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 complexity of an overlap type resistant cryoglobulinemia: a case report and review of the literature.

Type I cryoglobulinemia is associated with B cell proliferative diseases, whereas essential mixed cryoglobulinemia is classically associated with infections, malignancy, and autoimmune diseases, but may be idiopathic. Prognosis in patients with grave manifestations and renal involvement is often poor. We report a case of a 40-year-old woman, 2 weeks post-partum for pre-eclampsia who was hospitalized with nephritic syndrome and acute renal failure. The patient harbored type I and type II cryoglobulinemia. Renal and cutaneous biopsies confirmed the diagnosis; however, an underlying etiology was not established. A bone marrow biopsy suggested monoclonal gammopathy of undetermined source (MGUS). Despite therapy with intravenous cyclophosphamide, rituximab, plasmapheresis, dialysis, and bortezomib, the patient succumbed after 8 months of hospitalization. We suggest that an overlap entity of types I and II cryoglobulinemia with severe multi-organ involvement not only is rare but also may be resistant to conventional therapy and fatal.

3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism.

BACKGROUND AND AIMS: Concanavalin A is known to activate T cells and to cause liver injury and hepatitis, mediated in part by secretion of TNFα from macrophages. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been shown to prevent tissue damage in various animal models of inflammation. The objectives of this study were to evaluate the efficacy and mechanism of the PARP-1 inhibitor 3-aminobenzamide (3-AB) in preventing concanavalin A-induced liver damage. METHODS: We tested the in vivo effects of 3-AB on concanavalin A-treated mice, its effects on lipopolysaccharide (LPS)-stimulated macrophages in culture, and its ability to act as a scavenger in in vitro assays. RESULTS: 3-AB markedly reduced inflammation, oxidative stress, and liver tissue damage in concanavalin A-treated mice. In LPS-stimulated RAW264.7 macrophages, 3-AB inhibited NFκB transcriptional activity and subsequent expression of TNFα and iNOS and blocked NO production. In vitro, 3-AB acted as a hydrogen peroxide scavenger. The ROS scavenger N-acetylcysteine (NAC) and the ROS formation inhibitor diphenyleneiodonium (DPI) also inhibited TNFα expression in stimulated macrophages, but unlike 3-AB, NAC and DPI were unable to abolish NFκB activity. PARP-1 knockout failed to affect NFκB and TNFα suppression by 3-AB in stimulated macrophages. CONCLUSIONS: Our results suggest that 3-AB has a therapeutic effect on concanavalin A-induced liver injury by inhibiting expression of the key pro-inflammatory cytokine TNFα, via PARP-1-independent NFκB suppression and via an NFκB-independent anti-oxidative mechanism.

The effect of poly (ADP-ribose) polymerase inhibition on aminoglycoside-induced acute tubular necrosis in rats.

INTRODUCTION: Aminoglycosides (AG) cause nephrotoxicity in 10 - 20% of patients. One of the mechanisms is by generating reactive oxygen species (ROS), leading to DNA destruction and activation of poly(ADPribose) polymerase (PARP) causing necrotic tubular cell death. PARP inhibition on gentamicin-induced nephrotoxicity was studied. METHODS: 19 female Wistar-Kyoto rats divided into 3 groups: control (3 rats receiving no treatment); gentamicin-treated group (8 rats); and 8 rats treated with gentamicin combined with 3-aminobenzamide (3 AB). Kidney functions, protein, and gentamicin levels as well as urinary trypsin inhibitory activity (TIA) were measured. Tissue microscopic examination and immunohistochemical study for proliferative cell nuclear antigen (PCNA) were determined. The effect of PARP inhibitor on the bactericidal activity of gentamicin was also assessed. RESULTS: The following results were statistically significant: urea (mg/dL) 39.9 ± 5.86, 88.3 ± 50.3, and 48.5 ± 12.7 (p = 0.048); serum creatinine (mg/dL): 0.6 ± 0.26, 1.05 ± 0.7, 0.6 ± 0.06 (p = 0.043); proteinuria (mg/24-hours): 7.27 ± 3.65, 41.2 ± 18.1, and 17.6 ± 13.9 (p = 0.050); the number of tubular macronuclei (per 10 mm2): 18.33 ± 16.07, 218 ± 101.8, 41.7 ± 36.2 (p = 0.012); the number of dilated tubes (per 10 mm2): 61.67 ± 12.58, 276.3 ± 112.7, 140.0 ± 90.9 (p = 0.04); and the number of PCNA positive nuclei (per 10 mm2): 223.3 ± 95.69, 3,585 ± 2,215.3, 626.7 ± 236.9 (p = 0.034) in the control, gentamicin, and gentamicin+3AB-treated groups, respectively. The following biochemical and histologic parameters were also examined, however, they showed no statistically significant difference: TIA (p = 0.055), mitoses (p = 0.14), mononuclear infiltrate (p = 0.188), and intratubular cast formation (p = 0.084). No effect on bactericidal activity was observed. CONCLUSION: This study illustrates that PARP inhibitor significantly attenuates gentamicin-induced nephrotoxicity in rats with no effect on the bactericidal activity.

