Health-related quality of life as predictor of mortality in end-stage renal disease patients: an observational study.

BACKGROUND: Health-related quality of life (HRQoL) is an important component of patient-centered outcomes and a useful parameter for monitoring quality of care. We assessed HRQoL, its determinants, and associations with mortality in patients with end-stage renal disease (ESRD). METHODS: Short Form-36 was used to assess HRQoL, its domain components, and physical (PCS) and mental (MCS) composite summary scores in altogether 400 (338 incident and 62 prevalent) dialysis patients with median age 64 years, 37% women, 24% diabetes mellitus (DM), 49% cardiovascular disease (CVD), and median estimated glomerular filtration rate (eGFR) of 5.3 (3.0-9.4) ml/min/1.732. Results were analyzed separately for 338 incident patients starting on hemodialysis (HD; 68%) or peritoneal dialysis (PD; 32%), and 62 prevalent PD patients. Mortality risk was analyzed during up to 60 months (median 28 months). RESULTS: Linear multivariate regression analysis showed that in incident dialysis patients, 1-SD higher PCS associated negatively with 1-SD higher age, DM and CVD, and positively with 1-SD higher hemoglobin and sodium (adjusted r2 = 0.17). In 62 prevalent PD patients, 1-SD higher PCS was negatively associated with 1-SD higher age. MCS was not associated to any of the investigated factors. Multivariate Cox regression analysis showed that in incident dialysis patients, 1-SD increase of PCS associated with lower all-cause mortality, hazard ratio 0.65 (95% confidence interval 0.52-0.81), after adjustments for age, sex, DM, CVD, plasma albumin, C-reactive protein and eGFR whereas 1-SD lower MCS did not associate with mortality. In PD patients, neither PCS nor MCS associated with mortality. CONCLUSIONS: MCS did not associate with any of the investigated clinical factors, whereas lower PCS associated with higher age, CVD, DM, and lower hemoglobin and sodium levels. MCS was not associated with mortality, whereas lower PCS associated with increased mortality risk. These results suggest that HRQoL - in addition to its role as patient-centered outcome - matters also for hard clinical outcomes in ESRD patients. Our knowledge about factors influencing MCS in ESRD patients is limited and should motivate further studies.

Altered basophil function in patients with chronic kidney disease on hemodialysis
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AIMS: Chronic kidney disease (CKD) leads to impairment of immune cell function. Given the potential role of basophils in the pathogenesis of CKD, we aimed to study the basophil responsiveness towards microbial antigen exposure, judged as adhesion molecule expression and degranulation, in CKD patients on hemodialysis. MATERIALS AND METHODS: We selected markers linked to two crucial biological phases: the transmigration and degranulation processes, respectively. For the transmigration process, we selected the adhesion molecules CD11b, active CD11b epitope, and CD62L and for the degranulation process CD203c (piecemeal degranulation marker), CD63 (degranulation marker), and CD300a (inhibitory marker of degranulation). We measured basophil responsiveness after stimulation of different activation pathways in basophils using lipopolysaccharide (LPS), peptidoglycan (PGN), formyl-methyinoyl-leucyl-phenylalanine (fMLP), and anti-FcεRI-ab. RESULTS: The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared to matched healthy controls, but no differences were observed after activation by anti-FcɛI. CD300a expression was significantly higher in patients following activation by fMLP and anti-FcɛI, and the active epitope CD11b expression was significantly higher in patients after LPS activation. In addition, we found that CD62L was not shed from the cell surface after activation with LPS and fMLP. A slight downregulation was noted after activation with anti-FcɛI in healthy controls. CONCLUSION: Together, these data demonstrate that basophil functions related to adhesion and degranulation are altered in CKD patients on hemodialysis, which indicates a potential role for the basophil in the pathogenesis of complications related to infections.

Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study.

BACKGROUND: Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years. METHODS: The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls. Soluble markers of inflammation, such as cytokines, were analyzed using the Milliplex technique. RESULTS: Patients showed significantly lower CD11b expression after stimulation during the 3rd (p = 0.002) and the 5th year (p < 0.001), together with a lower oxidative burst in response to fMLP over time (p = 0.02). The expression of CD62L on resting monocytes was lower during the 3rd (p = 0.001) and the 5th (p = 0.001) year in patients. Levels of tumor necrosis factor-α and RANTES were significantly increased (p = 0.001, p = 0.006) and interleukin-12 levels were also higher in CKD patients during the 5th year (p = 0.007). CONCLUSION: Monocytes in CKD stages 2-3 show emerging functional abrasions, with altered adhesion molecule expression and impaired fMLP response. These findings suggest that a transformation of monocyte function occurs at an early phase of renal impairment and may together with increased plasma levels of pro-inflammatory cytokines contribute to the higher vulnerability of CKD patients to comorbidities, such as infections and cardiovascular disease.

