BACKGROUND: In patients with X-linked hypophosphatemia (XLH), conventional therapy with oral phosphate salts and active vitamin D has been associated with nephrocalcinosis. However, the nature of the relationships among XLH, its treatment, nephrocalcinosis, and kidney function remain poorly understood.
METHODS: Renal ultrasounds were performed and glomerular filtration rates were estimated (eGFR) at baseline in burosumab-naïve patients with XLH who participated in burosumab clinical trials (NCT02181764, NCT02526160, NCT02537431, NCT02163577, NCT02750618, NCT02915705) or enrolled in the XLH Disease Monitoring Program (XLH-DMP; NCT03651505). In this cross-sectional analysis, patient, disease, and treatment characteristics were described among patients with and without nephrocalcinosis.
RESULTS: The analysis included 196 children (mean [SD] age 7.6 [4.0] years) and 318 adults (40.3 [13.1] years). Mean (SD) height z-score was -1.9 (1.2) for children and -2.3 (1.7) for adults. Nearly all children (97%) and adults (94%) had previously received conventional therapy. Nephrocalcinosis was detected in 22% of children and 38% of adults. In children, reduced eGFR <90 ml/min/1.73 m2 was more prevalent in those with nephrocalcinosis (25%) than in those without (11%), a finding that was not observed in adults. Children with nephrocalcinosis had lower mean values of TmP/GFR (P<.05), serum 1,25(OH)2D (P<.05), and eGFR (P<.001) and higher mean serum calcium concentrations (P<.05) than did those without nephrocalcinosis. Adults with nephrocalcinosis had lower mean serum phosphorus (P<.01) and 1,25(OH)2D (P<.05) concentrations than those without. Exploratory logistic regression analyses revealed no significant associations between the presence of nephrocalcinosis and other described patient or disease characteristics.
CONCLUSIONS: Nephrocalcinosis was observed in nearly one quarter of children and more than one-third of adults with XLH. Further study is needed to better understand the predictors and long-term consequences of nephrocalcinosis, with surveillance for nephrocalcinosis remaining important in the management of XLH.
BACKGROUND: Conventionally, patients with X-linked hypophosphatemia (XLH) were treated with phosphate and vitamin D taken by mouth. However, this therapy might lead to a buildup of calcium in the kidney, called nephrocalcinosis. Here, we tried to better understand how XLH, conventional therapy, nephrocalcinosis, and kidney function are related.
METHODS: Nephrocalcinosis was detected with kidney ultrasounds. Kidney function, called the estimated glomerular filtration rate (eGFR), was determined using the blood level of creatinine. Patients had been part of burosumab clinical trials or part of the XLH Disease Monitoring Program. Data were collected from patients before they received burosumab.
RESULTS: The study included 196 children and 318 adults. Almost all children and adults had received conventional therapy. 22% of children had nephrocalcinosis and 38% of adults had nephrocalcinosis. In children, low eGFR was more common in those with nephrocalcinosis (25%) than in those without (11%). In adults, levels of eGFR were similar among those with and without nephrocalcinosis.Some lab values were different among patients with versus those without nephrocalcinosis. Children with nephrocalcinosis had significantly greater loss of phosphate by the kidneys, lower blood levels of the active form of vitamin D (1,25(OH)2D), lower eGFR, and higher blood levels of calcium than those without nephrocalcinosis. Adults with nephrocalcinosis had significantly lower blood levels of phosphorus and 1,25(OH)2D concentrations than those without.
CONCLUSIONS: Nearly one quarter of children and more than one-third of adults with XLH, most of whom had received conventional therapy, had nephrocalcinosis. Further study is needed to better understand what factors can predict who will get nephrocalcinosis and to understand the long-term consequences of nephrocalcinosis. It remains important to monitor patients with XLH for nephrocalcinosis.

