Urinary tract infections in patients with chronic renal insufficiency.
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Despite an increasing population of patients with chronic renal insufficiency, the literature on the management of urinary tract infections (UTI) in these patients is sparse. Patients with underlying diabetes are a specific population at risk. Antimicrobial treatment of UTI requires adequate serum, renal, parenchymal, and urine concentrations of drugs with antibacterial activity versus the etiologic organism. Sulfamethoxazole and nitrofurantoin are examples of drugs with low and likely inadequate urine concentrations in patients with creatinine clearances of <50 ml/min. Urine concentrations of ciprofloxacin and levofloxacin remain sufficient as renal function fails, whereas the concentrations of gemifloxacin and moxifloxacin are too low to predict efficacy. More investigative work is needed in the management of UTI in patients with poor renal function. (+info)
Acute injury with intravenous iron and concerns regarding long-term safety.
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Intravenous iron is widely used to maintain adequate iron stores and prevent iron deficiency anemia in patients with chronic kidney disease, yet concerns remain about its long-term safety with respect to oxidative stress, kidney injury, and accelerated atherosclerosis, which are the subjects of this review. Three parenteral iron formulations are available for use in the United States: Iron dextran, iron gluconate, and iron sucrose. Iron dextran, especially the high molecular form, has been linked with anaphylactoid and anaphylactic reactions, and its use has been declining. A portion of intravenous iron preparations is redox-active, labile iron available for direct donation to transferrin. In vitro tests show that commonly available intravenous iron formulations have differing capacities to saturate transferrin directly: Iron gluconate > iron sucrose > iron dextran. Intravenous iron treatment produces oxidative stress, as demonstrated by increases in plasma levels of lipid peroxidation products (malondialdehyde), at a point that is much earlier than the time to peak concentration of catalytically active iron, suggesting a direct effect of iron sucrose on oxidative stress. Furthermore, iron sucrose infusion produces endothelial dysfunction that seems to peak earlier than the serum level of free iron. Intravenous iron sucrose infusion also has been shown to produce acute renal injury and inflammation as demonstrated by increased urinary albumin, enzyme (N-acetyl-beta-glucosaminidase), and cytokine (chemokine monocyte chemoattractant protein-1) excretions. Although the long-term dangers of intravenous iron are unproved, these data call for examination of effects of intravenous iron on the potential for long-term harm in patients with chronic kidney disease. (+info)
Parenteral iron compounds: potent oxidants but mainstays of anemia management in chronic renal disease.
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Ferric iron (Fe)-carbohydrate complexes are widely used for treating Fe deficiency in patients who are unable to meet their Fe requirements with oral supplements. Intravenous Fe generally is well tolerated and effective in correcting Fe-deficient states. However, the complexing of Fe to carbohydrate polymers does not block its potent pro-oxidant effects; systemic free radical generation and, possibly, tissue damage may result. The purpose of this review is to (1) underscore the capacity of currently used parenteral Fe formulations to induce oxidative stress, (2) compare the severity of these oxidant reactions with those that result from unshielded Fe salts and with each other, and (3) speculate as to the potential of these agents to induce acute renal cell injury and augment systemic inflammatory responses. The experimental data that are reviewed should not be extrapolated to the clinical setting or be used for clinical decision making. Rather, it is hoped that the information provided herein may have utility for clinical hypothesis generation and, hence, future clinical studies. By so doing, a better understanding of Fe's potential protean effects on patients with renal disease may result. (+info)
Assessing iron status: beyond serum ferritin and transferrin saturation.
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The increasing prevalence of multiple comorbidities among anemic patients with chronic kidney disease has made the use of serum ferritin and transferrin saturation more challenging in diagnosing iron deficiency. Because serum ferritin is an acute-phase reactant and because the inflammatory state may inhibit the mobilization of iron from reticuloendothelial stores, the scenario of patients with serum ferritin >800 ng/ml, suggesting iron overload, and transferrin saturation <20%, suggesting iron deficiency, has become more common. This article revisits the basis for the Kidney Disease Outcomes Quality Initiative recommendations regarding the use of serum ferritin and transferrin saturation in guiding iron therapy, then explores some of the newer alternative markers for iron status that may be useful when serum ferritin and transferrin saturation are insufficient. These newer tests include reticulocyte hemoglobin content, percentage of hypochromic red cells, and soluble transferrin receptor, all of which have shown some promise in limited studies. Finally, the role of hepcidin, a hepatic polypeptide, in the pathophysiology of iron mobilization is reviewed briefly. (+info)
The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease?
