UNASSIGNED: To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
UNASSIGNED: A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities.
UNASSIGNED: No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria (p < 0.0001) and proteinuria (p < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, p = 0.0001 and p = 0.0002) and moderate disease activity (respectively p = 0.0001 and p = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls (p < 0.0001 and p < 0.0001, respectively).
UNASSIGNED: Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.

OBJECTIVE: Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers.
METHODS: We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43-multiparametric renal function assessment between January 1, 2021, and June 30, 2023.
RESULTS: All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte-free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m2 (95% CI 6-29) and +9 mL/min/1.73 m2 (95% CI 2-15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease - Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate- and measured creatinine clearance-based assessments.
CONCLUSIONS: This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute-free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.

Recent clinical studies have reported additive nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam. However, preclinical models have failed to replicate this finding. This study assessed differences in iohexol-measured glomerular filtration rate (GFR) and urinary injury biomarkers among rats receiving this antibiotic combination. Male Sprague-Dawley rats received either intravenous vancomycin, intraperitoneal piperacillin-tazobactam, or both for 96 h. Iohexol-measured GFR was used to quantify real-time kidney function changes. Kidney injury was evaluated with the urinary biomarkers kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to the control, rats that received vancomycin had numerically lower GFRs after drug dosing on day 3. Rats in this group also had elevations in urinary KIM-1 on experimental days 2 and 4. Increasing urinary KIM-1 was found to correlate with decreasing GFR on experimental days 1 and 3. Rats that received vancomycin plus piperacillin-tazobactam (vancomycin+piperacillin-tazobactam) did not exhibit worse kidney function or injury biomarkers than rats receiving vancomycin alone. The combination of vancomycin and piperacillin-tazobactam does not cause additive nephrotoxicity in a translational rat model. Future clinical studies investigating this antibiotic combination should employ more sensitive biomarkers of kidney function and injury, similar to those utilized in this study.

Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection.
Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies.
The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation.
The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.

For the first time, data (N = 1311) from US National Health and Nutrition Examination Survey for 2017-2018 were analyzed for gender and racial/ethnic differences for perfluoro-1-heptane sulfonate (PFHpS) for US adults aged ≥ 20 years. In addition, variability in adjusted concentrations across various stages of glomerular filtration (GF) was also studied. While no racial/ethnic differences were observed, males had statistically significantly higher concentrations of PFHpS than females (0.30 vs. 0.19 ng/mL, p < 0.01). Concentrations of PFHpS across various stages of kidney function were located on inverted U-shaped curves with point of inflection located at GF-3A (45 ≤ eGFR < 60 mL/min/1.73 m2) for all participants, males, as well as females. After moderate increase from GF-1 (eGFR ≥ 60 mL/min/1.73 m2) to GF-2 (60 ≤ eGFR < 90 mL/min/1.73 m2), the increase in PFHpS concentration from GF-2 to GF-3A was quite steep. For example, for females, concentration from GF-1 to GF-2 increased from 0.17 ng/mL to 0.23 ng/mL for an increase of 35% but from GF-2 to GF-3A, concentrations of PFHpS increased from 0.23 ng/mL to 0.43 ng/mL for an increase of about 87%. Following this, at GF-3B/4 (15 ≤ eGFR < 45 mL/min/1.73 m2), concentrations decreased sharply to the almost the same levels as for GF-1. For example, for males, the decrease from GF-3A (0.67 ng/mL) to GF-3B/4 (0.21 ng/mL) was about 69%. Concentration curves for each race/ethnicity were also located on inverted U-shaped curves but relatively very small sample sizes for Hispanics and non-Hispanic Asians, and others at GF-3A and GF-3B/4 lead to substantial variability. The balance between reabsorption-excretion in favor of reabsorption at GF-1 and GF-2 switched to in favor of excretion starting at the end of GF-3A.

