Comparison of all renal replacement therapy modalities in terms of COVID-19 infection rate & mortality in the COVID-19 pandemic and importance of home therapies.

BACKGROUND: This study aimed to compare the infection rate and infection-related mortality among all renal replacement therapies during the COVID-19 pandemics. METHODS: One thousand three hundred thirty-six end-stage renal disease (ESRD) patients who had applied for renal replacement therapy between March 2020 and January 2021 were included in the study. COVID-19 infection and mortality rates were compared between patient groups. RESULTS: The COVID-19 infection rate in the whole study group was 13.12% (n: 178). The highest infection rate was in the center hemodialysis, 16.33% (n: 139). There was no COVID-19 infection in home hemodialysis (HHD). Mortality rate was 2.87% (n: 39) in the whole cohort and 3.87% (n: 33) in center hemodialysis (CHD), 1.47% (n:5) in kidney transplant (Tx), and 0.81% (n: 1) in the peritoneal dialysis (PD) group. COVID-19 infection rate of home replacement therapy (HRT) (n: 39) patients was significantly lower than CHD (n: 139) (p < 0.001). CONCLUSION: The COVID-19 infection rate and mortality were significantly lower than those of CHD in all home-based modalities subgroups.

Middle-term outcomes in renal transplant recipients with COVID-19: a national, multicenter, controlled study.

Background: In this study, we evaluated 3-month clinical outcomes of kidney transplant recipients (KTR) recovering from COVID-19 and compared them with a control group. Method: The primary endpoint was death in the third month. Secondary endpoints were ongoing respiratory symptoms, need for home oxygen therapy, rehospitalization for any reason, lower respiratory tract infection, urinary tract infection, biopsy-proven acute rejection, venous/arterial thromboembolic event, cytomegalovirus (CMV) infection/disease and BK viruria/viremia at 3 months. Results: A total of 944 KTR from 29 different centers were included in this study (523 patients in the COVID-19 group; 421 patients in the control group). The mean age was 46 ± 12 years (interquartile range 37-55) and 532 (56.4%) of them were male. Total number of deaths was 8 [7 (1.3%) in COVID-19 group, 1 (0.2%) in control group; P = 0.082]. The proportion of patients with ongoing respiratory symptoms [43 (8.2%) versus 4 (1.0%); P < 0.001] was statistically significantly higher in the COVID-19 group compared with the control group. There was no significant difference between the two groups in terms of other secondary endpoints. Conclusion: The prevalence of ongoing respiratory symptoms increased in the first 3 months post-COVID in KTRs who have recovered from COVID-19, but mortality was not significantly different.

Trends of primary glomerular disease in Turkey: TSN-GOLD registry report.

BACKGROUND: Although several renal biopsy registry reports have been published worldwide, there are no data on primary glomerular disease trends in Turkey. METHODS: Three thousand eight-hundred fifty-eight native kidney biopsy records were assessed in the Turkish Society of Nephrology Primary Glomerulopathy Working Group (TSN-GOLD) Registry. Secondary disease and transplant biopsies were not recorded in the registry. These records were divided into four periods, before 2009, 2009 to 2013, 2013-2017, and 2017-current. RESULTS: A total of 3858 patients (43.6% female, 6.8% elderly) were examined. Nephrotic syndrome was the most common biopsy indication in all periods (58.6%, 53%, 44.1%, 51.6%, respectively). In the whole cohort, IgA nephropathy (IgAN) (25.7%) was the most common PGN with male predominance (62.7%), and IgAN frequency steadily increased through the periods (× 2 = 198, p < 0.001). MGN was the most common nephropathy in the elderly (> 65 years), and there was no trend in this age group. An increasing trend was seen in the frequency of overweight patients (× 2 = 37, p < 0.0001). Although the biopsy rate performed with interventional radiology gradually increased, the mean glomeruli count in the samples did not change over the periods. CONCLUSIONS: In Turkey, IgAN is the most common primary glomerulonephritis, and the frequency of this is increasing.

