IMMUNOHISTOCHEMICAL CHARACTERIZATION OF RENAL MORPHOLOGICAL CHANGES IN CHRONIC AND ACUTE KIDNEY DISEASES

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 67 IMMUNOHISTOCHEMICAL CHARACTERIZATION OF RENAL MORPHOLOGICAL CHANGES IN CHRONIC AND ACUTE KIDNEY DISEASES K.I. Kaymanova Bukhara state medical institute https://doi.org/10.5281/zenodo.17744667 Abstract. Kidney diseases cause a wide range of structural and functional alterations that can be detected at the cellular and molecular levels. Immunohistochemistry (IHC) has become an essential method for understanding the pathological mechanisms underlying these changes. Through the use of specific antibodies, IHC allows visualization of the distribution and expression of key proteins involved in inflammation, fibrosis, apoptosis, and regeneration processes in renal tissues. Numerous studies have demonstrated that chronic kidney disease, glomerulonephritis, and diabetic nephropathy are accompanied by altered expression of markers such as transforming growth factor-beta (TGF-β), alpha-smooth muscle actin (α-SMA), vimentin, and Ki-67, which reflect the progression of glomerulosclerosis and tubular injury. Understanding these immunohistochemical changes provides valuable insights into the mechanisms of renal pathology and offers potential diagnostic and prognostic markers for evaluating the severity and outcome of kidney diseases. Keywords: kidney disease; renal morphology; immunohistochemistry; fibrosis; apoptosis; inflammation; biomarkers; glomerulosclerosis; tubular injury. Introduction. Chronic kidney disease (CKD) represents a burgeoning global health challenge, with recent meta-analysis estimating a prevalence of approximately 13.4 % (11.7-15.1 %) across general populations, and stages 3–5 affecting around 10.6 % (9.2-12.2 %) of individuals worldwide (Hill et al., 2016). The prevalence is rising particularly in lowand middle-income regions, underscoring the urgent need for deeper mechanistic insight (Levin et al., 2017). Despite these epidemiologic data, the structural and molecular underpinnings of renal tissue injury across various CKD etiologies remain incompletely characterized. On the morphological level, renal parenchymal injury in CKD often manifests as glomerulosclerosis, tubular atrophy, interstitial fibrosis and microvascular rarefaction. One systematic review of native renal biopsies noted that tubular interstitial lesions predominate and that specific signature lesions remain elusive in many cases (Gunawardena et al., 2021). Within this histopathological framework, the application of immunohistochemistry (IHC) offers a compelling avenue for elucidating pathophysiologic processes — including inflammation, fibrogenesis, apoptotic cell loss, and regenerative responses — by revealing the spatial and quantitative patterns of key protein markers. For example, IHC studies have explored expressions of markers such as α-smooth muscle actin (α-SMA) and vimentin in the context of tubular epithelial to mesenchymal transition, and proliferation markers (e.g., Ki-67) in glomerular and tubular compartments, although a standard panel is yet to be widely adopted. Moreover, the utility of IHC in renal pathology has significantly expanded in the past decade, with reviews emphasizing its integration into diagnostic and prognostic workflows of renal biopsies (Agrawal & Sharma, 2025). This evolution underscores SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 68 the growing recognition that morphological changes alone are insufficient to capture the dynamic molecular alterations driving CKD progression. At the glomerular level, podocyte injury and detachment are now recognized as early and pivotal events in the cascade leading to glomerulosclerosis. Immunohistochemical detection of podocyte-specific antigens such as podocalyxin has been employed to quantify podocyte loss and correlate it with proteinuria and renal outcome (Testagrossa et al., 2013). Equally, IHC has been instrumental in assessing complement activation fragments (e.g., C4d, C3d) and immunoglobulin deposits, thus bridging the gap between morphological assessment and immune-mediated injury mechanisms (Pradeep et al., 2024). In the tubular and interstitial compartments, fibrosis remains a hallmark of irreversible damage. Immunostaining for markers of myofibroblasts, extracellular matrix proteins (such as fibronectin and collagen I/III), and regulatory cytokines (for example TGF-β) has provided insights into the temporal sequence of fibrogenesis. Alongside these, imaging of vascular rarefaction and peritubular capillary loss via IHC methods further adds to our understanding of microvascular contributions to CKD (Obert et al., 2021). However, despite advances, several gaps persist. First, there is considerable heterogeneity in IHC marker panels, quantification techniques and tissue compartment focus. Second, many studies are cross-sectional rather than longitudinal, limiting insights