Describe the clinical profile of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and analyze the risk predictors of hepatic fibrosis in outpatient follow-up at a university hospital.Demographic, clinical and laboratory data of a cohort of 143 patients with biopsy-proven NAFLD were retrospectively analysed under univariate analyses. Diagnostic accuracy, determined by AUROC, was evaluated for variables that showed a significant difference in univariate comparison analysis and diagnostic performances were determined by sensitivity and specificity.The mean age of studied patients were 48 years, 66.4% of them were women. Age, presence of diabetes mellitus, hypertension, metabolic syndrome and laboratory variables such as AST/ALT ratio, GGT, platelet count and fasting glucose were significantly associated with advanced fibrosis. FIB-4 and NAFLD fibrosis score  outperformed APRI (AUROC 0.73) for advanced liver fibrosis and cirrhosis (P of 0.04).In our study, metabolic syndrome, diabetes, hypertension, AST/ALT ratio, GGT, platelet count and fasting glucose were associated with hepatic fibrosis in patients with NAFLD. The non-invasive tests FIB-4 and NAFLD fibrosis score showed the best accuracy to stratify disease severity. Non-alcoholic fatty liver disease (NAFLD) is one of the most common etiologies of liver disease, with a worldwide prevalence of 25% . It is sNAFLD comprises a spectrum of diseases, ranging from isolated non-inflammatory steatosis, defined by lipid accumulation in the cytoplasm of more than 5% of hepatocytes, to non-alcoholic steatohepatitis (NASH), characterized by specific histological changes, such as steatosis, inflammatory infiltrate and hepatocyte ballooning with or without fibrosis . At leasEpidemiological, clinical, genetic and environmental factors contribute to the heterogeneity of NAFLD presentation. The purpose of this study is to describe the clinical profile of patients with biopsy-proven NAFLD and to evaluate the risk predictors of advanced hepatic fibrosis and cirrhosis in this population. As it is a highly prevalent disease, with different local realities, studies as this one serve as a basis for knowledge of the local reality and provide important information for the development of public health programs.This is a retrospective cross-sectional study on patients with biopsy-proven NAFLD, in the period of 2000 to 2018, followed-up at the Liver Metabolic Disease Outpatient Clinic of the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil. The local ethics committee approved the study .Patients aged > 18 with biopsy-proven NAFLD, as defined by Brunt and cols., were included , and presence of smoking, alcoholism, hypothyroidism, T2DM, prediabetes, insulin resistance, systemic arterial hypertension, dyslipidemia and metabolic syndrome. BMI was classified according to the World Health Organization and metabolic syndrome was diagnosed following the International Diabetes Federation criteria . AlanineThe dependent variable was liver fibrosis and to evaluate the association of histological characteristic with clinical-demographic and laboratory variables, absent or mild/moderate fibrosis (grades 0+1+2) versus advanced liver fibrosis/cirrhosis (grades 3+4) were analyzed.9/L) x √ALT (U/L). NFS: -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × diabetes  + 0.99 × AST/ALT ratio - 0.013 × platelet count (x109/L) - 0.66 × albumin (g/dL). APRI index: [ x 100]/Platelet count.Non-invasive tests based on clinical and biochemical variables developed to stage liver fibrosis were calculated for patients who had all variables in medical records. We calculated three scores: The Fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI), using the original formulas –13. FIB-P value less than 0.05 was considered significant. Statistical procedure interpretation of data was performed using Statistical Package for Social Sciences (SPSS) version 23.0 for Windows.Categorical variables were presented as frequency and percentage, and continuous variables as mean and median values, standard deviation, and range. A chi-square analysis and a chi-square for linear trend were used to compare categorical variables, and the continuous variables were analyzed using the non-parametric Kruskal-Wallis with post hoc test of Dunn and Mann-Whitney tests. Diagnostic accuracy was evaluated by determining the area under the receiver-operator characteristics curve (AUROC) for variables that showed a significant difference in univariate group comparison analysis, after calculating the cut-off with highest Youden Index . DiagnosA total of 219 patients with biopsy-proven NAFLD were reviewed, 76 were excluded due to the following reasons: alcohol consumption more than the considered limit (19.7%), viral hepatitis (50%), presence of another hepatopathy (21.1%) and lack of data in medical records (9.2%). Finally, 143 patients were included, 95 were female, aged 19-68 years (mean = 48 ± SD 11.8 years).Non-invasive scoring systems were evaluated in patients who had all variables in their medical record. FIB-4 index was calculated in 112 patients, 75 (67%) had a score < 1.3 and 5 (4.5%) ≥ 3.25. APRI’s determination included 118 individuals, 61 (51.7%) had a score < 0.5 and 9 (7.6%) > 1.5. NFS was estimated in 67 patients: 27 (40.3%) had a score < -1.475 and 7 (10.4%) > 0.675.We classified liver biopsies according to the severity of steatosis and fibrosis . Liver sAge, T2DM, hypertension, the presence of metabolic syndrome and laboratory data, such as AST/ALT ratio, GGT, platelet count and fasting blood glucose were significantly associated with advanced liver fibrosis and cirrhosis as well as the non-invasive scoring systems, as shown in AUROC and detailed test performances are shown in P of 0.04. There was no significant difference between FIB-4 and NFS AUROC’s.FIB-4 and NFS  outperformed APRI (AUROC 0.73) for advanced liver fibrosis and cirrhosis with a P = 0.001). The correlation with gender is controversial: early studies claimed that NAFLD was more common in women, but the latest concluded the opposite . Mild to moderate elevations of serum aminotransferases are the most common laboratory changes found in patients with NAFLD (P = 0.007). This enzyme has a prooxidant activity and a modulating influence on endothelial dysfunction. It is associated with metabolic syndrome and is often elevated in patients with NAFLD. There is also a role for this enzyme activity in several aspects of cardiovascular disease  and liver fibrosis in patients with NAFLD. As it is a silent disease with substantial heterogeneity of phenotypes, these factors, in combination with non-invasive scores such as FIB-4 and NFS, could help in patient stratification, selection for liver biopsy and identification of who will benefit from early intervention. Besides that, as NAFLD is a highly prevalent disease, with different local realities, studies as this one could be a basis for knowledge of the local reality and provide important information for the development of public health programs.


The clinical benefits of endovascular treatment in renal artery stenosis (RAS) remain controversial. This study used an intraoperative renal perfusion imaging technique, called flat-panel detector parenchymal blood volume imaging (FD-PBV), to observe the change in renal perfusion after endovascular treatment in RAS.In a prospective, single-center study, we assigned 30 patients with atherosclerotic RAS who underwent endovascular treatment between March 2016 and March 2021. The preoperative and postoperative results of renal perfusion, blood pressure, and renal function, were compared.p < 0.001) and median preoperative mean density of contrast medium (MDCM) (p = 0.028) increased significantly after endovascular treatment. The ratio of postoperative and preoperative MDCM differed greatly among the patients. For patients with preoperative MDCM <304.0 HU , MDCM significantly increased after treatment (p = 0.001) and 12 (80.0%) patients had more than 10% increase in renal perfusion. For patients who had relatively high preoperative renal perfusion , preoperative and postoperative MDCM were similar (p = 0.776). On the other hand, the serum creatinine levels significantly decreased in Subgroup A (p = 0.033) and fewer antihypertensive drugs were used after endovascular revascularization (p = 0.041). The preoperative and postoperative creatinine levels and number of antihypertensive drugs were similar in Subgroup B.Both median kidney volume (During the perioperative period, RAS patients with relatively low preoperative renal perfusion levels had greater improvement in renal perfusion, renal function, and blood pressure control after endovascular treatment. The improvement of renal function needs to be confirmed by long-term follow-up. HoweRenal perfusion is the blood flow at the level of the capillary bed, and is highly associated with the delivery of oxygen and nutrients . Renal pOur research group reported a new application named flat-panel detector parenchymal blood volume imaging (FD-PBV) in 2017, and it might be a new method for evaluating the perfusion of the target kidney during endovascular procedure . We desi2.2.1.This prospective, single-center study included 30 RAS patients who underwent renal artery stenting between March 2016 and March 2021 in the study hospital. The study complied with the Declaration of Helsinki (as revised in 2013) and the protocol was approved by the ethics committee and the institutional review board of the study hospital. We obtained written informed consent from each patient. The inclusion and exclusion criteria were as follows.2), and (7) patients whose affected kidney did not have total loss of function.Inclusion criteria: (1) patients who provided informed consent; (2) patients who were diagnosed with RAS by CTA, MRA, or Doppler ultrasonography; (3) patients who were aged 18 years or older; (4) patients whose intervened renal arteries were not completely occluded (confirmed by DSA); (5) the stenosis percentage exceeding 70%; (6) unexplained recurrent congestive heart failure, sudden pulmonary oedema, uncontrolled blood pressure (>140/90 mmHg after at least 2 antihypertensive medications) or impaired renal function (GFR of the affected kidney <40 ml/min/1.73mExclusion criteria: patients