Blood stream Infections in chronic hemodialysis patients - characteristics and outcomes.

INTRODUCTION: Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. The rates of BSI among HD patients vary and are influenced by local patient and pathogen characteristics. Modifications in local infection prevention protocols in light of active surveillance of BSI has been shown to improve clinical outcomes. The aim of this study was to further explore factors associated with BSI in a contemporary cohort of HD patients at a public teaching hospital dialysis center in Israel. METHODS: This was a retrospective cohort study of HD patients with a BSI in the years 2014 to 2018. The primary outcome was the occurrence of BSI. Secondary outcomes were to describe the causative pathogens of BSI, and to assess for risk factors for BSI, and mortality. RESULTS: Included were 251 patients. The mean age was 68.5 ± 13.4 years, 66.9% were male. The mean time from initiation of dialysis was 34.76 ± 40.77 months, interquartile range (IQR) 1-47.5 months and the follow up period of the cohort was 25.17 ± 15.9 months. During the observation period, 44 patients (17.5%) developed 54 BSI events, while 10 of them (3.9% of the whole cohort) developed recurrent BSI events. Gram-negative microorganisms caused 46.3% of all BSI events. 31.4% of these BSI were caused by resistant bacteria. In a multivariate logistic regression analysis, patients receiving dialysis through a central line had a significantly increased risk for BSI adjusted Odds Ratio (aOR) 3.907, p = 0.005, whereas patients' weight was mildly protective (aOR 0.971, p = 0.024). CONCLUSIONS: We noted an increased prevalence of gram-negative pathogens in the etiology of BSI in HD patients. Based on our findings, additional empirical antibiotics addressing gram negative bacteria have been added to our empirical treatment protocol. Our findings highlight the need to follow local epidemiology for implementing appropriate preventative measures and for tailoring appropriate empiric antibiotic therapy.

Association of Nutrition Status at Dialysis Start With Long-Term Survival: A 10-Year Retrospective Study.

OBJECTIVE: The objectives of the study are to explore the association between nutritional status at the initiation of dialysis and the improvement or worsening of nutrition status during first 3 months of dialysis and first 5 years of survival on dialysis. METHODS: Two hundred ninety-seven patients who started dialysis between March 2009 and March 2019 were enrolled in the study. The nutritional status of the patients at dialysis commencement was evaluated by the method of The Integrative Clinical Nutrition Dialysis Score (ICNDS). Improvement or worsening of nutrition status was monitored by calculating the ICNDS slope for each patient enrolled in the study from 3 ICNDS values from the first 3 months on dialysis. The baseline ICNDS and the slope of 3 subsequent monthly ICNDS values were tested for correlation with the odds of all-cause mortality for each of the first 5 years on dialysis. RESULTS: There was a significant difference between the survival odds of patients who started dialysis with an ICNDS at 75 and those who started dialysis with an ICNDS <75 (hazard ratio [HR] 2.505, confidence interval [Cl] 1.235-5.079, P = .011 after 1 year on dialysis;, HR 1.543, Cl 1.083-2.198, P = .016 after 5 years). Deterioration of nutritional status (a negative ICNDS slope) during the first 3 months of dialysis was associated with increased mortality during 1-3 years after dialysis start, compared to a positive ICNDS slope indicating a stable or improved nutritional status (HR 1.732, Cl 1.151-2.607, P = .008 after 3 years on dialysis). CONCLUSIONS: Nutritional status at initiation of dialysis is associated with long-term (5 years) survival. Deterioration of nutritional status during the first 3 months on dialysis significantly increases the risk of death during the first 3 years on dialysis.

The effect of hemodialysis on individual retinal layer thickness.

