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Aim: 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. [ABSTRACT FROM AUTHOR]

ObjectivesTo evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).MethodsA 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.ResultsNo 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

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic kidney disease of diabetic cause is a highly prevalent complication in diabetes mellitus patients. Complex phenotypes of the disease start to be recognized, such as albuminuria (micro- or macroalbuminuria) and non-albuminuric phenotype reduced glomerular filtration rate

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. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA)., Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Del Giudice, Marcellino, Hoxha, Martucci, Sanseviero, Bloise, De Maria, Leone, Ventriglia and Lubrano.)

Purpose of Review: To provide pathophysiological and clinical insights into the effects of sacubitril/valsartan on glomerular function. Recent Findings: 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. Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Amylase is a digestive enzyme which is secreted from salivary gland and pancreas; it cleaves cooked starch in the mouth, cooked and uncooked starch in the upper part of intestine mainly in jejunum. The final product of digestion is three glucose units then to glucose monosaccharide. There are 3 types of amylase enzymes which are: (α, β & γ) Amylase. The renal clearance of amylase enzyme ranges from 1 to 3 mL/min. Hypertension is an increase in the force which the blood places on blood vessels as it moves through the body. Hypertension in most of cases is clinically asymptomatic but it is one of the risk factors for cardiovascular disease and causes progressive damage to kidney in a long term process which leads to excessive excretion of low molecular weight compounds like albumin and amylase in urine. Objectives: Assay of alpha urinary amylase level and using it as a better reliable indicator for glomerular damage. Patients and Method: Our study is based on measuring the absorbance for samples by using spectrophotometer device; we collect 92 urine samples from different hypertensive patients, and then calculate the concentration of amylase level by using fixed rate colorimetric method: Δ E= A2-A1 Alpha amylase (U/L) = Δ E x 765 Results: approximately all samples show an in increase in amylase enzyme level above 450U/L. Conclusion: Amylase can serve as a better indicator of glomerular damage. [ABSTRACT FROM AUTHOR]

Associations between selected perfluoroalkyl acids (PFAAs) and biomarkers of renal function were evaluated for US adult aged ≥ 20 years (N = 8220) in the National Health and Nutrition Examination Survey for 2005–2014. Glomerular filtration (GF) stage-stratified regression models were classified by estimated glomerular filtration rate (eGFR) with GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (eGFR 60–89 mL/min/1.73 m2), GF-3A (45–59 mL/min/1.73 m2), and GF-3B/4 (15–44 mL/min/1.73 m2). For GF-1, PFOA, PFOS, and PFHxS were positively and significantly associated with serum creatinine. Serum albumin levels were positively associated with the PFAA considered at all stages and most associations were significant. Further, PFAS serum concentration associations to serum albumin were about 2–3 times stronger at GF-3B/4 than at GF-1. In contrast, urine albumin was negatively and significantly associated with PFOA and PFHxS serum concentrations at all stages of renal function, while, PFOS and PFNA were negatively and significantly associated to urine albumin at GF-3A and GF-3B/4. Urine albumin/creatinine ratios were negatively and significantly associated with PFOA, PFOS, and, and PFHxS serum concentrations at all stages of renal function, as well as with PFNA and PFDA at GF-3A and GF-3B/4. Recent work revealed that serum PFAAs have an inverted U-shaped association to the calculated stages of renal failure based on eGFR; this work adds that albuminuria makes additional negative contributions to already existing negative associations of PFAA to eGFR in advancing stages of renal failure. We hypothesize that both progressive renal failure per se and especially renal failure with albuminuria cause the kidneys to reabsorb less and to excrete more of the PFAAs studied. We suspect this finding may generalize to some other perfluoroalkyl substances (PFAS). The findings also imply study design considerations for evaluating associations to diseases and biomarkers associated with renal failure, such as diabetes. • Negative associations between urinary albumin and UACR and PFAAs increased incrementally from GF-1 to GF-3B/4. • Albuminuria is associated with and may drive enhanced excretion of PFAAs as kidney function declines. • We illustrate how results have implications for study design of biomarkers associated with renal failure. [ABSTRACT FROM AUTHOR]