The Effect of Smoking on Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease Patients with Preserved Renal Function.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), endothelial dysfunction (ED) is common and occurs much earlier than kidney function impairment. The impact of smoking on ED in ADPKD patients has not been previously studied. The aim of this study was to investigate the potential contribution of smoking habits to ED and subclinical atherosclerosis in these patients. METHODS: This case-control study included 54 ADPKD patients with preserved renal function and 45 healthy control subjects. ED was assessed using ischemia-induced forearm flow-mediated dilatation (FMD). Carotid intima-media thickness (CIMT) was measured from 10 mm proximal to the right common carotid artery. Clinical demographic characteristics and laboratory data were recorded for the patients and control group. Regression analysis was used to determine independent associations of ED and CIMT. RESULTS: FMD was significantly lower in the ADPKD patients (19.5 ± 5.63 vs. 16.56 ± 6.41, p = .018). Compared with nonsmoker ADPKD patients, smoker patients had significantly lower FMD values (18.19 ± 6.52 vs. 13.79 ± 5.27, p = .013). In multiple regression analysis, age (ß = -0.294, 95% CI: -0.392: -1.96, p = .001) for FMD and smoking (ß = 1.328, 95% CI: 0.251, 2.404, p = .017) for CIMT were independent predictors. CONCLUSIONS: Patients with ADPKD had more impaired endothelial function and subclinical atherosclerosis compared with control subjects. Smoking may increase the risk of subclinical atherosclerosis in ADPKD patients.

Morning blood pressure surge in early autosomal dominant polycystic kidney disease and its relation with left ventricular hypertrophy.

INTRODUCTION: The activation of the sympathetic nervous system, which usually leads to a swift surge in blood pressure in the morning hours (MBPS) may be the cause of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in early autosomal dominant polycystic kidney disease (ADPKD) patients. We studied the association between MBPS and LVH in ADPKD patients with preserved renal functions. METHODS: Patients with ADPKD with preserved renal functions were enrolled. Prewaking MBPS was calculated using ambulatory blood pressure monitoring. The patients were categorized as MBPS (≥median) and non-MBPS (

Epidemiological features of primary glomerular disease in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: The largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. METHODS: Data of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study. RESULTS: The mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467-6307) mg/day, 1.0 (IQR: 0.7-1.6) mg/dL, 82.9 (IQR: 47.0-113.0) mL/min and 3.2 ± 0.9 g/dL, respectively. CONCLUSIONS: The distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

The Comparison Spondin 2 Levels in Primary Glomerular Diseases.

Spondin 2 (SPON2) plays an important role in multiple processes and is a member of the Spondin 2/F-spondin family of extracellular matrix proteins. We investigated serum SPON2 levels and its correlation with renal functions and urine protein excretion in different glomerular diseases. The cohort included 97 consecutive adults with persistant proteinuria (>300 mg/day) with the diagnosis of focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), IgA nephropathy (IgAN), membranoproliferative glomerulonephritis (MPGN), and AA amyloidosis and the control groups with 15 polycystic kidney disease (PKD) and 32 healthy people. Serum SPON2 levels in MN (64.6 ng/mL), FSGS (47.8 ng/mL), IgAN (52.6 ng/mL), MPGN (54.6 ng/mL), and AA amyloidosis (60.7 ng/mL) groups were higher than those of the control (26.4 ng/mL) and nonglomerular disease groups (PKD) (15.3 ng/mL). Only serum SPON2 levels were correlated with serum uric acid and triglyceride levels in patients with glomerular disease. This is the first study to show that serum SPON2 levels are similar in different glomerular diseases and that there is no correlation between SPON2 and proteinuria grade.

The effect of hemodialysis, peritoneal dialysis and renal transplantation on nutritional status and serum micronutrient levels in patients with end-stage renal disease; Multicenter, 6-month period, longitudinal study.

