Early Marker Of Renal Damage Research Articles

The Relationship between Serum Sodium Concentration and Albuminuria: A Retrospective Cohort Study.

Lowering dietary salt intake reduces albuminuria, an early marker of renal damage and a sensitive predictor of adverse cardiovascular outcomes. The mechanisms underlying this effect are uncertain but small changes in serum sodium concentration may be important: this retrospective cohort study investigated the hypothesis that higher serum sodium concentration is a risk factor for albuminuria (defined as a urine albumin:creatinine ratio [UACR], ≥3 mg/mmol). Primary care data from the Royal College of General Practitioners Research and Surveillance Centre were used to identify 47,294 individuals with a UACR result available between April 2010 and March 2015, and no known albuminuria prior to this. Exclusion criteria were missing or abnormal serum sodium concentration at baseline (<135 or >146 mmol/L); age <18 years; diabetes mellitus; decompensated liver disease; heart failure; and stage 5 chronic kidney disease. After adjustment for known risk factors, there was a significant "U-shaped" relationship between serum sodium concentration and albuminuria. The lowest risk was associated with a serum sodium of 138-140 mmol/L. In comparison, the risk of albuminuria was 18% higher with a serum sodium of 135-137 mmol/L and 19% higher with a serum sodium of 144-146 mmol/L. There was no association between serum sodium concentration and blood pressure. The finding of a positive association between higher serum sodium concentration and albuminuria is in support of the hypothesis, but the inverse relationship between serum sodium concentration and albuminuria at lower concentrations warrants further explanation.

#2668 New treatments, new challenges: nephrotoxicity associated to naxitamab in patients with high-risk neuroblastoma

Abstract Background and Aims Neuroblastoma is the most common extracranial solid tumor in children, harboring a poor survival for those with high-risk (HR) tumors. Naxitamab (hu3F8) is a humanized monoclonal anti-disialoganglioside (GD2) antibody approved for the treatment of patients older than 1-year with refractory/relapsed HR-neuroblastoma limited to bone and/or bone marrow. First naxitamab (DanyelzaR) infusion was in 2017 in our institution and since then a large experience has been acquired with its use through several clinical trials as well as an expanded named patient access program. The objective is to describe the renal toxicity profile associated to naxitamab in patients with HR-neuroblastoma. Method Retrospective descriptive study including 244 patients treated with naxitamab (either on monotherapy or associated to chemotherapy) from June 2017 to December 2022 in whom renal involvement and/or hypertension (HT) was evaluated. Results Mean age of the cohort was 8 years (41% female -101- and 59% male -143-), presenting nephrotoxicity of some type up to 26.6% (n = 65): AHT (11.9%), acute renal damage (ARD 10.2%) and proteinuria (5.3%), developing all during the first 3 cycles. All of them were classified as mild adverse events (1-2) according to the Common Terminology Criteria for Adverse Events (CTCAE) scale, except for one patient with ARD grade 3 and two patients with HT grade 3. In the case of HT only in 6 patients an Ambulatory Blood Pressure Monitoring (ABPM) was performed, observing: 2 nocturnal-HT, 2 diurnal-HT without specific-pattern and 2 disautonomic-patterns. Among the ARD, all cases were tubular except for two patients who presented acute tubule-interstitial nephritis (AIN) (one with clinical-analytical pattern and another confirmed by biopsy). Eight of them (32%) had potential confounding factors (previous chemotherapy, ibuprofen or radiotherapy). Among patients with proteinuria (none in the nephrotic range): 38% tubular, 38% glomerular and 23% mixed. Two patients presented ARD + HT and 3 a combination of HT + ARD + proteinuria. All patients received prior chemotherapy and 2 developing chronic renal damage (CKD stage 2 and 3). Conclusion Short-and long-term follow-up, the systematic performance of ABPM, and the use of early markers of renal damage, could lead to a more efficient management of complications derived from this new treatment.

Glomerular Hyperfiltration: A Marker of Fibrosis Severity in Metabolic Associated Steatotic Liver Disease in an Adult Population.

