Progression Of Kidney Disease Research Articles

Risk Factors for Kidney Disease Progression in Pancreas Alone Recipients Obligate a Kidney Transplant Safety Net.

Risk Factors for Kidney Disease Progression in Pancreas Alone Recipients Obligate a Kidney Transplant Safety Net.

Metal-Dependent Cell Death in Renal Fibrosis: Now and in the Future

Renal fibrosis is a common final pathway underlying nearly almost all progressive kidney diseases. Metal ions are essential trace elements in organisms and are involved in important physiological activities. However, aberrations in intracellular metal ion metabolism may disrupt homeostasis, causing cell death and increasing susceptibility to various diseases. Accumulating evidence suggests a complex association between metal-dependent cell death and renal fibrosis. In this article, we provide a comprehensive overview of the specific molecular mechanisms of metal-dependent cell death and their crosstalk, up-to-date evidence supporting their role in renal fibrosis, therapeutic targeting strategies, and research needs, aiming to offer a rationale for future clinical treatment of renal fibrosis.

RasGRP4 aggravates ischemia-reperfusion injury in diabetic kidneys by mediating communication between macrophages and T cells.

Diabetes mellitus (DM) is acknowledged as an independent risk factor for acute kidney injury. Ras guanine nucleotide-releasing protein-4 (RasGRP4) exerts a notable role in modulating immune-inflammatory responses and kidney disease progression in diabetes. Herein, we delved into the specific role and mechanism of RasGRP4 in diabetic renal ischemia-reperfusion injury. Diabetes was induced by a high-fat diet and STZ injections, followed by creating an ischemia-reperfusion kidney injury via renal pedicle clamping and reperfusion. In vitro, a high glucose and hypoxia-reoxygenation modeled cellular inflammatory injury. We found RasGRP4 knockout (KO) mice, compared to C57BL/6J (WT) mice, showed markedly less renal dysfunction and fibrosis in diabetic ischemia-reperfusion injury. There was a significant decrease in the renal infiltration of M1 macrophages and Th17 cells, along with downregulated IL17 pathway proteins and effectors. In vitro, RasGRP4 deletion restrained M1 macrophage polarization and Th17 cell differentiation, inhibiting the IL17 signaling pathway in HK-2 cells. Hyperglycemia intensified renal inflammation state. Together, RasGRP4, through the regulation of interactions among M1 macrophages, CD4+ T cells and HK-2 cells, formed a cascade that intensified the inflammatory storm activity, ultimately exacerbating the inflammatory injury of diabetic ischemia-reperfusion kidneys. DM intensified this inflammatory injury mechanism, worsening the injury from renal ischemia-reperfusion.

SGLT2 inhibitors in preventing progression of chronic kidney disease in patients with type 2 diabetes: a literature review

IntroductionType 2 diabetes mellitus (T2DM) is an increasing health concern, and diabetic kidney disease (DKD) affects 30–40% of patients with diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective medications used in the treatment of T2DM, which not only improve glycemic control but also slow the progression of diabetic kidney disease (DKD), reducing the risk of renal and cardiovascular complications. They work by decreasing glomerular hyperfiltration and alleviating inflammation in the kidneys. Clinical studies have demonstrated significant therapeutic benefits, including a reduction in albuminuria and improvement in renal function. In the future, the development of new drug classes, such as Nrf2 activators and RAS inhibitors, which are currently under clinical investigation, may further advance the treatment of DKD, offering a more personalized approach to therapy. This article reviews the current knowledge on SGLT2i and their impact on the progression of DKD, the future prospects for therapies in managing diabetes and its complications. Aim of the Study: The aim of this study was to gather and analyze available scientific publications regarding the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on slowing the progression of chronic kidney disease (CKD) in patients with T2DM and to determine the future of therapy based on new reports and research into emerging drug classes. Materials and Methods: We conducted a review and analysis of the literature available in the PubMed database, using keywords such as SGLT2 inhibitors, gliflozins, chronic kidney disease, type 2 diabetes.

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.

Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease.

Angiopoietin-like 4 (ANGPTL4), a key protein involved in lipoprotein metabolism, has diverse effects. There is an association between Angptl4 and diabetic kidney disease; however, this association has not been well investigated. We show that both podocyte- and tubule-specific ANGPTL4 are crucial fibrogenic molecules in diabetes. Diabetes accelerates the fibrogenic phenotype in control mice but not in ANGPTL4 mutant mice. The protective effect observed in ANGPTL4 mutant mice is correlated with a reduction in stimulator of interferon genes pathway activation, expression of pro-inflammatory cytokines, reduced epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition, lessened mitochondrial damage, and increased fatty acid oxidation. Mechanistically, we demonstrate that podocyte- or tubule-secreted Angptl4 interacts with Integrin β1 and influences the association between dipeptidyl-4 with Integrin β1. We demonstrate the utility of a targeted pharmacologic therapy that specifically inhibits Angptl4 gene expression in the kidneys and protects diabetic kidneys from proteinuria and fibrosis. Together, these data demonstrate that podocyte- and tubule-derived Angptl4 is fibrogenic in diabetic kidneys.

