Juvenile-onset Takayasu arteritis: peculiar vascular involvement and more refractory disease

Objectives: To compare prognosis parameters and arterial site involvement in Takayasu arteritis (TA) patients with disease onset at age <= 18 and >= 21 years. Methods: Sixty-two TA patients [American College of Rheumatology (ACR) and European League Against Rheumatism/Paediatric Rheumatology European Society (EULAR/PreS) criteria] were enrolled consecutively and divided into two groups according to disease onset, and matched for disease duration: juvenile TA patients aged <= 18 years (n = 17) and adult TA patients aged >= 21 years (n = 45). The protocol evaluated the following prognostic factors: aortic insufficiency, ischaemic retinopathy, severe systemic hypertension, and arterial aneurysms. In addition, death and remission [defined as stable disease > 6 months (no complaints without immunosuppressive and prednisone use) and normal erythrocyte sedimentation rate (ESR)] were also analysed. Stenosis and aneurisms were investigated by magnetic angioresonance or arteriography and angiographic classification was defined according to Hata criteria. Results: Mean disease duration was similar in the juvenile and adult TA groups (13.50 +/- 10.73 vs. 13.80 +/- 7.17 years, p = 0.092) and a trend to a lower predominance of female gender in the juvenile TA group was observed (64.71% vs. 88.89%, p = 0.056). The prognosis was distinct in the two groups, with juvenile patients having a lower frequency of disease remission (23.53% vs. 55.56%, p = 0.04) and a significantly higher frequency of aneurism (41.0% vs. 11.1%, p = 0.013). Almost half of the juvenile TA patients had left renal stenosis, a frequency significantly higher than in the adult TA group (41.18% vs. 11.10%, p = 0.013), whereas the stenosis frequency was comparable in all other vascular sites evaluated. No differences were observed between the two groups regarding the frequency of aortic insufficiency, ischaemic retinopathy, severe systemic arterial hypertension, vascular procedures, and mortality. Angiographic classification revealed a similar distribution of arterial involvement in both groups (p > 0.05). Conclusions: Juvenile TA patients have distinct characteristics, with a peculiar renal vascular involvement, the presence of aneurism, and a more refractory disease compared with adult TA patients.

Unexplained sudden death in patients on the waiting list for renal transplantation

Background. The incidence of unexplained sudden death (SD) and the factors involved in its occurrence in patients with chronic kidney disease are not well known. Methods. We investigated the incidence and the role of co-morbidities in unexplained SD in 1139 haemodialysis patients on the renal transplant waiting list. Results. Forty-four patients died from SD of undetermined causes (20% of all deaths; 3.9 deaths/1000 patients per year), while 178 died from other causes and 917 survived. SD patients were older and likely to have diabetes, hypertension, past/present cardiovascular disease, higher left ventricular mass index, and lower ejection fraction. Multivariate analysis showed that cardiovascular disease of any type was the only independent predictor of SD (P = 0.0001, HR = 2.13, 95% CI 1.46-3.22). Alterations closely associated with ischaemic heart disease like angina, previous myocardial infarction and altered myocardial scan were not independent predictors of SD. The incidence of unexplained SD in these haemodialysis patients is high and probably a consequence of pre-existing cardiovascular disease. Conclusions. Factors influencing SD in dialysis patients are not substantially different from factors in the general population. The role played by ischaemic heart disease in this context needs further evaluation.

Treatment of Coronary Artery Disease in Hemodialysis Patients Evaluated for Transplant-A Registry Study

Background. We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). Methods. We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. Results. In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction >= 70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45). Conclusions. In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Validation of plasma clearance of (51)Cr-EDTA in adult renal transplant recipients: comparison with inulin renal clearance

Plasma clearance of (51)Cr-EDTA ((51)Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between (51)Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of (51)Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of (51)Cr-EDTA-Cl and In-Cl were performed. A single dose of 3.7MBq of (51)Cr-EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In-Cl and (51)Cr-EDTA-Cl and to determine the better concordance between all possibilities of measure for the (51)Cr-EDTA-Cl. The mean of In-Cl was 44.5 +/- 17.9 ml/min/1.73 m(2). There was a positive correlation between In-Cl and all possible measurements of (51)Cr-EDTA-Cl. (51)Cr-EDTA-Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for (51)Cr-EDTA-Cl was a reliable method to measure GFR compared with In-Cl and comprises a suitable method to be used in kidney transplanted patients.

