Xiayan Xu,1,* Haoting Huang,2,* Yan Xu,3 Ying Liu,3 Jiamei Yi,1 Qingrong Zou,1 Jianru Wu,2 Xiaoyu Liu21Department of Pharmacy, Shenzhen Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, Guangdong, People’s Republic of China; 2Drug Monitoring Section, Shenzhen Institute of Pharmacovigilance and Risk Management, Shenzhen, Guangdong, People’s Republic of China; 3Drug Monitoring Section, Center for ADR Monitoring of Guangdong, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyu Liu, Drug Monitoring Section, Shenzhen Institute of Pharmacovigilance and Risk Management, 16th Floor, Building E, Nanshan Zhigu Industrial Park, Nanshan District, Shenzhen, Guangdong, People’s Republic of China, Email liuxy4@mail.amr.sz.gov.cnBackground: Elderly individuals are particularly vulnerable to drug-induced acute kidney injury (DI-AKI) due to their distinct physiological and pathophysiological traits. DI-AKI’s non-specific symptoms complicate the identification of causative medications, highlighting the urgent need for accurate predictive tools to detect AKI risk early in this group.Aim: The objective is to construct a machine learning-based predictive model for DI-AKI in elderly patients utilizing real-world data, with the aim of offering a decision-support tool for the early clinical identification of DI-AKI risk.Methods: The electronic health records of 2,389 patients aged ≥ 60 years at Shenzhen Luohu People’s Hospital from January 2023 to December 2024 were retrospectively analyzed. Drug-induced AKI was defined by KDIGO creatinine criteria (≥ 0.3 mg/dL within 48h or ≥ 1.5×baseline within 7d) plus Naranjo score for drug attribution. Forty optimal features (30 original and 10 interaction terms) were selected, and seven machine learning algorithms were assessed using nested cross-validation with different feature selection and interactive feature construction methods. SHAP values were employed for model interpretability.Results: In a study of 2,389 patients, 39.9% (953 individuals) experienced drug-induced AKI. The Random Forest model performed best on the test set, with an Area Under the Curve (AUC) of 0.9209 [95% CI: 0.896– 0.946], showing 84.9% sensitivity, 89.1% specificity, and an 85.5% positive predictive value. Key predictors included a history of renal failure (importance score: 0.1703) and drug-disease interactions, such as those involving antihypertensives and renal failure (importance score: 0.1000).Conclusion: This machine learning model is capable of aiding in the identification of high-risk elderly patients within electronic medical record systems, with a particular emphasis on drug interactions and renal function as pivotal risk factors. By employing SHAP values for analysis, this study elucidates the contributions of these risk factors and offers support for making personalized medication decisions; However, external validation remains necessary prior to clinical implementation.Keywords: drug-induced AKI, machine learning, predictive modeling, geriatric patients
Background:Anemia is a common complication of chronic kidney disease (CKD) and is predominantly managed with erythropoiesis-stimulating agents (ESAs). Hemoglobin response to ESA therapy varies substantially among patients and remains difficult to predict owing to multiple interacting clinical and treatment-related factors. Machine learning approaches may help model hemoglobin dynamics using routinely collected clinical data. Purpose:To develop and evaluate machine learning models for predicting weekly hemoglobin changes in patients with CKD receiving ESA therapy. Patients and Methods:A retrospective cohort study was conducted using electronic medical records from a tertiary care center in Thailand (January 2012 to December 2022). Adult patients with CKD stages 3B-5 and an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2 receiving ESA therapy were included. Four machine learning algorithms (Decision Tree, Random Forest, XGBoost, and Support Vector Machine) were trained using data from 80% of patients and evaluated on an independent test set comprising the remaining 20% of patients, with all longitudinal observations from each patient kept within the same partition. Performance was assessed using root mean square error (RMSE) and Pearson correlation coefficient. Results:A total of 834 patients contributing 10,335 clinical visits and 9,935 time-series observations were included. The median age was 71 years and 58.6% were female. RMSE values were 0.121, 0.115, 0.117, and 0.115 for Decision Tree, Random Forest, XGBoost, and Support Vector Machine, respectively. Pearson correlation coefficients ranged from 0.457 to 0.553 (all p < 0.001). Conclusion:Machine learning models trained on routinely collected clinical data showed feasibility for predicting short-term hemoglobin variability in patients with CKD receiving ESA therapy. Larger multicenter and external validation studies are needed to refine predictive accuracy and evaluate clinical utility.
