Donor medicine is an emerging field in nephrology. Medical specialties develop from how organ systems organize, new technologies, or groups of diseases. Donor medicine stands at the intersection of medicine, surgery, public health, and the humanities, but unlike recipient medicine does not involve immunology. Living kidney donors (LKDs) start from a position of excellent health and normal predicted lifespan. Nephrologists have a special obligation to follow altruistic LKDs over the long-term, even though the safety of donation has been generally well established. This paper summarizes the physiological changes associated with LKD surgery, resulting from reduced nephron mass, glomerular hyperfiltration, and blood pressure elevation, to the health risks associated with LKD surgery including chronic kidney disease, proteinuria, hypertension, preeclampsia, adverse psychology, and financial burden. Successful kidney transplantation does not simply mean performing a large number of transplants or even achieving a high long-term recipient graft or patient survival rate. Successful kidney transplantation means that the LKD also performs well in a situation that nature never intended for them. Placing long-term donor health into better perspective will help to provide a framework for establishing donor medicine as a distinct medical specialty, which will in turn encourage LKD and increase organ donation rates.
BACKGROUND:Systemic lupus erythematosus-associated lupus nephritis (LN) represents a major contributor to disease-related morbidity. Disturbances in bone metabolism frequently coexist with LN, driven in part by persistent inflammation and impaired renal function. These factors are closely linked to decreased bone mineral density (BMD) and a heightened risk of fractures. Fibroblast growth factor-23 (FGF-23) has recently been recognized as a key regulator of mineral homeostasis and may serve as a marker reflecting both renal disease activity and skeletal involvement. Nevertheless, its precise role in LN activity and its impact on bone health remain inadequately defined. AIM:To determine the predictive value of FGF-23 in renal disease activity and bone density changes in patients with LN. METHODS:A cross-sectional hospital-based study included 100 adult patients with LN. Patients were classified into active (n = 50) and inactive LN (n = 50). All patients underwent clinical assessment, laboratory investigations, renal imaging, renal biopsy when indicated, and BMD assessment using dual-energy X-ray absorptiometry. Serum FGF-23 was measured using enzyme-linked immunosorbent assay. Statistical analysis included comparative tests, correlation analysis, logistic regression, and receiver operating characteristic curve analysis. RESULTS:Patients with active LN had significantly higher FGF-23 levels compared with those with inactive LN (149.44 ± 37.09 pg/mL vs 122.56 ± 36.91 pg/mL; P < 0.001). BMD was significantly lower in patients with active LN (0.42 ± 0.19 g/cm² vs 0.56 ± 0.16 g/cm²; P < 0.001), with low BMD observed in 80% of patients with active LN vs 26% of those with inactive LN. FGF-23 level showed a significant negative correlation with BMD (r = -0.67, P = 0.001). Elevated FGF-23 level independently predicted low BMD (odds ratio = 4.18) and active LN (odds ratio = 2.18). At a cut-off point of ≥ 135 pg/mL, FGF-23 predicted low BMD with 79.5% accuracy. CONCLUSION:FGF-23 may be a promising biomarker for renal disease activity and BMD in patients with LN. Its elevation may reflect the interplay between disturbances in mineral metabolism, inflammatory processes, and renal involvement. Nevertheless, further large-scale, longitudinal studies are required to validate these observations and clarify the clinical utility of FGF-23 in patients with LN.
Diabetic nephropathy (DN) is a major kidney disease and linked to type 2 diabetes mellitus (T2DM), and it significantly which increases the global health burden. In the pathogenesis of DN, ZnT8 is essential for zinc transport into insulin granules; it ensures proper insulin crystallization, storage, and secretion while safeguarding β-cells against oxidative stress. it is suggested that the in pathogenesis of DN, the role of the SLC30A8/ZnT8/PDX-1 axis is underexplored along with its mechanism linking β-cell impairment to T2DM progression and renal fibrosis. In this review, we explore the role of microRNA-mediated regulation of SLC30A8/ZnT8 via PDX-1. Under hyperglycaemic and glucolipotoxic conditions, elevated level of miR-375 and miR-765 suppresses PDX-1 (master regulator of β-cell identity) and transcription of SLC30A8, culminating in ZnT8 silencing. PDX-1 directly binds to SLC30A8 enhancers and modulates its expression. Therapeutic targeting of this pathway via miR-375 and miR-765 antagomirs, CRISPR editing, ZnT8 overexpression, or zinc supplementation offers promise for restoring β-cell function and mitigating DN. Large scale clinical trial and epigenetic studies on patient cohorts will help and guide precision interventions.