Glomerular hyperfiltration (GH) is an increase in the glomerular filtration rate, possibly progressing to chronic kidney disease (CKD). Metabolic-associated steatotic liver disease (MASLD) is linked to an increased risk of CKD, especially if fibrosis is present; however, the association between GH and MASLD has not been explored. To evaluate GH prevalence in MASLD and its possible correlation with liver fibrosis. 772 consecutive patients with ultrasound MASLD (mean age 47.3 ± 8.9 years, 67.1% males) were enrolled. GH was defined as estimated glomerular filtration rate (eGFR) greater than the upper quartile of values in the cohort. Liver stiffness measurement (LSM) by FibroScan ≥ 7.2 kPa suggested liver fibrosis. GH was present in 20% of patients, liver fibrosis in 30%. In total, 53.4% of the cohort was obese, 40.9% hypertensive, 36.3% diabetic and 70.8% dyslipidaemic. GH patients compared to non-GH were significantly younger (38.4 ± 8.3 vs. 49.5 ± 7.7, p < 0.001), with higher prevalence of LSM > 7.2 kPa (35.5% vs. 29%, p < 0.001), without any difference in metabolic comorbidities. In multivariate analysis, age (OR 0.85, CI 95% 0.82-0.87) and significant fibrosis (OR 1.83; CI 95%1.10-3.03) remained independently associated with GH, regardless of the presence of metabolic alterations and nephrotoxic drugs. GH, an early marker of renal damage, is highly prevalent in MASLD and is associated with hepatic fibrosis. GH may be considered an early marker of both liver and renal disease and its recognition could prompt the management of risk factors aimed at preventing the progression of both hepatic and renal disease.

NGAL and KIM-1 as early biomarkers of cisplatin-associated nephrotoxicity.

e24080 Background: Cisplatin can cause renal injury in one-third of the patients. After the uptake by tubular renal cells cisplatin causes TNF-a immediate inflammation and death of tubular cell, ischemia and vascular damage on the kidney, which results in glomerular filtration rate (GFR) decrease (Toyuz et al, 2019). Serum creatinine is increased at the time of approximately 50% of nephrons are damaged. The identification of predictors and early markers of renal damage will make it possible to identify a high-risk group and monitor renal damage (Touyz, 2018). NGAL is activated immediately after ischemic or direct toxic damage to the kidneys in the distal segments of the nephron (Schmidt-Ott et al, 2007; Mishra). KIM-1 is an early marker of proximal tubule damage (Prasaja et al, 2015). Both NGAL and KIM-1 demonstrated their role of renal damage biomarkers in contrast-induced acute kidney injury. The goal of this study was to assess NGAL and KIM-1 as biomarkers of early nephrotoxicity induced by cisplatin and to assess their role as risk factors. Methods: The study included 50 patients who received cisplatin. Nephrotoxicity was determined as a decrease in GFR to &lt; 60 ml/min/1.73 m2 at 8 weeks from the initiation of therapy. The levels of KIM-1 and NGAL in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity, a logistic regression analysis was performed with the inclusion of primary clinical and laboratory parameters. ROC-analysis was used to assess sensitivity and specificity of markers. Results: The decrease of GFR less then &lt; 60 ml/min/1.73 m2 at 8 weeks was observed in 11 (22%) of patients. There were no signs of increase of blood pressure in 8 weeks of observation. Serum creatinine increased clinically significant in 8 weeks after the start of therapy. The level of NGAL and KIM-1 rapidly increased in 1 week after the start of therapy (p &lt; 0.001) which is shown in Table. The unfavorable predictor of nephrotoxicity was a 1-week increase of urine NGAL and KIM-1: OR 8.37; 95%CI 4.64-95.84; p = 0.001. Both NGAL and KIM-1 demonstrated high sensitivity, specificity and area under the curve (AUC) – both 0.69 as early biomarkers of nephrotoxicity assessed after 8 weeks from the start of therapy. Conclusions: An increase of KIM-1 and NGAL observed earlier then serum creatinine increase. Elevation in 1 week after the initiation of therapy can predict nephrotoxicity with high specificity and sensitivity. At the same time an early increase in the concentrations of KIM-1 and in the urine is the independent risk factors for cisplatin-induced nephrotoxicity. [Table: see text]