who (1) were pregnant, (2) had nonatherosclerotic RAS, (3) had bilateral renal artery endovascular treatment, (4) had a history of renal transplantation or renal artery bypass surgery, (5) with multiple renal arteries of the affected side, (6) were allergic to iodine contrast medium, (7) had other contraindications of endovascular treatment, and (8) had technical failure in the endovascular treatment.2.2.99mTc-DTPA kidney dynamic imaging. Noninvasive blood pressure was measured at least twice a day (8 am and 4 pm) in the hospital, and the average pressure was calculated. Serum creatinine levels were tested in all patients before and the day after endovascular intervention. The kidney volumes were measured by FD-PBV.The mean density of contrast medium (MDCM), which reflected renal perfusion, was measured by FD-PBV. The ratio of MDCM was defined as postoperative MDCM divided by preoperative MDCM. Other endpoints included the change in blood pressure, number of antihypertensive drugs, serum creatinine levels, and kidney volumes. The GFR of the affected kidney was measured by 2.3.2.All endovascular interventions were performed by the same surgeon group. The detailed procedures are as follows. An introducer sheath was inserted into the femoral artery. Then, the 8F guiding catheter, 5F Cobra catheter, and guidewire were placed at the ostium of the target renal artery. DSA was used to evaluate the lesions. If the stenosis percentage was less than 70%, or the renal artery was completely occluded, the patients were excluded from the study. FD-PBV acquisition was run for the first time to analyze preoperative perfusion levels. All patients had either primary renal artery stenting, or PTRA plus stenting. DSA was performed a second time to confirm the patency of the arteries. Once again, we performed FD-PBV for postoperative results. The sheath was removed and a vascular closure device was used. A protocol for the reduction of contrast-induced nephropathy  was used in patients with eGFR less than 60 ml/min/1.73m2.4.The dedicated FD-PBV acquisition protocol on a flat-panel detector angiographic system  was employed based on two rotational runs, the mask run and fill run, with the following imaging parameters: acquisition time 8 s, tube voltage 70 kV, matrix 616 × 480, flat-panel detector size 30 cm × 40 cm, rotational angle 200°, 0.5°/frame, 400 frames in total, and dose 0.36 mGy/frame. After positioning of the catheter at the ostium of the renal artery, the mask run started before the contrast medium injection. Then, 20 ml diluted contrast medium  was injected at a rate of 4 ml/s through the catheter. Later, the fill run was triggered manually when opacification of the kidney cortex was seen, marking the steady state of contrast medium filling for renal parenchyma. To reduce motion artifacts, patients were instructed to hold their breath during PBV acquisition. The acquisition of all patients was performed by the same engineer from Siemens AG.2.5.The system automatically transferred the acquired data to the workstation  for postprocessing using commercially available imaging software . PBV reconstruction was visualized in the form of colored multiplanar reconstruction images, in which the pseudocolor corresponded to blood volume. The kidney volume and the mean density of CM of the whole kidney were measured using the syngo volume task card tool. The data of all patients were analyzed by the same engineer from Siemens AG.2.6.p-value less than 0.05 was considered statistically significant. A specialist in medical statistics participated in all statistical analyses. All analyses were conducted using IBM SPSS Statistics software for Windows, version 22.0 .Kidney volumes, MDCM and serum creatinine levels are presented as the median with interquartile range, and blood pressure, and antihypertensive drugs are presented as the mean ± standard deviation. The preoperative and postoperative results were compared by the Wilcoxon signed rank test, or paired Student’s t test. The correlations between the ratio of MDCM and other factors were analyzed by Pearson correlation analysis. In addition, stepwise multifactor linear regression model was used. The patients were divided into two subgroups depending on the preoperative MDCM. The cutoff value was the median of MDCM. Subgroup A included patients with relatively low preoperative MDCM, and Subgroup B included patients with relatively high preoperative MDCM. The kidney volumes, MDCM, serum creatinine levels, blood pressure, and antihypertensive drugs of different subgroups were compared by the Wilcoxon rank sum test or Student’s t test. A 3.Thirty patients were included in the study and the baseline characteristics are summarized in 3.1.p = 0.166), indicating that FD-PBV was safe for RAS patients. Compared with their baseline creatinine levels, only two patients had more than a 10 μmol/L increase . The creatinine levels of these two patients decreased to baseline in a week.p = 0.012). On the other hand, both systolic and diastolic blood pressure significantly decreased. The mean systolic blood pressure was 136.7 ± 16.0 mmHg before the operation and 128.1 ± 11.1 mmHg after the operation (p = 0.001). The mean diastolic blood pressure was 79.2 ± 11.2 mmHg before the operation and 74.7 ± 10.6 mmHg after the operation (p = 0.007).The mean preoperative number of antihypertensive drugs was 1.7 ± 0.9 and the mean postoperative number of antihypertensive drugs was 1.5 ± 1.0. The patients used fewer antihypertensive drugs during the perioperative period . The median MDCM was 304.0 HU before revascularization, and it increased to 339.9HU after revascularization (p = 0.028). However, not all patients had significant improvement in MDCM. The ratio of MDCM was distributed as follows (p = 0.009).We compared the preoperative and postoperative results acquired from the FD-PBV . The med follows : less th follows  and one  follows . In the 3.1.1.R = 0.698, p < 0.001). On the other hand, stenosis percentage and the ratio of MDCM were negatively correlated . In the stepwise multifactor linear regression model for predicting the natural logarithm of the ratio of MDCM, only preoperative MDCM was included .The correlations between the ratio of MDCM and other influencing factors are listed in 3.2.p = 0.003). The comparisons of kidney volumes, renal perfusion, blood pressure, and renal function between the two subgroups are shown in p = 0.001), but there was no significant change in Subgroup B (p = 0.776). On the other hand, the renal function of Subgroup A showed significant improvement (p = 0.033), but preoperative and postoperative serum creatinine levels were similar in Subgroup B (p = 0.937). The blood pressure of both subgroups decreased significantly after intervention. The postoperative number of antihypertensive drugs in Subgroup A was significantly lower than that before surgery (p = 0.041). The mean preoperative and postoperative numbers of antihypertensive drugs in Subgroup B were not significantly different (p = 0.164).We used the median of preoperative MDCM (304.0 HU) as the cutoff value. Both Subgroups A and B included 15 patients. The stenosis percentage was similar between the two subgroups . Twelve 4.Renal artery stenosis is one of the common causes of secondary hypertension and it may result in chronic renal dysfunction , 13. EndCurrent diagnostic imaging techniques include CTA, MRA, Doppler ultrasonography, and DSA . These mp < 0.001)   . Another< 0.001) . In live < 0.01) . The acc < 0.01) .This perfusion imaging technique has been used in some organs  and shows favorable outcomes , 28–31. In this study, the volumes of the intervened kidneys increased significantly after endovascular treatment due to the improvement in the patency of renal arteries. However, the change in renal perfusion varied in different patients. The change in MDCM was highly associated with preoperative MDCM, and patients with relatively low preoperative perfusion levels were more likely to have perfusion improvement. The subgroup analysis showed that renal perfusion after surgery in Subgroup A was significantly higher than before surgery. A total of 80.0% (12/15) of Subgroup A patients had a more than 10% perfusion increase. However, only 20.0% (3/15) of Subgroup B patients had a more than 10% perfusion increase. On the other hand, the changes in blood pressure and renal function were different between the two subgroups. The renal functions of Subgroup A patients improved after revascularization and they used fewer antihypertensive drugs. These changes were in accordance with the change in renal perfusion. A previous study demonstrated that low renal perfusion was associated with more blood pressure reduction after renal artery stenting in hypertensive patients . PatientBecause of its invasive nature, FD-PBV can only be utilized in RAS patients who are inclined to endovascular intervention. We did not have renal perfusion results of patients with mild or modest renal artery stenosis, or of normal people as a reference. Therefore, noninvasive, quantitative perfusion imaging techniques could be a feasible approach for preoperative assessment. Potential noninvasive perfusion imaging techniques include dynamic contrast-enhanced magnetic resonance imaging, arterial spin labeling, and contrast-enhanced ultrasound, but the clinical application of these perfusion imaging methods needs to be further studied , 33, 34.The study had the following limitations. First, to minimize the potential risks of renal damage, the FD-PBV results were not repetitively measured. Second, as the size of the study was relatively small, the strength of the evidence needs to be further improved. Third, the change in renal perfusion during follow-up could not be evaluated. Fourth, the creatinine levels of 48 h and 72 h after the procedure were not measured in most patients.In conclusion, during perioperative period, the perfusion improvement of RAS patients was negatively correlated with the preoperative perfusion levels. Patients who had relatively low initial perfusion levels tended to have more improvement in renal perfusion, renal function, and blood pressure reduction. The improvement of renal perfusion after endovascular revascularization needs to be confirmed by long-term follow-up.