PURPOSE: The aim of this study was to employ newly developed advanced image analysis software to evaluate changes in retinal layer thickness following hemodialysis. METHODS: A non-randomized prospective study of patients with end-stage renal disease assessed on the same day before and after hemodialysis. Intraocular pressure and central corneal thickness were analyzed, and spectral domain optical coherence tomography results were automatically segmented using the Orion software and then compared. All patients had normal retinal optical coherence tomography findings before hemodialysis. RESULTS: Of the 31 suitable end-stage renal disease patients treated with hemodialysis who provided consent to participate, seven were unable to complete all evaluations, leaving 24 patients for analysis in the final study group. Their mean age was 66.67±14.3 years (range: 35-88), and 62.5% were males. Mean central corneal thickness did not change following hemodialysis (563.4±30.2 µm to 553.1±47.2 µm, p=.247), while mean intraocular pressure decreased (14.48±2.5 mmHg to 13.16±2.28 mmHg, p=.028). Individual mean retinal layer thickness showed no significant change, including the retinal nerve fiber layer (40.9±6.8 µm to 40.1±5.2 µm, p=.412), the ganglion cell and the inner plexiform layer (68.66±8 µm to 69.03±7.6 µm, p=.639), and the photoreceptor layer (50.26±2.8 µm to 50.32±3.1 µm, p=.869). Total retinal thickness similarly remained constant, with a mean of 303.7±17.3 µm before and 304.33±18.4 µm after hemodialysis (p=.571). CONCLUSIONS: Thickness of retinal layers, as assessed by individual segmentation, and central corneal thickness were not affected by hemodialysis treatment, while intraocular pressure was significantly reduced among patients with end-stage renal disease without pre-existing ocular pathology who were undergoing hemodialysis. These results support the view that hemodialysis does not have a negative impact on the retinal morphology of end-stage renal disease patients, who comprise a population with high rates of diabetic and/or hypertensive retinopathy as well as vision-threatening complications.

Serum Obestatin: A Biomarker of Cardiovascular and All-Cause Mortality in Hemodialysis Patients.

BACKGROUND: Recent experimental studies have suggested that obestatin, a proposed anorexigenic gut hormone and a physiological opponent of acyl-ghrelin, has protective cardiovascular effects. We tested the hypothesis that obestatin is independent of inflammatory mediators and/or acyl-ghrelin in predicting outcomes of the maintenance hemodialysis (MHD) population. METHODS: It was a 6-year cohort study on 261 MHD patients. Obestatin, acyl-ghrelin, adipokines (leptin and adiponectin), markers of inflammation and nutrition, prospective all-cause and cardiovascular mortality were studied. RESULTS: During the follow-up, 160 patients died in total, with 74 deaths due to cardiovascular causes. For each ng/mL increase in baseline obestatin level in fully adjusted models (including malnutrition-inflammation score, Interleukin-6 [IL-6], adipokines and acyl-ghrelin), the hazard for death from all causes was 0.90 (95% CI 0.81-0.99) and for cardiovascular death 0.85 (95% CI 0.73-0.99). However, these associations were more robust in the subgroup of patients aged above 71 years: 0.85 (95% CI 0.73-0.98) for all-cause death and 0.66 (95% CI 0.52-0.85) for cardiovascular death. An interaction between high IL-6 (above median) and low obestatin (below median) levels for increased risk of all-cause mortality (synergy index [SI] 5.14, p = 0.001) and cardiovascular mortality (SI 4.81, p = 0.02) emerged in the development of multivariable adjusted models. Interactions were also observed between obestatin, Tumor necrosis factor-alpha, adipokines and acyl-ghrelin, which were associated with mortality risk. CONCLUSION: Serum obestatin behaves as a biomarker for cardiovascular and all-cause mortality in MHD patients. The prognostic ability of obestatin in this regard is independent of inflammation, nutritional status, acyl-ghrelin's and adipokines' activity and is modified by age being very prominent in patients older than 71 years.

Estimating of Residual Kidney Function by Multi-Frequency Bioelectrical Impedance Analysis in Hemodialysis Patients Without Urine Collection.

