Nikolina Basic-Jukic, Bozidar Vujicic, Josipa Radic, Dragan Klaric, Zeljka Grdan, Goran Radulovic, Klara Juric, Karmela Altabas, Marko Jakic, Valentina Coric-Martinovic, Ivana Kovacevic-Vojtusek, Marijana Gulin, Nikola Jankovic, Dragan Ljutic and Sanjin Racki
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Claudiu Puiac, Janos Szederjesi, Alexandra Lazăr, Codruța Bad and Lucian Pușcașiu
Introduction: Elevated intraabdominal pressure (IAP) it is known to have an impact on renal function trough the pressure transmitted from the abdominal cavity to the vasculature responsible for the renal blood flow. Intraabdominal pressure is found to be frequent in intensive care patients and also to be a predictor of mortality. Intra-abdominal high pressure is an entity that can have serious impact on intensive care admitted patients, studies concluding that if this condition progresses to abdominal compartment syndrome mortality is as high as 80%.
Aim: The aim of this study was to observe if a link between increased intraabdominal pressure and modification in renal function exists (NGAL, creatinine clearance).
Material and Method: The study enrolled 30 critically ill patients admitted in the Intensive Care Unit of SCJU Tîrgu Mures between November 2015 and August 2016. The study enrolled adult, hemodynamically stable patients admitted in intensive critical care - defined by a normal blood pressure maintained without any vasopressor or inotropic support, invasive monitoring using PICCO device and abdominal pressure monitoring.
Results: The patients were divided into two groups based on the intraabdominal pressure values: normal intraabdominal pressure group= 52 values and increased intraabdominal group= 35 values. We compared the groups in the light of NGAL values, 24 hours diuresis, GFR and creatinine clearance. The groups are significantly different when compared in the light of NGAL values and GFR values. We obtained a statistically significant correlation between NGAL value and 24 hour diuresis. No other significant correlations were encountered between the studied items.
Conclusions: NGAL values are increased in patients with high intraabdominal pressure which may suggest its utility as a cut off marker for patients with increased intraabdominal pressure. There is a significant decreased GFR in patient with elevated intraabdominal pressure, observation which can help in early detection of renal injury in patients due to high intraabdominal pressure. No correlation was found between creatinine clearance and increased intraabdominal pressure.
Introduction. Cardiovascular diseases are the leading cause of death in hemodialysis patients. The decline of residual renal function increases the prevalence and severity of risk factors of cardiovascular morbidity and mortality in these patients. Hypertension is common in dialysis patients and represents an important independent factor of survival in these patients.
Methods. The study included 77 patients who are on chronic HD for longer than 3 months. Depending on the measured residual diuresis patients were divided into two groups. The study group consisted of patients with residual diuresis >250 ml/day, while patients from control group had residual diuresis <250 ml/day. All patients had their blood pressure measured before 10 consecutive hemodialysis treatments. Collected data were statistically analyzed using SPSS 16.0.
Results. The study included 77 hemodialysis patients, mean age of 56.56±14.6 years and mean duration of hemodialysis treatment of 24.0 months. Of the total number of patients, 39(50.6%) had preserved residual renal function. Hypertension was more common in the group of patients who did not have preserved residual renal function (68.4% vs 25.6%). There was statistically significant negative linear correlation between the volume of residual urine output and the residual clearance of urea and values of systolic blood pressure [(rho=−0.388; p<0.0001); (rho=−0.392; p<0.0005)], values of mean arterial pressure [(rho =−0.272; p<0.05); (rho=−0.261; p=0.023; p<0.05)] and values of pulse pressure in hemodialysis patients [(rho =−0.387; p<0.001); (rho=−0.400; p<0.0005)].
Conclusions. Residual renal function plays an important role in controlling blood pressure in patients on hemodialysis. More attention should be directed to preserve residual renal function, and after the start of hemodialysis by avoiding intensive ultrafiltration with optimal antihypertensive therapy.