Association of common medical comorbidities with early renal damage in the Chinese tropics with essential hypertension

BackgroundUrine albumin/creatinine ratio (UACR) is an important marker of early renal damage (ERD) caused by hypertension. Recent studies showed that blood pressure was a significant inverse association with temperature and climate. The purposes of our study were sought to explore the association of common medical comorbidities with ERD, and find independent risk factors to ERD in Chinese tropics with essential hypertension.MethodsFrom January 2018 to December 2019, we assessed UACR in a total of 599 hypertensive Chinese Hainan patients. We defined ERD as a UACR between 30 mg/g and 300 mg/g. We analysed differences between qualitative variables using the chi-squared (χ2) test. We calculated correlations between UACR and age, hypertension duration (HD), systolic blood pressure (SBP), and diastolic blood pressure (DBP) using the Spearman’s rho test. To determine the odds ratio (OR), we evaluated binary logistic regression models.ResultsAmong the 599 patients, 281 (46.9%) were found to have ERD. ERD and factors related to sex, body mass index (BMI), and SBP did not differ significantly (all, p>0.05). Our main findings showed that age, HD, and DBP were associated with ERD (p<0.01, respectively). Furthermore, age ≥ 65 years, HD ≥10 years, DBP ≥ 90 mmHg, SBP ≥ 160 mmHg, and diabetes differed significantly according to ERD status (p < 0.05, respectively). In multivariate analysis using stepwise regression, age (OR = 1.468), DBP (OR = 1.853), and diabetes (OR = 2.031) were significant independent predictors of ERD. The area under the receiver operating characteristic (ROC) curve was 0.677, and the sensitivity and specificity of the optimal cut-off value were 44.5 and 81.1%, respectively.ConclusionsCommon medical comorbidities are associated with ERD; age, DBP, and diabetes are independent risk factors for ERD in patients with essential hypertension who live in the Chinese tropics. Early monitoring of the UACR, as well as control of blood glucose and DBP, can effectively delay ERD.

MARCADORES DA FUNÇÃO RENAL ATRAVÉS DA FILTRAÇÃO GLOMERULAR: UMA REVISÃO BIBLIOGRÁFICA

Currently, renal disease is a major public health problem that affects thousands of people in Brazil and worldwide, the kidneys are physiologically dynamic components of the system performing many functions, including the formation of urine, so it is paramount to early diagnosis the disease. The glomerular filtration rate is the main indicator of renal function in healthy subjects and patients. In this article the main markers of renal injury are assessed: creatinine, urea, proteinuria, cystatin, microalbuminuria. Early markers of renal damage are important because the glomerular filtration rate is reduced before the onset of symptoms or signs of renal disease are therefore important in the diagnosis of renal injury

Тактичні підходи до діагностики та лікування гепаторенального синдрому у хворих із бластоматозною механічною жовтяницею

The article discusses problems of early diagnosis and, accordingly, treatment of hepatorenal syndrome (HRS) in case of obstructive jaundice of blastomatous origin. The results of a comprehensive examination of 37 patients with blastomatous obstructive jaundice (OJ) with clinical and laboratory signs of HRS were analyzed. Patients were evaluated for clinical and biochemical parameters of blood and urine, blood electrolytes, indicators of the blood coagulation system according to unified methods. The main work is devoted to the determination of the biomarker of renal tubular damage, neutrophil-gelatinase-associated lipocaine (s-NGAL) as a marker and indicator of HRS severity, careful and detailed analysis, monitoring of levels (s-NGAL) and other bioactive substances as an indicator of treatment efficacy. Introduction of active ultrasound as a replacement for contrast computer tomography to reduce the load on precompromised kidneys. It has been proven that the level of renal tubular damage, neutrophil-gelatinase-associated lipocaine s-NGAL is an early marker of renal damage whose function is to reduce the severity of damage to the proximal tubules of the kidneys, normalize damaged tissue by participating in apoptosis, increase survival of damaged restoration of damaged epithelium, stimulation of differentiation and structural reorganization of renal epithelial cells. The fact that s-NGAL was not significantly reduced in the stage of recovery of diuresis, confirms the presence of patients with blastomatous MF severe and persistent toxic tubulointerstitial disorders. Based on this determination of the biomarker (s-NGAL) in the serum of patients with blastomatous mechanical jaundice and performing in them at primary ultrasound color Doppler mapping and pulsed wave Doppler imaging of the kidneys with the calculation of the resistance index may serve as early signs of damage.