• Adjusted levels of blood and urine lead increased from GF-1 to GF-3. • Increases from GF-1 to GF-3A in blood lead were faster than for urine lead. • Adjusted levels of blood and urine lead decreased from GF-3A to GF-3B/4. • Decreases from GF-3A to GF-3B/4 in urine lead were faster than for blood lead. • Smokers had sharper increases than nonsmokers from GF-1 to GF-3A. Data (N = 9882) from National Health and Nutrition Examination Survey for 2003–2014 for US adults aged ≥20 years were analyzed to evaluate the variabilities in concentrations of blood and urine lead across various stages of glomerular function. Those who had estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m2 were defined to be in glomerular function stage 1 (GF-1), those who had eGFR between 60 and 90 mL/min/1.73 m2 were defined to be in GF-2, those who had eGFR between 45 and 60 mL/min/1.73 m2 were defined to be in GF-3A, those who had eGFR between 15 and 45 mL/min/1.73 m2 were defined to be in GF-3B/4. There were consistent increases in adjusted geometric means (AGM) for both blood and urine lead from GF-1 to GF-3A even though increases were not uniform from one GF stage to another. For the total population, AGMs for blood lead were 1.23, 1.78, 2.25, and 2.25 μg/dL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. AGMs for urine lead were 0.49, 0.61, 0.68, and 0.47 μg/L for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, from GF-3A to GF-3B/4, AGMs for both blood and urine lead decreased. However, percent increases from GF-1 to GF-3A for urine lead were smaller than for blood lead and percent decreases from GF-3A to GF-3B/4 for urine lead were larger than for blood lead. Females had lower AGMs than males for both blood and urine lead. Also, smoker-nonsmoker differences for blood lead narrowed as kidney function deteriorated but smoker-nonsmoker differences for urine cadmium lead as kidney function deteriorated. Smokers had sharper increases in AGMs for blood and urine lead than nonsmokers from GF-1 to GF-3A but at GF-3B/4, this difference was reduced to 0.17 μg/dL. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to study the effect of 7 days of strict glycemic control with insulin on glomerular function and structure in streptozotocin (STZ)-diabetic rats.Materials and Methods: Three groups of adult male Fischer rats were studied: controls (n = 15), diabetics (n = 15), and insulin-treated diabetics (n = 15). Diabetes was induced by treating the rats with STZ (55 mg/kg i.p.). One week after the induction of diabetes, blood glucose, protein excretion rate (PER), glomerular filtration rate (GFR), and renal plasma flow (RPF) were estimated in each group. Furthermore, morphometric analysis was performed to estimate the tuft volume and changes in mesangial matrix area. The results are expressed as the mean ± SEM.Results: STZ diabetes caused significant increases in GFR (0.89 ± 0.1 to 1.21 ± 0.1 mL/min/100 g; p < 0.01) and RPF (1.78 ± 0.37 to 3.32 ± 0.6 mL/min/100 g; p < 0.05). Furthermore, the diabetic rats had higher glomerular volumes but mesangial matrix areas similar to controls. Insulin treatment prevented the increases in blood glucose (4.5 ± 0.2 mM), PER (66.1 ± 7.8 mg/day), GFR (0.6 ± 0.07 mL/min/100 g), and RPF (1.72 ± 0.36 mL/min/100 g), but did not prevent glomerular hypertrophy (21.7% increase), but induced mesangial matrix expansion (25% increase).Conclusions: Insulin prevented the diabetes-induced hyperfiltration and proteinuria, but did not prevent glomerular growth, and induced mesangial expansion. Hyperglycemic episodes could be partly responsible for persistent glomerular growth and accelerated mesangial growth. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare a conflict of interest. M.S. has ongoing research contracts with Nevakar and SuperTrans Medical as well as having filed patent US10688195B2. All other authors have no other related conflicts of interest to declare.

Introduction Pentoxifylline ( PTX) is a phosphodiesterase inhibitor that directly upregulates the expression of vascular endothelial growth factor mRNA. Pre-eclampsia (PE) is a pregnancy-specific vascular endothelial disorder with a characteristic glomerular lesion, glomerular endotheliosis, that is due to vascular endothelial growth factor deprivation. This study aimed to investigate the effect of PTX on the functional manifestations of the glomerular endothelial injury in patients with severe PE. Patients and methods Forty patients with severe PE admitted to the Ain Shams Obstetric ICU were assigned randomly in the immediate postpartum period to one of two groups (20 in each group): the PTX group received a continuous intravenous infusion of PTX 400 mg every 8 h daily for 3 days; the control group received normal saline solution as placebo every 8 h daily for 3 days. The primary endpoint was the improvement of renal assessment data in the form of the serum creatinine level, the urine protein/creatinine (P/C) ratio, and urine nephrin levels. Results PTX administration in patients with severe PE was associated with significant reduction of urinary nephrin compared with baseline values (day 1) as well as with the values on day 3 in the control group (P = 0.007 and P < 0.001, respectively). Further, administrating PTX showed significant reduction of the urine P/C ratio and serum creatinine levels. Acute kidney injury developed overall in 10 and 40% of the patients in the PTX group and the control group, respectively. Conclusion The current study demonstrates that PTX administration to patients with severe PE, as an additional treatment to standard therapy on admission to the ICU, exhibits a renoprotective effect. [ABSTRACT FROM AUTHOR]