Dialysis modality and nutritional status are associated with variability of inflammatory markers.

BACKGROUND: Inflammation is a common feature in dialysis patients and is associated with cardiovascular complications and poor outcome. Measuring the variability of inflammatory markers may help in understanding underlying factors triggering inflammation. Whether the inflammatory pattern in hemodialysis (HD) and peritoneal dialysis (PD) patients differs has scarcely been studied. Here we explored factors associated with the magnitude and variability of inflammation markers in HD and PD patients. METHODS: In two 3-month, prospective cohort studies comprising 228 prevalent HD and 80 prevalent PD patients, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRP) were measured in blood samples drawn each month and every week, respectively. Information on comorbidity, protein-energy wasting (PEW) and medications was gathered at baseline, and information on symptoms potentially related to inflammation was gathered weekly. A mixed-effect model was used for multivariate analysis of factors linked to CRP and IL-6 variation. RESULTS: IL-6 and CRP levels were higher and showed higher variability in HD versus PD patients [median IL-6 8.3 (interquartile range, IQR, 5.3-14.5) versus 6.7 (IQR 4.2-10.0) pg/mL, P < 0.001 and median CRP 6.1 (IQR 2.5-14.0) versus 5.4 (IQR 1.6-9.0) mg/L, P < 0.001). PEW predicted increased inflammation variability after correcting for age, sex, dialysis vintage, modality and comorbidity. Increased comorbidity predicted IL-6, but not CRP, variability. CONCLUSIONS: Circulating concentrations as well as variability of IL-6 and CRP levels were higher in HD as compared with PD patients. In HD and PD patients, short-term variability of IL-6 and CRP levels associated strongly with PEW, while comorbidity was related to IL-6 but not to CRP variability.

Activation of basophils is a new and sensitive marker of biocompatibility in hemodialysis.

The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood-membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fcε receptor I (FcεRI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-FcεRI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis.

The effect of sea buckthorn supplement on oral health, inflammation, and DNA damage in hemodialysis patients: a double-blinded, randomized crossover study.

OBJECTIVE: Chronic kidney disease is associated with inflammation, oxidative stress, malnutrition, poor oral health, and mouth dryness. The objective of this study was to evaluate effects of sea buckthorn oil (SBO) extract, which is rich in vitamins, phytochemicals, and polyunsaturated fatty acids, on oxidative stress, saliva production, and inflammation in hemodialysis patients. DESIGN SETTING AND SUBJECTS: This was a randomized, double-blinded, and placebo-controlled crossover study (2 × 8 weeks, 4-week washout). The study subjects were hemodialysis patients (n = 45) recruited from the Department of Renal Medicine at Karolinska University Hospital in Stockholm. INTERVENTION AND MAIN OUTCOME MEASURES: The patients received 4 capsules per day, each containing 500 mg of SBO or placebo, for 8 weeks. They were then crossed over to the other treatment after a 4-week washout period. Salivary gland biopsies, saliva, and blood samples were collected before and after each treatment period. Main outcomes were DNA breaks and oxidative DNA lesions in minor accessory salivary glands, salivary flow rates, and inflammation markers in blood (high-sensitivity C-reactive protein, antitrypsin, orosomucoid in plasma, leukocytes in blood). Blood markers including creatinine, urea in plasma, and hemoglobin in blood were investigated. RESULTS: The results showed no significant changes in DNA breaks, oxidative DNA lesions, salivary flow rates, or inflammation after SBO supplementation. However, plasma levels of phosphate and sodium increased and plasma levels of iron decreased. CONCLUSION: In conclusion, SBO supplementation as performed in this study did not protect against oxidative stress, nor improve oral health or inflammation status in hemodialysis patients.

Soluble CD14 and Osteoprotegerin Associate with Ankle-Brachial Index as a Measure of Arterial Stiffness in Patients with Mild-to-Moderate Chronic Kidney Disease in a Five-Year Prospective Study.