BACKGROUND: Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality, affecting 2-8% of all pregnancies. Typically, the increased glomerular filtration rate of pregnancy results in a decrease in serum creatinine. It is unknown if women without the expected decrease in serum creatinine during pregnancy are more likely to be diagnosed with preeclampsia.
OBJECTIVE: We sought to determine if the absence of a pregnancy-related decrease in serum creatinine was associated with the development of preeclampsia in patients deemed to be at high risk for developing preeclampsia. We hypothesized that the absence of the expected decrease in serum creatinine may be a marker of impaired renal function and therefore may be associated with increased risk of preeclampsia in this cohort.
METHODS: We conducted a retrospective cohort study of deliveries between November 2, 2017 and June 30, 2020 at a single institution. Pregnancies were included if a baseline serum creatinine (measured between one year prior to conception through 6 weeks gestation), and another serum creatinine value prior to 20 weeks of gestation were measured. Decrease in serum creatinine was defined as any decrease (at least 0.01 mg/dL) from baseline. The primary outcome was diagnosis of preeclampsia. Exclusion criteria included fetal anomalies, fetal demise, multiple gestation, or delivery prior to 20 weeks. Bivariable analyses were performed using Chi-square, ANOVA, and Student\'s t test. Logistic regression was used to determine odds of developing preeclampsia controlling for confounders.
RESULTS: We identified 392 pregnancies that met inclusion criteria. Preeclampsia was diagnosed in 56 (14.3%) pregnancies. Patients diagnosed with preeclampsia were more likely to have a history of preeclampsia in a prior pregnancy, chronic hypertension (HTN), and diabetes. They were also more likely to have aspirin prescribed in the current pregnancy. Prevalence of advanced maternal age, multiparity, obesity, smoking, history of autoimmune disease, history of CKD, gestational HTN, or multiple pregnancy were not significantly different between patients with and without a diagnosis of preeclampsia. After controlling for confounders, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia (OR 0.76, CI 0.32-1.78).
CONCLUSIONS: After controlling for risk factors associated with preeclampsia, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia in this high-risk cohort.

Renal dysfunction, including acute renal failure (ARF) and chronic kidney disease (CKD), continues to present significant health challenges, with renal ischemia-reperfusion injury (IRI) being a pivotal factor in their development and progression. This condition, notably impacting kidney transplantation outcomes, underscores the urgent need for innovative therapeutic interventions. The role of opioid agonists in this context, however, remains a subject of considerable debate. Current reviews tend to offer limited perspectives, focusing predominantly on either the protective or detrimental effects of opioids in isolation. Our review addresses this gap through a thorough and comprehensive evaluation of the existing literature, providing a balanced examination of the dualistic nature of opioids\' influence on renal health. We delve into both the nephroprotective and nephrotoxic aspects of opioids, dissecting the complex interactions and paradoxical effects that embody the \"two sides of the same coin\" phenomenon. This comprehensive analysis is vital for understanding the intricate roles of opioids in renal pathophysiology, potentially informing the development of novel therapeutic strategies for preventing or treating hypoxic kidney injury.

