Non-diabetic Chronic Renal Failure Research Articles

SGLT2 inhibitors for heart and kidney

Sodium-glucose co-transporter 2 (SGLT2) inhibitors can block glucose reabsorption in the proximal tubule and thus play an important role in glycemic control in diabetes mellitus. In addition to glucosuric effects, surprisingly very extensive other positive effects were observed in chronic renal dysfunction and strong cardioprotective effects in heart failure. In the meantime, numerous mechanisms have been identified apart from the pure sugar-influencing effect of the SGLT2 inhibitors, which can have a direct positive influence heart and kidneys.In recent years there has been an extensive clinical study program, which has dealt with the effects of SGLT2 inhibitors on the progression of diabetic and non-diabetic chronic renal failure. It could be shown that patients with albuminuria have a significant benefit from the use of SGLT2 inhibitors. Therefore, the progression of renal dysfunction is slowed down significantly, while at the same time, positive cardiovascular endpoints could be influenced. Numerous studies have also been conducted in patients with and without diabetes or with heart failure, with and without, preserved ejection fraction. Impressive protection was also shown here, with the benefit of using SGLT2 inhibitors to reduce heart failure worsening.In a short period of 10 years, the use of SGLT2 inhibitors was established as an essential therapy for cardio-renal indications to inhibit the progression of renal failure as well as to protect against heart failure apart from pure diabetes therapy. In numerous guidelines (ESC heart failure, KDGIO diabetes, ESH hypertension), the early use of SGLT2 inhibitors is now recommended for protection against cardio-renal events and is an important first-line addition to the previously established therapies. Apart from diabetes therapy, it offers patients completely new options in cardio-renal protection.

Oral Manifestations in Diabetic and Nondiabetic Chronic Renal Failure Patients receiving Hemodialysis

Aim: To assess the prevalence of oral findings in diabetic and nondiabetic chronic renal failure (CRF) patients receiving hemodialysis (HD). Materials and methods: This study was conducted on 144 CRF patients undergoing HD therapy. They were further classified into diabetic and nondiabetic groups and also according to the duration of CRF. An oral examination was performed, searching for CRF-associated oral findings, along with due considerations to duration of CRF. Results: The oral manifestations were found to be higher in diabetic CRF patients (97.14%) relative to nondiabetic CRF patients (89.18%). The diabetic group exhibited a significantly higher number of patients with poor oral hygiene index (p = 000), uremic fetor (p = 0.005), unpleasant taste (p = 0.009), dry-fissured lips (p = 0.002), and pale mucosa (p = 0.019) than the nondiabetic group. The oral manifestations were significantly higher in CRF patients of more than 24 months' duration. Conclusion: The CRF HD patients with diabetes mellitus exhibited a higher risk of oral uremic manifestations including uremic fetor, unpleasant taste, pale mucosa, and dry-fissured lips than nondiabetics. The oral health status of CRF HD patients becomes worse with the increase in the duration of CRF. Clinical significance: Oral health status is often a neglected aspect in CRF patients. It should be given prime importance for CRF patients receiving HD to improve the quality of life. Keywords: Chronic renal failure, Diabetes, Hemodialysis, Oral manifestations.

The effect of non-diabetic chronic renal failure on olfactory function

ObjectivesIn chronic renal failure (CRF), deterioration of glomerular filtration results in accumulation of metabolites in the body which affect all organs. This study was performed to investigate the olfactory functions, and determine if hemodialysis or peritoneal dialysis improves olfactory function in non-diabetic CRF patients. Materials and methodsThe olfactory functions were analyzed in CRF patients not on a dialysis program and had a creatinine level≥2mg/dL, in CRF patients on hemodialysis or peritoneal dialysis, and in healthy controls. Diabetic patients were excluded since diabetes alone is a cause of olfactory dysfunction. The study group consisted of a total of 107 individuals including 38CRF patients on a hemodialysis program, 15 CRF patients on peritoneal dialysis, 30 patients with a creatinine level ≥ 2mg/dL without any need for dialysis, and 24 healthy controls with normal renal functions. Olfactory functions were analyzed with “Sniffin’ sticks” test, and the groups were compared for the test results. ResultsAll test parameters were impaired in patients with CRF. The median TDI scores of the patients with CRF and the healthy subjects were 24.75 (13–36) and 32.5 (27.75–37.75), respectively, with a statistically significant difference in between (P<0.001). The olfactory functions for the dialysis patients were better than those for the CRF patients not on a dialysis program (P=0.020). ConclusionNon-diabetic CRF affects olfactory functions negatively. Dialysis improves olfactory functions in those patients.