BACKGROUND/AIMS: Residual kidney function (RKF) is a pivotal predictor of better clinical outcomes in maintenance hemodialysis (MHD) patients. So far there has been no attempt to use bioimpedance analysis (BIA) measurements to calculate residual glomerular filtration rate (GFR) in dialysis population. We hypothesized that performing of multi-frequency BIA at the beginning and end of hemodialysis session can enable us to predict the measured residual GFR in MHD patients. Thus our aim was to develop and validate a new RKF prediction equation using multi-frequency BIA in MHD patients. METHODS: It was diagnostic test evaluation study in a prospective cohort. Participants (n=88; mean age, 66.3±13.2 years, 59.1% males) were recruited from a single hemodialysis center. A new equation (eGFRBIA) to predict RKF, utilizing BIA measurements performed pre- and post-dialysis, was generated and cross-validated by the leave-one-out procedure. GFR estimated as the mean of urea and creatinine clearance (mGFR) using urine collections during entire interdialytic period. RESULTS: A prediction equation for mGFR that includes both pre- and post-dialysis BIA measurements provided a better estimate than either pre- or post-dialysis measurements alone. Mean bias between predicted and measured GFR was -0.12 ml/min. Passing and Bablok regression showed no bias and no significant deviation in linearity. Concordance correlation coefficient indicated good agreement between the eGFRBIA and mGFR (0.75, P<0.001). Using cut-off predicted mGFR levels >2 ml/min/1.73 m2 yielded an area under curve of 0.96, sensitivity 85%, and specificity 89% in predicting mGFR. The κ scores for intraobserver reproducibility were consistent with substantial agreement between first and second estimation of RKF according to eGFRBIA (weighted κ was 0.60 [0.37-0.83]). CONCLUSION: We present a valid and clinically obtainable method to predict RKF in MHD patients. This method, which uses BIA, may prove as accurate, convenient and easily reproducible while it is operator independent.

Prognostic significance of platelet count changes during hospitalization for community-acquired pneumonia.

The prognostic significance of platelet count (PC) changes during hospitalization for community-acquired pneumonia (CAP) has not been investigated. For 976 adults, clinical data during hospitalization for CAP and all-cause mortality following discharge were compared according to ΔPC (PC on discharge minus PC on admission): groups A (declining PC, ΔPC < -50 × 109/l), B (stable PC, ΔPC ± 50 × 109/l), and C (rising PC, ΔPC >50 × 109/l), and according to the presence of thrombocytopenia, normal PC, and thrombocytosis on admission/discharge. Groups A, B, and C comprised 7.9%, 46.5%, and 45.6% of patients, respectively. On hospital admission/discharge, thrombocytopenia, normal PC, and thrombocytosis were observed in 12.8%/6.4%, 84.1%/84.4%, and 3.1%/9.2% of patients, respectively. The respective 90-day, 3-year, and total (median follow-up of 54 months) mortality rates were significantly higher: in group A (40.3%, 63.6%, and 72.7%), compared to groups B (12.3%, 31.5%, and 39.0%) and C (4.9%, 17.3%, and 25.4%), p < 0.001; and in patients with thrombocytopenia at discharge (27.4%, 48.4%, and 51.6%), compared to those with normal PC (10.2%, 26.9%, and 35.4%) and thrombocytosis (8.9%, 17.8%, and 24.4%) at discharge (p < 0.001). Mortality rates were comparable among groups with thrombocytopenia, normal PC, and thrombocytosis at admission (p = 0.6). In the entire sample, each 100 × 109/l increment of ΔPC strongly predicted lower mortality (p < 0.001, relative risk 0.73, 95% confidence interval 0.64-0.83). In conclusion, PC changes are common among CAP inpatients. Rising PC throughout hospitalization is a powerful predictor of better survival, while declining PC predicts poor outcome. Evaluation of PC changes during hospitalization for CAP may provide useful prognostic information.

Interaction between acyl-ghrelin and BMI predicts clinical outcomes in hemodialysis patients.