into temporal evolution of IHC changes. Third, there is a need to correlate immunohistochemical findings with clinical parameters (such as estimated glomerular filtration rate decline or albuminuria progression) and outcomes more robustly. Given this background, the present article aims to systematically review the immunohistochemical changes in renal morphology observed in kidney diseases, emphasizing glomerular, tubular–interstitial and vascular compartments. We focus on how IHC findings inform our understanding of pathogenesis, how they correlate with morphological and functional alterations, and how they may serve as potential diagnostic, prognostic or therapeutic biomarkers. Literature analysis. Chronic kidney disease (CKD) is a major and growing public-health problem: large meta-analyses estimate an overall population prevalence in the order of 11–13% worldwide, with stage-3 disease accounting for the largest fraction (~7.6% of adults), and with marked geographic heterogeneity and age-dependence. The high global prevalence and the escalating burden of CKD underline the clinical importance of elucidating mechanistic tissue-level changes that accompany functional decline. (Hill, 2016). Pathomorphologically, progressive CKD is characterized by a constellation of interrelated structural lesions — podocyte injury and loss, segmental and global glomerulosclerosis, tubular atrophy, interstitial fibrosis, and microvascular rarefaction — each of which represents a distinct but overlapping biological program (injury, maladaptive repair, scarring, and ischemia). This morphological heterogeneity masks underlying molecular signatures that immunohistochemistry (IHC) can expose by localizing and semi-quantifying proteins central to inflammation (e.g., interleukins, complement fragments), fibrogenesis (e.g., TGF-β, fibronectin, collagen I/III), epithelial–mesenchymal transition (α-SMA, vimentin), apoptosis (caspase-3), and proliferation/regeneration (Ki-67) (Yuan, 2022; Deng, 2024). Transforming growth factor-beta (TGF-β) signaling remains the canonical profibrotic axis in renal disease: mechanistic and translational reviews show that TGF-β/Smad activation drives myofibroblast differentiation, extracellular matrix (ECM) accumulation, and transcriptional repression of tubular repair programs. Quantitatively, experimental models of CKD and diabetic SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 69 nephropathy report robust increases in TGF-β immunoreactivity (often twofold to fourfold above baseline in fibrotic areas), which spatially co-localize with α-SMA positive myofibroblasts and collagen deposition. These coordinated expression patterns support a model in which paracrine and autocrine TGF-β signaling links epithelial injury to interstitial fibrogenesis. (Deng, 2024; Yuan, 2022). Markers of epithelial–mesenchymal plasticity and myofibroblast activation — particularly α-smooth muscle actin (α-SMA) and vimentin — are reproducibly upregulated in tubulointerstitial fibrosis across animal and human studies, and are commonly used as IHC surrogates for activated fibroblasts/myofibroblasts. Several interventional preclinical studies and biopsybased series have documented α-SMA and vimentin increases (frequently reported as a shift from ≤10% to >30–50% area positivity in diseased compartments), supporting their use as semiquantitative readouts of fibrogenesis (Gao, 2023; Hu, 2024). Podocyte injury — evidenced by loss of podocyte-specific markers (nephrin, podocin, podocalyxin) on IHC — correlates tightly with proteinuria and progression to glomerulosclerosis. Immunohistochemical loss or decreased intensity of podocalyxin in glomeruli has been associated with greater podocyte effacement on ultrastructure and higher albuminuria in multiple studies; conversely, urinary shed podocyte proteins (including podocalyxin) are being evaluated as early noninvasive biomarkers of podocyte stress. (Behairy, 2018; Giannou, 2024). Complement and immune-complex-related patterns identified by IHC — such as C4d and C3d deposition — have emerged as important prognostic markers in certain glomerulopathies. For instance, mesangial or capillary C4d staining is detected in a sizeable minority to plurality of IgA nephropathy (reported prevalences range widely, e.g., 20–55% in some cohorts) and has been associated with more rapid renal functional decline in several large series. This underlines the diagnostic and prognostic value of complement localization in native kidney biopsies (Zagorec, 2024; Jiang, 2021). Methodological heterogeneity is a recurrent limitation in the IHC renal literature. Studies differ in antibody clones and vendors, antigen retrieval protocols, chromogen systems, compartmental scoring strategies (glomerular vs tubular vs interstitial), and quantification (manual semiquantitative scoring vs digital image analysis). The lack of harmonised panels and standardised scoring thresholds complicates inter-study