Evaluation of nasal mucociliary activity in patients with chronic renal failure.

The ability of respiratory mucosal surfaces to eliminate foreign particles and pathogens and to keep mucosal surfaces moist and fresh depends on mucociliary activity. Chronic renal failure (CRF) is an irreversible medical condition that may result in important extrarenal systemic consequences, such as cardiovascular, metabolic, and respiratory system abnormalities. Although there are studies describing nasal manifestations of CRF, data are lacking concerning the effects of the condition on nasal mucosa. The goal of the current study was to evaluate nasal mucociliary clearance (NMC) time in patients with CRF. This prospective cohort study conducted in a tertiary referral center included 32 non-diabetic end-stage CRF patients and 30 control individuals. The control group consisted of voluntary participants who had been referred to our clinic for symptoms other than rhinological diseases. The mean NMC times in CRF patients and control individuals were 12.51 ± 3.74 min (range 7-22 min) and 8.97 ± 1.83 min (range 6-13 min), respectively. The mean NMC time in patients with CRF was significantly longer than that in control individuals (p < 0.001). Clinicians must keep in mind that NMC time in CRF patients is prolonged and must follow-up these patients more closely for sinonasal and middle ear infections.

Tear function in patients with chronic renal failure undergoing hemodialysis

Objectives: To evaluate dry eye symptoms and clinical tear film alterations in patients with chronic renal failure (CRF). Materials and methods: Thirty-five non-diabetic CRF patients undergoing hemodialysis, and 31 healthy individuals were enrolled. An ocular surface disease index questionnaire (OSDI) was administered, and after a complete ocular examination, Schirmer and tear break-up time (TBUT) tests were performed. Results: OSDI scores were significantly higher (p < 0.01) and TBUT tests were significantly lower (p = 0.01) in CRF patients than in the control group. Schirmer test results were also lower in the CRF patients group, but lacked statistical significance (p = 0.20). Conclusion: Patients with CRF should be advised to obtain an ophthalmic examination, especially for dry eye.

Spatial distribution of unspecified chronic kidney disease in El Salvador by crop area cultivated and ambient temperature.

Chronic kidney disease of unknown etiology is occurring in various geographic areas worldwide. Cases lack typical risk factors associated with chronic kidney disease, such as diabetes and hypertension. It is epidemic in El Salvador, Central America, where it is diagnosed with increasing frequency in young, otherwise-healthy male farmworkers. Suspected causes include agrochemical use (especially in sugarcane fields), physical heat stress, and heavy metal exposure. To evaluate the geographic relationship between unspecified chronic kidney disease (unCKD) and nondiabetic chronic renal failure (ndESRD) hospital admissions in El Salvador with the proximity to cultivated crops and ambient temperatures. Data on unCKD and ndESRD were compared with environmental variables, crop area cultivated (indicator of agrochemical use) and high ambient temperatures. Using geographically weighted regression analysis, two model sets were created using reported municipal hospital admission rates are per thousand population for unCKD 2006-2010 and rates of ndESRD 2005-2010 [corrected]. These were assessed against local percent of land cultivated by crop (sugarcane, coffee, corn, cotton, sorghum, and beans) and mean maximum ambient temperature, with Moran's indices determining data clustering. Two-dimensional geographic models illustrated parameter spatial distribution. Bivariate geographically weighted regressions showed statistically significant correlations between percent area of sugarcane, corn, cotton, coffee, and bean cultivation, as well as mean maximum ambient temperature with both unCKD and ndESRD hospital admission rates. Percent area of sugarcane cultivation had greatest statistical weight (p ≤ 0.001; Rp2 = 0.77 for unCKD). The most statistically significant multivariate geographically weighted regression model for unCKD included percent area of sugarcane, cotton and corn cultivation (p ≤ 0.001; Rp2 = 0.80), while, for ndESRD, it included the percent area of sugarcane, corn, cotton and coffee cultivation (Rp2 = 0.52). Univariate unCKD and ndESRD Moran's I (0.20 and 0.33, respectively) indicated some degree of clustering. Ambient temperature did not improve multivariate geographically-weighted regression models for unCKD or ndESRD. Local bivariate Moran's indices with relatively high positive values and statistical significance (0.3-1.0, p ≤0.05) indicated positive clustering between unCKD hospital admission rates and percent area of sugarcane as well as cotton cultivation. The greatest positive response for clustering values did not consistently plot near the highest temperatures; there were some positive clusters in regions of lower temperatures. Clusters of ndESRD were also observed, some in areas of relatively low chronic kidney disease incidence in western El Salvador. High temperatures do not appear to strongly influence occurrence of unCKDu proxies. CKDu in El Salvador may arise from proximity to agriculture to which agrochemicals are applied, especially in sugarcane cultivation. The findings of this preliminary ecological study suggest that more research is needed to assess and quantify presence of specific agrochemicals in high-CKDu areas.