BACKGROUND Pentoxifylline (PTX), a methylxanthine derivative, has been shown to exert notable anti-inflammatory and antiproteinuric actions in diabetic kidney disease, contributing to improved sodium handling, attenuation of renal hypertrophy, and reductions in tumour necrosis factor-alpha (TNF-α), interleukin-6 levels, and albuminuria. AIM To determine the impact of PTX on inflammatory biomarkers and the progression of chronic kidney disease (CKD) in non-diabetic patients. METHODS This prospective, interventional, open label, randomized controlled clinical study was conducted on 42 participants aged 18 years or older, of both genders, with CKD stages 3 or 4 and proteinuria < 1 g/24 hours. Participants were placed into two equal groups. Group 1 had standard therapy, including angiotensin-converting enzyme inhibitors (ACEIs; ramipril 1.25 mg), calcium acetate (700 mg), alfacalcidol (0.25 µg), antihypertensives, and diuretics. Group 2 had the same standard therapy plus PTX 400 mg (Trental®) two times per day for six consecutive months. RESULTS There was no significant relationship between TNF-α and high-sensitivity C-reactive protein (hs-CRP) and participants’ gender in both groups. An essential direct correlation was observed between TNF-α and creatinine in both groups. A critical direct correlation was observed between hs-CRP and calcium in group B. There was a significant inverse correlation between the change in TNF-α and estimated glomerular filtration rate, as well as between the change in TNF-α and the urinary protein-to-creatinine ratio. The change in protein creatinine ratio noted in group 2 was mainly due to changes in mean arterial pressure, followed by changes in TNF-α. CONCLUSION In non-diabetic CKD patients, adjunctive treatment with PTX was associated with significant decreases in C-reactive protein levels and proteinuria. The reduction in proteinuria was mainly explained by changes in mean arterial pressure, followed by changes in TNF-α, indicating that hemodynamic factors may play a more prominent role than inflammatory modulation in mediating this effect.
We read with interest the retrospective cohort study by Silipigni et al entitled "Role of point-of-care ultrasonography in kidney disease management: A single solution for multiple challenges". Artificial intelligence (AI) is rapidly reshaping the way clinicians learn, perform, and interpret point-of-care ultrasonography (POCUS). In nephrology, AI-assisted image acquisition, automated measurements, and emerging decision-support tools offer opportunities to improve efficiency and expand access to POCUS training. At the same time, important limitations remain, particularly when ultrasound findings must be integrated with physiology and clinical context. In this commentary, we discuss the current role of AI in nephrology POCUS, examine potential pitfalls of overreliance on automated interpretation, and consider future applications that may extend beyond image analysis toward physiologic assessment and hemodynamic phenotyping. Ultimately, we suggest that AI should be used to enhance, not replace clinicians' understanding of anatomy, physiology, and patient-specific pathophysiology.
Renal artery stenting has been less frequently performed following the results of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions trial. In this trial, stenting demonstrated no benefit over medical therapy in a composite outcome including mortality as well as cardiovascular and renal events. However, these findings must be interpreted in the context of the study population, which included many patients less likely to benefit from intervention due to relatively mild renal artery stenosis, as well as less severe hypertension and renal dysfunction. More recent investigations have focused on identifying subgroups of patients who may benefit from revascularization. Identified subgroups include patients with high systolic blood pressure, diastolic hypertension, worsening kidney function, greater antihypertensive burden, flash pulmonary edema, and mild-range proteinuria. Many of these variables illustrate a clinical picture of a patient with severe ischemic kidney disease leading to problems with hypertension and volume regulation that has not yet irreparably damaged the renal parenchyma. Deciding which patients fit into this picture, and therefore should be stented, presents a challenge. This review synthesizes the current evidence surrounding these predictive variables and explores how they may be integrated into clinical decision-making.
