Aminoglycoside-induced nephrotoxicity studied by proton magnetic resonance spectroscopy of urine.

BACKGROUND: Acute kidney injury is a relatively common complication of aminoglycoside therapy that affects 10-20% of patients receiving antibiotics of this class. Although the vast majority of patients do recover, the presence of certain risk factors may alter the clinical presentation and result in permanent renal damage. Thus, aminoglycoside-induced nephrotoxicity is a major concern and early diagnosis is critical. The aim of the present study was to characterize the early stages of aminoglycoside-induced nephrotoxicity using proton nuclear magnetic resonance ((1)H NMR) spectroscopy of urine. METHODS: We studied 19 previously healthy patients who were hospitalized in our clinic due to bacterial infections. Combined antibiotic treatment with amikacin (1 g once daily) and a beta-lactam antibiotic was instituted in all patients. Urine and blood samples were collected before and after 5 days of aminoglycoside treatment. RESULTS: (1)H NMR spectroscopic data showed increased amounts of alanine and lactic acid (+138 and +255% compared to baseline values, respectively) and decreased hippurate (-50%) after aminoglycoside treatment. In addition, fractional excretions of sodium, magnesium and calcium were significantly increased (+271, +295 and +60%, respectively). These findings indicate that aminoglycosides can affect nephron tubules through two unrelated mechanisms that produce a partial 'Fanconi-like syndrome' and a 'Bartter-like syndrome'. However, because none of the study participants developed renal failure, these alterations are probably reversible and should not be used as sensitive or specific indicators of impending renal insufficiency. CONCLUSIONS: Our study findings confirm that aminoglycosides can induce both proximal and distal renal tubular dysfunction. However, it remains unclear whether the early functional changes detected by (1)H NMR spectroscopy in patients treated with aminoglycosides are of prognostic value.

Oxidative modification of albumin in predialysis, hemodialysis, and peritoneal dialysis patients.

BACKGROUND/AIMS: Oxidative damage has been reported to be involved in the pathophysiology of chronic kidney disease (CKD) as well as in the pathogenesis of cardiovascular complications of CKD patients. The aim of the present investigation was to evaluate the levels of plasma carbonyl formation, a sensitive marker of enhanced oxidative stress in predialysis, hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Plasma samples from 20 apparently healthy control individuals and 127 CKD (stages 2, 3, 4, HD and PD) patients were evaluated by Western blot analysis for the estimation of the levels of protein carbonyl formation. RESULTS: Albumin represented the main plasma carbonylated protein. Increasing carbonylation of albumin was detected along with the severity of CKD, reaching significance at stages 3 and 4 (p < 0.01, compared to healthy controls). The carbonylation of albumin was even higher in the plasma of HD patients (p < 0.001), while in PD patients it was not statistically significant compared to controls (p = 0.224). CONCLUSIONS: The data presented in this work indicate that oxidative stress in CKD patients gradually increased during the development of the disease. This stress is probably intensified during HD, but not in PD subjects.

Socio-demographic status and alcohol drinking patterns among Greek healthy adults.

AIM: To analyze socio-demographic correlates of alcohol drinking among Greek healthy adults. METHODS: Data related to alcohol consumption patterns of 5500 adult individuals, coming from 26 Hellenic provinces were abstracted from SESy-Europe database within a framework of the nationwide Hellenic anticancer-trial PACMeR 02 study. Statistic: chi2 test and logistic regression analyses were used. RESULTS: 42.5% of males and 82.5% of females did not consume alcoholic drinks. Among users, daily alcohol assumption was 28.50 g/day for men and 9.85 g/day for women. The mainland population presented higher proportions for both abstainers and moderate-heavy drinkers. Consumption rate was higher for sub-populations living in islands, but they were mostly light drinkers rather than heavy consumers. Among males, younger subjects, farmers and craftsmen had a higher tendency for alcohol abuse. Among females, the proportion of consumers and abusers was notably more elevated among younger individuals, especially among those living in urban areas of mainland, with higher educational level, employees and freelance professionals. A particular attention to the newly and rapidly growing patterns of alcoholism among young females should be given and prevention programs should be promptly developed.

Tyrosine nitration in plasma proteins from patients undergoing hemodialysis.