Diyabetik Olmayan Kronik Böbrek Yetmezliği Hastalarında Hemodiyalizin Gözdeki Etkileri

Amaç: Diyabetik olmayan kronik böbrek yetmezliği (KBY) hastalarında hemodiyalizin düzeltilmiş en iyi görme keskinliği (DEİGK), sferik ekivalan, merkezi kornea kalınlığı (MKK), göz içi basıncı (GİB), maküla hacmi ve retina sinir lifi tabakası (RSLT) kalınlığına etkisinin değerlendirilmesi. Gereç ve Yöntemler: Bu kesitsel çalışmaya, yaşları 46-78 yıl arasında değişen (ortalama 61,13±10,31 yıl) hemodiyaliz tedavisi altındaki 20 erkek, 4 kadın KBY hastasının 24 gözü dahil edildi. Hastaların hemodiyaliz öncesi ve sonrası DEİGK, sferik ekivalan, MKK, GİB, maküla hacmi ve RSLT kalınlığı ölçümleri kaydedildi. Verilerin istatistiksel değerlendirmesi eşleştirilmiş örneklem t-testi, Wilcoxon işaretli sıra testi ve Pearson korelasyon analizi ile yapıldı. Bulgular: Hemodiyaliz plazma ozmolalitesinde istatistiksel olarak anlamlı düşüşe (p<0,001), plazma kolloid onkotik basıncında ise artışa yol açarken (p<0,001), ortalama arter basıncında değişikliğe neden olmadı (p=0,139). Hemodiyaliz sonrası DEİGK, sferik ekivalan, MKK ve ölçülen tüm maküla segmenti hacimlerinde istatistiksel olarak anlamlı değişiklik izlenmedi (p değerleri >0,05). Hemodiyaliz sonrası GİB istatistiksel olarak anlamlı düzeyde azaldı (p=0,007) ve RSLT kalınlığında ise nazal ve temporal segmentler hariç diğer segmentlerde istatistiksel olarak anlamlı düzeyde artış saptandı (p değerleri global, superotemporal, superonazal, inferotemporal ve inferonazal segmentler için sırasıyla 0,005, 0,002, 0,021, 0.041 ve 0,024). Hemodiyaliz öncesi ve sonrası plazma kolloid ozmotik basıncı farkı ile MKK (r=-0,451, p=0,27) ve plazma kolloid ozmotik basıncı farkı ile GİB farkları (r=-0,415, p=0,044) arasında istatistiksel olarak anlamlı orta düzeyde korelasyon dışında değerlendirilen diğer parametreler ve bu parametrelerdeki değişiklikler arasında istatistiksel olarak anlamlı bir korelasyon gözlenmedi (p değerleri >0,05). Sonuç: Diyabetik olmayan KBY hastalarında hemodiyaliz; DEİGK, sferik ekivalan, MKK ve maküler hacmi etkilemezken, GİB ve retina sinir lif tabaka kalınlığını değiştirmektedir. Hemodiyaliz tedavisi alan KBY hastalarının göz muayeneleri hemodiyaliz seansı zamanı baz alınarak aynı zaman dilimlerinde yapılmalıdır.