Urinary transferrin as early marker of renal damage in type II diabetes mellitus: A case–control study

Microalbuminuria is a reversible stage of renal dysfunction and its detection allows early intervention and treatment of diabetic nephropathy. Therefore, a more reliable biomarker is required to diagnose early, reversible stage of renal dysfunction.To evaluate the utility of urinary transferrin (UTRANS) as an early predictive marker in type II diabetes mellitus (T2DM). This cross-sectional study included 40 normoalbuminuric and 20 microalbuminuric T2DM patients and 20 clinically healthy controls.Materials and methods: All baseline characteristics such as glucose (fasting and postprandial), serum creatinine, HbA1c, urinary albumin, creatinine, and UTRANS were estimated. SPSS software version 20, R studio 3.6.2. Shapiro test, Chi-square test, Analysis of variance, Kruskal Wallis, and receiver operating characteristic (ROC). Urinary albumin-to-creatinine ratio and UTRANS showed a significant difference among normoalbuminuric and microalbuminuric T2DM patients compared to controls (P = 0.000). UTRANS and TRANS/creatinine ratio positively correlated in normoalbuminuric, macroalbuminuric and control groups (P &amp;#60; 0.05). UTRANS was an excellent to outstanding discriminator (Area under the curve: 0.8 – &amp;#62;0.9), indicating UTRANS was able to differentiate between healthy controls, normoalbuminuric, and microalbuminuric T2DM subjects. UTRANS may act as a potential biomarker that can be used as an early screening marker for renal injury, even before progression to the stage of microalbuminuria.

DETECTION OF CHANGES IN RENAL BLOOD FLOW USING ARTERIAL SPIN LABELING MRI

Objective: Alteration in kidney perfusion is an early marker of renal damage. Magnetic resonance imaging (MRI) with arterial spin labeling (ASL) is a noninvasive approach to measure renal blood flow (RBF) without the use of contrast media. The purpose of this study consisting of two experiments was to evaluate whether both acute and short-term changes in RBF could be detected using ASL-MRI technique. Design and method: RBF as assessed by cortical (CRBF), medullary, and total renal blood flow (TRBF) were measured by ASL-MRI using FAIR True-FISP sequence. In the first experiment with 11 normotensive healthy individuals (NT) and 11 hypertensive patients (HT), RBF was measured at baseline and after both feet were covered with cold ice packs (cold pressor test) that activates the sympathetic nervous system. In the second experiment, RBF was measured in patients with chronic kidney disease (CKD) before and after a pharmacological intervention. Results: A significant reduction in CRBF (p = 0.042) and a trend in TRBF (p = 0.053) were observed in response to the activation of the sympathetic nervous system in both NT individuals and HT patients (Table 1). In the second experiment, a trend towards reduction of CRBF (p = 0.051) and TRBF (p = 0.059) has been detected after pharmacological intervention. An evaluation of RBF measurements between three different study populations reveals that TRBF were significantly lower in patients with HT (309.5 ± 17.3 mL/100 g/min) and CKD patients (260.4 ± 29.1 mL/100 g/min) compared to NT individuals (338.7 ± 30.0 mL/100 g/min) (NT vs. HT-p = 0.014, NT vs. CKD-p = 0.004). TRBF was also lower in patients with CKD compared to HT (p = 0.047). Conclusions: Our data indicate that both acute and short-term changes in RBF could be detected using ASL-MRI. Moreover, we were able to detect differences in RBF between healthy and diseased individuals by needing only small sample size per group. Thus, ASL-MRI offers an advantage in conducting clinical trials compared to other technologies.

