Vascular access considerations for therapeutic apheresis procedures.

The success of therapeutic apheresis (TA), similar to hemodialysis, depends on the integrity of the extracorporeal circuit as well as a reliable vascular access. However, unlike hemodialysis, which requires high flow of blood around 400 mL/minute through the extracorporeal circuit for effective clearance, TA is usually carried out with much lower blood flow rates (<100 ml/minute). Therefore, even peripheral venous access can be considered for TA. The main determinants of the choice of vascular access for TA is the duration of the planned treatment and, to a certain degree, the indication for its use. While peripheral venous access and temporary central venous catheters are sufficient for short-term TA, tunnelled catheters and arteriovenous fistulae (AVF) are usually used for long-term treatments. Because of the large body of evidence in the hemodialysis literature on the advantages of AVF over tunnelled catheters and AV grafts, they should be considered as the preferred access for chronic TA as well. However, advance planning for the care of AVF after creation is of critical importance especially since many of the healthcare providers dealing with TA are less familiar with caring for AVF than nephrologists and dialysis nurses. In this article we first review the similarities and differences between HD and TA procedures. The pros and cons of different vascular access options are discussed next. Finally, we have included a list of recommendations on maintenance of AVF created for TA based on our own experience.

Novel therapeutic approaches to lupus glomerulonephritis: translating animal models to clinical practice.

Systemic lupus erythematosus is a chronic autoimmune disease frequently affecting the kidney. Renal involvement is characterized by glomerular immune complex deposits and proliferative glomerulonephritis progressing to glomerulosclerosis and kidney failure. The development of systemic lupus erythematosus is regulated genetically, and lupus susceptibility genes have been linked to immune hyper-responsiveness and loss of immune regulation. In addition to the systemic immune defects, recent studies in animal models show that susceptibility to lupus nephritis is influenced by intrinsic renal factors. Thus, renal cell responses to immune-mediated glomerular injury determine disease outcome. This supports the idea that future treatments for lupus nephritis need to focus on regulating end-organ responses. The feasibility of this approach has been shown in animal models of kidney disease. For more than 50 years, the emphasis in management of lupus nephritis has been suppression of autoimmune responses and systemic control of inflammation. This review describes recently developed targeted drug delivery technologies and potential targets that can regulate glomerular cell responses, offering a novel therapeutic approach for lupus nephritis.

Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound.

Current methods for measuring renal blood flow (RBF) are time consuming and not widely available. Contrast-enhanced ultrasound (CEU) is a safe and noninvasive imaging technique suitable for assessment of tissue blood flow, which has been used clinically to assess myocardial blood flow. We tested the utility of CEU in monitoring changes in RBF in healthy volunteers. We utilized CEU to monitor the expected increase in RBF following a high protein meal in healthy adults. Renal cortical perfusion was assessed by CEU using low mechanical index (MI) power modulation Angio during continuous infusions of Definity. Following destruction of tissue microbubbles using ultrasound at a MI of 1.0, the rate of tissue replenishment with microbubbles and the plateau acoustic intensity (AI) were used to estimate the RBF velocity and cortical blood volume, respectively. Healthy adults (n = 19, mean age 26.6 yr) were enrolled. The A.beta parameter of CEU, representing mean RBF increased by 42.8%from a baseline of 17.05 +/- 6.23 to 23.60 +/- 6.76 dB/s 2 h after the ingestion of the high-protein meal (P = 0.002). Similarly, there was a 37.3%increase in the beta parameter, representing the geometric mean of blood velocity after the high protein meal (P < 0.001). The change in cortical blood volume was not significant (P = 0.89). Infusion time of Definity was 6.3 +/- 2.0 min. The ultrasound contrast agent was tolerated well with no serious adverse events. CEU is a fast, noninvasive, and practical imaging technique that may be useful for monitoring renal blood velocity, volume, and flow.

Isolated polyarticular septic arthritis: an atypical presentation of meningococcal infection.

We are presenting a case of a 19-year-old college student with sudden-onset, asymmetric polyarticular arthritis with Neisseria meningitidis 10 days after an acute upper respiratory infection consisting of fevers, chills, pharyngitis, and productive cough. Primary meningococcal septic arthritis is a rare entity. A majority of these cases present in a monoarticular fashion. The synovial fluid findings, although compatible with inflammatory arthritis, are not typical of septic arthritis. This entity, although rare, should be considered in the differential diagnosis of septic arthritis of large joints, especially since N. meningitiditis does not grow well on routine culture media. A literature review on the diagnosis, treatment, and prevention of primary meningococcal septic arthritis is presented.

Ultrasound Contrast Agents in the Study of Kidney Function in Health and Disease.

Ultrasound contrast agents are gas filled microbubbles that enhance the ultrasound image. They behave similarly to red blood cells and cross all capillary beds; making contrast enhanced ultrasonography (CEU) a suitable technique to study vasculature and tissue blood flow. Ultrasound contrast agents have been found to be safe after intravenous injection. CEU has been used extensively in the field of cardiology. Currently, study of renal vasculature and renal blood flow requires complicated, time consuming and expensive techniques, which are not commonly used in clinical settings. CEU potentially may serve as a relatively noninvasive and safe technique for studying renal hemodynamics in health and disease. In this article we have reviewed the literature on the use of CEU in the study of kidney disease.

The role of imaging in the management of cardiorenal syndrome.