Evaluation of choroidal and retinal thickness measurements using optical coherence tomography in non-diabetic haemodialysis patients

The aim of this study is to evaluate the effects of haemodialysis with a high ultrafiltration rate on the choroidal and retinal thickness of non-diabetic end-stage chronic renal failure (CRF) patients using optical coherence tomography (OCT). Twenty-one eyes of 21 male CRF patients aged between 46 and 80 years were included in this prospective study. Retinal and choroidal thicknesses of the patients were measured using high-resolution OCT line scans with the activated enhanced depth imaging mode before and shortly after haemodialysis. Retinal and choroidal thickness measurements were taken at the fovea and at two points that were 1,500 μm nasal and temporal to the fovea. The relationships between the haemodynamic changes, intraocular pressure (IOP) and central corneal thickness (CCT) were also evaluated. The mean choroidal thicknesses before haemodialysis at the subfoveal, temporal and nasal locations were 232.81 ± 71.92, 212.43 ± 70.50 and 182.14 ± 68.88 μm, respectively. The mean choroidal thicknesses after haemodialysis at the subfoveal, temporal and nasal locations were 210.90 ± 65.53, 195.38 ± 66.48 and 165.19 ± 66.73 μm, respectively. There were significant differences between the choroidal thicknesses before and after haemodialysis (p < 0.001 for all). The mean retinal thicknesses before haemodialysis at the foveal, temporal and nasal locations were 215.86 ± 41.06, 308.86 ± 37.73 and 338.00 ± 33.32 μm, respectively. The mean retinal thicknesses after haemodialysis at the foveal, temporal and nasal locations were 216.90 ± 39.70, 313.86 ± 32.89 and 335.29 ± 36.85 μm, respectively. There was no significant difference between the retinal thicknesses before and after haemodialysis (p > 0.05 for all). The mean CCT decreased insignificantly from 550.48 ± 17.46 to 548.10 ± 21.12 μm (p = 0.411). The mean IOP decreased significantly from 14.09 ± 2.58 to 12.54 ± 2.23 mmHg (p = 0.003), which did not correlate with the CCT [r = (-)0.134, p = 0.562]. Haemodialysis with a high ultrafiltration volume did not alter the retinal thickness but caused a significant choroidal thinning and an IOP decrease in non-diabetic end-stage CRF patients.

Oral Manifestations in Diabetic and Nondiabetic Chronic Renal Failure Patients on Hemodialysis

Introduction: Oral cavity reflects the general health status of an individual. Diagnosing and treating oral manifestations of systemic disease pose a greater challenge to oral physician. Chronic renal failure (CRF) is one such disease that demonstrates a complex set of oral findings due to disease itself and also due to treatment like hemodialysis- Diabetes, the most common cause of CRF also affects oral health. An attempt is made in this study to evaluate and compare oral health status of diabetic and nondiabetic CRF patients who were on maintenance hemodialysis Materials and methods: Study was done on 106 CRF patients who were on hemodialysis. Patients were divided into diabetic (55 patients) and nondiabetic (51 patients) group based on their blood sugar level Patients of both groups were examined for predialytic salivary pH, decayed, missing, filled teeth. periodontal condition and mucosal lesions. Results: Salivary pH in diabetic group was less when compared to nondiabetic group (p < 0.001). Diabetic group had higher caries prevalence (p < 0.001) and periodontal disease compared to nondiabetics. Conclusion: Study revealed decrease in salivary pH and increased prevalence of caries and periodontal disease in diabetic group. Differences in oral manifestations were also noticed between diabetic and nondiabetic uremic patients.

Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation

AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120–treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables–matched non–AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R2 = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation.

