Britta Hylander

Interleukin-6 and interleukin-8 in serum and urine in patients with acute pyelonephritis in relation to bacterial-virulence-associated traits and renal function

Urine and serum concentrations of interleukin (IL)-6 and IL-8 were determined in 43 women with acute pyelonephritis caused by Escherichia coli. Urine and serum samples were also collected 2 weeks after the infection and during a subsequent episode of cystitis (n = 8) or asymptomatic bacteriuria (n = 8). Concentrations of IL-6 and IL-8 were related to the expression of 5 virulence markers of E. coli and glomerular filtration rate (GFR) after pyelonephritis. Patients with acute pyelonephritis had elevated urine and serum IL-6 and IL-8 levels as compared to 37 healthy women (IL-6: p < 0.001 in both cases, and IL-8: p < 0.001 in both cases). Patients infected with E. coli producing hemolysin and/or cytotoxic necrotizing factor (CNF) had significantly higher IL-6 levels in serum during acute pyelonephritis as compared to patients infected with strains without the ability to produce these factors (p = 0.0025 and p = 0.0154, respectively). Patients who had high concentrations of IL-8 in urine during acute pyelonephritis had lower GFR at follow-up as compared to patients with lower levels of IL-8 in urine (r = -0.48, p = 0.0123). In conclusion, acute pyelonephritis is accompanied by elevated urinary and serum IL-6 and IL-8 levels. Bacteria producing hemolysin and CNF seem to induce higher concentrations of IL-6 in serum. The secretion of IL-8 from renal cells may participate in the initiation and maintenance of renal inflammation which in turn may influence renal function.

Correlation between Soluble Markers of Endothelial Dysfunction in Patients with Renal Failure

Aim: Damage to the endothelium is an important component of atherosclerosis. It has been suggested to be quantified by measuring plasma markers, such as von Willebrand factor and thrombomodulin and soluble adhesion molecules. We hypothesized there may exist a correlation between the plasma levels of von Willebrand factor and thrombomodulin as markers of endothelial cell dysfunction and the serum concentrations of soluble adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) in patients with renal insufficiency, and in patients on peritoneal dialysis or hemodialysis since these three groups of kidney patients are highly prone to develop cardiovascular diseases. Results: The concentrations of von Willebrand factor and thrombomodulin in plasma were significantly higher in patients with kidney diseases as compared to healthy subjects (p = 0.017 and p < 0.001, respectively). The patients also had significantly higher concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and MCP-1 compared to healthy controls (p < 0.001 for both comparisons). There were strong correlations between the concentration of soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor in patients with kidney failure (r = 0.63, p < 0.001) and between the concentration of thrombomodulin and sVCAM-1 (r = 0.61, p < 0.001). Furthermore, a negative correlation was observed between the concentration of thrombomodulin and the cell surface expression of CD11b on monocytes and granulocytes in the peripheral circulation (p < 0.01 in both cases). Conclusion: The strong correlation between markers of endothelial dysfunction and soluble adhesion molecules in patients with renal insufficiency and on dialysis strengthen the view that an ongoing stress on endothelial cells is present in this group of patients. This may play a pathophysiological role in the development of cardiovascular disease.

Tumor necrosis factor-α, interleukin-1β, and interleukin-1 receptor antagonist in dialysate and serum from patients on continuous ambulatory peritoneal dialysis

Abstract Dialysate and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-1ra were investigated in 20 patients on continuous ambulatory peritoneal dialysis (CAPD), who altogether had 30 episodes of peritonitis. Bacterial growth was found in 25 (83%) of the dialysate samples. Staphylococcus epidermidis was the single most common microorganism, found in 44% of the culture-verified peritonitis. Samples from dialysate bags were obtained during the first month of dialysis and during peritonitis from the first three bags on day 1 (the day of admittance) and from nightbags on days 3 and 10. Serum samples were drawn on days 1 and 10. The peak concentrations of cytokines occurred on the first day of infection. In dialysates, TNF-α was elevated in 96% of the patients, with a peak median concentration of 160 pg/mL (range, P P P

Clinical findings in oral health during progression of chronic kidney disease to end-stage renal disease in a Swedish population.

Objective. Early detection of oral infections plays an important role for dental referral during progression of renal disease and during dialysis treatment in uraemic patients. This study investigated how oral health is related to uraemia in a group of uraemic patients in Stockholm, Sweden. Material and methods. This cross-sectional study assessed oral diseases in chronic kidney disease (CKD) patients in different stages (n=93) compared with healthy age- and gender-matched controls. Differences in multiple oral outcomes, assessed by a dentist, were investigated in multivariate analyses, adjusted for tobacco habits, diabetes mellitus and uraemia status (predialysis, peritonealdialysis or haemodialysis). Results. Compared with healthy controls, uraemic patients had significantly worse dental status regarding the decayed, missing, filled teeth (DMFT) index (3.3, p=0.003), periodontal loss of attachment (0.9, p=0.00002) and periapical lesions (0.6, p=0.002). For haemodialysis patients DMFT (6.5, p=0.01), periodontal loss of attachment (2.2, p=0.007) and periapical lesions (1.0, p=0.01) were worse compared with controls. The differences between uraemic patients and controls remained after adjustment for age, gender, tobacco habits and diabetes (p<0.05 for all outcomes). Conclusions. Objective measurements showed that uraemic patients have more dental problems than healthy controls and the patients seem to develop their problems before they have progressed to dialysis. Therefore greater attention to dental problems may be warranted during the progression of uraemia to prevent deterioration of oral health.