Nutrition assessment and risk prediction in dialysis patients-a new integrative score.

OBJECTIVE: We developed a quantitative nutritional score, based on biochemical measures, taken as part of monthly routine care. The score can be accomplished within a short time after routine laboratory results completion and identify a monthly change in nutritional status. DESIGN: A longitudinal observational cohort study SETTING: The Institute of Nephrology, Wolfson Medical Center, Holon, Israel. SUBJECTS: A total of 179 hemodialysis patients were followed up for up to 2.5 years after study baseline. INTERVENTION: The Integrative Clinical Nutrition Dialysis Score (ICNDS) is based on the biochemical measures of albumin, creatinine, urea, cholesterol, C-reactive protein, dialysis adequacy, and weight change. Each parameter is ranked between 1 and 5, with the higher rank derived from recommended National Kidney Foundation Kidney Disease/Dialysis Outcomes and Quality Initiative values and the lower rank indicating deviation from those values. The final ICNDS is the sum of ranks over 7 parameters. MAIN OUTCOME MEASURE: The Pearson correlation coefficient was calculated for association between subjective global assessment and ICNDS in 63 randomly selected patients. In 179 dialysis patients, the baseline ICNDS, the slope of 3 subsequent monthly ICNDS values, were tested for their correlation with odds of all-cause mortality, hospitalization frequency, length of stay, after 31 months. Spline Cox regression was used to select the best cutoff point, associated with severe mortality risk. RESULTS: Score results were significantly correlated with nutrition evaluation by subjective global assessment (r = 0.842, P < .01). For a unit increase in baseline score, death odds were significantly decreased (hazard ratio [HR] = 0.929, 95% confidence interval [CI] 0.88-0.974, P < .002). Each unit increase in slope significantly reduced mortality risk (HR = 0.485, 95% CI 0.278-0.847, P < .011). Hospitalization frequency was significantly increased across worsening baseline score (HR = 0.935, 95% CI 0.906-0.964, P < .0001). A 1-unit increase in slope significantly decreased hospitalization (HR = 0.799, 95% CI 0.726-0.881, P < .0001). CONCLUSIONS: Results confirm that ICNDS is a useful prognostic tool that serves to detect nutrition deterioration at its very beginning.

Effect of atorvastatin on IgA nephropathy in the rat.

BACKGROUND: IgA nephropathy (IgAN) is the most common chronic glomerulonephritis in humans and is a major cause of end-stage kidney disease worldwide. There is no agreement on the exact underlying mechanism or therapeutic intervention for this disorder. Mesangial proliferation typifies the renal histopathology in IgAN. Statin drugs, as prenylationinhibitors, have been shown to have an antiproliferative effect on renal mesangial cells and to reduce IgAN-associated glomerulusclerosis and proteinuria. The aim of this study is to examine the effect of atorvastatin on kidney function, proteinuria and kidney histology changes in IgANinduced rats. METHODS: IgAN was induced in Wistar-Kyoto rats by bovine γ-globulin (BGG). Four groups of rats were treated in metabolic cages: 1) control; 2) atorvastatin (2 mg/kg body weight/day through nasogastric tube) - treated rats; 3) IgAN-rats; 4) IgAN-rats treated with atorvastatin. Urine volume, urine protein excretion, blood urea and creatinine concentrations in addition to creatinine clearance were examined every 14 days, throughout the duration of the study (56 days). All kidneys from sacrificed rats were examined for histology including glomerular cell nuclei count and immunofluorescence. RESULTS: There were no differences in blood creatinine concentrations between the groups. Creatinine clearance was lower on the 42nd day and proteinuria was higher on Days 14, 42 and 56, in rats in Group 3 compared to all others; additionally, histology examination revealed a higher glomerular cell nuclei count in this group. Immunofluorescence was equally positive for IgA in mesangial cells in the kidneys from rats of Groups 2, 3 and 4. CONCLUSIONS: Atorvastatin attenuates kidney-function impairment, proteinuria and mesangial cell proliferation in BGG model of IgANinduced rats.