Patients with treatment resistant hypertension (TRH) are at particular risk of cardiovascular disease. Life style modification, including sodium restriction, is an important part of the treatment of these patients. We aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH and to evaluate the effect of this intervention on blood pressure (BP). Moreover, we aimed to examine if mechanisms involving nitric oxide, body water content and BNP, renal function and handling of sodium were involved in the effect on nocturnal and 24-h BP. Also, measurement of erythrocyte sodium sensitivity was included as a possible predictor for the effect of sodium restriction on BP levels.TRH patients were included for this interventional four week study: two weeks on usual diet and two weeks on self-performed sodium restricted diet with supplementary handed out sodium-free bread. At the end of each period, 24-h BP and 24-h urine collections  were performed, blood samples  were drawn, and bio impedance measurements were made.p < 0.05). NOx increased, BNP and extracellular water content decreased, all significantly. Change in NOx correlated to the change in 24-h systolic BP. BP response after sodium restriction was not related to sodium sensitivity examined by salt blood test.Fifteen patients, 11 males, with a mean age of 59 years were included. After sodium restriction, urinary sodium excretion decreased from 186 (70) to 91  mmol/24-Self-performed dietary sodium restriction was feasible in a population of patients with TRH, and BP was significantly reduced. Increased NOx synthesis may be involved in the BP lowering effect of sodium restriction.The study was registered in Clinical trials with ID: NCT06022133. Elevated blood pressure is the main contributor to the risk of developing cardiovascular disease (CVD) and is yearly accountable for more than 10 million premature deaths worldwide . One subNon-adherence to medication is a general problem. It has been shown in several studies that non-adherence is commonly seen in patients diagnosed with TRH –11. In oA cornerstone in treatment of patients with hypertension is lifestyle modification . High soDietary sodium restriction does not result in equal BP response in all individuals. Sodium sensitivity may be one of the explainable mechanisms involved in the diverse response to sodium restriction. Sodium sensitivity is a result of many different individual features, i.e. renal function, age, and sodium buffering capacity in skin, bone and endothelia . Sodium In this study, we aimed to analyse if self-performed sodium restricted diet could be implemented in a group of patients with TRH. The diet was self-made, except for handed out sodium-free bread. The diet is therefore potentially implementable to general population. Moreover, we aimed to explore if the changes in nocturnal and 24-h BP in response to sodium restriction could be explained by mechanisms involving nitric oxide synthesis, water retention (extracellular water and BNP), renal function, or renal handling of sodium (ENaCɣ). Finally, we intended to analyse whether BP response to sodium restriction could be predicted by measurement of erythrocyte sodium sensitivity.This study was designed as an interventional study. The effect of the intervention was compared to a preceding non-interventional period (control period), and the patients therefore served as their own controls. The order of non-intervention and intervention period was not randomised.The study was carried out in the University Clinic in Nephrology and Hypertension and the Renal Outpatient Clinic, Gødstrup Hospital, Herning, Denmark. Patients were included from January 2018 until March 2021.The study included patients with treatment resistant hypertension according to the following inclusion criteria: men and women 20–70 years old, eGFR > 45 ml/min, unchanged prescriptions of antihypertensives for ≥ 3 months, and 24 h BP ≥ 130/80 mmHg performed after handed out, supervised and witnessed intake of usual antihypertensive medicine by study manager.Exclusion criteria: Symptoms of heart failure (NYHA class 3–4), clinically relevant peripheral oedema, treatment of obstructive sleep apnoea, forced expiratory volume of 1 s < 50% of expected, antihypertensive medication that cannot be dosed once daily, pregnancy or lactation, p-albumin < 34 g/l, urine albumin/creatinine > 1000 g/mg, INR > 1.2, and coelic disease.Withdrawal criteria: development of exclusion criteria, withdrawal of consent, or lack of compliance for attendance.14 patients had to be included, if the minimal relevant change in night-time SBP from baseline to end of intervention is 6 mmHg, SD is 8 mmHg, and a significance level of 5% and a power of 80% are used.Primary effect variable was change in nocturnal systolic BP (SBP).Secondary effect variables were changes in 24-h and day time BP, in relative nocturnal SBP decrease, in total urinary sodium excretion, in the ratio of day/night urinary sodium excretion, in total body water and extracellular water, in urinary excretion of u-AQP2 and u-ENaCɣ, in plasma NOx (nitrite + nitrate), BNP, and sodium sensitivity (SS) .Patients in the Outpatient Clinic were reviewed regarding age, renal function, and medicine prescriptions. If these were as listed in the inclusion criteria, recent home or 24-h BP measurements were evaluated. If these were above limits for normal BP and no antihypertensives had been added since, patients were regarded eligible. These patients were asked about the possibility of participating in the study at a planned control at the Renal Outpatient Clinic. If the patient was interested, an information meeting was planned, and after informed written consent was provided, screening examinations were performed (baseline). The screening consisted of health information obtained from a questionnaire, review of prescribed medications, blood tests , and urine examination . After the above mentioned, 24-h ABPM was performed after intake of usual antihypertensive medication witnessed by the study manager, and 24-h urine collection was carried out .If patients fulfilled inclusion criteria after the above completed examinations, they were included for participation and started 14-day standard period with usual diet. None of the patients had received any dietary counselling regarding sodium intake prior to study participation, and they were informed not to change anything in their usual diet.At day 11 to 14, examinations were performed. This is referred to as examination 1 (E1). At day 11, patients were weighted and lower leg circumference was measured 25 cm proximal to the medial malleolus. Patients answered questionnaire about medicine adherence, any symptoms of high or low blood pressure , bio impedance measurements were performed, and blood samples were drawn . Also 24-h ABPM was performed. Patients collected urine for 24 h in two cans¸ the first from morning until final voiding at bedtime, the second can for eventual voiding during night-time until final voiding when getting up in the morning.When examinations at E1 were completed, patients continued into the intervention period as described below. At day 11–14 in the intervention period, identical examinations as at E1 were performed. These examinations are referred to as E2. Measurements were performed on the same side as at E1.After completion of these examinations, patients had completed project participation.Planning of the examination days could diverge within a few days in order to optimal planning for the patients.In the two weeks intervention period, patients were instructed in self-performed sodium restriction in the diet. They received oral and written instruction on how to perform the sodium restriction, and two kinds of sodium-free bread were handed out for the two weeks period. The written instruction included general advice on how to reduce sodium intake: avoid / limit prefabricated bread, avoid take-away and industrially processed food, avoid industrially marinated food and industrially processed cold cuts, avoid cheese, limit the use of butter, avoid biscuits and chips, and avoid having a sodium container at the dinner table. Also, the written instruction included main meal suggestions and food items to avoid. For breakfast, patients were advised to eat oatmeal, dairy products, fruits, and avoid cereals and cheese. For lunch, patients were advised to eat the handed-out bread, leftovers from dinner, fruits, vegetables, eggs , salads, and cold cuts with sodium content less than 0.6 g/ 100 g and only one slice. They were advised to avoid cold cuts with higher sodium content than 0.6 g/ 100 g, sausages, tuna, smoked salmon, and marinated herring.For dinner, patients were advised to avoid fast food and prefabricated food, to prepare food themselves without addition of salt  but to use other spices instead. If they were planning to eat pies or pizza, they were advised to prepare the dough themselves, and they were advised to fry in cooking oil instead of butter.If patients had any questions to intervention, they were informed to contact the study manager for guidance.All medications were taken in the morning. The antihypertensive medication was dosed by the study manager into date- and weekday-marked boxes, and identical generic drugs were used for all the patients’ usual prescriptions, and all were given in the usual dosage. Medications for the whole study period were handed out in the beginning of the standard period. Any possible change in medication was registered in the patient’s study file, and patients were asked to bring their medication boxed at examination day as a control for adherence. They were also asked, how many dosings they had missed out in the preceding period.Patients were informed to contact the study manager, if any side effects occurred.Twenty-four hour BP measurement and office BP were measured with an oscillometric device, A&D TM-2430 . Circumference of the upper left arm was measured and an appropriate size cuff was chosen. Office BP was measured after a minimum of 5 min rest in sitting posture. Throughout the 24-h, BP was measured every 20 min. Day- and nocturnal blood pressure was defined from the patients’ information about bedtime. The same device was used for the patient for all three measurements .Hypertension and non-dipping were defined according to the 2018 guidelines from the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) [3]. Hypertension was defined as 24 h SBP/DBP ≥ 130/80 mmHg. Non-dipping was defined as relative nocturnal decrease in SBP ≤ 10%. Defined daily doses of antihypertensive medication were classified using the ATC/DDD kit from WHO.ESS was measured using Salt Blood Test Mini from K-EDTA blood. Blood samples were drawn and within 15 min. 50 μL blood was mixed with 50 μL Na + cocktail  and shaken by hand. Within 15 min. the mixture was reshaken thoroughly and filled into hematocrite tubes using gravity forces. The tubes were placed vertically in tube holders. The length of the supernatant was measured and read after exactly 60 min. ESS was then calculated based on standards according to the manufacturer.Erythrocyte sodium sensitivity (ESS) was measured from SaBT using the following two equations: *100 for men, and *100 for women. From ESS, patients are categorized as low, average, or high sodium sensitive based on ESS < 80, 80–120, or > 120, respectively . Continuous paired variables were tested for difference using the paired t-test, and Wilcoxon’s test was used if paired continuous data were not normally distributed. Categorical variables were listed as percentages with total number in parenthesis. To test for differences on a binary paired variable, McNemar’s test was used.Correlation analyses were performed to test the association between changes in BP and changes in sodium excretion and for the significance of sodium sensitivity . Associations between selected variables and change in blood pressure were investigated using correlation analyses following the “intention to treat” principle. Correlation analyses were performed using Pearson’s test, if data were normally distributed; otherwise Spearman’s test was used.Multivariate regression analyses were performed using a