Background:The modified furosemide response index (mFRI), derived from a standardized furosemide stress test, is a biomarker of diuretic responsiveness and AKI progression. Its prognostic value in chronic kidney disease (CKD) remains unclear. This study examined the association between mFRI and clinical outcomes in critically ill patients with CKD. Methods:We conducted a retrospective cohort study using the MIMIC‑IV database. Critically ill CKD patients receiving furosemide were included. Restricted cubic splines were used to examine the non‑linear relationship between mFRI and mortality. Patients were grouped by mFRI quartiles. Multivariable Cox and logistic regression assessed outcome associations, with subgroup analyses for robustness. Results:Among 3,311 patients, a significant L‑shaped non‑linear association was observed between mFRI and 28‑day mortality (P < 0.001). Mortality risk declined sharply as mFRI increased to 0.143, then plateaued. Kaplan‑Meier analysis showed progressively lower mortality from the lowest (Q1) to the highest (Q4) mFRI quartile. Higher mFRI quartiles were associated with lower all‑cause mortality and reduced use of renal replacement therapy. Conclusion:mFRI has a non‑linear, L‑shaped association with prognosis in critically ill patients with CKD. Because it is simple, low‑cost, and repeatable, mFRI could be a practical bedside tool for risk stratification in this population.
Objective:To systematically compare the clinicopathological features and prognostic outcomes of renal-limited thrombotic microangiopathy (RL-TMA) and systemic thrombotic microangiopathy (Sys-TMA) using a semiquantitative pathological scoring system. Methods:We retrospectively analyzed 47 patients with biopsy-proven TMA between 2018 and 2025, categorized as RL-TMA (n = 42) or Sys-TMA (n = 5) based on systemic manifestations. Clinical, pathological, and follow-up data were collected. A composite renal endpoint served as the primary outcome. Kaplan-Meier and Cox regression analyses were used for survival analysis and prognostic factor identification. Results:RL-TMA patients were older, with higher hemoglobin and platelet levels, lower lactate dehydrogenase, less complement C3 consumption, and significantly fewer multiorgan dysfunctions than Sys-TMA patients. Pathologically, Sys-TMA was dominated by acute microvascular lesions, whereas RL-TMA showed more chronic changes (glomerulosclerosis, arteriolar hyalinosis) and more frequent immune complex deposition. Total immunofluorescence intensity and IgG, IgG2, IgG4, and C1q deposition were significantly higher in RL-TMA (all P < 0.05). Over a median follow-up of 16-20 months, end-stage kidney disease incidence did not differ significantly between groups (9.5% vs 0%, P > 0.05). In RL-TMA, univariate analysis showed that lower hemoglobin was associated with worse renal outcomes (HR = 0.946, P = 0.004). Serum albumin showed no clear association (HR = 0.992, P = 0.862), while pathological scores lacked independent predictive value. Kaplan-Meier analysis showed no statistically significant difference in renal progression-free survival between the two groups (P = 0.97). Conclusion:This study delineates significant differences between RL-TMA and Sys-TMA across clinical, pathological, and prognostic dimensions, suggesting that RL-TMA may represent a distinct clinicopathological entity, warranting further validation in larger prospective studies. Given the small sample size of the Sys-TMA group, these results should be interpreted as exploratory and hypothesis-generating. Hemoglobin levels showed an association with renal outcomes in univariate analysis, but this finding requires further investigation in larger cohorts before any clinical utility can be established.