Noninvasive skin measurements to monitor chronic renal failure pathogenesis.

BACKGROUND/AIMS: Cutaneous manifestations are common in hemodialysis (HD) patients with chronic renal failure (CRF). Associated with uremia, pruritus is a frequently observed symptom in CRF patients and increases with deteriorating renal function. Skin hydrophilic biomarkers (SHB) may be altered in CRF compared to healthy controls. METHODS: A noninvasive skin wash sampling technique to detect the expression of SHB, by measuring their secretion on skin surface, was used on HD patients and healthy controls. Hydrophilic antioxidants such as total antioxidant scavenging capacity (TSC) and uric acid (UA) content, and cytokine inflammatory biomarkers such as TNFα and IL-10 levels were estimated. RESULTS: Our findings demonstrate significant alterations of the SHB level between HD patients and healthy volunteers. Furthermore, such alterations of secreted SHB correlated markedly with detected changes in blood biochemistry and dermatology severity score. CONCLUSION: Skin wash sampling of SHB is a noninvasive technique that distinguishes between HD patients and healthy controls. In HD patients, SHB is associated with biochemical markers in blood and dermatologic symptom severity. This technique is also suggested, as a monitoring tool for diagnosis and treatments of various diseases, in which skin dysfunction is involved.

Medication apprehension and compliance among dialysis patients--a comprehensive guidance attitude.

BACKGROUND: Compliance with treatment regimens is a continuing challenge for chronic dialysis patients and their medical caregivers. Poor patient adherence to prescribed medications can adversely affect treatment outcome. STUDY DESIGN: In this pre- versus post-intervention study, 89 chronic dialysis patients [75 hemodialysis (HD), 14 continuous ambulatory peritoneal dialysis (CAPD); mean age 62.7 +/- 12.39 years, 34 females] responded to a written questionnaire designed to assess knowledge about and compliance with 5 groups of prescribed medications: metabolic drugs, antihypertensives, cardiac-supporting agents, peptic disease therapy and hematological replacement therapy. Mode of intake, storage, means of supply and source of information for each class of drug were also assessed. Patients then received both oral and written instructions regarding their prescribed medications (intervention). This information was repeated 3 months later. Six months after the intervention, patients were re-administered the questionnaires. Response to the questionnaires and laboratory data were compared prior to and following the intervention. RESULTS: Overall, compliance with prescribed medications significantly improved following the intervention, from 89 to 95.7%, p = 0.0007. This relative improvement was greater in HD than CAPD patients (27 vs. 2%, p < 0.0001). Improvement in compliance was associated with lower initial scores, fewer years of education, and longer dialysis vintage. Compared to baseline values, post-intervention blood hemoglobin, hematocrit, mean corpuscular volume, ferritin and Ca levels were significantly improved. CONCLUSIONS: Dialysis patients appear to benefit from receiving comprehensive guidance about medications, in terms of compliance with medications and blood chemistry and hematology measures.

A randomized controlled clinical trial comparing the efficacy of dead sea mineral-enriched body lotion versus two types of placebo in the treatment of cutaneous dryness, itching, peeling and tightness in hemodialysis patients (EDIT).

BACKGROUND/AIMS: The present study was designed to investigate the short-term safety and efficacy of topical application with body lotion enriched with minerals from the Dead Sea versus 2 different placebo treatments in reducing symptoms of uremic pruritus. METHODS: In this single-center, randomized, double placebo-controlled clinical trial, 78 hemodialysis patients with self-reported uremic pruritus were randomized to twice-daily topical treatment with body lotion enriched with minerals from the Dead Sea (DS) or to each of 2 types of placebo: (1) lotion with no Dead Sea minerals but otherwise identical to DS (P1) or (2) lotion with no active ingredients (P2). Symptoms of uremic pruritus (itching, dryness, peeling, tightness) were evaluated at baseline and 2 weeks (14 days) after treatment intervention using a 5-point Likert scale. RESULTS: Following treatment, significant differences in symptom severity scores between DS and P1 and, separately, between group DS and P2, were not detected. Additionally, when DS was compared to the combined placebo groups (P1 and P2 together), significant post-treatment differences in symptom severity scores were not observed. Symptoms were less severe post-treatment regardless of treatment assignment. CONCLUSIONS: DS was not superior to either of the placebo treatments in the symptomatic relief of uremic pruritus.

