Effects of Induction Therapy on Graft Functions in Terms of Immunologic Risk.

BACKGROUND: Advances in immunosuppressive therapies and surgical techniques have led to a significant reduction in the incidence of rejection within 1 year after kidney transplantation. Immunologic risk is an important factor affecting graft functions and guiding the clinician in the selection of induction therapy. The aim of this study was to investigate graft functions based on serum creatinine levels, Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) and proteinuria levels, frequency of leukopenia, cytomegalovirus (CMV) and BK virus polymerase chain reaction (PCR) positivity in patients with low and high immunologic risk. MATERIAL AND METHODS: This retrospective study included 80 renal recipients. Recipients were divided into 2 groups: patients at low immunologic risk who received basiliximab only and those with high immunologic risk who received low-dose (1.5 mg/kg for 3 days) antithymocyte globulin and basiliximab. RESULTS: No significant differences were observed between the 2 risk groups in terms of first, third, sixth, and 12th-month creatinine levels, CKD-EPI, proteinuria levels, leukopenia frequency, and CMV and BK virus PCR positivity. CONCLUSION: One-year graft survivals did not differ significantly between these 2 treatment modalities. The combined use of low-dose antithymocyte globulin and basiliximab in the induction treatment of patients with high immunologic risk seems promising in terms of graft survival, leukopenia frequency, and CMV and BK virus PCR positivity.

The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. METHODS: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. RESULTS: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. CONCLUSIONS: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus.

The prevalence of diabetes mellitus (DM) is increasing secondary to increased consumption of food and decreased physical activity worldwide. Hyperglycaemia, insulin resistance and hypertrophy of pancreatic beta cells occur in the early phase of diabetes. However, with the progression of diabetes, dysfunction and loss of beta cells occur in both types 1 and 2 DM. Programmed cell death also named apoptosis is found to be associated with diabetes, and apoptosis of beta cells might be the main mechanism of relative insulin deficiency in DM. Autophagic cell death and apoptosis are not entirely distinct programmed cell death mechanisms and share many of the regulator proteins. These processes can occur in both physiologic and pathologic conditions including DM. Besides these two important pathways, endoplasmic reticulum (ER) also acts as a cell sensor to monitor and maintain cellular homeostasis. ER stress has been found to be associated with autophagy and apoptosis. This review was aimed to describe the interactions between apoptosis, autophagy and ER stress pathways in DM.

Serum uric acid may predict development of progressive acute kidney injury after open heart surgery.

OBJECTIVES: Acute kidney injury (AKI) is a common complication of cardiac surgery developing in 25-35% cases. Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine. Some studies demonstrated the predictive role of post-operative serum uric acid (SUA) as an early marker of AKI. We aimed to study the role of serum and urine NGAL as well as SUA to predict progression of AKI. DESIGN AND METHODS: This is a prospective observational study of patients undergoing cardiac surgery. Blood and urine samples for measurement of uric acid, serum and urine NGAL levels were collected prior to cardiac surgery (0 h), and in the time course at 2nd and 24th hours after surgery. Patients who developed AKI were divided into two subgroups as progressing and non-progressing AKI. RESULTS: Sixty patients (42 males, 18 females) were included. After cardiac surgery, 40 patients developed AKI, 20 of whom non-progressing AKI, and 20 progressing AKI. All of the markers significantly increased in AKI patients. A receiver operator characteristics (ROC) curve analysis showed higher predictive ability of SUA for progressing AKI compared with serum and urine NGAL. When compared markers obtained at the second hour after surgery, UA had significantly large AUC than NGAL to predict AKI developed at 24 and 48 h, particularly in patients, who require renal replacement therapy (RRT). CONCLUSION: Uric acid seems to predict the progression of AKI and RRT requirement in patients underwent cardiac surgery better than NGAL.

The relationship between neutrophil-to-lymphocyte ratio and vascular calcification in end-stage renal disease patients.