INTRODUCTION: Vascular lesions and arterial stiffness appear at early stages of chronic kidney disease (CKD) and follow an accelerated course with disease progression, contributing to high cardiovascular mortality. There are limited prospective data on mechanisms contributing to progression of arterial stiffness in mild-to-moderate CKD (stages 2-3). METHODS: We applied an affinity proteomics approach to identify candidates of circulating biomarkers with potential impact on vascular lesions in CKD and selected soluble cluster of differentiation 14 (sCD14), angiogenin (ANG), and osteoprotegerin (OPG) for further analysis. We studied their association with ankle-brachial index (ABI) and carotid intima-media thickness, as measures of arteriosclerosis and atherosclerosis, respectively, in 48 patients with CKD stages 2-3, who were prospectively followed and intensively treated for 5 years, and 44 healthy controls. RESULTS: Concentrations of sCD14 (p < 0.001), ANG (p < 0.001), and OPG (p < 0.05) were higher in patients with CKD 2-3 at baseline, and sCD14 (p < 0.001) and ANG (p < 0.001) remained elevated in CKD patients at follow-up. There were positive correlations between ABI and sCD14 levels (r = 0.36, p = 0.01) and between ABI and OPG (r = 0.31, p = 0.03) at 5 years. The changes in sCD14 during follow-up correlated to changes in ABI from baseline to 5 years (r = 0.41, p = 0.004). CONCLUSION: Elevated levels of circulating sCD14 and OPG in patients with CKD 2-3 were significantly associated with ABI, a measure of arterial stiffness. An increase in sCD14 over time in CKD 2-3 patients was associated with a corresponding increase in ABI. Further studies are needed to examine if early intensive multifactorial medication to align with international treatment targets may influence cardiovascular outcomes.

Health-related quality of life in different stages of chronic kidney disease and at initiation of dialysis treatment.

OBJECTIVES: To evaluate health-related quality of life (HRQoL) in patients in different stages of chronic kidney disease (CKD) up to initiation of dialysis treatment and to explore possible correlating and influencing factors. METHODS: Cross-sectional design with 535 patients in CKD stages 2-5 and 55 controls assessed for HRQoL through SF-36 together with biomarkers. RESULTS: All HRQoL dimensions deteriorated significantly with CKD stages with the lowest scores in CKD 5. The largest differences between the patient groups were seen in 'physical functioning', 'role physical', 'general health' and in physical summary scores (PCS). The smallest disparities were seen in mental health and pain. Patients in CKD stages 2-3 showed significantly decreased HRQoL compared to matched controls, with differences of large magnitude - effect size (ES) ≥ .80 - in 'general health' and PCS. Patients in CDK 4 demonstrated deteriorated scores with a large magnitude in 'physical function', 'general health' and PCS compared to the patients in CKD 2-3. Patients in CKD 5 demonstrated deteriorated scores with a medium sized magnitude (ES 0.5 - 0.79) in 'role emotional' and mental summary scores compared to the patients in CKD 4. Glomerular filtration rate <45 ml/min/1.73 m², age ≥ 61 years, cardiovascular disease (CVD), diabetes, C-reactive protein (CRP) ≥5 mg/L, haemoglobin ≤110 g/L, p-albumin ≤ 35 g/L and overweight were associated with impaired HRQoL. CRP and CVD were the most important predictors of impaired HRQoL, followed by reduced GFR and diabetes. CONCLUSIONS: Having CKD implies impaired HRQoL, also in earlier stages of the disease. At the time for dialysis initiation HRQoL is substantially deteriorated. Co-existing conditions, such as inflammation and cardiovascular disease seem to be powerful predictors of impaired HRQoL in patients with CKD. Within routine renal care, strategies to improve function and well-being considering the management of co-existing conditions like inflammation and CVD need to be developed.

