Renal Denervation in the Treatment of Resistant Hypertension and Difficult-to-Control Hypertension - Consensus Document of the Croatian Hypertension League - Croatian Society of Hypertension, Croatian Cardiac Society, Croatian Endovascular Initiative, Croatian Society for Diabetes and Metabolic Diseases, Croatian Renal Association, and Croatian Society of Family Physicians of the Croatian Medical Association.

Renal denervation (RDN) as a method of treating arterial hypertension (AH) was introduced in Croatia in 2012. A multidisciplinary team and a network of hospitals that diagnose and treat patients with severe forms of AH were established, and a very strict diagnostic-treatment algorithm was prepared. At monthly meetings patients with truly resistant hypertension who were candidates for RDN were discussed. According to the 2021 ESH position statement and 2023 ESH guidelines, RDN is considered an alternative and additional, not a competitive method of treating patients with various forms of AH which must be performed by following a structured procedure and the patient's preference should be considered. In view of the changes in the global scientific community, the Croatian Hypertension League brings this consensus document on RDN conducted with radiofrequency-based catheter, the only currently available method in Croatia. In this document, exclusion and inclusion criteria are shown, as well as three groups of patients in whom RDN could be considered. The new diagnostic-treatment algorithm is prepared and follow-up procedure is explained. In Croatia, RDN is reimbursed by the national insurance company, thus pharmacoeconomic analyses is also shown. Criteria required by an individual centre to be approved of RDN are listed, and plans for prospective research on RDN in Croatia, including the Croatian registry for RDN, are discussed.

Association of multiple retinal nodular hamartomas and "confetti" skin lesions with end-stage renal disease in patients with tuberous sclerosis.

PURPOSE: The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease. METHODS: This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods. RESULTS: This study enrolled 48 patients with a median age of 32.3 years (range, 18-46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis-83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (p-0.033 and 0.03, respectively). CONCLUSION: Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.

UROMODULIN - A LINK BETWEEN SODIUM EXCRETION AND ALTERATION IN CIRCADIAN BLOOD PRESSURE PATTERN IN PREHYPERTENSIVES.

Although changes in dietary sodium intake alter blood pressure (BP) in salt-sensitive individuals, pathophysiological mechanisms are still unknown. It has been reported that uromodulin is involved in sodium tubular transport, and genome-wide association studies pointed to UMOD gene as one of the most important gene candidates for arterial hypertension. Our aim was to analyze urinary uromodulin, salt intake and BP in 326 young middle-aged subjects (mean age 36±8 years, 49.4% male). In a subgroup of 175 individuals, ambulatory blood pressure monitoring and echocardiogram were performed. Uromodulin was determined by ELISA. According to the JNC-7 criteria, subjects were classified as optimal BP (n=103, men 72%), prehypertension (PHT) (n=143, men 43%) and hypertension (HT) (n= 80, men 38%). There were no differences in age, salt intake, estimated glomerular filtration rate, sodium excretion and uromodulin among BP groups. However, in PHT subjects, uromodulin was positively associated with fractional sodium excretion and negatively with 24-h sodium excretion and diastolic BP dip. These findings point to the effect of uromodulin on sodium reabsorption along the nephron and consequently circadian BP alteration in prehypertensives.

CHRONIC KIDNEY DISEASE IN RURAL POPULATION.

The aims of the study were to provide data on chronic kidney disease (CKD) prevalence in rural population and to analyze the association with cardiovascular risk factors and aging. A random sample of 2193 farmers (1333 female (F) and 860 male (M), mean age 50.61±17.12) were enrolled. Questionnaire and clinical examination were conducted. Participants provided a spot urine and fasting blood sample. Estimated glomerular filtration rate (eGFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Subjects were classified according to the KDIGO guidelines. The overall prevalence of CKD (eGFR <60 mL/min/1.73 m2) was 8.83% (F vs. M 9.9% vs. 6.3%; p<0.001). Albuminuria (albumin-to-creatinine ratio >30 mg/g) was found in 8.45% (F vs. M p>0.05). Sharp increase in CKD prevalence was found to begin after the sixth decade (29.44% in subjects older than 65 years; F vs. M 30.9% vs. 26.8%; p<0.01). The strongest predictor factors for CKD were age >65 years (OR 22.12), hypertension (OR 6.53), albuminuria (OR 5.71), fasting blood glucose >7 mmol/L (OR 5.49), diabetes (OR 3.07), abdominal obesity (OR 2.05) and non-smoking (OR 0.41). In multivariate analysis, age (OR 1.13), female gender (OR 0.60) and diabetes (OR 1.75) were the independent predictor factors for CKD. In conclusion, CKD prevalence is high in rural population, being higher in women than in men. In both genders, eGFR significantly decreased with aging. Aging is a significant independent predictor of CKD.