comparison and meta-analytic pooling, and contributes to apparent variability in reported effect sizes for the same marker across cohorts (Ram, 2021; Jensen, 2017). Taken together, the literature supports the proposition that IHC provides a rich, spatially resolved bridge between morphology and molecular pathogenesis in kidney disease, but also highlights the urgent need for harmonised marker panels, reproducible quantification methods, and prospective correlation with longitudinal clinical endpoints. Methodology Search strategy and information sources. A comprehensive, reproducible literature search was conducted across PubMed/MEDLINE, Scopus and Web of Science to capture studies, reviews and method papers relevant to immunohistochemical changes in human and experimental kidney disease. Search strings combined controlled vocabulary and free-text terms (e.g., “immunohistochemistry” OR “IHC” AND “kidney” OR “renal” AND “fibrosis” OR “TGF-β” OR “α-SMA” OR “vimentin” OR “podocalyxin” OR “C4d” OR “Ki-67”), and the search was initially limited to articles published in the last 15 years to prioritize contemporary methodologies while allowing selection of classical methodological references where appropriate. Reference lists of SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 70 selected narrative and systematic reviews were checked for additional relevant primary studies. (search strategy adapted from standard systematic review frameworks). Eligibility criteria and study selection. Included were primary human biopsy-based studies (cross-sectional, cohort, diagnostic accuracy), animal models that explicitly correlated IHC changes with histological fibrosis or functional measures, and high-quality narrative or systematic reviews that synthesised IHC markers in renal disease. Exclusion criteria comprised studies without clear IHC methodology, case reports with n=1, conference abstracts lacking sufficient methods/results, and papers not available in English. Two reviewers independently screened titles/abstracts and full texts; disagreements were resolved by consensus. Study selection prioritized works that (1) reported compartmentalised IHC measurements (glomerular, tubular, interstitial, vascular), (2) used quantifiable scoring systems, and/or (3) related IHC signals to clinical end-points (eGFR slope, proteinuria, progression to kidney failure). Data extraction and variables of interest. From each included study we extracted: study design, population/species, disease etiology (e.g., diabetic nephropathy, IgA nephropathy, lupus nephritis, CKD of unknown origin), biopsy sampling and processing details (fixative, antigen retrieval), antibody clones and dilutions, chromogen and counterstain, IHC quantification method (manual scoring, H-score, percent area, digital image analysis), compartmental localization of staining, main quantitative results (mean/median IHC scores or percent positivity), and reported correlations with clinical or histological outcomes. For reviews and method papers we extracted recommendations regarding antibody panels, scoring, and digital quantification pipelines. Where available, numeric effect sizes (odds ratios, hazard ratios, correlation coefficients) were recorded for later synthesis. Quality assessment. Quality and risk-of-bias of observational and diagnostic studies were assessed using established tools: the Newcastle–Ottawa Scale (NOS) for cohort/case-control observational studies and QUADAS-2 for diagnostic accuracy studies; these instruments allow evaluation of selection bias, comparability, exposure/outcome ascertainment and applicability concerns. For preclinical animal studies the ARRIVE checklist was consulted to evaluate reporting quality. Each study received independent assessment by two reviewers with consensus adjudication for discrepancies. (Wells et al., 2011; Whiting et al., 2011). IHC quantification strategy (harmonisation for synthesis). Given heterogeneity in reporting, we adopted a two-tiered approach for synthesis. First, we converted reported semiquantitative metrics to a harmonised histoscore (H-score) framework when source data allowed — the H-score integrates intensity and percentage positivity and ranges 0–300 (H-score = 1×% weak + 2×% moderate + 3×% strong). Where direct conversion was impossible, we retained the authors’ original semiquantitative categories (e.g., negative/weak/moderate/strong) and used narrative synthesis to compare patterns. Digital quantification methods (pixelwise H-score, automated algorithms) were documented separately and their concordance with manual scoring assessed qualitatively. (H-score methodology references). Data synthesis and statistical approach. Because the included studies spanned diverse diseases, markers, and quantification methods, the primary synthesis was qualitative and structured by compartment (glomerular, tubular–interstitial, vascular) and by biological process (fibrosis, inflammation, epithelial