Search Results (159)

Background and Objectives: Arterial hypertension is a major cause of systemic microvascular damage involving target organs such as the kidneys and retina. Because the retinal and renal microcirculations share common pathogenic mechanisms, retinal imaging may provide non-invasive biomarkers of hypertensive microvascular injury. This study investigated the association between the renal resistive index (RRI), systemic oxidative stress biomarkers, and retinal abnormalities in patients with essential hypertension. Retinal structural and microvascular parameters were evaluated using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Materials and Methods: In this cross-sectional exploratory study, 32 patients with essential hypertension (64 eyes) underwent comprehensive ophthalmic examination, OCT/OCTA imaging, renal Doppler ultrasonography for RRI assessment, and evaluation of systemic oxidative stress biomarkers. Associations between renal, ocular, and biochemical parameters were analyzed. Results: No significant differences were observed in most global OCT/OCTA parameters. However, higher RRI values were associated with localized macular thinning and reduced optic nerve head perfusion metrics. Patients with RRI values ≥ the 75th percentile showed significantly increased hydrogen peroxide levels (p = 0.004) and reduced nitric oxide bioavailability (p = 0.033), together with thinning of selected inner macular sectors. A trend toward reduced optic nerve head flow index was also observed, suggesting early microvascular impairment that may not be detected by conventional global OCT measurements. Conclusions: These exploratory findings suggest a possible association among increased renal vascular resistance, oxidative stress, and localized retinal structural alterations in patients with essential hypertension. The coexistence of systemic redox imbalance and sectorial retinal changes supports the hypothesis of an eye–kidney–redox interplay and indicates that advanced retinal imaging, particularly detailed sectorial OCT analysis, may represent a complementary non-invasive tool for the early detection of subclinical microvascular damage. Larger prospective studies are warranted to validate these findings. Full article

Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of type 2 diabetes mellitus (T2DM) and a recognised marker of systemic vascular injury. Whether DR—graded independently by two experienced ophthalmologists as part of routine institutional care—is independently associated with concurrent nephropathy (urine albumin-to-creatinine ratio [UACR] ≥ 30 mg/g) and subclinical cardiac stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥ 125 pg/mL) remains insufficiently examined. Methods: Retrospective cross-sectional study of 401 T2DM adults who underwent dilated fundus examination independently graded by two board-certified ophthalmologists (each ≥ 10 years’ experience in diabetic eye disease) using ETDRS-based classification. Inter-physician agreement was quantified by Cohen’s weighted kappa. The primary composite outcome was concurrent nephropathy and subclinical cardiac stress. Multivariable logistic regression adjusted for age, sex, HbA1c, diabetes duration, eGFR, hypertension, and pharmacological treatments. Results: The composite outcome was present in 120 (64.2%) DR-positive vs. 14 (6.5%) DR-negative patients (crude OR: 25.59 (13.78–47.51); p < 0.001; fully adjusted OR: 21.49 (11.02–41.81); p < 0.001). Inter-physician agreement was high (Cohen’s weighted κ = 0.88; 95% CI: 0.83–0.93). Nephropathy alone was found in 164 (87.7%) vs. 76 (35.5%) patients (OR: 12.95 (7.71–21.75); p < 0.001), and elevated NT-proBNP in 137 (73.3%) vs. 39 (18.2%) patients (OR: 12.29 (7.65–19.76); p < 0.001). A significant trend across DR severity grades was observed (p for trend < 0.001), although the gradient was not strictly monotonic. ROC AUC = 0.837 (95% CI: 0.784–0.860). Conclusions: Ophthalmologist-graded DR was independently associated with the concurrent presence of albuminuria and elevated NT-proBNP in T2DM. Because the design is cross-sectional, these findings describe association rather than prediction or causation. They generate the hypothesis that retinal grading may help flag patients in whom cardiorenal biomarker assessment is worth considering, but prospective validation is required before any screening application. Full article