linear regression model to investigate the relationship between variables. The dependent variable was absolute change in SBP . The first independent variable was change in 24-h sodium excretion . The second variable was either ESS1 or absolute change in NOx. In all, five analyses were performed, and the exact model is described in the A total of 27 patients were screened for participation. Flow chart is seen in Fig. These 15 patients, 11 75%) of them men, had a mean age of 59 5% of the. They haBaseline 24-h systolic/ diastolic BP was 144 /82 9] m m9] mmHgInformation on smoking history, diabetes, and medication is shown in Table The first period, from inclusion to end of examinations at E1, lasted a median of 13 days , while the second period from finishing examinations at E1 to finishing examinations at E2, lasted a median of 14 days .Medicine prescriptions regarding antihypertensive medication were identical at E1 and E2.p = 0.78). This is depicted in Table As seen in Table p = 0.25). At E1 and E2, 8 and 9 patients were non-dippers, respectively.At E1, three (20%) had controlled hypertension, and at E2, this number was 6 (40%). This change was non-significant . From E1 to E2, 24-h urinary sodium excretion decreased significantly by 96 mmol, as seen in Table From baseline to E1, 24-h urinary sodium excretion remained unchanged (192 (86) mmol vs. 186 (69) mmol, p = 0.034), whereas the nocturnal change in excretion rate was unchanged  Sodium-to-potassium excretion more than halved from E1 to E2 , and the difference between them was non-significant (p = 0.247).At E1, mean erythrocyte sodium sensitivity (ESS) was 88 . The patAs seen in Table 2, p = 0.089).eGFR did not change from E1 to E2 (74  vs. 69  mL/min/1p = 0.008).Median value of BNP decreased significantly from E1 to E2 ).Mean plasma NOx level was significantly higher at E2 than at E1 (30.5 (15.4) μmol/l vs. 40.4 (19.1) μmol/l (p = 0.85)).Urinary excretion rate of ENaCɣ did not change from E1 to E2 (1.02 (0.40) ng/min vs. 1.04 (0.46) ng/min (p = 0.03). This correlation is illustrated in Fig. Changes in BP parameters were not correlated to relative or absolute change in sodium excretion or to change in sodium-to-potassium excretion. The absolute change in 24-h SBP correlated significantly to the absolute change in NOx  at neither E1 nor E2. Changes in BP parameters were not correlated to ESS at E1 or to changes in ESS. The correlations between ESS at E1 and change in 24-h and nocturnal SBP are depicted in Fig. BNP was not correlated to the change in TBL, change in BP, or sodium excretion.Multivariate regression analyses with change in BP  as dependent variable, change in 24-h sodium excretion  and ESS1 as independent variables, did not show any correlation.2 = 0.432, p = 0.044 with absolute change in plasma NOx as the only significant independent variable (p = 0.025)).Multivariate regression analysis with absolute change in 24-h SBP as dependent variable, relative change in 24-h sodium excretion and absolute change NOx as independent variables, did show an association . Mean BP change for these three patients was not different than in the population without dizziness. One patient had increased creatinine and potassium at follow-up.In this population of patients with TRH, we found a significant reduction in BP parameters following dietary sodium restriction for two weeks. The change in BP was not correlated to the reduction in urinary sodium excretion or to the reduction in sodium-to-potassium excretion. Patients in this study completed dietary sodium restriction based on dietary instructions and handed-out sodium-free bread. Baseline sodium excretion for this population equalled 11 g of salt and was reduced to around 5.2 g. In this study, we used a new biochemical marker of sodium sensitivity; salt blood test. This marker could, however, not predict the effect of dietary sodium restriction on BP. Following the sodium restriction, plasma NOx levels increased, and this change correlated to 24-h SBP reduction. Patients had reduced body water content and BNP levels after sodium restriction as well.It is well-known, that dietary sodium restriction, even modest, can lower BP , 19, 30.Sodium restriction based on fully prepared sodium-restricted or sodium-free meals is not easy to adapt in the general population. A recent study by Riis et al. demonstrated that introduction of sodium-free bread to the diet of healthy families reduced sodium excretion by 0.6 g  in adults . In our The response to sodium loading in humans is highly variable . Sodium sodium sensitive according to this test. This is a low number if we compare to findings from previous studies of hypertensive individuals using other criteria for diagnosing sodium sensitivity [Only 20% of patients in this study was characterised as sitivity , 34, 35.The study from Pimenta et al. presented evidence of reduced volume load (lower BNP and higher renin activity) during sodium restriction . In our In our study, we did, however, demonstrate significantly lower BNP levels at follow-up. In a community study of a population without known heart failure, it was demonstrated that levels of BNP could predict the risk of developing cardiac disease, even at low levels of BNP . ConsequPrevious studies have related high nocturnal sodium excretion to high nocturnal BP and lack of nocturnal BP decrease . As a prIn our study, the relative nocturnal excretion rate of sodium of 24-h excretion rate increased after sodium restriction, whereas the relative nocturnal creatinine excretion of 24-h excretion remained unchanged. The decrease in 24-h sodium excretion was mainly attained though reduced daytime excretion, as nocturnal excretion was unchanged. As a consequence, the excretion rate of sodium was not correlated to nocturnal BP levels. Therefore, we could not demonstrate evidence of Guytons pressure natriuresis theory directly in our patients . The preFrom experimental animal models, it is proposed that the capability to store sodium non-osmotically actively is one of the traits that defines sodium-resistant individuals . Also, tThe endothelial cells elicits local vasodilation by producing NO . This abThe analyses of NOx in this study measure primarily nitrate. The effector molecule of the NO-system is NO. This molecule is generated by serial degradations of nitrate to nitrite and, finally, to NO . We founIn our study, we found no change in urinary excretion of potassium or urea. Urinary potassium excretion has been shown to correlate to dietary intake of potassium-containing food . Hence, Our patients reduced sodium-to-potassium excretion significantly. This was based on reduced sodium excretion, since potassium, as mentioned above, was unchanged. The change was, however, not correlated to changes in blood pressure. Previous population studies do not agree upon, whether blood pressure levels and sodium-to-potassium-ratio are correlated , 49. HypWe analysed urinary excretion of ENaCγ as a marker of renal handling of sodium. Excretion rate of ENaCγ remained unchanged. Hence, transport of sodium from the tubular lumen across the epithelial sodium channel in the principal cell to the intracellular space in the distal part of the nephron did not seem to be affected by changes in sodium intake.Aldosterone induces increased surface expression of ENaC in the endothelial cells, and it induces increased activity of ENaC in the principal cell leading to retention of sodium and loss of potassium . ReducedAll patients had hypertension at baseline. However, BP decreased non-significantly from baseline examination to E1, therefore three of the patients had controlled hypertension at E1. We screened patients after witnessed intake of antihypertensive medication to ensure that we included true resistant hypertensive patients. Moreover, we handed out the medication for the study period to heighten the compliance. Hence, we did some effort to accommodate non-adherence to medication, but we could not fully exclude the existence of it. Previous studies have shown, that despite efforts to increase hypertensive patients’ adherence to medication, many patients still remain non-adherent .Patients had, despite long term diagnosis of hypertension, a high baseline sodium excretion. Hence, either lifestyle modification talks had not been performed and/ or patients had been resistant to this. Neither way should health care professionals be very aware of this challenge.It is interesting that we observed decreased urinary sodium excretion, decreased body water content, and a decrease in BP parameters, and that these observations do not seem to be correlated. However, power calculation was based on the change in nocturnal BP, and lack of correlation between the latter mentioned effect variables may be related to statistical power.We used 24-h BP measurement, both at inclusion and at both examinations. We used the same equipment for all examinations on the same patient.Patients completed 24-h urine collection at baseline in order to control for the Hawthorne effect. Sodium excretion at baseline and E1 did not differ significantly; hence, patients did not implement sodium restriction before entering the intervention period.Patients completed sodium restriction for only two weeks in this study. This is a short period, and the magnitude of the sodium reduction may be influenced by high motivation because of the short period of time. Studies with longer follow-up are warranted to explore the possibilities of implementing longer term sodium restriction.The study was conducted as an interventional study. We did not include a control group. Therefore, we are not able to control for change in diets or behaviour in general  for patients included in a study analysing blood pressure.Moreover, we did not randomise the intervention as we expected that patients would be challenged in changing back to normal diet after a period of dietary sodium restriction. Patients received usual antihypertensive medication throughout the study period. Therefore, we avoided analyses on elements of the RAA system. It did, however, give us a view of the add-on effect of sodium restriction in addition to usual antihypertensive treatment.½ for sodium balance, when sodium intake is changed, is 21 h [We used 24-h urine collection for assessment of sodium intake. This is a robust method, but it is, however, affected by other circumstances. Among them weekly and/or monthly rhythmically changes in endogenous regulation of sodium homeostasis. However, Walsers analyses showed that T is 21 h . Hence, In a population of 15 treatment resistant hypertensive patients, we demonstrated that self-performed dietary sodium restriction could be implemented safely. After two weeks of sodium restriction, BP and urinary sodium excretion were reduced significantly. Increased nitric oxide synthesis may be involved in the BP lowering effect of sodium restriction alongside with reduced body water content.


