Search Results (122)

Background: Idiopathic nephrotic syndrome (NS) in children is characterized by urinary protein loss and potential disruptions in trace element homeostasis. The dynamic changes in zinc, copper, and magnesium levels in relation to disease activity remain incompletely defined. Objective: This study aimed to evaluate serum zinc, copper, and magnesium and urinary copper and magnesium alterations in homeostasis in pediatric nephrotic syndrome and to examine their associations with disease stage, proteinuria, disease duration, renal function, and corticosteroid response. Materials and Methods: This is a prospective cohort study involving 108 participants, including 74 pediatric patients with idiopathic nephrotic syndrome and 34 healthy controls, comprising 164 clinical and biological assessments. Serum and urinary concentrations of Zn, Cu, and Mg were analyzed, alongside clearance parameters and the fractional excretion of magnesium. Statistical analysis included non-parametric tests, Spearman correlations, ROC analysis, and multivariable logistic regression. Results: Serum zinc levels were significantly lower during active disease phases and normalized during remission (p < 0.001); however, these differences in serum zinc concentration with stages of the NS disappeared after adjustment for serum protein levels (p = 0.424), suggesting a transport deficit secondary to hypoproteinemia. Although serum zinc concentrations were also significantly reduced in patients with concomitant infection, adjustment for serum protein levels attenuated this association, and the zinc-to-protein ratio did not differ significantly according to infection status (p = 0.08). Urinary copper levels and clearance were elevated during active disease and positively correlated with proteinuria (rho = 0.35–0.38; p < 0.001); the Cu/Zn ratio varied significantly across disease stages (p < 0.001) and was associated with both disease activity and a tendency toward corticosteroid resistance. Magnesium demonstrated a pattern of tubular conservation during active phases, with elevated fractional excretion values during remission (p < 0.001) and inverse correlations with proteinuria. Disease duration, but not relapse burden, was positively correlated with serum zinc and fractional magnesium excretion and inversely correlated with serum magnesium. In the multivariable analysis, serum proteins emerged as the sole independent predictor of disease activity, while age and the Cu/Zn ratio were associated with corticosteroid resistance. Conclusions: Pediatric nephrotic syndrome induces significant alterations in zinc, copper, and magnesium homeostasis, dependent on glomerular permeability and plasma protein status. Zinc changes with stages of NS likely reflect a secondary transport defect. In contrast, zinc changes with infection likely occurred because of a shift of zinc to the intracellular compartment. Urinary copper serves as a marker of glomerular permeability and magnesium highlights tubular adaptation. The Cu/Zn ratio and magnesium handling parameters may prove clinically useful in monitoring disease activity and treatment response. Full article

Gout is a systemic metabolic inflammatory disease driven by hyperuricemia and monosodium urate crystal deposition, and is frequently accompanied by chronic kidney disease and uric acid nephrolithiasis. Current evidence indicates that acidic urine, hypocitraturia, and insufficient ammonium excretion are common in gout patients, and may be associated with insulin resistance, impaired renal ammoniagenesis, and abnormalities in tubular acid-base regulation. Persistent urinary acidification may contribute to the development and progression of uric acid stone formation and gout-related renal injury by reducing uric acid solubility, promoting crystal formation and intratubular deposition, and decreasing renal uric acid clearance. Urinary alkalization therapy can increase urine pH, thereby enhancing uric acid solubility and excretion, and has shown potential in some studies to improve serum urate levels, proteinuria, renal function parameters, and gout flare frequency, especially when using citrate-based alkali. However, the currently available evidence is mainly derived from observational studies and small prospective investigations, and recommendations across international guidelines remain inconsistent. High-quality evidence is still lacking regarding the optimal target population, urine pH range, choice of alkalizing agents, monitoring strategies, and long-term efficacy. Well-designed prospective studies are therefore needed to clarify the clinical role of urinary alkalization in renal protection among patients with gout. Full article