Quantitation and characterization of glutathionyl haemoglobin as an oxidative stress marker in chronic renal failure by mass spectrometry

Objectives: Glutathionyl haemoglobin (GS-Hb) belonging to the class of glutathionylated proteins has been investigated as a possible marker of oxidative stress in different chronic diseases. The purpose of this study was to examine whether glutathionyl haemoglobin can serve as an oxidative stress marker in non-diabetic chronic renal failure patients on different renal replacement therapies (RRT) through its quantitation, and characterization of the specific binding site of glutathione in haemoglobin molecule by mass spectrometric analysis. Design and methods: The study group consisted of non-diabetic chronic renal failure patients on renal replacement therapy (RRT): hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and renal allograft transplant (Txp) patients. Haemoglobin samples of these subjects were analyzed by liquid chromatography electrospray ionization mass spectrometry for GS-Hb quantitation. Characterization of GS-Hb was done by tandem mass spectrometry. Levels of erythrocyte glutathione (GSH) and lipid peroxidation (as thiobarbituric acid reacting substances) were measured spectrophotometrically, while glycated haemoglobin (HbA1c) was measured by HPLC. Results: GS-Hb levels were markedly elevated in the dialysis group and marginally in the transplant group as compared to the controls. GS-Hb levels correlated positively with lipid peroxidation and negatively with the erythrocyte glutathione levels in RRT groups indicating enhanced oxidative stress. De novo sequencing of the chymotryptic fragment of GS-Hb established that glutathione is attached to Cys-93 of the beta globin chain. Mass spectrometric quantitation of total glycated haemoglobin showed good agreement with HbA1c estimation by conventional HPLC method. Conclusions: Glutathionyl haemoglobin can serve as a clinical marker of oxidative stress in chronic debilitating therapies like RRT. Mass spectrometry provides a reliable analytical tool for quantitation and residue level characterization of different post-translational modifications of haemoglobin.

Oral administration of AST-120 (Kremezin) is a promising therapeutic strategy for advanced glycation end product (AGE)-related disorders

The pathological role of the non-enzymatic modification of proteins by reducing sugars has become increasingly evident in various disorders. It is now well established that early glycation products undergo progressive modification over time in vivo to the formation of irreversible cross-links, after which these molecules are termed "AGEs (advanced glycation end products)". AGEs have been implicated in the development of many of the pathological sequelae of diabetes and aging, such as diabetic microangiopathy, ischemic heart disease and neurodegenerative diseases. Recently, digested food-derived AGEs are also found to play an important role in the pathogenesis of AGE-related disorders. Diet is a major environmental source of pro-inflammatory AGEs. Indeed, restriction of dietary glycotoxins decreases excessive AGE levels and subsequently reduces the inflammatory responses in patients with diabetes. These observations suggest that inhibition of absorption of dietary AGEs may be a novel target for therapeutic intervention in the above-mentioned AGE-related disorders. AST-120 (Kremezin) is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) by removing uremic toxins. We have recently found that AST-120 binds to carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs in vitro and that administration of AST-120 decreases serum levels of AGEs in non-diabetic CRF patients. These findings suggest that digested food-derived AGEs such as CML may be a novel molecular target for oral adsorbent AST-120 and that AST-120 could exert beneficial effects on CRF patients by adsorbing diet-derived AGEs and subsequently decreasing serum AGE levels. If our speculation is correct, AST-120 may have therapeutic potentials for the treatment of patients with various AGE-related disorders as well. In this paper, we would like to propose the possible ways of testing our hypotheses. Does the long-term treatment of AST-120 decrease serum and tissue levels of AGEs in diabetic patients? Does this treatment also reduce the risk for the development and progression of diabetic vascular complications such as diabetic retinopathy or ischemic heart disease? If the answers are yes, do the serum and/or tissue levels of AGEs after AST-120 treatment predict its beneficial effects on diabetic vascular complications? How about the effects of AST-120 on Alzheimer's disease, another AGE-related neurodegenerative disorder? Does the treatment of AST-120 reduce the risk for Alzheimer's disease and/or improve the cognitive impairment of patients with this disorder? These prospective studies will provide further valuable information whether the inhibition of absorption of dietary AGEs by AST-120 could be clinically relevant.