Pattanan Buranasaksathien, Wanjak Pongsittisak, Padoemwut Teerawongsakul, Solos Jaturapisanukul, Thananda Trakarnvanich, Sathit KurathongDepartment of Internal Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandCorrespondence: Sathit Kurathong, Department of Internal Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand, Tel +66 2 244 3482, Fax +66 2 668 7066, Email sathit@nmu.ac.thBackground: Anemia is a common complication of chronic kidney disease (CKD) and is predominantly managed with erythropoiesis-stimulating agents (ESAs). Hemoglobin response to ESA therapy varies substantially among patients and remains difficult to predict owing to multiple interacting clinical and treatment-related factors. Machine learning approaches may help model hemoglobin dynamics using routinely collected clinical data.Purpose: To develop and evaluate machine learning models for predicting weekly hemoglobin changes in patients with CKD receiving ESA therapy.Patients and Methods: A retrospective cohort study was conducted using electronic medical records from a tertiary care center in Thailand (January 2012 to December 2022). Adult patients with CKD stages 3B– 5 and an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2 receiving ESA therapy were included. Four machine learning algorithms (Decision Tree, Random Forest, XGBoost, and Support Vector Machine) were trained using data from 80% of patients and evaluated on an independent test set comprising the remaining 20% of patients, with all longitudinal observations from each patient kept within the same partition. Performance was assessed using root mean square error (RMSE) and Pearson correlation coefficient.Results: A total of 834 patients contributing 10,335 clinical visits and 9,935 time-series observations were included. The median age was 71 years and 58.6% were female. RMSE values were 0.121, 0.115, 0.117, and 0.115 for Decision Tree, Random Forest, XGBoost, and Support Vector Machine, respectively. Pearson correlation coefficients ranged from 0.457 to 0.553 (all p < 0.001).Conclusion: Machine learning models trained on routinely collected clinical data showed feasibility for predicting short-term hemoglobin variability in patients with CKD receiving ESA therapy. Larger multicenter and external validation studies are needed to refine predictive accuracy and evaluate clinical utility.Keywords: chronic kidney disease, anemia of chronic kidney disease, erythropoiesis-stimulating agents, machine learning, hemoglobin variability, artificial intelligence
Background:Patients on maintenance hemodialysis (MHD) face cardiovascular mortality far exceeding that of the general population, yet the evidence on risk factors comes overwhelmingly from thrice-weekly cohorts. In Indonesia and many low- and middle-income countries, twice-weekly hemodialysis is the standard regimen funded by national insurance, and the risk factor profile of this underdialysed population has received little attention. Objective:To identify independent risk factors for cardiovascular mortality among Indonesian adults receiving twice-weekly MHD. Methods:We analysed the complete eligible population of 162 adults receiving twice-weekly MHD (8-10 hours/week) at a tertiary center in Bandung, followed for 18 months (May 2018-November 2019). Baseline variables were drawn from the unit's REDCap database. Severe hypoalbuminemia was defined as serum albumin ≤3.0 g/dL. Seven variables with bivariate p<0.25 entered modified Poisson regression with robust standard errors to estimate adjusted relative risks (aRR); dialysis vintage was entered in addition on clinical grounds. Model stability was assessed across progressively more parsimonious specifications. Results:Mean age was 49.7 ± 14.2 years, 47% were men, and cardiovascular events accounted for 92.1% of the 38 deaths. Eighteen-month cardiovascular mortality was 21.6% (35/162); 1-year survival was 80.7%. Six factors were independently associated with cardiovascular death: age >60 years (aRR 3.15, 95% CI 1.65-6.02), Kt/V <1.8 (aRR 2.52, 95% CI 1.35-4.69), diabetic kidney disease (aRR 2.05, 95% CI 1.16-3.63), hyperphosphatemia (aRR 1.94, 95% CI 1.12-3.35), abnormal serum potassium (aRR 1.91, 95% CI 1.09-3.34), and dialysis vintage >60 months (aRR 1.69, 95% CI 1.01-2.81). Age and Kt/V remained significant across all model specifications. Serum albumin discriminated poorly (AUC 0.587); the ≤3.0 g/dL cutoff is reported as exploratory. Conclusion:Older age, inadequate dialysis dose, diabetic etiology, hyperphosphatemia, dyskalemia, and prolonged vintage were independently associated with cardiovascular mortality, with age and dialysis dose the most robust. The findings argue for closer attention to dialysis adequacy and mineral metabolism in reduced-frequency programs.
Human orf is a zoonotic parapoxvirus infection that is typically self-limiting with resolution in 3-6 weeks but may cause severe disease in immunocompromised patients. We report a kidney transplant recipient who developed a rapidly progressive fingertip lesion following contact with raw meat during Eid al-Adha. Initial misdiagnosis and surgical excision were followed by marked lesion progression, mimicking a vascular tumor. Histopathology confirmed orf virus infection. However, PCR testing was not done as the test was not available. Topical imiquimod was not initiated due to an active wound. Weekly liquid nitrogen cryotherapy as monotherapy resulted in complete resolution after nine sessions without recurrence. Further modifications/reduction in immunosuppressive medication was not needed. This case highlights cryotherapy as a potential treatment option for orf infection in transplant recipients.
