Annual change in eGFR in renal hypouricemia: a retrospective pilot study.

BACKGROUND: Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients. METHODS: This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5 years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4 years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4). RESULTS: In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4-2.5) and 1.1 ± 0.7 mg/dL. The median and mean Uua were 44.3 (12.7-141.1) and 49.7 ± 36.2 mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3-73.6) and 43.3 ± 19.7%. Over 4 years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (- 1.09 ± 1.11 vs. - 1.09 ± 1.92 mL/min/1.73 m2/year, p = 0.996) (- 1.74 ± 1.96 vs. - 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (- 0.33 ± 1.03 vs. - 1.67 ± 0.85 mL/min/1.73 m2/year, p = 0.116) (- 0.61 ± 1.62 vs. - 2.59 ± 1.91%, p = 0.210). CONCLUSION: RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years.

Left Ventricular Diastolic Dysfunction across Levels of Kidney Function: A Cross-Sectional Study Based on Routine Clinical Practice Data.

Left ventricular diastolic dysfunction (LVDD) commonly coexists with kidney dysfunction. In this study, we investigated the presence of abnormalities in echocardiography parameters indicative of LVDD across stages of kidney function. Methods: We selected patients who visited a university hospital and had a serum creatinine and echocardiography reported in their medical records. Participants were categorized based on their kidney function: normal (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2), mildly decreased (eGFR: 60-90), moderately decreased (eGFR: 30-60), and severely decreased (eGFR < 30). The relationship between kidney function and echocardiography parameters was examined using logistic and linear regressions. Results: Among 4022 patients (age: 66.5 years [SD: 12.1], 41% women), 26%, 50%, 20%, and 4% had a normal, mildly, moderately, and severely decreased kidney function, respectively. Compared to patients with normal kidney function, patients with mildly decreased kidney function had higher odds for an abnormal E/e' ratio (OR: 1.51 [95% CI: 1.13, 2.02]). Patients with moderately decreased kidney function presented a higher risk of abnormal E/e' (OR: 2.90 [95% CI: 2.08, 4.04]), LAVI (OR: 1.62 [95% CI: 1.13, 2.33]), TR velocity (OR: 2.31 [95% CI: 1.49, 3.57]), and LVMI (OR: 1.70 [95% CI: 1.31, 2.20]), while patients with severely decreased kidney function had higher odds for abnormal E/e' (OR: 2.95 [95% CI: 1.68, 5.17]) and LVMI > 95 g/m2 in women or >115 g/m2 in men (OR: 2.07 [95% CI: 1.27, 3.38]). The linear regression showed a significant inverse association between eGFR and echocardiography parameters, meaning that with worse kidney function, the parameters for LVDD worsened as well. Conclusions: Abnormal echocardiography parameters of LVDD were present even in patients with mildly decreased kidney function. As the kidney function worsened, there was a gradual increase in the risk of abnormal parameters of LVDD.

Comparative Mortality Rates of Vasoconstrictor Agents in the Management of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis.

Hepatorenal syndrome (HRS) is an acute complication of advanced liver disease, which manifests with a rapidly progressive decline in kidney function. Though pharmacological treatment has been recently advanced, there are still high mortality rates. The study compares the mortality rate in patients using different vasoconstrictor agents in the management of HRS. A complete literature search was done in the following databases: PubMed, Cochrane Library, PubMed Central (PMC), and Multidisciplinary Digital Publishing Institute (MDPI). Studies were included according to previously established criteria, in which all studies reporting on adult patients with HRS treated with vasoconstrictor agents were eligible. The data extracted were analyzed with a random-effects model to express variability between studies, and the principal measure was the risk ratio (RR) for mortality. Of the 8,137 studies identified, 29 met the inclusion criteria. In the meta-analysis, vasoconstrictors, mainly terlipressin, significantly improved renal function and decreased the need for renal replacement therapy (RRT) versus placebo. However, a significant impact on mortality was lacking (0.94 (0.84-1.06), p = 0.31). The subgroup analysis found that mortality rates were not significantly different between vasoconstrictors, whether used in combination with or without albumin (0.97 (0.77-1.23), p = 0.79, and 0.98 (0.79-1.21), p = 0.86). Global heterogeneity was low, indicating consistent results in the studies. Vasoconstrictors are helpful in managing HRS, with improvement in renal function and reduction in RRT requirements. However, the effect on mortality was small and nonsignificant. Such findings support the use of terlipressin in HRS management; concomitantly, they emphasize the need for personalized treatment strategies and future research to find alternative therapies that may be more effective for improved survival results with fewer side effects.