UNASSIGNED: Despite the potential demonstrated by targeted plasma metabolite modulators in halting the progression of chronic kidney disease (CKD), a lingering uncertainty persists concerning the causal relationship between distinct plasma metabolites and the onset and progression of CKD.
UNASSIGNED: A genome-wide association study was conducted on 1,091 metabolites and 309 metabolite ratios derived from a cohort of 8,299 unrelated individuals of European descent. Employing a bidirectional two-sample Mendelian randomization (MR) analysis in conjunction with colocalization analysis, we systematically investigated the associations between these metabolites and three phenotypes: CKD, creatinine-estimated glomerular filtration rate (creatinine-eGFR), and urine albumin creatinine ratio (UACR). In the MR analysis, the primary analytical approach employed was inverse variance weighting (IVW), and sensitivity analysis was executed utilizing the MR-Egger method and MR-pleiotropy residual sum and outlier (MR-PRESSO). Heterogeneity was carefully evaluated through Cochrane\'s Q test. To ensure the robustness of our MR results, the leave-one-out method was implemented, and the strength of causal relationships was subjected to scrutiny via Bonferroni correction.
UNASSIGNED: Our thorough MR analysis involving 1,400 plasma metabolites and three clinical phenotypes yielded a discerning identification of 21 plasma metabolites significantly associated with diverse outcomes. Specifically, in the forward MR analysis, 6 plasma metabolites were determined to be causally associated with CKD, 16 with creatinine-eGFR, and 7 with UACR. Substantiated by robust evidence from colocalization analysis, 6 plasma metabolites shared causal variants with CKD, 16 with creatinine-eGFR, and 7 with UACR. In the reverse analysis, a diminished creatinine-eGFR was linked to elevated levels of nine plasma metabolites. Notably, no discernible associations were observed between other plasma metabolites and CKD, creatinine-eGFR, and UACR. Importantly, our analysis detected no evidence of horizontal pleiotropy.
UNASSIGNED: This study elucidates specific plasma metabolites causally associated with CKD and renal functions, providing potential targets for intervention. These findings contribute to an enriched understanding of the genetic underpinnings of CKD and renal functions, paving the way for precision medicine applications and therapeutic strategies aimed at impeding disease progression.

UNASSIGNED: This retrospective study aimed to investigate the effect of frequent computed tomography (CT) examinations with contrast media on the renal function of patients with oral squamous cell cancer (OSCC) that underwent radical surgery, by using estimated glomerular filtration rate (eGFR); to identify risk factors of occurrence of post-operative chronic kidney disease (CKD) in these patients; and to explore the relationship between risk factors and occurrence of postoperative CKD during follow-up.
UNASSIGNED: Herein, 188 patients (107 male; 81 female) who underwent radical surgery for OSCC were included. We evaluated the risk factors for postoperative CKD after treatment, including demographic, perioperative, and postoperative factors by univariate and multivariate analyses. Patients were divided into post-operative CKD and control groups based on eGFR evaluation. Overall survival (OS) rates were compared between the groups.
UNASSIGNED: eGFR decreased over time after treatment in both patient groups. Postoperative CKD was diagnosed in 56 (29.8%) patients. The average number of contrast-enhanced CT examinations was not an independent risk factor for postoperative CKD. However, lower hemoglobin on hospital discharge [odds ratio (OR) = 0.53], lower eGFR on hospital discharge (OR = 0.84), and common use of nonsteroidal anti-inflammatory drugs (OR = 48.79) were significant risk factors associated with postoperative CKD. The control group was associated with a better OS than the postoperative CKD group; however, this difference was not significant.
UNASSIGNED: Clinicians should pay close attention to these risk factor of post-operative CKD during the management of patients with OSCC that undergo radical surgery and frequent follow-up CT examinations with contrast media.

OBJECTIVE: To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD.
RESULTS: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk.
CONCLUSIONS: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD.

OBJECTIVE: To investigate the effect of Liraglutide in conjunction with routine therapy on renal function, renal fibrosis, immune status, and prognosis in patients with diabetes mellitus.
METHODS: The clinical data of patients with Type 2 diabetes mellitus (T2DM) treated at the First Affiliated Hospital of Jishou University from March 2021 to March 2022 were retrospectively analyzed. Patients were assigned into a control group (n=42) and a study group (n=42) according to their treatment regimen. The control group received routine treatment, and the study group received Liraglutide in addition to routine treatment. The therapeutic effects, blood glucose levels, renal function, renal fibrosis, and Immunoglobulin (Ig) levels as well as the incidence of adverse reactions, were compared between the two groups.
RESULTS: The effective rate was higher in study group (97.62%) than that of the control group (78.57%) (P<0.05). After treatment, the fasting blood-glucose (FBG), 2-hour postprandial plasma glucose (2hPG), and glycosylated hemoglobin (HbA1c) levels were decreased; and the study group displayed a significantly lower blood glucose level than the control group (all P<0.05). Also, the serum creatinine (Scr), blood urea nitrogen (BUN), and 24-hour urinary protein quantification (24h-UPor) were decreased after treatment; and the study group showed more pronounced improvement in renal function index than did the control group (all P<0.05). The levels of IgA, IgM, and IgG were increased after treatment compared to pre-treatment; and the study group exhibited significantly better improvement than the control group (all P<0.05). However, the study group reported a notably higher incidence of adverse reactions than the control group (19.05% vs 2.38%; P<0.05).
CONCLUSIONS: Liraglutide combined with routine therapy is effective in treating patients with diabetes, which can effectively reduce the levels of blood glucose andurinary protein, and the degree of renal fibrosis, while improving renal and immune functions and the clinical prognosis of diabetic patients.