Samreen M Rahmoon,1 Leen M AbuAfifeh,1 Osama A Alkhalidi,1 Farooq Ahmad,2 Gamal BS Alfitori11Department of Internal Medicine, Hamad General Hospital, Doha, Qatar; 2Department of Nephrology, Hamad General Hospital, Doha, QatarCorrespondence: Samreen M Rahmoon, Department of Internal Medicine, Hamad General Hospital, Doha, Qatar, Tel +974 5567 0203, Email samreenrahmoon99@gmail.comAbstract: Human orf is a zoonotic parapoxvirus infection that is typically self-limiting with resolution in 3– 6 weeks but may cause severe disease in immunocompromised patients. We report a kidney transplant recipient who developed a rapidly progressive fingertip lesion following contact with raw meat during Eid al-Adha. Initial misdiagnosis and surgical excision were followed by marked lesion progression, mimicking a vascular tumor. Histopathology confirmed orf virus infection. However, PCR testing was not done as the test was not available. Topical imiquimod was not initiated due to an active wound. Weekly liquid nitrogen cryotherapy as monotherapy resulted in complete resolution after nine sessions without recurrence. Further modifications/reduction in immunosuppressive medication was not needed. This case highlights cryotherapy as a potential treatment option for orf infection in transplant recipients.Keywords: orf virus, transplant, immunosuppression, cryotherapy
Purpose:Chronic kidney disease (CKD) is a major public health concern in the United States, with persistently rising incidence and mortality. This study aimed to quantify geographic and demographic disparities in CKD mortality across the United States and to examine the association between CKD mortality and ambient temperature variation. Patients and Methods:CKD deaths and age-adjusted mortality rates (AAMRs) for 1999-2023 were obtained from CDC WONDER and stratified by census region, state, sex, race, age group, and urbanization level. Mortality trends were quantified using joinpoint regression. Primary temperature-mortality analyses used CDC WONDER-linked NLDAS temperature data for 1999-2011, while supplementary descriptive analyses used independently retrieved NLDAS temperature estimates for 2012-2023. Temperature-mortality associations were evaluated using Spearman rank correlations, quasi-Poisson regression models, and distributed lag nonlinear models (DLNMs). Results:From 1999 to 2023, 628,937 CKD deaths occurred, with national AAMR increasing steadily. Mortality rates were consistently higher in men and nonmetropolitan areas. AAPC rose fastest in the West and Midwest, though recent AAMR declines were noted in the Northeast and South. Winter mortality exceeded summer across regions. In the primary DLNM analysis, cold exposure at the region-specific 5th percentile was associated with higher cumulative CKD mortality risk, with risk ration (RR) ranging from 1.065 in the Northeast to 1.505 in the Midwest; the association reached statistical significance only in the Midwest (RR 1.505, 95% CI: 1.091-2.075), while hot-exposure estimates at the 95th percentile were generally imprecise and not statistically significant. Conclusion:CKD mortality in the United States increased from 1999 to 2023 with marked geographic and demographic disparities. Cold air temperature was associated with higher short-term mortality risk.
Background:Hyperkalemia after a Long Interdialytic Interval (LIDI) is a potentially life-threatening complication in patients undergoing intermittent hemodialysis. The risk is exacerbated especially in populations known for Potassium-rich dietary habits and cultural tradition of weekend gatherings. Patiromer is a potassium binder that helps treat Hyperkalemia. This study aimed to evaluate the efficacy of Patiromer in the management of LIDI Hyperkalemia in patients with ESKD on Intermittent Hemodialysis, with Potassium rich dietary habits as in Saudi Arabia. Methods:Adult patients who had completed 3 months on Intermittent Hemodialysis, were screened for LIDI hyperkalemia pre dialysis (serum K >5.3 mmol/L).Patients with hyperkalemia were prescribed Patiromer on days off Hemodialysis during the LIDI (Thursday and Friday for Saturday group; Friday and Saturday for Sunday group). Pre HD serum potassium levels were monitored after the LIDI at weeks 1, 2, 4, 8, 12, 24, and 52. Patient Compliance was ensured through telephonic communication with the patient or the care giver. Results:Among the 127 patients on Intermittent Hemodialysis, 58 were identified with LIDI hyperkalemia out of whom 52 patients completed one year follow-up. 36 had serum K 5.3-5.9 mmol/l, 11 had serum K 6-6.5 mmol/l, 5 had serum K 6.5 mmol/l and above. Patiromer therapy resulted in a mean serum potassium reduction of 0.8-2.5 mmol/L, with a sustained average reduction of 1.57 mmol/L observed over 52 weeks. The treatment was well tolerated, with no drop outs reported due to side effects. Conclusion:Patiromer demonstrated sustained efficacy and excellent tolerance in preventing hyperkalemia after the LIDI in our potassium rich diet population undergoing Intermittent Hemodialysis.
