Nondialyzed Chronic Renal Failure Patients Research Articles

Prevalence of Severe Anemia (Hb ≤ 5 g/dl) in Non-Dialyzed Chronic Renal Failure Patients in the Nephrology and Hemodialysis Department of Point G University Hospital

Introduction: Chronic renal failure (CRF) is defined as glomerular filtration rate (GFR) less than 60 ml/min/1.73m2 for at least three (3) months. Anemia is one of its most common complications. Anemia increases the risk factor for cardiovascular mortality by 18% per gram of hemoglobin loss. Objectives: To determine the prevalence and characteristics of this severe anemia, to determine the indications for transfusion, the complications related to this anemia, the evolution and the prognosis of these patients. Materials and Methods: This was a descriptive study with retrospective data collection over 18 months (January 1, 2017 to June 30, 2018) that included hospitalized CRF patients. Were included, non-dialyzed chronic renal failure patients with Hb ≤ 5 g/dl hospitalized during the said period. Not included were chronic renal failure patients with an Hb level ≥ 5 g/dl, those followed up and/or hospitalized outside the study period. Results: Among 1176 patients, 26 had severe anemia (Hb level ≤ 5 g/dl) on CRF, a prevalence of 2.21%. The mean age was 40 years ± 32.62 with extremes of 15 and 67 years. Seventeen women and 9 men. The etiology of chronic renal failure (CRF) was hypertensive vascular nephropathy in 50% of cases. CRF was end-stage in 18 patients (69.2%). The mean hemoglobin level was 4.10 g/dl ± 0.64 with extremes of 2 and 5 g/dl. The anemia was microcytic hypochromic in 50% and aregenerative (96.2%). The main symptoms were asthenia in 20 cases (76.9%), dizziness in 20 cases (76.9%), exertional dyspnea in 19 cases (73.1%). Signs of cardiac decompensation (n = 12) were jugular turgor 10 cases (38.5%), hepato-jugular reflux 06 cases (23.1%), mitral insufficiency murmur 06 cases (23.1%). The main complication was left ventricular hypertrophy 17 cases (77.3%). There was no correlation between anemia and sex (p = 0.291), age (p = 0.778), malaria (p = 0.158), etiology of CRF (p = 0.26). The evolution after treatment of anemia was favorable in 19 patients (73.1%), unfavorable in 02 patients (7.7%) and 05 deaths (19.2%). The deaths were of cardiovascular cause: left ventricular insufficiency 04 cases, stroke 01 case. Conclusion: Anemia is frequent in patients with chronic renal failure and remains an important risk factor for cardiovascular disease and poor general condition.

Deceleration of Disease Progress Through Ayurvedic Treatment in Nondialysis Stages IV-V Patients with Chronic Renal Failure: A Quasi-Experimental Clinical Pilot Study with One Group Pre- and Postdesign and Two Premeasurements.

Objective: The aim of this study was to evaluate the effects of Ayurvedic treatment on deceleration of the disease progress of nondialysis patients with stage IV or V chronic renal failure (CRF). Materials and Methods: A complex oral and proctocolonic Ayurvedic multiherbal medication was administered daily for 1 month to inpatients. Thereafter, patients were treated as outpatients with oral medication for additional 5 months. Four renal function tests (RFTs) were evaluated at various time points (TPs): (1) 6 months before baseline (TP -6), (2) at baseline (TP 0), and (3) after completion of 6 months of treatment (TP +6). Repeated-measures analysis of variance (ANOVA) with Greenhouse-Geisser correction and Friedman's ANOVA by ranks were used to analyze the RFTs. For post hoc tests, the Bonferroni correction was applied. Bias-corrected effect sizes (Hedges) for the treatment were calculated. Results: Sixty-four nondialysis CRF patients with laboratory investigations of the preceding 6 months were included; 12 patients discontinued the treatment. Fifty-two patients with stage IV or V at baseline completed the study. Mean concentrations of estimated glomerular filtration rate (eGFR), serum creatinine, and hemoglobin differed significantly between TPs (eGFR: F = 15.3, p < 0.001; serum creatinine: F = 29.3, p < 0.001; blood urea: F = 2.0, p = 0.159; hemoglobin: F = 53.9, p < 0.001). Pairwise comparisons of the mean differences between TPs are significant for eGFR, creatinine, and hemoglobin. For blood urea, a significant decrease was observed for the treatment period [15.9(↓) mg/dL, standard error 4.0; n = 52], but a nonsignificant increase was observed for the pretreatment period [16.2(↑) mg/dL, standard error 9.8] due to insufficient data for TP -6 (n = 26). The effect sizes for eGFR, creatinine, blood urea, and hemoglobin were medium (0.45, 0.53, 0.44, and 0.30). Conclusions: After 6 months of treatment, statistically and clinically significant improvements of eGFR, creatinine, blood urea, and hemoglobin and a significant shift to better CRF stages were observed. Several cardinal symptoms were also significantly reduced. Randomized controlled trials are warranted to evaluate the effects in comparison to usual care.