Chronic inflammation was found to be correlated with coronary (CAC) and thoracic peri-aortic calcification (TAC) in end-stage renal disease (ESRD) patients. Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and noncardiac disorders. Data regarding NLR and its association with TAC and CAC are lacking. We aimed to determine the relationship between NLR and vascular calcification in ESRD patients. This was a cross-sectional study involving 56 ESRD patients (22 females, 34 males; mean age, 49.9 ± 14.2 years) receiving peritoneal dialysis or hemodialysis for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. TAC and CAC scores were measured by using an electrocardiogram-gated 64-multidetector computed tomography. NLR was calculated as the ratio of the neutrophils and lymphocytes. There was a statistically significant correlation between NLR, TACS and CACS in ESRD patients (r = 0.43, P = 0.001 and r = 0.30, P = 0.02, respectively). The stepwise linear regression analysis revealed that age, as well as NLR were independent predictors of TACS. However, increased age was the only independent predictor of CACS according to linear regression analysis. Simple calculation of NLR can predict vascular calcification in ESRD patients.

Soluble TWEAK independently predicts atherosclerosis in renal transplant patients.

BACKGROUND: Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in CKD patients. A novel markers, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers in inflammatory disorders including CKD. The role of Rtx in terms of atherogenesis is still unclear. We aimed to investigate the relationship between sTWEAK, NLR and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects. METHODS: Cross-sectional analysis in which CIMT measurements, NLR and serum TWEAK levels were assessed in 70 Rtx patients (29 females; mean age, 40.6 ± 12.4 years) and 25 healthy subjects (13 females, mean age; 37.4±8.8 years). RESULTS: sTWEAK levels were significantly decreased (p=0.01) and hs-CRP, NLR and CIMT levels of Rtx patients were significantly increased compared to healthy subjects (p<0.0001, p=0.001, p<0.0001, respectively). sTWEAK was also found to be decreased when eGFR was decreased (p=0.04 between all groups). CIMT was positively correlated with sTWEAK and NLR in Rtx patients (r=0.81, p<0.0001 and r=0.33, p=0.006, respectively). sTWEAK was also positively correlated with NLR (r=0.37, p=0.002). In the multivariate analysis only sTWEAK was found to be an independent variable of increased CIMT. CONCLUSION: sTWEAK might have a role in the pathogenesis of ongoing atherosclerosis in Rtx patients.

Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients.

Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end-stage renal disease (ESRD) patients. Recently, platelet-to-lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross-sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C-reactive protein, TNF-α, IL-6 levels were measured. PLR, NLR, serum high sensitive C-reactive protein, IL-6, and TNF-α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL-6, and TNF-α levels when compared to patients with PLR < 139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL-6, and TNF-α in this population. When we compared the association of PLR and NLR with IL-6 (r = 0.371, P = 0.003 vs. r = 0.263, P = 0.04, respectively) and TNF-α (r = 0.334, P = 0.008 vs. r = 0.273, P = 0.032, respectively), PLR was found to be superior to NLR in terms of inflammation in ESRD patients. Simple calculation of PLR can predict inflammation better than NLR in ESRD patients.

The relationship between oxidative stress, inflammation, and atherosclerosis in renal transplant and end-stage renal disease patients.

OBJECTIVES: Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and is also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in the end-stage renal disease (ESRD) patients. Ischemia-modified albumin (IMA), pentraxin-3 (PTX-3), and neutrophil-to-lymphocyte ratio (NLR) were introduced as oxidative stress and inflammatory biomarkers in ESRD. The role of Rtx in terms of atherogenesis, oxidative stress, and inflammation is still unclear. We aimed to investigate the relationship between IMA, PTX-3, NLR, and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects and ESRD patients receiving hemodialysis (HD) and peritoneal dialysis (PD). DESIGN AND METHODS: Cross-sectional analysis in which CIMT measurements, NLR, and serum PTX-3 and IMA levels were assessed in 18 Rtx patients (10 females; mean age: 40.0 ± 13.3 years), 16 PD patients (7 females; 40.2 ± 12.9 years), 14 HD patients (8 females; 46.6 ± 10.7 years), and 19 healthy subjects (9 females; 36.9 ± 8.9 years). RESULTS: IMA, PTX-3, and high-sensitive C-reactive protein (hs-CRP) levels, NLR, and CIMT of Rtx patients were found to be significantly higher compared with healthy subjects ( p = 0.04, p < 0.0001, p < 0.005, p = 0.005, and p = 0.005, respectively). IMA level was positively correlated with hs-CRP and PTX-3 levels, NLR, and CIMT when all participants were included (r = 0.338, p = 0.005; r = 0.485, p < 0.0001; r = 0.304, p = 0.013; and r = 0.499, p < 0.0001, respectively). CONCLUSION: There has been ongoing inflammation, oxidative stress, and atherosclerosis in Rtx patients.