Background:Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with advanced chronic kidney disease (CKD). However, data on its prevalence and patterns in Sub-Saharan Africa remain scarce. Purpose:To determine the prevalence and spectrum of CVD among patients with advanced CKD in Johannesburg, South Africa. Patients and Methods:This retrospective study enrolled adults aged ≥18 years with advanced CKD attending the renal clinic at Chris Hani Baragwanath Academic Hospital between 2009 and 2018. Demographic, clinical, laboratory, electrocardiographic, and echocardiographic variables were extracted from medical records. CVD was defined as heart failure, ischemic heart disease, arrhythmias, non-rheumatic valvular heart disease, pericardial disease, stroke, or peripheral vascular disease, supplemented by clinical, electrocardiographic, or echocardiographic findings. Patients were grouped by their CVD status. Multivariable logistic regression identified independent factors associated with CVD. Results:Among 300 participants (mean age of 55.3 ± 15.0 years, 54.3% males), CVD prevalence was 58.7%. The mean age at CVD diagnosis was 46.6 ± 13.7 years, with a median interval of 8.3 months (IQR, 2.5-27.6) between the onset of CKD and CVD diagnosis. Patients with CVD were younger than those without (52.8 ± 13.8 vs 58.8 ± 16.0 years; p<0.001), had higher diastolic blood pressure (88.5 ± 20.6 vs 81.3 ± 17.6 mmHg; p = 0.002), and a higher prevalence of obesity (54.6% vs 38.7%; p<0.001). Predominant CVD manifestations were ischemic ECG changes (95.1%) and diastolic dysfunction with heart failure (45.5%). Higher diastolic blood pressure (aOR 1.04; 95% CI 1.00-1.08; p = 0.029) and reduced estimated GFR (aOR 0.96; 95% CI 0.94-0.99; p = 0.022) were independent predictors of CVD. Conclusion:CVD is highly prevalent in advanced CKD and occurs at a young age. Early cardiovascular risk assessment and integrated cardio-renal management strategies are essential in this high-risk population.
Objective:Angiogenesis and oxidative stress contribute to the pathogenesis of diabetic nephropathy (DN). The isoflavone biochanin A (BCA) has reported anti-inflammatory and antioxidant properties; we evaluated whether BCA modulates inflammatory and angiogenic markers in renal tissue of streptozotocin-induced diabetic rats. Materials and Methods:Thirty-six male Wistar rats (180-200 g) were randomized into six groups (n = 6): non-diabetic control (vehicle), diabetic control (STZ 55 mg/kg, i.p.), and two diabetic groups treated with BCA (10 or 15 mg/kg; Oral). Treatments were administered for 42 days. On day 42 animals were sacrificed and blood and renal tissues collected. Renal VEGF, TNF-α, IL-1β, IL-6, IL-18, NF-κB, TGF-β, RAGE, CTGF, and MDA were measured by ELISA. Renal tissues evaluate histopathologically for mesangial expansion, cellularity, and angiogenesis. Results:BCA treatment reduced fasting blood glucose in diabetic rats and significantly decreased renal VEGF, TNF-α, and IL-1β concentrations versus diabetic controls (p < 0.05). No clear dose-response was observed between 10 and 15 mg/kg; other markers showed non-significant trends toward improvement. Conclusion/Discussion:BCA reduced key angiogenic and proinflammatory markers in diabetic rat kidney, suggesting potential nephroprotective effects; further studies are needed to define mechanisms, optimal dosing, and long-term safety.
Background: Secreted phosphoprotein 1 (SPP1), a glycoprotein encoded by the SPP1 gene, can be detected in body fluids and tumor tissues of various diseases, representing a promising candidate biomarker. However, its application in focal segmental glomerulosclerosis (FSGS) remains at the exploratory stage. Patients and Methods: In a small-scale cohort, Bulk-RNA sequencing was employed to screen for core differentially expressed genes in urinary cells of FSGS patients, with SPP1 identified as a key candidate. RT-qPCR and ELISA were subsequently used to detect SPP1 expression in clinical urine samples. An adriamycin (ADR)-induced FSGS mouse model was established, and renal histopathological changes were evaluated using hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining. Immunohistochemistry and immunofluorescence were performed to examine the expression of SPP1, fibronectin, and F4/80 in renal tissues, with assessment of the effects of prednisone intervention. Results: Urinary SPP1 expression was significantly elevated in FSGS patients, particularly in those with CKD stage III. In the ADR mouse model, as glomerulosclerosis progressed, albuminuria levels increased, accompanied by enhanced expression of SPP1 and F4/ 80-positive macrophages. Prednisone treatment attenuated these parameters. Conclusion: SPP1 is involved in the progression of FSGS and is closely associated with renal immune inflammation and fibrosis. Prednisone exerts renoprotective effects by downregulating SPP1 expression and inhibiting macrophage infiltration, suggesting that SPP1 represents a promising molecular marker for disease monitoring and targeted intervention in FSGS.