Correlation between Pentosidine and Endothelin-1 in Subjects Undergoing Chronic Hemodialysis

Advanced glycation end-products (AGEs), which accumulate in the blood and tissues of patients with chronic renal failure (CRF) undergoing chronic hemodialysis, play an important role in the pathogenesis of uremic complications. Endothelin 1 (ET1), a 21-amino acid peptide with vasoconstricting and mitogenic properties, is an important factor in the endothelial dysfunction occurring in uremia. The circulating levels of both AGEs and ET1 have been reported to be increased in chronic renal failure. In the present study we evaluated the possible relationship between pentosidine and ET1 plasma levels in CRF patients undergoing chronic hemodialysis treatment. The plasma concentrations of "free" and bound pentosidine (HPLC methods) and endothelin-1 (RIA method) were measured before the hemodialysis session in 40 nondiabetic CRF patients (22 males and 18 females; 54+/-3 years) on chronic hemodialysis for at least 1 year. Forty age- and sex-matched normal subjects served as a control group. In hemodialyzed patients, the overall pentosidine residues and pentosidine-free adduct plus pentosidine-free adduct bound reversibly to protein levels (24.9+/-2.04 pmol/mg protein and 110.5+/-5.9 pmol/ml, respectively) were significantly higher than those recorded in normal subjects (2.0+/-0.2 pmol/mg protein and 0.7+/-0.2 pmol/ml, respectively ). Endothelin-1 was also significantly (p<0.01) increased in CRF patients (10.6+/-0.4 pmol/ml in CRF patients and 2.7+/-0.3 pmol/ml in normal subjects). A significant positive correlation (p<0.01) was seen between "total" pentosidine (pentosidine residues and pentosidine-free adduct plus pentosidine-free adduct bound reversibly to protein) levels and endothelin-1 plasma values. The correlation between pentosidine and endothelin-1 provides further evidence that some AGEs exert a detrimental effect on the vascular endothelium, thereby contributing to the hypertension and other cardiovascular damage seen in CRF patients.

Oral Adsorbent AST-120 Decreases Serum Levels of AGEs in Patients with Chronic Renal Failure

Advanced glycation end products (AGEs) are senescent macroprotein derivatives that are formed at an accelerated rate in patients with chronic renal failure (CRF). AGE formation and accumulation in plasma and vascular tissues contribute to accelerated atherosclerosis in this devastating disorder. AST-120 is an oral adsorbent that attenuates the progression of CRF by removing uremic toxins. Recently, AST-120 has been reported to reduce the progression of atherosclerosis as well. However, whether AST-120 decreases serum levels of AGEs and subsequently exerts atheroprotective properties remains to be elucidated. Ten nondiabetic CRF patients were enrolled in this study. All patients were kept on regular therapeutic diet and medications throughout the study. Serum AGE levels before and after AST-120 treatments were measured using enzyme-linked immunosorbent assay. Effects of patient-derived serum on atherosclerosis-related gene expression in cultured human umbilical vein endothelial cells (HUVECs) were analyzed by semiquantitative RT-PCR. Administration of AST-120 (6 g/day) for 3 months significantly decreased serum levels of AGEs in nondiabetic CRF patients, whereas AGE levels remained unchanged in age- and renal function-matched CRF patients without AST-120 treatment (n = 6). Patient serum after AST-120 treatment significantly reduced mRNA levels of receptor for AGEs, monocyte chemoattractant protein-1, and vascular adhesion molecule-1 in HUVECs compared with serum before treatment. Moreover, in vitro, AST-120 was found to adsorb carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs. This study suggests that atheroprotective properties of AST-120 can be ascribed, at least in part, to its AGE-lowering ability via absorption of CML.

Exploring series of multivariate censored temporal data through fuzzy coding and correspondence analysis

We present an exploratory analysis methodology for a multiple series of multivariate temporal data subject to censoring, and thus requiring the introduction of a coding technique: fuzzy coding preserving a large amount of the distributional information is fully adapted. Correspondence analysis is performed on the array produced by fuzzy coding. Projections of mean paths on factorial mappings, according to subgroup characteristics, highlight the behaviour of the underlying process. This approach is illustrated with an application to a randomized controlled clinical trial designed for comparing non-diabetic chronic renal failure treatments. Our methodology has resulted in the identification of a difference between the treatments with an interpretation of the effects in subgroups of patients not obtainable with traditional survival methodology; it also provides some valuable insights for designing further studies on treatment of renal impairment.