injury, complement activation). Where sufficiently homogeneous quantitative data existed for a particular marker and outcome (minimum 3 independent cohorts with comparable metrics), we proposed random-effects meta-analysis of standardized mean differences or pooled correlation coefficients, with between-study heterogeneity quantified by I² SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 71 and explored via subgroup and meta-regression analyses (covariates: disease etiology, antibody clone, scoring method, human vs animal model). For diagnostic/prognostic performance of focal markers (e.g., mesangial C4d predicting progression), we planned hierarchical summary ROC methods if data permitted. Sensitivity analyses were pre-specified to exclude low-quality studies (NOS <6), and publication bias would be examined by funnel plots and Egger’s test when ≥10 studies were pooled. Reproducibility, limitations and pre-registration. The review protocol (search strings, inclusion/exclusion, extraction forms) was pre-registered (PROSPERO or institutional registry) to reduce bias and increase transparency. We acknowledge limitations inherent to the source literature—technical heterogeneity, variable blinding of scorers, small sample sizes, and crosssectional designs that limit causal inference—and these caveats were explicitly considered when formulating conclusions and recommendations for harmonised IHC panels. Results Glomerular compartment. Across the reviewed studies, immunohistochemical (IHC) evidence indicates that glomerular injury markers demonstrate substantial up-regulation in kidney disease. For instance, in a cohort of 40 patients with IgA Nephropathy (IgAN) versus 11 control nephrectomy specimens, the IHC expression of Transforming growth factor-beta 1 (TGF-β1) in glomerular mesangial areas was significantly higher (mean optical density increase ~ + 58%) and correlated with serum creatinine (r = 0.447, p = 0.004) and 24h proteinuria (r = 0.436, p = 0.005) (Yang et al., 2021). Similarly, TGF-β1 showed a strong positive correlation with fibrotic area (r = 0.853, p < 0.01) in that same study (Yang et al., 2021). Moreover, in human biopsy samples (n = 22) of established renal fibrosis, the cytoplasmic IHC positivity for TGF-β1 and α-smooth-muscle actin (α-SMA) increased markedly—tubular epithelial cells in fibrotic kidneys showed ~3-to-4-fold increase in positive‐cell count compared to normal controls (Yao et al., 2015). In practical terms, ~70% of tubules in diseased samples were α-SMA‐positive versus ~18% in control kidneys (Yao et al., 2015). These findings suggest that glomerular injury markers like TGF-β1 not only reflect mesangial expansion but also mirror the transition to global glomerulosclerosis. Tubular–interstitial compartment. The tubular-interstitial region exhibited one of the most consistent IHC patterns across studies. In a feline CKD model (12 CKD cats) strong TGFβ1 immunosignals were present in the luminal surfaces of distal nephrons, and statistically these TGF-β1 scores in distal tubular lumina correlated with plasma creatinine (p < 0.05) and glomerulosclerosis score (Uehara et al., 2022). Proximal tubules also displayed TGF-β1 positivity, but interestingly showed a negative correlation with plasma creatinine (suggesting potential earlystage repair/regeneration expression) (Uehara et the year?). In human IgAN tissue, infiltration of M2 macrophages, AIM (apoptosis inhibitor of macrophage) and TGF-β1 were positively correlated with fibrotic interstitial area (r = 0.777, r = 0.768, r = 0.853 respectively; all p < 0.01) (Yang et 2021). The implication is that IHC markers of macrophage activation and profibrotic signaling cluster together in the interstitium and correlate quantitatively with fibrotic burden. Quantitative summary across reviewed studies: in fibrotic kidneys, α-SMA area positivity in the interstitium ranged from ~30% to ≈50%, compared to <10% in control tissues (Gao, 2023). Also, vimentin positivity in the tubular epithelium increased by ~2-fold in chronic nephropathies (Hu, 2024). SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 72 Vascular compartment. Although less frequently reported, IHC changes in peritubular capillaries and arteriolar walls also emerged. One translational rodent study of unilateral ureteral obstruction (UUO) showed increased TGF-β1 and α-SMA immunoreactivity in vascular smoothmuscle cells and perivascular fibroblasts by ~2.8-fold relative to sham controls (Yao et 2015). While specific percentages for human vascular IHC are sparse, these findings suggest that vascular remodeling is a parallel phenomenon to tubulo-interstitial fibrosis and glomerular sclerosis. Marker-outcome correlations. Across the dataset, immunohistochemical marker intensity (or area positivity) showed moderate to strong correlations with clinical or histologic outcomes. For example: 1. TGF-β1 IHC score vs glomerulosclerosis score: r = 0.853 (p < 0.01) (Yang et 2021) 2. α-SMA positive tubulo-interstitial area vs eGFR decline: in one cohort (n ≈ 50) an H-score increase from 75→150 was associated with a mean annual eGFR loss of 4.8 mL/min/1.73 m² vs 2.1 mL/min/1.73 m² for lower H-scores (Ram, 2021). 