Search Results (538)

Chronic kidney disease (CKD) remains a leading cause of premature mortality and global disease burden, yet the molecular mechanisms underlying its progression are still incompletely understood. Accumulating evidence highlights circadian disruption as an underappreciated driver of CKD that warrants systematic re-examination. The kidney harbors an autonomous circadian oscillator, principally regulated by the CLOCK:BMAL1 transcription factor complex, which coordinates glomerular filtration, tubular electrolyte handling, blood pressure rhythmicity, inflammatory tone, and cellular repair. In CKD, retained uremic toxins, sustained oxidative stress, and persistent NF-κB activation collectively suppress this clock machinery, generating a self-reinforcing cycle of renal injury and circadian dysregulation. CKD is also accompanied by progressive attenuation of nocturnal melatonin secretion, weakening a central hormonal cue for peripheral clock entrainment and cytoprotection. Melatonin acts both as a chronobiotic and as a pleiotropic cytoprotective molecule. Through MT1/MT2 receptors, the nuclear receptor RORα, and receptor-independent antioxidant pathways, it may enhance Nrf2/HO-1 signaling, restrain NF-κB and NLRP3 inflammasome activity, suppress TGF-β1/Smad2/3-mediated fibrogenesis, preserve mitochondrial integrity, and engage SIRT1-linked clock regulation. Current clinical studies suggest that nightly melatonin supplementation can improve sleep quality and selected oxidative or circadian surrogate endpoints in hemodialysis patients; however, whether melatonin slows CKD progression or preserves renal function remains unproven. This review synthesizes the molecular interface between circadian dysregulation and CKD progression and articulates a rationale for adequately powered clinical trials evaluating melatonin as a candidate chronotherapeutic adjunct rather than an established renoprotective therapy. Full article

Background and Objectives: Anemia is a common complication of chronic kidney disease (CKD) and is associated with reduced quality of life, accelerated disease progression, and increased cardiovascular risk. Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated significant renal and cardiovascular benefits, and clinical trials have reported improvements in hematologic parameters during treatment. However, real-world evidence regarding their longitudinal effects on hemoglobin (Hb) and iron metabolism in patients with CKD remains limited. Materials and Methods: We conducted a pre–post analysis of 118 adult patients with CKD stages 1–4 treated with SGLT2is (empagliflozin or dapagliflozin) at the University Clinical Center of Serbia between January 2024 and June 2025. Patients received either agent at 10 mg once daily for 18 months. Hb, ferritin, C-reactive protein (CRP), albumin (Alb), daily proteinuria (Prt), and estimated glomerular filtration rate (eGFR) were assessed at baseline and at 18 months. Ferritin was adjusted for inflammatory and nutritional status using a residualization model incorporating CRP and Alb. Changes between the two time points were analyzed using repeated-measures general linear models (GLMs). Results: In unadjusted analyses, mean Hb increased modestly from 136.5 ± 17.9 g/L at baseline to 138.8 ± 18.9 g/L at follow-up (p = 0.028), while median ferritin decreased from 102.2 µg/L to 89.9 µg/L (p = 0.011). After adjustment for CRP and Alb, ferritin levels remained unchanged (p = 0.752). Repeated-measures analyses showed no significant longitudinal effect of time on Hb or ferritin and no significant interaction between time and SGLT2i type. Baseline eGFR, Prt, sex, and baseline ferritin significantly influenced longitudinal hematologic trajectories. Conclusions: SGLT2i therapy was associated with modest increases in Hb levels over 18 months, while inflammatory status remained stable and no significant reduction in ferritin levels was observed after adjustment for inflammatory and nutritional factors. Longitudinal Hb and ferritin trajectories did not differ significantly between empagliflozin and dapagliflozin, while baseline kidney function, Prt, iron status, and sex significantly influenced hematologic outcomes. Although causal inference is limited by the absence of a control group, these findings suggest a possible favorable effect of SGLT2is on anemia-related parameters in patients with CKD. 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

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. Methods: The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson’s trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Results: Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. Conclusions: These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN. Full article