Reassessing the increased glycation of hemoglobin in nondiabetic chronic renal failure patients: A hypothesis on the role of lipid peroxides

Background Glycated hemoglobin (HbA 1C) is considered clinically useful for assessing long-term integrated control of blood glucose in diabetes. However, an increased HbA 1C concentration has been documented in chronic renal failure (CRF) patients without any history of diabetes. Collective evidences reveal that lipid peroxidation (MDA) can modulate protein glycation. We evaluated the relationship between glycated hemoglobin (HbA 1C) and lipid peroxidation in non-diabetic CRF patients. Methods Twenty-eight nondiabetic CRF and 23 age- and sex-matched healthy subjects were enrolled for this study. Plasma urea, creatinine, lipid peroxides, fasting glucose and HbA 1C were analyzed in both the groups. The in-vitro effect of MDA on glycation of hemoglobin was studied by incubating healthy erythrocytes with either 5 or 50 mmol/l glucose concentration. Results The percentage of HbA 1C concentrations and plasma malondialdehyde (MDA) were significantly increased in CRF patients compared to control subjects. When the effects of uremia and blood glucose on the concentration of HbA 1C was refuted by partial correlation analysis, MDA was found to be a significant determinant of HbA 1C (r = 0.41, p = 0.04) in patients with renal failure. In-vitro incubation of RBC with glucose along with MDA was found to enhance the process of hemoglobin glycation. Conclusion Our results suggest that lipid peroxidation per se can contribute to glycation of hemoglobin, warranting extra-precaution in interpreting HbA 1C as a measure of glycemic control in CRF.

The Future of Angiotensin II Inhibition in Cardiovascular Medicine

Drugs, which interfere with the renin-angiotensin-aldosterone cascade such as angiotensin converting enzyme (ACE) inhibitors, have been available to clinicians for more than 20 years. They are now recognized as a very effective approach to treat patients with hypertension, heart failure, diabetic and non-diabetic chronic renal failure or patients with a high cardiovascular risk. The recent development of angiotensin II (Ang II) receptor antagonist has enabled to improve significantly the tolerability profile of this group of drugs while maintaining a high clinical efficacy. Yet, with the availability of Ang II receptor antagonists, new questions have arisen. Is it still possible to gain in efficacy with newer agents? What is the future of drugs such as neutral endopeptidase (NEP)/ACE inhibitors or renin inhibitors? The first objective of this review is to discuss the clinical implications of several large clinical trials that have been published recently with ACE inhibitors and Ang II receptor antagonists such as ALLHAT, LIFE, OPTIMAAL, Val-Heft, SCOPE, and more recently, CHARM, VALIANT and VALUE. With these trials, we can now define more precisely the role of these blockers of the renin-angiotensin system in the management of patients with cardiovascular complications. The second part of this review is devoted to new drugs interfering with the renin-angiotensin system. We discuss the recent results obtained with NEP/ACE inhibitors also named vasopeptidase inhibitors. Several compounds were or are in development but the experience with omapatrilat has blunted the enthusiasms for these compounds. Yet, vasopeptidase inhibitors remain very effective antihypertensive drugs and there is a great therapeutic potential for these agents provided one can define more accurately the risk/benefit ratio and the clinical indications. Finally, we present the recent data obtained with SPP 100, a new renin inhibitor that is actually under clinical development. SPP 100 has a sufficient bioavailability to induce a sustained blockade of the renin-angiotensin system when given orally to normal subjects. Recent studies have shown that SPP 100 lowers blood pressure in hypertensive patients as effectively as an Ang II receptor antagonist.

Elevated temporal QT variability index in patients with chronic renal failure.