Global disease burden attributable to kidney dysfunction, 1990-2019: A health inequality and trend analysis based on the global burden of disease study.

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.

Role of advanced glycation end-products in age-associated kidney dysfunction in naturally aging mice.

AIMS: 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. MATERIALS AND 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.

Kidney Dysfunction, Hepatic Impairment, and Lipid Metabolism Abnormalities in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a global health issue that has profound medical and research implications. METHODS: This retrospective study examined changes in renal and liver function, as well as lipid metabolism, over a 12-month period in 49 adult patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). All cases were admitted, managed, and followed up with in the PH Center, County Emergency Clinical Hospital of Targu Mures, Romania. RESULTS: Kidney dysfunction was observed in 12.24% of cases at baseline, decreasing to 8.16% at 12 months, and CTEPH patients were more affected. In particular, CTEPH patients exhibited an improvement in renal function, confirmed by an increase in their glomerular filtration rates. Hepatic impairment was present in 57.14% of subjects at baseline, declining to 42.86% at 12 months, with significant improvements noted in the PAH group. Lipid metabolic dysregulations were experienced by 22.45% of all patients at baseline, decreasing to 16.33% at 6 months, with a slow elevation to 24.49% at 12 months, but with no statistically significant differences. Pharmacological regimens were adjusted in accordance with the PH groups, a patient's functional and clinical response, and laboratory tests. CONCLUSIONS: Our results demonstrate the multi-organ damage in PH and the importance of individualized treatment approaches.

Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.

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 function assessment using cystatin C and serum creatinine in heart transplantation recipients: Implications for valganciclovir dosing.

BACKGROUND: Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in muscle mass. Cystatin C (cysC) is less influenced by muscle mass, but its levels may increase with obesity and steroid use. Herein, we (1) longitudinally compared eGFRcysC and eGFRsCr among HT recipients; (2) investigated the association of body mass index (BMI), steroid use, and muscle mass with discrepancies between eGFRs; and (3) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing. METHODS: cysC and sCr were measured in 294 blood samples obtained from 80 subjects. Intraindividual differences between eGFRs (eGFRdiffcysC-sCr) were calculated with negative values corresponding to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n = 21), pectoralis muscle measures were obtained. RESULTS: Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr -28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient postoperative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction. CONCLUSIONS: Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.

Cyclic Nitroxide 4-Methoxy-Tempo May Decrease Serum Amyloid A-Mediated Renal Fibrosis and Reorganise Collagen Networks in Aortic Plaque.

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.

Successful Treatment of Intractable Tuberculous Peritonitis in a Woman with Chronic Kidney Allograft Dysfunction Using Contezolid Containing Regimen.

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.

Platelet-Rich Plasma (PRP) Mitigates Kidney Dysfunction in Alloxan-Induced Diabetic Mice via Modulation of Renal Iron Regulatory Genes.

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.

Elevated Serum KIM-1 in Sepsis Correlates with Kidney Dysfunction and the Severity of Multi-Organ Critical Illness.

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.

Prevalence of Kidney Dysfunction and Associated Risk Factors in a Southwestern City in Nigeria: A Cross-Sectional Study.

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. AIM: 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. CONCLUSION: 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.

CONTEXTE: 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. OBJECTIF: Déterminer la prévalence de la dysfonction rénale et des facteurs de risque associés dans le cadre d'un programme de dépistage communautaire. MÉTHODES: 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. RÉSULTATS: 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). CONCLUSION: 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. MOTS-CLÉS: Filtration glomérulaire réduite; Dysfonction rénale; Facteur de risque ; Dépistage communautaire.

