Renal advances in ultrasound elasticity imaging: measuring the compliance of arteries and kidneys in end-stage renal disease.

BACKGROUND/AIMS: Ultrasound elasticity imaging visually represents tissue hardness measurements using high-resolution ultrasound speckle-tracking algorithms. This method has recently been applied in the renal setting to measure arterial compliance in end-stage renal disease (ESRD) and the mechanical properties of transplant kidneys in vivo. METHODS: Ultrasound radio-frequency signal measurements were made of the brachial artery in 5 ESRD subjects and 5 healthy controls and renal transplant measurements in 2 subjects, 1 with chronic allograft nephropathy (CAN) and 1 with normal graft function. RESULTS: Maximal brachial artery percent strain measurements for healthy controls were 32.9 +/- 10.2% (mean +/- SD) and for ESRD subjects maximal percent strains were 4.9 +/- 1.8%. Transplant renal cortical strain for the subject with CAN was approximately one third that of the healthy transplant recipient. CONCLUSION: Ultrasound elasticity imaging offers the potential to noninvasively measure the mechanical properties of structures within the body.

Vascular intramural strain imaging using arterial pressure equalization.

Peripheral vascular strain imaging has limited strain dynamic range because arterial wall deformations only exhibit small strains under physiologic pressures. A noninvasive freehand ultrasound (US) scanning procedure was performed to apply external force, comparable to the force generated in measuring a subject's blood pressure, to achieve higher strains by equalizing the internal arterial baseline pressure. When the applied pressure matched the internal baseline diastolic pressure, intramural strain and strain rate increased by a factor of 10 over a cardiac cycle. Radial arterial strain was assessed within the vessel wall over the entire deformation procedure using a phase-sensitive 2-D speckle-tracking algorithm. The feasibility of this technique to assess vascular nonlinear elastic properties is demonstrated in an ex vivo experiment and further supported by in vivo measurements. With some uncertainty associated with the elastic properties of surrounding tissue, an elastic modulus reconstruction procedure was developed to estimate the nonlinear elastic properties of the vascular wall.

Use of ACE inhibitors is associated with prolonged survival of arteriovenous grafts.

Vascular access complications are common in hemodialysis patients. To investigate whether the use of angiotensin-converting enzyme (ACE) inhibitors influences the rate of polytetrafluoroethylene (PTFE) graft complications, we compared the rate of intervention-free graft survival among patients treated versus not treated with ACE inhibitors. We retrospectively analyzed the survival of grafts placed at our institution between January 1, 1995, and October 31, 1999. Among 121 grafts, 25 grafts were placed in 19 patients treated with ACE inhibitors and 96 grafts were placed in 68 patients not treated with ACE inhibitors. Follow-up ranged from 1 month to 5 years. Ten of 25 grafts failed in the ACE-inhibitor group and 62 of 95 grafts failed in the non-ACE-inhibitor group. Actuarial intervention-free access survival rates (Kaplan-Meier) were significantly greater in the ACE-inhibitor than non-ACE-inhibitor group (71% versus 53% at 6 months, 58% versus 35% at 12 months, and 44% versus 22% at 24 months; P = 0.04). Using a Cox model adjusting for age, race, sex, and diabetes, the relative risk (RR) for access failure in the ACE-inhibitor group was 53% less than in the non-ACE-inhibitor group (RR, 0.47; p < 0.03). In a more complex Cox model with additional adjustment for comorbid conditions, the RR was even lower (RR, 0.32; P = 0.003) for the ACE-inhibitor compared with non-ACE-inhibitor group (reference = 1.00). The lower RR was observed for patients with and without congestive heart failure. These results suggest that ACE inhibitors offer clinical promise in the prevention of PTFE graft failure. A prospective randomized trial is warranted to confirm the benefit of ACE inhibitors.

Analysis of variable flow Doppler hemodialysis access flow measurements and comparison with ultrasound dilution.

The variable flow (VF) Doppler method determines access blood flow from the pump speed-induced change in Doppler signal between the arterial and venous needles. This study evaluated 35 patients in two analyses to assess VF Doppler measurement reproducibility (54 paired measurements) and compared VF Doppler and ultrasound dilution flow measurements (24 paired measurements). VF Doppler measurement variations were 4% for access flow less than 800 mL/min (n = 17), 6% for access flow of 801 to 1,600 mL/min (n = 22), and 11% for access flow greater than 1,600 mL/min (n = 15). The mean measurement coefficient of variation was 7% for VF Doppler compared with 5% for ultrasound dilution. Correlation coefficients (r) between VF Doppler and ultrasound dilution access flow measurements were 0.79 (n = 24; P < 0.0001), 0.84 for access flow less than 2,000 mL/min (n = 20; P < 0.0001), and 0.91 for access flow less than 1,600 mL/min (n = 18, P < 0.0001). VF Doppler measurements using indicated versus measured pump flow rates correlated highly (r = 0.99; P < 0.0001). VF Doppler therefore yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements. The VF Doppler method is dependent on the pump-induced change in access Doppler signal and therefore is inherently most accurate and reproducible at lower access blood flow rates. This method appears capable of determining access flow rates in the clinically useful range.