Background: Type 2 diabetes (T2DM) increases the risk of mild cognitive impairment (MCI); however, the mechanisms of this process have not yet been fully identified. The aim of the study was to determine the levels of vitamin B12 and homocysteine in elderly diabetic patients, with and without cognitive impairment, and identify the risk factors associated with MCI in this group. Methods: A total of 385 elderly diabetic patients were screened for MCI (using the Montreal Cognitive Assessment). Several clinical and biochemical data were recorded. Results: MCI subjects had lower vitamin B12 levels (251 ± 36.9 pg/mL) and higher homocysteine concentrations (15.9 ± 4 ng/mL) compared to controls (vitamin B12: 339.9 ± 40.7 pg/mL; homocysteine: 11.4 ± 3.1 ng/mL). In MCI subjects, vitamin B12 levels were negatively correlated with homocysteine or HbA_1c levels and positively correlated with MoCA scores. The univariate logistic regression showed factors associated with MCI in elderly diabetic patients were the following: older age and fewer years of education, longer history of diabetes, a higher number of co-morbidities, higher levels of HbA_1c, triglycerides and homocysteine, lower levels of vitamin B12, presence of cardiovascular disease, hypertension, hyperlipidemia, retinopathy, and nephropathy. Independent factors associated with MCI evaluated in the multivariate model included lower levels of vitamin B12, higher levels of triglycerides, and a higher number of co-morbidities and fewer years of formal education. Conclusions: Vitamin B12 is associated with MCI in elderly diabetic patients. The role of homocysteine and vitamin B12 in the common pathogenesis of cognitive impairment and diabetes requires future prospective and more extensive studies. Full article

Chronic kidney disease (CKD) has become a global health issue, affecting up to 14% of the population worldwide. Between 1990 and 2021, the number of patients grew from 351 million to almost 674 million, with projections warning that CKD may rank as the fifth leading cause of death globally by 2040. Clinically, CKD stems from a complex mix of etiologies, including lifestyle-driven civilization diseases, such as diabetes, hypertension, or obesity, immune-mediated glomerulonephritides (such as IgA, membranous nephropathy or focal segmental glomerulosclerosis), genetic (such as autosomal-dominant polycystic kidney disease, Fabry disease) and tubulointerstitial diseases, or causes of undetermined etiology. Time to diagnosis and the diagnosis of CKD before end-stage organ failure are crucial; therefore, new methods are actively being developed for early detection of kidney disease. Physicians emphasize the need to evaluate markers of kidney dysfunction faster and more accurately. Modern nephrology relies on multi-omics profiling, encompassing genomics, transcriptomics, proteomics, and metabolomics. Applying these technologies to identify molecular drivers of the disease can yield specific signatures that help clinicians stratify patients and decide on a treatment and follow-up plan. Our review addresses a fundamental transformation reshaping nephrology: the transition from a traditional to precision medicine approach. Full article