Detection of Changes in Renal Blood Flow Using Arterial Spin Labeling MRI

Background: Alteration in kidney perfusion is an early marker of renal damage. The purpose of this study was to evaluate if changes in renal blood flow (RBF) could be detected using MRI with arterial spin labeling (ASL) technique. Methods: RBF as assessed by cortical (CRBF), medullary, and total renal blood flow (TRBF) were measured by MRI with arterial spin labeling (ASL-MRI) using flow-sensitive alternating inversion recovery true fast imaging with steady-state precession sequence. In 11 normotensive healthy individuals (NT) and 11 hypertensive patients (HT), RBF was measured at baseline and after both feet were covered with cold ice packs (cold pressor test) that activates the sympathetic nervous system. In another experiment, RBF was measured in 10 patients with CKD before and after a pharmacological intervention. We compared RBF measurements between the 3 study populations. Results: A significant reduction in CRBF (p = 0.042) and a trend in TRBF (p = 0.053) were observed in response to the activation of the sympathetic nervous system. A trend toward reduction of CRBF (p = 0.051) and TRBF (p = 0.059) has been detected after pharmacological intervention. TRBF was significantly lower in patients with HT and CKD patients compared to NT individuals (NT vs. HT, p = 0.014; NT vs. CKD, p = 0.004). TRBF was lower in patients with CKD compared to HT (p = 0.047). Conclusion: Our data indicate that both acute and short-term changes in RBF could be detected using ASL-MRI. We were able to detect differences in RBF between healthy and diseased individuals by needing only small sample size per group. Thus, ASL-MRI offers an advantage in conducting clinical trials compared to other technologies.

A Study on an Early Marker of Renal Damage in Known Diabetics Living in an Urban Slum of Hyderabad, India

A Study on an Early Marker of Renal Damage in Known Diabetics Living in an Urban Slum of Hyderabad, India

Pentraxin-3 and adropin as inflammatory markers of early renal damage in type 2 diabetes patients.

Renal inflammatory response is involved in the development and progression of diabetic kidney disease (DKD). We sought to evaluate pentraxin-3 (PTX3) and adropin variability as inflammatory markers among type 2 diabetes mellitus (T2DM) patients with different urinary albumin, and to examine if these factors assist in the early diagnosis of diabetic kidney disease. We enrolled 447 T2DM patients and 100 healthy non-diabetic control subjects in this study. The patients with T2DM were divided into three groups based on their urinary albumin/creatinine ratio (UACR): the normoalbuminuric group (DM group, UACR < 30mg/g); the microalbuminuric group (DKD1 group, 30 ≤ UACR ≤ 300mg/g); the macroalbuminuric group (DKD2 group, UACR > 300mg/g). The levels of PTX3 and adropin were determined by enzyme-linked immunosorbent assay (ELISA). Spearman correlation and multiple linear regression analysis were performed to determine the correlations among these inflammatory markers and other clinical parameters. Receiver operating characteristic (ROC) curves analysis was used to assess the diagnostic potential of PTX3 and adropin for DKD. Compared to non-diabetes, serum levels of PTX3 were distinctly elevated, whereas the adropin were significantly declined in diabetic patients (p < 0.05). Significantly higher levels of PTX3 and lower levels of adropin were seen in the macroalbuminuric patients compared with the microalbuminuric patients (p < 0.05). Multiple stepwise linear regression analysis showed that the control of hemoglobin A1c (HbA1c) and UACR were independent factors associated with PTX3 and adropin. In addition, ROC curves analysis showed PTX3 and adropin could be used to evaluate the early detect of DKD, further adropin might be a better marker than PTX3 in compliance with their veracity. As inflammatory markers, the diverse changes of pentraxin-3 and adropin showed that they may forecast the renal damage in diabetic patients in varying degrees and link with the pathogenesis of diabetic kidney disease.