Introduction:Chronic kidney disease (CKD) is accompanied by systemic metabolic dysregulation, and metabolomics provides a robust approach for identifying disease-specific metabolic signatures and potential biomarkers. Hypertension may be closely associated with metabolic disturbances in CKD. This study aimed to characterize serum metabolic alterations and dysregulated pathways in CKD, and screen candidate metabolite biomarkers for distinguishing CKD patients from healthy individuals. Methods:A total of 65 participants (35 CKD patients and 30 healthy controls) were enrolled in this study. Serum metabolic profiling was performed using high-resolution mass spectrometry-based untargeted metabolomics, while targeted analysis of small molecule metabolites was conducted via liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squared-discriminant analysis (OPLS-DA) were applied to identify metabolic alterations between groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to annotate the functional roles of differentially expressed metabolites. Independent t-tests and Pearson correlation analyses were performed to validate the expression and correlation of key metabolites. Results:A total of 1,426 metabolites were detected in all serum samples, with 1,246 successfully identified by secondary mass spectrometry. Differential analysis revealed 397 significantly altered metabolites (216 up-regulated and 181 down-regulated) between the CKD and control groups. KEGG enrichment analysis indicated that these differential metabolites were mainly involved in phenylalanine metabolism, arginine and proline metabolism, and glutathione metabolism, suggesting systemic metabolic dysfunction in CKD. Targeted analysis of catecholamines showed that serum concentrations of adrenaline and nicotinamide mononucleotide (NMN) were significantly altered in CKD patients compared with healthy controls (P < 0.05), though no significant linear correlation was observed between these two metabolites and CKD progression via Pearson correlation analysis. Discussion:The identified metabolic pathway dysregulations (amino acid metabolism and redox-related pathways) are core metabolic characteristics of CKD, which are closely associated with renal function impairment, oxidative stress and hypertension in CKD. Adrenaline and NMN may serve as potential candidate biomarkers for CKD, and their abnormal expression may be linked to the activation of the renin-angiotensin system and dysregulation of renal energy metabolism. However, the specific mechanistic roles of these two metabolites in CKD pathophysiology remain to be elucidated. Conclusion:This study comprehensively characterized serum metabolic alterations in CKD and identified key dysregulated metabolic pathways, as well as adrenaline and NMN as potential candidate biomarkers. These findings enhance the understanding of biochemical dysregulation underlying CKD and provide novel insights for future diagnostic biomarker development and targeted therapeutic exploration for CKD.
IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a histopathological variant of staphylococcus-associated glomerulonephritis (SAGN) that occurs as a result of an immune response to S. aureus antigens, with subsequent deposition of IgA in the nephron. This can lead to acute kidney injury, hematuria, and proteinuria. It is important to differentiate IgAIRGN from primary IgA nephropathy (IgAN) because the treatment strategies differ. IgA-dominant IRGN requires treatment of the infection with antibiotics, whereas treatment of primary IgAN involves immunosuppression. Here, we present a case that highlights the clinical dilemma of distinguishing IgA nephropathy from IRGN. Our patient presented with chronic osteomyelitis secondary to Staph. The hospital course was complicated by acute renal failure that required dialysis. Renal biopsy showed IgA deposits, and the patient was initially treated with steroids for IgA Nephropathy. The patient did not respond to immunosuppressive treatments and had a second biopsy, clinical history, and course that closely resembled IgA-IRGN. The patient was eventually removed from dialysis after five months. In patients with documented S. aureus infection who present with acute kidney injury, hematuria, and proteinuria, IgA-IRGN should be considered as the etiology. Source control measures should be attempted when necessary and patients should be treated with an appropriate course of antibiotics. Proper diagnosis is important to avoid exposure to immunosuppressive medications and potentially worse outcomes in these patients.