Since their introduction as antidiabetic drugs, SGLT2 inhibitors (SGLT2i) have come a long way, proving to be beneficial on cardiovascular and renal outcomes independently of diabetes status. The benefits go far beyond glycemic control, and both the cardio- and nephroprotection are underpinned by diverse mechanisms. From the activation of tubule glomerular feedback and the consequent reduction in hyperfiltration to the improvement of hypoxia and oxidative stress in the renal cortex, SGLT2i have also been shown to inhibit hepcidin and limit podocyte damage. Likewise, they improve cardiac metabolism and bioenergetics, and reduce necrosis and cardiac fibrosis and the production of adipokines, cytokines, and epicardial adipose tissue mass. In terms of outcomes, the efficacy has been demonstrated on blood pressure control, BMI, albuminuria, stroke, heart disease, and mortality rate due to cardiovascular events. Patients with chronic kidney disease and proteinuria, with or without diabetes, treated with some SGLT2i have a reduced risk of progression. The analysis of subgroups of individuals with specific diseases such as IgA nephropathy has confirmed this solid effect on renal outcomes. Given these overarching activities on such a broad pathophysiological background and the favorable safety profile that goes with the use of SGLT2i, it is now certain that they are changing our approach to clinical interventions for important outcomes with an impressive impact. Diabetic kidney disease (DKD) is a microvascular complication associated with at least 30% of the diabetes cases worldwide and a well-established leading cause of chronic kidney diseases (CKDs) and the end-stage renal disease (ESRD) .DKD is a global burden, and in 2012, its mortality rose by 94% .DKD is associated with numerous structural alterations in the kidney, as reported by different authors. Most common structural alterations include an increased thickness in different kidney compartments, such as glomerular, capillary, tubular, and basement membrane –6. Moreo2)  and a reduction in eGFR (<60 ml/min per 1.73 m2) . However2) .Unfortunately, long-term therapies aimed at glycemic control are not sufficient to reduce the DKD risk. Nowadays, new therapeutic strategies aim to reduce glomerular hyperfiltration, inflammation, and fibrosis –15. SodiThe kidney plays an important role in the maintenance of glucose homeostasis. In fact, it is involved in gluconeogenesis and glucose reabsorption at the glomerular level. Glucose is a polar molecule, able to cross the cell membrane from the lumen to the tubule through an active transport mediated by two sodium/glucose carriers, called SGLT2 and SGLT1. SGLT2 is located in the first segment of the proximal tubule, and it is responsible for the reabsorption of 90% of the filtered glucose. On the contrary, SGLT1 is located in the third segment of the proximal tubule, and it is responsible for the reabsorption of the remaining 10%. The filtered glucose is totally reabsorbed into the tubule, reaching a maximal reabsorption threshold corresponding to 180–200 mg/dl of blood glucose –19.When the blood glucose levels are above the threshold, the system capacity will be exceeded, and glucose in the urine will be observed .In diabetic patients, in a condition of hyperglycemia, the amount of glucose filtering into the glomerulus is enhanced, leading to a condition called glomerular hyperfiltration .Glomerular hyperfiltration consists of an alteration of the early stages of the CKD in both T2DM and T1DM . HoweverSGLT2i mechanism of action is insulin independent –28 and aSGLT2i can be administered as monotherapy or in combination with other classes of glucose-lowering drugs .So far, numerous SGLT2i have been studied. To date, the available formulations are classified according to their selectivity for the SGLT2/1 transporters. Selective compounds include dapagliflozin, empagliflozin, and ertugliflozin, which are involved in the exclusive inhibition of the SGLT2 transporter. On the other hand, canagliflozin and sotagliflozin present an inhibitory effect even on SGLT1 . To dateVarious registrative trials have been conducted to evaluate the safety of these molecules. Interestingly, they demonstrated to be not only safe but also able to significantly reduce major CV events, hospitalizations, and the exitus due to CV events .2  have been recruited. In particular, the EMPA-REG OUTCOME included CV benefits in patients with a GFR of 30–60 ml/min/1.73 m2. Results showed that patients treated with SGLT2i presented a reduced risk of CV events than the placebo group. In particular, SGLT2i reduced the establishment of major CV events by 11%, as well as the CV death and hospitalizations  and in the DECLARE TIMI 58 (59%). Diabetic patients with a glomerular filtration rate (GFR) <60 ml/min/1.73 mizations . The relizations .These results encouraged new retrospective studies and new clinical trials to evaluate the protective effect of SGLT2i on the kidney. In particular, Toyama et al. conducted a metanalysis including 27 studies and 7,363 diabetic patients. SGLT2i demonstrated to be involved in the improvement of numerous outcomes, such as blood pressure control, BMI and albuminuria reduction, CV risk reduction, stroke, and heart disease reduction, as well as a decrease in the mortality rate due to CV events. Moreover, SGLT2i were safe and well tolerated .p < 0.001), end-stage kidney disease, and death from renal or cardiovascular causes in a broad population, regardless of the presence or absence of diabetes  and death from any cause. Results from the study highlighted a lower rate of CV death or hospitalization for heart failure and renal outcome in patients treated compared to the ones treated with placebo  and death or hospitalization for heart failure. Secondary outcomes were a renal composite  blockage and presented both albuminuria and an eGFR of 30 to <90 ml/min per 1.73 m62 years .In 2020, Bhatt et al. conducted a study to evaluate the effects of sotagliflozin on CV and renal events in patients with T2DM and moderate renal impairment (SCORED). The trial aimed to verify whether sotagliflozin was non-inferior to placebo in terms of heart failure events. SCORED was a multicenter, double-blind trial that enrolled T2DM patients with chronic kidney disease and CV risk. Patients were randomized 1:1 to receive sotagliflozin or placebo. Due to a loss of funding, the trial ended up early. However, results showed that sotagliflozin was able to reduce the risk of death for CV causes, in patients with diabetes and chronic kidney disease, with or without albuminuria .post hoc analysis among 231 participants from the eValuation of ERTugliflozin efficacy and Safety (VERTIS) renal trial affected by T2DM and stage 3 CKD. Patients were randomized 1:1 to receive ertugliflozin 5 or 15 mg daily or placebo. Clinical biomarkers have been measured at three time points: baseline, 26 weeks, and 52 weeks. The analysis included cardiac troponin, renin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), human erythropoietin (EPO), ACE, ACE2, and aldosterone. Results showed that plasma aldosterone was significantly higher at 26 weeks in patients treated with ertugliflozin. However, the effect was no longer significant at 52 weeks.Interestingly, SGLT2i might change CV biomarkers in patients with CKD and T2DM. Lawler et al. performed a On the contrary, NT-proBNP concentration was lower in patients treated with ertugliflozin at 26 and 52 weeks. Finally, the treatment with ertugliflozin did not cause any significant changes in cardiac troponin, EPO, ACE, ACE2, HbA1c, potassium, blood pressure, and eGFR. This study showed that the effects of ertugliflozin are maintained even in patients with moderate CKD . In VERTp < 0.001), regardless of the presence of diabetes. Moreover, the total number of hospitalizations for heart failure was lower in the treatment group compared to the placebo group   .Because of the benefits demonstrated in renal and CV protection, SGLT2i are likely to be incorporated as part of the guideline-directed medical therapy (GDMT) .Several clinical studies have evaluated kidney outcomes in non-diabetic patients with and without heart failure.Recently, two trials have tested dapagliflozin and empagliflozin in a population of patients affected by heart failure with reduced ejection fraction (HFrEF). In both trials, patients were in stable clinical conditions, with an NYHA class mainly between II and III, LVEF ≤ 40%, high levels of NT-proBNP, and recommended medical therapy. In both trials, patients with and without diabetes were enrolled and, among secondary endpoints, kidney outcomes were evaluated.p < 0.001]. Analogously, in EMPEROR-reduced , whereas no significant reduction was observed when CV death  and death for all causes were analyzed. In both DAPA-HF and EMPEROR-reduced, the favorable effects of SGLT2i were significant in diabetic as well as in non-diabetic patients , compared with placebo, significantly reduced the primary combined endpoint , i.e., c-reduced , during patients .2) per year: absolute difference 1.73 (95% CI: 1.10–2.37); p < 0.001]. This could be due to the lower baseline eGFR in the EMPEROR-reduced trial population , body weight, blood pressure, and the concentration of neurohormonal biomarkers , stopped early due to data showing benefits, has shown that the use of dapagliflozin in patients with CKD, with and without type 2 diabetes, was associated with less progression of CKD, renal mortality, and all-cause mortality. As mentioned above, the primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. The primary outcome event occurred in 9.2% of patients treated with dapagliflozin and 14.5% of patients treated with placebo . Moreover, the hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56, and the one for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71. Finally, 4.7% of the participants in the treatment group and 6.8% of the patients in the control group died. It is worth mentioning that all patients received ACE inhibitor/ARB and presented albuminuria. Thus, generalization to further categories of patients is needed. Nonetheless, this indication covers a broad range of patients with impaired kidney function and proteinuria, including patients with non-diabetic CKD .As reported above, SGLT2i showed numerous beneficial effects in different body locations, which extend beyond glycemic control. These beneficial effects include a reduction in body weight and blood pressure, and an improvement in uric acid concentration, oxidative stress, inflammation, and liver steatosis .Also, dapagliflozin has been investigated to evaluate organ protection in high-risk patients affected by COVID-19 , 82. In In 2020, Akuta et al. conducted a retrospective study among 7 Japanese patients with non-alcoholic fatty liver disease (NAFLD) and T2DM receiving long-term treatment with canagliflozin (100 mg/day). The study aimed to determine the long-term effects of SGLT2i in NAFLD patients in the clinical outcomes and the liver histopathology .During the study, liver biopsies were collected at the beginning of the trial, after 24 weeks, and after more than 1 year. As a result, the treatment with SGLT2i improved the scores of steatoses, lobular inflammation, ballooning, and fibrosis .In 2020, the COVID-19 pandemic challenged the global health system since SARS-CoV-2 may lead to the development of severe pneumonia and may cause multiorgan failure. Cardiovascular and kidney complications are the most common, leading to poor outcomes, including death .2 saturation of ≥94% on ≤5 L/min, a CXR finding c/w COVID-19, and ≥1 risk factor . Primary endpoints consisted of preventing respiratory, cardiovascular, renal, or death events and the recovery in terms of hospitalization and clinical status in case of organ failure.Since the important benefits showed by dapagliflozin in the cardio- and renal protection in patients with T2DM, the DARE-19 trial has been conducted. The study aimed to evaluate the organ protection provided by dapagliflozin in high-risk patients affected by COVID-19. DARE-19 was an international, multicenter, randomized, double-blind, placebo-control study, which involved hospitalized patients among the US, Brazil, Mexico, Argentina, India, Canada, and UK . InclusiIn this study, after the initial screening to confirm the COVID-19 diagnosis, patients were treated with dapagliflozin 10 mg or placebo once daily for 30 days, in addition to the local standard therapy. All patients had daily assessments until hospital discharge, death, or end of the 30-day treatment period, followed by a 60-day observational follow-up .Results showed that organ dysfunction or death occurred in 11.2% of the patients treated with dapagliflozin and 13.8% of the patients included in the placebo group (hazard ratio 0.80). Moreover, 87.5% of the patients in the dapagliflozin group and 85.1% in the placebo group showed clinical status improvement .In conclusion, the study showed that numerically fewer patients treated with dapagliflozin experienced organ failure and death and that dapagliflozin was well-tolerated, allowing the use of SGLT2i even in a setting of COVID-19 .SGLT2i are generally well tolerated . Table Urinary tract infections (UTIs) are a common side effect among SGLT2i, and they are frequently observed during treatments with other glycosuric drugs . In 2015Genital infections are mostly related to increased urinary glucose