Increased phagocytic nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production in patients with early chronic kidney disease

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of atherosclerosis that develops in patients with advanced chronic kidney disease (CKD). This study was designed to investigate whether a relationship exists between phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide anion (*O2-) production and subclinical atherosclerosis in patients with early CKD. METHODS: Superoxide production was assayed by chemiluminescence under baseline and stimulated conditions on mononuclear cells obtained from asymptomatic patients with stage 1 to 2 CKD (N=22) and healthy controls (N=21). Ultrasonographic determination of carotid intima-media thickness (IMT) was used to assess the presence of atherosclerosis. RESULTS: Although there were no differences in baseline *O2- production between controls and patients, the *O2- production in phorbol myristate acetate-stimulated mononuclear cells was increased (P<0.05) in patients compared with controls. The phorbol myristate acetate-induced *O2- production was completely abolished by apocynin, a specific inhibitor of NADPH oxidase. A direct correlation (r=0.441, P<0.05) was found between plasma insulin levels and NADPH oxidase-mediated *O2- production in patients. Carotid IMT was higher (P<0.005) in patients than in controls. Carotid IMT values above the upper normal limit in controls were found in 70% and 40% of patients with increased or normal NADPH oxidase-mediated *O2- production, respectively. CONCLUSION: Generation of *O2- that is mainly dependent on NADPH oxidase is abnormally enhanced in patients with early CKD. It is suggested that this alteration could be related to the development of subclinical atherosclerosis in these patients.     

Pregnancy in patients with kidney disease

QUESTIONS: - To what extent can ailing kidneys adapt their functions to the demands of pregnancy? - What risks is the nephropathic patient prone to throughout pregnancy compared with those of the general population, and which specific risks does her kidney disease determine? - What risks is the baby of a nephropathic prone to throughout pregnancy compared with those of the general population? - What changes have occurred over recent years? CONCLUSIONS: Current knowledge allows to conclude that pregnancy in the nephropathic woman can be started, provided that: - best timing is considered; - women are informed about their risk factors: functional levels and presence of hypertension, regardless of type of nephropathy.     

Increased incidence of sensitization among patients with polycystic kidney disease following pretransplant blood transfusions

Following pretreatment with at least 5 blood transfusions to 58 nontransfused uremic patients, 23 (40%) formed lymphocytotoxic antibodies against B cells and 9 (15%) against T cells as well. Significantly more (p less than 0.01) patients with polycystic kidney disease (6/16) formed T cell antibodies compared to patients with other diseases. The presence of antibodies delayed kidney transplantation, since significantly more (p less than 0.01) patients without antibodies (28 out of 35) received kidney grafts than patients with antibodies (9 out of 23). 5 patients received kidney grafts despite the occurrence of antibodies against donor B cells, but 3 of the patients lost their grafts within 1 month. In vitro lymphocyte subpopulations were studied in 4 patients before and after each of the planned blood transfusions. No persistent changes in lymphocyte responses to phytohemagglutinin and in mixed lymphocyte culture were seen. T cell subpopulations identified by monoclonal antibodies were unchanged, but the proportion of macrophages/monocytes (OKMl-positive cells) increased from 22 +/- 6 to 46 +/- 10% (p less than 0.05).     

Cardiovascular disease in patients with chronic kidney disease

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with renal failure. Patients with chronic kidney disease have significant CVD, and carry a high cardiovascular burden by the time they commence renal replacement therapy (RRT). The severity of CVD that has been observed in dialysis patients lead to a growing body of research examining the pathogenesis and progression of CVD during the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) (ie, predialysis phase). Multiple factors are involved in the development of CVD in CKD. More importantly, critical and key factors seem to develop early in the course of CKD, and result in preventable worsening of CVD in this patient population. Anemia is common in patients with CKD, and has been shown to have an independent role in the genesis of left ventricular hypertrophy (LVH) and subsequent CVD. Unfortunately, it is underdiagnosed and undertreated in patients with CKD. Early intervention, and better correction of anemia, seems to gain a great momentum in the prevention and management of CVD in CKD. Hypertension is another risk factor that has been targeted by the National Kidney Foundation Task Force on CVD in chronic kidney disease. This article reviews the different factors involved in the pathogenesis of CVD in CKD and the evidence supporting early and aggressive intervention.     

Increased night heart rate is associated with worse large artery elasticity in chronic kidney disease patients

Background

Chronic kidney disease (CKD) is associated with high overall and cardiovascular mortality. Numerous studies have reported that increased heart rate is a risk factor for all-cause mortality. We investigated the link between sleep heart rate and artery stiffness in CKD patients.