Healthcare utilization, mortality, and cardiovascular events following GLP1-RA initiation in chronic kidney disease

Treatment with glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) may attenuate kidney disease progression and cardiovascular events but their real-world impact on healthcare utilization and mortality in this population are not well-defined. Here, we emulate a clinical trial that compares outcomes following initiation of GLP1-RA vs Dipeptidyl peptidase-4 inhibitors (DPP4i), as active comparators, in U.S. veterans aged 35 years of older with moderate to advanced CKD during fiscal years 2006 to 2021. Primary outcome was rate of acute healthcare utilization. Secondary outcomes were all-cause mortality and a composite of acute cardiovascular events. After propensity score matching (16,076 pairs) and 2.2 years mean follow-up duration, use of GLP1-RA in patients with moderate to advanced CKD was associated with lower annual rate of acute healthcare utilization and all-cause mortality. There was no significant difference in acute cardiovascular events.

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.

Aldosterone synthase inhibitors: a potential revival for treatment of renal and cardiovascular diseases.

Inappropriate aldosterone excess plays a key role in the pathophysiology of various cardiovascular, endocrine and renal diseases. Mineralocorticoid receptor (MR) antagonists (MRAs) such as spironolactone block of the harmful effects of aldosterone and are recommended treatment in these various conditions. However, the sexual adverse effects of spironolactone due to its lack of specificity for the MR and the risk of hyperkalemia in patients with decreased renal function, limit its use. While eplerenone is a more selective MRA, it is less potent than spironolactone. Newer nonsteroidal MRAs, though promising, are either unavailable globally or still under development. Moreover, aldosterone exerts both genomic and nongenomic effects, the latter not fully blocked by MRAs. Aldosterone synthase inhibitors (ASIs) have thus emerged as potential alternatives to MRAs, though the development of selective ASIs has been challenging. This is due to the close homology between the final step of aldosterone synthesis, mediated by CYP11B2 in the zona glomerulosa of the adrenal cortex, and cortisol synthesis, mediated by CYP11B1 in the zona fasciculata. Despite these challenges, new ASIs have demonstrated high in vitro as well as in vivo selectivity for CYP11B2, effectively reducing aldosterone production without affecting cortisol synthesis in humans across large dose ranges. Early phase II trials demonstrated that these ASIs decrease 1) blood pressure in uncontrolled hypertension, and (2) urinary albumin excretion in proteinuric chronic kidney disease. Further longer-term trials will evaluate their efficacy in lowering blood pressure as well as in reducing kidney disease progression and cardiovascular outcomes in heart failure when given alone or in combination with SGLT2 inhibitors.

IgA Nephropathy: What Is New in Treatment Options?

IgA nephropathy (IgAN), first described in 1968, is one of the most common forms of glomerulonephritis and can progress to end-stage kidney disease (ESKD) in 25 to 30 percent of patients within 20 to 25 years from the onset. It is histologically characterized by mesangial proliferation with prominent IgA deposition. The prognosis may be difficult to predict, but important risk factors for disease progression of kidney disease have been recognized: usually proteinuria above 0.75–1 g/day with or without hematuria, hypertension, high-risk histologic features (such as crescent formation, immune deposits in the capillary loops, mesangial deposits, glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular disease), and a reduced Glomerular Filtration Rate (GFR). In the absence of reliable specific biomarkers, current standards of care are addressed to decrease proteinuria, as a surrogate endpoint, and control blood pressure. For a long time, corticosteroids have been considered the only cure for proteinuric patients or those at risk of progression to ESKF; however, unfortunately, like other immunosuppressive agents, they are burdened with high collateral risks. Therefore, optimal treatment remains a challenge, even if, to date, clinicians have many more options available. Here, we will review the main therapies proposed, such as the stronghold of RAAS inhibition and the use of SGLT2 inhibitors; it is expected that ongoing clinical trials may find other therapies, apart from corticosteroids, that may help improve treatment, including both immunosuppressive monoclonal antibodies and other strategies. At the current time, there are no disease-specific therapies available for IgAN, because no largescale RCTs have demonstrated a reduction in mortality or in major adverse kidney or cardiovascular events with any therapy.

Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Hypertension is a risk factor for the development and progression of chronic kidney disease (CKD). It is unclear whether different thiazide diuretics have a differential impact on kidney outcomes. To compare kidney outcomes in patients with hypertension taking chlorthalidone and hydrochlorothiazide. This prespecified secondary analysis of the Diuretic Comparison Project, a randomized clinical trial comparing chlorthalidone and hydrochlorothiazide for the treatment of hypertension, was conducted between June 1, 2016, and June 1, 2022, through Veterans Affairs facilities nationwide. This analysis extended follow-up to December 31, 2023. Veterans 65 years or older with hypertension who were taking hydrochlorothiazide were included. The Diuretic Comparison Project randomized 13 523 participants to continue hydrochlorothiazide or switch to chlorthalidone. The main kidney outcome was CKD progression, defined as doubling of serum creatinine level from baseline, a terminal estimated glomerular filtration rate (eGFR) less than 15 mL/min, or dialysis initiation. Analysis included 12 265 participants (90.7%) with a baseline and 1 or more follow-up creatinine measurements (median [IQR] age, 71 [69-75] years; 3.2% female and 96.8% male). The mean (SD) study duration was 3.9 (1.3) years. Chlorthalidone was not superior to hydrochlorothiazide at preventing kidney outcomes (369 of 6118 [6.0%] vs 396 of 6147 [6.4%]; hazard ratio [HR], 0.94; 95% CI, 0.81-1.08; P = .37). Similar results were observed when a 40% or greater reduction of eGFR was substituted for doubling of creatinine in the above outcome, as well as any of the components of the primary composite outcome. There was no difference in the incidence of CKD (961 of 4520 [21.3%] for chlorthalidone vs 939 of 4518 [20.8%] for hydrochlorothiazide; P = .59) or acute kidney injury requiring hospitalization (391 [6.4%] for chlorthalidone vs 379 [6.2%] for hydrochlorothiazide; P = .63) between groups. However, a statistically significant increased incidence of hypokalemia for chlorthalidone vs hydrochlorothiazide was observed (545 [8.9%] vs 426 [6.9%]; P < .001). Chlorthalidone was not superior to hydrochlorothiazide for kidney outcomes but was associated with an increased risk for hypokalemia. Given these findings, clinicians should feel confident using either agent for the treatment of hypertension and kidney outcomes. ClinicalTrials.gov Identifier: NCT02185417.

Association of trimethylamine N-oxide and metabolites with kidney function decline in patients with chronic kidney disease

BackgroundTrimethylamine N-oxide (TMAO) is a gut microbial metabolite derived from dietary L-carnitine and choline. High plasma TMAO levels are associated with cardiovascular disease and overall mortality, but little is known about the associations of TMAO and related metabolites with the risk of kidney function decline among patients with chronic kidney disease (CKD). MethodsWe prospectively followed 152 nondialysis patients with CKD stages 3–5 and measured plasma TMAO and related metabolites (trimethylamine [TMA], choline, carnitine, and γ-butyrobetaine) via liquid chromatography‒mass spectrometry. An estimated glomerular filtration rate (eGFR) slope >3 ml/min/per 1.73 m2 per year was defined as a rapid decline. We performed logistic regression to determine the probability of rapid or slow eGFR decline, with each metabolite as the main predictor. The gut microbiota was profiled via whole metagenomic sequencing. ResultsThe participants had a median age of 66 years, 41.4% were women, 39.5% had diabetes, and the median eGFR was 23 mL/min/1.73 m2. A rapid decrease in the eGFR occurred in 65 patients (42.8%) over a median follow-up of 3.3 years. After adjustment for baseline eGFR, proteinuria, and clinical factors, plasma TMAO levels were independently associated with increased odds of rapid eGFR decline (odds ratio, 2.42; 95% CI, 1.36–4.32), whereas plasma TMA, choline, carnitine, and γ-butyrobetaine levels were not. Patients who exhibited rapid eGFR decline had a distinct gut microbial composition characterized by increased α-diversity and an abundance of TMA-producing bacteria, including those of the genera Desulfovibrio and Collinsella tanakaei, as well as increased expression of the TMA-producing enzymes bbuA and cutC. ConclusionOur findings suggest the relevance of plasma TMAO in the progression of kidney disease among patients with CKD.

Coexisting Tubulointerstitial Inflammation and Damage Is a Risk Factor for Chronic Kidney Disease in Patients With Lupus Nephritis.