Polymyxin B and colistimethate are comparable as to efficacy and renal toxicity

We compared 41 patients who received colistimethate with 41 who received polymyxin B for the treatment of serious infections caused by carbapenem-resistant Acinetobacter spp. and found both polymyxins have similar efficacy and toxicity. (C) 2009 Elsevier Inc. All rights reserved.

Evaluation of antibody response to the heptavalent pneumococcal conjugate vaccine in pediatric chronic kidney disease

Pneumococcal vaccination has been recommended for immunocompromised children, including patients with chronic kidney disease. We determined pneumococcal immunoglobulin (Ig) G antibodies to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F before and after 48 pediatric patients with chronic renal failure were administered heptavalent conjugated pneumococcal vaccine. The patients were between 1 and 9 years of age and were separated into a conservative treatment group (Group 1) and a dialysis group Group 2). The antibody response to the vaccinal serotypes was evaluated by measuring antibody concentrations before the first dose and 60 days after the second one. Pre-vaccinal IgG concentrations >= 0.35 mu g/ml were detected for all serotypes in at least 50% of the patients in both groups. Patients from both groups showed a statistically indistinguishable behavior in terms of the medians of post-vaccination IgG levels. An ""adequate"" vaccine response was defined as a post-immunization level of specific pneumococcal serotype antibody >= 0.35 mu g/ml, based on the World Health Organization`s (WHO) protective antibody concentration definition for pneumococcal conjugate vaccines, or on a fourfold increase over baseline for at least five of the seven antigens of the vaccine. An ""adequate"" vaccinal response was obtained in 100% of the patients of both groups using WHO`s definition, or in 45.8% of Group 1 patients and 37.5% of Group 2 patients when the criterion was a fourfold antibody increase over baseline antibody concentrations.

Negative Anti-C1q Antibody Titers May Influence Therapeutic Decisions and Reduce the Number of Renal Biopsies in Systemic Lupus Erythematosus

In a cross-sectional study involving 62 patients with systemic lupus erythematosus (SLE), we found that patients with biopsy-proven lupus nephritis (LN) had higher titers of anti-C1q antibodies than active SLE without nephritis patients. Anti-C1q was associated with a negative predictive value of 94.59%, a positive predictive value of 52%, a sensitivity of 86.66% and a specificity of 74.47% for the diagnosis of LN. We conclude that high titers of anti-C1q antibodies are strongly associated with the presence of active LN, and the negative predictive value of this test for diagnosing LN is very high; therefore, it can influence therapeutic decisions and reduce the number of renal biopsies in patients with SLE. Copyright (C) 2011 S. Karger AG, Basel

The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Mutations in PKD1 cause the majority of cases of autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, cell differentiation, and apoptosis, its lower biologic activity observed in ADPKD might influence the degree of injury after renal ischemia/reperfusion. We induced renal ischemia/reperfusion in 10- to 12-wk-old male noncystic Pkd1(+/-) and wild-type mice. Compared with wild-type mice, heterozygous mice had higher fractional excretions of sodium and potassium and higher serum creatinine after 48 h. In addition, in heterozygous mice, also cortical damage, rates of apoptosis, and inflammatory infiltration into the interstitium at time points out to 14 d after injury all increased, as well as cell proliferation at 48 h and 7 d. The mRNA and protein expression of p21 was lower in heterozygous mice than wild-type mice at 48 h. After 6 wk, we observed dilated tubules, microcysts, and increased renal fibrosis in heterozygotes. The early mortality of heterozygotes was significantly higher than that of wild-type mice when we extended the duration of ischemia from 32 to 35 min. In conclusion, ischemia/reperfusion induces a more severe injury in kidneys of Pkd1-haploin-sufficient mice, a process that apparently depends on a relative deficiency of p2l activity, tubular dilation, and microcyst formation. These data suggest the possibility that humans with ADPKD from PKD1 mutations may be at greater risk for damage from renal ischemia/reperfusion injury.

The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Introduction: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. Purpose: To assess the behavior of C-reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). Methods: A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. Results: When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver-operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). Conclusion: The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.