BACKGROUND: Ghrelin, a gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients. However, it is unclear whether the interaction between ghrelin and BMI is associated with a risk of all-cause and CV death in this population. METHODS: A prospective observational study was performed on 261 MHD outpatients (39% women, mean age 68.6 ± 13.6 years) recruited from October 2010 through April 2012, and were followed until November 2014 (median follow-up-28 months, interquartile range-19-34 months). We measured acyl-ghrelin (AG) levels, appetite, nutritional and inflammatory markers, prospective all-cause and cardiovascular (CV) mortality. RESULTS: During follow-up, 109 patients died, 51 due to CV causes. A significant interaction effect of high BMI and high AG (defined as levels higher than median) on all-cause mortality was found. Crude Cox HR for the product termed BMI x AG was 0.52, with a 95% confidence interval (CI): 0.29 to 0.95 (P = 0.03). Evaluating the interaction on an additive scale revealed that the combined predictive value of BMI and AG is larger than the sum of their individual predictive values (synergy index was 1.1). Across the four BMI-AG categories, the group with high BMI and high AG exhibited better all-cause and cardiovascular mortality irrespective of appetite and nutritional status (multivariable adjusted hazard ratios were 0.31, 95% CI 0.16 to 0.62, P = 0.001, and 0.35, 95% CI 0.13 to 0.91, P = 0.03, respectively). Data analyses made by dividing patients according to fat mass-AG, but not to lean body mass-AG categories, provided similar results. CONCLUSIONS: Higher AG levels enhance the favourable association between high BMI and survival in MHD patients irrespective of appetite, nutritional status and inflammation.

A rise in mean platelet volume during hospitalization for community-acquired pneumonia predicts poor prognosis: a retrospective observational cohort study.

BACKGROUND: Clinical characteristics and the prognostic significance of changes in mean platelet volume (MPV) during hospitalization for community-acquired pneumonia (CAP) have not been investigated. METHODS: Among 976 adults hospitalized for CAP, clinical characteristics, in-hospital outcomes (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay and death), and all-cause mortality following discharge, were compared according to ΔMPV (MPV on discharge minus MPV on admission): groups A (no rising MPV, ΔMPV < 0.6 fL) and B (rising MPV, ΔMPV ≥ 0.6 fL). RESULTS: Groups A and B comprised 83.8% and 16.2% of patients, respectively. Patients with a rise in MPV were more likely to be older, and to present with renal dysfunction, cerebrovascular disorder and severe pneumonia than were patients with no rise in MPV. On discharge, lower values of platelets and higher levels of neutrophils were observed in group B. Rising MPV strongly predicted a need for mechanical ventilation and in-hospital death (the respective relative risks: 2.62 and 6.79; 95% confidence intervals: 1.54-4.45 and 3.48-13.20). The respective 90-day, 3-year and total (median follow-up of 54 months) mortality rates were significantly higher in group B (29.1%, 43.0% and 50.0%) than group A (7.3%, 24.2% and 32.6%), p < 0.001 for all comparisons. A rise in MPV was a powerful predictor of all-cause mortality (relative risk 1.26 and 95% confidence interval 1.11-1.43). CONCLUSIONS: Rising MPV during hospitalization for CAP is associated with a more severe clinical profile than no rise in MPV. A rise in MPV strongly predicts in-hospital and long-term mortality.

Heart failure and orthostatic hypotension.

Orthostatic hypotension (OH) is traditionally defined as a fall of ≥20 mmHg in systolic and/or ≥10 mmHg in diastolic blood pressure within 3 min of active standing. OH is a common comorbidity among patients with heart failure (HF). A comprehensive review regarding the relationship between OH and HF has not been published in the English literature. Here we provide current information about concomitant HF and OH, including: pathophysiology, methods of evaluation, prevalence, risk factors, prognosis and management of OH in HF patients, as well as the incidence of HF among patients with OH. The prevalence of OH in HF ranges from 8 % among community-living individuals to 83 % in elderly hospitalized patients. Dizziness and palpitations are the most frequent OH symptoms. Main predisposing factors for OH are HF severity, non-ischemic HF etiology, prolonged bed rest, hypertension and polypharmacy. OH in HF is generally managed according to recommendations for treatment of OH in the non-HF population. However, since acceptable pharmacotherapy with fludrocortisone and midodrine is problematic in HF due to adverse effects, the management of OH is based mainly on non-pharmacologic interventions. Several prospective epidemiological studies reported that OH is independently associated with an increased risk of developing HF. Since OH is a common and frequently symptomatic condition in HF patients, its clinical implications should be emphasized. Longitudinal studies should be conducted to investigate the prognostic significance and optimal management of OH in the HF population.