Retrograde hemodialysis access flow during dialysis as a predictor of access pathology.

We have detected retrograde flow by Doppler ultrasound within the hemodialysis access of 10 patients during routine dialysis. Nine of these accesses were prosthetic grafts, and 1 was an autogenous fistula. All 9 of the grafts had access pathology demonstrated by angiography. The single patient with the fistula exhibiting reversed access flow had a poorly developed access with no focal stenoses on angiogram, but 18% recirculation by ultrasound dilution. All patients with retrograde flow had access flow rates below 650 mL/min. While 3 of these patients had substantial access recirculation (2 grafts, 12% and 40%; and 1 fistula, 18%) 2 of these patients had 3% recirculation (2 needle urea method), and 4 patients had 0% access recirculation (ultrasound dilution and 2 needle urea method). We report that retrograde access flow during dialysis may be a specific indicator of access dysfunction. These findings further suggest that retrograde access flow develops before access recirculation, indicating that this finding is more sensitive than recirculation for detecting access dysfunction. Further study is needed to determine the utility of this finding in access surveillance.

Variable flow Doppler for hemodialysis access evaluation: theory and clinical feasibility.

Access thrombosis remains an enormous problem for patients on hemodialysis. Current evidence suggests that decreasing access blood flow rate is an important predictor of future access thrombosis and failure. This article describes a method for determining access volume flow and detecting access pathology. The Doppler ultrasound signal downstream from the arterial needle as a function of the variable hemodialysis blood pump flow rate, is used to determine access blood flow. By using this variable flow (VF) Doppler technique compared with duplex volume flow estimates measured in 18 accesses (16 patients with 12 polytetrafluorethylene [PTFE] grafts and 6 autogenous fistulas), the results showed a correlation of 0.83 (p < 0.0001) between these methods. In grafts with lower blood flow rates, aberrant flow patterns were observed, including stagnant or reversed flow during diastole while forward flow was maintained during systole. When reversed diastolic flow was severe, it was accompanied by access recirculation. In conclusion, we report the theory and clinical feasibility of determining access blood flow by using a VF Doppler technique. Measurements are made without the need to determine the access cross sectional area required for duplex volume flow calculations and without the need to reverse the lines required for various indicator dilution techniques. Important information is also obtained about aberrant flow patterns in patients at risk of access failure.

Replacement of renal function in uremic animals with a tissue-engineered kidney.

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.

Elasticity imaging for early detection of renal pathology.

Early detection of renal pathology may be possible with elasticity imaging. This hypothesis was experimentally tested by quantitatively imaging internal mechanical strain due to surface deformations in an in vitro animal model of nephritis. Preliminary data support the hypothesis that kidney elasticity changes with renal damage and concomitant scarring before problems are detectable by traditional diagnostic techniques such as laboratory measurements of renal function.

Steady-state concentration of cyclosporin G (OG37-325) and its metabolites in renal transplant recipients.

The steady-state concentrations of cyclosporin G (OG37-325) (CsG) and six of its metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) were measured throughout the 12-h dosing interval in six renal transplant recipients receiving CsG as prophylaxis against acute cellular rejection. The mean 12-h whole-blood trough concentrations (micrograms/L) were CsG, 131 +/- 26; GM1, 79 +/- 55; GM9, 110 +/- 114; GM4N, 28 +/- 18; GM1c, 31 +/- 18; GM1c9, 216 +/- 145; and GM19, 303 +/- 217. The relative concentration of the primary metabolites (GM1, GM9, GM4N) remained stable with respect to CsG throughout the dosing interval, whereas that of the secondary metabolites increased. The secondary metabolites GM19 and GM1c9 exhibited extensive between-patient variation. We investigated the effect of these metabolites on commercially available monoclonal antibody-based fluorescence polarization immunoassays (FPIA) and RIAs adapted for measurement of CsG. The 12-h whole-blood trough concentrations measured by FPIA and RIA exceed those measured by HPLC by 19% and 36%, respectively. These measured biases corresponded closely with the calculated biases (FPIA 19%, RIA 28%) based on the known cross-reactivities of CsG metabolites and their concentrations. These results suggest that cross-reactivity with metabolites account for a large part of the bias observed in immunoassays of CsG.