PURPOSE: Nutritional status and micronutrient levels of end stage renal disease (ESRD) patients may vary depending on the mode of renal replacement therapy (RRT). We aimed to compare the effects of hemodialysis, peritoneal dialysis (PD) and renal transplantation (RT) on micronutrient levels and nutritional status in ESRD patients. PATIENTS AND METHODS: A total of 77 ESRD patients who had not received RRT were included in this prospective longitudinal study. All ESRD patients underwent a blood serum analysis that assessed the micronutrients such as selenium, copper, zinc, chromium, retinol, thiamine and vitamin B6 as well as a nutritional status assessment. After the baseline assessments and the initiation of RRT was accomplished, all patients were followed for 6 months. RESULTS: The study showed significant improvements in subjective global assessment scores (percentage increases in score A were 26.6 and 36.6; p = 0.039 and p = 0.001; respectively), mid-arm circumference and the skin-fold thicknesses (p < 0.001, p < 0.001; respectively) in the RT and hemodialysis groups. The examinations at sixth month revealed a significant increase in body weight (4.8 kg; p = 0.002) and albumin levels (0.6 g/dL; p < 0.001) in only RT group. Zinc, thiamin and vitamin B6 were the most deficient micronutrients (44.1 %, 24.7 % and 35.1 %; respectively) in ESRD patients. There was a significant increase in selenium and retinol levels (p = 0.020 and p < 0.001; respectively) but a significant decrease in thiamin levels (p = 0.041) in RT patients. A significant increase in retinol levels (p = 0.028) and a significant decrease in thiamin levels (p = 0.022) was observed in the hemodialysis patients. However, no significant change in micronutrient levels was observed in the PD patients. CONCLUSION: The results support the recommendation that ESRD patients should be supplemented with water-soluble vitamins, especially thiamine and vitamin B6, and trace elements, especially zinc. RT appears to be superior to other modes of RRT when examining SGA score, anthropometric measurements, albumin and micronutrient levels.

Cytokine signal suppressor (SOCS) 1-1478 CA/del gene polymorphism in Turkish patients with polycystic ovary syndrome.

Eighty-four subjects, premenopausal female patients (n = 42, mean (SD) age: 26.4 (4.2) years) diagnosed with polycystic ovary syndrome (PCOS) and age-matched healthy volunteers (n = 42, mean (SD) age: 27.6(3.4) years), were included in this study. Data on physical examination, anthropometric measurements and blood biochemistry analysis were recorded for each subject along with analysis for SOCS1-1478 CA/del polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The relation of SOCS1-1478 CA/del polymorphism to PCOS status and insulin resistance was analysed via logistic regression analysis. Mean (SD) levels for BMI (28.5(6.5) vs.22.5 (4.9) kg/m2, p < .001), HOMA-IR (3.1(1.8) vs.1.5 (1.0), p < .001), LDL-cholesterol (115.9(32.7) vs.100.7 (27.3)mg/dL, p = .03) and triglyceride (113.8(64.9) vs.83.3(36.3)mg/dL, p = .017) were significantly higher in patients. Groups were similar in terms of SOCS1-1478 CA/del polymorphism. No significant relation of this polymorphism was noted to PCOS and HOMA-IR. Our findings revealed no difference between groups in terms of the rate of SOCS1-1478 CA/del polymorphism, and no significant relation of this polymorphism to insulin resistance and PCOS status. Impact statement Polycystic ovary syndrome (PCOS), the most common cause of anovulation and the most commonly encountered form of female endocrine disease. SOCS proteins have been suggested to play a fundamental role in the negative feedback regulation of the JAK-STAT pathway, which is the major signalling pathway involved in a wide range of physiologic and pathologic processes, including inflammatory diseases, malignancies and immune disorders. Pathways involving the induction of suppression of SOCS proteins were also shown likely to be involved in mediating cytokine-induced insulin resistance. The present study was designed to determine the frequency of SOCS1-1478 CA/del gene polymorphism in patients with PCOS in relation to healthy controls and insulin resistance. Our findings revealed significantly higher rates of insulin resistance, obesity and dyslipidaemia in Turkish patients with PCOS compared with age-matched healthy controls, while no difference between study groups in terms of the rate of SOCS1-1478 CA/del polymorphism along with no significant relation of SOCS1-1478 CA/del polymorphism to insulin resistance and PCOS status. Future larger scale studies with the application of standardised diagnostic methods and criteria, and of state-of-the-art modern techniques including genomics, proteomics and pharmacogenetics would provide better understanding of the association between PCOS and genomic variants.

Restless-legs syndrome and insomnia in hemodialysis patients.