excretion . The EMPFournier’s gangrene is a severe necrotizing infection of the external genitals and perineum that often requires a complex surgical approach, with a fatal prognosis in 7.5% of patients. Since their approval, several authors have reported cases of Fournier gangrene in subjects treated with SGLT2i . HoweverSurprisingly, in the CANVAS study, canagliflozin was associated with a double risk of foot and leg amputations . Volume During the CANVAS study, an increased risk of non-vertebral fractures, mainly of the limbs, emerged with canagliflozin already after 3 months of treatment. This result has not been confirmed in CANVAS-R or in DECLARE TIMI-58 , 70. FolThe scientific literature agrees on the increased risk of diabetic ketoacidosis associated with treatment with SGLT2i. However, a small number of events have been reported .Moreover, some potential deleterious events on kidney function have been reported, such as the SGLT2i impact on electrolyte balance in exposed subjects .In conclusion, SGLT2i showed a good safety profile. The knowledge of possible adverse events must guide the clinician in identifying those at increased risk and, where possible, intervene on modifiable risk factors, educate the patient to implement effective prevention, and ensure adequate follow-up for the early identification of side effect .2.According to the growing evidence that highlights the benefits of SGLT2i, various scientific societies have gradually updated guidelines and acts of direction, progressively expanding the indications of using these molecules. According to the new Standards of Medical Care in Diabetes 2021 of the American Diabetes Association (ADA), metformin remains the first-line therapy in the diabetic subject, also nephropathic, without prejudice to conditions of intolerance or adverse reactions and for GFR > 30 ml/min/1.73 mNowadays, SGLT2i are also indicated in subjects where metformin has earned a good glycometabolic compensation, therefore even when HbA1c is targeted. In addition, whereas previously, the use of these molecules was recommended in the presence of heart failure, chronic kidney disease, and/or atherosclerotic vasculopathy, the existence of CV risk factors that pose a high risk is now sufficient. In people with diabetes with CKD, SGLT2i are preferred to GLP-1 agonists due to stronger evidence in terms of slowing the decline of GFR. In fact, GLP-1 agonists have reduced albuminuria and the risk of composite renal endpoints, while the effects on GFR are controversial , 95.Since the CV and renal benefits from SGLT2i are only to a small extent attributable to the improvement of blood glucose control, it has been hypothesized that even non-diabetic subjects with CV pathology and/or MRC can benefit from this therapy .In parallel with DAPA-HF, DAPA-CKD was a randomized, double-blind, placebo-controlled trial that also recruited diabetic and non-diabetic patients, as mentioned above. Arguably, obesity-induced CKD, which recognizes glomerular hyperfiltration as one of the main pathogenic factors, could benefit from the use of SGLT2i , 98.In this direction, DAPA-HF was the first trial with SGLT2i to recruit non-diabetic subjects as well, assessing the effectiveness of dapagliflozin in the treatment of heart failure, in addition to the standard of care. Dapagliflozin emerged as a powerful therapy, with an excellent safety profile and a great efficacy even in subjects without DM . AccordiBased on the currently available data, SGLT2i show important benefits at the socio-health and pharmacoeconomic levels. In fact, although their cost is higher compared to other hypoglycemics, the advantages are greater .Despite current measures against DM, the residual risk of ESKD, CV morbidity, and mortality remain high. SGLT2i have shown very promising results on renal outcomes and good safety profile. Therapeutic efficacy, tolerability, and costs support the broad use of these drugs in the diabetic population. In addition, SGLT2i can be widely used even in non-diabetic patients, and patients with risk factors and/or CV disease, nephropathy to different etiopathogenesis, and up to the more advanced stages of CKD. Of course, the evidence in CKD patients is still relatively limited and additional data are needed to draw a robust conclusion.Further studies are needed to clarify any differences between different SGLT2i in CKD and between the different phenotypes . The SGLT2i represent another challenge to create an integrated management model and to apply therapeutic care diagnostic pathways, which lead to the involvement of a multidisciplinary team of professionals to ensure the optimization of the treatment and the follow-up management.All authors contributed to the research, development, and content of the manuscript.Editorial support was provided by Edra S.p.A. and unconditionally funded by AstraZeneca. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.MI received honoraria as a consultant in advisory boards from Astra Zeneca, Boehringer Ingelheim, Lilly, and Novartis. LG had provided research support for Abionyx and Sanofi; has served as a speaker for Fresenius, Estor, Werfen, Astellas, AstraZeneca, and Travere; and has served as a consultant for Sandoz, Sanofi, Baxter, Mundipharma, Estor, Pharmadoc, Retrophin, Travere, AstraZeneca, GSK, Novartis, and Chinook.The remaining 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Solitary functioning kidney (SFK) can be defined as the absence or hypofunction of a kidney due to acquired or congenital reasons. A congenital solitary functioning kidney (cSFK) is more common than is an acquired one (aSFK) and is characterized by the anatomical absence (agenesis) or hypofunction  of one kidney from birth. Among the acquired causes, the most important is nephrectomy (Nx) . Patients with SFK are at risk for the development of chronic kidney disease (CKD) in the long term. This risk potential is also significantly affected by hypertension. The relationship between hypertension and subclinical chronic inflammation is a connection that has not yet been fully clarified pathogenetically, but there are many studies highlighting this association. In recent years, studies examining different fibrosis and inflammation biomarkers in terms of the evaluation and prediction of renal risks have become increasingly popular in the literature. Oxidative stress is known to play an important role in homocysteine-induced endothelial dysfunction and has been associated with hypertension. In our study, we aimed to investigate the relationship between ambulatory blood pressure monitoring (ABPM) and urinary/serum fibrosis and inflammatory markers in patients with SFK. We prospectively investigated the relationship between ABPM results and soluble urokinase plasminogen activator receptor (suPAR), procollagen type III N-terminal peptide (PIIINP), homocysteine and other variables in 85 patients with SFK and compared them between cSFK and aSFK groups. In the etiology of SFK, a congenital or acquired origin may differ in terms of the significance of biomarkers. In particular, the serum homocysteine level may be associated with different clinical outcomes in patients with cSFK and aSFK. Congenital anomalies of the kidney and urinary tract (CAKUT) are responsible for nearly 30% of all prenatal anomalies. The CAKUT general rate in live and stillbirths, respectively, is 0.3 to 1.6 per 1000  and SFK In patients with SFK in an intact kidney, there can be a continuous increase in hyperfiltration, primarily to keep the glomerular filtration rate (GFR) at a stable level. Secondary to glomerular hypertension that develops over time, glomerular sclerosis develops, and a decrease in the number of healthy nephrons can be observed, which is an important risk factor for proteinuria and hypertension. The onset of compensatory renal hypertrophy, which has been described in patients with both cSFK and aSFK, is faster in patients with aSFK. With the reflex of remaining nephrons to provide a rapid stabilizing response to the sudden decrease in GFR, the glomerular workload increases and the progression to glomerulosclerosis and renal fibrosis accelerates.Hypertension is the leading cause of cardiovascular disease and premature death. As a result of the increasingly aging world population, it is predicted that the prevalence of hypertension will reach 1.5 billion people globally in 2025 . AccordiABPM has been accepted as the reference standard for the diagnosis of hypertension and is considered to be a better indicator of potential cardiovascular events compared to traditional office-based blood pressure measurements. Current guidelines state that ABPM should be preferable to office-based blood pressure measurements in diagnostic/screening examinations . StudiesIn patients with SFK, serious clinical conditions such as proteinuria, hypertension and progression to CKD may occur in the long term, requiring periodic follow-up . ControlsuPAR is the systemic circulating (soluble) form of a membrane protein expressed by immune and endothelial cells, fibroblasts, cancer cells and vascular smooth muscle cells. suPAR serum levels reflect immune and inflammatory activation and are correlated with well-known inflammatory markers such as CRP and IL-6. It has been stated that it may play a role in the etiopathogenesis of renal diseases. It has been shown in a large cohort study that high levels may be associated with CKD progression .The relationship between hypertension and serum homocysteine has been evaluated in many studies, although it is not clear from a pathogenetic perspective. Specifically, homocysteine can induce oxidative stress in endothelial cells by mediating the production of reactive oxygen species or by impairing the antioxidant system . As a reOur hypothesis was that when we compare patients with SFK etiologically , markers such as ABPM, homocysteine, PIIINP and suPAR levels may differ in predicting renal risk factors. The fact that most studies conducted in this population have evaluated patients with SFK holistically in a heterogeneous manner and that the comparisons between congenital and acquired groups did not go beyond traditional risk factors led us to this study. The aim of our study was to review the hypertension control with ABPM measurements in patients with solitary kidneys who are routinely followed up in our center, to evaluate their renal functions and to evaluate the relationship of urinary/serum fibrosis and inflammatory markers with these parameters and other clinical and routine laboratory findings.This was a prospective, observational, cross-sectional study. Patients with SFK followed in nephrology outpatient clinics were included in the study, which was carried out between 1 June 2023 and 1 September 2023. After ethics committee approval was obtained, demographic, chronic disease and medication data of the volunteers who wanted to participate in the study and met the inclusion criteria were recorded. The diagnosis of solitary kidney was made using an abdominal ultrasonography + scintigraphy and/or abdominal computed tomography protocol. Routine biochemical examinations, hemogram and hemogram sub-parameters, 24 h urine protein, albumin, sodium, and potassium excretion, and PIIINP and suPAR were also measured in the same 24 h urine samples. Urine samples in Eppendorf tubes were stored at −80 °C until the period of study. ABPM measurements were made. Laboratory findings and their relationships with demographic data and ambulatory blood pressure results were investigated.The study population consisted of patients between the ages of ≥18 and <80, who were followed up in the adult nephrology outpatient clinic, had URA/hypoplasia and unilateral Nx, and did not receive renal replacement therapy. Patients with active solid organ and hematological malignancy , dementia or Alzheimer’s disease, acute or chronic liver disease, cerebrovascular disease, acute kidney injury, physical disability, coronary artery disease, heart failure, active infection, and those who were incompatible with ABPM measurement, aged <18 years and ≤80 years and active smokers were not included in the study.suPAR (Cat# E3759Hu) and N-terminal procollagen 3 