INTRODUCTION:Chronic kidney disease (CKD), particularly hypertension-associated CKD (HCKD), is a significant global health burden, with hypertension and diabetes as leading causes. Rising global temperatures and climate variability exacerbate HCKD risks by triggering mechanisms like dehydration, renal ischemia, and increased blood pressure. Using Global Burden of Disease (GBD) 2021 data and predictive models, this study examines trends in HCKD attributable to high and low temperatures. METHOD:This study utilizes GBD 2021 data, focusing on HCKD burden from temperature extremes. Age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years rates (ASDR) were analyzed using descriptive statistics and trend evaluations through estimated annual percentage change (EAPC). Forecasts employed the exponential smoothing (ES) and autoregressive integrated moving average (ARIMA) models. P <0.05 is considered statistically significant, with uncertainty intervals enhancing robustness. RESULT:In 2021, 5,013 (95% UI: -117-12,053) deaths and 117,175 (95% UI: 4,333-270,676) DALYs from HCKD attributable to high temperature were recorded worldwide, with increases in ASMR (EAPC: 3.43) and ASDR (EAPC: 3.18) since 1990. Low temperature caused 22,892 deaths and 420,310 DALYs, with slower ASMR and ASDR growth. Men consistently exhibited higher ASMR and ASDR than women. Mortality and burden peaked in the 95+ age group and varied across SDI regions, with the highest burdens in low-SDI areas. ARIMA and ES models project continued growth in HCKD burden due to temperature, though growth rates may decelerate by 2050. CONCLUSION:Males, the elderly, and people living in LMICs need to be particularly concerned about the threat of HCKD attributed to high and low temperatures.
BACKGROUND:Glaucoma is the leading cause of irreversible blindness worldwide, and chronic kidney disease (CKD) is associated with progression to end-stage renal disease, cardiovascular events, and increased mortality. Although both conditions share common vascular and metabolic risk factors, the long-term relationship between intraocular pressure (IOP) and CKD progression remains unclear. We investigated whether elevated IOP is associated with advanced CKD progression in a long-term observational cohort. METHODS:A total of 4,170 participants who visited a preventive medicine research center were followed for up to 20 years. Progression to an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² was defined as the primary endpoint. Hazard ratios (HRs) were estimated using competing risks regression with cumulative incidence function analyses. Multivariable analysis was performed using the Fine-Gray subdistribution hazard model. Propensity score matching was applied to validate the robustness of the results. RESULTS:Participants with baseline IOP ≥17.5 mmHg had a significantly higher risk than those with IOP <17.5 mmHg (HR 1.49; 95% CI: 1.08-2.05; p = 0.015) in multivariate analysis. The annual decline in eGFR associated with higher baseline IOP was -0.939 mL/min/year, based on ROC-derived risk stratification. Multivariable Fine-Gray analysis identified IOP ≥17.5 mmHg as an independent risk factor for advanced CKD, together with older age, obesity, diabetes, and proteinuria. These findings were consistent in the propensity score-matched cohort (HR 1.56; 95% CI: 1.01-2.39; p = 0.043). CONCLUSION:Elevated intraocular pressure is independently associated with progression to advanced CKD. Incorporating IOP into conventional risk assessment may improve identification of individuals at high risk for CKD progression.
OBJECTIVE:High-altitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine (CR) mediates the relationship between altitude acclimatization (AAI) peripheral oxygen saturation (SpO2)/hematocrit (HCT) ratio and frontal neural oscillations. METHODS:In 190 adults at 3,650 m (Lhasa), we measured SpO2, hematocrit, CR, and resting-state frontal electroencephalography. Power spectral density was calculated across multiple frequency bands (1-80 Hz) and Z-standardized. Mediation analysis with bootstrap tested the indirect effect of AAI on each band via CR. RESULTS:AAI significantly negatively predicted CR (p < 0.001). CR significantly negatively predicted frontal Z-PSD in theta (4-7 Hz), alpha (8-13 Hz), and beta (14-30 Hz) bands (all p < 0.01), but not in other bands. The indirect effect via CR was significant for theta (p = 0.011, partial mediation), alpha (p = 0.031, full mediation), and beta (p = 0.020, full mediation). CONCLUSION:The kidney-brain axis mediates hypoxic neurocognitive adaptation with frequency-specific patterns. CR dynamics reflect acclimatization efficacy, suggesting a target for preserving frontal executive function at high altitude.