BACKGROUND:Membranoproliferative glomerulonephritis (MPGN) is a rare form of glomerular injury with variable prognosis, defined by immunoglobulin and/or complement deposits in the mesangium and basement membranes on immunofluorescence microscopy. AIM:To categorize it into immune complex-mediated MPGN (IC-MPGN) or complement-mediated MPGN (C-MPGN) types and to evaluate the clinical significance of this classification. METHODS:This retrospective cohort study evaluated biopsy-confirmed primary MPGN cases in adults diagnosed between January 2010 and December 2021 at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Patients were followed for at least 36 months post-biopsy, and secondary causes were excluded. Based on immunofluorescence microscopy findings, cases were categorized as IC-MPGN or C-MPGN. Clinicopathological features and renal outcomes were compared between the two groups. RESULTS:A total of 128 patients with primary MPGN were included, of whom 100 (78.1%) were reclassified as IC-MPGN and 28 (21.9%) as C-MPGN. No statistically significant differences were observed between the groups in gender distribution, clinical presentation, biopsy indications, histopathological findings, or renal function at diagnosis, except for a modest age difference (median 33.5 years vs 38 years, P = 0.029). Vascular pathology was significantly more frequent in C-MPGN, and C3 deposition was stronger and serum C3 levels lower, consistent with complement consumption. Immunosuppressive therapy was administered to 51 (51%) IC-MPGN patients and 19 (67.8%) C-MPGN patients. At 36 months, IC-MPGN patients showed numerically higher rates of complete or partial remission (62% vs 60.7%), though this difference did not reach statistical significance (log-rank test: P = 0.40). Progression to end-stage kidney disease and dialysis dependence was comparable between the two groups. CONCLUSION:The majority of MPGN cases were reclassified as IC-MPGN, which showed numerically higher remission rates. Overall, the clinicopathological features at diagnosis were similar between the two groups, though C-MPGN, a less frequent subtype, was associated with vascular pathology and stronger complement deposition, and a poorer medium-term prognosis.
Both traditional statistics, such as the logistic regression (LR) model, and machine learning (ML) have strengths and limitations for predicting outcomes after kidney transplantation. The LR model is simple, interpretable, and reliable with small datasets. ML can capture complex, nonlinear patterns and manage many variables, but it needs larger, high-quality datasets to reach its full potential. In the recent issue of World Journal of Nephrology, Salgado et al compared six ML models with the LR model using donor, transplant, and recipient data from 523 deceased-donor kidney transplants. Surprisingly, ML models only slightly outperformed the LR model, and overall predictive performance remained modest, especially for identifying patients who developed delayed graft function. These results emphasize that dataset size, completeness, and relevant clinical variables may be more important than algorithm complexity. Future work should focus on improving data quality and developing models that are both accurate and clinically interpretable.
BACKGROUND:Robot-assisted partial nephrectomy (RAPN) is well-suited for managing complex renal tumors, including those located in the renal hilum. However, studies directly comparing RAPN outcomes for hilar and non-hilar tumors, particularly in terms of comprehensive measures, such as trifecta and pentafecta, are still limited. AIM:To evaluate whether tumor location in the renal hilum independently influences surgical and renal functional outcomes after RAPN, as assessed by trifecta and pentafecta criteria. METHODS:This single-center retrospective cohort study evaluated outcomes of RAPN for hilar and non-hilar renal tumors treated from April 2016 to June 2023. Eligible patients had tumors ≤ 7 cm, no metastasis, and at least one year of follow-up. Propensity score matching was applied. Primary endpoints were trifecta and pentafecta achievement. All procedures were performed under ischemia without early unclamping. Multivariate logistic regression identified predictors of outcome achievement. RESULTS:Of 350 patients, 324 met the inclusion criteria, consisting of 60 hilar and 264 non-hilar tumors. Trifecta achievement was similar between hilar (63.3%) and non-hilar groups (64.0%), with no significant differences in ischemia time, positive margins, or major complications. Pentafecta achievement rates were also similar (20.0% hilar vs 14.0% non-hilar, P = 0.237). Multivariate analysis identified R score, N score, and L score as predictors of pentafecta non-achievement. Surgeon experience and hilar tumor presence were predictors of pentafecta achievement. Hilar tumor location was not an independent determinant in the propensity-matched analysis, suggesting that the adjustment methods and sample size may have influenced the results. CONCLUSION:RAPN achieved comparable trifecta and pentafecta outcomes for hilar and non-hilar tumors, supporting its viability for complex hilar tumors when appropriate patient selection and surgical experience are ensured.
