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.

Adiponectin is not associated with blood pressure in normotensives and untreated hypertensives with normal kidney function.

The role of adiponectin in hypertension is still a matter of debate. Obtained conflicting results could be mostly explained with diversity of subjects included in different studies. Our aim was to analyze association of adiponectin with blood pressure (BP) in a group of normotensive and untreated hypertensive subjects. Participants (N=257) were selected from a random sample of 2487 subjects enrolled in an observational cross-sectional study. Subjects with diabetes and chronic kidney diseases were excluded. BP was measured using Omron M6 device following ESH/ESC guidelines. Adiponectin concentration was determined by ELISA. There were no differences in adiponectin values (mg/L) between hypertensives and normotensives (median 9.75; iqr: 7.44-17.88 vs 11.35; iqr: 7.43-12.63; P=0.17). On univariate linear regression adiponectin was not associated with systolic or diastolic BP (P>0.05). Furthermore, multivariate analysis did not show significant contribution of log-transformed adiponectin either to systolic (ß=-0.040; P=0.43) or diastolic BP (ß=0.066; P=0.33). In our group of normotensives and untreated hypertensives with normal kidney function adiponectin was not associated with BP even after adjustment for other risk factors. Our results and conclusions should not be extrapolated to subjects with other characteristics.

[Classification of glomerulopathies]. / Klasifikacija glomerulopatija.

Glomerular diseases may be classified as acute or chronic, primary or secondary, hereditary or acquired, proliferative or non-proliferative etc. The most commonly used is the classification according to the histopathological finding. For certain types of glomerulonephritides histopathological image, as well as clinical presentation, may vary widely. A while ago there was no classification based on the pathogenesis of certain types of glomerular diseases. However, as scientists ellucidate the underlying pathogenetic mechanism, current classifications change. The latter is best shown at the example of membranoproliferative glomerulonephritis.

Arterial stiffness in atherosclerotic renovascular hypertension.

OBJECTIVE: Arterial stiffness is an independent cardiovascular risk factor. Aging, high blood pressure and increased renin-angiotensin system activity contribute to increased arterial stiffness in patients with atherosclerotic renovascular hypertension (aRVH). A literature search failed to identify any study related to this topic. Therefore, our aim was to determine the arterial stiffness in patients with aRVH and analyze whether stenting in addition to multifactorial drug therapy has beneficial effects on markers of stiffness and the clinical course. METHODS: In this 6-month longitudinal study, 37 patients with refractory hypertension and unilateral aRVH were enrolled. After stenting, all patients received multifactorial dug therapy including 80 mg of telmisartan. Arterial stiffness indices were determined using Arteriograph. The control group consisted of 44 patients with essential hypertension. RESULTS: There were no differences in brachial blood pressure values between the two groups (P > 0.05). At baseline, adjusted pulse wave velocity (PWV) was higher in aRVH patients than that of essential hypertensive patients (12.8 ±â€Š0.4 vs. 11.6 ±â€Š0.3 m/s; P = 0.029). In the aRVH group, at the end of the follow-up, a significant decrease in the aortic augmentation index (37.7 ±â€Š9.9 vs. 33.7 ±â€Š11.4; P = 0.02) without changes in PWV was observed (P > 0.05). CONCLUSION: This study is the first to show that arterial stiffness is higher in patients with refractory aRVH than in those with essential hypertension. Multifactorial therapy based on stenting and intensive medical treatment reduced central blood pressure and augmentation index. Failure to obtain PWV reduction is likely a consequence of the present irreversible structural vessel changes. Longer follow-up might enable us to resolve whether arterial stiffness indices have better predictive ability in patients with aRVH than brachial blood pressure.

Impact of angiotensin-converting enzyme gene polymorphism on proteinuria and arterial hypertension.