Background: Endothelial dysfunction and renal injury are emerging as a common feature of long COVID, especially in those with hypertension. It is not yet well characterised whether SARS-CoV-2 infection exacerbates podocyte dysfunction, fibrotic signalling and renal hemodynamic remodelling, over and above the effects of hypertension alone and there are no reliable early biomarkers in this population. Methods: We conducted a comparative cross-sectional study with prospective 6-month treatment response follow-up in 120 adult patients (aged 30–60 years) with essential hypertension (Stage I, II or III; n = 40 per stage), at Bukhara Regional Multidisciplinary Hospital. Each stage subgroup was further divided into post-COVID (3–6 months after recovery; n = 20) and non-COVID (n = 20) strata. Patients with diabetes, known chronic kidney disease, previous myocardial infarction or stroke and other major comorbidities were excluded. Serum cystatin-C, creatinine, aldosterone, TGF-β1 and VEGF-A; urinary nephrin and microalbumin; cystatin-C-derived eGFR (CKD-EPI) and oral protein-loaded renal functional reserve (RFR); and renal Doppler indices (Vps, Ved, RI, PI) of the main, segmental and interlobar arteries were assessed before and after 6 months of guideline-based renin–angiotensin–aldosterone system (RAAS) blockade (enalapril 5–10 mg or azilsartan 40–80 mg, ±eplerenone). Comparisons were made by Student’s t-test—associations by Pearson correlation. Results: At baseline, post-COVID hypertensive patients exhibited consistently higher endothelial–podocyte injury markers than non-COVID counterparts. Urinary nephrin was elevated across all stages (Stage I: 126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01; Stage III: 203.3 ± 11.2 vs. 164.5 ± 9.7 pg/mL, p < 0.05), as were VEGF-A (Stage III: 286.1 ± 16.4 vs. 223.2 ± 12.6 pg/mL, p < 0.01) and TGF-β1 (Stage III: 186.4 ± 10.1 pg/mL, 1.3-fold higher; p < 0.01). The detection of microalbuminuria was 100% in Stage III post-COVID patients and 85% in non-COVID controls. The post-COVID groups had selective loss of renal functional reserve (7.8 ± 1.1% in Stage III compared to 12.5 ± 1.6% in non-COVID controls, p < 0.001). Nephrinuria correlated strongly with RFR (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001) and aldosterone (r = 0.613, p < 0.001). Six months of RAAS blockade reduced nephrinuria, microalbuminuria and TGF-β1 in both arms but the magnitude of biomarker reduction appeared smaller in the post-COVID group, particularly in Stage III. Conclusions: Long COVID appears to be associated with persistent endothelial dysfunction and podocyte injury in hypertensive patients. These results indicate that nephrinuria, VEGF-A, TGF-β1 and renal functional reserve are potential exploratory markers of endothelial and renal abnormalities in hypertensive patients following COVID-19. Before clinical utility can be determined, larger studies with multivariable modelling, diagnostic-performance analyses and correction for multiple testing are needed. The differences in biomarker response between groups observed in this study need to be confirmed in larger prospective studies with multivariable modelling and formal interaction analyses. Full article

Background: Hypertension (HTN) and type 2 diabetes mellitus are major global health challenges, and diabetic nephropathy (DN) is a critical complication of diabetes. Although observational studies link HTN to DN progression, causal evidence remains limited. We investigated the potential causal relationship between HTN and DN and quantified the global burden of HTN-attributable type 2 diabetic nephropathy (HTN-T2DN). Methods: We integrated two-sample Mendelian randomization (MR), Bayesian weighted MR, and sensitivity analyses with Global Burden of Disease (GBD) 2021 analyses. The burden of HTN-T2DN was assessed from 1990 to 2021 and projected to 2045. Results: MR provided genetic evidence supporting a potential causal role of HTN in DN (inverse-variance weighted odds ratio = 4.219, 95% CI: 1.807–9.853; p = 0.001). Globally, HTN-T2DN deaths increased to 50,689 and DALYs to 1,151,216 in 2021. Females had higher age-standardized mortality and DALY rates than males, and low-middle sociodemographic index (SDI) regions had the highest burden. By 2045, deaths and DALYs were projected to reach 162,392 and 4.04 million, respectively. Conclusions: HTN may play a potential causal role in DN development and progression. Strengthened blood pressure control, early screening, and tailored policies are essential, particularly for women, older adults, and populations in lower-SDI settings. Full article

Background: Distinguishing diabetic nephropathy (DN) from non-diabetic kidney disease (NDKD) in patients with diabetes remains clinically challenging, particularly when renal biopsy is not routinely performed. We aimed to identify clinical predictors of biopsy-proven NDKD. Methods: We conducted a retrospective cohort study of patients with type 2 diabetes who underwent native kidney biopsy at a tertiary referral center. Patients were classified as DN alone, mixed DN with NDKD, or pure NDKD. Baseline clinical and laboratory variables were analyzed. Logistic regression models were used to identify factors associated with NDKD. Results: Among 664 patients, 18.7% had DN alone, 27.0% had mixed lesions, and 54.3% had pure NDKD. In multivariable analysis, higher HbA1c, lower body mass index, lower low-density lipoprotein cholesterol, and higher urine albumin-to-creatinine ratio were independently associated with NDKD. For pure NDKD, lower HbA1c, lower serum albumin, lower body mass index, higher IgA levels, and absence of hypertension were significant predictors. Conclusions: NDKD is common among patients with diabetes undergoing biopsy and can be partially predicted using routinely available clinical parameters. These findings may aid in identifying patients who could benefit from timely renal biopsy and individualized management. Full article