BACKGROUND: A growing body of evidence suggesting that oxidative stress might be one of the most important complications occurring during hemodialysis (HD) has accumulated. However, although the role of reactive oxygen species has been investigated extensively, little is known about the involvement of reactive nitrogen species. In the present investigation, levels of protein modifications in the form of tyrosine nitration in patients undergoing long-term HD therapy were evaluated. METHODS: Tyrosine nitration of plasma proteins was detected by means of Western blotting using a specific nitrotyrosine-recognizing monoclonal antibody, and band intensity was evaluated by using image analysis software. Immunoprecipitation of plasma proteins by antinitrotyrosine-agarose--conjugated antibodies, followed by Western blotting, was used in an attempt to identify the nitrated proteins. RESULTS: Although several proteins with nitrated tyrosine residues were observed in plasma of healthy individuals, increased nitration levels were observed in some specific proteins in all patients tested (n = 25) compared with controls (n = 6). At least 6 apparent bands appeared to be more nitrated than their counterparts in plasma from controls. Ceruloplasmin was identified as 1 of the proteins with significantly increased nitration in patients. CONCLUSION: Results of the present investigation show that specific plasma proteins of HD patients are post-translationally modified by nitration of their tyrosine residues. The nature of these proteins, as well as the exact molecular mechanisms and consequences of these modifications, warrant additional investigation.

Combination therapies of DPP4 inhibitors and GLP1 analogues with insulin in type 2 diabetic patients: a systematic review.

OBJECTIVE: The use of dipeptidyl-peptidase 4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) analogues for the treatment of diabetic mellitus (DM) type 2 is growing. Currently some of these agents have been approved in combination with insulin. METHODS: We considered randomised controlled trials (RCTs) evaluating GLP1 analogues or DDP4 inhibitors combined with basal insulin in diabetic patients. We were limited to trials published in English language. RESULTS: PubMed search retrieved 207 items. After excluding irrelevant items we ended with 7 eligible studies with 1808 participants. Mean baseline HbA1c was 8.5% and median follow up was 24 weeks. Exenatide combined with insulin was used in 2 studies; DPP4 inhibitors were used in 5 studies (2 with sitagliptin, 1 with saxagliptin, 1 with vildagliptin and 1 with alogliptin). CONCLUSION: Incretin-based therapies combined with basal insulin are able to reduce HbA1c by 0.5-0.7%. DPP4 inhibitors have no significant effect on weight, whereas GLP1 analogues reduced weight by 1-2 kg. Hypoglycaemia rates were generally comparable in all treatment groups. These are promising results, but the available evidence is limited. This is a poorly investigated field with few RCTs. New studies focusing on head-to-head comparisons with short-acting insulin on top of basal insulin are needed.

Dyslipidemia associated with chronic kidney disease.

Cardiovascular disease is a major cause of morbidity and mortality in patients with impaired renal function. Dyslipidemia has been established as a well-known traditional risk factor for cardiovascular disease (CVD) in the general population and it is well known that patients with chronic kidney disease (CKD) exhibit significant alterations in lipoprotein metabolism. In this review, the pathogenesis and treatment of CKD-induced dyslipidemia are discussed. Studies on lipid abnormalities in predialysis, hemodialysis and peritoneal dialysis patients are analyzed. In addition, the results of the studies that tested the effects of the hypolipidemic drugs on cardiovascular morbidity and mortality in patients with CKD are reported.

Electrolyte disturbances in patients with hyponatremia.

OBJECT: Electrolyte abnormalities are frequently observed in patients with hyponatremia. The aim of this study was to determine the incidence of various electrolyte abnormalities encountered in hyponatremic patients admitted to an internal medicine clinic, as well as to investigate the possible pathogenetic mechanisms responsible for these abnormalities. PATIENTS AND METHODS: We prospectively studied 204 adult patients who either on admission to our clinic or during their hospitalization were found to have hyponatremia. RESULTS: Ninety-two patients (45.5%) had at least one additional electrolyte abnormality. Hypophosphatemia was the most frequent electrolyte disorder observed (35 patients, 17%). Hypokalemia was seen in 32 patients (15.8%), hypomagnesemia in 31 patients (15.2%) and hyperkalemia in 12 patients (5.9%). Moreover, 5 patients (2.5%) had hyperphosphatemia, 4 patients (1.9%) exhibited hypermagnesemia, 3 patients (1.4%) had hypercalcemia, and 6 patients (2.9%) had true hypocalcemia. There were no statistically significant differences regarding the incidence of these electrolyte abnormalities (as a whole) between the main subgroups of hyponatremic patients (diuretic-induced, syndrome of inappropriate antidiuretic hormone, hypovolemia-induced and edematous state-related). However, hypokalemia and hypomagnesemia were more frequently observed in patients with diuretic-induced hyponatremia, while hyperkalemia was more frequently seen in edematous state-related hyponatremia. CONCLUSIONS: Additional electrolyte abnormalities are frequently encountered in patients with hyponatremia of any origin admitted to an internal medicine clinic.