Expression of FGF-23 and FGFR1 is increased in uremic rat skin.

PURPOSE: Alterations in skin structure and function are very common in uremic patients, but still there is no unifying hypothesis for uremic skin disorders. Fibroblast growth factor-23 (FGF-23) deficiency has been linked to skin disorders in non-uremic animals. We aimed to study alterations in FGF-23 and fibroblast growth factor-23 receptor 1 (FGFR1) expression in uremic rat skins. MATERIAL AND METHODS: Wistar albino rats were divided into two groups: sham group (SG, n = 8) and uremic group (UG, n = 8). Uremia was induced by reduction of the total kidney mass in the UG. Animals were sacrificed after 14 weeks of the follow-up. RESULTS: Serum creatinine and blood urea nitrogen levels in the UG increased significantly, compared to the SG, at the end of the experiment (0.69 ± 0.08 vs. 0.3 ± 0.04 Mann-Whitney U test (MWU), p = 0,003 and 55.2 ± 8.9 vs. 29.6 ± 6.8 MWU, p = 0.002, respectively). Serum FGF-23 level in the UG was increased non-significantly, compared to the SG (53.5 ± 20.9 vs. 37.2 ± 9.7 MWU, p = 0.072), whereas serum 1,25(OH)2D3 level was significantly lower in the UG (149.4 ± 33.5 vs. 213.8 ± 43.8 MWU, p < 0.05). Expression of FGF-23 in UG skins, assessed by western blot, was significantly higher than that in the SG (186.3 ± 16.8 vs. 148.9 ± 25.9, MWU, p < 0.01). FGFR1 expression was increased in almost all parts of the uremic skin. Receptor expression was most dense at the epidermis and hair follicles. Normal skin appendages and cells either expressed no receptor, or expressed it very weakly. CONCLUSION: This study shows increased FGF-23 levels and FGFR1 expression in uremic rat skins. It deserves further study to fully place this finding in the pathophysiology and clinical picture of uremic skin diseases.

Health literacy in chronic kidney disease patients: association with self-reported presence of acquaintance with kidney disease, disease burden and frequent contact with health care provider.

BACKGROUND: Limited data suggest that health literacy (HL) is associated with kidney functions and clinical outcomes in patients with non-dialysis chronic kidney disease (CKD). We aimed to identify factors associated with the level of HL in a CKD population that has not been studied previously. METHODS: Patients with stage I-V (non-dialysis) CKD according to the Kidney Disease Outcomes Quality Initiative classification were enrolled in the study from two tertiary healthcare centers. Data were collected cross-sectionally using the European Health Literacy Survey (HLS-EU). RESULTS: Data of 208 participants were analyzed. HLS-EU scores had the highest correlations with age (r = - 0.494, p = 0.0001) and education (r = 0.476, p = 0.0001). Estimated glomerular filtration rate (e-GFR) was significantly correlated with HLS-EU score (r = 0.186, p = 0.01). Presence of a self-reported acquaintance with any kind of kidney disease was associated with higher HL. On the other hand, participants with multiple comorbidities, and therefore with more frequent contact with the health system, had lower HL than those without such frequent contact. Similarly, those with a high disease burden had lower HL than those without. HLS-EU scores were also significantly associated with gender, marital status, occupational status, self-perception of health, restriction of daily activities, participation in social activities, place of residence, blood pressure, body mass index, and serum parathyroid hormone and albumin levels. CONCLUSION: Low HL is prevalent among CKD patients and is associated with e-GFR. Presence of an acquaintance with any kind of kidney disease is positively associated with HL. Presence of multiple comorbidities might be a limiting factor for the improvement of HL, which might also be expected to improve as a result of frequent contact with healthcare providers.