Changes in Red Cell Distribution Width During Hospitalization for Community-Acquired Pneumonia: Clinical Characteristics and Prognostic Significance.

PURPOSE: We investigated outcomes of patients hospitalized with community-acquired pneumonia (CAP) according to the changes in red cell distribution width (RDW). METHODS: For 980 adults, clinical characteristics, outcomes during hospitalization for CAP (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay, and death), and all-cause mortality following discharge were compared: according to RDW changes versus stable RDW during hospitalization, and according to normal (≤14.7 %) versus high (>14.7 %) RDW values on admission/discharge. RESULTS: RDW changes (n = 386) during hospitalization were associated with more severe clinical and laboratory characteristics than stable RDW (n = 594). Changes in RDW strongly predicted poor in-hospital outcomes (p < 0.001). The respective 30, 90-day, and total (median follow-up 54 months) mortality rates were significantly higher (9.8, 16.0 and 43.5 %) among patients with RDW changes, compared to 4.0, 7.6 and 30.5 % among those with stable RDW (p < 0.001 for all comparisons). RDW changes, as well as high RDW (each 1 % increment) on admission and discharge, were powerful predictors of mortality (the respective relative risks 1.41, 1.13, and 1.15, and 95 % confidence intervals 1.13-1.74, 1.08-1.19, and 1.10-1.21). CONCLUSIONS: RDW changes during hospitalization for CAP are common and associated with a severe clinical profile. Time-dependent RDW changes strongly predict poor in-hospital outcomes and increased short- and long-term mortality. Repeated RDW determinations during hospitalization for CAP may provide useful prognostic information.

Amlodipine treatment of hypertension associates with a decreased dementia risk.

Hypertension has been shown to be a risk factor for development of dementia. However, medical treatment of hypertension failed to reduce consistently the risk of dementia. Experimental study pointed to the possibility of difference between different calcium channel blockers (CCB) in their neuro-protective effect. The aim of our study was to evaluate the risk of dementia during treatment of hypertension with different CCBs. This is a retrospective cohort study based on electronic database of a large public health care organization. Study period was 11 years and it included patients aged 40-75 years old, having diagnosis of hypertension without diagnosis of dementia at the starting point, treated with either single specific CCB (study group) or with other than CCBs antihypertensive medications (control group) for at least 30 months during the study period. A total of 15,664 patients that satisfied these criteria were identified: 3,884 were treated with amlodipine, 2,062 were treated with nifedipine, 609 were treated with lercanidipine, and 9,109 never received CCBs. Dementia developed in 765 (4.9%) patients. Adjusted hazard ratio (HR) for dementia in patients treated with amlodipine, nifedipine, and lercanidipine was 0.60 (p < 0.001), 0.89 (NS), and 0.90 (NS). Decreased adjusted HR of dementia with amlodipine was demonstrated in the patients aged 60 or more (HR 0.61 [0.49-0.77], p < 0.001), but not in the patients aged less than 60 years old. This study shows that amlodipine therapy may be associated with a decreased dementia risk in hypertensive individuals older than 60 years, compared to those treated without CCBs.

Factors associated with prevention of postural hypotension by leg compression bandaging.

AIM: We evaluated the eventual effects of leg compression on seating-induced postural hypotension (PH) in the context of various relevant clinical variables. METHODS: Included were 73 hospitalized patients with various acute conditions, aged ≥ 60 years, bedridden for ≥ 8 h, with diagnosed PH [≥ 20 mmHg systolic and/or ≥ 10 mmHg diastolic blood pressure (BP) falls] at the first seating. BP, heart rhythm, dizziness and palpitations were recorded before and during 5 min of sitting. The next day, the patients were reevaluated, this time using compression bandages applied along both legs before seating. RESULTS: Compared with the non-bandaged state, PH was registered in only 53% of bandaged patients (p < 0.001). Moreover, the appearance of PH symptoms decreased (p < 0.001). On the second day (bandaged), supine diastolic BP values were higher in the persisting vs non-persisting PH group (p = 0.027). In the bandaged state, PH symptoms were significantly reduced in the non-persisting PH group (p = 0.003). Even in patients with persistent PH, the magnitude of BP decline and appearance of PH symptoms were decreased while wearing bandages (p = 0.004 and 0.002, respectively). CONCLUSION: During mobilization of inpatients, leg compression seems to reduce the seating-induced PH and relevant symptoms. Even in patients with persisting PH, bandaging may improve hemodynamics and attenuate associated symptoms.

