Performance of urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and N-acetyl-ß-D-glucosaminidase to predict chronic kidney disease progression and adverse outcomes.

Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-ß-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients.

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age +/- SD: 51.3 +/- 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age ± SD: 51.3 ± 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

CAPD in southern Brazil: an epidemiological study.

There are many studies on the performance of continuous ambulatory peritoneal dialysis (CAPD) in developed countries, but studies in the third world are scarce. The aim of this study is to analyze CAPD experience in the southernmost state of Brazil (Rio Grande do Sul, RS). Records were obtained from the Health Secretary of RS to assemble a cohort of all patients treated with CAPD. Another cohort study followed all patients initiating treatment for uremia in 1993 in the state capital, Porto Alegre, and compared CAPD, hemodialysis, and transplanted patients. In RS, 1316 patients (50.4% male, mean age 45.9 years) were treated in 40 CAPD programs. Despite the initial growth of the CAPD population, it subsequently leveled off. Survival was 78.6% and 40.7% in years 1 and 5, being worse for initial patients of each program, infants, and elders. Technique survival was 57.4% and 10.1% at years 1 and 5. Patients interrupting treatment for any reason had a higher chance of dropout. In Porto Alegre, 294 patients started dialysis during 1993; 21 performed CAPD, 44 had a transplant, and the others were hemodialyzed. Children were treated mostly by CAPD. CAPD patients had less diabetes and ischemic heart disease and received more transplants. Their adjusted actuarial survival (100% year 1; 67% year 3) was no different than hemodialysis. CAPD is not a popular form of renal therapy in RS, and dropout rates are significant.

Vascular angiotensin II receptors in SHR.

We investigated the density (Bmax) of angiotensin II (ANG II) receptors in the mesenteric vascular bed of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats. In 12-week-old SHR, the Bmax and the dissociation constant (Kd) of ANG II binding sites were not different from those of WKY rats in the sodium replete state or after sodium depletion. In prehypertensive (4- and 6-week-old) SHR, the Bmax of the vascular ANG II receptors was significantly higher (p less than 0.05) than in age-matched WKY rats. This result could not be attributed entirely to differences in the circulating renin-angiotensin-aldosterone system in 4-week-old-rats. In 6-week-old WKY rats, the plasma renin activity was significantly higher (p less than 0.05), which may account in part for the higher density of ANG II binding sites in SHR. There was an age-related decrease in the number of ANG II receptors in SHR. The increased density of vascular ANG II receptors in young SHR may play a role in the development of high blood pressure in this model of spontaneous hypertension. The higher number of ANG II binding sites in young SHR is not selective for ANG II receptors, since an increased density of alpha 1-adrenergic receptors was also found in the mesenteric arteries of 4-week-old SHR.

Vascular angiotensin II receptors in renal and DOCA-salt hypertensive rats.

To determine the contribution of receptor number and affinity to changes in vascular reactivity to angiotensin II (AII) in hypertensive rats, we have investigated the binding of 125I-AII to a particulate fraction of the rat mesenteric artery of hypertensive rats. In two-kidney, one clip hypertensive rats, receptor concentration (Bmax) was 83 +/- 13 fmol/mg and the dissociation constant (Kd) 0.6 +/- 0.1 nM vs 75 +/- 5.3 fmol/mg and 0.6 +/- 0.1 nM in normotensive controls, although PRA was much higher in the former. Bmax was reduced in these hypertensive rats after sodium depletion, as in normal rats. One-kidney, one clip hypertensive rats (Bmax 88 +/- 17 fmol/mg, Kd 0.6 +/- 0.1 nM) did not differ from uninephrectomized control rats (96 +/- 9 fmol/mg, Kd 0.5 +/- 0.1 nM). In DOCA-salt hypertensive rats, binding capacity was increased (125 +/- 2 fmol/mg, Kd 0.7 +/- 0.0 nM) vs uninephrectomized salt-loaded rats (Bmax 95 +/- 6 fmol/mg, Kd 0.6 +/- 0.1 nM), although PRA was suppressed comparably in both groups. The salt-loaded rats did not differ from uninephrectomized controls drinking water. We conclude that changes in the circulating renin-angiotensin system do not explain all the variations in receptor number in hypertensive rats. Our results suggest a role of mineralocorticoids in the regulation of vascular AII receptors.