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Although the emergence of erythropoiesis-stimulating agents has revolutionized the anemia management of chronic kidney disease (CKD) in the past two decades, strategies to assess iron (Fe) status and to provide Fe supplementation have remained indistinct. The reported cases of hemochromatosis in dialysis patients from the pre-erythropoiesis-stimulating agent era along with the possible associations of Fe with infection and oxidative stress have fueled the "iron apprehension." To date, no reliable marker of Fe stores in CKD has been agreed on. Serum ferritin continues to be the focus of attention. Almost half of all maintenance hemodialysis patients have a serum ferritin >500 ng/ml. In this ferritin range, Fe supplementation currently is not encouraged, although most reported hemochromatosis cases had a serum ferritin >2000 ng/ml. The moderate-range hyperferritinemia (500 to 2000 ng/ml) seems to be due mostly to non-Fe-related conditions, including inflammation, malnutrition, liver disease, infection, and malignancy. Recent epidemiologic studies have shown that a low, rather than a high, serum Fe is associated with a poor survival in maintenance hemodialysis patients. In multivariate adjusted models that mitigate the confounding effect of malnutrition-inflammation, serum ferritin <1200 ng/ml and Fe saturation ratio in 30 to 50% range are associated with the greatest survival in maintenance hemodialysis patients. Although ferritin is a fascinating molecule, moderate hyperferritinemia is a misleading marker of Fe stores in patients with CKD. It may be time to revisit the utility of serum ferritin in CKD and ask ourselves whether its measurement has helped us or has caused more confusion and controversy. (+info)
Adiponectin in children with chronic kidney disease: role of adiposity and kidney dysfunction.
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Low serum adiponectin is a known cardiovascular risk in adult chronic kidney disease (CKD). However, adiponectin concentrations and their relation with other cardiovascular risks have not been studied in children with preterminal CKD. Forty-four children and adolescents who were aged 6 to 21 yr and had stages 2 to 4 CKD had serum adipocytes, lipoproteins, markers of inflammation, homocysteine, and insulin levels determined cross-sectionally. There were 29 lean (body mass index [BMI] <85th percentile) and 15 nonlean (BMI > or =85th percentile) patients. Mean serum adiponectin level was 30.6 +/- 14.1 microg/ml (range 7.1 to 67.8 microg/ml). A total of 83% of patients had elevated adiponectin level. Despite similar kidney function, lean patients had significantly higher adiponectin levels than nonlean patients (34.1 +/- 13.4 microg/ml versus 23.6 +/- 13.3 microg/ml; P = 0.02). In univariate analysis, serum adiponectin negatively correlated with age (r = -0.34, P = 0.02), BMI (r = -0.47, P = 0.001), leptin (r = -0.41, P = 0.006), GFR (r = -0.39, P = 0.02), and insulin (r = -0.36, P = 0.01) and positively correlated with ApoA2 (r = 0.30, P = 0.04); no significant associations were found with markers of inflammation or homocysteine. Multivariate stepwise analysis showed that GFR (beta = -0.008, P = 0.001), BMI (beta = -0.16, P = 0.015), and age (beta = -0.04, P = 0.018) independently predicted serum adiponectin levels. Separate analysis of lean patients showed no significant relations with age or BMI; only GFR independently predicted serum adiponectin level (beta = -0.01, P = 0.0008). It is concluded that serum adiponectin is elevated in children and adolescents with stages 2 to 4 CKD and that decreased kidney function is a major determinant of elevated adiponectin concentrations. Despite overall elevated adiponectin, overweight patients display lower serum adiponectin levels and might be at risk for future cardiovascular complications. (+info)
Implications of method specific creatinine adjustments on General Medical Services chronic kidney disease classification.
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AIMS: To evaluate the impact of different equations for calculation of estimated glomerular filtration rate (eGFR) on general practitioner (GP) workload. METHODS: Retrospective evaluation of routine workload data from a district general hospital chemical pathology laboratory serving a GP patient population of approximately 250 000. The most recent serum creatinine result from 80 583 patients was identified and used for the evaluation. eGFR was calculated using one of three different variants of the four-parameter Modification of Diet in Renal Disease (MDRD) equation. RESULTS: The original MDRD equation (eGFR(186)) and the modified equation with assay-specific data (eGFR(175corrected)) both identified similar numbers of patients with stage 4 and stage 5 chronic kidney disease (ChKD), but the modified equation without assay specific data (eGFR(175)) resulted in a significant increase in stage 4 ChKD. For stage 3 ChKD the eGFR(175) identified 28.69% of the population, the eGFR(186) identified 21.35% of the population and the eGFR(175corrected) identified 13.6% of the population. CONCLUSIONS: Depending on the choice of equation there can be very large changes in the proportions of patients identified with the different stages of ChKD. Given that according to the General Medical Services Quality Framework, all patients with ChKD stages 3-5 should be included on a practice renal registry, and receive relevant drug therapy, this could have significant impacts on practice workload and drug budgets. It is essential that practices work with their local laboratories. (+info)
Mammalian target of rapamycin inhibition halts the progression of proteinuria in a rat model of reduced renal mass.
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Many kidney transplant patients experience an increase in proteinuria when converted from a calcineurin inhibitor-based regimen to one based on a mammalian target of rapamycin (mTOR) inhibitor, and preexisting proteinuria and poor renal function have been identified as risk factors for this increase. Our aim was to evaluate the effect of sirolimus, an mTOR inhibitor, on renal function and histology in a proteinuric model of reduced renal mass. Sirolimus-treated animals had approximately half as much proteinuria as vehicle-treated animals (P < 0.05), and had less glomerulosclerosis, tubular atrophy, interstitial fibrosis, and inflammation. Immunohistochemistry showed that sirolimus attenuated the increased expression of renal vascular endothelial growth factor (VEGF), as well as the expression of VEGF receptors 1 and 2. In conclusion, sirolimus halted the progression of proteinuria and structural damage in a rat model of reduced renal mass, possibly through a reduction in renal VEGF activity. (+info)