A Cross-Sectional Analysis Investigating Pregnant Women's Renal Function and Its Association with Lead and Cadmium Exposures-The DSAN Birth Cohort Study in Recôncavo Baiano, Brazil.

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.

Pediatric early-phase anorexia nervosa without hypokalemia exhibiting acute tubular injury: a case report.

Anorexia nervosa can lead to kidney complications. Few studies reported kidney biopsy results in young adults, most of whom had chronic anorexia nervosa, and kidney biopsy findings in pediatric patients with early-phase anorexia nervosa are rarely reported. A 14-year-old girl who lost weight due to excessive exercise and reduced diet was admitted for kidney dysfunction. She was 147 cm tall and weighed 32.9 kg, with a body mass index of 15.2 kg/m2. She was 39 kg about a year earlier. Her heart rate and blood pressure were 30-40 beats/min and 108/68 mmHg, respectively. She had kidney dysfunction (estimated glomerular filtration rate, 56.6 mL/min/1.73 m2). Urine ß2-microglobulin was slightly elevated (393 µg/L), and percent tubular phosphate reabsorption was low (75.2%), suggesting tubular damage; however, hypokalemia was absent. Kidney dysfunction did not improve with fluid loading. Kidney biopsy revealed that all glomeruli were intact, with no vasculitis, interstitial inflammation or fibrosis on light microscopy. However, proximal tubular epithelial walls were flattened and the brush border was absent, suggesting acute tubular injury. Immunofluorescent staining was negative for immunoglobulins and complement proteins, and electron microscopy showed no significant electron-dense deposition. The patient's serum creatinine gradually declined, normalizing on the 17th day of admission. Unlike previous reports in young adults, kidney dysfunction was observed even in the absence of hypokalemia in the current pediatric patient with early-phase anorexia nervosa. Proximal tubular injury in early-phase anorexia nervosa may be caused by bradycardia without hypokalemia, leading to subsequent kidney dysfunction.

Clinical Impact of Malnutrition According to the Global Leadership Initiative on Malnutrition Criteria Combined With Kidney Dysfunction to Determine Mortality in Inpatients.

OBJECTIVE: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). METHODS: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and the incidence of all-cause mortality was evaluated using a multivariate Cox proportional hazards model. Malnutrition was defined as at least one phenotype (weight loss, low body mass index, or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). RESULTS: Multivariate Cox proportional hazards model showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. CONCLUSION: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

A systematic evaluation of population pharmacokinetic models for polymyxin B in patients with liver and/or kidney dysfunction.

Polymyxin B (PMB) is considered a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections. Model-informed precision dosing with population pharmacokinetics (PopPK) models could help to individualize PMB dosing regimens and improve therapy. However, the external prediction ability of the established PopPK models has not been fully elaborated. This study aimed to systemically evaluate eleven PMB PopPK models from ten published literature based on a new independent population, which was divided into four different populations, patients with liver dysfunction, kidney dysfunction, liver and kidney dysfunction, and normal liver and kidney function. The whole data set consisted of 146 patients with 391 PMB concentrations. The prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. In the overall evaluation process, none of the models exhibited satisfactory predictive ability in both prediction- and simulation-based diagnostic simultaneously. However, the evaluation of the models in the subgroup of patients with normal liver and kidney function revealed improved predictive performance compared to those with liver and/or kidney dysfunction. Bayesian forecasting demonstrated enhanced predictability with the incorporation of two to three prior observations. The external evaluation highlighted a lack of consistency between the prediction results of published models and the external validation dataset. Nonetheless, Bayesian forecasting holds promise in improving the predictive performance of the models, and feedback from therapeutic drug monitoring is crucial in optimizing individual dosing regimens.

Multiple Facets of Multiple Myeloma in Kidney Biopsy: A Multicenter Retrospective Study.