Sleep quality, depression, and quality of life in elderly hemodialysis patients.

OBJECTIVE: Both the incidence and the prevalence of end-stage renal disease (ESRD) in elderly patients are increasing worldwide. Elderly ESRD patients have been found to be more prone to depression than the general population. There are many studies that have addressed the relationship between sleep quality (SQ), depression, and health related quality of life (HRQoL) in ESRD patients, but previous studies have not confirmed the association in elderly hemodialysis (HD) patients. Therefore, the aim of the present study was to demonstrate this relationship in elderly HD patients. PATIENTS AND METHODS: Sixty-three elderly HD patients (32 females and 31 males aged between 65 and 89 years) were included in this cross-sectional study. A modified Post-Sleep Inventory (PSI), the Medical Outcomes Study 36-item short form health survey, and the Beck Depression Inventory (BDI) were applied. RESULTS: The prevalence of poor sleepers (those with a PSI total sleep score [PSI-4 score] of 4 or higher) was 71% (45/63), and the prevalence of depression was 25% (16/63). Of the 45 poor sleepers, 15 had depression, defined as a BDI score of 17 or higher. Poor sleepers had a significantly higher rate of diabetes mellitus (P = 0.03), significantly higher total BDI scores, and lower Physical Component Scale scores (ie, lower HRQoL) than good sleepers. The PSI-4 score correlated negatively with Physical Component Scale (r = -0.500, P < 0.001) and Mental Component Scale scores (r = -0.527, P < 0.001) and it correlated positively with the BDI score (r = 0.606, P < 0.001). In multivariate analysis, independent variables of PSI-4 score were BDI score (beta value [ß] = 0.350, P < 0.001), Mental Component Scale score (ß = -0.291, P < 0.001), and age (ß = 0.114, P = 0.035). CONCLUSION: Poor SQ is a very common issue and is associated with both depression and lower HRQoL in elderly HD patients.

Fenofibrate-induced rhabdomyolysis in a patient with chronic renal failure due to nephrotic syndrome: a rare case report.

OBJECTIVES: Fenofibrate is a fibric acid derivative that is used alone or combination with statins in the treatment of hyperlipidemia. These drugs have potential risks, including rhabdomyolysis and acute renal failure. Despite reports of rhabdomyolysis with the use of fenofibrate alone or with statin-fibrate combinations, there have been no cases of rhabdomyolysis described when fenofibrate was used alone to treat patients with chronic renal failure owing to nephrotic syndrome. DESIGN AND METHODS: We report on a 26-year-old male who presented with fenofibrate-induced rhabdomyolysis with chronic renal failure due to nephrotic syndrome. RESULTS: After the discontinuation of fenofibrate, the patient was treated with intravenous fluid replacement and urine alkalization. Subsequently, his clinical and biochemical findings improved. CONCLUSIONS: Before starting fenofibrate therapy, the causes of secondary hyperlipidemia, especially nephrotic syndrome, should be investigated. In the presence of chronic renal failure and hypoalbuminemia, the fenofibrate dose should be adjusted. Physicians should be aware of the potential toxicities of fenofibrate, and patients should be informed about its potential side effects.

Relationship between Plasma Pentraxin-3, Neutrophil-to-Lymphocyte Ratio, and Atherosclerosis in Renal Transplant Patients.