Background: The determinants of glomerular filtration rate (GFR) and its changes over time are multiple and diverse. Nephron endowment is the starting point for GFR. Low renal endowment due to maternal undernutrition or premature birth as well as the loss of renal mass because of surgical procedures have a major impact of GFR Eventually low renal mass may lead to organ damage when combined with metabolic syndrome and obesity or diabetes. The kidney has a major role in maintaining homeostasis. Changes in metabolic demand have a major influence in renal function. Increments in metabolic demand may determine a compensatory increase in GFR to cope with the new metabolic status. Clear examples of these conditions are pregnancy and obesity. Also, GFR may vary in response to the stimulation of renal reserve and the ageing process. All these aspects are different in men and women and may explain gender differences in renal function in health and disease. Summary. In general, women have lower renal mass and lower metabolic demand. However, the study of these aspects in humans is complex. A living donor has two healthy kidneys and after nephrectomy, one of them remains in the same subject undergoing mechanisms of compensation whereas the other is transplanted in a patient with CKD that might have different body size, sex or age, than the donor. This makes the living kidney donation a unique setting to study the determinants of GFR. In this review, we take advantage of data from living kidney donors and recipients to understand diverse determinants of GFR, focusing on gender differences in renal function. Key Messages. In health and disease, several factors influence GFR like renal mass, the presence or absence of renal reserve, metabolic demand, the capacity of the kidney to adapt to it and the effect of ageing and senescence. In all of them, gender differences play a relevant role, making differences between men and women a factor to consider in the analysis of GFR.
Background: In patients with chronic kidney disease (CKD), lower and sub-functional high-density lipoprotein cholesterol (HDL-C) is associated with poor cardiovascular outcomes. Notwithstanding such poor outcomes, the primary therapeutic target in patients with CKD is low-density lipoprotein cholesterol (LDL-C), and the comparative effectiveness of commonly used lipid-lowering therapies (LLTs) in changing HDL-C levels in patients with non-dialysis-dependent CKD (NDD-CKD) remains unclear. Methods: In this retrospective cohort study, using a target trial emulation framework, we examined a nationwide cohort of 3,562,882 US Veterans with normal kidney function enrolled between October 2004 and September 2006 and identified 247,270 incident CKD patients eligible for de novo LLT exposure, occurring during longitudinal follow-up until October 2019. We defined de novo LLT initiation using pharmacy dispensation data and followed patients for up to 1 year. We compared the intraindividual slopes of HDL-C levels in de novo fibrates and niacin users with those in statin users, using mixed-effects models adjusted for baseline and time-varying covariates. We also compared the odds of having a clinically meaningful (>10% from baseline) increase in HDL-C following LLT initiation. Results: A total of 38,223 patients with incident CKD initiated de novo LLT (statin [n=35,284], fibrate [n=1,805], and niacin [n=1,134]). The mean (SD) age was 67.3 (10.5) years; 95.0% were men, and 20.6% were Black. Compared to statin users, the multivariable-adjusted annualized intraindividual increase of HDL-C was significantly higher following fibrate (1.15 mg/dL/year [95% CI: 0.43, 1.87]; p=0.002) and niacin monotherapy (2.51 mg/dL/year [95% CI: 1.62, 3.41]; p<0.001). Furthermore, niacin (OR: 1.37 [95% CI: 1.07, 1.75]; p=0.012) was more likely than statins to provide a clinically meaningful elevation in HDL-C. Our findings were consistent in several sensitivity analyses. Conclusion: Among patients with NDD-CKD, de novo prescription of fibrates and niacin is associated with a greater increase in HDL-C levels compared to statins. Further studies are warranted to investigate whether such differences have meaningful effects on clinical outcomes.