Methods

In a cross-sectional study, we enrolled 100 prevalent Chinese CKD patients (55 males, aged 52.5 ± 16.40 years). Heart rate was measured with an automatic system. Arterial stiffness was evaluated by using a calibrated tonometer.

Results

Large artery elasticity index (LAEI) was positively correlated with body mass index and hemoglobin but negatively associated with age and systolic blood pressure. Furthermore, LAEI was negatively associated with glomerular filtration rate (GFR) and sleep heart rate. In multivariate regression, LAEI was independently predicted by SBP, BMI, age, sleep heart rate, and gender. Adjusted R ² of the model was 0.486.

Conclusion

Elevated sleep heart rate is significantly associated with increased arterial stiffness in CKD patients. Further investigation is needed to explore the potential benefits of sleep heart rate lowering therapy in this patient group.     

Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease

BACKGROUND: The prevalence of increased oxidative stress and acute-phase inflammation in patients with chronic kidney disease (CKD) has not been thoroughly investigated. METHODS: Biomarkers of oxidative stress and acute-phase inflammation were measured in a cohort of 60 patients with stage 3-5 CKD compared to a healthy subject cohort. Levels of oxidative stress and inflammation were also compared to estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: All biomarkers of oxidative stress (plasma protein carbonyl group content, plasma free F2-isoprostane content, plasma protein reduced thiol content) and all markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6)] differed significantly between CKD patients and healthy subjects. There was no significant relationship between estimated GFR and any oxidative stress or inflammation biomarker. CRP levels were higher in patients with known coronary vascular disease (CVD) and in patients not taking angiotensin II inhibitors. Plasma IL-6 levels were significantly higher in patients with known coronary vascular disease and lower in patients taking statins. Biomarkers of oxidative stress were significantly higher in patients with diabetes and hypercholesterolemia. CONCLUSION: There is evidence of increased oxidative stress and acute-phase inflammation in patients with stage 3-5 chronic kidney disease compared to healthy subjects that does not closely correlate with estimates of GFR. Among CKD patients, inflammatory biomarkers correlate with known CVD and inversely correlate with the use of angiotensin II inhibitors and statins. A further increase in oxidative stress was noted in diabetic and hypercholesterolemic patients. Inflammation and oxidative stress may contribute to cardiovascular risk in CKD patients.     

Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn's disease

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is implicated in early wound healing and fibrosis. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of VEGF. The aim of this study was to examine VEGF expression and regulation in fibroblasts isolated from patients with Crohn's disease. METHODS: Fibroblasts were isolated by a primary explant technique from serosal biopsies of non-strictured and strictured segments of bowel from eight patients undergoing resection for Crohn's disease, and normal colon from six patients undergoing resection for benign and malignant colorectal disease. Fibroblasts were cultured with transforming growth factor (TGF) beta and corticosteroids. After 24 h the culture supernatant was collected for VEGF assay by enzyme-linked immunosorbent assay. RESULTS: VEGF production was significantly higher in fibroblasts isolated from strictures (mean(s.e.m.) 1980(260) pg/ml) than from non-strictured segments (1116(165) pg/ml) in patients with Crohn's disease or control fibroblasts (898(93) pg/ml). TGF-beta increased VEGF production in normal and non-strictured Crohn's fibroblasts. Corticosteroids suppressed unstimulated VEGF production in all groups. CONCLUSION: Enhanced serosal fibroblast VEGF production might play a role in initiating stricture formation in Crohn's disease. VEGF production in serosal fibroblasts is sensitive to stimulation with TGF-beta. Corticosteroids may reduce stricturing through suppression of VEGF.     

Increased incidence of cardiac complications in kidney transplant recipients with cytomegalovirus disease

BACKGROUND: The transplant literature has not shown cytomegalovirus (CMV) disease to be a significant risk factor for posttransplant cardiac complications. A large number of nontransplant studies have, however, reported an association between coronary heart disease (CHD) and CMV disease. Pathology studies have demonstrated a high incidence of CMV in atheromatous plaques from the coronary circulation. METHODS: We performed multivariate analysis to determine if posttransplant CMV disease was a significant risk factor for cardiac complications in kidney transplant recipients. We also performed univariate analysis to determine which cardiac complications were more common in the recipients with CMV disease. RESULTS: Between January 1, 1984 and June 30, 1997, 1859 adults underwent kidney transplants at our institution. Of these, 377 developed one of the following cardiac complications posttransplant: myocardial infarction, angina, arrhythmia, congestive heart failure, and angiographic vessel occlusion. By multivariate analysis, significant risk factors for one of the above cardiac complications were recipient age >50 years [odds ratio (OR)=2.5, P=0.0001], diabetes (OR=1.99, P=0.0001), a history of cardiac disease pretransplant (OR= 1.34, P=0.04), and CMV disease (OR=1.5, P=0.01). Univariate analysis demonstrated that recipients with CMV disease had a higher overall incidence of cardiac complications. Arrhythmias, congestive heart failure, and vessel occlusion were more common in those with CMV disease. The incidence of myocardial infarction, angina, and cardiac arrest did not differ between the two groups (recipients with versus without CMV disease). CONCLUSIONS: CMV disease is associated with an increased risk of cardiac complications in kidney transplant recipients. In our series, angiographic vessel occlusion was more common in recipients with CMV disease. This interesting finding may support the theory that CMV plays some role in the pathogenesis of CHD.     