Background/Objectives: To date, approximately 360 pathogenic variants of the OCRL gene have been reported, including frameshift, substitution, gross inversion, nonsense, and missense mutations. These genetic alterations have been associated with a broad phenotypic spectrum of Lowe syndrome, contributing to considerable variability in disease severity and clinical presentation. Missense variants are typically associated with preserved messenger RNA expression in fibroblasts, whereas more deleterious mutations result in markedly reduced expression of the OCRL transcript or protein product. Pathogenic variants in the OCRL gene have also been identified in patients with Dent’s disease type 2. Case presentation: This case report describes a pediatric male patient with autism spectrum disorder and renal dysfunction, who was found to harbor a variant of uncertain clinical significance in the OCRL gene and a pathogenic 16p11.2 chromosomal deletion. The patient, a 12-year-old boy with autism, presented with proteinuria during hospitalization for febrile gastroenteritis and streptococcal infection. Further evaluation revealed focal glomerulosclerosis, tubular calcium phosphate deposits, albuminuria, and hypercalciuria. Ophthalmologic examination additionally demonstrated bilateral lens opacities in the absence of congenital cataracts, as well as hyperopia. The coexistence of these clinical manifestations together with the identified OCRL gene variant raises the possibility of an atypical presentation of Dent disease type 2. Nevertheless, continued clinical and genetic follow-up remains warranted to further clarify the pathogenic significance of the detected variant and to establish a definitive diagnosis. Conclusions: The uniqueness of this case resides in the coexistence of two independent genetic findings presenting a phenotype-attribution challenge. Furthermore, the identified phenotype may warrant consideration as a possible previously unreported phenotypic presentation situated along the clinical spectrum between Lowe syndrome and Dent disease type 2. The main contribution of this report is to illustrate the interpretative challenges of a concurrent pathogenic 16p11.2 deletion and an OCRL variant of uncertain significance in a patient with renal disease and neurodevelopmental features. Full article

Background: Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease and kidney failure worldwide. Although most patients with diabetes are diagnosed clinically on the basis of albuminuria, estimated glomerular filtration rate decline, and diabetic retinopathy, clinical parameters alone may not reliably distinguish biopsy-proven diabetic nephropathy (DN) from non-diabetic kidney disease (NDKD) or mixed lesions. The role of kidney biopsy in diabetic patients therefore remains selective rather than routine, but its diagnostic and prognostic value is increasingly relevant in precision nephrology. Methods: This narrative review summarizes clinicopathological evidence on kidney biopsy in patients with diabetes, with particular emphasis on the Renal Pathology Society classification of DN, the prognostic significance of glomerular, tubulointerstitial, and vascular lesions, indications for biopsy, and emerging digital and molecular approaches to renal tissue assessment. Results: Histopathological evaluation provides information that cannot be fully captured by routine clinical markers. While glomerular lesions remain central to the classification of DN, tubulointerstitial fibrosis and tubular atrophy are among the strongest predictors of kidney disease progression. Vascular lesions, particularly arteriolar hyalinosis, also carry renal and cardiovascular prognostic significance. Kidney biopsy is especially valuable in patients with atypical clinical features, including rapid decline in kidney function, acute-onset nephrotic-range proteinuria, active urinary sediment, short diabetes duration, absence of diabetic retinopathy, or suspicion of immune-mediated glomerular disease. In these settings, biopsy may identify NDKD or mixed DN/NDKD, with direct therapeutic implications, including the potential use of disease-specific or immunosuppressive treatment. Emerging technologies, including artificial intelligence-assisted digital pathology, spatial transcriptomics, multi-omics profiling, and biomarker-based “virtual biopsy” models, may further refine lesion quantification and risk stratification, although they currently complement rather than replace tissue-based diagnosis. Conclusions: Kidney biopsy remains a clinically important tool in selected patients with diabetes. Beyond confirming DN, it enables the detection of NDKD, improves prognostic stratification, and supports individualized therapeutic decision-making. A selective, indication-driven biopsy strategy should be regarded as an essential component of precision nephrology in DKD, particularly as histopathology becomes increasingly integrated with digital, molecular, and computational approaches. Full article

The Kidney Disease: Improving Global Outcomes (KDIGO) CGA framework remains the essential basis for chronic kidney disease (CKD) classification, risk stratification, and guideline-based therapy. However, eGFR and albuminuria do not always explain the physiological mechanism maintaining the current filtration level or the heterogeneity of treatment responses. This narrative review proposes a hypothesis-generating functional–hemodynamic extension of KDIGO CGA that incorporates renal functional reserve (RFR), blood pressure, volume status, proteinuria phenotype, and selected tubular markers. RFR is discussed as a dynamic stress test of nephron reserve rather than as a replacement for eGFR or albuminuria. A low, zero, or negative RFR may suggest reserve exhaustion or relative hyperfiltration, but its interpretation depends on standardized testing conditions and clinical context. We distinguish established evidence-based therapy—RAAS blockade in albuminuric or hypertensive CKD, SGLT2 inhibition for kidney and cardiorenal protection, and non-steroidal MRA therapy in selected patients—from conceptual sequencing hypotheses such as RAASi-prioritized, SGLT2i-prioritized, early dual, or staged triple renoprotection. The review also summarizes albuminuria as a two-compartment phenomenon involving both glomerular passage and proximal tubular handling of filtered proteins. The proposed framework is not a validated treatment algorithm. It is intended to support physiological phenotyping, interpretation of early eGFR changes, and the design of prospective studies that test whether RFR adds independent prognostic or therapeutic value beyond KDIGO CGA. Full article

Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m², and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease. Full article

Dengue remains a major public health problem in tropical and subtropical regions, particularly in Latin America. Acute kidney injury (AKI) is one of the severe complications associated with dengue and has been linked to worse clinical outcomes, including prolonged hospitalization, need for renal replacement therapy, and increased mortality. This review aimed to summarize the available evidence on the epidemiology, pathophysiology, clinical manifestations, diagnosis, management, and prognosis of dengue-associated AKI, while also providing an overview of the literature from Latin America. This manuscript was developed as a narrative review. For the Latin America-specific overview, a focused structured search was conducted in PubMed, ScienceDirect, Cochrane Library, LILACS, and Web of Science, including studies published up to December 2025. The available data suggest that AKI in dengue is multifactorial, involving plasma leakage, renal hypoperfusion, endothelial dysfunction, tubular injury, rhabdomyolysis, thrombotic microangiopathy, and inflammatory renal damage. Clinically, AKI has been associated with oliguria, proteinuria, elevated serum creatinine, renal replacement therapy, and higher mortality. Only four eligible indexed studies from Latin America were identified in our search, all from Brazil, with small sample sizes and incomplete reporting of renal outcomes; however, additional unpublished or non-indexed local data may exist. In summary, dengue-associated AKI is a relevant complication of severe dengue, but the evidence available from Latin America remains limited. These findings highlight the need for improved renal surveillance and standardized reporting in dengue-endemic settings across Latin America. Full article

Background and Clinical Significance: Autosomal dominant tubulointerstitial kidney disease caused by a mutation in the uromodulin gene (ADTKD-UMOD) is a rare kidney disorder characterized by progressive tubulointerstitial damage and a slowly progressive loss of renal function. ADTKD is often under-recognized in the clinical setting. Diagnosis of ADTKD-UMOD can be challenging due to its nonspecific symptoms and is confirmed by genetic testing alone. Case presentation: We report the case of a 42-year-old male patient referred for evaluation of renal dysfunction, which was accidentally discovered during routine laboratory checks. He had no significant medical history and no known family history of kidney disease or gout. Physical examination was unremarkable. Renal dysfunction was confirmed, with serum creatinine at 1.44 mg/dL and eGFR at 59.5 mL/min/1.73 m². Urinalysis was within physiological limits, proteinuria being 75 mg/day. Uric acid was mildly elevated (7.5 mg/dL) without a history of gout. Other laboratory findings, including autoantibodies, were in the normal range. The patient underwent a kidney biopsy, though it was not diagnostic, showing mild focal tubular atrophy and interstitial fibrosis without glomerular involvement. Immunofluorescence staining was negative for complement and immunoglobulins. Given the above nonspecific findings, the patient was suspected of having possible ADTKD. Genetic investigation using a clinical exome next-generation sequencing approach identified a novel heterozygous missense variant in the UMOD gene (c.409T>C; p.Cysteine137Arginine (p.Cys137Arg)) that is likely pathogenic. The patient is under regular clinical-laboratory monitoring. After one year, his overall health is good, renal function is stable with no proteinuria, and uric acid is mildly increased without gout attacks. Conclusions: Increased clinical awareness is crucial for detecting ADTKD-UMOD. Genetic testing can help to resolve clinical diagnostic challenges in patients with unexplained decreased kidney function. Full article

