In addition, although less well-studied, increasing evidence suggests that tubule injury, whether primary or secondary, can also promote glomerular damage. This feedback from the tubule to the glomerulus might be mediated by changes in the reabsorptive capacity of the tubule, which can affect the glomerular filtration rate, or by mediators released by injured proximal tubular cells that can induce damage in both podocytes and parietal epithelial cells. Examining the crosstalk between the various compartments of the kidney is important for understanding the mechanisms underlying kidney pathology and identifying potential therapeutic interventions.

Aspartate/alanine aminotransferase ratio and development of chronic kidney disease in non-diabetic men and women: a population-based longitudinal study in Kagawa, Japan.

The relationship between serum aspartate/alanine aminotransferase ratio (AST/ALT) and subsequent development of chronic kidney disease (CKD) in non-diabetic Asian adults has not yet been fully investigated in longitudinal studies. The study included all middle-aged and older non-diabetic Japanese citizens who received health check-ups in Zentsuji, Kagawa, Japan (1998-2023). AST/ALT was classified into three categories: < 1.0 (reference), 1.0- < 1.5, and ≥ 1.5. CKD was defined as an estimated glomerular filtration rate of < 60mL/min/1.73 m2. The Weibull accelerated failure time model was used to examine the association between AST/ALT categories and subsequent CKD onset because the proportional hazards assumption was violated. Of 6309 men and 9192 women, 2966 men and 4395 women remained in the final cohort. After a mean follow-up of 7.50years for men and 8.34years for women, 33.7% of men and 34.0% of women developed CKD. Women had higher AST/ALT than men. In women, a dose-response relationship was observed, with a 9% shorter survival time to CKD onset for AST/ALT ≥ 1.5 compared with AST/ALT < 1.0. In contrast, men had a shorter survival time to CKD onset by point estimates, but the 95% confidence intervals crossed 1 in all models. In this study comparing the risks of CKD development in non-diabetic men and women by AST/ALT levels, a dose-response relationship was only observed in women. Differences in the distribution of AST/ALT by sex may have affected the results. Therefore, in non-diabetic Japanese women, AST/ALT may be used as an indicator of future CKD development.

Aortic stiffness after living kidney donation: a systematic review and meta-analysis

ObjectivesIncreased aortic stiffness measured with carotid-femoral pulse wave velocity (cf-PWV) has been associated with adverse cardiovascular outcomes. Some studies have reported increased cf-PWV in living kidney donors after nephrectomy. This...

The importance of kidney response over hematologic response in predicting kidney outcome in amyloid light-chain amyloidosis.

Light chain amyloidosis, characterized by amyloid fibril deposition in multiple organs, often leads to progression to endstage kidney disease. This study aimed to identify predictors of kidney survival in patients with kidney amyloidosis, focusing on hematologic and kidney response. This retrospective study included 138 patients diagnosed with kidney amyloidosis between 2011 and 2019. Palladini criteria were applied to categorize kidney stage and kidney response based on initial glomerular filtration rate and proteinuria, and their changes after treatment. Hematologic response was assessed based on the 2012 International Society of Amyloidosis criteria. Deep hematologic response was defined as the achievement of at least a very good partial response. Overall, 17 (12.3%) progressed to end-stage kidney disease. Multivariable analysis, considering baseline characteristics, revealed that stage II had an increased risk of end-stage kidney disease compared to stage I (hazard ratio, 3.75; 95% confidence interval [CI], 1.38-10.15; p = 0.01). Compared to kidney response, the risk of end-stage kidney disease increased by 8.42 (95% CI, 1.72-41.35; p = 0.01) and 7.36 (95% CI, 1.25-43.33; p = 0.03) times in stable disease and kidney progression at 6 months, respectively, whereas deep hematologic response showed no association with kidney outcome. Kidney survival was longer in patients with deep hematologic response and kidney response than in those with only hematologic response (p = 0.004). The study underscores the importance of kidney response over hematologic response in predicting end-stage kidney disease and emphasizes the need to assess treatment endpoints, considering organ response alongside hematologic response.