Comparison of dialysate and plasma NTproBNP in prediction of clinical outcomes of diabetic and nondiabetic peritoneal dialysis patients
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BACKGROUND: Plasma level of N-terminal pro-brain natriuretic peptide (P-NTproBNP) is a useful marker in prediction of mortality in peritoneal dialysis (PD) patients. However, the predictive value of spent dialysate counterpart (D-NTproBNP) of plasma NTproBNP on mortality and dropout is not known. MATERIALS AND METHODS: Simultaneous P-NTproBNP and D-NTproBNP assays were performed after an overnight dwell in 44 scheduled ambulatory PD patients. Patients were followed for ~ 47 months. Deceased patients or patients who were transferred to hemodialysis were regarded as dropouts. RESULTS: 14 patients (31.8%) dropped out at ~ 4 years (9 deaths and 5 transfers to hemodialysis). Diabetics, males, and patients with higher membrane permeability had higher dropout rates. Patients with P- and D-NTproBNP higher than median values had higher mortality and dropout rates (Kaplan-Meier test, log-rank Test p < 0.05). Odds ratios of D-NTproBNP for death and dropouts were (3.807 (0.907 - 15.971), p = 0.068) and (2.87 (1.009 - 8.138) p = 0.048), respectively; odds ratios of P-NTproBNP for death and dropouts were (4.652 (0.914 - 23.693), p = 0.064) and (2.67 (0.924 - 7.716), p = 0.07), respectively; in ROC analysis for death, AUC for P- and D-NTproBNP were 0.762 (0.578 - 0.946, p = 0.016) and 0.765 (0.590 - 0.940, p = 0.015), respectively. Exclusion of diabetic patients from the analyses resulted in significant changes in the predictive value P- and D-NTproBNP. Although death and dropout rates were still higher in nondiabetic patients with higher NTproBNP levels, the differences between groups lost statistical significance. CONCLUSIONS: Both P-NTproBNP and D-NTproBNP are significant predictors of outcomes of interest. Predictive value of NTproBNP might be different in diabetics and non-diabetic CAPD patients.
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Elimination of NTproBNP in peritoneal dialysis patients. Does peritoneal membrane type make a difference in plasma level and elimination of NTproBNP?

BACKGROUND: Brain natriuretic peptide and its derivative peptide NTproBNP are utilized to exclude cardiac diseases, and predicting risk of mortality in dialysis patients. Our aim was to evaluate both elimination of NTproBNP through dialysate and a possible relationship between plasma and/or dialysate NTproBNP level and membrane transport status of peritoneal dialysis patients. METHODS: 57 plasma (P) and dialysate (D) samples of 44 peritoneal dialysis (PD) patients were analyzed for NTproBNP. Modified peritoneal equilibration test (PET) results and other variables were obtained from the charts. RESULTS: Median (IQR) NTproBNP concentrations (pg/mL × 1,000) in P and D were 3.3 (1 - 13) and 0.5 (0.2 - 3.6), respectively. There was a linear correlation between P-NTproBNP and D-NTproBNP (r = 0.928, p = 0.0001; regression equation was y = 0.897*x -0.28). Mean P/D-NTproBNP ratio was 5.5 ± 0.5. Median P and D-NTproBNP levels by the membrane transport status were aligned as high (H) > high average (HA) > low average (LA), and the difference between H and LA was statistically significant (p < 0.001). Mean arterial pressure (MAP), residual Kt/V and dialysate/plasma ratio of crearinine (D/P Cr) were significant predictors of D-NTproBNP; whereas only MAP and residual Kt/V were significant predictors of P-NTproBNP in multiple regression analysis. Both P- and D-NTproBNP have significant and similar size of correlations with MAP, albumin, D/P Cr ratio, and Na. CONCLUSIONS: D-NTproBNP level is ~ 1/5 of P-NTproBNP, and the issue of relationship between membrane transport status and natriuretic peptide levels needs more work.

Course of encephalopathy in a cirrhotic dialysis patient treated sequentially with peritoneal and hemodialysis.

End-stage kidney disease and advanced cirrhosis are sometimes seen concomitantly. There is no consensus on dialysis modality in terms of determining the optimal way of treating these patients. It has been suggested that peritoneal dialysis is a better choice for these patients, but efficacy of hemodialysis in stable cirrhotic patients has not been evaluated sufficiently. We report a case with advanced cirrhosis and end-stage kidney disease who was faced with hepatic encephalopathy episodes up on starting renal replacement therapy. The case is also interesting in that it reveals effects of hemodialysis and peritoneal dialysis on hepatic encephalopathy episodes and quality of life of the patient.

Brucella and peritoneal dialysis related peritonitis: case report and review of literature.

Isolated case reports of peritonitis due to Brucella spp. during peritoneal dialysis (PD) continue to surface in the medical literature. However, the optimal treatment regimen for these patients, in particular with regards to the fate of PD catheter, is still largely unknown. We report a case of brucella peritonitis successfully treated with intraperitoneal administration of amikacin, along with oral rifampicin and doxycycline but without catheter removal. Furthermore, we have reviewed the literature up until present day.

Effects of resveratrol on blood homocysteine level, on homocysteine induced oxidative stress, apoptosis and cognitive dysfunctions in rats.