BACKGROUND:Omicron variants of COVID-19 have driven global waves of infection. Hemodialysis patients are particularly vulnerable to severe outcomes. However, clinical data on the impact of Omicron infection in hemodialysis patients remain limited. METHODS:We retrospectively collected clinical data on hemodialysis patients infected with the COVID-19 Omicron variant at Huashan Hospital between March 31 and May 3, 2022, a period marked by a rapid increase in COVID-19 cases. Patients were categorized into two groups based on chest CT: the non-COVID-19 pneumonia group and the COVID-19 pneumonia group. Additionally, 74 diabetic patients who did not receive hemodialysis and who contracted COVID-19 during the study period were analyzed as controls. RESULTS:A total of 150 hemodialysis patients were admitted to the hospital during this period, and 3 were excluded because of a lack of chest CT. At admission, 105 (71.4%) patients were diagnosed with COVID-19 pneumonia on the basis of chest CT. In contrast, 41.9% of non-hemodialysis diabetic patients exhibited manifestations of COVID-19 pneumonia. In dialysis patients, compared to the non-pneumonia group, the pneumonia group was older (65.7 ± 12.0 vs. 59.9 ± 16.3 years; p = 0.041) and had a higher prevalence of diabetes (39.0% vs. 11.9%; p = 0.003). The median time from the initial positive RT-PCR result for SARS-CoV-2 to the first negative result was similar between the two groups. Serum levels of fibrinogen, NT-pro-BNP, and creatinine were independent factors associated with CT-defined COVID-19 pneumonia. CONCLUSIONS:Hemodialysis patients had a higher prevalence of COVID-19 pneumonia. The fibrinogen level was an independent factor associated with CT-defined COVID-19 pneumonia.
INTRODUCTION:Lysozyme-associated nephropathy (LyN) is an underrecognized cause of kidney dysfunction, commonly associated with chronic myelomonocytic leukemia (CMML). CASE PRESENTATION:We present 2 cases of LyN with distinct clinical manifestations. In Case 1, an 80-year-old man with primary myelofibrosis developed progressive monocytosis, kidney dysfunction, proteinuria, and elevated serum and urinary lysozyme levels. Kidney biopsy revealed lysozyme-positive intracytoplasmic granules within proximal tubular cells, confirming the diagnosis of LyN. Notably, the progressive increase in the number of lysozyme-positive bone marrow cells may serve as an indicator of LyN activity. Treatment with hydroxycarbamide, a cytoreductive agent, and ruxolitinib, a Janus kinase inhibitor, successfully stabilized kidney function. In Case 2, a 63-year-old man with CMML developed acute kidney injury. Although the etiology of kidney dysfunction could not be determined during life, autopsy revealed diagnostic features of LyN. To further investigate LyN pathophysiology, we performed the first mass spectrometry-based proteomic analysis of proximal tubules in 2 cases. LyN samples showed marked lysozyme accumulation and upregulation of proteins involved in lysosomal system, lipid metabolism, cellular stress, and chronic inflammation. These findings suggest that chronic lysozyme overload disrupts intracellular homeostasis and contributes to kidney injury. CONCLUSION:LyN is underdiagnosed as unexplained tubular damage or chronic kidney disease, highlighting the need for awareness of the clinicopathological features.