Difference in the Blood Monocyte Phenotype Between Uremic Patients and Healthy Controls: Its Relation to Monocyte Differentiation into Macrophages in the Peritoneal Cavity

The phenotypic alterations between blood monocytes from 11 patients with end-stage renal disease, who had been on peritoneal dialysis for less than one week, and blood monocytes from 10 healthy controls, were analyzed. In addition, peritoneal macrophages in the dialysate effluent were enclosed. Analysis of functional receptor density was performed using immunostaining and flow cytometry. The phenotypic characterization was selected to represent various biological functions such as adhesion, phagocytosis (CD11b/CD18, CD11c/CD18, CD16), antigen-presentation (HLA-DR, ICAM-1), differentiation (transferrin receptor, CD71), receptor for LPS (CD14) and initiation of the coagulation cascade (Tissue factor, CD142). The proportion of CD16-positive blood monocytes and the quantitative level of ICAM-1 were higher in the patient group, compared to healthy controls. A significant increase in the quantitative level of CD11b/CD18, CD11c/CD18, HLA-DR and ICAM-1, transferrin receptor, CD 14 and CD 16, was found on peritoneal macrophages, compared to monocytes, harvested both from the corresponding patients, as well as from healthy donors. In contrast, we did not find any significant differences in the expression of tissue factor between monocytes and peritoneal macrophages. In conclusion, phenotypic differences exist between monocyte populations in the blood circulation of CAPD patients, and healthy individuals. We also show that transmigration of monocytes into the peritoneal cavity implies a selective up-regulation of functional receptors, preferentially related to adhesion, and antigen-presentation in a steady-state situation in non-infected CAPD patients.

Increased Levels of Transforming Growth Factor β1 and Basic Fibroblast Growth Factor in Patients on CAPD: A Study During Non-Infected Steady State and Peritonitis

Long-term influence of continuous ambulatory peritoneal dialysis (CAPD) on concentrations of transforming growth factor β1 (TGF-β1) and basic fibroblast growth factor (bFGF) in the peritoneal effluent, and the effect of peritonitis on these cytokines were investigated. TGF-β1 and bFGF were assayed in effluent samples from dialysate bags collected during the initial week of treatment with CAPD and at 5 months. To determine the effect of peritonitis, dialysate bags were collected on admission to the hospital and on days 3 and 10 and also during non-infected steady state. Serum was drawn prior to infection and on days 1 and 10. TGF-β1 increased more than threefold during the longitudinal follow-up period, median concentrations of 35 pg/ml to 106 pg/ml (P < 0.05). No change in bFGF was seen during this initial 5 months. TGF-β1 was increased on the first day of peritonitis (median concentration 169 pg/ml) and reached its maximum on day 3 of infection, (median concentration 216 pg/ml) (P < 0.05 vs non-infected state, median concentration 39 pg/ml). Basic FGF reached a maximum on day three of infection (median concentration 7.7 pg/ml; P = 0.01 vs non-infected state) and then slowly declined. In conclusion, TGF-β1 is influenced by CAPD treatment per se, and together with bFGF is increased during peritonitis, indicating its importance in the peritoneum and its potential involvement in the development of tissue fibrosis and eventually ultrafiltration failure.

Inflammatory cytokines in saliva: Early signs of metabolic disorders in chronic kidney disease. A controlled cross-sectional study

OBJECTIVE The aim of this study was to evaluate correlations between levels of cytokines in secreted stimulated saliva in patients with chronic kidney disease (CKD) and hyposalivation. STUDY DESIGN Seventy patients with clearance <20 mL/min/1.73 m(2) were evaluated; 40 were predialysis, 21 hemodialysis, and 9 peritoneal dialysis, and they were matched with 70 control subjects. Salivary flow rate was measured and submandibular/sublingual saliva collected. Analyses were performed for whole protein content using a protein assay, and levels of tumor necrosis factor (TNF) α, interleukin (IL) 1β, γ-interferon (γ-INF), IL-6, IL-8, IL-10, monocyte chemotactic protein (MCP) 1, and soluble intercellular adhesion molecule (sICAM) 1, by using Luminex technology. RESULTS Patients with CKD had lower (P = .03) stimulated salivary secretion rate and higher salivary whole protein concentration (P = .002) than control subjects. Concentrations of IL-8 (P = .03) and MCP-1 (P = .002) were decreased and TNF-α/IL-10 (P = .05) and IL-8/IL10 (P = .03) ratios were decreased in CKD patients. CKD patients with low secretion levels of stimulated saliva expressed decreased levels of TNF-α (P = .04), IL-1β (P = .02), γ-INF (P = .03), IL-6 (P = .003), IL-8 (P = .005), MCP-1 (P = .006), and sICAM-1 (P = .02). CONCLUSIONS Salivary cytokines and secretion rates are significantly decreased in CKD patients. Further research is necessary to understand operating mechanisms and clinical implications of the down-regulation of inflammatory markers in saliva.