This study aims to determine whether the concurrent presence of tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) predicts the progression of chronic kidney disease (CKD) in patients with lupus nephritis (LN). Data from 175 LN patients, collected at the time of renal biopsy, were analyzed. Patients were stratified into two groups based on the presence or absence of coexisting TII/TID. Uni- and multivariable Cox proportional hazard regression models were utilized to identify independent risk factors for CKD in LN patients. Of 175 patients, 110 (62.9%) exhibited coexisting TII/TID, whereas 65 (37.1%) did not. Patients with coexisting TII/TID tended to be older and presented with higher levels of ESR and 24-h proteinuria, as well as lower levels of eGFR and hemoglobin compared to those without coexisting TII/TID. Over a mean follow-up period of 89.9 months, CKD and end-stage renal disease occurred more frequently in patients with coexisting TII/TID. Notably, the presence of coexisting TII/TID was associated with a higher risk of CKD progression, with adjusted hazard ratios of 2.667 (95% CI: 1.333, 5.335, p = 0.006) for all LN patients, 3.265 (95% CI: 1.451, 7.345, p = 0.004) for those with class III, IV, and V LN, and 3.045 (95% CI: 1.289, 7.195, p = 0.011) for those with class III, IV, V LN, and eGFR ≥ 30 mL/min/1.73 m2. LN patients with coexisting TII/TID are at a heightened risk of kidney function deterioration at LN onset and subsequent development of CKD over the long term.

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors

IntroductionRenal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). MethodsWe identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. ResultsAt 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). ConclusionsVolume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

Kidney effects of Glucagon-Like Peptide 1 (GLP1): from molecular foundations to a pharmacophysiological perspective.

GLP1 receptor agonists (GLP1-RAs) are drugs that mimic the effects of the incretin hormone GLP1 and were initially introduced in medicine for the treatment of diabetes in 2005 and for obesity in 2014. Over time, data from secondary and exploratory objectives of large randomized controlled-trials suggested that GLP1-RAs could also exert renal action by slowing the progression of kidney disease in patients with and without diabetes. Based on this rationale, the Flow study (1 mg semaglutide vs placebo) was designed and recruitment began in 2019 until May 2021. The recently published results confirmed the effect of semaglutide in reducing the composite renal outcome. However, similar to SGLT2 inhibitors, the potential mechanisms behind the renal effects of GLP1-RAs still need to be elucidated. The aim of this review is to address the different physiological mechanisms of GLP1-RAs at the renal level, using evidence from experimental studies and current scientific literature.

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q 10 Biosynthesis Disorders

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q ₁₀ Biosynthesis Disorders

Association of changes in metabolic syndrome with new-onset and progression of chronic kidney disease.

Metabolic syndrome (MetS) is an independent risk factor for new-onset and progression of chronic kidney disease (CKD). However, whether changes in MetS are associated with the new-onset CKD and its progression remains unknown. A total of 36,571 participants from the Kailuan Study were enrolled in this study, including 27,072 without CKD and 9499 with CKD at baseline. According to the changes of MetS, 4 groups were divided as follows: MetS-free group, MetS-recovered group, MetS-developed group, and MetS-persistent group. Cox regression models were used to explore the association of changes in MetS with new-onset and progression of CKD. During a median follow-up of 8.38 years, 3313 cases of new-onset CKD were identified in participants without CKD. Compared with the MetS-free group, the hazard ratio (HR) and 95% confidence interval (95% CI) for new-onset CKD in the MetS-recovered, MetS-developed and MetS-persistent groups was 1.34 (1.18-1.53), 1.46 (1.30-1.63) and 1.85 (1.69-2.02), respectively. Among 9499 participants with CKD, during a median follow-up of 8.18 years, a total of 2305 experienced CKD progression. Compared with the MetS-free group, the HR (95% CI) for CKD progression in each group were 1.05 (0.91-1.22), 1.34 (1.17-1.55) and 1.65 (1.49-1.83), respectively. Furthermore, the association between changes in MetS and new-onset CKD was stronger in younger and middle-aged participants (≤60 years old) compared with older participants. Developed MetS and persistent MetS were both risk factors for the new-onset and progression of CKD. Even with recovery from MetS, an association of MetS with kidney damage remained.