Background:Preoperative Doppler ultrasound (DUS) is routinely used to map upper-limb vessels before arteriovenous fistula (AVF) creation, yet the predictive value of individual morphologic and hemodynamic parameters remains inconsistent. This study evaluated whether preoperative vessel diameters and flow velocities predict functional AVF maturation in end-stage renal disease (ESRD). Methods:In a prospective cohort (January 2023-June 2025), adults with ESRD undergoing first-time upper-limb AVF creation received standardized DUS within 2 weeks preoperatively. Arterial and venous internal diameters and peak systolic velocities were measured at planned access sites; measurements were obtained in triplicate and averaged. Functional maturation was defined as sustained two-needle cannulation for hemodialysis at ≥300 mL/min for ≥3 consecutive sessions within 6 months, without endovascular or surgical intervention. Results:Ninety patients were enrolled; one patient was lost to follow-up before the primary outcome assessment, leaving 89 patients for analysis. Radiocephalic (Type 1) AVFs accounted for 32/90 (35.6%) and brachiocephalic (Type 2) AVFs for 58/90 (64.4%). Overall, 66/89 (74.2%) fistulas matured and 23/89 (25.8%) failed (12 early, 11 late). Maturation was not associated with fistula type, diabetes, or hypertension. Our study suggests that Larger distal radial artery diameter was paradoxically associated with failure (2.27±0.54 mm vs 1.98±0.52 mm; p=0.037) and remained significant after multivariable adjustment (coefficient=-1.892; p=0.006). No other assessed arterial or venous diameter or peak systolic velocity predicted outcome. Conclusion:Most preoperative DUS measurements did not predict AVF maturation; however, larger distal radial artery diameter paradoxically correlated with failure. Larger multicenter studies incorporating arterial wall pathology, venous outflow resistance, and detailed hemodynamics are warranted to refine preoperative decision-making. Arterial quality may be as important as size alone.
Background: Acute kidney injury (AKI) is a sudden decline in kidney function that poses a significant risk to patients undergoing surgery. Those who develop AKI face higher morbidity and mortality rates, extended hospital stays, and an increased risk of progressing to chronic kidney disease. Previously, we recruited two distinct patient cohorts, one undergoing elective cardiac surgery and one undergoing orthopaedic fracture surgery, to investigate biomarkers involved in the pathophysiology of AKI. This study is a retrospective analysis of data from the two surgical cohorts to examine if there are any similarities between cytokine responses. Methods: Pre- and post-operative blood and urine biomarker data from elective cardiac surgery patients (n=401) and orthopaedic fracture surgery patients (n=237) were analysed to compare baseline, ratio, and delta change differences. Results: Pre-operatively, baseline levels of most biomarkers were significantly higher in orthopaedic fracture patients compared to elective cardiac surgery patients. Post-operatively, most biomarker levels remained significantly higher in orthopaedic fracture surgery patients with the exception of urinary anti-inflammatory biomarkers which were higher in cardiac patients. Pre-operatively, renally favourable biomarker ratios were significantly higher in orthopaedic fracture surgery patients compared to elective cardiac surgery patients. In contrast, post-operatively, renally favourable biomarker ratios were significantly higher in elective cardiac surgery patients. The delta differences between pre- and post-operative biomarker levels were generally higher in the elective cardiac surgery patients compared with orthopaedic fracture surgery patients. Discussion: In this study, in patients which have experienced a fracture, the trauma of the initial injury activated their pro- and antiinflammatory cytokine responses such that renally favourable ratios prevailed pre-operatively. The further pro-inflammatory response from fracture repair (during surgery) was compensated for by an already established anti-inflammatory perioperative response, suggesting that post-operative compensatory anti-inflammatory responses do not need to be of the same magnitude compared to a non-preconditioned (eg, elective cardiac) response. Cytokine profiling perioperatively could inform clinical decision making and improve patient outcomes by reducing the likelihood of an AKI event.