The lack of understanding of the mechanism of renal injury in IgA nephropathy (IgAN) hinders the development of personalized treatment plans and targeted therapies. Improved insight into the cause of renal dysfunction in IgAN is necessary to enhance the effectiveness of strategies for slowing the progression of the disease. This study examined single cell RNA sequencing (scRNA seq) and bulk-RNA seq data and found that the gene expression of renal intrinsic cells (RIC) was significantly changed in patients with renal impairment, with a primary focus on energy metabolism. We discovered a clear metabolic reprogramming of RIC during renal function impairment (RF) using the \'scMetabolism\' package, which manifested as a weakening of oxidative phosphorylation, alterations in fatty acid metabolism, and changes in glycolysis. Cellular communication analysis revealed that communication between macrophages (Ma) and RIC became more active and impacted cell function through the ligand-receptor-transcription factor (L-R-TF) axis in patients with RF. Our studies showed a notable upsurge in the expression of gene CLU and the infiltration of CLU+ Ma in patients with RF. CLU is a multifunctional protein, extensively involved in processes such as cell apoptosis and immune responses. Data obtained from the Nephroseq V5 database and multiplex immunohistochemistry (mIHC) were used to validate the findings, which were found to be robustly correlated with estimated glomerular filtration rate (eGFR) of the IgAN patients, as demonstrated by linear regression (LR). This study provides new insights into the cellular and molecular changes that occur in IgAN during renal impairment, revealing that elevated expression of CLU and CLU+ Ma percolation are common features in patients with RF. These findings offer potential targets and strategies for personalized management and targeted therapy of IgAN.

MT-1207 (MT) as a new antihypertensive drug is under clinical trial. However, its hypotensive mechanism has not been experimentally explored, and it is unknown whether MT can be used for bilateral renal artery stenosis hypertension. Using two-kidney two-clip (2K2C) to mimic bilateral renal artery stenosis in rats, a stroke-prone renovascular hypertension model, the present study further verified its antihypertensive effect, cardiovascular and renal protection, mortality reduction and lifespan prolongation, as well as demonstrated its two novel pharmacological effects for uric acid-lowering and cognition-improving. Notably, MT did not aggravate renal dysfunction; instead, it had beneficial effects on reducing serum uric acid level and maintaining serum K+ at a relatively stable level in 2K2C rats. In contrast, angiotensin receptor blocker losartan aggravated renal dysfunction in 2K2C rats. Mechanistically, MT hypotensive effect was dependent on its blockade of α1 and 5-HT2 receptors, since MT pretreatment abolished these receptor agonists-induced blood pressure elevations in vivo. Further evidence showed MT bound to and interacted with these receptor subtypes including α1A, α1B, α1D, 5-HT2A, 5-HT2B, and 5-HT2C receptors known for control of blood pressure. In conclusion, MT may be used for treatment of bilateral renal artery stenosis hypertension, different from losartan that is prohibited for treatment of bilateral renal artery stenosis hypertension. Targets validation of MT hypotensive mechanism and beneficial effects of MT on uric acid and cognitive function provide new insights for this novel multitarget drug, deserving clinical trial attention.

OBJECTIVE: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS).
METHODS: This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr\'s association with 1-year stroke outcomes.
RESULTS: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence.
CONCLUSIONS: In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.