N-acetylcysteine use for amelioration of aminoglycoside-induced ototoxicity in dialysis patients.

Use of aminoglycoside antibiotics is associated with significant ototoxicity, especially on patients with decreased renal function. The risk of aminoglycoside ototoxicity may approach 60%. Oxidative stress has been suggested as a general mechanism of aminoglycoside ototoxicity and is prevalent in dialysis population. N-acetylcysteine (NAC) is an effective antioxidant and has been safely used in dialysis patients. New experimental and clinical data, explored in this review, provide a good case to recommend NAC administration to all dialysis patients, receiving aminoglycosides.

Longitudinal study of leptin levels in chronic hemodialysis patients.

BACKGROUND: The influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients. METHODS: Leptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters. RESULTS: Significant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2 y; p < 0.001) with a more rapid decline in leptin levels in the highest leptin tertile in both unadjusted (p = 0.007) and fully adjusted (p = 0.047) models. A significant reduction in body composition parameters over time was observed, but was not influenced by leptin (leptin-by-time interactions were not significant). No significant associations were noted between leptin levels and changes in dietary protein or energy intake, or laboratory nutritional markers. Finally, cumulative incidences of survival were unaffected by the baseline serum leptin levels. CONCLUSIONS: Thus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

Objective Score of Nutrition on Dialysis (OSND) as an alternative for the malnutrition-inflammation score in assessment of nutritional risk of haemodialysis patients.

BACKGROUND: Evaluation of nutritional risk, one of the strongest predictors of morbidity and mortality in maintenance haemodialysis (HD) patients, is a difficult process especially in patients with compounding conditions that prevent subjective assessment by subjective global assessment or malnutrition-inflammation score (MIS). METHODS: In this study, we developed and characterized a score for the assessment of nutritional status in dialysis patients based solely on objectively measurable criteria. Our prospective observational cohort included 81 prevalent HD patients (53 men and 28 women) with a mean age of 64.3 +/- 11.9 years. The study period encompassed 26.9 +/- 14.3 months. The quantitative and comprehensive scoring system, named Objective Score of Nutrition on Dialysis (OSND), was calculated by combining anthropometric measurements (the change in end-dialysis dry weight in the past 3-6 months, body mass index, skinfold thickness and mid-arm circumference) with three laboratory tests: albumin, transferrin and cholesterol levels. The sum of all seven components of OSND results in a score from 5 (severely malnourished) to 32 (normal). We compared our OSND system with the accepted MIS and phase angle (PA) measurements derived by bioelectric impedance analysis. RESULTS: The OSND correlated significantly with hospitalization days (r = -0.334; P = 0.002) and frequency of hospitalization (r = -0.373; P = 0.001), as well as with lean body mass and fat mass, MIS, PA and interleukin-6 levels. The Cox proportional hazard-calculated relative risk for death for each five-unit decrease in the OSND was 2.2 (95% CI, 1.3 to 3.8; P = 0.003) comparable with the predictions provided by MIS [for each five-unit increase in MIS, hazard ratio (HR) was 1.8 with 95% CI, 1.2 to 2.8; P = 0.007] and PA (for each 1-unit decrease in PA, HR was 2.9 with 95% CI, 1.5 to 5.6; P = 0.001). CONCLUSIONS: The OSND thus provides a comprehensive scoring system with significant associations with prospective hospitalization and mortality in chronic HD patients as well as measures of nutrition and inflammation.