propeptide (Cat# E1353Hu) concentrations were measured in 24 h urine samples using human-specific enzyme-linked immunosorbent assays (ELISA)  in accordance with the instructions of the manufacturer. suPAR assay sensitivity was 3.82 ng/L with inter-assay and intra-assay coefficients of variation of less than 10%. PIIINP assay sensitivity was 31.2 ng/L with inter-assay and intra-assay coefficients of variation of less than 10%. Measurements were performed on a Thermo Scientific Multiskan GO ELISA plate reader . The working principle of the ELISA kit is enzyme-linked immune sorbent analysis (ELISA) based on Biotin double-antibody sandwich technology. The sample was added to wells pre-coated with monoclonal antibody and then incubated. Biotin-labeled antibodies formed a complex with streptavidin-HRP. After incubation, the unbound conjugate was washed away. The color intensity formed after adding the substrate solution was measured at 450 nm and the concentrations were calculated using the calibration chart drawn in accordance with the standards. Protein and albumin concentrations in 24 h urine samples were determined using colorimetric methods on a COBAS 8000 (c702) biochemical analyzer .2).Demographic and epidemiological  parameters, comorbid conditions (diabetes and hypertension), a history of nephrolithiasis, etiology in patients with Nx, and the number and group of antihypertensives were examined. Body mass index (BMI) was calculated as weight (kg)/height ). Measurements were taken every 30 min during the day (06:00–21:59) and every 60 min at night (22:00–05:59). Appropriate-sized BP cuffs were used for ABPM. The daily routine activities of the patients were not restricted. Necessary information was given about sleep/wake schedules. BP-recorded readings exceeding 75% of the expected measurements were considered for analysis in accordance with the European Society of Hypertension guidelines [ABPM measurement was performed with a previously validated device ,11 . The minimum sample size required to test the correlation between 24 h arterial blood pressure measurement parameters and urinary type PIIINP and suPAR levels, with a significance level of 0.05 and 80% power under the one-way hypothesis test, 0.25 in the Ho hypothesis and 0.5 in the alternative H1 hypothesis, was calculated as 74. Considering the missing data, a total of 80 people was found to be sufficient.n (%). The compliance of the data with normal distribution was evaluated using the Kolmogorov–Smirnov test. Student’s t test and the Mann–Whitney U test were used for the comparison of the normally distributed and non-normally distributed data, respectively. The ANCOVA test was used for age adjustment in parametric data. The chi-square test was used to compare qualitative variables. Spearman’s correlation coefficient was used to evaluate the correlation analysis due to the concomitance of the non-normally distributed data. Backward multiple linear regression analysis was applied on correlated variables. A p value of <0.05 was considered significant.The SPSS-22 program was used for statistical evaluation. Quantitative data were expressed as mean ± standard deviation or median (minimum–maximum), and qualitative data were shown as Permission was obtained from the local University Faculty of Medicine Health Sciences Ethics Committee, dated 1 June 2023 and allocated as no. 12/XIII. All procedures performed in human studies were carried out in accordance with the ethical standards of the institutional and/or national research committee, as well as with the Declaration of Helsinki (1964) and its later amendments or comparable ethical standards. Each patient was informed about inclusion in the study, and their consent was obtained.We evaluated 85 patients with SFK, aged between 19 and 80 years old, who were being monitored in the nephrology outpatient clinics at Muğla Sıtkı Koçman University Faculty of Medicine, Training and Research Hospital. We divided them into two groups: congenital and acquired. The basic demographic characteristics of the patients are shown in p < 0.001) had a history of nephrolithiasis. There was no significant difference in terms of healthy kidney parenchymal thickness. The frequency of hypertension was similar in both groups.There was no difference between the two groups in terms of variables such as gender and BMI. Those with Nx(+) were significantly older. Of all the patients, 20 (23.5%)  inhibitors, 22.4% were using thiazides, 31.8% were using calcium channel blockers, 23.5% were using beta blockers and 2.4% were using alpha blockers.Laboratory test results comparing the two groups are shown in The results were similar between groups. PIIINP and suPAR levels were higher in Nx(+) patients, and natriuria was higher in the Nx(−) group, although it was not statistically significant.The correlation between age and GFR, some ABPM symptoms, BMI, CIMTs and the number of antihypertensives is shown in Newly diagnosed hypertension was detected in 4 of 27 patients (14.8%) who were not previously diagnosed with hypertension. High arterial blood pressure was detected in 34.5% of those under treatment with a diagnosis of hypertension. While arterial blood pressure was non-regulated in 25.7% of those with Nx(+), it was non-regulated in 30% of those with Nx(−).The ABPM results and CIMT results of the patients according to the groups are shown in According to ambulatory systolic blood pressure measurements, among those with Nx(+), 28 patients (80%) were in the non-dipper (ND + RD) group and 7 patients (20%) were in the dipper group. Among those with Nx(Nx(−), 42 patients (84%) were in the non-dipper (ND + RD) group and 8 patients (16%) were in the dipper group. According to ambulatory diastolic blood pressure measurements, among those with Nx(+), 25 patients (71.4%) were in the non-dipper (ND + RD) group and 10 patients (28.6%) were in the dipper (dipper + ED) group. Among those with Nx(−), 33 patients (66%) were in the non-dipper (ND + RD) group and 17 patients (34%) were in the dipper (dipper + ED) group. There was no significant relationship between Nx(+) and Nx(−) patients in terms of ABPM and CIMT measurements, except for a higher mean SD in Nx(−) patients .p = 0.004, r: 0.312; p = 0.012, r: 272; p = 0.008, r: −0.286). meanDiast was correlated with BMI and age . When we compared the two groups, in Nx(+) patients, there was a positive correlation between BMI and CRP and CRP/alb, and a negative correlation between that and alb/glob . In Nx(−) patients, there was a significant correlation between BMI and UA, CRP, homocysteine, proteinuria, albuminuria, meanSyst, 24 hMAP, pulse pressure, dSyst, dMAP, nSyst, nMAP and CRP/alb .There was a positive correlation between meanSyst and BMI and age, and a negative correlation between that and GFR decline . This was a finding we encountered for the first time in the literature. (p = 0.02 r: −0.251). While there was a significant negative correlation between suPAR and nDiast in those with Nx(+), the significance disappeared in those with Nx(−) (see p = 0.026) and nORT  were found to be the main determinants. Additionally, when variables correlated with homocysteine were evaluated in multiple linear regression analysis in Nx(−) patients, eGFR  and pulse pressure  were found to be the main determinants.PIIINP levels and suPAR levels measured in 24 h urine showed a strong correlation in the same direction in both groups (erature. . While tx(−) see . When vaIn those with Nx(−), homocysteine had an inverse correlation with eGFR, albumin and Alb/Glob, and a significant correlation with BMI, UA, proteinuria, albuminuria, meanSyst, pulse pressure, dSyst, nSyst, CIMTr and the number of antihypertensives. In Nx(+) patients, there was only an inverse correlation with eGFR and Alb/Glob .p = 0.013 r: −0.269; p = 0.013 r: 0.270). There was a significant relationship between CRP/albumin and proteinuria, albuminuria, meanSyst, meanDiast, MAP, pulse, dSyst, dDiast, dMAP, nSyst, nDiast and nMAP .There was a significant negative correlation between Alb/glob and CIMTr and between neutrophil/platelet and CIMTr , neutrophil count , proteinuria (p = 0.000 r: 0.395), albuminuria , natriuria , meanSyst (p = 0.022 r: 0.248), meanDiast , MAP  and pulse (p = 0.026 r: 0.241), and an inverse correlation with albumin .CRP showed a significant correlation with BMI . There was a negative correlation between 25 OH Vitamin D and natriuria  and natriuria/kaliuria  in those with Nx(+), whereas there was a negative correlation between 25 OH Vitamin D and dMAP (p = 0.021 r: −0.336) in those with Nx(−).There was a negative correlation between serum 25 OH Vitamin D and BMI, proteinuria, dMAP and natriuria/kaliuria , albuminuria  and diastolic SD .There was a significant correlation between natriuria and proteinuria , proteinuria , albuminuria  and CIMTr , and an inverse correlation with GFR . In Nx(+) patients, UA was inversely correlated only with alb/glob . In those with Nx(−), UA was significantly correlated with BMI , homocysteine , proteinuria , albuminuria , CIMTr  and CIMTl , and inversely correlated with GFR .Serum uric acid (UA) levels had a significant correlation with homocysteine ; CRP ; proteinuria ; meanSyst ; meanDiast ; MAP ; dSyst ; CIMTl ; and the number of antihypertensives . It was inversely correlated with GFR  and 25 OH Vitamin D .The BMI mean value was 28.3197 ± 4.69408 kg/mDuring the nephrogenesis process, renal anomalies may occur due to genetic changes, environmental factors and nutritional effects. The frequency of urogenital anomalies is approximately 1–3/500 live births. This accounts for 40–50% of pediatric CKD cases . In unilAs the number of functioning nephrons decreases in patients with SFK due to both acquired and congenital causes, physiological adaptive changes secondary to renal compensation—such as an increase in single-nephron GFR, an increase in filtration fraction, an increase in intra-glomerular pressure and an increase in renal blood flow—can occur. These changes are referred to as the hyperfiltration response. The aim is to maintain a stable GFR for a while, but in the long run, as a result of these hemodynamic changes, varying degrees of glomerulosclerosis, proteinuria, hypertension and chronic kidney damage develop in the kidneys. In this context, Srivasta et al. demonstrated in rats that glomerular hyperfiltration leads to an increase in fluid flow shear stress (FFSS) on podocytes in conditions characterized by a decrease in the number of nephrons. They emphasized that FFSS also potentiates podocyte damage and CKD progression .2 was 37%. In total, 72% of the patients had < 150 mg/day of proteinuria; 30–300 mg/day of albuminuria in 24 h urine was detected in 23 patients; and 300 mg/day < of albuminuria was detected in 23 patients. In total, 68.2% patients had hypertension. Compared to other series, the frequency of hypertension and proteinuria/albuminuria was higher in our study population. Oldrizzi et al. found that the prevalence of hypertension was 40%, the prevalence of proteinuria was 46% and the prevalence of renal dysfunction was 15% in 39 patients with URA, with a mean age of 33 years [CKD is a progressive, irreversible clinical condition that can lead to many serious complications throughout life, especially cardiovascular abnormalities. According to 2019 reports, the number of deaths caused by CKD was 1.4 million (11th) and the percentage of deaths due to CKD among all the causes of death was 2.5%. Patients with SFK are considered to be in the risk group for CKD due to the frequent occurrence of hypertension, especially in the long term, and due to the pathophysiological conditions that may occur in a solitary kidney. Sanna-Cherchi et al.’s clinical follow-up study on this subject is very important in terms of taking this risk into consideration. The study showed that 20–50% of 312 children who had SFK (only patients with CAKUT) in childhood developed ESRD in their third decade . In our 33 years . In anot33 years . However33 years . A signi33 years .In the current approach, in SFK patients, in addition to traditional renoprotective approaches, there is a need for markers based on biochemical or technical measurement methods