Antihypertensive effect of low calcium dialysis.

BACKGROUND: During maintenance hemodialysis acute elevation in serum calcium is common. Low calcium dialysis is advocated as a therapy for prevention of dialysis-induced hypercalcemia. Approximately 16% of our chronic hemodialysis patients experience elevated arterial blood pressure during the hemodialysis session, becoming hypertensive by the end of the treatment. All these patients exhibited post-dialysis hypercalcemia. OBJECTIVES: To investigate the effect of low calcium dialysis on post-dialysis hypertension in view of an evident link between serum calcium and blood pressure in both normal renal function and chronic renal failure patients. METHODS: We evaluated 19 chronic hemodialysis patients in whom both post-dialysis hypertension and PDHCa were observed. We investigated changes in serum total calcium, ionized calcium, intact parathormone levels and arterial blood pressure in response to 4 weeks low calcium dialysis as a treatment for PDHCa. RESULTS: When PDHT patients were treated with low calcium dialysis, post-dialysis blood pressure was significantly decreased compared to pre-dialysis values (155.3 +/- 9.7/82.2 +/- 7.9 mmHg pre-dialysis vs. 134.1 +/- 20.8/80 +/- 8.6 mmHg post-dialysis, P = 0.001). Additionally, post-dialysis blood pressure was significantly lower than post-dialysis blood pressure prior to the low calcium dialysis treatment (176.1 +/- 15/86 +/- 10.8 mmHg post-standard dialysis, 134.1 +/- 20.8/80 +/- 8.6 mmHg after low calcium dialysis, P = 0.001). A decline in post-dialysis serum calcium (2.34 +/- 0.2 vs. 2.86 +/- 0.12 mmol/L, P= 0.04) and ionized calcium (1.17 +/- 0.12 vs. 1.3 +/- 0.06 mmol/L, P = 0.03) compared to pre-dialysis levels was also achieved by this treatment, with no significant changes in iPTH levels. CONCLUSIONS: These data suggest a role for low calcium dialysis in treating acute serum calcium elevation and post-dialysis hypertension in patients receiving maintenance hemodialysis.

Baseline oxysterols and other markers of oxidative stress, inflammation and malnutrition in the vitamin e and intima media thickness progression in end-stage renal disease (VIPER) cohort.

BACKGROUND AND OBJECTIVES: Oxysterols are markers of oxidative stress, levels of which have not yet been reported in hemodialysis (HD) patients. This study was designed to compare levels of the oxysterols 7-ketocholesterol (7KC) and 7beta-hydroxycholesterol (7betaOH) between a cohort of HD patients and healthy controls. METHODS: This nested cross-sectional study reflects baseline (pre-intervention) values for markers of oxidative stress, inflammation and nutrition status in the 160-member vitamin E and carotid intima media thickness progression in end-stage renal disease (VIPER) cohort (age 64.1 +/- 8.8, 33.5% female). Age- and sex-matched healthy volunteers served as controls. Plasma oxysterols 7KC and 7betaOH were determined by isotope dilution gas chromatography/mass spectrometry. RESULTS: Despite higher plasma alpha-tocopherol levels in HD patients than controls (36.0 +/- 9.3 vs. 31.8 +/- 8.4 micromol/l, p = 0.007), 7KC levels (9.8 +/- 6.9 vs. 5.9 +/- 2.8 nmol/mmol cholesterol, p < 0.0001) and 7betaOH levels (8.7 +/- 4.3 vs. 2.7 +/- 1.6 nmol/mmol cholesterol, p < 0.0001) were higher in HD patients. The oxysterol 7betaOH was significantly, inversely associated with prealbumin (r = -0.18, p = 0.03), though neither oxysterol was significantly associated with any other marker of oxidative stress, inflammation or nutrition status and did not discriminate for CVD in HD patients. CONCLUSIONS: Elevated levels of the oxysterols 7KC and 7betaOH indicate that HD patients are in a state of oxidative stress compared to healthy controls. However, oxysterols 7KC and 7betaOH did not appear to contribute additional information about oxidative stress among HD patients.