AIM/BACKGROUND: Restless legs syndrome (RLS) is a common neurological movement disorder which is commonly seen in hemodialysis (HD) patients. Insomnia, depression, and anxiety disorders frequently show concurrence. In this study, we aimed to investigate RLS and insomnia prevalence and related factors in HD patients. SUBJECTS AND METHODS: Patients who were under HD treatment and healthy controls with similar mean age, sex ratio, and hypertension and diabetes mellitus frequency were included in this study. Depression, insomnia, and daytime sleepiness assessments were performed by using Beck Depression Inventory, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of RLS was made using the International RLS Study Group consensus criteria. RESULTS: About 156 HD patients and 35 controls were enrolled. The mean age was 50.6 in the HD group and 49.7 in the control group. Female sex was 43.9% in the HD group and 57.1% in the control group. RLS was significantly more frequent in HD patients compared with controls. The rate of sub-threshold insomnia and insomnia with moderate severity was higher in HD patients. While insomnia severity score and diabetes mellitus were significantly associated with the presence of RLS, depression, RLS, older age, and being under HD treatment were independently associated with insomnia severity. CONCLUSIONS: HD patients commonly have RLS and insomnia. Insomnia and diabetes mellitus seem to be major factors underlying RLS in HD patients. Furthermore, depression and RLS seem to be closely related to insomnia in these patients. Treatment of depression, insomnia, and RLS may be beneficial to improve quality of life in HD patients.

Correlation between arterial stiffness and inflammatory markers in autosomal dominant polycystic kidney disease patients with preserved renal function.

AIM: To evaluate the association between arterial stiffness and inflammatory markers including C-reactive protein (CRP), pentraxin 3 (PTX3) and neutrophil-to-lymphocyte ratio (NLR) in autosomal dominant polycystic kidney disease (ADPKD) patients with preserved renal function. METHODS: A total of 52 ADPKD patients [mean (SD) age 38.2 (12.8) years, 69.2 % were females] with preserved renal function and 25 healthy volunteers [mean (SD) age 35.5 (6.5) years, 48.0 % were females] were included. Data on patient characteristics, blood biochemistry, inflammatory markers [PTX3 (pg/mL), CRP (mg/dL) and NLR] and arterial stiffness [large artery elasticity index (LAEI) (mL/mmHg × 10) and small artery elasticity index (SAEI) (mL/mmHg × 100)] were recorded in patient and control groups. Correlation between inflammatory markers and arterial stiffness parameters was analysed in patients. RESULTS: Overall, 42.3 % of ADPKD patients were hypertensive and 44.4 % were receiving renin-angiotensin-aldosterone system (RAAS) blockade therapy. Median levels for PTX3 [442.0 (20.0-4140.0) pg/mL vs. 220.5 (14.7-393.0) pg/mL, p < 0.001] and SAEI [4.90 (1.60-11.80) mL/mmHg × 100 vs. 6.45 (2.80-15.70) mL/mmHg × 10, p = 0.013] were significantly higher in ADPKD patients than in controls. PTX3 and CRP were not correlated with arterial elasticity, while NLR was significantly correlated with LAEI negatively (Rho = -0.278, p = 0.042). CONCLUSION: In conclusion, our findings revealed increased PTX3 levels and reduced SAEI in patients as compared with controls, while no correlation between inflammatory markers studied and the small artery elasticity.

Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic nephropathy.

AIM: We aimed to determine whether serum SPON2 is a useful biomarker in the detection of Diabetic Nephropathy (DN) and to compare serum SPON2 levels with 24-hour urinary albumin excretion rate (UAER) in patients with DN at different stages. METHODS: The cohort included 80 adult patients with T2D and 20 healthy controls. The patients with T2D were divided into four groups according to UAER and serum creatinine (sCr) levels. Group 1 consisted of patients with normoalbuminuria (n = 20), Group 2 with microalbuminuria (n = 20), Group 3 with macroalbuminuria (n = 20) and Group 4 with albuminuria and sCr > 1.5 mg/dL (n = 20). RESULTS: There were no significant differences between the groups in terms of demographic data, C-reactive protein, HbA1c, lipids, serum uric acid levels and leukocyte counts. SPON2 levels were observed to increase linearly with increasing severity of diabetic nephropathy levels. The SPON2 levels of Group 4 were significantly higher than Group 1 and the controls, and SPON2 levels of Group 3 were significantly higher than Group 1. Blood urea nitrogen, creatinine and UAER were significantly positively correlated with SPON2; serum total protein and calcium levels were negatively correlated with SPON2 in patients with DN. CONCLUSION: We observed a linear and significant increase in SPON2 levels of patients with T2D as the stage of DN increased, but serum SPON2 level was not as effective as microalbuminuria in reflecting nephropathy. Also, serum SPON2 level was not as good as urine and tissue levels of SPON2 in detection of renal damage in DN.