BACKGROUND:Monoclonal gammopathy of renal significance (MGRS) is a rare group of renal disorders caused by monoclonal immunoglobulins from non-malignant B-cell or plasma cell clones, with distinct amyloid (MGRS-A) and non-amyloid (MGRS-NA) subtypes. Although these are often grouped together, whether they share similar clinical phenotypes and outcomes is uncertain. We therefore examined similarities and differences between these subtypes in a contemporary real-world cohort. METHODS:We performed a single-centre retrospective evaluation of 17 biopsy-confirmed MGRS patients (10 MGRS-A, 7 MGRS-NA). Baseline parameters, treatment exposure, renal and haematologic responses, survival, and relapse were analysed descriptively with exploratory subgroup comparisons. RESULTS:MGRS-NA patients presented with significantly worse baseline renal function (median estimated glomerular filtration rate 18.0 mL/min/1.73 m2 vs. 49.0 mL/min/1.73 m2 in MGRS-A, p < 0.05) and progressed faster to dialysis (p < 0.01). Haematologic responses (≥VGPR) were achieved in 57.1% of MGRS-NA and 50% of MGRS-A patients, but these did not significantly correlate with renal improvement. Survival was similar between groups, with deaths in 28.6% of MGRS-NA and 20% of MGRS-A. Relapse occurred in 47.1% of patients, with median times of 51 months in MGRS-NA and 69 months in MGRS-A. Treatment, primarily bortezomib-based chemotherapy, was associated with toxicities (94.1%), yet renal responses remained limited. CONCLUSION:The findings highlight the poor prognosis and rapid renal decline in MGRS-NA. We highlight the need for early diagnosis and an integrated renal-haematologic service to improve outcomes in this rare population.
BACKGROUND:Progress in nephrology is still constrained by the limited ability of conventional experimental models to faithfully recapitulate the complex structure and function of the human kidney. Human pluripotent stem cell-derived kidney organoids provide a three-dimensional in vitro experimental system that allows investigation of kidney development and disease-related mechanisms in a human cellular context, although still limited in their ability to reproduce the full structural and physiological complexity of the native kidney. SUMMARY:Kidney organoids have emerged as a powerful system to investigate both inherited and acquired kidney disorders. Genetic applications include cystic kidney diseases and ciliopathies, as well as inherited tubular and storage disorders, and glomerular genetic diseases. For acquired diseases and injuries, organoids support modeling of kidney damage (including exposure to pathogenetic factors, metabolic, diabetic, and profibrotic stress) and drug nephrotoxicity. These platforms enable research on mechanistic pathways through transcriptomic, proteomic, imaging, and functional readouts that can be applied at the level of specific nephron segments. Methodological advances, including improved differentiation protocols and organoid-on-chip systems, are enhancing maturation and physiological relevance. Nevertheless, kidney organoids remain immature, showing variable cellular composition and lacking a fully integrated vasculature and urinary outflow system, which currently limit their applicability as experimental models. KEY MESSAGES:Kidney organoids provide a human-based platform for mechanistic and translational nephrology research. At present, kidney organoids are mainly used for disease modeling and nephrotoxicity testing, while their broader applicability remains limited by current technical and biological challenges. Regenerative translation will depend on advances in maturation and integration of fully developed vascular and urinary system components.
BACKGROUND:The objective of a multicentre, prospective, observational study of an eculizumab biosimilar (Elizaria®) was to analyse the efficacy and safety of long-term complement inhibitor therapy in patients with atypical haemolytic uraemic syndrome (aHUS). MATERIALS AND METHODS:The study included 50 patients aged 1-55 years, with 42% of them under the age of 18. The patients received the eculizumab biosimilar in routine clinical practice within 56 weeks; 19 patients (38%) had been treated with eculizumab prior to enrolment, whereas 31 patients (62%) were naive to complement inhibitors. RESULTS:By the end of the study, an increase in platelet count of 39.48 ± 21.7 × 109/L and 33.61 ± 24.06 × 109/L was reported in treatment-naive and treatment-experienced patients, respectively. By the end of the study, 96% of treatment-experienced patients and 100% of treatment-naive patients had normal platelet counts. The mean LDH activity did not change significantly, with levels of 253.84 ± 122.22 U/L registered at screening and 245.24 ± 93.52 U/L at the end of the study. In total, 39 patients (77.6%) at week 21 and 40 patients (80%) at week 52 had no thrombotic microangiopathy (TMA) events. During the study, the proportion of patients with a complete TMA response increased significantly, rising to 8% (p = 0.046). The proportion of patients with an estimated glomerular filtration rate improvement of 15 mL/min/1.73 m2 and more at week 52 was 12%. During the safety assessment, 63 adverse events not related to the investigational medicinal product were reported. CONCLUSION:Long-term complement inhibitor therapy with the eculizumab biosimilar in patients with aHUS has demonstrated a stable effect, a favourable safety profile, and low immunogenicity.