that have predictive potency and can detect possible differences according to SFK etiologies.Hyperfiltration is the main player at the beginning of the scenario that includes all abnormal glomerular changes in patients with SFK. According to the study of Cachat et al., urinary albumin showed a weak relationship with hyperfiltration markers in patients with SFK (19% was Nx(+)), and it was suggested that factors other than glomerular hyperfiltration may contribute to the development of CKD . In SrivAcute reduction—such as nephrectomy—in kidney mass has a variable effect on renal function compared with that under congenital etiologies. The most important point here is the timing of the decrease in renal mass. There may be significant differences in the expression of renal pathologies between those with congenital and acquired SFK; while cSFK still has the potency of ongoing new nephron formation, nephrogenesis is stopped during Nx in aSFK. This finding may imply a higher sensitivity to significant glomerular hyperfiltration in those with aSFK . Sudden Spira et al. argued that one of the main differences between congenital/acquired SFKs that aSFKs is that the latter have a lower number of nephrons to compensate for hyperfiltration and hypertrophy than in congenital conditions . SurgicaLenihan et al. showed that glomerular hyperfiltration was not accompanied by a significant increase in glomerular pressure in adult kidney donors. Similarly, it was shown that glomerular capillary pressure increased minimally in adult rats. In contrast, nephrectomy in newborn guinea pigs, where nephrogenesis ceases before birth, resulted in a 30% increase in glomerular filtration pressure ,33. ThesIn various animal models where kidney mass decreases during nephrogenesis, the number of nephrons in the SFK increased by 4% to 50%. Larsson et al. showed that when renal mass decreases during active nephrogenesis in rats, the level of glomerular hyperfiltration doubles compared to that later in life . AlthougIn a large cohort study of over 270,000 young to middle-aged individuals without CKD at the baseline and with an average follow-up of nearly 5.5 years, SFK was independently and modestly associated with an increased risk of CKD, and CKD risk was higher in those with aSFK than in those with cSFK . SimilarThe KIMONO study also found that SFK due to acquired kidney loss in childhood was associated with a higher incidence of kidney damage compared with that under congenital loss . In YazıGadalean et al. showed that in patients with congenital renal mass reduction, adaptive tubular changes occur earlier than they do in those with acquired ones, thus leading to better renal outcomes . Bohle eHomocysteine may not be the same potential risk factor between aSFK and cSFK patients. Homocysteine is a non-proteinogenic, sulfhydryl-group-containing, non-essential intermediate amino acid formed during the conversion of methionine, a sulfur-containing, essential amino acid, into cysteine. As an established risk factor for hypertension, hyperhomocysteinemia is positively associated with blood pressure. Fu et al. found that the average homocysteine concentration was higher in hypertensive patients than that in non-hypertensive patients, and revealed a reasonable relationship between high homocysteine levels and an increased risk of hypertension . It has Homocysteinemia can occur in the early stages of CKD and increases with the progression of kidney damage. The positive correlation of the plasma homocysteine level with the creatinine level has been shown in one study . In our In one study, homocysteine was associated with a non-dipping pattern, a strong predictor of cardiovascular mortality and morbidity in hypertensive individuals . AlthougABPM is a simple, non-invasive examination that can be used to monitor a patient’s blood pressure at different time points over a 24 h period, as well as to detect the circadian rhythm of blood pressure, blood pressure variability and morning peak blood pressure. Many studies have shown that a higher BP in ABPM is a stronger predictor than is office BP in predicting target organ damage and CVD events . In the In healthy conditions, arterial blood pressure exhibits a circadian rhythm, with blood pressure falling by 10% to 20% during nocturnal sleep due to a decrease in sympathetic tone and a parallel increase in vagal activity during the sleep period. This nighttime decrease is called normal dipping (Dipper pattern). When the nocturnal drop in blood pressure during sleep becomes blunted or disappears (<10% of the daytime blood pressure level), this is called non-dipping (NonDipper pattern). When nocturnal blood pressure during sleep rises above awake levels, this is called reverse dipping (Reverse Dipper/Risers). When the nocturnal drop in blood pressure is severe (>20% of the daytime blood pressure level), this is called extreme dipping (ED pattern). In the ESH/ESC Hypertension 2023 guideline, ABPM/HBPM is recommended with strong evidence for the evaluation of nocturnal hypertension  and monitoring when evaluating treatment strategies in CKD patients, since the ND pattern or increased nocturnal BP is common .Night values of SBP ≥ 120 mmHg or DBP ≥ 70 mmHg were considered nocturnal hypertension in most studies. Isolated nocturnal hypertension  has been shown to have a significantly higher risk of cardiovascular events compared to that under normotension, while another study has also shown it to be associated with hypertension-induced target organ damage ,53. VinyIn our study, the serum homocysteine level did not generally correlate with ABPM measurements. In addition, although there was no significant difference in concentration between the Nx(+) and Nx(−) groups, there was a significant positive correlation with mSys, PP, dSys and nSYS in Nx(−) groups. This correlation was not present in those with Nx(+). In addition to this significant relationship in hypertension parameters, pulse pressure was also significantly higher in these patients. High ambulatory pulse pressures have also been shown to be associated with cardiovascular morbidity and mortality . CurrentuPAR is a membrane receptor protein produced in the podocytes, endothelium and immature myeloid cells. Activated uPAR can be degraded and detected in systemic circulation in its soluble form, suPAR (glycosyl-phosphatidyl inositol anchored 3-domain membrane protein). uPAR/suPAR can cause glomerular damage in podocytes via the αvβ3 integrin pathway . ConcentSystemic chronic inflammation is a central problem for many diseases and clinical conditions. suPAR is a potential biomarker that reflects the state of chronic inflammation  and is relatively stable  . It is pThere are conflicting publications regarding the predictive potency of suPAR in CKD progression ,63. In aFunctional adaptations secondary to a decrease in renal mass include intrarenal vasodilation, leading to increased glomerular capillary pressure and hyperperfusion injury to the glomeruli. This process leads to glomerular cell proliferation, the infiltration of macrophages, and the progressive accumulation of components such as fibronectin, collagen type I and type III, and decorin. This non-immunological process can lead to damage being sustained to podocytes and the glomerular microvasculature, leading to proteinuria, widespread fibrosis and a progressive deterioration in renal function. In a normal kidney, interstitial type III collagen expression is small in proportion; however, in scarred kidneys, the expression of collagen type III increases in the interstitium during the earliest stages of fibrosis, and PIIINP accumulates in sclerotic glomeruli. During the synthesis and deposition of type III collagen, an amino terminal pro-peptide of type III collagen, called the N-terminal pro-peptide of type III collagen, is produced. During the processing of pro-collagen prior to its deposition in the ECM, a portion of PIIINPs are cleaved and released into the ECM and fluids, including blood and urine.El Ghoul et al., in their prospective, non-SFK study of 199 individuals, showed an inverse correlation between UPIIINP/Cr and eGFR and a significant correlation with renal fibrosis . In a stIn our study, unlike in the literature, we examined PIIINP levels in 24 h urine, not in spot urine samples. We could not show a relationship with GFR decline, but a significant inverse correlation with nighttime ABPM measurements and meanSyst in the Nx(+) group was a finding encountered for the first time in the literature. In the study by Söylemezoğlu et al., although urinary and serum PIIINP levels showed a strong histopathological correlation with the degree of renal fibrosis, no correlation was found between them and creatinine values . AlthougIncreased CIMT is associated with higher blood pressure and an increased left ventricular mass index. Its predictive significance for the risk of developing atherosclerosis and cardiovascular disease is well established. In our study, CIMT showed a relationship with variables such as age, BMI and UA, as expected. In group analyses, there was no significant difference between Nx(+)/Nx(−). However, in Nx(−) patients, homocysteine was correlated with CIMT. This significance in terms of atherosclerotic clinical outcomes in Nx(−) patients may be a guide for future studies.As shown in a retrospective study, BMI was likely a factor associated with the progression of renal function loss in patients with a single kidney . In a poAs a result, with the improvement in medical conditions, more and more children with congenital renal disease are surviving and reaching adulthood. However, the number of renal donors is also increasing. This shows us that we will encounter possible nephrological complications in patients with SFK more frequently. Hypertension target values should be determined especially in this patient group and should be included in hypertension guidelines. In line with the current literature, it seems rational for ABPM to become a priority in hypertension screening and monitoring treatment response in patients with SFK. In our study, the high rate of patients who were aware of their hypertension or whose course was unregulated even while under antihypertensive treatment supports this. Our study also showed that although there is no difference in ABPM findings between patients with Nx(+) and Nx(−), there may be various differences in markers that correlate with ABPM findings.Our study has some limitations. In terms of patient selection, our hospital is the main tertiary referral hospital in our region. Almost all SFK patients (with or without nephrectomy) are referred to our nephrology out-patient clinic . We have many SFK patients in our routine follow-up list. Hence, in accordance with the inclusion/exclusion criteria, we selected these patients. Furthermore, regression analysis results may be of limited value. The number of patients in our study was small. We think this is due to the broad scope of inclusion and exclusion criteria. Additionally, it was a disadvantage that it was a single-center study. We could not provide an etiological explanation for six patients with nephrectomy due to lack of documentation. Another limitation was that there was also no widely accepted consensus on GFR measurement in patients with SFK ,75. In oIt would be informative if future studies on the population of SFK patients are able to predict inflammatory, fibrotic and cardiovascular risk markers among different etiologies of this group. Studies to develop preventive strategies for long-term complications in this patient group are important. Developing similar guidelines for adults as well as pediatric patients may be instructive . The phoNx(+) or Nx(−) status may change the clinical approach when evaluating patients with SFK. To the best of the authors’ knowledge, although our study population is small, it is the first study to evaluate the correlations of ABPM measurements with biomarkers such as 24 h urinary PIIINP, serum homocysteine and 24 h urinary suPAR by grouping patients with SFK as Nx(+)/Nx(−). Serum homocysteine levels may play a key role in the renal and cardiovascular outcomes of patients with cSFK and aSFK.