Clinical Features, Outcomes, and Response to Corticosteroid Treatment of Acute Tubulointerstitial Nephritis: A Single-Centre Retrospective Cohort Study in the Czech Republic.

INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

Catecholamines Induce Left Ventricular Subclinical Systolic Dysfunction: A Speckle-Tracking Echocardiography Study.

Background: Pheochromocytomas (PHEO) are tumors arising from chromaffin cells from the adrenal medulla, having the ability to produce, metabolize and secrete catecholamines. The overproduction of catecholamines leads by many mechanisms to the impairment in the left ventricle (LV) function, however, endocardial measurement of systolic function did not find any differences between patients with PHEO and essential hypertension (EH). The aim of the study was to investigate whether global longitudinal strain (GLS) derived from speckle-tracking echocardiography can detect catecholamine-induced subclinical impairments in systolic function. Methods: We analyzed 17 patients (10 females and seven males) with PHEO and 18 patients (nine females and nine males) with EH. The groups did not differ in age or in 24-h blood pressure values. Results: The patients with PHEO did not differ in echocardiographic parameters including LV ejection fraction compared to the EH patients (0.69 ± 0.04 vs. 0.71 ± 0.05; NS), nevertheless, in spackle-tracking analysis, the patients with PHEO displayed significantly lower GLS than the EH patients (-14.8 ± 1.5 vs. -17.8 ± 1.7; p < 0.001). Conclusions: Patients with PHEO have a lower magnitude of GLS than the patients with EH, suggesting that catecholamines induce a subclinical decline in LV systolic function.

Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized PRAGUE-15 study.

OBJECTIVES: The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. METHODS: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ±â€Š17 and 155 ±â€Š17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients. RESULTS: Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001). CONCLUSION: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study.

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Long-term effects of adrenalectomy or spironolactone on blood pressure control and regression of left ventricle hypertrophy in patients with primary aldosteronism.

INTRODUCTION: Primary aldosteronism (PA) represents the most common cause of secondary hypertension. Beyond increased blood pressure, additional harmful effects of aldosterone excess including inappropriate left ventricle (LV) hypertrophy were found. We evaluated the effect of adrenalectomy and spironolactone on blood pressure and myocardial remodelling in a long-term follow-up study. METHODS: Thirty-one patients with PA were recruited. Fifteen patients with confirmed aldosterone-producing adenoma underwent adrenalectomy; in the remaining 16 patients, treatment with spironolactone was initiated. Laboratory data, 24-hour ambulatory blood pressure monitoring (ABPM) and echocardiography parameters were evaluated at baseline and at a median follow-up of 64 months. RESULTS: Both approaches reduced blood pressure (p = 0.001 vs. baseline). In both groups we observed a decrease in end-diastolic (p = 0.04, p = 0.01) and end-systolic LV cavity diameters (p = 0.03, p = 0.01). Interventricular septum and posterior wall thickness reduction was significant only after adrenalectomy (p = 0.01, p = 0.03) as was reduction of LV mass index (p = 0.004). A trend to lower LV mass on spironolactone was caused predominantly by diminution of the LV cavity, which was reflected in increased relative wall thickness (p = 0.05). CONCLUSIONS: Although both surgical and conservative treatment can induce a long-term decrease of blood pressure, adrenalectomy seems to be more effective in reduction of LV mass, as it reverses both wall thickening and enlargement of the LV cavity.

Long-term effect of specific treatment of primary aldosteronism on carotid intima-media thickness.