Achievement of recommended treatment targets for bone and mineral metabolism in haemodialysis patients using paricalcitol: an observational study.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) is a common problem among patients with chronic kidney disease (CKD) on haemodialysis. This study was conducted to assess the use, effectiveness and safety of intravenous paricalcitol in haemodialysis patients with various degrees of SHPT. MATERIAL AND METHODS: This observational, multicentre, prospective study was conducted in 14 Swedish dialysis centres from May 2007 to June 2008 and included 92 haemodialysis patients with a diagnosis of SHPT associated with CKD. The decision to initiate treatment with intravenous paricalcitol was made by the treating physician. No treatment algorithms were provided. RESULTS: Mean patient age was 64 years. Of the 92 patients included, 74 had an intact parathyroid hormone (iPTH) level of >300 pg/ml at baseline. Median iPTH was 584 pg/ml in patients with a baseline PTH of >300 pg/ml. During follow-up there was a decrease in iPTH to 323 pg/ml at 6 months (-45%, p < 0.0001). In parallel, there was a small increase in serum calcium, but serum phosphorus and the calcium × phosphorus product remained unchanged. CONCLUSIONS: This study showed that intravenous paricalcitol substantially and safely decreased iPTH in haemodialysis patients with a baseline iPTH above the Kidney Disease Outcomes Quality Initiative recommended target range (150-300 pg/ml) and had minimal impact on serum minerals.

Cardiovascular changes in patients with mild-to-moderate chronic kidney disease compared with healthy subjects: a 5-year follow-up study.

BACKGROUND: There is limited knowledge about how cardiovascular parameters change over time in patients with mild-to-moderate chronic kidney disease (CKD). We studied several cardiovascular biomarkers over a 5-year period in patients with mild-to-moderate CKD and in healthy controls. METHODS: Fifty-four patients with CKD stages 2-3 and 54 controls were included. The CKD patients were closely monitored and well controlled for hypertension and other cardiovascular risk factors. Ambulatory blood pressure (BP) monitoring, ankle-brachial index (ABI), carotid and cardiac ultrasound (including measurement of the left ventricular mass index (LVMI)), and biochemical analyses were evaluated. RESULTS: Renal function decreased in both groups, with no significant difference in the change over time. In the CKD patients, none of the BP variables increased over time, but in the controls, average 24-h and daytime systolic BP increased significantly. ABI increased slightly in the CKD patients (P<0·001), but not in the controls (P = 0·963), and phosphate had a significant positive effect on ABI. Although in the CKD patients, there was no significant increase over time in common carotid artery diameter (P = 0·274), there was a small but significant increase in the controls (P = 0·001). LVMI increased significantly over time in both groups. CONCLUSIONS: In our study of patients with mild-to-moderate CKD, the progression of cardiovascular changes over time was relatively slow. Good BP control and treatment of other risk factors may have contributed to slow the progress of cardiovascular involvement, which emphasizes the importance of dedicated care in this population.

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.

Aspects of carotid structure and function in health and different stages of chronic kidney disease.

INTRODUCTION: Arterial remodelling and stiffening have been demonstrated in end-stage renal disease (ESRD). The presence of vascular alterations in earlier-stage chronic kidney disease (CKD) is less studied. We evaluated vascular structure and function in mild-to-moderate CKD (stages 2-3) compared with healthy subjects and advanced CKD (stages 4-5). METHODS: Carotid ultrasound was performed in 103 non-dialysis CKD patients and 54 healthy controls. Carotid intima-media thickness (CIMT) and common carotid artery (CCA) diameter were measured. Strain, stiffness and the pressure-strain elastic modulus (Ep ) of the right CCA were calculated. RESULTS: There was no significant difference in CCA diameter between CKD 2-3 and controls. The CCA diameter was larger in CKD 4-5 compared with CKD 2-3 and controls (CKD 4-5, 6·50 ± 0·79 mm versus CKD 2-3, 6·08 ± 0·56 mm, P = 0·003; and versus controls 5·97 ± 0·53 mm, P<0·001). However, after adjustments, the difference in CCA diameter was valid only for older ages and also dependent on systolic blood pressure (SBP). There were no significant differences in CIMT, strain or stiffness between the groups, but Ep was higher in CKD 4-5 compared with controls (P = 0·006). CONCLUSION: In mild-to-moderate CKD, there were no significant differences in carotid artery structure or function compared with healthy subjects. Only patients with advanced CKD and older ages showed signs of arterial remodelling. Our study indicates that vascular alterations occur in advanced CKD, with SBP and age as important contributing factors.

Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) show elevated levels of inflammatory markers and have an increased risk of infections as well as cardiovascular morbidity. Recent studies have implied effects of fibroblast growth factor 23 (FGF23) on inflammation in CKD. We analyzed potential correlations between levels of FGF23 with pro-inflammatory chemokines and markers of leukocyte transmigration in CKD patients. METHODS: One hundred three patients with CKD 2-5ND and 54 healthy controls, had biochemical markers in blood and urine analyzed according to routine protocol. Pro-inflammatory cytokines were analyzed by Milliplex technique and leukocyte CD11b adhesion molecule expression was measured by flow cytometry. FGF23 levels were measured with ELISA technique. Treatment of leukocytes from healthy blood donors with FGF23 was performed in vitro and effects analyzed by flow cytometry. RESULTS: Tumor necrosis factor-alpha, RANTES and interleukin (IL)-12 levels were significantly higher (p = 0.001, p < 0.001, and p < 0.001) in patients with CKD. Elevated FGF23 levels in the CKD group correlated to glomerular filtration rate, parathyroid hormone, urinary albumin excretion and phosphate as well as to IL-12 and RANTES. CD11b expression on resting granulocytes and monocytes, and on activated monocytes, was associated with FGF23. In vitro treatment of leukocytes with FGF23 reduced CD11b expression in resting as well as in formyl-methyinoyl-leucyl-phenylalanine-stimulated granulocytes (p = 0.03). CONCLUSION: FGF23 levels are associated with various inflammatory markers such as pro-inflammatory cytokines and adhesion molecules on innate immune cells. However, further studies are warranted to define the direct role of FGF23 in modulation of the innate immune system in CKD.

Hemodialysis Patients Display a Declined Proportion of Th2 and Regulatory T Cells in Parallel with a High Interferon-γ Profile.

BACKGROUND: A high prevalence of cardiovascular diseases (CVDs) and infections in patients with chronic kidney disease (CKD) arises partly due to a high inflammatory state and aberrations in immune cells function. Following in vitro stimulation of leukocytes with different T-cell mitogens, we observed a lower level of interleukin (IL)-2 and IL-10 production in CKD patients. To gain more knowledge as to whether this is the result of an alteration in T-cell function, we investigated the T-cell subsets profile and cytokine production in hemodialysis patients. METHODS: CD4+ cells were isolated from whole blood of 10 hemodialysis patients and 10 age- and gender-matched healthy controls. Following in vitro stimulation with an antigen-independent T-cell mitogen, Th1, Th2, and regulatory T (Treg) cell subsets were analyzed by flow cytometry through the expression of specific transcription factors. The levels of cytokines, interferon (IFN)-γ, IL-4, and IL-10 were analyzed by enzyme-linked immunosorbent assay in the supernatants. RESULTS: The proportion of CD4+CD25+FOXP3+ (Treg) and CD4+GATA3+ (Th2) cells was significantly lower in patients compared to healthy controls, while the proportion of CD4+T-bet+ (Th1) cells was similar. Moreover, levels of IL-4 were significantly lower in supernatants from patients, while IFN-γ levels were higher. IL-10 levels did not differ compared to those of the healthy controls. CONCLUSIONS: Our findings indicate a diminished anti-inflammatory Treg, and Th2 cell profile in hemodialysis patients, accompanied by a high pro-inflammatory IFN-γ profile. Since this profile is characterized in CVDs, we propose that an imbalance between the inflammatory and anti-inflammatory responses may contribute to the pathogenesis of CVD in advanced CKD.

Sexual Function and Testosterone Level in Men With Conservatively Treated Chronic Kidney Disease.

Sexual dysfunctions are common, but underrecognized, in patients with chronic kidney disease (CKD) and are inversely associated with the glomerular filtration rate (GFR). Sexual dysfunctions may affect quality of life in males with CKD. The aim of this study was to analyze the relationship among sex hormones, sexual function, and sexual satisfaction in a group of men between 18 and 50 years of age with CKD Stages 1 to 5 not treated with hemodialysis or peritoneal dialysis. Fasting blood samples for hemoglobin, testosterone, prolactin, and luteinizing hormone and questionnaire surveys (Sexual Complaints Screener for Men, International Index of Erectile Function, and Aging Male Symptom scale) were evaluated in 100consecutive men. Higher CKD stage (i.e., lower renal function) had a statistically significant ( p < .01) correlation with lower total testosterone, free testosterone, and hemoglobin levels, and higher luteinizing hormone and prolactin levels. Sexual function/dysfunctions were not significantly associated with CKD stage, even after adjustment for age and serum testosterone. The results indicate that CKD stage is a factor affecting testosterone levels in combination with age in men between 18 and 50 years of age at different stages of CKD but not treated with hemodialysis or peritoneal dialysis. Sexual dysfunctions are common but not strongly correlated to testosterone levels, prolactin levels, and survey (Sexual Complaints Screener for Men, International Index of Erectile Function, and Aging Male Symptom scale) responses in patients with CKD.