Bojana Djokovic, Marina Gazdic Jankovic, C. Randall Harrell, Crissy Fellabaum, Nebojsa Arsenijevic and Vladislav Volarevic
Cisplatin (cis-diamminedichloroplatinum II) is a widely used chemotherapeutic agent. However, efficacy and clinical utility of this drug is significantly limited by severe side effects such as nephrotoxicity which develops due to renal accumulation and bio-transformation in proximal tubular epithelial cells. Cisplatin-induced nephrotoxicity can be manifested as acute kidney injury (AKI), or as different types of tubulopathies, salt wasting, loss of urinary concentrating ability, and magnesium wasting. The attenuation of cisplatin-caused AKI is currently accomplished by hydration, magnesium supplementation or mannitol-induced forced diuresis. However, mannitol treatment causes over-diuresis and consequent dehydration, indicating an urgent need for the clinical use of newly designed, safe and efficacious renoprotective drug, as an additive therapy for high dose cisplatin-treated patients. Accordingly, we emphasized current knowledge regarding molecular mechanisms responsible for cisplatin-caused nephrotoxicity and we described in detail the main clinical manifestations of cisplatin-induced renal dysfunction in order to pave the way for the design of new therapeutic approaches that can minimize detrimental effects of cisplatin in the kidneys. Having in mind that most of cisplatin-induced cytotoxic effects against renal cells are, at the same time, involved in anti-tumor activity of cisplatin, new nephroprotective therapeutic strategies have to prevent renal injury and inflammation without affecting cisplatin-induced toxicity against malignant cells.
Kalina Gjorgjievska, Maja Slaninka-Miceska and Gordana Petrusevska
Protective Effects of Aliskiren, Enalapril and Valsartan on Hypertension Target Organs in Spontaneously Hypertensive Rats
Aim: Aliskiren is the first orally active renin inhibitor approved for treatment of essential hypertension. There are as yet no clinical data regarding the ability of aliskiren to prevent clinical end-points or reduce end-organ damage over and above the presumed effects of blood pressure reduction. The aim of this study was to find out if aliskiren has a potential to improve renal function and if it has a protective effect on hypertension target organs (kidney, heart and aorta).
Materials and Methods: The study was conducted on 64 SHR rats (male and female), 20 weeks old, weighing from 250-300 g. Animals were divided into 4 groups and treated with aliskiren (100 mg/kg bw/24 h), enalapril (10 mg/kg bw/24 h) and valsartan (10 mg/kg bw/24 h). Effects of investigated drugs were evaluated by urinalysis and histopathological analysis.
Results: Diuresis was significantly increased in the group of animals treated with enalapril and valsartan. Effect on diuresis with aliskiren was mild and statistically insignificant. No significant difference in urine pH between treated and control group of SHR rats was noted. Albuminuria was decreased in animals treated with enalapril and valsartan. Aliskiren after 28 days of treatment had a statistically insignificant effect on albuminuria in SHR rats. Only certain changes of wall thickness of arteries and arterioles were noted that led to improved perfusion and function of the kidneys more pronounced in rats treated with valsartan and enalapril. Effects of aliskiren on target organs were inferior compared to valsartan and enalapril.
Conclusion: In SHR experimental model aliskiren has minor effects on hypertension target organs when compared to enalapril and valsaratan.
Bogdan Timar, Cristian Serafinceanu, Adrian Vlad and Romulus Timar
Type 2 diabetes is a progressive metabolic disorder, accounting for more than 90% of all cases of diabetes. Treatment strategies target blood glucose reduction and non-glycemic effects that can reduce long-term complications, such as cardiovascular disease. Although metformin is often initially effective as monotherapy, the progressive nature of diabetes frequently requires additional therapies. Sodium-glucose transporter 2 (SGLT2) became a very attractive therapeutic target in diabetes management. The mechanism of action of SGLT2 inhibitors is not dependent on insulin, thus making them attractive options anytime over the course of the disease. Dapagliflozin is a stable and highly selective inhibitor of SGLT2. The reductions in fasting plasma glucose concentration and bodyweight recorded during the first week of treatment in the dapagliflozin groups continued over weeks and years of treatment. Early weight loss with dapagliflozin might be partly due to a mild osmotic diuresis, while the gradual progressive reduction in bodyweight is consistent with a reduction of fat mass. Although dapagliflozin is well tolerated, signs and symptoms suggestive for urinary and/or genital infections were reported during clinical trials in more patients assigned to the drug than in placebo groups.
