The effect of hypertension and antihypertensive therapies on the course of COVID-19 infection: Turkish national health system data.

AIM: The effect of hypertension (HT) and antihypertensive therapies such as renin-angiotensin-aldosterone system (RAAS) blockers on the disease course in COVID-19 patients is controversial. The purpose of this study was to evaluate the effect of HT and antihypertensive therapies on the course of COVID-19 disease. METHOD: The age, sex, comorbid diseases, and antihypertensive therapies of 132,790 patients with positive COVID-19 real-time transcriptase polymerase chain reaction (RT-PCR) tests in the Turkish Health Ministry National COVID-19 database between 11 March and 31 May 2020, were examined and analyzed. RESULTS: Forty-one percent of the 132,790 patients in this study (median age: 40, 47.3% female) were hospitalized for treatment, and 4.5% were followed-up in the intensive care unit (ICU). The most frequent comorbid disease, at 19.5%, was HT (n = 25,863). Mortality was determined in 4.9% of HT patients and 1.9% of non-HT patients (p < .001). HT, age, and male gender emerged as independent predictors of hospitalization and admission to the ICU, while HT was not a predictor of mortality. In addition, no adverse effect of any antihypertensive treatment, including RAAS inhibitors, on mortality was detected. CONCLUSION: Based on Turkish national data, HT is common in COVID-19 patients, but does not appear to be an independent predictor of mortality, and no adverse effect of RAAS inhibitors on COVID-19-related mortality was observed.

MicroRNA 21 and microRNA 155 levels in resistant hypertension, and their relationships with aldosterone.

AIM: MicroRNAs (miRNAs) are non-coding RNA molecules that serve as regulators following gene expression transcription. While studies have investigated the role of miRNAs in the pathogenesis of essential hypertension (HT), very few have considered their place in the pathogenesis of resistant hypertension (RH). The purpose of this study was to investigate levels of miRNA 21 and miRNA 155 in RH and their relationships with aldosterone. METHOD: Thirty-two normotensive patients, 30 newly diagnosed HT patients, and 20 RH patients were included in the study. Patients' demographic data were recorded, and office blood pressure measurement and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed. Blood specimens were collected for miRNA 21, miRNA 155 and aldosterone measurement. MiRNA 21 and miRNA 155 levels in the control and patient groups and their relations with other demographic and biochemical parameters were then subjected to analysis. RESULTS: No difference was determined in miRNA 155 levels between the groups, but miRNA 21 and aldosterone levels were significantly higher in the RH group (p < 0.001 and <0.05, respectively). At correlation analysis, miRNA 21 exhibited positive correlation with aldosterone, age, office SBP, 24-h ABPM all-day SBP. A 9.6 copy/uL level for miRNA 21 predicted presence or absence of RH with 95% sensitivity and 71% specificity (AUC:0.823, 95% CI (0.72-0.92). CONCLUSION: The study results revealed significantly higher miRNA 21 and aldosterone in RH patients than in healthy individuals and newly diagnosed hypertensives.

Elevated serum levels of procollagen C-proteinase enhancer-1 in patients with chronic kidney disease is associated with a declining glomerular filtration rate.

BACKGROUND: Procollagen C-proteinase enhancer-1 (PCPE-1) is a 55 kDa glycoprotein, which increases the activity of procollagen C-proteinases that break down C-terminal propeptides. Studies have shown that PCPE-1 is involved in the fibrotic process that occurs in various tissues and organs. Our review of the literature revealed no data concerning the relation between PCPE-1 and chronic kidney disease (CKD). The purpose of this study was to determine PCPE-1 levels in CKD. METHODS: One hundred thirty-one CKD patients and 34 healthy controls were included in our study. Demographic data were recorded, and routine biochemical tests were performed. Blood specimens were collected for PCPE-1 investigation. Demographic data, biochemical test results and PCPE-1 levels were compared between the control and patient groups. Parameters affecting PCPE-1 levels in our patient group were assessed. RESULTS: Procollagen C-proteinase enhancer-1 levels were significantly higher in our patient group compared to the control group. Parameters affecting PCPE-1 elevation in the patient group were identified as systolic blood pressure, blood urea nitrogen, phosphorus, haemoglobin, intact parathormone levels, glomerular filtration rate and body mass index. CONCLUSION: We determined high PCPE-1 levels in CKD patients. PCPE-1 levels being negatively correlated with glomerular filtration rate suggests that PCPE-1 may be associated with progression in CKD patients.