We aimed to examine the protective effects of resveratrol against homocysteine induced oxidative stress, apoptosis and cognitive impairment. Rats were randomly divided into three groups. Control group received standard rat food; homocysteine group (Hcy group) received daily methionine at a dose of 1g/kg-body weight dissolved in drinking water for thirty days; third group (Hcy+Res group) received same amount of methionine plus 20mg/kg/day resveratrol intraperitoneally for thirty days. Cognitive performances of the animals were tested by Morris water maze test. Then all animals were sacrificed to study lipid peroxidation (LPO), DNA fragmentation and p53 mRNA expression in the rat brain. The aortas of the sacrificed rats were processed for histopathological examination. Apoptosis in the aortas was assessed by TUNEL staining. Resveratrol significantly decreased serum levels of homocysteine, reversed Hcy induced LPO increase, decreased DNA fragmentation and p53 mRNA expression in the rat brains, and improved homocysteine induced impairment of long term spatial memory. Resveratrol could inhibit homocysteine induced apoptosis and histopathological deterioration in the rat aortic sections. In conclusion, resveratrol is effective in preventing homocysteine induced vascular and neural defects. In hyperhomocysteinemic rat model, our findings consequently warrant in future studies to reveal the true improvement mechanism of resveratrol.

Screening for celiac disease among patients with chronic kidney disease.

AIM: Celiac disease (CD) is considered to be a risk factor for chronic kidney disease (CKD) but there is no study determining the prevalence of CD, among patients with CKD. We aim to determine the prevalence of CD in patients with CKD. MATERIALS AND METHODS: Anti-endomysial IgA (EMA) antibody was screened in patients with CKD (glomerular filtration rate <60 mL/min). Patients who were EMA positive underwent upper gastrointestinal system endoscopy and intestinal biopsy for confirmation of definite diagnosis for CD. RESULTS: Two hundred and ninety-two patients (161 males, mean age was 47.3 ± 16.3 years) with CKD were included. The EMA testing was positive in 10 patients (6F/4M). Of these, eight underwent upper gastrointestinal endoscopy and biopsies, two of them rejected endoscopy. Biopsy specimen of one of the patients was not appropriate for histopathological examination. Specimens of remaining cases (4F/3M) were compatible with CD on histopathological examination. The EMA-positive CKD patients were 3.42% (1/29 cases) and frequency of CD was 2.39% (1/42 cases). Frequency of CD was 3.1% in females and 1.85% in males. Female/male ratio was 1.67. We did not find statistically significant difference between two groups according to age and gender. Apparent chronic gastrointestinal symptoms such as abdominal pain, distension, constipation, dyspepsia, and diarrhea were absent in patients diagnosed with CD. Differences between some laboratory parameters (such as complete blood count, albumin, calcium, phosphate, total cholesterol, ferritin, parathormone) of CD and non-CD patients were not significant statistically. CONCLUSION: Our results showed increased frequency of CD among patients with CKD and screening for CD in CKD population can be helpful.

Gingko biloba extract inhibits oxidative stress and ameliorates impaired glial fibrillary acidic protein expression, but can not improve spatial learning in offspring from hyperhomocysteinemic rat dams.

We aimed to study the effects of gingko biloba extract (EGb) on oxidative stress, astrocyte maturation and cognitive disfunction in offspring of hyperhomocysteinemic rats. Hyperhomocysteinemia was induced in the pregnant rats by administration of methionine (1 gr/kg body weight) dissolved in drinking water throughout pregnancy. One group of animals has received same amount of methionine plus 100 mg/kg/day EGb during pregnancy. On the postnatal day 1, half of the pups from all groups were sacrificed to study the lipid peroxidation (LPO) in different subfractions of brain. Other half of pups were tested in Morris water maze to assess differences in learning and memory performance at the 75 days of age. Maternal hyperhomocysteinemia significantly increased LPO levels especially in mitochondrial subfraction of fetal pup brains. EGb significantly prevented this LPO inrease. Methionine administration to animals reduced glial fibrillary acidic protein (GFAP) expression in pup brains significantly. EGb administration improved GFAP expression significantly. Offspring of hyperhomocysteinemic animals had poor long term spatial memory performance on Morris water maze and EGb administration had no effect on impaired spatial memory. In conclusion, maternally induced hyperhomocysteinemia significantly increased oxidative stress, decreased expression of GFAP and impaired learning performance.