EFFECTS OF OCCUPATIONAL STRESS ON THE ACTIVATION OF HEMOSTATIC AND INFLAMMATORY SYSTEM.

A 24-hour shift is one of the major stressors for physicians because, apart from causing fatigue and circadian rhythm disorders, it often requires making vital decisions for patients within a short time frame. It is known that workplace stress leads to the activation of the coagulation system, which can result in imbalance of the coagulation and fibrinolysis system. The state of stress can also generate proinflammatory mediators. The aim of this study was to examine the effect of 24-hour shift on global coagulation tests of D-dimers and fibrinolysis, and on C-reactive protein (CRP) as an acute inflammatory agent and proatherosclerotic factor. Sixty physicians (residents) aged 25-35 participated in this study (30 participants in the experimental group and 30 participants in the control group). In experimental group, blood samples were collected on three occasions: shortly before 24-hour shift, twelve hours after the shift had begun, and at the end of the shift. Blood samples were collected from control group participants at the same time points. The results showed that there was no statistically significant difference in the values of D-dimer and fibrinolysis between the experimental and control groups. CRP values were statistically significantly higher in the experimental (1.57, 1.49 and 1.50) than in the control group (0.79, 0.75 and 0.84) on all three measurements (p=0.024, p=0.020 and p=0.030, respectively). These results confirmed the existence of proinflammatory changes in the endothelium of blood vessels, which is a factor associated with accelerated atherosclerosis.

Forearm bone mass predicts mortality in chronic hemodialysis patients.

We aim to determine the relationship between bone mineral density (BMD), measured by T- and Z-score, and mortality risk in hemodialysis (HD) patients. We also investigate which are the most suitable skeletal sites for predicting mortality rate. We analyzed the survival of 102 patients who had been treated with chronic HD according to BMD. Patients with a T-score ≤2.5 at the middle, ultradistal and proximal part of the forearm had a higher mortality risk than those with a T-score of -2.5 or higher. Furthermore, no statistically significant association was found between loss of bone mass at other measuring points-lumbar spine (anteroposterior orientation from L1-L4) and hip (neck, trochanter, intertrochanter, total and Ward's triangle)-and mortality risk. We were also interested in exploring the relationship between Z-score at different skeletal regions and mortality risk. We found that patients with a Z-score of -1 or lower at all three parts of the forearm had a greater mortality risk. It is also worth noting that the Z-score at all three parts of the forearm was a more apparent predictor of mortality, compared to the T-score at the same skeletal regions. This empirical analysis showed that BMD assessments should be obtained at the forearm, due to the good predictability of this skeletal site regarding mortality of HD patients. Moreover, data concerning bone density should be reported as Z-scores.

Vitamin d in the patients with chronic kidney disease: when, to whom and in which form.

Alteration in vitamin D metabolism has a central role in the pathogenesis of secondary hyperparathyroidism (SHPT) and is also associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). For more than sixty years, vitamin D, nutritional vitamin D (ergocalciferol, cholecalciferol or calcifediol) and nonselective vitamin D receptor (VDR) activators (calcitriol, alfacalcidol) have been used in the prevention and treatment of SHPT. In the last twenty years, selective VDR activators (paricalcitol, maxacalcitol) have been used to target SHPT. However, there are many open questions regarding use of nutritional vitamin D or VDR activators. The K/DOQI and KDIGO guidelines recommended testing for vitamin D insufficiency and deficiency in patients with CKD, but there is no consensus on the definition of vitamin D insufficiency in CKD. There are a many open questions, for example, regarding the optimal nutritional vitamin D type and the dose and co-administration of nutritional vitamin and VDR activators. Therapy with VDRAs is required in the majority of patients with CKD, particularly in dialysis patients. However, when to start with VDRAs is not so apparent. Is PTH level the only indication of when to start therapy? Although VDRAs are very effective in lowering PTH levels and bone metabolism the effect of patients mortality is not so straightforward. Despite many unanswered questions, there is a large body of experimental and clinical data to support vitamin D use in patients with CKD. To obtain answers to the open questions, we need more randomized controlled trials.

