Evidence suggests an imbalance between antioxidant and oxidant-generating systems resulting in oxidative stress in uremic patients. As plasma proteins are critical targets for oxidants, we developed a novel spectrophotometric assay which allows to detect advanced oxidation protein products (AOPP) in uremic plasma. By size-exclusion chromatography AOPP are retrieved in two distinct peaks at 600 and below 80 kDa in uremic plasma, while no such peaks are found in control plasma. Further biochemical characterization revealed that AOPP are carried by oxidized plasma proteins, especially albumin and do not have oxidant properties. AOPP increased in a dose-dependent manner following in vitro exposure of plasma or purified human serum albumin (HSA) to hypochlorous acid. Advanced glycation end products of human serum albumin (AGE-HSA) also increased AOPP levels. In vivo, plasma level of AOPP was the highest in patients on hemodialysis, followed by those on peritoneal dialysis and by undialyzed patients with advanced chronic renal failure. AOPP levels correlated with plasma concentrations of dityrosine and AGE-pentosidine, as indices of oxidant-mediated protein damage, but not with thiobarbituric reactive substances as lipid peroxidation markers. A close correlation was also found between AOPP and neopterin levels, suggesting that AOPP could be part in the monocyte-mediated inflammatory disorders associated with uremia. In conclusion, we propose the measurement of AOPP as a reliable marker to estimate the degree of oxidant-mediated protein damage in uremic patients and to predict the potential efficacy of therapeutic strategies aimed at reducing such an oxidative stress.

This meta-analysis of observational studies suggests that elevated homocysteine is at most a modest independent predictor of IHD and stroke risk in healthy populations. Studies of the impact on disease risk of genetic variants that affect blood homocysteine concentrations will help determine whether homocysteine is causally related to vascular disease, as may large randomized trials of the effects on IHD and stroke of vitamin supplementation to lower blood homocysteine concentrations.

Abstract. The fate of octogenarians reaching end-stage renal disease (ESRD) is poorly defined, and implicit dialysis rationing may be practiced in this age group. The main objectives of this study were to analyze the characteristics of pre-ESRD octogenarians offered dialysis or not and to identify factors influencing mortality while on dialysis, to improve prognosis assessment and decision-making. In this single-center cohort, 146 consecutive pre-ESRD octogenarians were referred to a nephrology unit over a 12-yr period (1989 to 2000). Main outcome measures were baseline characteristics of patients offered dialysis and conservative therapy and overall and 1-yr survival according to effective treatment. A therapeutic decision was made for 144 patients. Octogenarians who were not proposed dialysis (n ϭ 37) differed from those who were proposed dialysis (n ϭ 107) mainly in terms of social isolation (43.3% versus 14.7%; P ϭ 0.03), late nephrologic referral (51.4% versus 28.9%; P ϭ 0.01), Karnofsky score (55 Ϯ 18 versus 63 Ϯ 20; P ϭ 0.03), and diabetic status (22.2% versus 6.5%, P ϭ 0.008). Six patients refused the dialysis proposal.During the 12-yr observation period, 99 patients died (68.7%). Median survival was 28.9 mo (95% CI, 24 to 38) in patients undergoing dialysis, compared with 8.9 mo (95% CI, 4 to

An increased prevalence of nephrolithiasis has been reported in patients with diabetes. Because insulin resistance, characteristic of the metabolic syndrome and type 2 diabetes, results in lower urine pH through impaired kidney ammoniagenesis and because a low urine pH is the main factor of uric acid (UA) stone formation, it was hypothesized that type 2 diabetes should favor the formation of UA stones. Therefore, the distribution of the main stone components was analyzed in a series of 2464 calculi from 272 (11%) patients with type 2 diabetes and 2192 without type 2 diabetes. The proportion of UA stones was 35.7% in patients with type 2 diabetes and 11.3% in patients without type 2 diabetes (P < 0.0001). Reciprocally, the proportion of patients with type 2 diabetes was significantly higher among UA than among calcium stone formers (27.8 versus 6.9%; P < 0.0001). Stepwise regression analysis identified type 2 diabetes as the strongest factor that was independently associated with the risk for UA stones (odds ratio 6.9; 95% confidence interval 5.5 to 8.8). The proper influence of type 2 diabetes was the most apparent in women and in patients in the lowest age and body mass index classes. In conclusion, in view of the strong association between type 2 diabetes and UA stone formation, it is proposed that UA nephrolithiasis may be added to the conditions that potentially are associated with insulin resistance. Accordingly, it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome. 17: 202617: -203317: , 200617: . doi: 10.1681 I ncidence of urinary stone disease rose considerably in recent decades in all industrialized countries (1,2), as did the incidence of obesity, the metabolic syndrome, and type 2 diabetes (3-6). These epidemiologic changes took place in parallel with marked modifications in dietary habits and lifestyle that occurred in all Western and westernized populations, characterized by a high calorie intake coupled with reduced physical activity (7-9). This temporal parallelism suggested that an association might exist among diabetes, obesity, and urinary stone disease. Two recent studies revealed an increased prevalence of nephrolithiasis in patients with diabetes as compared with patients without diabetes (10,11), but in these studies, the chemical type of nephrolithiasis was not identified. Therefore, it was not defined whether calcium (Ca) or uric acid (UA) stones or both contributed to the increased prevalence of urinary stone disease in patients with diabetes, as alterations in urine biochemistry associated with obesity and type 2 diabetes may favor the formation of UA as well as of Ca stones (12-15). J Am Soc NephrolInsulin resistance, which constitutes the fundamental metabolic disorder that is associated with the metabolic syndrome and type 2 diabetes (16,17), results in defective renal ammoniagenesis and low urine pH (18,19) and therefore may be expected to favor the production of UA ...