Soluble endothelial protein C is associated with blood pressure variability and salt consumption but not mean blood pressure in patients with newly diagnosed primary hypertension.

BACKGROUND: Hypertension is a widespread disease involving frequent thrombotic complications. Blood pressure variability (BPV) has recently been shown to be associated with end-organ damage and cardiovascular events. However, the pathogenesis of the relation between BPV and cardiovascular events has not yet been explained. Soluble endothelial protein C (sEPCR) exhibits a procoagulant effect by reducing the anticoagulant and anti-inflammatory effects of protein C and activated protein C. The purpose of this study was to evaluate sEPCR levels in hypertensive individuals and the parameters affecting that level, particularly BPV. METHODS: Fifty-one newly diagnosed hypertensive subjects and 31 healthy individuals were included in the study. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed after office control, and simultaneous 24-h urine was collected. BPV was calculated with average real variability (ARV) from ABPM data. Blood specimens were collected under appropriate conditions for sEPCR levels and biochemical tests. sEPCR levels were compared between the patient and healthy groups, after which parameters affecting sEPCR elevation in the hypertensive group were evaluated. RESULTS: sEPCR levels were significantly high in the hypertensive group (p < 0.05). At multivariate regression analysis in the hypertensive group, sEPCR was determined to be independently associated with 24-h systolic ARV (ß = 0.572, p < 0.05) and 24-h urine Na (ß = 0.428, p < 0.05). CONCLUSION: In our study, sEPCR was high in hypertensive individuals, and this elevation was related to ARV and urine Na excretion independently of mean blood pressure.

The Relation Between Variability of Intact Parathyroid Hormone, Calcium, and Cardiac Mortality in Hemodialysis Patients.

Chronic kidney disease-mineral and bone disorder (CKD-BMD) is a condition known to be associated with cardiovascular disease and mortality in hemodialysis (HD) patients. The relation between calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) variability in HD patients and cardiac mortality is unknown. The purpose of this study was to assess the relation between variability in these parameters and cardiac mortality. Baseline demographic and biochemical parameters of 218 HD patients together with Ca values corrected with albumin and P values measured on a monthly basis and iPTH levels measured at 3-monthly intervals were recorded over 2 years. Standard deviation (SD) and smoothness index (SI) for each parameter were calculated to assess Ca, P, and iPTH variability. The relations between all parameters and cardiac mortality were then analyzed. Cardiac mortality was observed in 38 patients in the 2-year study period. Nonsurviving patients' ages, systolic and diastolic blood pressure (DBP), high sensitivity C-reactive protein (HsCRP) levels, mean iPTH, and SD iPTH were significantly higher than those of surviving patients, while albumin levels, SI iPTH and SI Ca were significantly lower. Age, low albumin, high DBP, SI iPTH, and SI Ca were identified as independent predictors of cardiac mortality at multivariate analysis. Our study shows that Ca and iPTH variability affect cardiac mortality independently of mean and baseline values. When supported by further studies, the relation between Ca and iPTH variability and cardiac mortality in HD patients can lead to a new perspective in terms of prognosis and treatment planning.

The Frequency and Outcome of Acute Kidney Injury in a Tertiary Hospital: Which Factors Affect Mortality?