Infections and cardiovascular disease in patients with chronic kidney disease

Although interest in the nexus of cardiovascular disease and chronic kidney disease (CKD) has mushroomed, especially in the in past 5 years, activity in the arena of CKD-related infection has been much more modest. This development is surprising when one considers the increasing evidence that links inflammation, kidney disease, and cardiovascular disease. Also, major infections, such as pneumonia and septicemia, are paradigmatic inflammatory states, and accumulating evidence indicates that they are a common antecedent of new cardiovascular events in dialysis patients. Major infections are associated with higher rates of cardiovascular events and death in dialysis patients, and similar associations have been observed in community settings. Although recent studies suggest that hospitalization for major infections is much more common in nondialysis CKD than in the general population, the prognostic implications remain unexplored.     

Traumatic hematuria in patients with polycystic kidney disease

Autosomal dominant polycystic kidney disease (PKD) is the most prevalent hereditary disorder in this country and a common cause of chronic renal failure. Patients frequently present with hematuria as the initial manifestation of PKD. We describe a patient with gross hematuria after blunt trauma who was found to have previously undiagnosed PKD. We review present diagnostic and treatment modalities and suggest potential management strategies for surgeons caring for patients presenting with traumatic hematuria and PKD.     

Pain patterns in patients with polycystic kidney disease

BACKGROUND: Pain is a common problem in patients with polycystic kidney disease (PKD), but patterns have not been characterized as to frequency and severity. Physicians should be aware of pain problems so an approach to chronic pain management can be pursued. METHODS: One hundred seventy-one completed questionnaires out of 300 distributed to PKD patients whose renal function ranged from normal to end-stage renal disease (ESRD) were analyzed. Age at diagnosis of PKD was documented, and patients noted how the diagnosis was made. Location, severity, and frequency of pain were characterized. The Visual Analogue Scale (VAS) was used to measure pain intensity. RESULTS: There were 94 females and 77 male respondents, with a mean age of 47.4 years. Initial diagnosis of PKD occurred at a mean age of 31.6 years. Caucasians comprised 92.2% of the respondents. Patients' symptoms, a family history of PKD, and discovery of PKD during evaluation for hypertension or hematuria were the most frequent factors that led to the diagnosis. Order of frequency of pain was: low back pain, abdominal pain, headache, chest pain, and leg pain. Severity of pain, documented by the VAS intensity, was 4 to 5/10 in the majority of patients. CONCLUSION: Pain, which can be diffuse, is the most frequent symptom that led to the diagnosis of PKD in patients who responded to this questionnaire, and occurs with greater frequency than generally appreciated. Physicians need to obtain a detailed history about pain in their PKD population so as to allow an approach to pain management.     

Adynamic bone in patients with chronic kidney disease

Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern because of its potential increased risk for fracture and cardiovascular disease (CVD). Prevalence rates for adynamic bone are reportedly increased, although the variance for its prevalence and incidence is large. Differences in its prevalence are largely attributed to classification and population differences, the latter of which constitutes divergent groups of elderly patients having diabetes and other comorbidities that are prone to low bone formation. Most patients have vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably decreases to very low levels during CKD progression. Fortunately, therapy with vitamin D receptor activators (VDRAs) appears to be useful in preventing bone loss, in part, by its effect to stimulate bone formation and in decreasing CVD morbidity, and should be considered as essential therapy regardless of bone turnover status. Future studies will depend on assessing cardiovascular outcomes to determine whether the risk/reward profile for complications related to VDRA and CKD is tolerable.     

Increased oestrogen production and adrenal cortical hyperfunction in patients with pulmonary disease and clubbing of the fingers

Raised serum oestradiol levels were demonstrated in men and postmenopausal women with pulmonary disease and clubbing of the fingers. The site of production is thought to be a hyperfunctioning adrenal cortex; this conclusion is supported by the finding of elevated adrenocortical responses to intramuscular injection of adrenocorticotrophic hormone.