UNASSIGNED: Kidney disease is a major public health issue arising from loss of glomerular podocyte function, and there are considerable sex differences in its prognosis. Evidence suggests a renoprotective effect of estrogen and soy diet-derived phytoestrogens, although the molecular basis for this is poorly understood.
UNASSIGNED: Here, we aim to assess sex differences in expression of key proteins associated with podocyte survival and determine the effects of dietary soy on glomerular and podocyte signaling.
UNASSIGNED: Male and female FVB mice were fed control, low (1%), and high (20%) doses of isolated soy protein (ISP) in utero and until 100 days of age. Spot urine was collected to measure proteinuria and isolated glomeruli were used to quantify activated and total levels of nephrin, Akt, and ERK1/2. To investigate protective effects of specific soy phytoestrogens, cultured podocytes were treated with or without daidzein and subject to control or high glucose as a model of podocyte injury.
UNASSIGNED: Nephrin and Akt were elevated at baseline in glomeruli from females compared to males. Both sexes that were fed 1% and 20% ISP displayed robust increases in total glomerular Akt compared to controls, and these effects were more prominent in females. A similar trend at both doses in both sexes was observed with activated Akt and total nephrin. Notably, males exclusively showed increased phosphorylation of nephrin and extracellular signal-regulated kinase (ERK) at the 1% ISP dose; however, no overt changes in urinary albumin excretion or podocin levels were observed, suggesting that the soy diets did not impair podocyte function. Finally, in cultured male and female podocytes, daidzein treatment suppressed high glucose-induced ERK activation.
UNASSIGNED: Together, our findings reveal a putative mechanism to explain the protective influence of sex on kidney disease progression, and they provide further evidence to support a beneficial role for dietary soy in preserving glomerular function.
UNASSIGNED: L’insuffisance rénale est un problème majeur de santé publique résultant d’une perte de fonction des podocytes glomérulaires, et son pronostic diffère selon le sexe. Bien que le fondement moléculaire en soit mal compris, des données suggèrent que les œstrogènes et des phytoestrogènes dérivés du soja alimentaire auraient un effet néphroprotecteur.
UNASSIGNED: Évaluer les différences selon le sexe dans l’expression des protéines clés associées à la survie des podocytes, et déterminer les effets du soja alimentaire sur la signalisation glomérulaire et les podocytaire.
UNASSIGNED: Des souris FVB mâles et femelles ont reçu un régime alimentaire témoin ou un regime à faible dose (1 %) ou à dose élevée (20 %) de protéines de soja isolées (PSI) in utero et jusqu’à l’âge de 100 jours. Des échantillons aléatoires d’urine ont été recueillis pour mesurer la protéinurie et des glomérules isolés ont été utilisés pour quantifier les niveaux activés et totaux de néphrine, d’Akt et d’ERK1/2. Pour évaluer l’effet protecteur de certains phytoestrogènes du soja, des podocytes cultivés ont été traités avec ou sans daidzéine et soumis à une dose témoin ou à une dose élevée de glucose comme modèle de lésion podocytaire.
UNASSIGNED: Les taux initiaux de néphrine et d’Akt étaient plus élevés dans les glomérules des souris femelles. Les souris mâles et femelles nourries avec des doses de 1 % et de 20 % de PSI ont montré des augmentations significatives de l’Akt glomérulaire totale par rapport aux témoins, et ces effets étaient plus importants chez les femelles. Une tendance semblable a été observée chez les deux sexes et pour les deux doses en ce qui concerne l’Akt activée et la néphrine totale. Seuls les mâles ont montré une augmentation de la phosphorylation de la néphrine et de l’ERK à 1 % de PSI; aucun changement manifeste n’a cependant été observé dans l’excrétion urinaire d’albumine ou dans le taux de podocine, ce qui suggère que le soja alimentaire n’a pas altéré la fonction des podocytes. Dans les podocytes cultivés, tant mâles que femelles, le traitement à la daidzéine a inhibé l’activation de l’ERK induite par une forte dose de glucose.
UNASSIGNED: Ensemble, nos résultats révèlent un mécanisme putatif pouvant expliquer l’effet protecteur du sexe du patient sur la progression de l’insuffisance rénale. Ces résultats fournissent des preuves supplémentaires soutenant l’hypothèse d’un rôle bénéfique du soja alimentaire dans la préservation de la fonction glomérulaire.

Nephropathic cystinosis is a rare lysosomal storage disease whose basic defect, impaired transport of cystine out of lysosomes, results in intracellular cystine storage. Affected individuals exhibit renal Fanconi Syndrome in infancy, end-stage kidney disease at approximately 10 years of age, and many other systemic complications. Oral cysteamine therapy mitigates the detrimental effects on glomerular function and prevents most of the late complications of the disease but has not shown benefit with respect to the early tubular damage of cystinosis. This is because cystinosis is generally diagnosed in the second year of life, after the damage to kidney tubular function has already occurred. We longitudinally evaluated 6 infants diagnosed and treated with cysteamine from before 2 months of age. The 4 infants with good compliance with cysteamine and consistently low leucocyte cystine levels maintained normal eGFR values, exhibited only minor degrees of renal Fanconi Syndrome, and maintained normal serum levels of potassium, bicarbonate, phosphate, and calcium without electrolyte or mineral supplementation through 2, 4, 10 and 16 years of age. Thus, renal Fanconi syndrome can be attenuated by early administration of cysteamine and renew the call for molecular-based newborn screening for cystinosis.