Healthcare costs in chronic kidney disease and renal replacement therapy: a population-based cohort study in Sweden.

OBJECTIVE: To compare healthcare costs in chronic kidney disease (CKD) stage 4 or 5 not on dialysis (estimated glomerular filtration rate <30 mL/min/1.73m2), peritoneal dialysis, haemodialysis and in transplanted patients with matched general population comparators. DESIGN: Population-based cohort study. SETTING: Swedish national healthcare system. PARTICIPANTS: Prevalent adult patients with CKD 4 or 5 (n=1046, mean age 68 years), on peritoneal dialysis (n=101; 64 years), on haemodialysis (n=460; 65 years) and with renal transplants (n=825; 52 years) were identified in Stockholm County clinical quality registers for renal disease on 1 January 2010. 5 general population comparators from the same county were matched to each patient by age, sex and index year. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual healthcare costs in 2009 incurred through inpatient and hospital-based outpatient care and dispensed prescription drugs ascertained from nationwide healthcare registers. Secondary outcomes were annual number of hospital days and outpatient care visits. RESULTS: Patients on haemodialysis had the highest mean annual cost (€87 600), which was 1.49 (95% CI 1.38 to 1.60) times that observed in peritoneal dialysis (€58 600). The mean annual cost was considerably lower in transplanted patients (€15 500) and in the CKD group (€9600). In patients on haemodialysis, outpatient care costs made up more than two-thirds (€62 500) of the total, while costs related to fluids ($29 900) was the largest cost component in patients on peritoneal dialysis (51%). Compared with their matched general population comparators, the mean annual cost (95% CI) in patients on haemodialysis, peritoneal dialysis, transplanted patients and patients with CKD was 45 (39 to 51), 29 (22 to 37), 11 (10 to 13) and 4.0 (3.6 to 4.5) times higher, respectively. CONCLUSIONS: The mean annual costs were ∼50% higher in patients on haemodialysis than in those on peritoneal dialysis. Compared with the general population, costs were substantially elevated in all groups, from 4-fold in patients with CKD to 11, 29 and 45 times higher in transplanted patients and patients on peritoneal dialysis and haemodialysis, respectively.

Testosterone and gonadotropins but not SHBG vary with CKD stages in young and middle aged men.

BACKGROUND: The aim of this study was to assess the effects chronic kidney disease (CKD) had on sex hormones and lipids in a subgroup of men between 18 and 50 years old with CKD 1-5 stage without diabetes and not treated with hemodialysis. METHODS: Data were collected from 101 men with different CKD stages. RESULTS: Higher CKD stage (lower function) had a significant negative linear trend on total testosterone level (p < 0.01) and free testosterone level (p < 0.01), with a significant increase of luteinizing hormone (LH) (p < 0.01), and prolactin (p < 0.01), while SHBG remained unchanged between the CKD stages. Triglycerides but not total cholesterol, HDL -cholesterol or LDL-cholesterol increased with higher CKD stage. A negative correlation was observed between BMI, SHBG and free testosterone (p < 0.01 for both) but not with other sex hormones. Age per se was related to a significant decrease of total and free testosterone level (p < 0.01 for both) even after correction for BMI. Decreased levels of total testosterone and estimated free testosterone levels had a significant correlation with an increased level of triglyceride levels (p <0.01). CONCLUSIONS: Our results indicate that CKD stage per se is a factor affecting testosterone levels in combination with age in men between 18 and 50 years old with CKD 1-5 stage, not treated with hemodialysis. With increased CKD stage there was a significant increase in LH level and a pattern of hypergonadotropic hypogonadism. SHBG remained unchanged between the CKD stages.