Association between rosiglitazone use and decline in renal function in patients with type 2 diabetes mellitus.

BACKGROUND: Use of thiazolidinediones (TZDs) in treatment of type 2 diabetes mellitus (T2DM) has recently become a matter of major controversy regarding their cardiovascular and renal safety. The aim of this study is to investigate the association between rosiglitazone use and renal function in diabetic patients. METHODS: This is a retrospective cohort study conducted on a population of patients with T2DM treated at a large public health service organization. All patients who received continuous rosiglitazone therapy for at least 1 year were included in the study group. For each patient in the study group, control patients with T2DM never treated with rosiglitazone were selected from the same population and matched for age, sex, HbA1c% and date of study entry. Level of renal function was expressed as estimated glomerular filtration rate (eGFR), calculated by the simplified Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS: In total, 5,666 patients were included in the study: 1,304 were treated with rosiglitazone, and 4,362 were matched controls. Baseline eGFR was similar in both groups (74.6 +/- 22.9 vs. 73.8 +/- 23.3 ml/min per 1.73 m(2), respectively; p=0.291). After 5 years of follow-up, eGFR was significantly lower in the rosiglitazone-treated group than in control group (67.7 +/- 23.6 vs. 73.8 +/- 25.2 ml/min per 1.73 m(2), p<0.001). CONCLUSION: The use of rosiglitazone may be associated with a decline of renal function in patients with T2DM. Further studies are needed to better quantify the risk-benefit trade-offs associated with rosiglitazone therapy.

The cyclin kinase inhibitor p57kip2 regulates TGF-beta-induced compensatory tubular hypertrophy: effect of the immunomodulator AS101.

BACKGROUND: Compensatory tubular cell hypertrophy following unilateral nephrectomy is a cell cycle-dependent process. Our previous study showed that treatment of unilaterally nephrectomized rats with the immunomodulator AS101 partially inhibits compensatory hypertrophy of the remaining kidneys through the inhibition of IL-10-induced TGF-beta secretion by mesangial cells. The present study is focused on understanding the intracellular mechanism(s) of this phenomenon. METHODS: A total of 120 male Sprague-Dawley rats were unilaterally nephrectomized or sham-operated and treated with AS101 or PBS. Kidney weight and protein/DNA ratio were assessed for each experimental animal. The expression of TGF-beta, PCNA, CDK 2, pRb, ppRb, p21(Waf1), p27(kip1) and p57(kip2) proteins in renal tissues was determined by western blot analysis and immunohistochemistry, and the immunoprecipitation of cyclin E complexes was performed. RESULTS: Compensatory renal growth is initiated by proliferation of resident renal cells that precedes hypertrophy. Changes in TGF-beta expression were positively correlated with the amounts of p57(kip2), but not with p21(Waf1) and p27(kip1) expression in the remaining kidneys. Moreover, there was a marked abundance of p57(kip2) but not p21(Waf1) and p27(kip1) binding to the cyclin E complex in PBS-treated unilaterally nephrectomized rats compared to sham-operated animals. Treatment of uninephrectomized rats with AS101 reduced kidney weight and protein/DNA ratio, inhibited TGF-beta and p57(kip2) expression in the remaining kidneys, and decreased the level of p57(kip2) binding to cyclin E complexes. CONCLUSION: These results demonstrate that TGF-beta-induced compensatory tubular cell hypertrophy is regulated in vivo by p57(kip2) but not by the p21(Waf1) and p27(kip1) cyclin kinase inhibitor proteins.

Non-urate transporter 1-related renal hypouricemia and acute renal failure in an Israeli-Arab family.