Mild chronic kidney dysfunction and treatment strategies for stable coronary artery disease

Objective: Our objective was to evaluate the association of chronic kidney dysfunction in patients with multi-vessel chronic coronary artery disease, preserved left ventricular function, and the possible interaction between received treatment and cardiovascular events. Methods: The glomerular filtration rate was determined at baseline on 611 patients who were randomized into three treatment groups: medical treatment, percutaneous coronary intervention, and coronary artery bypass surgery. Incidence of myocardial infarction, angina requiring a new revascularization procedure, and death were analyzed during 5 years in each group. Results: Of 611 patients, 112 (18%) were classified as having normal renal function, 349 (57%) were classified as having mild dysfunction, and 150 (25%) were classified as having moderate dysfunction. There were significant differences among the cumulative overall mortality curves among the three renal function groups. Death was observed more frequently in the moderate dysfunction group than the other two groups (P < .001). Interestingly, in patients with mild chronic kidney dysfunction, we observed that coronary artery bypass treatment presented a statistically higher percentage of event-free survival and lower percentage of mortality than did percutaneous coronary intervention or medical treatment Conclusions: Our results confirm that coronary artery disease accompanied by chronic kidney dysfunction has a worse prognosis, regardless of the therapeutic strategy for coronary artery disease, when renal function is at least mildly impaired. Additionally, our data suggest that the different treatment strategies available for stable coronary artery disease may have differential beneficial effects according to the range of glomerular filtration rate strata.

Percutaneous ultrasound-guided renal biopsy in children - safety, efficacy, indications and renal pathology findings: 14-year Brazilian university hospital

Introduction: Pediatric percutaneous renal biopsy (Bx) is a routine procedure in pediatric nephrology to obtain renal tissues for histological study. We evaluated the safety, efficacy, indications and renal findings of this procedure at a tertiary care pediatric university hospital and compared our findings with the literature. Methods: Retrospective study based on medical records from January 1993 to June 2006. Results: In the study period, 305 Bx were performed in 262 patients, 127 (48.5%) male, aged 9.8 +/- 4.2 years. A 16-gauge needle was utilized in 56/305 Bx, an 18-gauge needle in 252/305 Bx (82.6%). 56.1% Bx were performed under sedation plus local anesthesia, 43.9% under general anesthesia. The number of punctures per Bx was 3.1 +/- 1.3. Minor complications occurred in 8.6% procedures. The 16-gauge needle caused a higher frequency of renal hematomas (p = 0.05). The number of glomeruli per puncture was >= 5 in 96.7% and >= 7 in 92%. Glomeruli number per puncture and frequency of complications were not different according to the type of anesthesia used. A renal pathology diagnosis was achieved in 93.1% Bx. The main indications of Bx were nephrotic syndrome (NS), lupus nephritis (LN) and hematuria (HE). The diagnosis of minimal change disease (MCD) (61.3%), class V (35.6%) and IgA nephropathy (26.3%) predominated in NS, LN and HE patients, respectively. Conclusion: Pediatric real-time ultrasound-guided percutaneous renal biopsy was safe and effective. The main clinical indications for Bx were NS and LN, the predominant renal pathology diagnoses were MCD and class V LN.

Programmed hypertension in rats treated with a NF-kappa B inhibitor during nephrogenesis: renal mechanisms

Suppression of the renin-angiotensin system (RAS) during murine lactation causes progressive renal injury, indicating a physiological action of angiotensin II on nephrogenesis. The nuclear factor NF-kappa B system is one of the main intracellular mediators of angiotensin II. We investigated whether inhibition of this system with pyrrolidine dithiocarbamate (PDTC) during rat nephrogenesis would lead to similar hypertension and renal injury as observed with RAS suppressors. Immediately after delivery, 32 Munich-Wistar dams, each nursing 6 male pups, were divided into 2 groups: C, untreated, and PDTC, receiving PDTC, 280 mg kg(-1) day(-1) orally, during 21 days. After weaning, the offspring were followed until 10 months of age without treatment. Adult rats that received neonatal PDTC exhibited stable hypertension and myocardial injury, without albuminuria. To gain additional insight into this process, the renal expression of RAS components and sodium transporters were determined by quantitative real-time PCR (qRT-PCR) at 3 and 10 months of life. Renal renin and angiotensinogen were upregulated at 3 and downregulated at 10 months of age, suggesting a role for early local RAS activation. Likewise, there was early upregulation of the proximal sodium/glucose and sodium/bicarbonate transporters, which abated later in life, suggesting that additional factors sustained hypertension in the long run. The conclusions drawn from the findings were as follows: (1) an intact NF-jB system during nephrogenesis may be essential to normal renal and cardiovascular function in adult life; (2) neonatal PDTC represents a new model of hypertension, lacking overt structural injury or functional impairment of the kidneys; and (3) hypertension in this model seems associated with early temporary activation of renal RAS and sodium transporters. Hypertension Research (2011) 34, 693-700; doi: 10.1038/hr. 2011.4; published online 17 February 2011