Background: Early external validation studies demonstrated the robust and consistent predictive performance of the International IgA Nephropathy Prediction Tool (IIgAN-PT) across diverse ethnic populations. However, emerging evidence suggests that, in contemporary cohorts of patients with IgA nephropathy, the IIgAN-PT increasingly tends to overestimate the risk of adverse renal outcomes. Subclassification of segmental glomerulosclerosis (S lesions) in the Oxford Classification system (MEST-C) could identify high-risk IgAN patients, with evidence that different S subclassifications respond differently to treatment. Our study aimed to evaluate the predictive performance of the IIgAN-PT in a contemporary Chinese external validation cohort and to optimize its prognostic accuracy by incorporating the most severe and prevalent pathological subclassification of S lesions, NOS⁺Adh⁺, into the original model. Methods: A total of 746 Chinese patients were included with biopsy-proven IgAN in this study. Major adverse kidney events (MAKEs) were defined as death from any cause, initiation of renal replacement therapy, or a 50% decline in eGFR. This study evaluated the discrimination and model fit of three predictive models. The performance of the original and modified IIgAN-PT models was compared and evaluated through reclassification, survival analysis, calibration, decision curve analyses and subgroup analyses. Results: In the study cohort, the median follow-up duration was 4.2 years, during which 77 patients experienced MAKEs. The discriminative ability of the three original models was relatively limited. In contrast, the modified IIgAN-PT incorporating the NOS⁺Adh⁺ subtype of S subclassification demonstrated improved global performance for predicting 5-year risk, achieving a C-index of 0.808 (95% CI, 0.756–0.861). Kaplan–Meier survival curves showed clear risk stratification, particularly between low- and intermediate-risk categories. Reclassification analyses (continuous NRI and IDI) and decision curve analysis further supported enhanced predictive performance, while calibration curves corrected the original model’s risk overestimation. The modified model maintained stable performance across clinically relevant subgroups, including patients with hypertension, proteinuria, or receiving immunosuppression. Conclusions: This study further confirms the independent and clinically relevant prognostic value of the S pathological subclassification. The modified IIgAN-PT model, incorporating the NOS⁺Adh⁺ subtype of S subclassification, demonstrated consistent performance in individualized risk assessment for patients with IgA nephropathy. Full article

Objective: Atherosclerotic renal artery stenosis (ARAS) is increasingly prevalent among aging populations and in patients with diabetes, hyperlipidemia, aortoiliac obstructive disease, coronary artery disease, and/or hypertension. Patients with severe ARAS are at a substantially elevated risk of cardiovascular disease, recurrent congestive heart failure, stroke, ischemic nephropathy, and chronic kidney disease. Therefore, the ARAS-TR study aims to evaluate the effect of renal artery stenting on the clinical outcomes in patients with severe ARAS and renovascular hypertension. Materials: This study was conducted as a multicenter, prospective study between July 2024 and September 2025. It encompassed 278 patients with angiographically confirmed severe ARAS who underwent renal artery stent implantation. Patients were subsequently monitored for 6 months. A paired-samples t-test was used to compare continuous variables pre- and post-intervention, while categorical variables were analyzed using the Pearson chi-square test and Fisher’s exact test. Results: The mean age of the patients was 63.6 [±13.4] years, and the male gender ratio was 52.5%. After renal artery stenting, systolic and diastolic blood pressures decreased significantly at the 6-month follow-up compared with the pre-procedure levels (SBP 166.99 [21.24] vs. 135.40 [15.69], p < 0.001; DBP 96.28 [13.03] vs. 80.39 [11.03], p < 0.001, respectively). GFR (61.23 [28.33] vs. 63.35 [26.36], p = 0.029) and creatinine (1.40 [0.93] vs. 1.29 [0.66], p = 0.004) levels improved compared to baseline. The mean number of antihypertensive drugs required for patients to remain normotensive decreased significantly (3.19 [1.04] vs. 2.48 [1.13], p < 0.001) during the follow-up period. Conclusions: Percutaneous renal artery intervention appears to be a promising and safe strategy for carefully selected high-risk patients presenting with severe ARAS, renovascular hypertension, and non-atrophic kidneys. In this specific clinical context, restoring renal artery patency through percutaneous stenting was associated with improved renal function and observed reduction in the burden of antihypertensive drugs required to sustain normotension. Full article