Prevalence and factors linked to renal involvement in prediabetes patients across Europe in the ePREDICE trial

This sub-analysis of the ePREDICE trial, investigated the prevalence and determinants of renal complications, specifically glomerular hyperfiltration, albuminuria, and reduced kidney function, in individuals with prediabetes (PD). The cohort consisted of 967 participants from diverse backgrounds across seven countries. The kidney function was evaluated using the MDRD-4 equation, and the influence of various clinical and demographic factors on renal involvement was assessed by multivariable regression models. Additionally, insulinogenic and disposition indices were examined. Overall, the prevalence of renal abnormalities in this PD cohort was 9.2% (n = 89). Key findings included the detection of hyperfiltration in 20 (2%) individuals, albuminuria in 45 (4.7%), and CKD stage G3a in 29 (3%). Hyperfiltration was inversely correlated with age and height, while albuminuria showed a significant direct association with the disposition index (DI). Age and waist circumference were significantly and directly associated with estimated glomerular filtration rate (eGFR). The ePREDICE study highlights critical factors that affect renal involvement in PD individuals, revealing complex interactions among various parameters. These findings further emphasize the necessity for the search of early kidney abnormalities in people with PD especially in those in older age groups and with a large waist circumference.

Influence of Treatment Effect Modifiers in Fabry Disease: A Systematic Literature Review.

Fabry disease (FD) is a rare metabolic disorder which presents with considerable heterogeneity in disease characteristics. Given the absence of interventional studies comparing all available treatments, it is important for indirect treatment comparisons (ITCs) to account for potential treatment effect modifiers (TEMs). This systematic literature review (SLR) aimed to identify patient characteristics that may impact clinical outcomes by analyzing real-world evidence (RWE) in FD. An SLR was conducted according to PRISMA guidelines, with searches performed in the EMBASE, MEDLINE, and Cochrane databases (1946-2022; with a recent update in April 2023). Full-text articles reporting clinical outcomes from RWE studies of pharmacological therapies for the treatment of FD were included. Including studies from the recent SLR update, a total of 119 original studies met the PICOS criteria and 25 studies provided insights into TEMS. Potential TEMs in FD were identified: sex, age, timing of treatment initiation (early/delayed), left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), proteinuria, presence of anti-drug-antibodies (ADAs) at baseline, and previous enzyme replacement therapy (ERT). In three studies (two including ERT-treated patients and one study of migalastat-treated patients) males showed worse renal outcomes than females. Five studies found that younger patients and those who received initial ERT before the age of 25years had greater reductions in plasma-lysoGb3, as well as more favorable renal, cardiac, and biochemical outcomes. Seven studies identified associations between LVH and reduced eGFR at baseline, along with an increased risk of cardiovascular, renal, and neurological events. In four studies, lower baseline eGFR and proteinuria were associated with faster annual eGFR decline despite ERT; high baseline proteinuria was a significant predictor of renal disease progression. Baseline ADAs were linked to lower eGFR, increased left ventricular mass, and reduced treatment impact on plasma/urine-lysoGb3. Migalastat was effective in treatment-naïve patients, while those previously treated with ERT experienced deteriorations in mean lysoGb3, eGFR, and left ventricular mass. This SLR highlighted several patient characteristics that influence treatment effectiveness in FD. It is important to account for these characteristics in ITCs to ensure unbiased outcomes.

Integrating Sglt-2 Inhibitors into the Clinical Management of Type 2 Diabetes Mellitus and Chronic Kidney Disease: Current Evidence and Future Outlook

Objective and Background: The prevalence of type 2 diabetes mellitus (T2DM) is steadily increasing globally. A significant complication of T2DM is diabetic kidney disease, which contributes to increased morbidity and mortality. Sodium-Glucose Co-Transporter-2 (SGLT-2) inhibitors are a class of oral antidiabetic agents that effectively lower blood glucose levels and provide protective benefits for kidney health. Methods: A comprehensive review of studies was conducted focusing on the use of SGLT-2 inhibitors in patients with T2DM, including those with chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m², or urine albumin/creatinine ratio ≥ 30 mg alb/g creatinine. The studies evaluated clinical outcomes such as cardiovascular events, kidney disease progression, and mortality. Results: Research findings demonstrate that SGLT-2 inhibitors significantly reduce the risk of hospitalization due to heart failure, myocardial infarction, and stroke. Additionally, these medications lower the incidence of cardiovascular-related and all-cause mortality. Renal-specific benefits include slowing the progression of albuminuria, reducing the decline in GFR, lowering the need for renal replacement therapy, and decreasing kidney-related deaths.

