Sevelamer hydrochloride suppresses proliferation of parathyroid cells during the early phase of chronic renal failure in rats.

AIM: We examined the effects of sevelamer on parathyroid cell proliferation and secondary hyperparathyroidism in rats following induction of early-phase of chronic renal failure (CRF) by unilateral ureteral obstruction (UUO). METHODS: For 5 days, rats in the control group received normal food, rats in the sevelamer group (SH) received control food plus 5% sevelamer, and rats in the low protein group (LP) received low protein food. Five rats of each group were killed at baseline (day 0). All other rats were given UUO, and five rats per group were killed on days 3, 7, 14, and 28 after UUO. Changes in body weight, serum phosphorus, calcium, intact-parathyroid hormone (i-PTH), creatinine (SCr), creatinine clearance rate (CCR), blood urea nitrogen (BUN), and 24-h urinary phosphorus were determined. Parathyroid tissues were removed for histological examination of proliferating cell nuclear antigen-positive (PCNA+) cells. RESULTS: Measurement of body weight, BUN, and SCr in the controls indicated successful establishment of this model of early-phase CRF. The controls also had remarkable proliferation of PCNA+ cells beginning on day 3, but this did not occur in the SH or LP groups. After 28 days, serum phosphorus had decreased more in the SH and LP groups than in the control group, and phosphorus excretion was much greater in the control group than in the SH and LP groups. The three groups had similar increases in serum i-PTH. CONCLUSION: Sevelamer rapidly lowered the serum phosphorus and inhibited the proliferation of PCNA+ cells in this experimental model of early-phase CRF.

[Effects of Niaoduqing granule on urine metabolic profile in chronic renal failure rats].

OBJECTIVE: To investigate the effects of Niaoduqing granule on the urine metabolic profile in chronic renal failure (CRF) rats. METHODS: Thirty six male SD rats were divided into the normal control group, the model group, and the Niaoduqing group with 12 rats in each group. The CRF was induced by gavage of 250 mg·kg-1·d-1 adenine for 21 d. UPLC-Q-TOF-MS/MS technique was used in combination with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the urine metabolic profiles in three groups. The endogenous substances with the variable importance projection (VIP)>1 and P<0.05 were screened as the potential biomarkers for CRF, and enrichment analysis of metabolic pathways was carried out. RESULTS: Compared with the normal control group, the model group had lower body weight, higher kidney coefficient, higher serum creatinine and urea nitrogen levels (all P<0.01), while the above indexes in the Niaoduqing group were ameliorated compared with the model group (all P<0.01). Fifteen potential biomarkers were found in the urine of the model group, which were involved in 9 metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylate and dicarboxylate metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle, glycerophosphatide metabolism, tryptophan metabolism and tyrosine metabolism. CONCLUSIONS: Niaoduqing granules has therapeutic effect on rats with CRF, which may be related to the regulation of amino acid metabolism, lipid metabolism and energy metabolism.

Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids.

ETHNOPHARMACOLOGICAL RELEVANCE: The flower of Abelmoschus manihot (Linn.) Medicus (A. manihot), as a traditional Chinese Herbal medicine, was used widely in China with efficacy of inducing diuresis for treating strangurtia, and subdhing swelling and detoxicating. It has been reported that Huangkui capsule, prepared by the extract of the flower of A. manihot, can reduce the content of urinary protein, serum creatinine and serum urea nitrogen in nephropathy rats and processes renoprotective activity, while the action mechanism need to illuminate deeply. AIMS OF THE STUDY: In this study, we investigated the protection effect of Huangkui capsule on tubulointerstitial fibrosis in chronic renal failure (CRF) rats and its mechanism against high glucose-induced epithelial to mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2) of its bioactive components. MATERIALS AND METHODS: The animals were divided into normal group, CRF model group and Huangkui capsule-treated group. Hematoxylin eosin (HE) staining and Masson staining were applied to observe pathological changes in renal tissue of different groups. Biochemical indicators including serum urea nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured according to the manufacturer's instructions of kits. HK-2 cell damaged model was established to access the protection effect and action mechanism of five main flavonoids from Huangkui capsule. The experimental cells were divided into eight groups: control group, model group, positive drug group and five main flavonoids treated groups. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine the reactive oxygen species (ROS) in different groups. Western blot was applied to analyze the expression of pathogenesis-related proteins in different groups. RESULTS: The results stated that Huangkui capsule significantly inhibited the elevation of Scr, BUN, UP, the expression of α-smooth muscle actin (α-SMA), phosphorylation-extracellular signal-regulated kinase (p-ERK1/2), NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in adenine-induced CRF rats. The main bioactive components of quercetin (QT), hyperoside (HY), isoquercitrin (IQT), gossypetin-8-O-ß-D-glucuronide (GG) and quercetin-3'-O-glucoside (QG) at the dosage of 100µM, like NADPH oxidase inhibitor diphenyleneiodonium, exhibited a significant effect on inhibiting the expression of α-SMA, p-ERK1/2, NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in high glucose-induced HK-2 cells, especially GG. CONCLUSIONS: These results demonstrated that Huangkui capsule and the flavonoids components prevent tubulointerstitial fibrosis in CRF rat involvement in the action mechanism of inhibiting NADPH oxidase/ROS/ERK pathway.

End-Stage Renal Disease Outcomes among the Kaiser Permanente Southern California Creatinine Safety Program (Creatinine SureNet): Opportunities to Reflect and Improve.

OBJECTIVES: The Kaiser Permanente Southern California (KPSC) creatinine safety program (Creatinine SureNet) identifies and outreaches to thousands of people annually who may have had a missed diagnosis for chronic kidney disease (CKD). We sought to determine the value of this outpatient program and evaluate opportunities for improvement. METHODS: Longitudinal cohort study (February 2010 through December 2015) of KPSC members captured into the creatinine safety program who were characterized using demographics, laboratory results, and different estimations of glomerular filtration rate. Age- and sex-adjusted rates of end-stage renal disease (ESRD) were compared with those in the overall KPSC population. RESULTS: Among 12,394 individuals, 83 (0.7%) reached ESRD. The age- and sex-adjusted relative risk of ESRD was 2.7 times higher compared with the KPSC general population during the same period (94.7 vs 35.4 per 100,000 person-years; p < 0.001). Screening with the Chronic Kidney Disease Epidemiology Collaboration (vs Modification Diet in Renal Diseases) equation would capture 44% fewer individuals and have a higher predictive value for CKD. Of those who had repeated creatinine measurements, only 13% had a urine study performed (32% among patients with confirmed CKD). CONCLUSION: Our study found a higher incidence of ESRD among individuals captured into the KPSC creatinine safety program. If the Chronic Kidney Disease Epidemiology Collaboration equation were used, fewer people would have been captured while improving the accuracy for diagnosing CKD. Urine testing was low even among patients with confirmed CKD. Our findings demonstrate the importance of a creatinine safety net program in an integrated health system but also suggest opportunities to improve CKD care and screening.

Effect of cholecalciferol supplementation on urine podocyte-associated messenger RNAs in patients with chronic kidney disease. / Efeito da suplementação de colecalciferol nos RNA mensageiros urinários associados ao podócito em pacientes com doença renal crônica.

INTRODUCTION: Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. OBJECTIVE: To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. METHODS: A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months. Serum 25(OH)D level, estimated glomerular filtration rate (eGFR), proteinuria, and urine mRNA of nephrin, podocin, podocalyxin, transient receptor potential cation channel 6, vascular endothelial growth factor A, and transforming growth factor beta were assessed before and after intervention. RESULTS: eGFR declined at an average rate of -4.71 mL/min/1.73 m2 (p = 0.010 vs. baseline), being 28 ± 16 mL/min/1.73 m2 at six months. No changes in proteinuria or mineral and bone metabolism parameters were observed after cholecalciferol supplementation. Urinary podocyte-associated mRNAs did not change significantly after treatment. However, patients who achieved 25(OH)D level > 20 ng/mL at six months showed a trend of reduction of urinary nephrin and podocin mRNA levels; in patients with 25(OH)D that remained < 20 ng/mL there was a significant increase in urinary podocalyxin, and a trend of higher expression of urinary nephrin and podocin mRNA. CONCLUSION: Six months of cholecalciferol supplementation had no effect on urine podocyte-associated mRNA profile of patients with advanced CKD. The protective effect of vitamin D or its analogues on the glomerular podocyte should be investigated in early stages of CKD with a longer treatment period.

Efeito da suplementação de colecalciferol nos RNA mensageiros urinários associados ao podócito em pacientes com doença renal crônica / Effect of cholecalciferol supplementation on urine podocyte-associated messenger RNAs in patients with chronic kidney disease

RESUMO Introdução: A vitamina D reduz a albuminúria em pacientes com doença renal crônica (DRC), mas o seu efeito sobre os podócitos glomerulares ainda não é claro. Objetivos: Avaliar se a suplementação de colecalciferol reduz os RNAm urinários associados ao podócito em pacientes com DRC. Métodos: Vinte e sete pacientes com DRC estágios 2 a 4 e níveis sub-ótimos de 25-hidroxi-vitamina D [25(OH)D] sérica foram tratados com colecalciferol por seis meses. Foram medidos antes e após a intervenção a 25(OH)D sérica e o RNAm urinário da nefrina, podocina, podocalixina, receptor transitório potencial do canal de cátions, subfamília C, membro 6 (TRPC6), fator A de crescimento do endotélio vascular (VEGF-A) e fator de crescimento transformador beta (TGF-β1). Resultados: A TFGe reduziu em média 4,71 mL/min/1,73 m2 (p = 0,010 vs. basal), sendo 28 ± 16 mL/min/1,73 m2 aos seis meses. Os RNAm dos produtos do podócito na urina não tiveram alteração significativa após o tratamento. Entretanto, pacientes que atingiram níveis de 25(OH)D ≥ 20 ng/mL aos 6 meses tiveram tendência de redução do RNAm da nefrina e da podocina na urina; nos pacientes em que a 25(OH)D permaneceu < 20 ng/mL houve aumento significativo da podocalixina, e tendência de maior expressão do RNAm da nefrina e da podocina. Conclusão: A reposição de colecalciferol por seis meses não teve efeito sobre os RNAm associados ao podócito nestes pacientes com DRC avançada. O efeito protetor da vitamina D ou seus análogos sobre o podócito glomerular deve ser investigado em estágios mais precoces da DRC e com maior tempo de tratamento.

ABSTRACT Introduction: Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. Objective: To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. Methods: A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months. Serum 25(OH)D level, estimated glomerular filtration rate (eGFR), proteinuria, and urine mRNA of nephrin, podocin, podocalyxin, transient receptor potential cation channel 6, vascular endothelial growth factor A, and transforming growth factor beta were assessed before and after intervention. Results: eGFR declined at an average rate of -4.71 mL/min/1.73 m2 (p = 0.010 vs. baseline), being 28 ± 16 mL/min/1.73 m2 at six months. No changes in proteinuria or mineral and bone metabolism parameters were observed after cholecalciferol supplementation. Urinary podocyte-associated mRNAs did not change significantly after treatment. However, patients who achieved 25(OH)D level > 20 ng/mL at six months showed a trend of reduction of urinary nephrin and podocin mRNA levels; in patients with 25(OH)D that remained < 20 ng/mL there was a significant increase in urinary podocalyxin, and a trend of higher expression of urinary nephrin and podocin mRNA. Conclusion: Six months of cholecalciferol supplementation had no effect on urine podocyte-associated mRNA profile of patients with advanced CKD. The protective effect of vitamin D or its analogues on the glomerular podocyte should be investigated in early stages of CKD with a longer treatment period.

Urinary metabonomic study of the surface layer of Poria cocos as an effective treatment for chronic renal injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus. The epidermis of the sclerotia ("Fu-Ling-Pi" in Chinese) is used as a diuretic and traditionally used for promoting urination and reduce edema. AIM OF THE STUDY: Traditional Chinese medicines (TCM) treat many diseases through multi-components, multi-ways and multi-targets. However, the molecular mechanisms of TCM are not yet well understood. In the present work, ultra performance liquid chromatography-based metabonomics analysis was applied to investigate the urinary metabolite profiling of the renoprotective effect of FLP on adenine-induced chronic kidney disease (CKD) rat model and involved possible mechanism. MATERIAL AND METHODS: A metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) data collection technique was developed. The resulting dataset was analyzed by principal component analysis and partial least squares discriminant analysis. The identification of all potential biomarkers was performed using reference standard by comparing their mass spectra, MS(E) fragments information, isotopic pattern and MassLynx i-FIT algorithm. RESULTS: By partial least squares-discriminate analysis, 15 biomarkers in rat urine were identified and 11 of them were related to the pathway of adenine metabolism and amino acid metabolism. Among these biomarkers, eight biomarkers like adenine, L-acetylcarnitine, 8-hydroxyadenine, hypoxanthine, creatine, methionine, phytosphingosine and phenylalanine were reversed to the control level in FLP-treated group and six biomarkers like 2,8-dihydroxyadenine, indole-3-carboxylic acid, 3-methyldioxyindole, ethyl-N2-acetyl-L-argininate, 3-O-methyldopa and xanthurenic acid were reversed to high control group by FLP, which indicates that the urinary metabolic pattern significantly changed after FLP treatment. CONCLUSIONS: Our study indicates that FLP treatment can ameliorate CKD by intervening in some dominating metabolic pathways, such as adenine metabolism and amino acid metabolism. The metabonomic results not only supplied a systematic view of the development and progression of CKD and mechanism studies of FLP but also provided the theoretical basis for the prevention or treatment of CKD.

Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus.

PURPOSE: Diabetic nephropathy and proteinuria are important risk factors for both end-stage renal disease and cardiovascular events. The present study aimed to identify the factors associated with nephrotic-range proteinuria in patients with advanced diabetic nephropathy. METHODS: This cross-sectional study enrolled 386 diabetic patients with chronic kidney disease (CKD) stages 3-5, from our outpatient Department of Nephrology. Urinary protein-to-creatinine ratio was recorded. Additionally, other laboratory parameters, body mass index, blood pressure, comorbidities, and medications were also reviewed. RESULTS: The mean age of the patients was 65.1 ± 11.6 years. Among patients with CKD stage 3 and 4, the odds ratio (OR) for nephrotic-range proteinuria in relation with systolic blood pressure significantly increased starting from 121 mmHg (OR 7.04 and 11.79 for systolic blood pressure of 121-140 and ≥141 mmHg, respectively, in comparison with systolic blood pressure below 121 mmHg). In addition, serum phosphorus ≥4.7 mg/dl was associated with significantly higher risk (OR 15.45) for severe proteinuria, compared with a phosphorus level ≤2.6 mg/dl. Finally, hypertriglyceridemia ≥241 mg/dl was also associated with higher OR for severe proteinuria, compared with a triglyceride level ≤200 mg/dl. Similar associations were found in patients with CKD stage 5. CONCLUSIONS: Higher systolic blood pressure, serum phosphorus, and triglyceride levels are associated with nephrotic-range proteinuria in patients with diabetic nephropathy and CKD stage 3-5. Further studies should clarify whether a reduction in serum phosphorus would lead to a decrease in proteinuria in these patients.

Hyperphosphatemia is associated with overt proteinuria in non-diabetic patients with late-stage chronic kidney disease: a cross-sectional study.

PURPOSE: Proteinuria plays an important role in the progression of chronic kidney disease (CKD), as well as a powerful predictor of cardiovascular morbidity and mortality. The aim of our study was to investigate the potential determinants associated with overt proteinuria in non-diabetic patients with late-stage CKD. METHODS: Between January 2006 and September 2011, a total of 418 non-diabetic patients with CKD stage 3-5 were enrolled from the outpatient department of nephrology. Urinary protein-to-creatinine ratio and serum phosphorus were determined. Other laboratory parameters, associated comorbidities, medication use, body mass index, and blood pressure were also assessed. RESULTS: The mean age of the patients was 66.7 ± 14.0 years. In multiple logistic regression analysis and adjusting for established risk factors, the odds ratios for overt proteinuria were 3.96 (95 % confidence interval, 1.80-8.76; p = 0.001) for higher serum phosphorus level (≥4.3 mg/dl) and 3.56 (95 % confidence interval, 1.47-8.63; p = 0.005) for hypercholesterolemia (≥217 mg/dl), compared to subjects with serum phosphorus <3.3 mg/dl and cholesterol level 158-184 mg/dl. The similar significant findings remained robust in individuals not receiving phosphate binder. CONCLUSIONS: Hyperphosphatemia and high serum cholesterol are associated with overt proteinuria in non-diabetic patients with late-stage CKD. Further studies should clarify whether this relation is causal and whether serum phosphorus level should be a new therapeutic target for proteinuria reduction.

[Study on proteins in urine of chronic renal failure patients of different TCM syndrome types].

OBJECTIVE: To study different protein expressions in urine of chronic renal failure (CRF) patients of different Chinese medicine (CM) syndrome types. METHODS: Recruited were 251 CRF inpatients at the Department of Nephrology, Affiliated Longhua Hospital, Shanghai University of Traditional Chinese Medicine from January 2009 to January 2010. Of them, there were 34 patients in Gan-Shen yin deficiency group (GSYDG), 75 in Pi-Shen qi deficiency group (PSQDG), 56 in Pi-Shen qi-yin deficiency group (PSQYG), 32 in Pi-Shen yang deficiency group (PSYDG), and 54 in yin-yang deficiency group (YYDG). Another 50 healthy subjects were recruited as the control group. The proteomic study of the urine was performed with H4 gene chip using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS). The gene chips were scanned and analyzed using protein array reader PBSII. RESULTS: A total of 49 differential protein peaks were detected between CM syndrome types groups and the control group (P<0.01). The area under the ROC curve of different CM syndrome types showed that obvious difference existed between GSYDG and PSQDG, PSQYG, PSYDG, and YYDG. Obvious difference existed between PSQYD and PSYDG. General difference existed between PSQDG and PSQDG as well as PSYDG. General difference existed between PSQYD and YYDG or between PSYDG and YYDG. No obvious difference existed between PSQDG and YYDG. CONCLUSION: Urine protein biomarkers could reflect different biological features of CRF patients of different CM syndrome types to some extent.

Lanthanum carbonate reduces urine phosphorus excretion: evidence of high-capacity phosphate binding.

The effectiveness of phosphate binders can be assessed by evaluating urinary phosphorus excretion in healthy volunteers, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. Healthy volunteers were enrolled into one of five separate randomized trials; four were open label and one double blind. Following a screening period of ≤28 days, participants received differing tablets containing lanthanum carbonate [LC, 3000 mg/day of elemental lanthanum (in one study other doses were also used)]. Participants received a standardized phosphate diet and remained in the relevant study center throughout the duration of each treatment period. The end point in all studies was the reduction in urinary phosphorus excretion. Reductions in mean 24-h urinary phosphorus excretion in volunteers receiving a lanthanum dose of 3000 mg/day were between 236 and 468 mg/day over the five separate studies. These data in healthy volunteers can be used to estimate the amount of reduction of dietary phosphate absorption by LC. The reduction in 24-h urinary phosphorus excretion per tablet was compared with published data on other phosphate binders. Although there are limitations, evidence suggests that LC is a very effective phosphate binder in terms of binding per tablet.

[Study on correlated proteins in the urine of chronic renal failure patients of Chinese medicine damp syndrome based on SELDI-TOF-MS technique].

OBJECTIVE: To investigate the protein markers in the urine of chronic renal failure (CRF) patients of Chinese medicine damp syndrome (CMDS) based on surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technique. METHODS: The urine was sampled from 90 CRF patients of CMDS and 60 CRF patients of non-CMDS. Then the proteomics of the urine was studied by H4 gene chip. The chips were scanned and analyzed using PBS II (a protein chip reader). RESULTS: (1) Totally 25 differential protein peaks were identified in the e/m range of 1 000-20 000 of the protein atlas of the two groups (P < 0.01). (2) The urine protein predictive model of CFR patients of CMDS was established after bioinformatic analysis. Totally 4 biomarkers consisting of M/Z 8 654.96, M/Z 2 081.65, M/Z 18 667.3, and M/Z 2 242.14 were obtained, which could better classify the samples of CMDS and those of non-CMDS. Its accuracy rate was 84.7%, the sensitivity was 92.2%, and the specificity was 73.3%. (3) Between the CMDS group and the non-CMDS group, 7 kinds of proteins in the urine were possibly identified by SwissProt Database. CONCLUSIONS: This study had primarily screened the protein markers in the urine of CRF patients of CMDS, and established the predictive model. The protein markers in the urine were identified by database, thus providing certain experimental evidence for clinical typing of CRF patients of CMDS.

Clinical metabolomics and urinary NGAL for the early prediction of chronic kidney disease in healthy adults born ELBW.

BACKGROUND: Clinical metabolomics is a recent "omic" technology which is defined as a global holistic overview of the personal metabolic status (fingerprinting). This technique allows to prove metabolic differences in different groups of people with the opportunity to explore interactions such as genotype-phenotype and genotype-environment type, whether normal or pathological. AIM: To study chronic kidney injury 1) using urine metabolomic profiles of young adults born extremely low-birth weight (ELBW) and 2) correlating a biomarker of kidney injury, urinary neutrophil gelatinase-associated lipocalin (NGAL), in order to confirm the metabolomic injury profile. METHOD: Urine samples were collected from a group of 18 people (mean: 24-year-old, std: 4.27) who were born with ELBW and a group of 13 who were born at term appropriate for gestational age (AGA) as control (mean 25-year-old, std: 5.15). Urine samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy, and then submitted to unsupervised and supervised multivariate analysis. Urine NGAL (uNGAL) was measured using ARCHITECT (ABBOTT diagnostic NGAL kit). RESULTS: With a multivariate approach and using a supervised analysis method, PLS-DA, (partial least squares discriminant analysis) we could correlate ELBW metabolic profiles with uNGAL concentration. Conversely, uNGAL could not be correlated to AGA. CONCLUSIONS: This study demonstrates the relevance of the metabolomic technique as a predictive tool of the metabolic status of exELBW. This was confirmed by the use of uNGAL as a biomarker which may predict a subclinical pathological process in the kidney such as chronic kidney disease.

[Clinical and biochemical characteristics of predialysis patients in terms of 25 hydroxy vitamin D levels]. / Características clínicas y bioquímicas de pacientes en prediálisis con respecto a los niveles de 25 hidroxivitamina D.

INTRODUCTION: Decreased levels of 25 hydroxyvitamin D (25[OH]D) have been reported in patients with chronic kidney disease (CKD). The pleiotropic effects of vitamin D are known to go beyond mineral metabolism. OBJECTIVES: The aims of this study were to: 1) Determine the 25(OH)D levels in predialysis outpatients. 2) Find out the clinical and biochemical characteristics of patients with 25(OH)D deficiency, and predictive factors for the deficiency. PATIENTS AND METHODS: An observational study in 79 predialysis outpatients was performed. Clinical and biochemical parameters were analysed in terms of nutrition, inflammation and mineral metabolism in relation to serum levels of 25(OH)D. Levels of 25(OH)D lower than 15ng/ml were considered to be deficient. RESULTS: Serum levels of 25(OH)D were deficient in 41 patients (52%). The comparative study regarding levels of vitamin 25(OH)D showed the group of patients with a deficiency, i.e. those with less than 15ng/ml, were older (70 ± 11.97 vs. 61 ± 14.5; p = 0.005), had a greater body mass index, BMI, (30±4.06 vs. 27.1 ± 5.08; p = 0.003) and increased proteinuria (1.42g/24h (0.53-2.96) vs. 0.51 (0.20-1.48), p = 0.009). This group included a greater number of diabetic patients: 20 (76.9%) vs. 6 (23%), p = 0.002. They had a higher level of parathyroid hormone (PTH): 359 (239-658) vs. 233 (129-323), p = 0.000; and more patients were under treatment with Calcitriol: 28 (62.2%) vs. 17 (37.8%), p = 0.024. In the multivariate analysis, high levels of PTH (OR 13.38; CI 95% [2.94-60.89]; p=0.001), increased proteinuria (OR 4.41; CI 95% [1.12-17.25]; p = 0.033); and being diabetic (OR 5.713; CI 95% [1.43-22.77]; p = 0.014) were independent predictor factors for patients with 25(OH)D deficiency. CONCLUSIONS: In our study, we observed a high prevalence of 25(OH)D deficiency among patients with CKD. The increased levels of PTH, the increase of proteinuria and the presence of diabetes were independent predictors for 25(OH)D deficiency.

[Effect of total saponins of Panax notoginseng on urinary albumin in patients with chronic renal failure].

OBJECTIVE: To observe the curative effect of total saponins of Panax notoginseng (PNS) on chronic renal failure (CRF). METHODS: Sixty patients with CRF (non-uremic) were randomly divided into the experimental and the control groups, with 30 cases in each group. Patients in experimental group were given PNS extract Xueshuantong 0.45 g on the basis of the general symptomatic treatment, once a day. While the patients in the control group were treated with Bailing capsule of 1.0 g, three times a day. Total therapeutic courses were 2 months for both groups. The changes in renal function, hemoglobin, 24-hour urinary protein, parathyroid hormone (PTH), N-acutely-ß-D-glucosaminidase (NAG) were observed in two groups. RESULTS: After 2 months, the changes in serum creatinine (SCr), clearance rate of endogenous creatinine (CCr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin, 24-hour urinary protein were improved in both groups, while the changes in CCr, BUN, hemoglobin, 24-hour urinary protein in the experimental group were more obvious [CCr (ml/s): 0.36±0.13 vs. 0.34±0.12, BUN (mmol/L): 15.66±9.05 vs. 20.32±8.30, hemoglobin (g/L): 101.2±9.4 vs. 95.4±8.7, 24-hour urinary protein (mg): 1 040±450 vs. 2 360±390, all P<0.05]. After treatment, NAG (U/L) were decreased significantly only in control group (18.2±9.8 vs. 28.9±12.0, P<0.05). CONCLUSION: PNS has a good therapeutic effect for the treatment of CRF (non-uremic). It possesses such therapeutic effects as improving the renal function, and lowering urine protein.

Inferring disease mechanisms from epidemiological data in chronic kidney disease: calcium and phosphorus metabolism.

BACKGROUND/AIMS: By applying numerical filtering to epidemiological data of 2,512 chronic kidney disease patients, we aimed to identify some of the underlying mechanisms of the calcium/phosphorus metabolism perturbations. METHODS: The measured variables, serum calcitriol, calcidiol, total calcium ([Ca](s)) and phosphorus ([P](s)) and the urinary excretions of calcium and phosphorus, were paired in the same patients with the glomerular filtration rate (GFR) or the serum concentrations of parathormone (i[PTH](s)) (used as independent variables) numerically filtered with a moving average and partitioned into 15-25 frequency classes. All variables exhibited unimodal frequency distributions. RESULTS: There was a steep fall of i[PTH](s), [P](s), and urinary excretion fractions of Ca and P up to a value of GFR in the range of 25-45 ml/min/1.73 m2. The increase in the phosphorus urinary excretion preceded the steep increase in i[PTH](s). Except [Ca](s), all factors exhibited their physiological correlation with i[PTH](s) when GFR was above 90 ml/min/1.73 m2 and reverted to a feedback correlation below 80 ml/min/1.73 m2. CONCLUSION: The perturbation of mineral metabolism in chronic kidney disease results in the maintenance of a normal range of [Ca](s) and [P](s) acting as the controlled factors at the cost of large variations of i[PTH](s), and calcium and phosphate urinary excretions behaving as controlling factors.

Fermentable carbohydrate supplementation alters nitrogen excretion in chronic renal failure.

BACKGROUND: Considerable attention has been given to the impact of nutrition on kidney disease. Most dietary attempts to treat chronic renal failure (CRF) and to decrease uremia use a protein restriction. An alternative dietetic approach based on fermentable carbohydrate (FC) supplementation of the diet could lead to the same urea-lowering effect by increasing urea nitrogen (N) excretion in stool, with a concomitant decrease of the total N quantity excreted in urine. METHODS: In the present prospective study, the impact of FC (40 g/d) on uremia and on N excretion routes was investigated during 5 weeks in nine CRF patients in the presence of a moderated restrictive protein diet (0.8 g/kg/d). Patients were their own controls and were treated by the cross-over method after randomization (5 weeks with FC versus 5 weeks without FC). RESULTS: Feeding FC significantly increased the quantity of N excreted in stool from 2.1 +/- 0.8 to 3.2 +/- 1.1 g/d (+51%) (P < .01) and decreased, in parallel, the urinary N excretion from 9.4 +/- 1.7 to 8.3 +/- 1.4 g/d (-12%) (P < .01). The total N quantities excreted by the two routes were unchanged by the FC, which shows that the FC was efficient to shift N excretion from the urinary route toward the digestive route. As a result of the increase of urea transfer into the colon, the plasma urea concentration was significantly decreased from 26.1 +/- 8.7 to 20.2 +/- 8.2 mmol/L (-23%) (P < .05). CONCLUSIONS: These results show the same beneficial effects in CRF as those obtained with a restrictive protein diet without its nutritional drawbacks. This should be confirmed by other prospective works over a longer duration and a larger number of patients to study the effects of FC on CRF progression and on CRF terminal stage tolerance.

Phase I and pharmacokinetic study of pemetrexed administered every 3 weeks to advanced cancer patients with normal and impaired renal function.

PURPOSE: This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function. PATIENTS AND METHODS: Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from > or = 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12. RESULTS: Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and non-supplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR > or = 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2. CONCLUSION: Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR > or = 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.

Ozone therapy on rats submitted to subtotal nephrectomy: role of antioxidant system.

Chronic renal failure (CRF) represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy). Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg) for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks). Renal plasmatic flow (RPF), glomerular filtration rate (GFR), the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function) in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group) showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP) figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD) and catalase (CAT) showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone rectal administrations produced a delay in the advance of the disease, protecting the kidneys against vascular, hemorheological, and oxidative mechanisms. This behavior suggests ozone therapy has a protective effect on renal tissue by downregulation of the oxidative stress shown in CRF.