Incidence of atherosclerotic CV complications is abnormally high in predialysis CRF patients, suggesting that the uraemic state per se is associated with atherogenesis. As several of the identified clinical and metabolic risk factors for such accidents are potentially remediable by specific therapeutic interventions, prophylactic measures should be initiated long before start of renal replacement therapy.

Urinary stone incidence and composition have changed markedly over the past half-century in industrialized countries, in parallel with profound changes in living standards and dietary habits, with a dramatic increase in the incidence of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We report the results of a study based on 27,980 calculi (from 19,442 males and 8,538 females) analyzed by infrared spectroscopy between 1976 and 2001. The relationships between age and sex and stone composition were investigated using a multivariate approach, based on correspondence factor analysis (CFA). We found a male predominance for calcium oxalate and uric acid, a female preponderance for calcium phosphate and struvite stones, and an increasing prevalence of uric acid stones with age in both genders. CFA was able to reconstruct in blind the age curve from stone composition. The first two axes of the multidimensional classification, which correspond to age, included 86.9% of the total variance, indicating that age was the main factor involved in stone type. Superimposition of age classes and stone components showed a strong relationship between age and whewellite, weddellite, brushite, carbapatite, octacalcium phosphate and uric acid, while other substances (whitlockite, amorphous carbonated calcium phosphate, struvite, proteins, mucopolysaccharides, triglycerides or ammonium urate) appeared weakly related to age. In addition, CFA suggests the role of common lithogenic factors between weddellite, carbapatite and brushite, which clustered in the same area, whereas the various crystalline forms of phosphate stones segregated into two different clusters, suggesting distinct pathogenic factors. In conclusion, this study provides a picture of the present epidemiology of urinary stones in France. CFA helped to confirm: (1) an etiopathogenic distinction between weddellite and whewellite, (2) etiopathogenic associations between chemical compounds, which were only suspected on a clinical basis, and (3) suggested yet unrecognized associations, especially with respect to the heterogeneous group of phosphate stones.

Our study provides evidence that a regularly followed medical program based on high diuresis and alkalization with second line addition of thiols may arrest or markedly decrease cystine stone formation and preclude the need for urological procedures in more than half of the patients. However, patients poorly compliant with hyperdiuresis remain at risk for recurrence. We suggest that maintaining a daily urine volume of greater than 3 l. is essential for therapeutic success regardless of whether thiol derivatives are administered.

Drug-induced calculi represent 1-2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment. Calculi analysis by physical methods including infrared spectroscopy or X-ray diffraction is needed to demonstrate the presence of the drug or its metabolites within the calculi. Some drugs may also provoke heavy intra-tubular crystal precipitation causing acute renal failure. Here, the identification of crystalluria or crystals within the kidney tissue in the case of renal biopsy is of major diagnostic value. The second group includes drugs that provoke the formation of urinary calculi as a consequence of their metabolic effects on urinary pH and/or the excretion of calcium, phosphate, oxalate, citrate, uric acid or other purines. Among such metabolically induced calculi are those formed in patients taking uncontrolled calcium/vitamin D supplements, or being treated with carbonic anhydrase inhibitors such as acetazolamide or topiramate. Here, diagnosis relies on a careful clinical inquiry to differentiate between common calculi and metabolically induced calculi, of which the incidence is probably underestimated. Specific patient-dependent risk factors also exist in relation to urine pH, volume of diuresis and other factors, thus providing a basis for preventive or curative measures against stone formation.