Background: Elevated anticardiolipin IgG (aCL IgG) has been reported in end-stage renal disease (ESRD), but its association with specific etiologies of kidney failure remains unexplored. The unique pathophysiology of diabetic–hypertensive nephropathy may be associated with a microenvironment that could potentially contribute to antiphospholipid antibody production and thrombotic complications. This study aimed to investigate whether aCL IgG elevation in hemodialysis (HD) patients is associated with combined diabetes–hypertension (DM + HTN) etiology and thrombocytopenia, thereby identifying a clinically distinct potential high-risk subgroup. In this hypothesis-generating study, we focused on within-HD patient comparisons rather than healthy controls. Methods: We enrolled 242 participants: 150 healthy controls (included only to establish local reference ranges) and 92 patients with maintenance HD. The study was conducted from 01 September to 20 November 2025 in Madinah, Saudi Arabia. Serum aCL IgG was measured by chemiluminescence immunoassay (positive ≥ 12 GPL units). Comprehensive hematological and biochemical parameters were analyzed. Multivariable logistic regression identified predictors of aCL positivity. Results: In the HD cohort, 21% demonstrated aCL positivity; this represents a substantially higher rate than the 2% observed in local healthy controls (p < 0.001). This elevation was not uniform across etiologies. Strikingly, 94.7% (18/19) of aCL-positive HD patients had DM + HTN aetiology, compared with only 17.8% of aCL-negative patients (p < 0.001). Thrombocytopenia was significantly more severe in aCL-positive patients (median platelets: 100 vs. 191 × 10⁹/L, p < 0.001). In multivariable analysis, DM + HTN etiology (HTN-alone vs. DM + HTN odds ratio [OR]: 0.0013, 95% confidence interval [CI]: 0.00002–0.0999, p = 0.003; confirmed by Firth’s penalized logistic regression sensitivity analysis, and lower platelet count (OR: 0.92 per 1 × 10⁹/L increase, 95% CI: 0.87–0.98, p = 0.006) independently predicted aCL positivity. Conclusions: These hypothesis-generating findings suggest a potential association between metabolic–vascular disease and antiphospholipid immunity in ESRD. Causality cannot be inferred from this cross-sectional design. At present, routine aCL screening is not recommended outside of research protocols; prospective studies are needed to confirm these associations. Full article

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease and end-stage renal disease worldwide and results from the long-term effects of hypertension on renal structure and function. The pathogenesis of HN is complex and involves haemodynamic disturbances, renal vascular injury, oxidative stress, chronic inflammation, and progressive interstitial fibrosis. In recent years, increasing attention has focused on the role of non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—as key regulators of gene expression involved in these processes. This review summarises the current understanding of the molecular mechanisms underlying HN, with particular emphasis on the roles of oxidative stress, activation of the renin–angiotensin–aldosterone system, transforming growth factor beta signalling, and inflammatory and fibrogenic pathways. The contribution of dysregulated ncRNAs to endothelial dysfunction, inflammatory responses, apoptosis, angiogenesis, and renal remodelling and fibrosis is also discussed. Particular attention is given to miRNAs and lncRNAs as mediators of disease progression and potential biomarkers, as well as to the emerging role of circRNAs in hypertensive kidney injury, including their involvement in the regulation of redox balance and intercellular communication. Collectively, available evidence indicates that ncRNAs represent a critical link between haemodynamic stimuli and persistent molecular alterations in renal tissue, highlighting their potential as diagnostic markers and therapeutic targets in HN. Full article