Changes in Freet3;T4 Thyroxine and Thyrotropin in Hemodialysis and Non-Dialysis Chronic Renal Failure Patients

The metabolism, degradation and excretion of thyroid hormones is associated with renal function. The study was aimed to evaluate the serum urea, creatinine and thyroid function in hemodialysis and non-dialysis patients. The levels of creatinine increased in non-dialysis. T3, FT3 and FT4 decreased in hemodialysis chronic renal failure, but T4 and TSH were within normal values.

Incidence of Infection and Inhospital Mortality in Patients With Chronic Renal Failure After Total Joint Arthroplasty

BackgroundPatients with chronic renal failure (CRF) may require total joint arthroplasty (TJA) to treat degenerative joint disease, fractures, osteonecrosis, or amyloid arthropathy. There have been conflicting results, however, regarding outcomes of TJA in patients with chronic renal disease. The aim of this case-controlled study was to determine the outcome of TJA in patients with CRF, with particular interest in the incidence of infections and inhospital mortality. MethodsWe queried our electronic database to determine which patients among the 29,389 TJAs performed at our institution between January 2000 and June 2012 had a diagnosis of CRF. A total of 359 CRF patients were identified and matched for procedure, gender, age (±4 years), date of surgery (±2 years), and body mass index (±5 kg/m2) in a 2:1 ratio to 718 control patients. ResultsThe incidence of infection and inhospital mortality was not significantly different between the nondialysis CRF patients and controls, whereas it was significantly higher in dialysis-dependent end-stage renal failure patients compared to controls. Of the 50 CRF patients receiving hemodialysis, 10 (20%) developed surgical site infection, of which 4 (8%) were periprosthetic joint infection, and 4 (8%) died during hospital stay. The odds ratio for infection in the dialysis group was 7.54 (95% confidence interval: 2.83-20.12) and 10.46 (95% confidence interval: 1.67-65.34) for the inhospital mortality. ConclusionWe conclude that end-stage renal failure patients receiving hemodialysis have higher postoperative infection and inhospital mortality rates after an elective TJA procedure, whereas nondialysis CRF patients have similar outcomes compared with the general TJA population.

Effect of continuous care family visiting on disease uncertainty and psychological conditions in non-dialysis chronic renal failure patients

Objective To explore the effect of continuous care family visiting on disease uncertainty and psychological conditions in non-dialysis chronic renal failure patients. Methods Totals of 120 non-dialysis chronic renal failure patients admitted to our department from July 2011 to June 2013 were selected. In accordance with the principle of randomized controlling, patients were divided into observation group and control group, with 60 cases in each. The control group received conventional family supervision, while the observation group underwent continuous care family visiting in addition to traditional family supervision. The illness uncertainty and psychological conditions of two groups were assessed and compared before and after the intervention. Results Before the intervention, disease uncertainty and psychological conditions of the two groups were not significantly different (P>0.05). After the intervention, the scores of sense of uncertainty, complexity, unpredictability, lack of disease-related information or inconformity were (35.3±5.1), (8.7±3.0), (8.8±3.5) and (12.5±2.8), which were significantly better than those in the control group (t=11.70, 11.10, 10.70, 8.21, respectively; P 0.05). After the intervention, the scores of anxiety and depression were (42.1±5.8) and (41.3±5.6) in the observation group, which were significantly lower than those in the control group (t=3.440, 5.740, respectively; P<0.05). Conclusions Continuous care family visiting cannot only significantly alleviate the uncertainty of illness in non-dialysis chronic renal failure patients, but also improve their mental condition and quality of life, and enhance their motivation and adherence to treatment. Key words: Chronic renal failure; Anxiety; Depression; Continuous care family visiting

Carotid artery intima media thickness as a surrogate marker of atherosclerosis in patient with chronic renal failure on hemodialysis.