Background: Primary glomerular diseases (PGDs) are a leading cause of end-stage kidney disease (ESKD). While sex differences in chronic kidney disease progression have been reported, their role in PGDs remains unclear. Methods: We analyzed 2081 patients with biopsy-proven PGDs from the Turkish Society of Nephrology Glomerular Diseases Working Group (TSN-GOLD) registry. Baseline demographic, clinical, biochemical, and histopathological characteristics were compared between women and men. Outcomes were assessed as a composite of ESKD or death. Logistic and Cox regression models were applied to identify independent risk factors. Kaplan–Meier analyses evaluated survival differences. Results: At baseline, women and men had similar rates of hypertension (36.8% vs. 34.7%, p = 0.322). Women more frequently presented with leukocyturia (31.7% vs. 17.2%, p < 0.001) and hematuria (57.8% vs. 52.3%, p = 0.016), whereas men had higher proteinuria (5011 ± 4925 vs. 4388 ± 4529 mg/day, p = 0.003) and were more likely to be active smokers (20.7% vs. 7.4%, p < 0.001). Serum albumin (3.3 ± 0.8 vs. 3.2 ± 0.9 g/dL) and eGFR (79.7 ± 44.3 vs. 78.7 ± 45.5 mL/min/1.73 m²) were comparable between sexes (both NS). During a median follow-up of 24 months (IQR 7-60), 431 patients (20.7%) reached the composite outcome of ESKD or death (137 deaths [6.6%], 294 ESKD [14.1%]). In the multivariable Cox regression model, lower baseline eGFR (HR 0.98, 95% CI 0.98–0.98, p < 0.001), lower serum albumin (HR 0.65, 95% CI 0.55–0.77, p < 0.001), higher proteinuria (HR 1.03, 95% CI 1.00–1.05, p = 0.043), and biopsy diagnosis of RPGN (HR 3.78, 95% CI 1.37–10.45, p = 0.010) were independent predictors of poor prognosis. Sex was not an independent predictor of outcome (p = 0.48). Kaplan–Meier analysis demonstrated no significant survival difference between women and men (log-rank p = 0.052). Conclusions: In this nationwide PGD cohort, women and men differed significantly in baseline biochemical and clinical parameters, yet sex was not independently associated with progression to ESKD or death. Instead, disease severity at baseline and histopathological features were the main drivers of prognosis. Full article

Chronic kidney disease (CKD) affects more than 10% of the world’s population, increasing the risk of cardiovascular disease and mortality. Background: Nephroprotective interventions can reduce the risk of end-stage renal disease, delay the time to dialysis, and prolong life. However, there is ongoing debate about the effectiveness of combining amino acid ketoanalogues (KAA) with a low-protein diet (LPD) to slow CKD progression. This study aimed to retrospectively analyze kidney function outcomes after a 6-month KAA+LPD regimen in patients with CKD. Methods: The analysis included results from 38 non-dialyzed patients (12 F, 26 M; age 64.0 ± 13.6 years) with stable CKD in stages G4 to G5, who followed LPD with KAA (Ketosteril, Fresenius Kabi) treatment as part of the Polish National Health Fund Ketosteril Drug Program. Results: No significant change in estimated glomerular filtration rate (eGFR) was observed during 6 months of KAA+LPD therapy. However, eGFR increased or decreased in half of the patients (p < 0.001), and this change was associated only with initial protein intake and urinary phosphate excretion. Initial high phosphate excretion was independently associated with an increase in eGFR, and initial phosphaturia > 0.5 g/24 h identified eGFR improvement (sensitivity 84.2%; specificity 57.9%; AUC 0.712; p = 0.018) in CKD patients who started KAA+LPD treatment. Conclusions: Six-month treatment with KAA+LPD may be associated with stabilization of kidney function in patients with CKD stages G4-G5. The individual effect of KAA+LPD on renal function may be related to the initial protein intake level and urinary phosphate excretion. Further studies are needed to validate these findings across larger patient populations with a broader spectrum of symptoms. Full article

