Potential identification of a claudicant group vulnerable to acute kidney injury.

This observational study aimed to investigate the relationship between renal injury, endothelial function and oxidative stress in claudicants undergoing maximal treadmill exercise. Twenty patients with claudication were identified in whom the urinary N-acetyl-ß-D-glucosaminidase (ß-NAG)/creatinine ratio, plasma oxidative state and endothelial function were tested pre- and post-maximal treadmill walking exercise. Of the 20 participants in this study, the urinary NAG/creatinine (Cr) rose from a pre-exercise level of 8.9, 6.7 to 14.3 (µmol/L/mmol Cr; median, IQR) to 12.9, 9.1 to 17.7 post exercise (p = 0.0003, Mann Whitney U test). Of the 20 participants, eight participants had a rise of the NAG/Cr ratio post exercise whereas 12 did not. Participants with a rise in the NAG/Cr ratio post exercise had a greater ability to increase endothelial reactivity (%; median, IQR; 2.56, 0.1 to 3.7) cf. (0.1, -4.8 to 0.9, p = 0.03); they also walked further (metres; median, IQR; 415, 208 to 908) cf. (170, 100 to 315, p = 0.04), had a lower pre-exercise H2O2 (median, IQR; 1.9, 1.4 to 2.3 cf. 2.7, 2.1 to 3.3; p = 0.04) and a greater rise in H2O2 post exercise (18.8, -1.5 to 129.7 cf., -7.7, -13.9 to -2.0, p = 0.04). The mechanism by which the phenotypically distinct sub-group of patients with intermittent claudication who experience a NAG/Cr rise involves complex interactions between systemic oxidative stress and endothelial function. Implications on cardiovascular risk in this group requires further investigation.

Patients with critical ischemia of the lower limb are at risk of developing kidney dysfunction.

BACKGROUND: The aim of this study is to establish a relationship between critical ischemia of the lower limb and kidney dysfunction. MATERIALS AND METHODS: At rest, urine samples were collected from three groups: group A, 16 patients with critical ischemia; group B, 22 patients with stable intermittent claudication; and group C, 12 normal individuals. Urinary N-acetyle-beta-D-glucosaminidase (NAG) enzyme was measured using spectrophotometer. Microalbuminuria was measured by radioimmunoassay. RESULTS: There was a significant difference in the NAG activity between groups A and B, P = 0.001. Also, between group A and C, P = 0.01. There was no significant difference between groups B and C, P = 0.13. Microalbuminuria was not significantly different among the three groups: A versus B, P = 0.27; A versus C, P = 0.22; B versus C, P = 0.11. CONCLUSIONS: Elevated levels of NAG enzyme in patients with critical ischemia of the lower limb suggest that they are at greater risk of developing kidney dysfunction. This could be caused by the release of more free radicals into the systemic circulation.

A role for near infrared spectroscopy in the assessment of intermittent claudication.

BACKGROUND: Near infrared spectroscopy (NIRS) can be used to monitor muscle oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and cytochrome oxidase (CytOx) oxidation. We evaluated the changes in NIRS in patients with intermittent claudication (IC) pre- and postexercise. Microalbuminuria is an index of endothelial dysfunction. Therefore, we also assessed whether the urinary excretion of albumin increased postexercise in patients with IC. METHODS: Each participant (14 patients with IC and 10 controls) underwent a treadmill test; NIRS was continuously recorded. The urinary albumin:creatinine ratio (ACR) and ankle: brachial systolic pressure index (ABPI) were measured pre- and postexercise. RESULTS: The ABPI in the claudicants dropped significantly (p<0.001) postexercise. The pre-exercise ACR did not differ between claudicants and controls but postexercise, the ACR increased significantly (p<0.001) in the claudicants. There was a significant (p<0.001) difference in the degree of HbO2 deoxygenation between claudicants and controls; the rate of deoxygenation was significantly higher in claudicants than in controls (-8.4 vs. -3.4 mol/L.min, p=0.024). The period of recovery of HbO2 postexercise was also significantly slower in claudicants (192 vs 68 sec, p=0.003). There was a significant correlation between the increase in the ACR and time of recovery of HbO2 levels postexercise (r=0.86, p<0.001, n=24). A similar pattern was seen with CytOx. CONCLUSIONS: NIRS may provide a simple, non-invasive assessment of the severity of IC. Furthermore, because the ACR is a marker of endothelial damage, it is possible that NIRS changes also reflect endothelial integrity. These applications of NIRS technique should be assessed in a larger study.

Tc-99m diethylenetriamine pentaacetic acid (DTPA)-human serum albumin (HSA) radionuclide lymphography for detecting the location of chyluria.

The cause of chyluria cannot be easily detected by CT scan or other imaging methods, except conventional lymphography, but Tc-99m diethylenetriamine pentaacetic acid radionuclide lymphography clearly revealed the location of chyluria in the left renal pelvic area. Radionuclide lymphography is one of the choices in investigating chyluria due to its noninvasive and simple technique.

Urinary microalbumin as a marker for intermittent claudication.