Background: The long-term kidney outcomes in paediatric osteosarcoma survivors treated with nephrotoxic chemotherapeutic agents are not well-described. Methods: We conducted a multi-centre retrospective cohort study and recruited paediatric osteosarcoma survivors who survived beyond 5 years from cancer diagnosis over a 20-year period. Chronic kidney disease (CKD) was defined as evidence of kidney impairment, chronic tubulopathy, and proteinuria upon last follow-up. Results: We included 89 patients (57% males) with a mean follow-up period of 14.9 years. A total of 42 subjects (47.2%) developed CKD, 28 of whom had CKD stage 1 with either chronic tubulopathy or proteinuria; 14 patients had CKD stage 2 (eGFR < 90 mL/min/1.73 m²), while two had CKD stage 3 (eGFR < 60 mL/min/1.73 m²). Chronic tubular dysfunction was reported in 34 patients (38%), with hypomagnesemia being the most common manifestation. Proteinuria and hypertension were infrequently observed, in 3% and 8% of cases, respectively. We found that a history of severe AKI and aminoglycoside exposure during the treatment course were significant risk factors for CKD, but the dose-dependent relationships between the development of CKD and cisplatin, ifosfamide, and methotrexate could not be demonstrated. Conclusions: CKD is prevalent among paediatric osteosarcoma survivors. Caution is needed when using multiple nephrotoxic agents at the same time, as this could increase the risk of CKD in the long run. Multi-disciplinary regular surveillance should be performed to identify and manage CKD early, including kidney function, electrolyte, and proteinuria monitoring. Full article

Early diagnosis of chronic kidney disease (CKD) remains a major clinical challenge. Periostin (POST) and kidney injury molecule-1 (KIM-1) have been proposed as biomarkers of tubular injury and fibrosis. This study aimed to evaluate their utility as markers associated with CKD stage and their associations with renal function and proteinuria in children. Twenty-three children with CKD stages I–IV and 23 healthy controls were enrolled. Serum and urinary POST and KIM-1 were measured together with creatinine (CR), cystatin C (CysC), proteinuria, albuminuria, and urinary α1- and β2-microglobulin. Patients were classified as early stage (ES; CKD I–II) or late stage (LS; CKD III–IV). Serum and urinary POST and KIM-1, uPOST/CR, uKIM-1/CR, fractional excretion indices (FePOST, FeKIM-1), and UPCR were higher in CKD patients than in controls. Absolute biomarker concentrations did not differ between ES and LS and were not associated with eGFR, UPCR, UACR, or tubular protein excretion. In contrast, uPOST/CR, uKIM-1/CR, FePOST, and FeKIM-1 increased with CKD stage, were higher in LS than ES, correlated positively with CysC, and inversely with eGFR. FePOST and FeKIM-1 also correlated strongly with tubular protein markers. The FePOST/FeKIM-1 ratio was elevated in ES patients compared with controls and remained stable across CKD stages. Fractional excretion of POST and KIM-1 is associated with CKD stage and reflects ongoing tubular injury in children. The FePOST/FeKIM-1 ratio may represent a sensitive marker of early CKD. Full article

Patients without overt glomerular dysfunction may develop tubular injury, referred to as subclinical acute kidney injury. The burden of COVID-19-related renal damage may therefore be underestimated, as current KDIGO criteria do not include tubular damage biomarkers (TDBs). This study evaluated kidney injury in patients with long COVID by assessing TDBs alongside glomerular biomarkers, proteinuria (UPCr) and albuminuria (UACr). In this cross-sectional study, 75 patients without prior chronic kidney disease were recruited from a long COVID outpatient clinic and stratified according to the time since SARS-CoV-2 infection into 6-, 12-, and 24-month post-COVID-19 groups (referred to as 6-, 12-, and 24-MPC, respectively). Overall, 49.3% of patients had normal estimated glomerular filtration rate (eGFR >90 mL/min/1.73 m²), 34.7% showed mildly reduced eGFR (90–60), and 16% exhibited marked eGFR reduction (<60). Among patients with normal eGFR, the combined mean prevalence (mean ± SD) of abnormal TDBs, UACr, and UPCr was 29.7 ± 4.9%, indicating early tubular injury. Temporal analysis revealed a higher prevalence of TDB abnormalities at 6-MPC, whereas glomerular dysfunction was more pronounced at 24-MPC. These findings suggest that renal injury in long COVID is more prevalent than previously recognized and that TDB assessment may improve early detection of kidney damage. Full article

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus that contributes substantially to chronic kidney failure and increased cardiovascular risk. Beyond progressive deterioration of renal function, DKD is associated with disturbances in endocrine and vascular regulation. Among these, alterations in vitamin D homeostasis and blood pressure (BP) control represent clinically relevant, yet incompletely integrated aspects of DKD pathophysiology. This narrative review synthesizes current evidence on the multidirectional relationships between DKD, vitamin D deficiency, and arterial hypertension (AH). Attention is given to renal mechanisms responsible for reduced vitamin D availability in DKD, including proteinuria-related loss of vitamin D-binding proteins, impaired proximal tubular reabsorption, decreased renal activation of vitamin D, and hormonal regulators such as fibroblast growth factor-23. It further discusses how insufficient vitamin D signaling may influence renal and vascular pathways involved in BP regulation. Mechanistic links between vitamin D deficiency and AH in DKD are discussed, with emphasis on maladaptive activation of the renin–angiotensin–aldosterone system (RAAS), persistent inflammation, oxidative stress, endothelial dysfunction, and insulin resistance. These interdependent processes promote both renal injury progression and sustained elevations in BP, forming a self-reinforcing pathogenic loop. Finally, available data on vitamin D-based therapeutic strategies in DKD are reviewed, including native vitamin D supplementation, active vitamin D metabolites, and vitamin D receptor agonists. Although experimental and observational studies suggest potential nephroprotective and vasculoprotective effects, evidence from randomized clinical trials remains heterogeneous. Further well-designed prospective studies are required to clarify the clinical utility of vitamin D interventions in patients with DKD and coexisting AH. Full article

Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to investigate the role of this pathway in IgAN and examine related tissue inflammatory markers. Methods: We analyzed 63 biopsy-confirmed patients with IgAN and performed immunohistochemical analysis on renal samples. A panel of antibodies targeting the JAK/STAT pathway, including JAK2, JAK3, p-STAT, STAT3, and MAPK/ERK, was used for this analysis. Six kidney tumor border samples were used as controls. Additionally, CD68 staining was used to evaluate tissue inflammation in the kidney biopsies. Results: Patients with IgAN showed a significantly higher cellular density of JAK3 staining at the glomerular level compared to controls, indicating JAK3 activation (p < 0.0002). Nevertheless, the correlation between JAK3 positivity in glomeruli and clinical parameters such as the initial and final estimated glomerular filtration rate (eGFR) and proteinuria was not statistically significant. Identical results were obtained with CD68+ macrophage counts in the glomerular compartment, which did not show any correlation with clinical parameters, while CD68+ tubulointerstitial staining demonstrated a significant correlation with both initial (p = 0.002) and final eGFRs (p = 0.0014), proteinuria (p = 0.010), and interstitial fibrosis (p < 0.001), as well as with renal disease progression (p = 0.005). Conclusions: Activation of the JAK/STAT pathway was observed in patients with IgAN relative to controls, notwithstanding the inability to assess the full pathway due to technical limitations. Macrophage CD68 staining in the tubulointerstitial area increased and was associated with clinical and laboratory parameters such as eGFR and proteinuria. Additionally, MEST-C histological parameters, such as segmental glomerulosclerosis (S0/S1), tubular atrophy/interstitial fibrosis (T0/T1/T2), and crescents (C0/C1/C2), were associated with a higher number of CD68+ cells. Full article

Plasma cell disorders often have urinary excretion of monoclonal immunoglobulins and renal injury that are evaluated using total protein assays and electrophoresis. Proteinuria was evaluated for 100 patients with plasma cell disorders and 24 h collections. A turbidimetric method on the Abbott Alinity quantified protein. Electrophoresis used agarose gels. Most specimens (66%) had protein concentrations below the manufacturer’s limit of quantitation (LOQ), 6.8 mg/dL (68 mg/L). After validating an LOQ of 3 mg/dL (30 mg/L), 34% of urine specimens still were below the LOQ. After excluding 40 patients with other causes of increased protein excretion (decreased estimated glomerular filtration rate (eGFR), diabetes mellitus, or overflow proteinuria), almost all patients had protein excretion below an upper reference limit of 150 mg/d. Median total protein excretion for these 60 patients was 75 mg/d; only one patient excreted >132 mg/d. However, 32% of these patients without increased total protein excretion had albumin excretion ≥ 30 mg/d, suggestive of kidney injury. Electrophoretic patterns included glomerular, tubular, and overflow proteinuria; 32 specimens contained monoclonal immunoglobulins. Protein concentrations of urine are often below LOQs of total protein assays, raising questions about whether LOQs should be improved. Urine albumin measurements and electrophoretic patterns may serve as more sensitive indicators of kidney injury in patients with plasma cell disorder than measurements of total protein excretion or increased serum creatinine. Full article

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance. Full article