Anti-nucleosome and anti-chromatin antibodies are present in active systemic lupus erythematosus but not in the cutaneous form of the disease

The objective of this study is to investigate the presence of anti-nucleosome (anti-NCS) and anti-chromatin (anti-CRT) antibodies in patients with cutaneous lupus erythematosus (CLE) compared with active and inactive systemic lupus erythematosus (SLE). A total of 154 subjects were evaluated: 54 patients presenting CLE, 66 patients with active SLE and 34 with inactive SLE. Lupus activity was assessed using the disease activity index (SLEDAI). Anti-NCS and anti-CRT antibodies were detected by enzyme-linked immunosorbent assay ( ELISA). Only one of 54 patients with CLE tested positive for both anti-NCS and anti-CRT antibodies. The prevalence of anti-CRT antibodies was significantly higher in active SLE (84.8%) when compared with inactive SLE (26.4%) and CLE (1.8%) ( P < 0.001). Anti-NCS antibodies were also more prevalent in active SLE patients (74.2%) than inactive SLE (11.7%) and CLE patients ( 1.8%) ( P < 0.001). The presence of anti-CRT and anti-NCS antibodies was correlated to disease activity in patients with SLE (r = 0.4937, r = 0.5621, respectively). Furthermore, the detection of both antibodies was correlated with disease activity in patients with SLE who tested negative for anti-dsDNA antibodies ( r = 0.4754 for anti-NCS and r = 0.4281 for anti-CRT). The presence of these two auto-antibodies was strongly associated with renal damage in patients with SLE ( OR = 13.1, for anti-CRT antibodies and OR = 25.83, for anti-NCS antibodies). The anti-NCS and anti-CRT antibodies were not found in CLE. In patients with SLE, there is a correlation of these antibodies with disease activity and active nephritis. When compared with anti-dsDNA antibodies, anti-NCS and anti-CRT antibodies were more sensitive in detecting disease activity and kidney damage in lupus patients. Lupus (2009) 18, 223-229.

Renal redox-sensitive signaling, but not blood pressure, is attenuated by Nox1 knockout in angiotensin II-dependent chronic hypertension

We demonstrated previously that, in mice with chronic angiotensin II-dependent hypertension, gp91phoxcontaining NADPH oxidase is not involved in the development of high blood pressure, despite being important in redox signaling. Here we sought to determine whether a gp91phox homologue, Nox1, may be important in blood pressure elevation and activation of redox-sensitive pathways in a model in which the renin-angiotensin system is chronically upregulated. Nox1-deficient mice and transgenic mice expressing human renin (TTRhRen) were crossed, and 4 genotypes were generated: control, TTRhRen, Nox1-deficient, and TTRhRen Nox1-deficient. Blood pressure and oxidative stress (systemic and renal) were increased in TTRhRen mice (P < 0.05). This was associated with increased NADPH oxidase activation. Nox1 deficiency had no effect on the development of hypertension in TTRhRen mice. Phosphorylation of c-Src, mitogen-activated protein kinases, and focal adhesion kinase was significantly increased 2-to 3-fold in kidneys from TTRhRen mice. Activation of c-Src, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and focal adhesion kinase but not of extracellular signal regulated kinase 1/2 or extracellular signal regulated kinase 5, was reduced in TTRhRen/Nox1-deficient mice (P < 0.05). Expression of procollagen III was increased in TTRhRen and TTRhRen/Nox1-deficient mice versus control mice, whereas vascular cell adhesion molecule-1 was only increased in TTRhRen mice. Our findings demonstrate that, in Nox1-deficient TTRhRen mice, blood pressure is elevated despite reduced NADPH oxidase activation, decreased oxidative stress, and attenuated redox signaling. Our results suggest that Nox1-containing NADPH oxidase plays a key role in the modulation of systemic and renal oxidative stress and redox-dependent signaling but not in the elevation of blood pressure in a model of chronic angiotensin II-dependent hypertension.