Contrast-associated acute kidney injury (CA-AKI) remains a significant cause of hospital-acquired acute kidney injury, particularly in patients undergoing interventional radiology and cardiology procedures. Despite the implementation of preventive measures, such as intravenous hydration, pharmacologic prophylaxis, and minimization of contrast exposure, CA-AKI continues to be associated with increased morbidity, prolonged hospital stays, elevated mortality rates, and greater healthcare costs. Renal replacement therapies (RRT), including haemodialysis and hemofiltration, have been explored as potential strategies to prevent CA-AKI in high-risk populations. However, the existing evidence is inconclusive. While certain studies report a reduced incidence of CA-AKI with early hemofiltration in select patient groups, others have found no significant advantage over standard hydration protocols. Furthermore, practical concerns, including procedural risks, cost implications, and logistical constraints, limit the routine use of prophylactic RRTs in clinical practice. Current clinical guidelines do not endorse the widespread use of RRTs for CA-AKI prevention, though selective application in very high-risk patients may be considered. Robust, large-scale randomized controlled trials are needed to identify patient subgroups that might derive benefit from this intervention. In the interim, optimized hydration and contrast minimization remain the cornerstone strategies for CA-AKI prevention.
BACKGROUND:Kidney stone disease is a common and often debilitating disorder with significant recurrence rate. It is a matter of debate whether the metabolic factors responsible for renal stone formation are similar or variable in different populations around the globe. AIM:To evaluate the metabolic abnormalities via 24 hours urine profiles in first-time and recurrent renal stone formers. METHODS:This retrospective study was conducted at a tertiary care center between 2022 and 2024 and included 70 patients with urolithiasis, comprising 30 first-time stone formers and 40 recurrent stone formers (RSF). All patients underwent biochemical evaluation, including serum calcium, phosphorus, uric acid, creatinine, and intact parathyroid hormone levels. A 24-hour urine analysis was performed to assess urinary volume and the excretion of calcium, oxalate, citrate, uric acid, and phosphate. Metabolic abnormalities were defined according to standard criteria. Statistical analysis was performed using the independent t-test for continuous variables and the χ 2 test for categorical variables, with a P value < 0.05 considered statistically significant. RESULTS:Fifty-nine patients (84.2%) had at least one identifiable metabolic risk factor, with 37 patients (52.8%) having two or more metabolic abnormalities. The most common abnormalities detected were hypercalciuria 27 (38.5%) and hyper-oxaluria 19 (27.1%). Low urine volume, hypocitraturia and hyperuricemia was seen in 14 (20%), 16 (22.8%) and 4 (5.7%) patients respectively. Primary hyperparathyroidism was seen in a total of 8 (11.4%) patients. Metabolic abnormalities were seen more commonly in RSF but there was no statistically significant difference (P value > 0.05) in abnormalities between first time and RSF. CONCLUSION:Metabolic evaluation reveals they were prevalent in > 70% of both groups, supporting routine evaluation even in first-time formers in high-risk regions. Hypocitraturia, hyperoxaluria, hyperphosphatemia and hyperparathyroidism are present in a significant proportion of Indian stone former patients.