OBJECTIVE: The urinary microalbumin concentration was analysed in patients with intermittent claudication in order to investigate its usefulness as a marker for intermittent claudication. MATERIALS AND METHODS: Urinary samples were collected prior to and following exercise in 15 patients with claudication. The patients walked on a treadmill as far as possible until they were stopped by pain. Urinary microalbumin concentration was measured by a latex agglutination system, and the result was considered abnormal when the concentration exceeded 10 mg/g creatinine. The ankle brachial pressure index (ABI) at rest and the time taken for the ankle pressure to return to the resting level following exercise (ABI recovery time) also were measured. RESULTS: In seven (47%) of the patients, the urinary microalbumin concentration was elevated to more than 10 mg/g creatinine following exercise, while in eight (53%) it remained normal. The ABI recovery time was significantly longer in the patients in whom the microalbumin concentration was elevated, compared to that in patients without an elevated concentration. The urinary microalbumin concentration following exercise was reduced significantly when the walking distance was decreased 50% or 15%. Following vascular bypass surgery, the elevation in urinary microalbumin concentration was reduced. CONCLUSIONS: The use of urinary microalbumin as a diagnostic marker for intermittent claudication is limited. However, in cases where the concentration is elevated, it can be used to follow the course of the disease.

Thromboxane and neutrophil changes following intermittent claudication suggest ischaemia-reperfusion injury.

OBJECTIVES: It has been postulated that ischaemia-reperfusion occurs in intermittent claudication resulting in neutrophil activation and release of soluble mediators, increasing systemic vascular permeability and enhancing atherogenesis. METHODS: We measured neutrophil deformability, plasma thromboxane levels, and urinary microalbumin excretion in 30 male claudicants, and 10 age- and sex-matched controls, before and after exercise to maximum walking distance. Blood was taken from an antecubital vein. RESULTS: There was an increase in urinary microalbumin excretion after exercise in claudicants. Statistically significant increases in the median and 90th percentile transit times (markers of neutrophil deformability) for isolated neutrophils from blood drawn 5 min after exercise in the claudicants were observed with no change in control subjects. Plasma thromboxane concentrations in claudicants increased within 10 min post-exercise. Plasma concentrations in controls were significantly lower throughout the study period. In the claudicant group, a positive correlation between the percentage change in the median transit time for neutrophils, and the percentage change in plasma thromboxane at 60 min post-exercise was found. CONCLUSIONS: The results lend further support to the concept of ischaemia-reperfusion events in patients with intermittent claudication, leading to a systemic increase in vascular permeability as a result of endothelial injury or dysfunction (a crucial step in atherogenesis), associated with thromboxane production and neutrophil activation. We suggest that the above changes may contribute to the increased mortality seen in such patients.

Assessment of intermittent claudication by quantitation of exercise-induced microalbuminuria.

Urinary albumin excretion rates, expressed as albumin-creatinine ratios (ACR, mg/mmol) were measured before and after exercise in 23 claudicants and 10 controls. The mean (range) resting ACRs in the claudicants and controls were 4.42 (0.2-34.6) and 0.77 (0.3-2.8) respectively (P less than 0.001). ACR increased after exercise by a mean of 153% in claudicants to 9.7 (0.2-48.1; P less than 0.001) with no change in controls, 0.79 (0.2-2.1). In patients with claudication there was a positive correlation between ankle pressure recovery time and the relative increase in ACR after exercise (r = 0.64, P less than 0.01). The post-exercise increase in ACR was reduced in all nine patients who underwent bypass surgery. Measurement of ACR after exercise appears to be related to severity of muscle ischaemia and may assist in the assessment of patients with intermittent claudication.

Systemic effects associated with intermittent claudication. A model to study biochemical aspects of vascular disease?

Patients with intermittent claudication were used as a clinical model to study the effects of transient episodes of ischaemia. Compared with age and sex matched controls significantly greater increases in serum lipid peroxides and urinary microalbumin occurred after exercise. These results suggest that even relatively minor ischaemic episodes, as occur with claudication, are sufficient to cause tissue damage which may be mediated by oxygen derived free radicals. There are also changes in renal permselectivity suggestive of a generalised increase in vascular permeability. These preliminary findings may have important diagnostic, aetiological and therapeutic implications for patients with vascular disease.

Excretion of thromboxane A2 and prostacyclin metabolites during treadmill exercise in patients with intermittent claudication.

Platelet activation, with subsequent formation of thromboxane A2 (TxA2), is thought to play a role in the development of arterial occlusion. In patients with severe atherosclerosis of the lower limbs, characterized by leg ulcers and rest pain, the basal formation of TxA2 and prostacyclin (PGI2) is increased. Corresponding data in patients with more moderate atherosclerosis of the lower limbs have not been reported. Since the capacity to physical exercise is not blunted in such patients proper evaluation of their TxA2-PGI2 synthesis should comprise not only assessment of the basal formation, but also TxA2/PGI2 biosynthesis during conditions of elevated cardiovascular activity. To address this, we analysed these eicosanoids in patients with a history of intermittent claudication. Urinary dinor-metabolites of TxB2 and PGI2 (Tx-M and PGI-M, respectively) were estimated by gas chromatography/negative ion-chemical ionization mass spectrometry in samples collected prior to, during and immediately after 20 min of severe treadmill exertion. The basal excretion of Tx-M was 105 +/- 26 pg/mg creatinine. It was not changed during exercise, but increased to 176 +/- 48 pg/mg creatinine (P less than 0.05) during the recovery. The basal excretion of PGI-M was 142 +/- 25 pg/mg creatinine. The PGI-M response to exercise varied from no change at all to a 30-fold increase, without any obvious correlation to experienced leg pain, walking distance or other recorded variables. During the recovery period the outflow of PGI-M was significantly higher than at rest (482 +/- 145 pg/mg creatinine; P less than 0.01). We conclude that in patients with intermittent claudication due to atherosclerosis (1) platelet activation does not occur during the course of the exercise, and (2) vascular prostacyclin formation can be dissociated from of TxA2 synthesis. The observed increase in PGI-M in some of the patients is suggested to reflect tissue ischaemia induced by the lack of adequate hyperaemia during exercise.