Arterial dysfunction in early autosomal dominant polycystic kidney disease independent of fibroblast growth factor 23.

INTRODUCTION: Recent studies report reduced vascular compliance and elevated levels of fibroblast growth factor 23 (FGF23) in patients with autosomal dominant polycystic kidney disease (ADPKD) and preserved kidney function. In the present study, we investigated the relationship between vascular compliance and FGF23 in patients in early phases of ADPKD. MATERIALS AND METHODS: We studied 54 ADPKD patients with preserved kidney function and 24 healthy individuals. All participants underwent noninvasive pulse wave analysis in order to determine large arterial elasticity index (LAEI) and small arterial elasticity index (SAEI) using a modified Windkessel model. Levels of FGF23 in addition to several cardiovascular risk factors were evaluated. Linear regression analyses were performed to determine independent correlates of LAEI, SAEI, and FGF23. RESULTS: In the ADPKD group, 33 patients were hypertensive and the remaining patients were normotensive. Serum FGF23 levels of both ADPKD groups were significantly higher than that in the controls. Both hypertensive and normotensive ADPKD patients had lower LAEI and SAEI levels compared to the controls. There was no significant correlation between vascular compliance parameters and FGF23 levels. Having ADPKD was independently associated with increased FGF23 levels and decreased SAEI. CONCLUSIONS: Fibroblast growth factor 23 was found substantially elevated and arterial compliance was found significantly decreased in early ADPKD patients regardless of hypertension. However, there was no significant correlation between FGF23 levels and arterial function parameters. Additional studies are required to determine possible mechanisms of these disturbances and cardiovascular effects of FGF23 in ADPKD patients.

Relationship between glycemic control, microalbuminuria and cognitive functions in elderly type 2 diabetic patients.

AIM: The prevalence of diabetes is increasing in elderly populations, and is thought to be an important risk factor for cognitive dysfunction in this age group. METHODS: The study included 104 patients aged over 60 years who were followed-up for type 2 diabetes for at least 6 months, in addition to 44 controls. Glycemic parameters, microangiopathic complications, microalbumin elimination, and the Standardized Mini Mental State Examination (SMMSE) scores were used as indicators of cognitive function. RESULTS: The SMMSE scores of diabetic patients were significantly lower than the control group (p < 0.05). The average SMMSE score for normoalbuminuric diabetic patients was 22.36 ± 4.66, compared with 22.61 ± 4.90 for the microalbuminuria patients (p = 0.84). A positive correlation was found between SMMSE scores and patients' hemoglobin values and education levels, whereas a negative correlation was noted between SMMSE scores and systolic and diastolic blood pressures and hemoglobin A1c levels (p < 0.05). Patients with diabetic neuropathy, a microvascular complication of diabetes, were found to have significantly lower SMMSE scores (p = 0.011). CONCLUSION: Elderly diabetic patients showed decreased cognitive function compared to volunteers. No relationship was established between microalbuminuria and cognitive functions, although diabetic neuropathy was found to be related to decreased cognitive function.

Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study.

This cross-sectional, observational pilot study was designed to investigate the frequency of different endpoints of genotoxicity (sister-chromatid exchange, total chromosome aberrations, and micronucleus formation) and cytotoxicity (mitotic index, replication index, and nuclear division index) in the peripheral lymphocytes of patients with type-2 diabetes treated with different oral anti-diabetic agents for 6 months. A total of 104 patients who met the American Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical nutrition therapy (control group). The results for all the genotoxicity endpoints were significantly different across the four study groups. Post hoc analysis revealed that the genotoxicity observed in the sitagliptin group was significantly higher than that observed in the medical nutrition therapy group, but lower than that occurring in subjects who received thiazolidinediones. All of the three cytotoxicity endpoints were significantly lower in patients treated by oral anti-diabetic agents compared with those who received medical nutrition therapy. However, the three indexes did not differ significantly in the sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot data indicate that sitagliptin and thiazolidinediones may exert genotoxic and cytotoxic effects in patients with type-2 diabetes. Further investigations are necessary to clarify the possible long-term differences between oral anti-diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can modulate the risk of developing diabetic complications in general and cancer in particular.

Ki-67 proliferation index in renal biopsy samples of patients with systemic lupus erythematosus and its correlation with clinical findings.