Purpose:To assess the effectiveness and safety of telmisartan-amlodipine (TA) versus telmisartan-cilnidipine (TC) fixed-dose combinations (FDCs) in patients with hypertension and renal impairment. Patients and Methods:This open label, randomized, multicentric, post-marketing study was conducted in India. Adult patients with hypertension and renal impairment, receiving a stable dose of telmisartan and not on calcium channel blockers, were enrolled. Participants were randomized (1:1) to receive the TA or TC FDC for 12 months. The primary endpoint was change in the urine albumin-creatinine ratio (UACR) from baseline to 12 months. Secondary endpoints included changes in estimated glomerular filtration rate (eGFR), serum creatinine, and serum uric acid at 6 and 12 months, and office systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 3, 6, 9, and 12 months. Similar parameters were assessed in the diabetic subpopulation. Adverse events were recorded and classified using system organ classification. Results:At 12 months, the TA and TC groups showed significant reductions in UACR by 119±157.7 mg/g and 97.5±128.6 mg/g, respectively (p<0.0001 for both). Improvements in eGFR and serum creatinine were comparable between groups (p>0.05). SBP reduction was significantly greater with TA at both 9 months (20.74±12.75 vs. 16.9±13.66) mmHg, (p=0.0430)] and 12 months (25.4±14.25 vs. 20.6±10.94) mmHg, (p=0.0397)], while DBP reductions were similar. The diabetic subgroup showed a superior SBP reduction favoring the TA group -24.5 (±13.75) mmHg (p≤.0001) Vs -18.9 (±10.68) mmHg (p≤.0001) while the renal parameters were similar between the two groups. A total of 17 mild drug-related adverse events were reported (TA: 8; TC: 9), with no serious events. Conclusion:Both the TA and TC FDCs were effective and well tolerated when treating hypertension with renal impairment. The TA FDC may provide better BP reduction with similar reno-protective benefits than the TC FDC.
Aim: The mixed lymphocyte reaction (MLR) is a critical assay for evaluating immunological compatibility between donors and recipients prior to transplantation. Purpose: This prospective study aimed to evaluate the association of the renal allograft function with outcomes of the pre-transplant carboxyfluorescein diacetate succinimidyl ester (CFSE)-MLR assay and the levels of donor-specific antibodies (DSAs). Patients and Methods: The study included 14 live donors and non-sensitized recipient pairs. Peripheral blood samples were collected from donor and recipient pairs, and then peripheral blood mononuclear cells (PBMCs) were isolated. Donor cells were treated with Mitomycin-C as inactivated stimulators, and recipient PBMCs were labeled with CFSE as responder cells for flow cytometric analysis of the responder cell proliferation. Post-transplant renal function was monitored by serial measurements of serum creatinine levels, which were then correlated with MLR proliferation rates. Additionally, the relationship between pre-transplant MLR proliferation and DSA titers was examined. Correlative analyses were also performed between MLR outcomes and DSA levels, as well as the panel reactive antibody (PRA) outcomes. Results: Significant increases in the percentage of proliferating responder cells were observed at days 3 and 5 relative to baseline (day 0). A positive correlation was identified between day 5 proliferation rates and PRA Class II levels. Pre-transplant cellular proliferation did not significantly correlate with serum DSA titers measured at six months post-transplant. Conversely, a statistically significant positive correlation was detected between day 5 MLR proliferation and serum creatinine levels at six months post-transplantation. Conclusion: The CFSE-MLR assay represents a reliable association with post-transplant immunological status and allograft function. Nevertheless, further evidence-based research with larger cohorts is warranted to validate these findings and strengthen their clinical applicability.
Background:Malaria remains a major global health challenge, particularly in endemic regions where severe disease contributes substantially to morbidity and mortality. Among its systemic complications, malaria-associated acute kidney injury (MAKI) is increasingly recognized as a significant yet underappreciated contributor to poor clinical outcomes. Despite advances in antimalarial therapy, MAKI continues to be associated with high mortality and growing evidence suggests a link to long-term renal sequelae, including chronic kidney disease (CKD). This review synthesizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, management, and long-term outcomes of MAKI. Methods:A focused PubMed/MEDLINE search (2015-2025) was conducted to identify relevant studies across different age groups and Plasmodium species. Emphasis was placed on epidemiology, mechanisms of kidney injury, clinical features, management strategies, and renal outcomes. Studies were selected based on relevance to the review objectives. Results:MAKI is a serious complication of severe malaria, resulting from a multifactorial process involving intravascular hemolysis, microvascular obstruction, inflammation, endothelial dysfunction, and volume depletion. Plasmodium falciparum remains the most commonly implicated species, although Plasmodium vivax and Plasmodium knowlesi are increasingly recognized causes. Clinically, MAKI is associated with prolonged hospitalization, increased need for renal replacement therapy, and higher mortality. Emerging evidence also indicates that survivors are at risk of incomplete renal recovery and progression to CKD. Conclusion:MAKI is a critical driver of both acute mortality and long-term kidney disease in malaria. Early recognition, prompt management, and post-recovery renal monitoring are essential to improve outcomes. Greater awareness and further research are needed to define preventive strategies and long-term renal implications, particularly in resource-limited endemic regions.