Ambulatory blood pressure monitoring in diabetic hypertensive patients, single center report--preliminary results.

ABPM (ambulatory blood pressure monitoring) has been considered to be a useful tool for the diagnosis and management of arterial hypertension and is a better predictor of future cardiovascular events as compared with conventional office-based BP measurements. Despite its potential values, ABPM is not yet widely used in many clinical offices mainly because of lack of knowledge and unavailability. Aims of this preliminary study are to determine the control of hypertension and circadian BP characteristics in patients referred to our Centre whom we enrolled in the "HRKMAT" Study-Croatian Registry of ABPM. Although patients included in HRKMAT Study had other risk factors for cardiovascular diseases, in this paper we analyzed differences between hypertensive diabetics (N = 20) and nondiabetics (N = 57). 24-hours ABPM was performed with an automated oscillometric device Mobil-O-Graph NG Vers.20 and office BP using mercury sphygmomanometer. Average office BP was 139/90 mmHg, and average 24h ABPM was 130/82 mmHg. Majority of hypertensive patients used antihypertensive drugs (79.2%). Diabetic patients had higher systolic BP but lower diastolic BP. There were no statistically significant differences in dipping status, but earlier BP surge was noticed in reverse diabetic dippers than in reverse non-diabetic dippers. Though no significant, there was higher prevalence of WCH ("white coat hypertension") in diabetics, and we found MH (masked hypertension) in only two patients. These are preliminary results on ABPM from our centre and of HRKMAT registry. Further and more valuable data and results are awaited from the main HRKMAT database.

[Chronic kidney disease--mineral and bone disorder: why and how to control phosphate]. / Kronicna bubrezna bolest--poremecaj metabolizma minerala i kosti: zasto i kako kontrolirati fosfor.

Chronic kidney disease (CKD) is a global public health problem. Metabolic bone disease and mineral metabolism disturbance are common disturbance of CKD. A critical role of phospohorus in metabolic bone disease, i.e. secondary hyperparatyhroidism is well known. There is growing evidence that hyperphosphatemia isa strong predictor of mortality in CKD, i.e. is a novel risk factor for vascular calcification, left ventricular hypertrophy and kidney disease progression. Prevention and treatment of phosphate disturbace in CKD is still great challenge and new phosphate binders ofer new and advanced possibilites.

[Peritoneal dialysis in a patient with right hemiparesis, lupus nephritis, significant insufficiency of arteries of aortic arch and celiac disease: case report]. / Peritonejska dijaliza u bolesnice s desnostranom hemiparezom, lupus nefritisom, znacajnom insuficijencijom arterija luka aorte i glutenskom enteropatijom--prikaz slucaja.

Peritoneal dialysis (PD) is a method of choice in patients in whom there are difficulties concerning creation of AV fistula. A 38-year old female patient came to our hospital because of a need of making an AV fistula. She had end-stage renal insufficiency of unknown origin. She had a right hemiparesis with a contracture of the right fist and epilepsy because of the stroke she suffered in 1993. After doing the diagnostics, we have found that patient had lupus nephritis, occlusion of brachiocephalic trunk, right and left common carotid artery and left subclavian artery. We also diagnosed celiac disease and a significant anemia. It was not possible to form an AV fistula, as it was not possible to do an assisted PD. Because of the right hemiparesis and contracture of the right fist, the possibility of performing PD independently was questionable. Despite the handicap, the patient had strong motivation and she managed to master the technique of PD independently. Even though it was estimated that she had a high risk score for applying anesthesia (ASA IV), the insertion of the peritoneal catheter went without complications. Because of the comorbidity, especially because of the significant stenosis and occlusions of the arteries of aortic arch, the kidney transplantation will not be performed. In the last fifteen months, the patient is performing PD independently, without any infectious complications, she is feeling well and is satisfied with the quality of her life. The consequences of the renal insufficiency are under control, systemic lupus erythematosus is, with a low dose of corticosteroids, in a steady state, malnutrition is corrected, but there is still hypoalbuminemia noted.

[Age and arterial hypertension in hemodialysis patients]. / Povezanost dobi i arterijske hipertenzije u bolesnika na hemodijalizi.

UNLABELLED: Hypertension is common in the elderly (here defined as people older than 60 years), affecting 60%-70% of this population. In this group, isolated systolic hypertension (ISH), defined as elevated systolic blood pressure (SBP) > or = 140 mm Hg and normal diastolic blood pressure (DBP) <90 mm Hg is the predominant subtype of hypertension. AIM: The aim of this cross-sectional study was to investigate blood pressure differences according to age, especially the prevalence of ISH, in patients with end-stage renal disease (ESRD) undergoing regular maintenance hemodialysis, and to determine the importance of the interdialysis weight gain as a factor contributing to ISH. METHODS: Blood pressure was measured manually using mercury sphygmomanometer prior to and after dialysis procedure. Measurements were performed by educated staff members. Data on patient sex and age, duration of dialysis in total and weekly in hours, diabetic status, number of different antihypertensives used, and interdialysis weight gain were recorded. Patients were classified into four subgroups based on their systolic and diastolic blood pressure: normotensive (<140/<90 mm Hg); systolic-diastolic hypertension (SDH; > or = 140/> or = 90 mm Hg); ISH (> or = 140/<90 mm Hg); and isolated diastolic hypertension (IDH; <140/> or = 90 mm Hg). A total of 687 patients were included in final analysis and classified into 5 age groups: group 1, < or = 50; group 2, 50-59; group 3, 60-69; group 4, 70-79; and group 5, > or = 80. Student's t-test and ANOVA were used for continuous, normally distributed data, and chi2-test and Kruskal-Wallis test if otherwise. To identify the influence of IDWG on ISH, binary logistic regression was performed. The alpha <0.05 was considered statistically significant. RESULTS: There were 376 male and 311 female patients, mean age 63.13. In the above age groups, a decrease in the prevalence of SDH by 29.8%, 28.4%, 19.8%, 19.5% and 8.3%. (chi2=12.438, df=4, p=0.014) and an increase in the prevalence of ISH by 25.4%, 25.2%, 39.0%, 35.9% and 50.0%, respectively, was recorded (chi2=15.670, df=4, p=0.003). There was no significant statistical difference in the prevalence of IDH. Using binary logistic regression, we tried to identify the predictors of ISH. ISH was treated as a dichotomous dependent variable. Independent variables were sex, age, diabetic status, percent of body weight reduction during the process of hemodialysis, antihypertensive therapy and duration of hemodialysis in months. Age, diabetic status, usage of antihypertensive medication and IDWG were identified as significant predictors of ISH. Compared to age group 1, groups 3, 4 and 5 were associated with a 1.875-fold (1.064-3.305; p=0.030), 1.981-fold (1.116-3.519; p=0.020) and 3.963-fold (1.667-9.421; p=0.002) increase in the risk of developing ISH. Diabetic status was associated with a 1.833-fold (1.106-3.039; p=0.019) and antihypertensive medication with 2.731-fold (1.477-5.051; p=0.001) risk increase. IDWG >3% was associated with a 1.543-fold (1.074-2.217 p=0.019) risk increase of ISH. DISCUSSION: This study showed HTN to be still largely uncontrolled in patients undergoing hemodialysis. SBP remained constant in all age groups, even in the youngest, while a decrease in DBP was evident across age groups. A variety of factors contribute to this issue. Volume overload with other metabolic disorders that usually accompany chronic kidney disease (CKD) make these patients incline towards higher BP. Although IDWG in kilograms and percentage was significantly lower in older age groups, in logistic regression analysis IDWG larger than 3% was indicated as a positive predictor of ISH. When the same model was applied to SDH, IDWG >3% was not recognized as a statistically significant predictor of SDH (OR=1.225; 95%CI=0.819-1.832; p=0.323). CONCLUSION: It is possible that dietary modification involving sodium restriction may provide more benefit for patients with ISH than for those with SDH. Nevertheless, dietary modifications need to be encouraged in all patients undergoing hemodialysis.