Successful use of cuffed central venous hemodialysis catheters inserted percutaneously.

Although endogenous fistulae and grafts are preferred for permanent hemodialysis access, central venous catheters are often required for varying intervals when creating permanent access is not feasible. The prospective experience with 118 catheters in over a 3.5-yr period is reported; 93 (79%) were placed by percutaneous techniques, and 25 (21%) were placed by operative techniques. Seventy seven catheters (65%) were placed in the subclavian vein, 36 (31%) were placed in the internal jugular vein (usually right side), and 5 (4%) were placed in the femoral vein. Early postplacement complications were infrequent. Catheter function at last local follow-up ranged from several days to nearly 2 yr, averaging approximately 3 mo, even though many patients returned to their referring centers with a functioning catheter after only a short follow-up. Actuarial survival for percutaneously placed catheters was approximately 60% at 6 mo and 30% at 12 mo. Catheter failure occurred in 36% of cases, equally divided between malfunction (thrombosis refractory to fibrinolysis, extrusion, kinking, or related event) and infection with septicemia requiring removal. Such failure was not more frequent after percutaneous placement than after operative placement. Failure due to mechanical malfunction, but not that due to infection, tended to be less frequent among catheters placed in the internal jugular vein than among catheters placed in the subclavian vein. Finally, infection with septicemia involved 22% of all catheters and occurred at an average cumulated rate of approximately one infection per patient-year. Coagulase-positive staphylococcus was the most common organism isolated.(ABSTRACT TRUNCATED AT 250 WORDS)

A Markov model of the natural history of prostate cancer.

The objective of this study was to lay a foundation for future cost-benefit analyses evaluating the public health impact of treatment and screening protocols for prostate cancer. Specifically we wanted to define the relative impact on cancer-specific mortality rates of the individual epidemiological components: pathological incidences by age groups, cancer progression rates, and the effect of competing causes of death, assuming expectant management (i.e. no definitive treatment). A biological model of prostate cancer incidence and progression was converted into a standard Markov tree where competing causes of death could occur. Weighted averages of progression rates were obtained from clinical studies. Separate cohorts of 30 year old black and white men were followed for 50 years. The model yielded cancer-specific mortality rates, overall mortality rates, and pathologic prevalences for both white and black males, consistent with the literature. Sensitivity analyses showed that of all the parameters studied, the pathological incidence of cancer in men under 50 years of age had the greatest impact on the cancer-specific mortality rates. Also important was the annual probability of progression of A1 lesions. However the other parameters including pathological incidence in older males, and progression from locally-extensive to metastatic lesions had much smaller effects. In summary, this model correlates the clinical literature with the epidemiology of prostate cancer and can be used for further decision analyses. We recommend that future research be done to more precisely quantify the pathological incidence of prostate cancer in men under 50-60 years of age. More certainty is also needed before generalizing the results of relatively small A1 series to millions of men, since A1 progression rates critically affect the eventual cancer-specific mortality. Enough uncertainty remains at this point however, that we cannot advocate widespread screening for prostate cancer until its merit be demonstrated either by the definitive long term study, or by examination of costs and quality-of-life-adjusted benefits.

Successful use of indwelling cuffed femoral vein catheters in ambulatory hemodialysis patients.

Three hemodialysis patients with multiple upper extremity vascular access complications and central vein stenosis were treated for as long as 3 months using an indwelling femoral vein catheter having a buried felt cuff in its subcutaneous tunnel. Four catheters were placed in these three patients. In one case, initial failure due to poor flow and clotting occurred using a straight catheter with its tunnel crossing the inguinal ligament and exiting caudally on the anterior thigh. Otherwise, each patient had successful placement of a 180-degree, curved catheter that exited the femoral vein in the usual fashion but had a subcutaneous tunnel and skin exit pointing cephalad in the inferior portion of the right lower quadrant. The three successful devices functioned immediately after placement, having acceptable outflow pressures and recirculation values. One of three catheters was removed 3 weeks after placement when persisting infection was thought to reside on the device. No other bleeding, thromboembolic, or infectious complications occurred in these patients. In conclusion, short-term indwelling femoral vein access may be feasible in ambulatory hemodialysis patients with previous access difficulties that complicate temporary dialysis treatment.