Acute kidney injury (AKI) is a major cause of mortality and morbidity in hospitalized patients. Incidence and mortality rates vary from country to country, and according to different in-hospital monitoring units and definitions of AKI. The aim of this study was to determine factors affecting frequency of AKI and mortality in our hospital. We retrospectively evaluated data for 1550 patients diagnosed with AKI and 788 patients meeting the Kidney Disease: Improving Global Outcomes (KDIGO) guideline AKI criteria out of a total of 174 852 patients hospitalized in our institution between January 1, 2007 and December 31, 2012. Staging was performed based on KDIGO Clinical Practice for Acute Kidney Injury and RIFLE (Risk, Injury, Failure, Loss of kidney function and End-stage renal failure). Demographic and biochemical data were recorded and correlations with mortality were assessed. The frequency of AKI in our hospital was 0.9%, with an in-hospital mortality rate of 34.6%. At multivariate analysis, diastolic blood pressure (OR 0.89, 95% CI 0.87-0.92; P < 0.001), monitoring in the intensive care unit (OR 0.18, 95% CI 0.09-0.38; P < 0.001), urine output (OR 4.00, 95% CI 2.03-7.89; P < 0.001), duration of oliguria (OR 1.51, 95% CI 1.34-1.69; P < 0.001), length of hospitalization (OR 0.83, 95% CI 0.79-0.88; P < 0.001), dialysis requirement (OR 2.30, 95% CI 1.12-4.71; P < 0.05), APACHE II score (OR 1.16, 95% CI 1.09-1.24; P < 0.001), and albumin level (OR 0.32, 95% CI 0.21-0.50; P < 0.001) were identified as independent determinants affecting mortality. Frequency of AKI and associated mortality rates in our regional reference hospital were compatible with those in the literature. This study shows that KDIGO criteria are more sensitive in determining AKI. Mortality was not correlated with staging based on RIFLE or KDIGO. Nonetheless, our identification of urine output as one of the independent determinants of mortality suggests that this parameter should be used in assessing the correlation between staging and mortality.

Fragmented QRS is associated with subclinical left ventricular dysfunction in patients with chronic kidney disease.

OBJECTIVE: We aimed to investigate the association of fragmented QRS (fQRS) with subclinical left ventricular (LV) dysfunction in patients with chronic kidney disease (CKD). METHODS AND RESULTS: Patients with CKD who had a normal LV ejection fraction (> or = 50%) were enrolled.The tissue Doppler-derived Tei index was measured for all patients. A Tei index of > or = 0.5 was considered abnormal. Subclinical LV dysfunction was defined as the presence of an abnormal Tei index in the absence of impaired LV ejection fraction (< 50%). The fQRS was defined as the presence of an additional R wave (R') or notching of R or S wave or the presence of fragmentation in two contiguous ECG leads. The study group consisted of 82 patients (45 male, mean age 54 +/- 14 years). Overall, prevalence of fQRS was 60% among CKD patients who had a preserved LV ejection fraction. Of these, 52 (63%) had an abnormal (> or = 0.5) and 30 (37%) a normal Tei index (< 0.5). The prevalence of fQRS was significantly higher in patients with an abnormal Tei index than in patients with a normal Tei index (71% vs. 40%, P = 0.006). Patients with an abnormal Tei index had a lower E/A ratio as compared to patients with a normal Tei index (P = 0.03). Groups were similar with respect to all other variables. In multivariate logistic regression analysis, the presence of fQRS was independently associated (OR 3.52, 95% CI 1.28-9.64) with the presence of an abnormal Tei index after adjustment for potential confounders. CONCLUSION: Fragmented QRS is independently associated with subclinical LV dysfunction in patients with CKD and normal ejection fraction.

Relationship between fragmented QRS complex and left ventricular systolic and diastolic function in kidney transplant patients.

BACKGROUND: Kidney transplant is a most important replacement therapy. It reduces cardiovascular mortality and morbidity but does not fully correct impairments in cardiac function. Fragmented QRS (fQRS) complex includes various RSR' patterns with different QRS complex morphologies on electrocardiograms. OBJECTIVE: To analyze fQRS frequency and the relationship between fQRS and left ventricular function in kidney transplant patients. METHOD: -After demographic data on 39 kidney transplant patients were recorded and biochemical parameters were investigated, electrocardiograms were evaluated for the presence of fQRS. Left ventricular ejection fraction, mitral annular plane systolic excursion, peak early diastolic mitral annular velocities, late diastolic mitral annular velocities, and systolic mitral annular velocity were analyzed. RESULTS: Fragmented QRS was detected in 16 patients. A history of hypertension was associated with the presence of fQRS. Patients with fQRS had significantly lower systolic and peak early diastolic mitral annular velocities, mitral annular plane systolic excursion, and left ventricular ejection fraction than did patients without fQRS (P= .03, .01, <.001, and .03, respectively). CONCLUSION: Detection of fQRS on electrocardiograms may be useful in predicting systolic and diastolic dysfunction of the left ventricle in kidney transplant patients.

How many blood pressure measurements should we take in the office?