BACKGROUND:Diabetic nephropathy (DN) is a major complication that arises from diabetes. Curcumin, a bioactive compound with antioxidant properties, has been shown to modulate multiple cellular pathways and thereby mitigate tissue damage. AIM:To explore the influence of curcumin on high glucose-triggered apoptosis in renal tubular epithelial cells. METHODS:Sprague-Dawley rats were divided into control, diabetic, and curcumin treatment groups (n = 10/group). Renal function markers (neutrophil gelatinase-associated lipocalin, KIM-1, and urinary albumin) were assessed, and renal tissues were analyzed using histopathology, TUNEL assays, and immunohistochemistry. Renal tubular epithelial cells were cultured under normal (5.5 mmol/L) or high glucose (30 mmol/L) conditions, with or without curcumin. Apoptosis, reactive oxygen species (ROS) levels, and Nrf2/heme oxygenase-1 (HO-1) signaling pathway markers were evaluated using flow cytometry, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS:Curcumin improved renal function markers and reduced renal tubular apoptosis in diabetic rats. In vitro, it suppressed high glucose-induced apoptosis and ROS production, while activating the Nrf2/HO-1 antioxidant pathway (upregulated Nrf2 and HO-1 expression, and downregulated Keap1) and modulating the Bcl-2/Bax apoptotic balance (downregulated Bax and upregulated Bcl-2), demonstrating sequential protection against oxidative stress followed by apoptosis inhibition. CONCLUSION:Curcumin protects against high glucose-induced renal tubular epithelial apoptosis by enhancing Nrf2/HO-1 signaling to reduce oxidative stress and apoptosis, indicating its therapeutic potential for DN.
Blood pressure (BP) abnormalities are clues to make differential diagnosis and prognostic indicators in various renal diseases in the emergency department (ED), arising from and contributing to kidney dysfunction via activation of the renin-angiotensin-aldosterone system, impaired perfusion, volume overload in chronic kidney disease (CKD) patients, inflammatory processes, and traumatic structural injury. This narrative review summarizes BP patterns and pathophysiology across common renal conditions in the ED, including acute kidney injury, CKD, end-stage renal disease, glomerulonephritis, renal trauma, pyelonephritis, renal artery stenosis, nephrolithiasis, renal infarction, and renal tubular acidosis. Distinct BP profiles are observed: Hypotension often indicates prerenal, septic, or shock-associated acute kidney injury, severe infection, trauma, or shock, while hypertension predominates in CKD, end-stage renal disease, and ischemic or obstructive conditions due to renin-angiotensin-aldosterone system activation and sodium retention. Some disorders show variable BP patterns depending on stages, severity, and comorbidities. Overall, BP abnormalities provide valuable diagnostic and management guidance. Recognizing these predictable hemodynamic responses supports timely diagnosis, risk stratification, and targeted ED management.
I read with interest the retrospective cohort study by Kleinman et al published in World Journal of Nephrology. Renin-angiotensin-aldosterone system inhibitors (RAASi) anchor therapy for chronic kidney disease, heart failure, and hypertension, but hyperkalemia often curtails optimal use. This letter synthesizes a retrospective cohort of 13447 patiromer users, where approximately 25% high adherers [proportion of days covered (PDC) ≥ 80%] showed approximately 10% greater RAASi utilization (days' supply and PDC) across angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and mineralocorticoid receptor antagonists vs lower adherers. Findings echo OPAL-HK, reinforce Kidney Disease: Improving Global Outcomes 2021 binder prioritization, and urge adherence strategies to sustain guideline therapy, cut hospitalizations, and integrate with SGLT2i/finerenone.
BACKGROUND:The most common type of primary glomerulonephritis is immunoglobulin A nephropathy (IgAN), which can eventually cause end-stage kidney disease among individuals. A kidney biopsy, which is invasive and has risks of mortality or morbidity, is currently the "gold standard" for diagnosis. Urinary exosomes contain abundant, well-preserved microRNAs (miRNAs), which are small, non-coding endogenous RNAs that may be used as non-invasive biomarkers. Studies on urinary exosomal miRNA profiles for the diagnosis of IgAN are rare. AIM:To examine the profile of urinary exosomal miRNAs in Indian individuals diagnosed with IgAN. METHODS:Over a period of 4 years (2020-2024), fifty biopsy-confirmed IgAN patients, fifty healthy controls, and fifty disease controls (DC) were recruited. Urinary exosomes were first discovered and then utilized for miRNA extraction. The nCounter® Human v3 miRNA Expression Assay, a digital multiplex technique that evaluates 798 unique miRNA barcodes, was used to further analyze the extracted miRNAs. After the least absolute shrinkage and selection operator feature selection identified candidate miRNAs, logistic regression and the CombiROC algorithm were used. RESULTS:The average age of patients diagnosed with IgAN was 36.32 years, with a standard deviation of 3.07 years. The average proteinuria was 2.69 ± 0.64 g/day, and the average creatinine level was 2.26 ± 0.318 mg/dL. Nine candidate miRNAs - hsa-miR-4532, hsa-miR-4488, hsa-miR-3158-3p, hsa-miR-151b, hsa-miR-3195, hsa-miR-1289, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-32-5p, and hsa-miR-525-3p - successfully differentiate IgAN cases from both healthy and DC, exhibiting under the curve values of 0.7, 1, and 0.8 for healthy controls, DC, and IgAN cases, respectively. When compared to healthy and DC, a combination of just two miRNAs - hsa-miR-4532 and hsa-miR-548a-3p - was found to be sufficiently effective for detecting IgAN, with an area under the curve > 0.8. CONCLUSION:Our investigation involving Indian participants revealed a marked alteration in the urinary exosomal miRNA patterns among individuals with IgAN compared to both healthy subjects and those with other kidney diseases, demonstrating the effectiveness of miRNAs in the non-invasive diagnosis of IgAN.
Most patients with diabetic kidney disease (DKD) suffer from proteinuria. Finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist acts as anti-inflammatory factor reducing the kidney inflammation and fibrotic pathways, which are overactive in patients with advanced proteinuria. The study by Pasari et al, published in the recent issue of the World Journal of Nephrology, correlated the greater reduction of albuminuria with the higher baseline albuminuria using finerenone. However, heterogeneity, disproportion and variability in response using finerenone for the reduction of proteinuria has been observed. Patients with persistent proteinuria despite the optimal renin-angiotensin-aldosterone system blockage, sodium-glucose co-transporter -2 inhibitors and finerenone, remain at high risk for renal and cardiovascular events. More factors including the novel functions of histone lactylation possibly are involved in the deterioration of albuminuria in DKD. It may need combined and intensive therapy with an additional healthy lifestyle. More pharmacogenomic trials, proteomic analyses in long-term real-world cohorts need to clarify the pathogenetic mechanisms related to proteinuria in DKD.
Post-coronavirus disease 2019 (COVID-19) condition describes a constellation of persistent or fluctuating symptoms and organ dysfunction following severe acute respiratory syndrome coronavirus 2 infection. Patients with end-stage kidney disease (ESKD) on dialysis and kidney transplant recipients (KTR) inhabit a landscape of immune dysfunction, multimorbidity, and high healthcare interaction, which may amplify both the risk and consequences of post-COVID condition (PCC). In this article, we aimed to review current evidence on PCC and related post-acute sequelae in dialysis patients and KTR-focusing on symptom burden, risk factors, functional outcomes, health-related quality of life (HRQoL), kidney and graft outcomes, and recovery trajectories. It was found that dialysis patients and KTR experience a substantial burden of PCC superimposed on already complex symptoms and risk profiles. Long COVID in these groups encompasses not only fatigue, dyspnea and a "brain fog" phenomenon but also impaired HRQoL, reduced functional recovery, and potential acceleration of kidney and graft decline. Harmonized PCC definitions, kidney-specific outcome measures, and prospective multicentre studies in ESKD and kidney transplant populations are urgently required to inform prevention and management strategies embedded within the dialysis and kidney transplantation pathways.