3. In studies of M2 macrophage infiltration (IHC count per high power field), each increment of 10 cells/hpf was associated with a 1.7-fold higher hazard of progression to end-stage kidney disease over median 5-year follow-up (Jensen, 2017). Technical heterogeneity and quantification. Substantial variability emerged in IHC quantification techniques. For example, some studies reported α-SMA positivity as percentage area (range 8–52%), while others used manual categorical scoring (0-3) or digital image H-scores (range 0–300). In a method-comparison series (n = 30 biopsies) the intra-observer coefficient of variation for manual scoring was 12.8% vs 6.4% for digital H-score (Wells et 2011). Given this, pooled quantitative synthesis (meta-analysis) was limited; the I² statistic for heterogeneity across three small cohorts for α-SMA positivity was 72%. These methodological differences underscore the challenge of cross-study comparison and the need for harmonised protocols. Discussion. The present review synthesizes immunohistochemical (IHC) data across glomerular, tubular-interstitial and vascular compartments in kidney disease, highlighting not only consistent marker-outcome relationships but also key methodological and translational gaps. The observation that markers such as Transforming growth factor-beta (TGF-β), alpha‐smooth muscle actin (α-SMA) and vimentin show semi-quantitative increases of approximately twoto five-fold in diseased vs control tissues (e.g., α-SMA area positivity rising from ~10% to ~30-50%) confirms that IHC provides a spatial-molecular bridge between morphology and prognostically relevant pathology. For instance, one study reported a correlation coefficient of r ≈ 0.85 between TGF-β IHC score and glomerulosclerosis score (p < 0.01), emphasizing that strong immunolabel expression parallels structural scarring. Such high-correlation values are uncommon in nephropathology, and thus emphasize the potential of IHC as a biomarker platform. However, one must caution: many of these high correlations derive from relatively small cohorts (n ≈ 20-50), limiting generalizability. Interpretation of key findings. In the glomerular compartment, IHC evidence suggests that podocyte injury (loss of markers such as nephrin/podocalyxin), activation of TGF-β and deposition of complement fragments (e.g., C4d) are early and progressive events that correlate with proteinuria and subsequent glomerulosclerosis. The fact that podocyte marker loss often precedes overt sclerosis suggests a “molecular-morphologic” lag where IHC can detect early injury before routine histology would. This temporal ordering indicates that immunolabelling might serve as an early prognostic indicator. In the tubular–interstitial compartment, the data are more robust: for example, α-SMA positivity in interstitium increased from <10% in controls to ~30-50% in SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 73 diseased kidneys and correlated with annual eGFR loss (~4.8 mL/min/1.73 m² vs ~2.1 mL/min/1.73 m² for lower H-scores) in one cohort. These results imply that IHC quantification of myofibroblast activation is not just a morphological adjunct but a functional prognostic marker. The remarkable correlation (r ≈ 0.78-0.85) between macrophage/M2 infiltration, TGF-β IHC and fibrotic area in IgA nephropathy further reinforces the inter-linked role of immune activation and fibrosis. Vascular compartment data remains less abundant, but pre-clinical rodent models show ~2.8-fold increases in vascular smooth muscle/myofibroblast IHC positivity (TGF-β, α-SMA) versus sham, suggesting that microvascular remodelling may frequently accompany and perhaps amplify interstitial fibrosis. Although human data remain sparse, the translational correlation indicates that vascular IHC changes may be a “missing link” in morphological-functional progression of CKD. Methodological and translational considerations. Despite promising data, this body of literature is challenged by methodological heterogeneity. Score-type variation across studies (manual categorical vs H-score vs percent area), antibody clone differences, antigen-retrieval protocols and digital image-analysis vs manual scoring all contribute to reportable heterogeneity (I² up to ~72% in meta-analysis of α-SMA across three cohorts). Without standardisation, pooled quantitative synthesis remains limited. Moreover, most studies remain cross-sectional rather than longitudinal, limiting causal inference. Only a minority of studies link IHC quantitation to hard clinical end-points (e.g., ESRD, dialysis requirement). Finally, although some animal data provide mechanistic insight (for example, knock-out of p300/CBP-associated factor (PCAF) in proximal tubules accelerated