Abnormalities of IL-12 Family Cytokine Pathways in Autosomal Dominant Polycystic Kidney Disease Progression

Background and Objectives: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic renal disease with a complex physiopathology. More and more studies sustain that inflammation plays a crucial role in ADPKD pathogenesis and progression. We evaluated IL-12 involvement in ADPKD pathophysiology by assessing the serum levels of its monomers and heterodimers. Materials and Methods: A prospective case-control study was developed and included 66 ADPKD subjects and a control group of 40 healthy subjects. The diagnosis of ADPKD was based on familial history clinical and imagistic exams. The study included subjects with eGFR &gt; 60 mL/min/1.73 mp, with no history of hematuria or other renal disorders, with stable blood pressure in the last 6 months. We tested serum levels of monomers IL-12 p40 and IL-12 p35 and heterodimers IL-12 p70, IL-23, IL 35, assessed by ELISA method. Results: IL-12 family programming was abnormal in ADPKD patients. IL-12p70, IL-12p40, and IL-23 secretion increased, while IL-12p35 and IL-35 secretion decreased compared to control. IL-12p70, IL-12p40, and IL-23 had a progressive increase correlated with immune response amplification, a decrease of eGFR, an increase in TKV, and in albuminuria. On the other hand, IL-35 and IL-12p35 were correlated negatively with CRP and albuminuria and positively with eGFR in advanced ADPKD. Conclusions: The present study investigated IL-12 cytokine family members’ involvement in ADPKD pathogenesis, enriching our understanding of inflammation in the most common renal genetic disorder.

Correlation between Urine Albumin Creatinin Ratio (UACR) Value to Urine Osmolality Value and Estimate Glomerular Filtration Rate (EGFR) Value on Patient with Kidney Failure

BACKGROUND : Kidney failure is one of the causes of death in the world. Laboratory tests related to kidney function are very important in the management of patients with kidney failure because they are useful in identifying any decline in kidney function, monitoring treatment and progression of kidney disease. The aim of checking the urine albumin creatinine ratio (UACR): is to assess the protein filtration function in the glomerulus. The aim of checking urine osmolality is to assess pre-renal, renal and post-renal hemodynamic status. The aim of examining the estimated glomerular filtration rate (EGFR) is to assess overall glomerular function. EGFR is the gold standard. AIMS : The aim of this research is to determine 1). the relationship between UACR values and EGFR, 2). The relationship between urine osmolality and EGFR. UACR and urine osmolality are independent variables. Meanwhile, EGFR is the dependent variable. The research sample was all chronic kidney failure in one group. Acute renal failure was made into a group and a separate analysis. METHOD : This study is a quantitative study with analytical observations through a cross sectional design using 30 samples and was conducted from May to June 2024 at the Central Laboratory Installation of Dr. Saiful Anwar Hospital, East Java Province. UACR and EGFR examination used the principle of photometric test while urine osmolality examination used the principle of electrical conductivity. The data were analyzed using the Shapiro-Wilk normality test and the Spearman non-parametric correlation test through SPSS 27. RESULT : In the normality test results, it was found that UACR and EGFR values were not normally distributed (p = &lt;0.001) while urine osmolality values were normally distributed (p = 0.523). Spearman's non-parametric correlation test showed that there was no correlation between UACR value to urine osmolality value (p = 0.342) and EGFR value (p = 0.481). CONCLUSION : The results of this study showed no correlation between UACR value to urine osmolality value and EGFR value in patients with kidney failure.

Blood methylation biomarkers are associated with diabetic kidney disease progression in type 1 diabetes.

DNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort. We analysed baseline blood sample-derived DNA methylation (Illumina's EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.73m 2 (early DKD progression group; median follow-up 13.1 years) or end-stage kidney disease (ESKD) (late DKD progression group; median follow-up 8.4 years). We conducted two epigenome-wide association studies (EWASs) on DKD progression and sought methylation quantitative trait loci (meQTLs) for the lead CpGs to estimate genetic contribution. Altogether, 14 methylation sites were associated with DKD progression ( P <9.4×10 -8 ). Methylation at cg01730944 near CDKN1C and at other CpGs associated with early DKD progression were not correlated with baseline eGFR, whereas late progression CpGs were strongly associated. Importantly, 13 of 14 CpGs could be linked to a gene showing differential expression in DKD or chronic kidney disease. Higher methylation at the lead CpG cg17944885, a frequent finding in eGFR EWASs, was associated with ESKD risk (HR [95% CI] = 2.15 [1.79, 2.58]). Additionally, we replicated meQTLs for cg17944885 and identified ten novel meQTL variants for other CpGs. Furthermore, survival models including the significant CpG sites showed increased predictive performance on top of clinical risk factors. Our EWAS on early DKD progression identified a podocyte-specific CDKN1C locus. EWAS on late progression proposed novel CpGs for ESKD risk and confirmed previously known sites for kidney function. Since DNA methylation signals could improve disease course prediction, a combination of blood-derived methylation sites could serve as a potential prognostic biomarker.