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications. Full article

Background: In patients with diabetes or hypertension, if appropriate intervention is not initiated early in the course of kidney disease, not only does the risk of progressing to end-stage renal failure increase, but mortality associated with vascular complications also rises as the disease progresses; therefore, there is an urgent need to develop urinary biomarkers that enable early diagnosis and prediction of disease progression. Methods: This two-year prospective observational study involved 185 outpatients. Patients were classified into two groups based on their baseline urinary L-FABP levels relative to the reference value of 8.4 μg/g·Cr at the start of the study. The rate of eGFR decline during the observation period was evaluated. Results: The results showed an interaction (synergistic effect) between urinary L-FABP and time in patients with diabetes or hypertension who had an eGFR of at least 60 mL/min/1.732 m²/kg/1.732 m². Patients with high urinary L-FABP levels (>8.4 μg/g·Cr) exhibited a notably faster eGFR decline compared with those with low levels (≤8.4 μg/g·Cr). This finding suggests the potential of urinary L-FABP as a predictor of renal function decline; we evaluated this utility using the area under the ROC curve (AUC) and logistic regression analysis. The results indicate that urinary L-FABP holds potential as a predictor of renal function decline in diabetic or hypertensive patients with preserved eGFR. Conclusions: Among the analysis groups in which the validation was conducted, it was demonstrated that urinary L-FABP holds potential as a predictor of renal function decline in patients with diabetes or hypertension who have a maintained eGFR. Given that urinary L-FABP is thought to reflect tubulointerstitial damage associated with renal microcirculatory impairment, its future utility as a urinary biomarker for the early diagnosis and prognosis of chronic kidney disease (CKD) is anticipated. Full article

Rho GTPases are a group of guanosine triphosphate (GTP)-binding proteins with a relative molecular weight of about 20–30 kD, and 22 different Rho GTPases have been identified in mammalian cells, among which RhoA, Rac1 and Cdc42 are the most well-studied. Rho-associated coiled coil forming protein kinase (ROCK) is the most well-researched downstream effector of Rho GTPases. The Rho/ROCK signaling pathway widely participates in the reorganization of the cytoskeleton through cascade phosphorylation/dephosphorylation reactions and modulates cellular biological behaviors including cell adhesion, migration and phenotypic transformation. Abnormal activation of the Rho/ROCK signaling pathway is closely associated with the occurrence and progression of acute kidney injury, diabetic nephropathy, hypertension-related nephropathy and chronic allograft nephropathy, which contributes to podocyte injury, renal tubular epithelial-to-mesenchymal transition (EMT), mesangial cell proliferation and inflammatory infiltration in the kidney. This review focuses on the research progress and regulatory mechanisms of the Rho/ROCK signaling pathway in the above four major kidney diseases and discusses the therapeutic potential of targeting this pathway for kidney disease treatment, aiming to provide new insights for elucidating the pathogenesis of kidney diseases and developing novel therapeutic strategies. Full article

According to the Global Burden of Disease 2019 analysis, there were 606,300 new cases of chronic kidney disease due to glomerulonephritis worldwide, with 17.3 million prevalent cases and 183,700 deaths More interestingly, between 1990 and 2019, the global burden of glomerulonephritis increased by 77% in incidence and 81% in prevalence, mainly due to demographic aging and population growth. Among primary glomerulopathies, IgA Nephropathy (IgAN), also known as Berger’s disease, is the most common primary glomerulopathy worldwide, with significant geographic and ethnic variation in incidence, with the highest prevalence in Europe and Asia and the lowest in Africa. Its pathogenesis reflects a complex interaction between polygenic susceptibility and environmental modifiers, mucosal immune activation, infections of the upper respiratory and gastrointestinal tracts, dietary factors, and alterations in the gut microbiome. In addition, IgAN increasingly coexists with other chronic diseases, such as hypertension and diabetes, which complicates both diagnosis and treatment in aging societies. All these observations suggest that in the coming years, the epidemiology of IgAN will gradually transform from a description of “case counts” to a predictive tool that integrates genetic, environmental, and molecular biomarker data. In this sense, epidemiology is increasingly becoming the foundation of precision nephrology—allowing not only for disease risk prediction but also for the design of effective therapeutic strategies. The conceptual shift in IgAN—from a disease defined by biopsy prevalence to one understood through integrative epidemiology—illustrates the broader transition of GN research toward biomarker-based risk stratification and precision medicine. This review focuses on IgA nephropathy as the most prevalent primary glomerulonephritis and uses it as a reference disease to illustrate broader epidemiological patterns, outcome trajectories, and methodological limitations relevant to primary glomerulonephritides. Full article