Microalbuminuria and Serum Cystatin C in Prediction of Early-Renal Insufficiency in Children with Obesity.

Serum cystatin-C (SCysC) and microalbuminuria are well-recognized early markers of renal damage. This study aims to assess whether these early markers are elevated in children with obesity and normal serum creatinine (SCr). Pediatric patients diagnosed with obesity were included (n = 105, ages 4-18y) in this study. The patients were divided into three groups as follows: solely obese, metabolic syndrome and type 2 diabetes. Serum cystatin-C, 24-h microalbuminuria, SCr and glomerular filtration rate (GFR) were evaluated in all patients. All patients were examined with history, physical examination, laboratory analysis and ultrasonography evaluation. The findings showed that renal function, GFR and SCr levels were normal in all patients. There was microalbuminuria in six patients and SCysC was elevated in eight patients. There were also both elevated SCysC and microalbuminuria in eight patients. Significant elevations of both microalbuminuria and SCysC were detected in cases with type 2 diabetes (p < 0.05). The findings suggest that SCysC may have a diagnostic value in early-renal insufficiency. Although there was not any statistically significant difference between groups in GFR, significant elevations for both microalbuminuria and SCysC in patients with type 2 diabetes were detected. This suggests that the risk factors of diabetes may have a direct relation with renal damage. Regarding renal function in type 2 diabetic and obese pediatric patients, microalbuminuria and SCysC may be screened to observe early-renal damage, even in cases with normal GFR and SCr levels.

Equine urinary N-acetyl-β-D-glucosaminidase assay validation and correlation with other markers of kidney injury.

Detection of equine acute kidney injury (AKI) is hindered by limited markers of early renal damage in horses. N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme in renal tubular epithelium released into urine during tubular insult, has shown promise for early identification of AKI in humans and other species. We validated an assay for NAG in equine urine and measured urinary NAG in 7 azotemic and 7 non-azotemic client-owned adult horses. The enzymatic NAG assay was validated using within- and between-run coefficients of variation (CVs), recovery following standard addition, and linearity of dilution. Intra- and inter-run CVs (21% and 3.2%, respectively), average recovery following standard addition (99-109%), and linearity under serial dilution (R2 = 0.997) were satisfactory. Urine NAG index was significantly correlated with urinary fractional excretion of sodium (FENa; ρ = 0.76, p < 0.001) and plasma creatinine (ρ = 0.74, p = 0.001). Median urine NAG indices were higher in azotemic horses (p = 0.006), in horses with increased urinary FENa (p = 0.006), and in horses with increased urine gamma-glutamyl transferase index (p = 0.032). Urine NAG can be measured in horses and shows positive correlation with 2 current renal biomarkers. Additional work is needed to establish normal equine reference intervals and characterize the increase of urine NAG index in horses in relation to tubular injury.

Podocyturia in pediatric patients with Fabry disease

IntroductionFabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome. ObjectivesThe objectives of the study were: 1. To quantify the presence of podocytes in pediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria. MethodsWe performed an analytical, observational study of Fabry and control subjects, which were separated into 2 groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group). ResultsWe studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years.The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p=0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p=0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values. ConclusionThe detection of podocyturia in pediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria.