BACKGROUND/AIMS: Atherosclerosis and inflammation are the most important risk factors in the pathogenesis of cardiovascular diseases (CVD) in patients with end-stage renal disease (ESRD). Pentraxin-3 (PTX-3) was shown to predict inflammation and atherosclerosis in ESRD patients. However, the role of renal transplantation (Rtx) in terms of atherogenesis is still unclear. We aimed to investigate the relationship between PTX-3, neutrophil-to-lymphocyte ratio (NLR), and carotid intima-media thickness (CIMT) in Rtx patients and healthy controls. METHODS: This was a cross-sectional study involving 29 Rtx patients (12 females, 40.1 ± 11.9 years) without overt CVD and 19 healthy subjects (9 females, 36.9 ± 8.9 years), testing the relationship between CIMT, assessed by ultrasonography, and selected biomarkers. RESULTS: CIMT, PTX-3, and high-sensitivity C-reactive protein (hs-CRP) levels of Rtx patients were found to be significantly higher compared to healthy subjects. CIMT was positively correlated with age, creatinine, uric acid, triglyceride, PTX-3, hs-CRP, and NLR, and negatively correlated with estimated glomerular filtration rate in all participants. In Rtx patients, CIMT was positively correlated with age, BMI, serum phosphorus, low-density lipoprotein, and hs-CRP. The multivariate analysis revealed that hs-CRP was found to be an independent variable of CIMT in Rtx patients. CONCLUSION: Our data showed that inflammation and atherosclerosis persist in Rtx patients. Serum hs-CRP might be a useful marker to assess these parameters in this population.

Serum paraoxonase activity and oxidative stress in patients with adult nephrotic syndrome.

OBJECTIVE: It has been shown that low paraoxonase-1 (PON1) activity is associated with a risk of an early development of atherosclerosis. In the present study, we investigated serum paraoxonase, and arylesterase activities and oxidative stress in patients with adult nephrotic syndrome (NS). In addition, we examined the relationship between these measurements and atherosclerosis. METHODS: Twenty-one patients with NS and 21 healthy controls were enrolled in the study. Serum basal and salt-stimulated paraoxonase activities, arylesterase activity, lipid hydroperoxide (LOOH) and total thiol (SH) levels were measured. RESULTS: Serum basal and salt-stimulated paraoxonase activities, arylesterase activity and total SH levels were significantly lower in patients with NS than in controls (p<0.05, p<0.05, p<0.01 and p<0.05, respectively), whereas LOOH levels were significantly higher (p<0.05). Serum LOOH levels were significantly correlated with total-SH levels in patients with NS (r=-0.467; p<0.01). Moreover, proteinuria levels were significantly correlated with serum LOOH levels (r=0.397; p<0.01), whereas no correlation was found among serum paraoxonase activity, arylesterase activity and total-SH levels in NS patients (p>0.05). CONCLUSIONS: We concluded that oxidative stress is increased, while serum PON1 activity is decreased in patients with adult NS. In addition, these results indicate that lower PON1 activity is associated with an oxidant-antioxidant imbalance that may contribute to atherosclerosis in adult patients with NS.

Hepatic Encephalopathy in Connection With Budd-Chiari Syndrome due to Infection With Echinococcus Multilocularis: A Case Report.

Budd-Chiari syndrome (BCS) is a hepatic venous outflow block generally resulting from disorders affecting hepatic venous system. Elevated hepatic venous pressure results in portal hypertension. BCS may also cause hepatic encephalopathy. Echinococcus multilocularis is a tapeworm parasite and the natural course of the disease may affect liver parenchyma as well as hepatic venous tree. It is the most terrible parasitic disease of the liver and is easily confused with hepatic malignancies. Albendazole therapy may suppress disease progression. Alveolar echinococcosis of the liver rarely causes Budd-Chiari syndrome-related hepatic encephalopathy (HE). We report a rare case of alveolar echinococcosis-related BCS with HE, who was successfully managed by rifaximin and albendazole.