Lenka Bartošíková, Jiří Nečas, Tomáš Bartošík, Martin Pavlík and Petr Fráňa
Effect of pomiferin administration on kidney ischaemia-reperfusion injury in rats
The aim of the study was to analyse protective effects of different doses of pomiferin in therapy of reperfusion injury. Rats were randomly divided into five groups (n=10). One group was intact. Three medicated groups and one placebo group were subjected to ischaemia and reperfusion of the left kidney. Pomiferin was administrated by single gastric gavage in 2 ml of 0.5% Avicel solution in doses of 5, 10 and 20 mg/kg. The placebo group was given only Avicel solution. On day 15, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers were assessed in blood: antioxidative enzymes, total antioxidative capacity, malondialdehyde, creatinine, urea and uric acid. Creatinine, urea and total proteins were analysed in urine and 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination.
The results confirmed the expected protective effects of pomiferin. Pomiferin supported defensive reactions of the body against free radicals (increased levels of superoxide dismutase, total antioxidative capacity), decreased lipid peroxidation (decreased malondialdehyde) and contributed to the recovery of kidney functions (creatinine and urea in blood). The best biochemical and histopathological results were achieved after pomiferin administration in the dose of 5 mg/kg.
A. Janchevska, V. Tasic, Z. Gucev, M. Krstevska-Konstantinova and H. I. Cheong
Nephrogenic diabetes insipidus (NDI) is caused by the inability of renal collecting duct cells to respond to arginine vasopressin (AVP)/antidiuretic hormone (ADH). We present the case of a 7-year-old boy with a history of excretion of large amounts of dilute urine and polydipsia since infancy. The boy had several vomiting episodes with mild dehydration during the first 3 years of life. There was no evidence of headaches, dizziness or visual problems. He drinks between 2 and 3 L/day and has 24-hour diuresis of 2 liters, now. He has prepubertal appearance with appropriate weight [+0.85 standard deviation score (SDS)] and height (+0.15 SDS) for his age. His intelligence was also normal. The water deprivation test showed low urine osmolality after 8 hours of dehydration. After desmopressin administration, urine osmolality remained low. Serum osmolality was in the normal range for sex and age before and after desmopressin administration. This indicated a nephrogenic form of diabetes insipidus. Molecular analyses revealed a P286L [p.Pro(CCC)286Leu(CTC)] mutation in the AVPR2 gene, that was inherited from his mother. This patient is the first case with genetically confirmed X-linked inherited form of NDI in the Republic of Macedonia. Molecular analysis confirmed the clinical diagnosis and enabled genetic advice for this family.
Grzegorz Mizerski, Pawel Kicinski and Andrzej Jaroszynski
The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the administration of dapagliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes, is associated with the reduction of HbA1c concentration by 0.45-1.11%. Additional benefits from the treatment with dapagliflozin are the reduction of arterial blood pressure and a permanent reduction of body weight. This outcome is related to the effect of osmotic diuresis and to the considerable loss of the glucose load by way of urine excretion. Dapagliflozin may be successfully applied in type 2 diabetes monotherapy, as well as in combined therapy (including insulin), where it is equally effective as other oral anti-diabetic drugs. Of note: serious adverse effects of dapagliflozin administration are rarely observed. What is more, episodes of severe hypoglycaemia related with the treatment occur only sporadically, most often in the course of diabetes polytherapy. The most frequent effects of the SGLT2 inhibitors are inseparably associated with the mechanism of their action (the glucuretic effect), and cover urogenital infections with a mild clinical course. At present, clinical trials are being continued of the administration of several subsequent drugs from this group, the most advanced of these being the use of canagliflozin and empagliflozin.
Mehmet Can Ugur, Ferhat Ekinci, Utku Erdem Soyaltın and Harun Akar
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