No consensus has emerged among different guidelines concerning how many blood pressure (BP) measurements should be performed at office visits in the diagnosis of hypertension. The purpose of this study was to examine the compatibility of various multiple average office BP measurements and 24-h BP monitoring (ABPM) in patients followed up in the posthoc analysis of the Cappadocia hypertension cohort. A total 1158 office BP measurements by 207 patients were examined. The results were then classified as G1 (average of the 1st and 2nd BP), G2 (average of the 2nd and 3rd), G3 (average of the 2nd, 3rd, and 4th), G4 (average of the 2nd, 3rd, 4th, and 5th), and G5 (average of all five measurements). Compatibility between the average values in the groups and concomitant 24-h ABPM data was examined. While a significant difference was observed between daytime 24-h ABPM SBP and G1 (p = .002), no difference was found in the other groups. Office DBP approached the daytime 24-h ABPM values as the number of measurements in the five groups increased, although average office DBP data in all groups were higher than daytime 24-h ABPM DBP (p = .000 for all). In light of our study results, we recommend that three office BP measurements be performed and that the average of the 2nd and 3rd measurements be used for SBP, while in terms of DBP, we recommend that as many measurements as possible be taken without the 1st value being included in the average.

Is Mean Platelet Volume a Predictive Marker for the Development of Thrombosis in Patients with COVID-19 Infection?

Mean platelet volume (MPV) can provide important information about the course and prognosis of many diseases. MPV is an early indicator of platelet activation, which has an important role in the pathogenesis of thrombosis. In this study, we aimed to investigate whether MPV was a predictive marker for the development of thrombosis in hospitalized patients with COVID-19 infection. Fifty-seven patients whose courses were followed after the diagnosis of COVID-19 infection using a polymerase chain reaction test during the pandemic were included in the study. Our results demonstrated that there was a negative correlation between platelet count and MPV (r=0.470, p≤ 0.01), and there was a positive correlation between Platelet Distribution Width (PDW) and MPV (r=0,933, p≤ 0.01), but no significant correlation was found between the other variables and MPV.

How does colistin-induced nephropathy develop and can it be treated?

Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin+GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin+GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

Do hemodialysis adequacy data reflect reality?

Hemodialysis (HD) adequacy requires monitoring in line with standards and at appropriate intervals. However, the use of inappropriate or incorrectly applied techniques in the determination of HD adequacy can lead to highly unfortunate results. This study was intended to identify the path to a solution by determining how far HD adequacy in HD centers in our region reflects reality. Three hundred and thirty HD patients from eight centers were included. On the first visit, predialysis and postdialysis blood collection with the centers' own methods being used were observed and errors were recorded. Kt/V1 was calculated from pre- and postdialysis blood specimens taken by the units themselves. On the second visit, one session later, pre- and postdialysis blood samples were collected in line with guidelines by ourselves, the authors, and Kt/V2 was calculated from these samples. The eight units' total Kt/V2 value was significantly lower compared with Kt/V1 (<0.0001). The level of patients in all centers with Kt/V1 <1.2 was 13.5%, and that of patients with Kt/V2 <1.2 was 22.1%. No center, apart from one unit, managed to complete the collection of blood specimens as recommended by the guidelines. With one exception, blood collection for HD adequacy was not performed using proper technique in any center. This simple but easily overlooked situation, HD being regarded as adequate though in fact it is not, may lead to patients not being treated effectively and accurately and to a rise in mortality and morbidity in the long term.

Thrombin activatable fibrinolysis inhibitor (TAFI) levels in hypertensive patients and a comparison of the effects of amlodipine and ramipril on TAFI levels.

Hypertension is associated with fibrinolysis abnormality. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a novel molecule-linking coagulation and fibrinolysis. The aim of this study was to investigate the levels of TAFI in primary hypertensive patients and to compare the effects of amlodipine and ramipril on TAFI levels. The study was performed with 58 hypertensive subjects and 27 healthy volunteers. Biochemical and hematological parameters and TAFI levels were measured at baseline and after 1-month follow-up. TAFI concentrations increased in hypertensive patients compared with the controls (P = .030). Additionally, TAFI levels decreased with blood pressure control at 1-month follow-up (P = .026). There was no significant difference between TAFI levels in the amlodipine and ramipril groups at baseline. However, after 1-month follow-up, TAFI levels were decreased in the amlodipine group (P = .037) but not in the ramipril group. Our study is the first in the literature to determine increased TAFI levels in primary hypertension patients. In addition, we determined a decrease in TAFI levels in the amlodipine group after 1 month, but none in the ramipril group.