Role of sclerostin, fibroblast growth factor-23, and Klotho in hemodialysis patients

Introduction Chronic kidney disease–mineral bone disorder leads to decreasing bone health. Sclerostin is produced by osteocytes similar to fibroblast growth factor-23 (FGF-23) and might upregulate the FGF-23 production by the osteocyte. FGF-23 may act as a mineralization inhibitor. Klotho serves as an obligate coreceptor for the FGF-23 and represents a marker of chronic kidney disease–mineral bone disorder. Aim We examined the association between serum sclerostin, FGF-23, Klotho, parathyroid hormone, high-sensitivity C-reactive protein (hsCRP), and phosphorus levels in hemodialysis (HD) patients. Patients and methods A total of 63 HD patients in the National Institute of Urology and Nephrology and 20 controls were enrolled in the study. Serum sclerostin, FGF-23, Klotho, parathyroid hormone, hsCRP, and phosphorus levels were assayed. Results We found that serum sclerostin, FGF-23, Klotho, and hsCRP levels of the HD patients were higher than controls [median and interquartile range are 1.379 (0.217–11.680) ng/ml, 61.71 (9.821–565.5) pg/ml, 201.74 (90.53–402.73) pg/ml, and 25.79 (12.10–41.92) mg/l vs. 0.535 (0.169–0.830) ng/ml, 33.077 (10.45–67.342) pg/ml, 349.49 (201.23–721.5) pg/ml, and 4.375 (2.27–6.21), respectively; P Conclusion There is an association between serum levels of sclerostin, phosphorus, and FGF-23 in HD patients, and Klotho may represent an early marker of renal damage.

Organoprotection with arterial hypertension 2-3 degrees

Objective. Arterial hypertension (AH) is one of the most common and socially significant diseases worldwide. Despite years of experience gained in studying hypertension, the problems concerning selection of antihypertensive therapy with pleiotropic organ-protecting effects are still of current importance. Purpose - to assess therapeutic efficacy and pleiotropic organ-protective capability of third-generation calcium antagonist lercanidipine in patients with stage 2-3 hypertension. Materials and methods. Our study enrolled a total of ninety-two 31-to-84-year-old patients. Of these, 72 patients diagnosed as having stage 2 or 3 AH composed the Study Group and 20 apparently healthy subjects were included into the Control Group. At baseline and after 6 months, all patients of the Study Group underwent examinations consisting in measuring biochemical parameters [total cholesterol (TCH), triglycerides, low-density lipoprotein cholesterol (LDL CH), uric acid, urea, creatinine, glucose], 24-hour ambulatory BP monitoring, echocardiography in order to assess the dimensions and volume of the cardiac chambers, thickness of the left ventricular posterior wall (LVPW) and left-ventricular myocardium mass index (LVMMI), studying microalbuminuria (MAU), a known marker of endothelial dysfunction and early renal lesion; assessing the state of the vascular wall by the ankle-brachial index (ABI) and pulse pressure (PP). Antihypertensive therapy consisted in lercanidipine alone taken at a dose of 10-20 mg/day, failure to thereby achieve the target BP level was followed by additionally prescribing an angiotensin converting enzyme (ACE) inhibitor, enalapril, given at a dose of 5-20 mg twice daily. Results. All patients by the end of the study achieved the target level of AP (p≤0.05), also demonstrating significantly improved (p≤0.01) parameters of endothelial dysfunction and an early marker of renal damage (MAU), indices of elastic properties of the vascular wall ABI (p≤0.05) and PP (p=0.01). Significantly positive dynamics was observed for the following parameters: decreased creatinine concentration (p≤0.001), increased GFR (p≤0.001), decreased levels of TCH (p≤0.01) and LDL CH (p≤0.001). Conclusion. Lercanidipine therapy of patients with stage 2-3 AH proved highly efficient, well tolerated, metabolically neutral with pleiotropic organprotecting properties in the form of improved condition of the vascular wall, correction of endothelial dysfunction, nephroprotective action

Podocituria en pacientes pediátricos con enfermedad de Fabry

IntroductionFabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome. ObjectivesThe objectives of the study were: 1. To quantify the presence of podocytes in paediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria. MethodsWe performed an analytical, observational study of Fabry and control subjects, which were separated into 2groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group). ResultsWe studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years.The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p=0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p=0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values. ConclusionThe detection of podocyturia in paediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria.