INTRODUCTION: Systemic lupus erythematosus is an autoimmune disease that may affect almost all organ systems. Renal involvement is the most significant prognostic factor. Renal biopsy findings play an important role in treatment decision. Ki-67 is a monoclonal antibody that is only found in proliferative cells. This study aimed to investigate the proliferative activity in renal biopsy specimens of patients with lupus nephritis using the Ki-67 monoclonal antibody, and to compare the proliferative index between different subgroups of patients. MATERIALS AND METHODS: Renal biopsy specimens of 29 patients with systemic lupus erythematosus were retrospectively evaluated. Type of lupus nephritis and activity and chronicity indexes were determined. Ki-67 immunostaining was performed. For each patient, 1000 cells were counted and the number of Ki-67 positive cells was determined. The Ki-67 activity index was compared between different subgroups of lupus nephritis and correlated with systemic lupus erythematosus disease activity index, serum creatinine, proteinuria, anticardiolipin antibodies, and complement levels. RESULTS: A positive correlation between Ki-67 proliferation index, serum creatinine levels, and systemic lupus erythematosus disease activity index were found. Although conventional activity indexes were low, in 3 of 9 patients with class II lupus nephritis, Ki-67 proliferation indexes were high, indicating proliferation. CONCLUSIONS: Ki-67 can be used as a proliferation marker in renal biopsy specimens for patients diagnosed with systemic lupus erythematosus.

Effect of the direct renin inhibitor aliskiren in the prevention of experimental contrast-induced nephropathy in the rat.

BACKGROUND: Renal vasoconstriction, activated by the renin-angiotensin system, plays a pivotal role in the pathogenesis of contrast-induced nephropathy (CIN). The purpose of this study was to evaluate the effect of aliskiren, a direct renin inhibitor, for the prophylaxis of experimental CIN in the rat. METHODS: Thirty-two Wistar albino rats were divided into four groups of 8 rats each, namely the control (C), aliskiren (A), contrast media (CM) and aliskiren plus contrast media (ACM) groups. Aliskiren was given orally at a dose of 50 mg/kg/day once daily for 5 consecutive days. CIN was induced by intravenous administration of indomethacin, N-nitro-L-arginine methyl ester and high-osmolar contrast medium meglumine amidotrizoate. Renal function parameters, kidney histology and tubular expression of vascular endothelial growth factor were determined. RESULTS: Mean serum creatinine was significantly lower (p < 0.001) and mean creatinine clearance was higher (p < 0.001) in the ACM group compared with the CM group. However, there were no differences between the ACM and CM groups in terms of tubular necrosis, proteinaceous casts, medullary congestion and vascular endothelial growth factor expression. CONCLUSION: Our preliminary data seem to suggest a potential role of aliskiren for the prophylaxis of CIN in an experimental rat model.

Effect of sitagliptin monotherapy on serum total ghrelin levels in people with type 2 diabetes.

AIM: Sitagliptin is not associated with weight gain and has neutral effects on body weight. It is unclear whether sitagliptin treatment alters serum ghrelin levels in people with type 2 diabetes. METHODS: Forty-four subjects with type 2 diabetes were randomly assigned to receive sitagliptin or medical nutrition therapy (MNT) for 12 weeks. Changes in anthropometric variables, glycemic control, insulin resistance, lipid parameters, and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. RESULTS: Significant decreases in body weight and body mass index were observed over the entire study period in both treatment groups. Glycosylated hemoglobin and postprandial plasma glucose levels were statistically significant decreased in the groups receiving sitagliptin compared with baseline values (p=0.021 and p=0.021, respectively), while they were unchanged in the groups receiving MNT. There was a significant decrease in total ghrelin in the groups receiving sitagliptin (p=0.04) compared with baseline values but not in the groups receiving MNT (p=0.46) at the end of the 12 weeks. CONCLUSIONS: In this study of patients with type 2 diabetes, treatment with sitagliptin was associated with a significant decrease in serum ghrelin levels. These results suggest that the neutral effect of sitagliptin on weight might be associated with the suppression of fasting serum ghrelin levels.

Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients.

Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P < .001) group had a significant increase from baseline in sRAGE values that was not seen in the medical nutrition therapy and rosiglitazone groups. We conclude that, in type 2 diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.