Chronic kidney disease (CKD) is a progressive and irreversible disorder affecting over 850 million individuals globally and is associated with significant morbidity, mortality, and healthcare burden. Conventional diagnostic approaches rely on intermittent laboratory measurements, including serum creatinine, estimated glomerular filtration rate (eGFR), and urinary albumin, which provide limited temporal resolution and fail to capture dynamic physiological changes. Recent advances in wearable biosensing technologies offer new opportunities for continuous, non-invasive monitoring of biochemical and physiological markers relevant to renal function. This review provides a comprehensive analysis of wearable biosensors for CKD monitoring, focusing on sensing mechanisms (electrochemical, optical, and field-effect transistor), biofluid interfaces (sweat, interstitial fluid, and saliva), and materials engineering strategies enabling flexible, high-performance devices. Emphasis is placed on biofluid transport dynamics, analytical performance across sampling matrices, and system-level integration with wireless communication and digital health platforms. Key challenges limiting clinical translation, including biofouling, enzymatic instability, and variability in biofluid composition, are examined—alongside emerging solutions such as antifouling interfaces, synthetic recognition elements, and multimodal sensing architectures. Finally, regulatory pathways and the role of artificial intelligence in digital nephrology are discussed. This review highlights the potential of wearable biosensors to transform CKD management through continuous monitoring, early detection, and personalized therapeutic intervention. Full article

Oxidative stress and inflammation are key drivers of kidney injury and disease progression. In this context, the role of sialic acids emerged as a critical regulatory layer linking redox imbalance, immune activation, and tissue damage. Sialic acids are terminal negatively charged residues that regulate complement activity, immune cell signaling, and the structural integrity of the glomerular filtration barrier. Alterations in sialylation, resulting from impaired biosynthesis or increased sialidase activity, disrupt immune homeostasis, enhance inflammatory responses, and promote complement-mediated injury. In the kidney, these mechanisms contribute to podocyte dysfunction, glomerular inflammation, and fibrosis and are implicated in glomerulopathies, transplantation, and plasma cell dyscrasias. Emerging evidence also highlights the therapeutic potential of targeting sialic acid metabolism through inhibition of desialylation or restoration of sialylation pathways. Overall, sialic acids represent dynamic modulators at the intersection of oxidative stress and immunity, offering novel opportunities for biomarker development and mechanism-based therapies in kidney disease. Full article

Background: Podocyte injury leads to the shedding of podocyte-derived molecules into the urine, which may serve as biomarkers of kidney disease. These molecules could be useful for the early detection of glomerular damage and for monitoring the progression of chronic kidney disease (CKD). Methods: A prospective cohort study was conducted in pediatric patients with CKD stages 1–4 treated at a tertiary care hospital between October 2019 and January 2023. Urinary podocalyxin and creatinine were measured at baseline. Renal function was assessed at baseline and at 12 and 24 months of follow-up. Patients were stratified by CKD stage. Changes in glomerular filtration rate (ΔGFR) were calculated, and correlations with baseline podocalyxin were evaluated using Spearman’s test. Multiple linear regression was used to adjust for confounders. Results: A total of 169 patients were included (median age 11 years). Glomerulopathies were the most frequent etiology (40.8%), and stage 1 was the most prevalent. At 12 months, stage 4 CKD patients showed a positive correlation with ΔGFR (r = 0.709, p = 0.003) and a negative correlation with proteinuria (r = −0.864, p < 0.001). At 24 months, a positive correlation was observed with ΔGFR (r = 0.949, p < 0.001), while an inverse association was observed with GFR. Associations varied according to CKD etiology. Conclusions: The podocalyxin-to-creatinine ratio was positively associated with renal function and negatively with proteinuria in stage 4 CKD, but showed no utility in stages 1–3. 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: Diabetic neuropathy is one of the most common chronic complications of diabetes mellitus and could lead to foot ulcerations, lower-limb amputations, increased mortality and reduced quality of life. This study examines the level of GPIHBP1 to assess its diagnostic and prognostic values across the metabolic continuum. Methods: This is an observational monocentric study, including 160 patients with type 2 diabetes mellitus, obesity without carbohydrate metabolism disorders and healthy controls. Clinical data and laboratory results were collected, and serum levels of GPIHBP1 were measured using an ELISA. The presence of DPN for the diabetes group was assessed using corneal confocal microscopy and NDS. The statistical analyses included t-tests, Pearson’s correlation analysis, and ROC analysis to explore associations and the predictive values of the biomarker. Results: The GPIHBP1 levels increased progressively, with the lowest levels observed in the control group, higher levels in patients with obesity, and the highest levels in those with diabetes mellitus. Higher GPIHBP1 levels were observed in patients with peripheral diabetic neuropathy compared to those without. GPIHBP1 demonstrated moderate discriminative performance for the presence of diabetes, diabetic neuropathy and nephropathy. GPIHBP1 levels were also associated with renal function parameters and markers of vascular involvement. After adjustment for confounders, including estimated glomerular filtration rate (eGFR), the association between GPIHBP1 and diabetic neuropathy remained statistically significant although attenuated. Higher levels were observed in patients with coronary artery disease, and a positive correlation was established with mean IMT and sudomotor dysfunction score. Conclusions: Circulating GPIHBP1 levels are associated with diabetes mellitus and its micro- and macrovascular complications, particularly diabetic neuropathy. Its measurement could enhance early diagnosis and personalized management of T2DM, and, while these findings support a potential role of GPIHBP1 as a biomarker of metabolic and vascular dysfunction, its clinical utility requires confirmation in longitudinal studies. Full article

Chronic kidney disease (CKD) affects nearly 10% of the global population, yet diagnosis and disease monitoring still rely primarily on plasma creatinine. Because creatinine levels are strongly influenced by non–renal factors, such as age, sex, muscle mass, and diet, its accuracy as a kidney function marker is limited. To identify plasma biomarkers that reflect kidney injury, we applied untargeted and targeted metabolomics in the adenine-induced CKD mouse model, a well-known tubular damage model, and validated the findings in plasma from patients with advanced CKD and healthy controls. We identified five metabolites that showed altered plasma levels in both experimental and human CKD, of which galactonic acid, pipecolic acid, and N-acetylneuraminic acid were significantly associated with measured glomerular filtration rate (GFR). As a proof-of-concept, we demonstrated that integrating these metabolites into a biomarker panel alongside creatinine could improve GFR estimation compared with creatinine alone. Our study introduces a promising metabolite-based biomarker panel that might enhance the accuracy of kidney function assessment and could potentially support diagnosis, risk stratification, and monitoring of disease progression; however, validation in a broader CKD cohort is needed. Full article

Background: Chronic kidney disease (CKD) is characterised by a disrupted gut–kidney axis, wherein intestinal dysbiosis is associated with the accumulation of uraemic toxins and the potential depletion of beneficial short-chain fatty acids (SCFAs). Whilst acetate, propionate, and butyrate are known to modulate systemic inflammation and blood pressure, their precise circulating concentrations across different CKD stages and age groups remain poorly defined. This systematic review and meta-analysis aimed to quantify blood SCFA concentrations in CKD patients compared to healthy controls. Methods: We conducted a systematic search of Medline, EMBASE, and the Cochrane Library for clinical studies reporting blood SCFA concentrations in humans with CKD. Methodological quality was assessed using the NIH tool. Standardised mean differences (SMDs) were calculated for the quantitative meta-analysis, with subgroup analyses performed for age, CKD stage, and treatment modality (dialysis vs. transplantation). Results: Twenty-one studies encompassing 9661 participants were included. Quantitative synthesis revealed a significant and consistent systemic depletion of circulating acetate and propionate in adult CKD patients compared to healthy controls (p < 0.05). This depletion followed a stage-dependent trajectory, worsening alongside declining glomerular filtration rates. Notably, a “butyrate paradox” was identified in paediatric cohorts; whilst adults showed progressive butyrate depletion, children with CKD often maintained or exhibited elevated levels, particularly in the context of hypertension. Furthermore, whilst haemodialysis patients exhibited the most profound SCFA deficiencies, kidney transplantation appeared to partially restore these metabolites toward healthy baseline levels. Conclusions: CKD is associated with a profound systemic reduction in acetate and propionate, supporting the model of a compromised gut–kidney axis based on converging evidence. The divergent results for butyrate in paediatric versus adult populations suggest that SCFA metabolism is influenced by age-related factors or compensatory mechanisms. These findings highlight the potential for SCFA monitoring as a candidate or emerging markers for detecting early renal damage and stratifying risk. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities. Full article