Hypertension and nephrology

[The role of sodium-glucose cotransporters in diabetic nephropathy]

HODREA judit1,2, BALOGH Dóra Bianka1, LÉNÁRT Lilla1,2, KŐSZEGI Sándor1,2, HOSSZÚ Ádám1,2, VANNAY Ádám2,3, WAGNER J. László4, REUSZ György2, SZABÓ J. Attila2,3, FEKETE Andrea1,2

SEPTEMBER 20, 2015

Hypertension and nephrology - 2015;19(04)

[Diabetic nephropathy is the main cause of chronic kidney disease affecting about one-third of type 2 diabetic patients. The exact pathomechanism is not known, therefore the treatment and the prevention is still unsolved. However appropriate glycemic control and lowering blood pressure significantly slow the progression of kidney damage these treatment options are still not enough to stop renal injury. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest drugs in the treatment of diabetes. By inhibiting the glucose reabsorption in the proximal tubules SGLT2 inhibitors lower blood glucose level and facilitate glucosuria. This paper summarizes the effect of SGLT2 inhibitors currently approved in Europe paying particular attention to their possible renoprotective effects.]

AFFILIATIONS

  1. MTA-SE, „Lendület” Diabétesz Kutatócsoport, Budapest
  2. Semmelweis Egyetem, I. Sz. Gyermekgyógyászati Klinika, Budapest
  3. MTA-SE, Gyermekgyógyászati és Nephrológiai Kutatócsoport, Budapest
  4. Semmelweis Egyetem, Transzplantációs és Sebészeti Klinika, Budapest

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Further articles in this publication

Hypertension and nephrology

[Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism on survival of hemodialyzed patients]

KISS István, SZEGEDI János, KULCSÁR Imre, AMBRUS Csaba, KERKOVITS Lóránt, TISLÉR András, KISS József Zoltán

[Introduction: There are inconsistent observations regarding the earlier studies of the connection between ACE gene I/D polymorphism and the cardiovascular mortality. In the case of hemodialyzed patients suffering from chronic kidney disease the DD polymorphism connected to the elevated ACE levels was pointed out to be connected to the mortality rate primarily in patients with diabetes. The previous observations were verified by us during the analyzation of the short-term (three year period) survival data. We hypothesized that the significance of the ACE gene I / D polymorphism in chronic kidney disease would be verified and that during long-term observations (10 year period) the previous results could be validated. Method: In our non-invasive, prospective and multicentre study clinical data was collected from 746 patients whose blood samples were genotyped for ACE gene I/D single nucleotide polymorphism. Three genotype groups (I/I, I/D és D/D) were created during the analyzation of the mortality that was done using multivariate Cox proportional hazard models. Results: The mean age of the HD patients was 54.9 years, 46,8% of all patients were female. The prevalence of diabetes was 19.3%. ACE inhibitor therapy was prescribed for 47.9% of all patients. The median duration of dialysis before the start of the study was 23.8 months (IQR 11.2-47.1). The most frequent genotype was I/D (42.6%), followed by D/D (37.7%) and I/I (19.7%) genotypes. During the ten year follow- up of patients, the median follow-up was 29.8 months (IQR 12.6-63.4). The D/D genotypes showed lower survivability (I/I vs. D/D: log-rank test: p=0.04) from the group of patients without ACE inhibitor therapy. In multivarite Cox regression models D/D genotype compared with I/I genotype only showed that it significantly determines mortality in patients with no ACE inhibitor therapy (HR 0.67, 95% CI 0.46-0.97, p=0.03). Conclusions: There was no difference in survival among unselected patients with different genotypes. Our data suggests that hemodialyzed patients with the D/D genotype might have inferior outcome, and ACE inhibitor therapy may be associated with improved survival in this subgroup.]

Hypertension and nephrology

[Case report of resistent hypertension with failed renal denervation]

ALFÖLDI Sándor, KOVÁTS Viktória, SIMONYI Gábor, MERKELY Béla, FARSANG Csaba

[A 48 year old male patient with hypertension, resistant to the combined administration of seven antihypertensive drugs had an associated hypertrophic nonobstructive cardiomyopathy. Bilateral renal denervation has been performed with the Symplicity catether of Medtronic after the exclusion of possible secondary forms of hypertension, but his blood pressure did not decrease. Preventive intracardiac cardioverter defibrillator implantation has also been performed because of progressive congestive heart failure. We planned a witnessed intake of antihypertensive medication before qualifying ABPM study but without success because of noncompliance of the patient. According to the database of the Hungarian National Health Insurance Fund (OEP) on request of his general practitioner, the patient payed for prescripted medicine only once in the previous year, on the day before his planned witnessed intake of antihypertensive medication. The witnessed intake of medication before qualifying ABPM study was finally successful two years after the renal denervation and both his office and ambulatory blood pressure decreased substantially. The witnessed intake of antihypertensive medication for the exclusion of nonadherence as a cause of therapy resistant hypertension is warranted, especially before device or operative interventions for the treatment of hypertension.]