Patients with CRF (chronic renal failure) are at increased risk of cardiovascular diseases, and 60% of cardiovascular mortality in CRF is attributed to sudden death. Various abnormalities in myocardial repolarization are associated with the risk of ventricular arrhythmia. The aim of this study was to evaluate an index of temporal myocardial repolarization lability, the temporal QTVI (QT variability index), in patients with CRF. ECGs were recorded in 153 patients with CRF on haemodialysis (n=67), continuous ambulatory peritoneal dialysis (n=43) or conservative treatment (n=43) during 30 min of rest. QTVI was calculated as the logarithm of the ratio between the variances of the normalized QT and RR intervals. Age-matched healthy subjects (n=39) were examined for comparison. QTVI was increased by 47% in CRF patients compared with healthy subjects (-0.82+/-0.56 compared with -1.54+/-0.27 respectively; P<0.01). QTVI did not differ among patients on dialysis or conservative treatment, whereas QTVI was elevated further in patients with diabetes compared with non-diabetic CRF patients (-0.56+/-0.54 compared with -0.94+/-0.52 respectively; P<0.01). In a multiple linear regression analysis, diabetes and a history of coronary artery disease were the only independent predictors of QTVI in the CRF population. The present study demonstrates that elevated QTVI in patients with CRF is associated with diabetes and coronary disease. The present findings are important given that repolarization instability may predispose to ventricular arrhythmia and sudden death, events that occur frequently in CRF patients.

The mechanism of hypoglycemia caused by hemodialysis

Although it is well-known that plasma glucose concentration ((G)p) decreases during hemodialysis, the precise mechanism underlying this decrease has not yet been fully elucidated. The aim of the present study was to investigate the mechanism underlying hemodialysis-induced decrease (HID) in (G)p during the dialysis in vivo or in vitro. Using high CO2/ HCO3- dialysate, we measured (G)p by a hexose kinase method ((G)pHK) and concentrations of electrolytes, as well as pH, PCO2 and PO2 for both plasma and dialysate samples at pre- and postdialyzer sites obtained from hemodialysis patients with nondiabetic chronic renal failure (CRF). Furthermore, we studied the effect of PCO2 and acetazolamide (ACZ) on the changes in (G)pHK during the dialysis in vitro. After the first dialysis of CRF patients, the (G)pHK decreased from 118.3 +/- 18.0 to 98.6 +/- 5.7 mg/dl (p < 0.05), the latter value being significantly lower than glucose concentration in dialysate samples (approximately 105 mg/dl) at predialyzer sites. In the experiments of blood samples from healthy volunteers, (G)pHK decreased significantly after elevating or lowering CO2 level in the dialysates. In contrast, when the difference in PCO2 between the blood and dialysate was reduced, the HID in (G)pHK was abolished during hemodialysis. The addition of 10(-4) M ACZ to the blood samples completely prevented the development of HID in (G)pHK caused by the perfusion of high or low CO2/HCO3- dialysates. During hemodialysis using high CO2/HCO3- dialysate, the HID in (G)p results from the diffusion of glucose from plasma into erythrocytes, probably due to the consumption of glucose resulting from the accelerated anaerobic metabolism induced by the changes in the cytoplasmic pH of erythrocytes.

Cardiovascular autonomic neuropathy in non-diabetic Nigerian patients with chronic renal failure.

To determine the frequency of cardiovascular autonomic neuropathy (CAN), its pattern and clinical predictors in Nigerians with non-diabetic chronic renal failure (CRF). A total of 120 subjects comprising 60 pre-dialysis CRF patients and an equal number of age- and sex-matched healthy controls were studied. Five standard cardiovascular reflex (CVR) tests namely: heart rate response to deep breathing, Valsalva manoevre and posture, as well as blood pressure response to hand grip and posture were used to evaluate the cardiac autonomic functions. A pre-tested questionnaire was administered, with neurological examination and serum biochemical investigations also included in the evaluation. The frequency of CAN in non-diabetic CRF was 65%. Dysfunction of both the parasympathetic and sympathetic divisions of the ANS occurred in CRF patients. Significant impairment in all the heart rate reflex tests (39%) and blood pressure response to the handgrip tests (28%) occurred in patients with CAN. Symptoms of autonomic neuropathy with clinical correlation with CAN included: constipation (60%), hyposialism (51%) and hypohidrosis (33%), whilst those of peripheral neuropathy were: loss of sensation (50%) and numbness (40%). Of the biochemical parameters, serum creatinine and urea had significant correlation with autonomic neuropathy. Autonomic neuropathy is common in Nigerian patients with non-diabetic CRF, especially in those with symptoms of constipation, hypohidrosis, numbness and prickly sensations.