Proteinuria is the hallmark of renal disease. In essential hypertension the onset of de novo proteinuria is associated with faster rate of progression of disease. Some authors have suggested that the DD genotype of the angiotensin-converting enzyme (ACE) gene would be an adverse renal prognosis factor. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. Observations on the association between the ACE gene polymorphism and hypertension have been inconsistent, which might be due to ethnic and geographical variations. In this study was to investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (ramipril) and to evaluate the possible association between I/D polymorphism and hypertension. We recruited 66 hypertensive patients (male 42, female 24) with overt proteinuria (urinary protein excretion over 500 mg/day). Patients were classified into three groups in accordance with ACE genotypes (17 DD; 35 ID; 14 II). They were treated with ramipril and prospectively followed up for one year. Various clinical parameters including age, body mass index (BMI), 24-h urine protein, creatinine, creatinine clearance (Ccr), systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP) were measured in the pre- and post-treatment periods. The ACE gene insertion/deletion(I/D) polymorphisms in intron 16 were determined by PCR. Results showed that there were no significant differences in the clinical parameters such as age, gender, serum creatinine, Ccr, SBP, DBP, MAP, and daily urinary excretion of protein among three groups (P > 0.05). ID genotype patients were found to have lower BMI (p = 0.031). ACE inhibition significantly reduced proteinuria in all genotype groups (p < 0.05). The percentage reductions of 24-h urinary excretion of protein were significantly different between the genotype groups (p = 0.042) and for DD genotype were significantly greater than in ID (79.2 +/- 28.9% vs 49.2 +/- 64.8%, P = 0.015). The slope of SBP was the main factor related to the slope of the percentage reduction of proteinuria, however, a significant negative correlation coefficient between these parameters was found (rs = -0.382, p = 0.002). We failed to find significant difference in outcomes of treatments with ACE inhibitor between male and female according the I/D polymorphism of the ACE gene. D allele in the ACE genotype could be a useful genetic marker with important clinical, therapeutic and prognostic implications in recognizing patients with proteinuria that are at greater risk of renal damage.

[Value of ultrasound-guided percutaneous renal biopsy in diagnosis of the renal diseases]. / Znacenje perkutane biopsije u dijagnostici bubreznih bolesti.

Percutaneous renal biopsy (PRB) is an integral part of the clinical practice of nephrology. It is a safe and effective tool in the diagnosis of glomerular, vascular and tubulointerstitial diseases of the kidney, providing information that is invaluable in prognosis and patient management. PRB of native kidneys was performed by nephrologists in 249 patients consecutively from May 1997 through May 2005 at the Department of Nephrology, Dubrava University Hospital, Zagreb, Croatia. The biopsy was done using continuous ultrasound guidance and a 16-gauge biopsy needle (Tru-Cut) in an automated gun (Biopty Bard). All biopsies were processed for light, immunofluorescence and electron microscopy. We analyzed yield of diagnostically useful material and frequency of postbiopsy complication. Adequate tissue for histologic diagnosis was obtained in 95% of the procedures. The mean glomerular yield was 11.9 glomeruli. The main indications for renal biopsy were nephrotic syndrome (33%) hematuria and/or non-nephrotic proteinuria (13%) and renal failure (12%). The dominant types of primary glomerulonephritis (GN) were focal segmental glomerulosclerosis (FSGS) in 27%, mesangioproliferative in 13%, IgA nephropathy in 11%, membranous GN in 11%, membranoproliferative GN in 5%, crescentic GN--5%, and minimal change disease (MCD) in 3% of cases. The most frequent complications were perirenal hematoma (clinically asymptomatic) in 3.6%, macrohematuria in 1.2%; bleeding complications requiring blood transfusion and/or therapeutic radiologic intervention were not seen, and surgical procedure was indicated in one (0.4%) patient. We conclude that real-time ultrasound is a safe, accurate method in localizing the kidney for percutaneous renal biopsy and a very effective approach for early detection of perirenal hematoma and other potential postbiopsy complications. The present data are an important contribution to the epidemiology of renal disease, highlighting significant epidemiological differences in European countries, particularly a higher incidence of FSGS as a proportion of primary GN in our population. This report represents a basis for the future Croatian Registry of Renal Biopsies and is intended to serve as a source of information for further studies.

[Rhabdomyolysis as a side effect of simvastatin treatment]. / Rabdomioliza kao nuspojava lijecenja simvastatinom.

Myopathy and rhabdomyolysis are rare adverse effects of treatment with hydroxymethylglutaryl-coA reductase inhibitors. The risk of adverse effects is increased with the concomitant use of statin and specific drugs that can induce myopathy, in patients with liver and renal function impairment, hypothyroidism and diabetes mellitus. The clinical picture of rhabdymyolysis with acute renal failure caused by the use of simvastatin in a 54-year-old patient with diabetes mellitus and hypertension is described.

[Renovascular hypertension due to Takayasu arteritis--a case report]. / Renovaskularna hipertenzija uzrokovana Takayasu arteritisom--prikaz bolesnice.

A 18-year old women with bilateral renal artery stenosis and renovascular hypertension as a part of Takayasu's disease is presented. Takayasu's disease is a chronic arteritis of unknown origin, primary affecting aorta and its branches. The disease is the most common in young women and is more common in the countries of eastern Asia in comparison with Western countries. Takayasu's disease can be severe and lifetreating disease. Mortality and morbidity depend on both the direct effect of the vascular lesions and the complications od disease. The mainstay of Takayasu's disease is based on the use of glucocorticoids alone or in association with cytotoxic drugs (cyclofosfamid, azatioprin, metotrexate). In the majority of cases, the partial control of disease is obtained.