Inflammation and Arterial Stiffness as Drivers of Cardiovascular Risk in Kidney Disease.

Patients with chronic kidney disease (CKD) have an increased cardiovascular (CV) risk. The lower the glomerular filtration rate, the higher the CV risk. Current data suggest that several uremic toxins lead to vascular inflammation and oxidative stress that, in turn, lead to endothelial dysfunction, changes in smooth muscle cells' phenotype, and increased degradation of elastin and collagen fibres. These processes lead to both functional and structural arterial stiffening and explain part of the increased risk of acute myocardial infarction and stroke reported in patients with CKD. Considering that, at least in patients with end-stage kidney disease, the reduction of arterial stiffness is associated with a parallel decrease of the CV risk, vascular function is a potential target for therapy to reduce the CV risk. in this review, we explore mechanisms of vascular dysfunction in CKD, paying particular attention to inflammation, reporting current data in other models of mild and severe inflammation, and discussing the vascular effect of several drugs currently used in nephrology.

Establishment of reference intervals for estimated glomerular filtration rate in apparently healthy adults based on the full age spectrum equation: A single-centre study.

Identifying gender and age-related eGFR trends is crucial for precise renal function assessment. This study aims to analyse eGFR distribution with the full age spectrum (FAS) equation and establish reference intervals based on gender and age in a single-centre cohort. Following the inclusion and exclusion criteria outlined in this study, a total of 24,024 reference individuals were ultimately selected. Using the approach recommended by the CLSI C28-A3 guidelines, we assessed the distribution of eGFR across different gender and age groups. The two-sided nonparametric method (P2.5-P97.5) was applied to establish the eGFR reference intervals for a healthy Chinese population. The eGFR levels in healthy adults exhibited a non-normally distributed pattern. Notably, there were significant differences in eGFR levels between males and females, with females showing a notably higher eGFR level than males. Additionally, eGFR levels demonstrated significant variations across different age groups within both male and female cohorts. As age increased, eGFR showed a significant decline, except in individuals aged 20-29 and 30-39 years. Therefore, reference intervals for eGFR were created based on both gender and age. We established the reference interval for eGFR using the FAS equation, drawing from a large sample population at a single centre. This establishes a potential framework for evaluating renal function in healthy individuals and for diagnosing and treating kidney-related diseases.

Comparison of robotic-assisted and laparoscopic partial nephrectomy based on the PADUA score and the predictive value of the PADUA score and the Mayo Adhesive Probability score for postoperative complications: a single-center retrospective study

PurposeThis study compared perioperative outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) through the PADUA score as well as assessed the predictive value of the PADUA score and the Mayo Adhesive Probability (MAP) score for postoperative complications.MethodsTotally 196 patients suffering from RAPN or LPN for renal tumors were reviewed retrospectively. Patients were categorized by PADUA score (low-, moderate-, high-complexity) and MAP score (low-, intermediate-, high-grade). Evaluated outcomes included operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), drainage duration, postoperative length of stay, and absolute change in estimated glomerular filtration rate (eGFR) at three months post-surgery, along with intra- and postoperative complications.ResultsRAPN outperformed LPN in the low-complexity group by lowering WIT (P = 0.022) and absolute eGFR change (P = 0.011). For moderate-complexity group, RAPN reduced WIT (P = 0.021), absolute eGFR change (P = 0.027), and postoperative length of stay (P = 0.008). In the high-complexity group, RAPN reduced OT (P = 0.015), WIT (P = 0.023), EBL (P = 0.036), absolute eGFR change (P = 0.024), and postoperative length of stay (P = 0.019). Drainage duration showed no significant differences across groups (P = 0.442, P = 0.327, P = 0.260). RAPN incurred significantly higher total costs than LPN across groups (P < 0.001). ROC analysis suggested PADUA and MAP scores as reliable predictors of postoperative complications in RAPN (AUC = 0.880,0.828) and LPN (AUC = 0.757,0.702).ConclusionRAPN provides significant advantages over LPN in managing complex renal tumors (PADUA score ≥ 10), significantly in reducing OT, WIT, EBL, and absolute eGFR change at three months post-surgery, while minimizing postoperative stay. The PADUA and MAP scores are valuable in predicting postoperative complication.Trial registration number and date of registrationRetrospectively registered.