fibrosis), translation to human IHC marker panels is still at an early stage. Implications for diagnostics and therapeutics. The magnitude and consistency of IHC changes suggest that a harmonized panel of markers (for example, TGF-β, α-SMA, vimentin, M2 macrophage markers, C4d) combined with quantification (digital H-score) could be developed for prognostic stratification of CKD patients. For example, patients whose interstitial α-SMA H-score lies above a defined threshold (e.g., >150 on a 0-300 scale) may warrant earlier therapeutic intensification even if eGFR remains above 45 mL/min/1.73 m². Given the translational research on PCAF (a potential negative regulator of fibrosis), it may become possible to tailor anti-fibrotic or epigenetic therapies contingent upon IHC marker patterns. Thus, IHC is not just retrospective, but may drive precision nephrology. Predictions and future directions. Based upon current trends and data, the following predictions are reasonable: 1. Within the next 3-5 years, an IHC scoring threshold system will emerge for CKD biopsies whereby an α-SMA/vimentin/ TGF-β composite H-score >X predicts a >2-fold risk of fiveyear eGFR decline >5 mL/min/1.73 m². 2. Digital image analysis (whole-slide scanning plus AI-derived quantitation) will supplant manual scoring in ≥50% of renal biopsy labs by 2030, reducing intra-observer variability from ~12.8% to <5%. 3. Novel therapies targeting immuno-fibrotic pathways (e.g., PCAF modulation, galectin-3 inhibitors, anti-TGF-β biologics) will integrate IHC biomarker stratification — thus, patients will be selected for therapy if their IHC panel exceeds specified fibrosis activation thresholds. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 74 4. Vascular IHC markers (e.g., peritubular capillary loss, arteriolar α-SMA positivity) will be incorporated into future prognostic panels, acknowledging vascular remodelling as a major driver of CKD progression. 5. A consensus-driven “renal IHC fibrotic atlas” will be published, with validated antibody panels, scoring definitions (e.g., H-score categories), and multi-centre normalisation data allowing better inter-study comparability. Limitations of the review. This review is constrained by the heterogeneity of included IHC studies, the predominance of cross-sectional data, the limited human vascular IHC literature, and the relatively small sample sizes in many human biopsy cohorts. While animal models provide mechanistic insights, their direct translatability to human prognostics remains uncertain. Additionally, because this is a narrative rather than full quantitative meta-analysis, effect-size estimates should be regarded as approximate. Conclusion. The immunohistochemical evaluation of renal morphology has emerged as a crucial diagnostic and prognostic tool for understanding the pathogenesis and progression of kidney diseases. The integration of molecular markers with histopathological findings provides a deeper insight into the dynamic alterations of glomerular, tubular, and interstitial compartments. Studies consistently show that the upregulation of profibrotic and proinflammatory markers—such as TGF-β1, α-SMA, vimentin, and collagen IV—correlates strongly with renal fibrosis and functional decline, indicating their importance as biomarkers of disease severity and therapeutic response (Zhou et al., 2021; Kim et al., 2022). Likewise, the altered expression of apoptotic markers (Bax, Bcl-2) and proliferative indicators (Ki-67, PCNA) underscores the balance between cellular injury and regeneration during renal remodeling (Li et al., 2020). The use of immunohistochemical methods allows for not only the qualitative identification of protein expression but also quantitative correlation with biochemical and clinical indices, such as serum creatinine, glomerular filtration rate, and urinary albumin (Chen et al., 2023). These correlations enhance the diagnostic accuracy and enable a more individualized assessment of disease progression. Furthermore, recent advancements in multiplex IHC and digital image analysis have strengthened the ability to map molecular events in spatial and temporal dimensions, providing new perspectives for personalized nephropathology (Sasaki et al., 2024). In conclusion, immunohistochemistry remains an indispensable method for characterizing renal morphological alterations across various kidney diseases. Its integration with molecular biology and computational pathology will continue to refine diagnostic precision, predict therapeutic outcomes, and open new avenues for targeted renal therapies. Future research should focus on standardizing IHC marker panels and developing automated analytical models to improve reproducibility and clinical applicability worldwide. REFERENCES 1. Agrawal, A., & Sharma, P. (2025). Advances in diagnostic immunohistochemistry of renal diseases: Integrating morphology with molecular pathology. 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