Introduction: Multiple myeloma is a type of plasma cell dyscrasia, which causes clonal proliferation of plasma cells and deposition in various organ systems. At presentation, 50% of patients with multiple myeloma have kidney dysfunction, which is considered a poor prognostic indicator. Data on the histopathological manifestations of multiple myeloma are sparse. Objective: To look at the kidney histopathological lesions in patients with the clinical diagnosis of multiple myeloma. Materials and Methods: A retrospective analysis of all kidney biopsies in patients with the clinical diagnosis of multiple myeloma was performed from June 1, 2020 to May 30, 2022, from three tertiary care nephrology referral centers. Results: A total of 61 patients with multiple myeloma and biopsy-proven kidney involvement were included in the study. The mean age at presentation was 55.39 ± 11.91 years, with male predominance (male to female ratio -1.6:1). The most common lesion on kidney biopsy was myeloma cast nephropathy (72.1%), followed by light chain deposition disease (21.3%) and AL amyloidosis (18%). About 26% of patients had dual lesions on kidney biopsy, 3% had three types of lesions on kidney biopsy In 48% of patients, the diagnosis of multiple myeloma was made only after the kidney biopsy. Conclusion: Patients with multiple myeloma and kidney involvement should be biopsied as the type of histopathological lesion influences the treatment options and prognosis.

Dotinurad restores exacerbated kidney dysfunction in hyperuricemic patients with chronic kidney disease.

BACKGROUND: In this study, we aimed to clarify the beneficial effects of urate-lowering treatment with the novel agent dotinurad on renal function in patients with chronic kidney disease (CKD) and hyperuricemia (HUA). METHODS: Thirty-five patients with CKD (mean age 65.4 ± 14.8 years, 23 men) diagnosed with HUA were recruited. Changes in eGFR before and after dotinurad administration were assessed. Patients first underwent a 3-month observation period and then 3 months treatment with dotinurad. RESULTS: During the observation period, mean eGFR (mL/min/1.73 m2) declined significantly. The baseline eGFR was 31.8 ± 16.4 and the serum urate level (sUA, mg/dL) was 8.1 ± 1.7. During the treatment period, eGFR recovered to 36.5 ± 17.5 and sUA decreased to 6.7 ± 1.0. The increase in eGFR after dotinurad administration was correlated with a decrease in sUA (R = 0.375, p = 0.0263). CONCLUSION: Dotinurad administration to patients with CKD and HUA appears to be beneficial in restoring kidney function. Dotinurad may represent a potential medication for the prevention of kidney function decline caused by HUA.

Using 1/2 Descending Time in CEUS to Identify Renal Allograft Rejection.

RATIONALE AND OBJECTIVES: This study investigates the potential of quantitative Contrast-Enhanced Ultrasound (CEUS) parameters to distinguish between graft dysfunction due to rejection and non-rejection in kidney transplant recipients. METHODS: In this retrospective study, 50 kidney transplant patients who presented elevated serum creatinine or proteinuria were analyzed. They were categorized as rejection or non-rejection based on biopsy outcomes. These classifications were applied in both derivation (n = 33) and validation cohorts (n = 17). Prior to the biopsy, all patients underwent a CEUS. Quantitative parameters derived from the CEUS were further analyzed for their consistency and reliability. Additionally, the relationship between the Banff scores, a standard for diagnosing transplant rejections, and these CEUS parameters was explored. RESULTS: Significant differences between rejection and non-rejection groups were observed in the CEUS parameters of derivation cohorts. Specifically, Peak Intensity (PI), 1/2 Descending Time (DT/2), Area Under Curve (AUC), and Mean Transit Time (MTT) stood out. Sensitivity and specificity for these parameters were 76.5% and 87.5% for PI, 76.5% and 81.2% for DT/2, 76.5% and 87.5% for AUC, and 68.8% and 94.1% for MTT, respectively. DT/2 and MTT showed superior interobserver agreement compared to PI and AUC. When extrapolating the cutoff values from the derivation cohort to the validation group, DT/2 and AUC exhibited optimal diagnostic precision with positive and negative predictive values being 91.7% vs. 100% and 100% vs. 85.7%, respectively. Additionally, DT/2 effectively differentiated between mild and moderate to severe microvascular inflammation, pivotal in diagnosing antibody-mediated renal transplant rejection. CONCLUSION: DT/2 from CEUS parameters presents as a reliable tool to differentiate rejection from non-rejection causes in renal transplant dysfunction. Yet, large-scale, multi-center studies are essential for further validation.