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FARSANG Csaba, KISS István, ANDRZEJ Tykarski, KRZYSZTOF Narkiewicz

Hypertension and nephrology

[Adherence to the Prescribed Medicines and their Dosing is Almost as Important as Reaching the Target Value in Hypertensive Patients]

KISS István, KÉKES Ede

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[Influencing the renin-angiotensin system through receptor blockade has become a new therapeutic approach toward the treatment of several morbidities, i.e. hypertension, cardiac failure and diabetic nephropathy. The current paper reviews the importance of diabetic nephropathy, the physiology of the renin-angiotensin system and specific effects of receptor blockade on different organs based on 3 new studies (published last year) using angiotensin-II receptor blockers. The paper gives a summary of the IRMA, IDNT and RENAAL studies, including their clinical and therapeutic significance in general practice as well as in specialized diabetes care. The new therapeutic approach (with an excellent safety profile, and infrequent side effects) could delay the progression or might even prevent the manifestation of diabetic nephropathy not only with lowering blood pressure but with its direct effects on target tissues as well. The angiotensin-II receptor blocking agents might be useful for the treatment of cardiac failure in hypertensive patients.]

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[INTRODUCTION - The importance of measuring microalbuminuria is well established, however, controversy still exists regarding the type of urine specimen to be used for detecting early renal impairment of diabetic patients. PATIENTS AND METHODS – To evaluate practical aspects, albumin concentration and albumin to creatinine ratio of first void urine samples as well as urinary albumin excretion in timed specimens were determined by immunoturbidimetric method 3 times within 3 weeks in 192 adult diabetic patients (136 men, 56 women; type 1/type 2: 90/102; age: 51.4=10.8 years; duration of diabetes: 15.3+9.1 years; body mass index: 27.9+4.6 kg/m2; HbA1c: 8.5+1.5 %; actual blood pressure: 13814/82+8 mmHg; serum creatinine: 94+20 umol/l; x+SD). RESULTS - According to the urinary albumin excretion values, one third of patients (31.2%-30.7%-34.4%) were normoalbuminuric (<30 mg/24 hours), more than half of the patients (55.8%-57.3%-53.6%) proved to be microalbuminuric (30-300 mg/24 hours), while the remaining group of patients (13.0%-12.0%–12.0%) was macroalbuminuric (>300 mg/24 hours). Comparing the results of successive measurements good correlation was found between the same laboratory values (urinary albumin excretion: K=0.64; K=0.67; urinary albumin concentration: K=0.60; K=0.62; albumin to creatinine ratio: K=0.54; K=0.61; first vs. second and second vs. third measurements, respectively). The percentage of patients being in the same range of albuminuria (i.e. normo-, micro-or macroalbuminuria) at successive measurements was 79.7-81.2% with urinary albumin excretion values, 77.1-77.6% with urinary albumin concentration and 74.5-78.6% with albumin to creatinine ratio. Good correlations were found between urinary albumin excretion and urinary albumin concentration (K=0.54; 0.54; 0.57) and nearly the same correlations were observed between urinary albumin excretion and albumin to creatinine ratio (K=0.49; 0.47;0.54) at different series. Using values of urinary albumin excretion for comparison at all measurements, 79.3% sensitivity and 69.5% specifity were found for urinary albumin concentration whereas 74.6% sensitivity and 68.8% specifity were documented for albumin to creatinine ratio. CONCLUSION - Beside the standard measurement of urinary albumin excretion in timed urine samples, the use of the more convenient morning urinary spot collection could also provide useful results (urinary albumin concentration or albumin to creatinine ratio) for detecting early renal involvement in diabetic patients. ]

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Over the second half of the 19th century, numerous theories arose concerning mechanisms involved in understanding of action, imitative learning, language development and theory of mind. These explorations gained new momentum with the discovery of the so called “mirror neurons”. Rizzolatti’s work inspired large groups of scientists seeking explanation in a new and hitherto unexplored area of how we perceive and understand the actions and intentions of others, how we learn through imitation to help our own survival, and what mechanisms have helped us to develop a unique human trait, language. Numerous studies have addressed these questions over the years, gathering information about mirror neurons themselves, their subtypes, the different brain areas involved in the mirror neuron system, their role in the above mentioned mechanisms, and the varying consequences of their dysfunction in human life. In this short review, we summarize the most important theories and discoveries that argue for the existence of the mirror neuron system, and its essential function in normal human life or some pathological conditions.