BACKGROUND:Frailty and chronic kidney disease (CKD) are common, interrelated conditions in ageing populations, yet the association between kidney function and frailty remains incompletely characterized, particularly when estimated using different estimated glomerular filtration rate (eGFR) equations. METHODS:We analyzed 17,864 participants aged ≥45 years from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Frailty was defined primarily by the deficit-accumulation frailty index, with the Fried physical frailty phenotype applied in a prespecified sensitivity analysis. Kidney function was estimated using the CKD-EPI creatinine (eGFRcr), cystatin C (eGFRcys), and combined creatinine-cystatin C (eGFRcr-cys) equations. Multivariable logistic regression, restricted cubic splines, and threshold effect models were used to assess linear and nonlinear associations, with adjusted predicted probabilities derived to quantify absolute risk. RESULTS:Overall, 10.0% of participants were frail and 38.6% prefrail. Lower eGFR was independently associated with higher odds of frailty across all three equations, with the strongest and most consistent associations observed for eGFRcys (eGFRcys: <30 vs. ≥90 mL/min/1.73 m2; odds ratios [OR]: 4.39; 95% confidence interval [CI]: 2.32-8.32; p for trend <0.001), corresponding to an adjusted absolute risk difference of 18.9 percentage points. eGFRcr-cys showed similar but attenuated associations, whereas eGFRcr was associated with frailty only at severely reduced levels (<30 mL/min/1.73 m2). Nonlinear relationships were evident for eGFRcys and eGFRcr-cys, with inflection points at 58.78 and 51.65 mL/min/1.73 m2, respectively. Sensitivity analyses using the Fried phenotype and a model excluding laboratory parameters yielded directionally consistent results. CONCLUSION:Cystatin C-based eGFR was more strongly and consistently associated with frailty than creatinine-based estimates in middle-aged and older Chinese adults, with associations emerging at earlier stages of kidney dysfunction. Incorporating eGFRcys into kidney function assessment in this population may aid the identification of individuals at increased risk of frailty, pending confirmation in longitudinal and interventional studies.
BACKGROUND:Kidney replacement therapies (KRT) such as dialysis have a significant environmental impact, yet clinician engagement with sustainable kidney care remains limited. Our objective was to develop a mobile phone application to raise awareness of clinicians about Green Nephrology. METHODS:We developed and piloted a web-based mobile application designed to raise awareness of "Green Nephrology" through short, interactive information modules. The app was introduced at the World Congress of Nephrology 2025. It presented users with real-world dilemmas and evidence-based facts about the environmental impact of kidney care choices. We discuss the possibilities of using such interactive modules for sensitizing doctors, nurses and technicians. RESULTS:Thirty-eight delegates used the app and reported it as intuitive, enjoyable, and thought-provoking. CONCLUSION:This feasibility pilot suggests that lightweight, gamified digital tools can effectively promote reflection and discussion on environmentally sustainable nephrology practices.
BACKGROUND:Preterm birth disrupts kidney development, resulting in reduced nephron number and structural immaturity of glomeruli and podocytes that increases the risk of hypertension, proteinuria, and subsequently chronic kidney disease (CKD) later in life. Since nephrogenesis ceases around 36 weeks of gestation, preterm infants cannot generate new nephrons after birth, making them vulnerable to long-term renal dysfunction. Unravelling the mechanisms behind this impaired development has been limited by the complexity of human nephrogenesis and the lack of physiologically relevant experimental models. SUMMARY:Recent advances in human-induced pluripotent stem cell-derived kidney organoids have made it possible to model nephrogenesis in vitro. These organoids replicate key processes such as nephron differentiation, ureteric bud branching, and kidney vascularization, allowing detailed study of kidney development and injury. Moreover, molecular interventions - including retinoic acid (RA), glial-cell-line-derived neurotrophic factor (GDNF), and insulin-like growth factor 1 (IGF1) - show the potential to enhance nephron formation and protect against kidney injury. KEY MESSAGES:(1) Kidney organoids provide a powerful, human-relevant system to study nephrogenesis and CKD mechanisms. (2) Integration of the ureteric bud and enhanced vascularization significantly improves organoid maturity towards a more in vivo-like state. (3) Targeted molecular interventions such as RA, GDNF, and IGF1 offer potential strategies to enhance nephron endowment and mitigate CKD risk in preterm-born individuals and may be studied using kidney organoids.
BACKGROUND:Kidney xenotransplantation has reemerged as a viable therapeutic strategy to address the global shortage of donor organs, driven by substantial advances in porcine genetic engineering and immunomodulatory therapies. Clinical experiences in brain-dead decedents and, more recently, in living recipients have demonstrated that genetically modified pig kidneys can provide life-sustaining renal function in humans, marking a pivotal milestone in the field. SUMMARY:Elimination of major carbohydrate xenoantigens, particularly through GGTA1 deletion, has effectively abrogated hyperacute rejection, enabling short- to intermediate-term xenograft survival. However, emerging data reveal that xenotransplantation elicits a uniquely aggressive and persistent immune response involving both innate and adaptive immunities. Conventional immunosuppressive regimens used in kidney allotransplantation appear insufficient when reduced in intensity and require full-dose application combined with B-cell depletion and costimulation blockade to control preexisting xenoreactive T cells and de novo antibody formation. Complement activation remains a central pathogenic mechanism despite extensive donor genetic modification, with emerging evidence suggesting that sustained control of both terminal and proximal complement activation may be beneficial in selected settings. An additional, unexpected challenge is the development of early and often persistent nephrotic-range proteinuria, which may reflect species-specific glomerular barrier incompatibilities, immune-mediated injury, or both, and may have important implications for graft survival by promoting urinary loss of biologic immunosuppressive agents. KEY MESSAGES:Hyperacute rejection in kidney xenotransplantation has been effectively overcome through targeted genetic modifications of donor pigs. However, xenotransplantation remains characterized by a sustained adaptive and innate immune response and ongoing complement activation, necessitating intensified and multimodal immunosuppression. An additional emerging challenge is early and sometimes persistent nephrotic-range proteinuria, which may compromise graft function and alter the pharmacokinetics of biologic immunosuppressive agents. Future progress will depend on integrated strategies combining genetic engineering, costimulation blockade, and appropriately targeted complement inhibition to achieve long-term xenograft survival.
BACKGROUND:Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is increasingly recognized as a chronic inflammatory disorder driven by immune dysregulation. SUMMARY:This review examines key immunogenetic pathways in DKD, focusing on genetic variants affecting innate and adaptive immunity. We explore how polymorphisms in genes regulating immune cell function, cytokine production, and inflammatory signaling contribute to renal damage. Recent evidence demonstrates that these immunogenetic factors significantly influence DKD development and progression. KEY MESSAGES:The pathogenesis of DKD is profoundly influenced by an individual's genetic predisposition to immune dysregulation. Numerous genetic variants can exacerbate inflammatory responses, promoting disease development. A deeper understanding of these immunogenetic pathways not only clarifies the pathophysiology of DKD but also opens avenues for novel biomarker discovery and the development of targeted, personalized immunomodulatory therapies.
INTRODUCTION:Anticoagulant-related nephropathy (ARN) is an emerging and often unrecognized form of acute kidney injury. Histologically characterized by glomerular hemorrhage and intratubular erythrocyte casts, ARN is a serious complication associated with increased morbidity and progression to chronic kidney disease. Although it has been described in association with oral anticoagulants, the literature regarding ARN induced by non-oral agents, such as low-molecular weight heparin (LMWH), remains extremely scarce. This report aims to fill this gap, highlighting the importance of early diagnosis in complex clinical settings. CASE PRESENTATIONS:We present two cases of biopsy-proven ARN induced by LMWH in patients with concomitant active renal disease. The first case is a 53-year-old man with ANCA-associated vasculitis who, after starting enoxaparin for deep vein thrombosis, experienced worsening renal function despite improvement in his pulmonary and serological vasculitis markers. A second renal biopsy was crucial to diagnose the superimposed ARN, leading to a change in therapy and renal recovery. The second case is a 73-year-old man with chronic kidney disease who developed an acute kidney injury initially attributed to post-infectious glomerulonephritis. The initiation of prophylactic LMWH was followed by further, severe deterioration of renal function requiring dialysis. In this case as well, a second biopsy revealed the presence of superimposed ARN. The discontinuation of anticoagulant therapy led to the resolution of hematuria and the cessation of dialysis. In both cases, the diagnosis was confirmed by positive Perl's staining and immunohistochemical findings of tubular damage. CONCLUSIONS:These cases demonstrate that ARN is not an exclusive complication of oral anticoagulants but can also be induced by LMWH. ARN can mask or overlap with other renal pathologies, making diagnosis difficult. Renal biopsy, sometimes repeated, remains the gold standard for an accurate differential diagnosis. This makes it possible to avoid inappropriate therapy escalation and to guide correct clinical management. Greater awareness of this clinical entity is necessary in all anticoagulated patients who develop acute kidney injury.
Background: Acute kidney injury (AKI) worsens outcomes in low- and middle-income countries, largely due to delayed diagnosis and limited access to renal replacement therapy. Its true epidemiology remains unclear, partly due to delayed biochemical testing. In a prior phase of our work, we evaluated point-of-care creatinine (POC Cr) technology and its use in implementing a clinical algorithm to select patients at risk of AKI in a Nigerian hospital emergency department. In this study, POC Cr was used in a large primary care health center in Nigeria. METHODS:The study was conducted at Ozuoba Model Comprehensive Primary Health Care Centre in Nigeria, where renal function tests are rarely available and external laboratory results typically take over 48 h. POC Cr testing was introduced for high-risk adults using the clinical algorithm developed in the previous phase of this programme and for children with suspected severe illness based on clinical judgement or reduced urine output. Adjusted POC Cr values were calculated (POC Cr - 27.2 µmol/L), and AKI was staged using KDIGO criteria, with baseline creatinine defined as 100 µmol/L for adults and age-specific norms for children. RESULTS:A total of 424 patients were tested using POC Cr, comprising 301 adults and 123 children. Malaria was the most frequent diagnosis, accounting for 293 cases (61.1%). The median adjusted POC Cr across the entire cohort was 72.8 µmol/L (interquartile range [IQR]: 36). Among adult patients, AKI was diagnosed in 2 out of the 301 individuals (0.6%), one stage 1 and one stage 2, both of whom had malaria. In the paediatric group, the median age was 5 years (IQR: 7), with females comprising 65% of the cohort. Malaria was diagnosed in 69.9% of the children. AKI was identified in 70 out of 123 children (56.9%), with AKI stage 1 in 25 (20.3%), stage 2 in 26 (21.2%), and stage 3 in 19 children (15.4%). Among the 70 paediatric AKI cases, 49 (70%) had malaria. The highest prevalence of AKI was seen in children under 5 years of age, with the incidence declining steadily and reaching zero beyond age 12. CONCLUSION:Our study found that more than half of paediatric patients diagnosed with malaria at a primary health care level had AKI, highlighting AKI as a common complication of malaria in young children. These findings emphasise the need for further research to support informed potential updates to WHO malaria treatment guidelines to incorporate the KDIGO definition of AKI, particularly in the context of paediatric care in low-resource settings. .