Effective end-organ protection in arterial hypertension: possibilities of third-generation calcium antagonists

Objective:Arterial hypertension (AH) is one of the most common and socially significant diseases worldwide. Despite years of experience gained in studying hypertension, the problems concerning selection of antihypertensive therapy with pleiotropic organ-protecting effects are still of current importance. The purpose of the study was to assess therapeutic efficacy and pleiotropic organ-protective capability of third-generation calcium antagonist lercanidipine in patients with stage 2-3 hypertension.Method:Our study enrolled a total of ninety-two 31-to-84-year-old patients. Of these, 72 patients diagnosed as having stage 2 or 3 AH composed the Study Group and 20 apparently healthy subjects were included into the Control Group. At baseline and after 6 months, all patients of the Study Group underwent examinations consisting in measuring biochemical parameters [total cholesterol (TCH), triglycerides (TG), low-density lipoprotein cholesterol (LDL CH), uric acid, urea, creatinine, glucose], 24-hour ambulatory BP monitoring, echocardiography (EchoCG) in order to assess the dimensions and volume of the cardiac chambers, thickness of the left ventricular posterior wall (LVPW) and left-ventricular myocardium mass index (LVMMI), studying microalbuminuria (MAU) , a known marker of endothelial dysfunction and early renal lesion; assessing the state of the vascular wall by the ankle-brachial index (ABI) and pulse pressure (PP). Antihypertensive therapy consisted in lercanidipine alone taken at a dose of 10-20 mg/day, failure to thereby achieve the target BP level was followed by additionally prescribing an angiotensin converting enzyme (ACE) inhibitor, enalapril, given at a dose of 5-20 mg twice daily.Results:All patients by the end of the study achieved the target level of AP (p<0.05), also demonstrating significantly improved (p<0.01) parameters of endothelial dysfunction and an early marker of renal damage (MAU), indices of elastic properties of the vascular wall ABI (p<0.05) and PP (p=0.01). Significantly positive dynamics was observed for the following parameters: decreased creatinine concentration (p<0.001), increased GFR (p<0.001), decreased levels of TCH (p<0.01) and LDL CH (p<0.001).Conclusion:Lercanidipine therapy of patients with stage 2 - 3 AH proved highly efficient, well tolerated, metabolically neutral with pleiotropic organ-protecting properties in the form of improved condition of the vascular wall, correction of endothelial dysfunction, nephroprotective action.

GLOMERULAR HYPERFILTRATION AS AN EARLY MARKER OF RENAL DYSFUNCTION IN MASKED HYPERTENSION

Objective: Glomerular hyperfiltration, an early marker of renal dysfunction, is prevalent in the early stage of hypertension but had not been investigated in masked hypertension. The aim of the present study is to investigate the association of hyperfiltration with masked hypertension. Design and method: We recruited consecutive untreated outpatients who were referred for 24-h ambulatory blood pressure monitoring to the Hypertension Clinic. Masked hypertension was defined as an elevated 24-hour ambulatory blood pressure (> = 130/80 mm Hg) with a normal office blood pressure (<140/90 mm Hg). Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) above the sex-and age- specific 95th percentile of normotensive subjects. Results: Among the 1768 participants (mean age, 50.9 years; 52.9% women), 646 (36.5%) had masked hypertension, 88 (5.0%) had microalbuminuria, and 176 (10.0%) had glomerular hyperfiltration. In multivariate analyses, glomerular hyperfiltration was independently associated with younger age, female sex, increased body mass index, 24-h systolic blood pressure and heart rate, and the presence of diabetes mellitus. The prevalence of glomerular hyperfiltration was significantly higher in masked hypertension compared with that in normotensives (12.2% vs.5.1%, P < 0.001), with an adjusted odds ratio of 2.42 (95% CI: 1.20–4.89, P = 0.01). The corresponding difference in prevalence (12.4% vs. 5.2%, P < 0.001) and the adjusted odds ratio (2.33, 95%CI, 1.44–3.76, P = 0.005) remained significant after excluding 88 patients with microalbuminuria. Conclusions: In conclusion, glomerular hyperfiltration was prevalent in masked hypertension as an early marker of renal damage.