Growth failure,risk of hospitalization and death for children with end-stage renal disease

Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<–3 SDS), moderate growth failure (>–3 and <–2 SDS), and normal growth (>–2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I–IV), those with severe and moderate growth failure had higher hospitalization rates {relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]} respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth (P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure. Received: 15 August 2001 / Revised: 14 January 2002 / Accepted: 15 January 2002     

Surveillance with serial serum carcinoembryonic levels detect colorectal cancer recurrences in patients who are initial nonsecretors

Serum carcinoembryonic antigen (CEA) levels, elevated in a subgroup of patients with colorectal cancer (CRC) at presentation, are serially followed as part of recommended surveillance after initial resection. The value of following serial CEA levels in patients who initially present with less than or normal levels of CEA (nonsecretors) is controversial. This study sought to determine the use of follow-up CEA levels in nonsecretors. A retrospective review was performed of patients with resected Stage I, II, and III CRC. We excluded patients who did not have a pretreatment CEA level, at least two follow-up CEA levels, or in whom CEA levels did not normalize after resection. The patients were grouped by initial CEA values: CEA 5 ng/mL or less (nonsecretors) and CEA 5 + ng/mL: (secretors). We identified 186 patients with CRC; 146 were initial nonsecretors. We identified 22 patients with recurrent colorectal cancer; 6 were secretors and 16 patients were nonsecretors. In the secretors group, CEA was elevated with recurrence in four (66%) of the patients. In the nonsecretors, CEA was elevated with recurrence in eight (50%) of the patients. In summary, many recurrences of CRC are marked by an elevation of CEA regardless of whether the patients initially presented as secretors or nonsecretors.     

Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol

We investigated the expression of nitric oxide synthase (NOS) isoforms -1, -2 and -3 in the retina and optic nerve head (ONH) in an experimental rat model of elevated intraocular pressure (IOP) before and after treatment with timolol, to assess whether its neuroprotective action is associated with the activity of these enzymes. Episcleral vein cauterization in unilateral eyes of Wistar rats was performed to produce elevated IOP. Histological sections of retina and ONH from animals with normal IOP, with elevated IOP, and elevated IOP treated with timolol, were studied by immunohistochemistry with antibodies to NOS-1, NOS-2, and NOS-3. In the control rats, NOS-1 was localized to photoreceptor inner segments, amacrine cells and bipolar cells in the retina, and in astrocytes, pericytes and vascular nitrergic terminals in the ONH. NOS-3 immunostaining localized to the endothelial cells. The rats with elevated IOP showed increased expression of NOS-1 in the plexiform layers of the retina and reactive astrocytes in the ONH. These cells also showed NOS-2 positivity. The rats treated with timolol showed reduced expression of NOS-1 in the retina and ONH. NOS-2 was only detected in a few groups of astrocytes in the ONH. NOS-3 was unchanged in both elevated IOP and timolol-treated groups. These results show that excessive levels of NO synthesized by the NOS-1 and -2 isoforms, considered neurotoxic, might contribute to the progressive lesions of retinal ganglion cell axons. Their reduction after treatment suggests a possible neuroprotective effect of timolol in neurons exposed to excessive amounts of NO.     

Use of aerosolized aminoglycosides in the treatment of Gram-negative ventilator-associated pneumonia

BACKGROUND AND PURPOSE : Ventilator-associated pneumonia (VAP) in the surgical intensive care unit (ICU) is associated with substantial morbidity and mortality. Affected patients are at higher risk for infection with multi-drug-resistant (MDR) pathogens, often necessitating therapeutic regimens of two parenteral antibiotics. Aerosolized antibiotics achieve high alveolar concentrations and have been reported anecdotally to have value in the treatment of VAP. This study examined the role of aerosolized aminoglycosides in the treatment of VAP in surgical ICU patients. METHODS: We reviewed retrospectively the medical records of 22 patients who received aerosolized aminoglycosides in conjunction with parenteral antibiotics for VAP in the surgical ICU. Sixteen patients received inhaled tobramycin, and six received inhaled amikacin. Demographic information and data on the length of stay (LOS), mortality rate, days of antibiotic therapy, days of mechanical ventilation, and recurrence of VAP were collected. Results of bronchoscopic and sputum cultures were reviewed to identify bacterial pathogens and antimicrobial susceptibilities. RESULTS: The average duration of mechanical ventilation was 31 +/- 12 days, the mean ICU LOS was 41 +/- 13 days, and the mean hospital LOS was 71 +/- 25 days. There were three deaths. The average duration of mechanical ventilation after initiation of aerosolized antibiotics was 4.3 days. Seven patients (40%) developed recurrent pneumonia with the same pathogen, but only one had a change in antibiotic susceptibility pattern. There were no renal or pulmonary complications of aminoglycoside treatment. CONCLUSIONS: Ventilator-associated pneumonia in critically ill patients is associated with substantial morbidity, longer ICU stays, and prolonged mechanical ventilation. Along with systemic therapy, aerosolized aminoglycosides are valuable adjuncts in select patients with minimal risk of antibiotic resistance.     

Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin

BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. METHODS: In a cohort of 204 (62% males) ESRD patients aged 52 +/- 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2 years) and gender-matched (64% males) healthy subjects served as control subjects. RESULTS: Markedly (P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 microg/mL), especially type 1 diabetic patients (36.8 microg/mL), compared to control subjects (12.2 microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P < 0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral fat mass (P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene -11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype. CONCLUSION: The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD.     

Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure.

BACKGROUND: The relative roles of endothelin (ET)-1 and angiotensin (ANG) II in post-ischaemic acute renal failure (ARF) have not been fully established so far. With the aim of contributing to this goal, we assessed in this study the effect of ANG II and ET-1 blockade on the course of post-ischaemic-ARF. METHODS: Anaesthetized Wistar rats received i.v. either bosentan (a dual ET receptor antagonist; 10 mg/kg body weight) or losartan [ANG II type 1 (AT(1)) receptor antagonist; 5 or 10 mg/kg body weight] or both, 20 min before, during and 20 min after ischaemia. Rats in the control group received the vehicle via the same route. Survival and renal function were monitored up to 8 days after the ischaemic challenge, while haemodynamic parameters were measured 24 h after ARF. RESULTS: Our results demonstrate that bosentan treatment has a more beneficial effect on experimental ARF than losartan. The survival rate was remarkably higher in bosentan-treated rats than in both rat groups treated with losartan. In the ARF group treated with bosentan, renal blood flow (RBF) was increased by 129% in comparison with the untreated ARF group, whereas in the losartan-treated ARF groups, RBF was only approximately 35 or 38% higher than in control ARF rats. The glomerular filtration rate was markedly higher in bosentan-treated rats than in all other ARF groups on the first and second day after ischaemia. Tubular cell injury was less severe in bosentan-treated rats than in the control ARF rats, but in losartan-treated groups it was similar to that in the ARF group. Concurrent blockade of both ET and AT(1) receptors did not improve ARF because this treatment induced a marked decrease in blood pressure. CONCLUSIONS: These results suggest that ET-1 blockade is more efficient in improving the early course of post-ischaemic renal injury than ANG II inhibition, and that blockade of ET-1 might be effective in prophylaxis of ischaemic ARF.