Idiopathic renal hypouricemia (IRHU) is a rare hereditary disease, predisposing the individual to exercise-induced acute renal failure (EIARF) and nephrolithiasis, and it is characterized by increased clearance of renal uric acid. Most of the described patients are Japanese, who have loss-of-function mutations in the SLC22A12 gene coding for the human urate transporter 1 (URAT1) gene. An 18-year-old youth, who was admitted for EIARF due to IRHU, and six consanguineous Israeli-Arab family members were included in the study. The family members were tested for fractional excretion of uric acid and molecular analysis of the URAT1 gene. Four family members, including the proband, had very low levels of blood uric acid and high rate of fractional excretion (FE urate> 100%) of uric acid. Genetic analysis of the affected family members did not reveal a mutation in the coding regions and intron-exon boundaries of SCL22A12. Haplotype analysis excluded SCL22A12 involvement in the pathogenesis, suggesting a different gene as a cause of the disease. We herein describe the first Israeli-Arab family with IRHU. A non-URAT1 genetic defect that causes decreased reabsorption or, more probably, increased secretion of uric acid, induces IRHU. Further studies are required in order to elucidate the genetic defect.

Nutritional and inflammatory status of hemodialysis patients in relation to their body mass index.

OBJECTIVE: The study tested whether obese hemodialysis (HD) patients have a better nutritional and inflammatory state than those with overweight or normal body mass index (BMI). DESIGN: This was a single-center, cross-sectional study. SETTING AND PATIENTS: Ninety-six stable HD patients from a local HD unit were divided into 3 groups according to BMI (normal, overweight, and obese). MAIN OUTCOME MEASURES: Anthropometry, body composition by multifrequency bioelectrical impedance analysis, biochemical nutritional markers, as well as interleukins (IL-1, IL-6, and IL-10), tumor necrosis factor, leptin, and soluble leptin receptor (sOB-R) were measured. RESULTS: Serum creatinine was significantly elevated in the highest BMI category. Albumin and transferrin were significantly elevated in higher BMI groups after adjustment for age, sex, and diabetes status. The higher BMI group had greater lean body mass (P = .001) and fat mass (P = .0001), higher phase angle (PA), and lower extracellular mass-to-body-cell-mass ratio (ECM/BCM) (P < .05). Inflammatory cytokine levels were not different in the 3 BMI groups. In parallel with increasing BMI, a gradual increase in serum leptin and a trend for decreasing sOB-R were detected (P = .0001 and P = .055, respectively). Both PA (r = 0.295, P = .008) and ECM/BCM (r = -0.345, P = .002) significantly correlated with serum leptin concentration. According to a multiple linear regression analysis, with PA as the dependent variable, age (beta = 0.274, P = .008), creatinine (beta = 0.355, P = .001), and log sOB-R/leptin ratio (beta = -0.465, P = .008) were significant independent predictors of PA. CONCLUSION: HD patients with elevated BMI demonstrate better nutritional status compared to normal BMI or overweight patients, whereas the severity of inflammation is not related to BMI in HD patients.

Serum Chromium Levels Are Higher in Peritoneal Dialysis than in Hemodialysis Patients.

Background:An elevation in serum chromium levels in individuals treated with renal replacement therapy has been previously described, but chromium levels have not been systematically studied in patients treated with different dialysis modalities. The aim of this study was to compare serum chromium levels in patients treated with chronic peritoneal dialysis (PD) and hemodialysis (HD).Methods:We studied 169 chronic dialysis patients in a single medical center, of which 148 were treated with HD and 21 with PD. Serum chromium levels were measured by atomic absorption spectrometry.Residual renal function was accessed using a timed urine collection for the measurement of urine output and calculation of glomerular filtration rate (GFR).Results:The median (interquartile range) serum chromium level was significantly higher in patients treated with PD than in patients treated with HD: 5.00 (3.24 - 6.15) vs 1.83 (1.29 - 2.45) mcg/L, p < 0.001. In a univariate analysis, serum chromium level was associated with PD modality: Exp (B) 7.46 (95% confidence interval [CI] 2.1 - 26.4), p = 0.002. The association of PD modality with serum chromium level was even more significant using a multivariate logistic regression model: odds ratio (OR) 11.87 (95% CI 2.85 - 49.52), p = 0.001 after adjustment for age, gender, diabetes, smoking, dialysis vintage, use of diuretics, and residual renal function.Conclusions:In patients treated with chronic dialysis, serum chromium levels are higher in patients treated with PD than in those treated with HD.