Prevalence and early detection of oral fungal infection: A cross-sectional controlled study in a group of Swedish end-stage renal disease patients

Objective. Early detection and treatment of local oral fungal infection (OFI) minimize the risk of overgrowth and more serious complications such as invasive infections. Generalized fungal infection increases both morbidity and mortality in end-stage renal disease (ESRD) patients. This study reports the prevalence of ongoing OFI in patients with ESRD and presents correlations with dental microbial plaque formation and mouth dryness. It also describes how oral fungal growth correlates with oral lesions associated with fungal infection. Material and methods. From March 2007 to October 2008, 93 ESRD patients and 45 age- and gender-matched controls were consecutively asked to participate in the study. In total, 34 patients were treated with peritoneal dialysis (PD) and 59 with haemodialysis (HD). OFI was diagnosed by taking two smear layers from the buccal mucosa. The samples from each side of the mouth were stained with the periodic acid Schiff (PAS) method. The associations between histological findings, age, gender, type of dialysis treatment, tobacco habits, self-experienced mouth dryness, taste disturbances, dental plaque and gingivitis were investigated. The presence of erythematous oral stomatitis, membranous candidiasis and angular cheilitis was noted to clarify how the presence of fungal hyphae correlate with oral lesions associated with OFI. Results. OFI was found in 32% of the ESRD patients and 11% of the controls (p=0.007). An extensive OFI, defined as frequent fungal hyphae formations in oral mucosal smear layers, was found in 3% of the PD and 17% of the HD patients. Oral lesions, defined as clinical signs associated with OFI such as erythematous oral stomatitis, membranous candidiasis or angular cheilitis, were found in 37% of the patients with OFI, while 5% of the patients without findings of fungal infection presented oral lesions associated with OFI (p=0.0002). Furthermore, patients with self-reported mouth dryness were three times more likely (p=0.02) to be diagnosed with OFI. Conclusions. ESRD patients are found to have significantly more OFI than controls. Patients with ESRD experiencing mouth dryness and dental plaque formation also seem to be at risk of developing OFI. Detection of oral lesions associated with OFI should be combined with a histopathological diagnosis before antifungal treatment.

DNA damage in salivary gland tissue in patients with chronic kidney disease, measured by the comet assay

OBJECTIVE The aim of this observational study was to investigate the relationship between DNA damage in minor accessory salivary glands, hyposalivation, and inflammation in patients with chronic kidney disease (CKD). STUDY DESIGN DNA strand breaks and oxidative DNA lesions in salivary glands, inflammatory markers, and uremic state were measured in 79 patients with CKD and matched controls. RESULTS CKD patients not yet on dialysis had significantly more, and dialysis patients significantly less, DNA strand breaks in salivary tissue compared with controls. All measured inflammatory markers were higher in patients with CKD compared with controls. Salivary secretion rates were significantly lower in dialysis patients compared with controls. A high level of salivary secretion rate at rest significantly predicted a high level of DNA strand breaks in patients with CKD. CONCLUSIONS Dialysis patients had fewer DNA strand breaks in minor accessory salivary glands than controls, suggesting that peripheral tissue is differently affected by CKD than leukocytes.

Sexual function in patients with end-stage renal disease

Objective. Patients with chronic renal disease have sexual dysfunction to a great degree, but not many studies have been performed to study desire and sexual function in both men and women and the effects of active treatment for end-stage renal disease (ESRD). The aim of this study was to compare sexual function in patients with and without treatment for ESRD, where the patients served as their own controls. Material and methods. Sexual function was investigated in 117 patients with ESRD using a questionnaire in which the patients compared their sexual function before and after the onset of renal disease. Results. An overall decrease was seen in sexual desire (46%) and initiative (68%), and a pronounced decrease in sexual function, with regard to erection/lubrication (68%) and frequency of intercourse (64%). More than 50% of the patients admitted that the decrease in sexual function affected them considerably. Predialysis patients experienced less sexual dysfunction than patients undergoing active treatment. Women reported a minor ability to enjoy sex compared with men. No other gender differences in sexual dysfunction were identified in this study. No correlation between degree of sexual dysfunction and treatment modality or medication was found. Conclusion. A majority of the ESRD patients in this study report a substantial decrease in sexual desire, initiative and ability.