The role of catecholamines in the distribution of intrarenal blood flow and in single-nephron glomerular filtration rate (SNGFR) was evaluated in anesthetized Wistar rats by the Hanssen technique. Epinephrine (EPI) and norepinephrine (NOR) were infused to produce elevations of 20-30 mmHg in mean arterial pressure. Superficial and juxtamedullary nephron perfusion and filtration were determined by the presence of Prussian blue dye. In the control group, 100% of the nephrons presented a homogeneous pattern of perfusion and filtration. In contrast, a heterogeneous distribution of the dye was found even in the larger arteries (arciform and radial), indicating variable perfusion and filtration in both superficial and juxtamedullary nephrons. The effects of EPI and NOR were also evaluated in the superficial cortex by the micropuncture technique in two additional groups of Munich-Wistar rats. Mean SNGFR was 27% and 54% lower in the EPI- and NOR-treated groups, respectively. No change in mean intraglomerular hydraulic pressure was observed after EPI or NOR infusion in spite of a highly scattered pattern, indicating an important variability in perfusion along the superficial cortex, and/or different sensitivity of the pre- and post-glomerular arterioles. The present data suggest that EPI and NOR may affect intrarenal hemodynamics by modifying perfusion and filtration in both superficial and juxtamedullary glomeruli and not by shifting blood flow from superficial to juxtamedullary nephrons. The heterogeneous pattern of perfusion was a consequence of differential vasoconstriction along the intrarenal arteries, probably due to different density and/or sensitivity of the adrenergic receptor subtypes present in the intrarenal vascular tree.

Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infected patients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy.A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11.7%), between 40 and 90 (36.8%), and >90 (high-level group, 51.5%) ng/mL. GFR was measured by Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulae at the times of TDF initiation and Ctrough-TDF determination and after 12 months.At the time of Ctrough-TDF measurement, median duration of TDF-based therapy was 21.1 months. GFR was significantly decreased in high-level group (-8.5 mL/min; P < 0.001) whatever the method used. GFR decline was significantly associated with an older age. Gender-stratified analysis showed that the early impact of Ctrough-TDF >90 ng/mL was significant in women only. After 12 months, the decrease in GFR in patients with high Ctrough-TDF was observed in both men and women (-8.27; P = 0.003).The high prevalence of elevated Ctrough-TDF and its correlation with an increased risk of renal impairment support the usefulness of therapeutic drug monitoring for TDF, particularly in women and older patients. [ABSTRACT FROM AUTHOR]

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Anastaze Stelle K, Belli DC, Parvex P, Girardin E, Giroud A, Wildhaber B, McLin VA. Glomerular and tubular function following orthotopic liver transplantation in children treated with tacrolimus. Abstract: The aim of this study was to analyze the impact of TAC on medium term (three-yr follow-up) renal function in pediatric liver transplant (OLT) recipients. Glomerular and tubular indices were retrospectively analyzed in 24 consecutive OLT pediatric recipients on TAC. CrCl increased significantly each month post-OLT (p = 0.003), with a trend toward significance between pre-OLT and 36 months (p = 0.17). There was no correlation between CrCl and TAC troughs (p = 0.783). Sixteen percent of patients had CrCl <60 mL/min/1.73 m2 pre-OLT vs. none at 36 months post-OLT. TRP values were normal throughout the study. UPr/Cr decreased insignificantly over time and correlated significantly with TAC trough levels (p = 0.031). UCa/Cr values normalized by the third-month post-OLT, decreasing significantly over the time (p = 0.000) but did not correlate with TAC troughs. At three months post-OLT, 65.2% of patients needed antihypertensive therapy, and no patients needed more than one antihypertensive treatment after one yr. Despite nephrotoxic side effects in the early postoperative phase, this study shows that 65.5% patients had a normal renal function by three yr post-OLT. Tubular indices correlated with TAC trough levels. [ABSTRACT FROM AUTHOR]