Imaging of the kidney and the heart can provide valuable information in the diagnosis and management of cardiorenal syndromes. Ultrasound- (US-) based imaging (echocardiogram and renal US) is an essential component in the initial diagnostic workup of CRS. Echocardiography provides information on the structure and function of heart, and renal ultrasound is useful in differentiating between acute and chronic kidney disease and excluding certain causes of acute kidney injury such as obstructive uropathy. In this paper we overview the basic concepts of echocardiogram and renal ultrasound and will discuss the clinical utility of these imaging techniques in the management of cardiorenal syndromes. We will also discuss the role of other imaging modalities currently in clinical use such as computerized tomography and magnetic resonance imaging as well as novel techniques such as contrast-enhanced ultrasound imaging.

Novel imaging techniques in acute kidney injury.

Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain information on renal blood flow and GFR. Ultrasound is the most widely used imaging modality used in the initial work up of AKI. The utility of contrast enhanced computerized tomography and magnetic resonance imaging is limited because of toxicities associated with contrast agents used. In this review the basics of ultrasonography are reviewed with an emphasis on findings in AKI. The new developments in different imaging modality and their potential uses in AKI are reviewed as well.

The renin-angiotensin system and its blockade in diabetic renal and cardiovascular disease.

Diabetic nephropathy, the most common cause of end-stage renal disease in the United States, is also associated with increased cardiovascular mortality. The renin-angiotensin-aldosterone system (RAAS) plays a central role in the development and progression of kidney disease and cardiovascular disease. Randomized, controlled trials have demonstrated renoprotection with the use of angiotensin receptor blockers (ARBs) in type 2 and angiotensin-converting enzyme inhibitors (ACEIs) in type 1 diabetes. More recent studies have demonstrated similar cardiovascular benefits with the use of ARBs compared with ACEIs. The combination of the two classes of RAAS blockers has been investigated in large studies of patients with heart failure and after myocardial infarction, and a few small studies of patients with diabetic nephropathy. In this review, we summarized the results of the studies on the benefits of ARBs, ACEIs, and their combination in patients with diabetic nephropathy or cardiovascular diseases.

Management of lipid abnormalities associated with end-stage renal disease.

The management of lipid abnormalities in patients with end-stage renal disease (ESRD) remains controversial. Large, well-designed studies investigating the effects of dyslipidemia on cardiovascular (CV) morbidity and mortality and the role of cholesterol lowering drugs in reducing mortality in ESRD patients are lacking. While it seems reasonable to suspect that dyslipidemia and its treatment in ESRD patients will affect CV morbidity and mortality similar to that in the general population, recent studies have suggested that this may not be the case. Furthermore, the pharmacokinetics of lipid lowering drugs are altered in patients with ESRD and must be considered when treating this group of patients. This article reviews the major classes of drugs used to treat dyslipidemia, emphasizing their role in patients with ESRD.

The choice of antihypertensive drugs in patients with diabetes: angiotensin II and beyond.

Affecting over 16 million individuals, diabetes mellitus is among the leading causes of mortality in the United States. Hypertension is a common finding among diabetic patients and increases their morbidity and mortality. Control of blood pressure in this population has been shown to improve outcomes. Recent randomized trials have proven the benefit of lower blood pressure goals in the treatment of hypertensive patients as compared with nondiabetic patients. Randomized controlled trials have also demonstrated that the selection of the antihypertensive agent used to treat hypertension in diabetic patients is as important as the reduction of blood pressure levels to the recommended levels. In this article, we first focus on the importance of the renin angiotensin system in the development of diabetic complications, and then we review the results of the recent studies that have had a major impact on the treatment of hypertension in diabetes.

Urinary and renal interstitial concentrations of TNF-alpha increase prior to the rise in albuminuria in diabetic rats.

BACKGROUND: The development of diabetic nephropathy has been linked to the release of vasoactive hormones and growth factors. Currently the role of inflammatory cytokines in this pathogenic process is not clear. METHODS: We utilized the microdialysis technique to monitor early changes in tumor necrosis-alpha (TNF-alpha) levels in the renal interstitial fluid and urine of conscious Sprague-Dawley rats (N = 8) before and after induction of diabetes with streptozotocin (STZ). Measurement of the urinary albumin excretion (UAE) was utilized to monitor the development and progression of diabetic nephropathy. RESULTS: UAE increased from 0.56 +/- 0.20 microg/min to 8.14 +/- 2.98 microg/min 17 days after induction of diabetes (P = 0.01). Renal interstitial fluid TNF-alpha increased from 11.96 +/- 5.32 pg/mL at baseline to 45.02 +/- 11.69 pg/mL 5 days after induction of diabetes (P = 0.03). Renal interstitial fluid TNF-alpha levels remained elevated throughout the remainder of the study period. Urinary TNF-alpha also increased significantly compared to baseline 3 days after induction of diabetes (294.18 +/- 36.94 pg/mL vs. 16.05 +/- 6.07 pg/mL, P < 0.002). There was a second significant rise in urinary TNF-alpha concentration to 638.16 +/- 36.94 pg/mL 21 days after induction of diabetes (P < 0.001). Serum TNF-alpha levels were undetectable before STZ injection and remained undetectable by the end of the study. Urinary and renal interstitial fluid TNF-alpha in the control rats (N = 5) did not change throughout the study. CONCLUSION: We found an early rise in renal TNF-alpha levels after induction of diabetes with STZ, which precedes the rise in UAE by about 2 weeks. These findings suggest a possible contribution of TNF-alpha in the complicated pathogenic process resulting in microalbuminuria in diabetes.