OBJECTIFS: Le but de cette étude était d'évaluer les effets d'une maladie rénale chronique (MRC) sur les hormones sexuelles et les lipides dans une sous-population d'hommes âgés de 18 à 50 ans porteurs d'une MRC de stade 1-5, non diabétiques et non traités par hémodialyse. MÉTHODES: Les données ont été obtenues chez 101 hommes qui présentaient différents stades de MRC. RÉSULTATS: Un stade plus élevé de MRC (fonction plus réduite) a une tendance linéaire négative sur les taux de testostérone totale (p<0,01) et de testostérone libre (p<0,01), avec une augmentation significative de la LH (p<0,01) et de la prolactine (p<0,01), alors que les taux de SHBG ne diffèrent pas entre les stades. Les triglycérides augmentent avec les stades plus élevés de MRC, ce qui n'est pas le cas du cholestérol total, du cholestérol HDL, ou du cholestérol LDL. L'IMC est négativement corrélé à la SHBG (p<0,01) et à la testostérone libre (p<0,01), mais n'est pas corrélé aux autres hormones sexuelles. L'âge per se est lié à une diminution significative des taux de testostérone totale (p<0,01) et de testostérone libre (p<0,01), corrélation qui persiste après ajustement sur l'IMC. Des taux diminués de testostérone totale et de testostérone libre estimée sont significativement corrélés à un niveau augmenté des taux de triglycérides (p<0,01). CONCLUSIONS: Nos résultats indiquent que le stade de la MRC per se est un facteur qui affecte les taux de testostérone en combinaison avec l'âge chez les hommes de 18 à 50 ans porteurs d'une MRC de stade 1-5 et non traités par hémodialyse. L'élévation du stade de MRC est associée à une augmentation significative du taux de LH et à un profil d'hypogonadisme hypergonadotrophique. La SHBG n'est pas modifiée par le stade de MRC.

A MULTI-DIMENSIONAL SUPPORT PROGRAMME FOR PATIENTS WITH DIABETIC KIDNEY DISEASE.

BACKGROUND: Diabetes is currently the most common cause of kidney disease among patients receiving renal replacement therapy. Pedagogical interventions to promote self-management and secondary prevention have been shown to be effective in delaying disease progression. OBJECTIVES AND DESIGN: A non-randomised, quasi-experimental design ('uncontrolled before and after') to evaluate the effects of a group-based, multidisciplinary and multidimensional support programme in patients with diabetic kidney disease. The programme comprised 1) Disease-related knowledge, 2) Skills training and increased self-care agency 3) A motivational approach, with group discussions, participant questions and narratives, setting and follow-up of individual health goals. PARTICIPANTS: Fifty-eight patients with diabetic kidney disease. OUTCOME MEASURES: Glycated haemoglobin (HbA1c), urine albumin/creatinine ratio, blood pressure, body mass index, waist, physical activity and participant experiences from the programme. RESULTS: The evaluation indicated positive effects on HbA1c, albuminuria and physical activity at follow-up after four months. The proportion of patients achieving blood pressure targets increased. The participants reported improved understanding of their health condition and treatment regime. CONCLUSION: The multidimensional support programme, addressing health-promoting factors and self-management in small patient groups, has a potential to effectively reduce HbA1c and may have some beneficial effects which contribute to health promotion in patients with diabetic kidney disease. This mode of a multidimensional support programme should continue to develop, with longer term follow-up and further evaluations with appropriate research designs.

Cardiac remodelling and functional alterations in mild-to-moderate renal dysfunction: comparison with healthy subjects.

INTRODUCTION: Left ventricular (LV) hypertrophy (LVH) and reduced LV function correlate with poor prognosis in patients with chronic kidney disease (CKD). Our aim is to investigate whether mild-to-moderate CKD is associated with cardiac abnormalities. METHODS: Echocardiography, including tissue Doppler imaging, was performed in 103 patients with CKD at stages 2-3 and 4-5, and in 53 healthy controls. The systolic (s') and diastolic myocardial velocity (e'), and the transmitral diastolic flow velocity (E) were measured, and E/e' was calculated. RESULTS: Patients with chronic kidney disease had higher mean E/e' than controls (mean E/e': controls 5·00 ± 1·23 versus CKD 4-5 6·36 ± 1·71, P<0·001 and versus CKD 2-3 5·69 ± 1·47, P = 0·05), indicating altered diastolic function in the patients. The CKD groups showed lower longitudinal systolic function than controls, as assessed by atrio-ventricular plane displacement and s' (mean s': controls 11·5 ± 1·9 cm s(-1) versus CKD 4-5 10·4 ± 2·1 cm s(-1) , P = 0·03 and versus CKD 2-3 10·4 ± 2·1 cm s(-1) , P = 0·02). The prevalence of LVH was higher in patients with CKD than in controls (controls 13% versus CKD 4-5 37%, P = 0·006 and versus CKD 2-3 30%, P = 0·03). CONCLUSION: Alterations in systolic and diastolic myocardial function can be seen in mild-to-moderate CKD compared with controls, indicating that cardiac involvement starts early in CKD, which may be a precursor of premature cardiac morbidity.