The Effect of Ambient Air Pollution on Office, Home, and 24-Hour Ambulatory Blood Pressure Measurements.

BACKGROUND: Air pollution has recently been linked to a number of cardiovascular diseases, particularly hypertension (HT). In our study, we aimed to evaluate the association between air pollution and blood pressure (BP) and compare the relationship of BP measurement results obtained using different methods (office, home, and 24-hour ambulatory BP monitoring [ABPM]). METHODS: This retrospective nested panel study performed with prospective Cappadocia cohort data investigated the relationships between particulate matter (PM) 10 and sulfur dioxide (SO2) and concurrent home, office, and 24-hour ABPM data at each control performed over a 2-year period. RESULTS: A total of 327 patients in the Cappadocia cohort were included in this study. On the day of office blood pressure measurement, there was an increase of 1.36 mm Hg in systolic BP and 1.18 mm Hg in diastolic BP for every 10 µm/m3 rise in SO2 values. A mean 3-day 10 µm/m3 increase in SO2 was linked to an increase of 1.60 mm Hg in systolic BP and 1.33 mm Hg in diastolic BP. A 10 µm/m3 rise in mean SO2 on the day of 24-hour ABPM measurement was found to be associated with an increase of 1.3 mm Hg in systolic BP and 0.8 mm Hg in diastolic BP. SO2 and PM 10 had no effect on home measurements. CONCLUSION: In conclusion, increased SO2 levels, during winter months in particular, can be associated with an elevation in office BP values. Our study findings show that air pollution in the setting in which BP is measured may be associated with the results.

Is there any way to protect from tacrolimus-induced renal and pancreas injury?

BACKGROUND: The aim of this study was to explore effects of erythropoietin and pentoxifylline in tacrolimus-induced pancreatic beta cell and renal injury in rats. METHODS: Rats in group I were given saline; rats in group II were injected with tacrolimus; rats in group III were received erythropoietin (Epo) and tacrolimus; while rats in group IV were injected pentoxifylline (Ptx) plus tacrolimus for nine d. On 10th day, blood and tissue samples were taken for biochemical and pathological evaluations. RESULTS: Tacrolimus-injected animals exhibited significant elevation in blood urea nitrogen (BUN), and serum BUN levels were improved in rats pretreated with Ptx. Significantly more apoptotic nuclei were observed in kidneys of tacrolimus group. In rats subjected to tacrolimus and pretreated with Epo, there was significant decrease in apoptotic nuclei staining than those in tacrolimus group. Blood trough levels of tacrolimus were significantly higher in erythropoietin-pretreated group, although same amount of tacrolimus was injected with other groups. CONCLUSION: Results of our study demonstrated significant antiapoptotic effects of erythropoietin on renal tubules, increasing effect of erythropoietin on tacrolimus blood levels, and insignificant antioxidant effects of both erythropoietin and pentoxifylline on renal and pancreas tissues. Study with clinically greater tacrolimus levels may be useful to confirm these findings.

Protective effect of the grape seed proanthocyanidin extract in a rat model of contrast-induced nephropathy.

AIM: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. MATERIALS AND METHODS: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. CONCLUSION: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy.

AIM: Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti-oxidant and anti-apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue. RESULTS: The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels. CONCLUSION: We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

Rhabdomyolysis and severe muscle weakness secondary to colistin therapy.

Rhabdomyolysis is a clinical condition that causes renal failure up to 40%. Rhabdomyolysis may be traumatic or nontraumatic. Colistin (polymyxin E) is an effective antibiotic. Nephrotoxicity is a frequently encountered side effect. The nephrotoxic effect of colistin is thought to be associated with increased membrane permeability, cell swelling and lysis, and the development of acute tubular necrosis. Here, we report a case of nontraumatic rhabdomyolysis associated with the use of colistin. There is only one report of rhabdomyolysis secondary to colistin in the literature, and there is no report of a case developing severe tetraparesis, as in our case.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.

BACKGROUND/AIMS: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. METHODS: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. RESULTS: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. CONCLUSION: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity.

OBJECTIVES: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. CONCLUSION: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities.