OBJECTIVE: Advanced glycation end-products (AGEs) are implicated in the age-related decline of renal function, exacerbated by conditions, such as hyperglycemia and oxidative stress. The accumulation of AGEs in the kidneys contributes to the progressive decline in renal function observed with aging. However, the precise role and mechanisms of AGEs in the age-related decline of renal function remain unclear. In this study, we investigated the impact and potential mechanisms of AGEs on aging kidneys in naturally aging mice.
METHODS: Male C57BL/6 mice were divided into three groups: 6-, 57-, and 107-week-old. First, the 6- and 107-week-old mice were euthanized. The remaining mice were divided into young (6 weeks) and old (57 weeks) groups. The 57-week-old mice were orally administered aminoguanidine (100 mg/kg/day), an AGEs inhibitor, or vehicle for 13 weeks, resulting in a final age of 70 weeks. The serum and kidney tissues were collected for biochemical measurement, histological examination, immunohistochemistry staining, and immunoblotting analysis.
RESULTS: Our findings revealed a notable accumulation of AGEs in both serum and kidney tissue specimens and renal dysfunction in naturally aging mice. Aminoguanidine not only reversed AGEs accumulation but also ameliorated renal dysfunction. Additionally, aminoguanidine attenuated the upregulation of fibrosis markers (phosphorylated p38/α-SMA and C/EBP homologous protein, CHOP), senescence markers (p53 and p21), and oxidative stress marker (4-HNE) in the aging kidneys.
CONCLUSIONS: These findings underscore the critical role of AGEs in age-related renal dysfunction and highlight the therapeutic potential of aminoguanidine in mitigating fibrosis and senescence, offering prospective avenues for combating age-associated renal ailments.

OBJECTIVE: This study aimed to evaluate the burden of kidney dysfunction (KD), assess socioeconomic inequalities, and project trends in the future.
METHODS: Data on deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were from Global Burden of Disease Study 2019. The Joinpoint regression model was utilized to analyze the temporal trend by the annual percentage change (APC). The slope index and concentration index were employed to evaluate cross-country disparities. The future trend was predicted using an age-period-cohort analysis.
RESULTS: In the past three decades, the death numbers of KD increased from 1,571,720 to 3,161,552, DALYs from 42,090,331 to 76,486,945, YLDs from 5,003,267 to 11,282,484, and YLLs from 37,087,065 to 65,204,461, respectively. The age-standardized rate (ASR) of deaths, DALYs, and YLLs exhibited a declining trend. The ASR of YLDs increased until 2017, then decreased. The slope index and concentration index for DALYs increased from 248.1 to 351.9 and from 40.70 to 57.8. In the future, the ASR of deaths, DALYs, YLDs, and YLLs will remain stable, while their numbers will continue to rise, except for YLLs.
CONCLUSIONS: The disease burden of KD remained serious. Tailored interventions should be developed based on national contexts.

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3\',5\'-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ-iNOS-p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes.

Typical hemolytic uremic syndrome (HUS) can occur as a severe systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli. Its pathology can be induced by Stx types, resulting in toxin-mediated damage to renal barriers, inflammation, and the development of acute kidney injury (AKI). Two sphingosine kinase (SphK) isozymes, SphK1 and SphK2, have been shown to be involved in barrier maintenance and renal inflammatory diseases. Therefore, we sought to determine their role in the pathogenesis of HUS. Experimental HUS was induced by the repeated administration of Stx2 in wild-type (WT) and SphK1 (SphK1-/-) or SphK2 (SphK2-/-) null mutant mice. Disease severity was evaluated by assessing clinical symptoms, renal injury and dysfunction, inflammatory status and sphingolipid levels on day 5 of HUS development. Renal inflammation and injury were found to be attenuated in the SphK2-/- mice, but exacerbated in the SphK1-/- mice compared to the WT mice. The divergent outcome appeared to be associated with oppositely altered sphingolipid levels. This study represents the first description of the distinct roles of SphK1-/- and SphK2-/- in the pathogenesis of HUS. The identification of sphingolipid metabolism as a potential target for HUS therapy represents a significant advance in the field of HUS research.

Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5 g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160 mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5 ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.

Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, p < 0.001) and thrombocytopenia (<150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.

UNASSIGNED: There has been improvement in the overall outcomes of people living with human immunodeficiency virus (PLWHIV) following the advent and use of highly active antiretroviral therapy (HAART). However, there is an increased risk of nephrotoxicity from using HAART in PLWHIV as their life expectancy improves. This study assessed and compared renal dysfunction among PLWHIV on tenofovir-based and non-tenofovir-based HAART.
UNASSIGNED: This comparative cross-sectional study determined and compared glomerular and tubular dysfunction among PLWHIV on tenofovir-based and non-tenofovir-based HAART. Urine beta2-microglobulin, fractional excretion of bicarbonate, uric acid, and Phosphate were used to assess proximal tubular function. The modification of diet in renal disease (MDRD) formula was used to estimate the glomerular filtration rate (eGFR).
UNASSIGNED: There were 120 participants with a mean age of 42.2 ±9.2 years. Sixty participants were on tenofovir-based HAART, and 60 were on non-tenofovir-based HAART. The overall prevalence of proximal renal tubular dysfunction among PLWHIV on HAART was 9.1%. The proximal renal tubular dysfunction prevalence was higher in the tenofovir-based group (15.0%vs3.3% P= 0.01). The mean urine β2 MG level was higher in the tenofovir-based HAART group (0.21±0.15ug/ml vs 0.14±0.12ug/ml; P= 0.01). The mean eGFR was lower in the tenofovir-based HAART group (86.99±18.51mls/min/1.73m2 vs 99.59±34.48mls/min/1.73m2; P=0.01).
UNASSIGNED: Tenofovir-based HAART was associated with a significant decrease in GFR and proximal renal tubular dysfunction compared to non-tenofovir-based HAART. Those on tenofovir should be regularly monitored with markers of tubular dysfunction.

BACKGROUND: The burden of chronic kidney disease (CKD) is huge, especially in countries such as Nigeria where majority of patients succumb to the disease early due to inability to afford care. Early diagnosis through regular screening of at-risk population is pivotal to stemming the scourge of the disease.
OBJECTIVE: To determine the prevalence of kidney dysfunction and associated risk factors in a community screening program.
METHODS: This cross-sectional study assessed kidney dysfunction and associated risk factors among adults in Ondo City, Nigeria. Information about socio-demographic characteristics and some risk factors for kidney dysfunction was sought. Blood pressure, weight and height were measured. Blood samples were collected for random blood glucose check and serum creatinine while urine sample was collected for urinalysis. Kidney dysfunction was defined by estimated glomerular filtration rate (eGFR) below 60mls/min/1.73m2. Prevalence of kidney dysfunction and associated factors were determined. P value<0.05 was taken as significant.
RESULTS: There were 410 participants with a mean age of 58.96±13.78 years. Majority (75.1%) were female. One hundred and forty-seven (35.9%) participants had kidney dysfunction. Identified risk factors for kidney dysfunction were hypertension (72.7%), diabetes mellitus (18.0%), alcohol intake (13.2%), tobacco smoking (2%), analgesic use (82.7%), use of herbal preparations (81.7%), proteinuria (6.1%), overweight (27.8%), generalized obesity (28.5%), and central obesity (33.9%). Significant factors associated with kidney dysfunction were older age (p=<0.001), lower level of education (p=<0.001), and being hypertensive (p=0.019). On binary logistic regression, older age (AOR: 9.14; CI: 3.68-22.7; p=<0.001) was the only significant factor associated with kidney dysfunction.
CONCLUSIONS: The prevalence of kidney dysfunction and that of associated risk factors were relatively high in the screened population. Regular assessment of kidney function should be done in those with higher risk of kidney dysfunction, especially older patients with hypertension.
BACKGROUND: Le fardeau de la maladie rénale chronique (MRC) est énorme, en particulier dans des pays tels que le Nigeria, où la majorité des patients succombent à la maladie tôt en raison de l\'incapacité à se permettre des soins. Le diagnostic précoce par le dépistage régulier des populations à risque est crucial pour endiguer le fléau de la maladie.
OBJECTIVE: Déterminer la prévalence de la dysfonction rénale et des facteurs de risque associés dans le cadre d\'un programme de dépistage communautaire.
UNASSIGNED: Cette étude transversale a évalué la dysfonction rénale et les facteurs de risque associés chez des adultes à Ondo City, au Nigéria. Des informations sur les caractéristiques sociodémographiques et certains facteurs de risque de dysfonction rénale ont été recueillies. La pression artérielle, le poids et la taille ont été mesurés. Un échantillon de sang a été prélevé pour vérifier la glycémie aléatoire et la créatinine sérique, tandis qu\'un échantillon d\'urine a été collecté pour une analyse d\'urine. La dysfonction rénale a été définie par un taux de filtration glomérulaire estimé (TFGe) inférieur à 60 ml/min/1,73 m2. La prévalence de la dysfonction rénale et des facteurs associés a été déterminée. Une valeur de p<0,05 a été considérée comme significative.
UNASSIGNED: Il y avait 410 participants avec un âge moyen de 58,96 ± 13,78 ans. La majorité (75,1 %) étaient des femmes. Cent quarante-sept (35,9 %) participants avaient une dysfonction rénale. Les facteurs de risque identifiés pour la dysfonction rénale étaient l\'hypertension (72,7 %), le diabète sucré (18,0 %), la consommation d\'alcool (13,2 %), le tabagisme (2 %), l\'utilisation d\'analgésiques (82,7 %), l\'utilisation d\'herbes médicinales (81,7 %), la protéinurie (6,1 %), le surpoids (27,8 %), l\'obésité générale (28,5 %) et l\'obésité centrale (33,9 %). Les facteurs significativement associés à la dysfonction rénale étaient l\'âge plus avancé (p=<0,001), un niveau d\'éducation plus bas (p=<0,001) et l\'hypertension (p=0,019). Dans la régression logistique binaire, le seul facteur significatif associé à la dysfonction rénale était l\'âge plus avancé (RA : 9,14 ; IC : 3,68-22,7 ; p=<0,001).
CONCLUSIONS: La prévalence de la dysfonction rénale et des facteurs de risque associés était relativement élevée dans la population examinée. Une évaluation régulière de la fonction rénale devrait être réalisée chez ceux présentant un risque élevé de dysfonction rénale, en particulier chez les patients plus âgés souffrant d\'hypertension.
UNASSIGNED: Filtration glomérulaire réduite; Dysfonction rénale; Facteur de risque ; Dépistage communautaire.

Kidney dysfunction is increasing worldwide and is exacerbated by exposure to toxic metals. Also, pregnancy poses an overload on kidney function. We investigated how blood lead (PbB) and cadmium (CdB) levels were associated with kidney function in pregnant women from Recôncavo Baiano, Brazil, during their second trimester. In this cross-sectional study, the estimated glomerular filtration rate (eGFR) was calculated from serum creatinine and whole blood metal levels were measured by graphite furnace atomic absorption spectrophotometry in 136 volunteers. Sociodemographic data were collected using semi-structured questionnaires. The medians (IQR) of PbB, CdB, and eGFR were 0.85 µg/dL (0.45-1.75), 0.55 µg/L (0.08-0.91), and 121.8 mL/min/1.73 m2 (106.0-127.9), respectively. PbB medians were significantly higher in the eGFR < 90 group at 2.00 µg/dL (0.83, 3.10). After age-adjusted logistic regression, pregnant women with elevated PbB levels had decreased eGFR (OR = 1.82; 95%-CI, 1.14-3.14). However, the participants with elevated PbB levels who reported consuming alcohol during pregnancy or had CdB in the highest tertile had higher odds of reduced eGFR (OR = 2.44; 95%-CI, 1.30-5.47) and (OR = 11.22; 95% CI, 2.53-103.51), respectively. These results suggest that low Pb exposure may affect kidney function in pregnant women and calls for further investigation into toxic metal co-exposures on kidney function during pregnancy in at-risk communities.