BACKGROUND: Aldosterone has been shown to substantially contribute to the accumulation of different types of collagen fibres and growth factors in the arterial wall, thus increasing wall thickness. A previous study showed reduction of increased common carotid intima-media thickness (IMT) in patients with primary aldosteronism 1 year after adrenalectomy. Our study in patients with primary aldosteronism was aimed at comparing the long-term effect of adrenalectomy vs. spironolactone therapy on common carotid IMT regression. METHOD: Forty-two patients with confirmed primary aldosteronism (21 with aldosterone-producing adenoma treated by unilateral laparoscopic adrenalectomy, 21 treated with spironolactone) were investigated by carotid ultrasound at baseline and 1 and 6 years after the specific treatment. RESULTS: There was a decrease in common carotid IMT from 0.956 ±â€Š0.140 to 0.900 ±â€Š0.127 mm (-5.9%; P < 0.05) at 1 year and to 0.866 ±â€Š0.130 mm (-9.4%; P < 0.01) at 6 years after adrenalectomy; in the spironolactone group, common carotid IMT decreased from 0.917 ±â€Š0.151 to 0.900 ±â€Š0.165 mm (-1.8%; NS) at 1 year and to 0.854 ±â€Š0.176 mm (-6.8%; P < 0.01) at 6 years of treatment. The magnitude of improvement at 1 year was significantly higher (by 70%; P < 0.05) in the adrenalectomy group; however, the difference (by 27%) became nonsignificant at 6 years. Comparing the adrenalectomy and spironolactone groups, there was no significant difference in blood pressure decrease after treatment. CONCLUSION: In the long term, spironolactone therapy in patients with primary aldosteronism had significant effect on regression of IMT, which was comparable to surgical treatment in patients with unilateral forms of primary aldosteronism.

Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis.

BACKGROUND: The aim of our study was to assess the prevalence of pseudo-resistance caused by noncompliance with treatment among patients with severe resistant hypertension and to analyze the contributing factors. METHOD: Three hundred and thirty-nine patients (195 men) with resistant essential hypertension were studied. The first group consisted of 176 patients admitted for hospitalization for exclusion of a secondary cause to our hypertension centre (103 men); the second one consisted of 163 out-patients (92 men) investigated for the first time in an out-patient hypertension clinic. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by means of liquid chromatography-mass spectrometry was performed in all patients. RESULTS: Our main finding is a surprisingly low compliance with drug treatment in out-patients with resistant hypertension (23% partially noncompliant and 24% totally noncompliant - in total, 47% prevalence of noncompliance). Eighty-one percent of hospitalized patients were positive, in 10% the results were partially positive and in 9% of the patients, the drugs were all negative. The compliance among hospitalized patients was probably better due to lower numbers of prescribed drugs and expected thorough investigation. More frequently, noncompliance was found in nonworking (potential purpose-built behaviour), younger and less well educated patients. The most frequent noncompliance was to doxazosine, spironolactone and hydrochlorothiazide. We have observed a surprisingly low compliance with treatment among out-patients with severe hypertension. CONCLUSION: We conclude that the evaluation of antihypertensive drugs concentrations is a useful and precise method for assessment of noncompliance in patients with resistant hypertension. This evaluation is useful before starting the diagnostic work-up of secondary forms of hypertension and before assignment patients into protocols with new therapy modalities such as renal denervation.

Left ventricle remodeling in men with moderate to severe volume-dependent hypertension.

We evaluated the influence of increased intravascular volume on the heart anatomy in salt-sensitive types of hypertension, represented by primary aldosteronism (PA) and low-renin essential hypertension (LREH). Echocardiography was performed in 128 males with moderate to severe or resistant hypertension: 44 patients had PA, 40 patients had LREH and 44 patients had normal-renin essential hypertension (NREH). Groups were comparable in demographic characteristics, blood pressure, duration of hypertension and previous antihypertensive treatment. Patients with PA and LREH, in comparison with NREH patients, showed both greater end-systolic (37.6±5.4 and 35.6±4.5 vs 32.6±4.4 mm, p<0.001 and p<0.05) and end-diastolic (56.1±4.5 and 54.0±4.8 vs 50.4±5.1 mm; p<0.001 and p<0.01) left ventricle (LV) diameter. There were no significant differences either in LV wall thicknesses or LV mass, although a higher percentage of patients with PA and LREH met the criteria of eccentric hypertrophy (p<0.001 and p<0.05 respectively). Aldosterone concentration was positively related to LV cavity dimensions, whether wall thicknesses were rather associated with blood pressure levels. In conclusion, plasma volume overload was identified as an important factor influencing LV remodeling in PA and LREH, whether due to excessive aldosterone levels in PA or other pathophysiological mechanisms.