Infantile nephropathic cystinosis, due to impaired transport of cystine out of lysosomes, occurs with an incidence of 1 in 100-200,000 live births. It is characterized by renal Fanconi syndrome in the first year of life and glomerular dysfunction progression to end-stage kidney disease by approximately 10 years of age. Treatment with oral cysteamine therapy helps preserve glomerular function, but affected individuals eventually require kidney replacement therapy. This is because glomerular damage had already occurred by the time a child is diagnosed with cystinosis, typically in the second year of life. We performed a retrospective multicenter study to investigate the impact of initiating cysteamine treatment within the first 2 months of life in some infants and comparing two different levels of adherence in patients diagnosed at the typical age. We collected 3983 data points from 55 patients born between 1997 and 2020; 52 patients with 1592 data points could be further evaluated. These data were first analyzed by dividing the patient cohort into three groups: (i) standard treatment start with good adherence, (ii) standard treatment start with less good adherence, and (iii) early treatment start. At every age, mean estimated glomerular filtration rate (eGFR) was higher in early-treated patients than in later-treated patients. Second, a generalized additive mixed model (GAMM) was applied showing that patients with initiation of treatment before 2 months of age are expected to have a 34 ml/min/1.73 m2 higher eGFR than patients with later treatment start while controlling for adherence and patients\' age. These data strongly suggest that oral cysteamine treatment initiated within 2 months of birth preserves kidney function in infantile nephropathic cystinosis and provide evidence of the utility of newborn screening for this disease.

Data (N = 10,590) from National Health and Nutrition Examination Survey for 2005-2016 for US adults aged ≥ 20 years were analyzed to study how concentrations of arsenobetaine (UAB), monomethylarsonic acid (UMMA), dimethylarsenic acid (UDMA), and total arsenic (UAS) in urine vary across the stages of renal function (RF). Data were analyzed over RF-1A (eGFR > 110 mL/min/1.73 m2), RF-1B (eGFR between 90 and 110 mL/min/1.73 m2), RF-2 (eGFR between 60 and 90 mL/min/1.73 m2), RF-3A (eGFR between 45 and 60 mL/min/1.73 m2), and RF-3B/4 (eGFR between 15 and 45 mL/min/1.73 m2). Adjusted geometric mean (AGM) concentrations of the total population, males, and females for UAS, UAB, and UDMA were observed to follow inverted U-shaped distributions with points of inflection located at RF-3A. For example, adjusted concentrations for the total population for UAS were 8.8, 8.8, 9.5, 11.7, and 9.6 μg/L for those in RF-1A, RF-1B, RF-2, RF-3A, and RF-3B/4 respectively. While statistically significant differences were only occasionally observed, males, in general, had lower AGMs than females for UAS and UDMA, but females had lower AGMs than males for UAB. Among the various racial/ethnic groups, non-Hispanic whites had the lowest adjusted concentrations of all four arsenic variables. Adjusted levels of all four arsenic variables were observed to decrease over survey years of 2005-2006 through 2015-2016. However, statistical significance was not necessarily reached for all RF stages. Smoking was associated with reduced levels of four arsenic variables over RF-1A through RF-2. Diabetes was associated with increased levels of UMMA and UDMA at RF-2.

To provide pathophysiological and clinical insights into the effects of sacubitril/valsartan on glomerular function.
Heart failure and glomerular dysfunction are closely intertwined. In addition to reduced heart failure hospitalization and all-cause mortality, patients treated with sacubitril/valsartan have a slower deterioration of glomerular filtration rate over time compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects of sacubitril/valsartan are probably mediated through enhancement of natriuretic peptides, reduction of glomerular inflammation and fibrosis, and relaxation of mesangial cells and podocytes. Further studies will elucidate underlying pathophysiological mechanisms of sacubitril/valsartan on glomerular function and their prognostic significance in subjects with and without heart failure.