Background:In patients with chronic renal failure (CRF), carotid artery intima media thickness (CAIMT) is increased when the patients are on hemodialysis. Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis.Aims:This study was done to find out the relationship between carotid artery intima media thickness and hemodialysis in chronic renal failure patients independent of classical risk factors and also the relationship between CAIMT of hemodialyzed patients and nonhemodialyzed CRF patients.Materials and Methods:In this observational study, CAIMT of 78 CRF patients was examined by B-mode ultrasonography. Glomerular filtration rate (GFR) was calculated by using the “Modification of Diet in Renal Disease” formula. CRF patients, who had been on regular hemodialysis treatment (treated thrice weekly) for at least 6 months, were identified as hemodialyzed patients. Data were analyzed by software Statistical package for the social Sciences (SPSS) (17th version).Results:There was significant positive correlation between CAIMT and hemodialysis (P=0.045) independent of traditional risk factors. Hemodialyzed patients had higher mean CAIMT (1136.30±21.21 μm, P<0.001) than mean CAIMT of age and sex matched nondialyzed patients (959.30±23.01 μm).Conclusion:Hemodialysis is an independent risk factor for atherosclerosis in CRF patents. Hemodialyzed patients have significantly higher CAIMT than nondialyzed CRF patients.

A case‐control study on restless legs syndrome in nondialyzed patients with chronic renal failure

Restless legs syndrome (RLS) is a possible consequence of end-stage renal disease. However, conclusive data on the association between RLS and chronic renal failure (CRF) in nondialyzed patients are still lacking. The aims of this study were: (1) to look for an association between RLS and CRF in nondialyzed patients; (2) to analyze the characteristics of RLS and its consequences on nocturnal rest in nondialyzed patients with CRF; (3) to identify possible predictors of RLS occurrence in nondialyzed patients with CRF. We recruited 138 nondialyzed patients with CRF (mean age: 69.8 +/- 11.7 years; male: 61.6%) and 151 controls (mean age: 60.2 +/- 18.6 years; male: 42.4%). An expert in sleep medicine investigated the presence of RLS by means of a face-to-face interview. Fifteen nondialyzed CRF patients and five controls were diagnosed as RLS affected. A multivariate analysis confirmed that RLS was independently associated with CRF in nondialyzed patients (P = 0.004). CRF patients RLS(+) were more commonly women and showed the presence of an iron deficiency compared with the RLS(-) ones. Independent predictors of RLS in nondialyzed CRF patients were: female sex (OR: 10.7, 95% CI: 2.2-31.3; P = 0.004) and percentage of transferrin saturation (OR: 0.6, 95% CI: 0.4-0.9; P = 0.04). This is the first case-control study able to recognize an association between RLS and CRF in patients not yet on dialysis. Nephrologists should investigate and treat RLS in their nondialyzed patients with CRF. In particular, physicians should carefully investigate women and patients with iron deficiency in the presence of RLS symptoms.

Why Are Chronic Kidney Disease Patients Anorexic and What Can Be Done About It?

The progressive decline of glomerular filtration rate in chronic kidney disease patients is associated with a significant reduction in food intake. Approximately one third of chronic dialysis patients complain of a fair or poor appetite and this is related directly to poor patient outcomes. Appetite regulation involves the gastrointestinal tract (ghrelin as an appetite stimulant, and cholecystokinin, glucagon-like peptide-1, and neuropeptide YY as appetite inhibitors); the adipose tissue with leptin, a potent appetite inhibitor; the vagal system; and the brain, which integrates the stimuli in the hypothalamus area. Satiety relies on the melanocortin receptors with serotonin as the main neurotransmitter and is challenged with hunger peptides, namely, neuropeptide Y and agouti-related peptide. In nondialyzed chronic renal failure patients and in maintenance dialysis patients, anorexia is related mainly to the accumulation of unidentified anorexigenic compounds, inflammatory cytokines, and alterations in appetite regulation, such as amino acid imbalance, which increases the transport of free tryptophan across the blood-brain barrier. This creates a hyperserotoninergic state that is prone to low appetite. Treatment of anorexia involves counseling, starting dialysis treatments in uremic chronic kidney disease patients, increasing the dialysis dose, and possibly using appetite stimulants.

Increased Levels of Soluble TNF-α Receptors and Cellular Adhesion Molecules in Patients Undergoing Bioincompatible Hemodialysis

Background: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-α (TNF-α) and TNF-α receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. Methods: The serum concentrations were determined with standard ELISA assays. Results: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 ± 6.2 and 27.1 ± 5.6 ng/ml) and HD patients (45.6 ± 18.4 and 28.7 ± 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 ± 18.4 and 28.5 ± 7.3 ng/ml) and after (HD 240) the HD session (52.1 ± 17.4 and 30.9 ± 8.2 ng/ml) in comparison to control values (5.6 ± 1.3 and 2.4 ± 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-α levels if (HD 0) 22.7 ± 21.5 ng/ml and (HD 240) 21.1 ± 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 ± 761.8 and 567.3 ± 218.8 ng/ml, during HD (T20): 2,172.7 ± 759.2 and 602.3 ± 379.9 ng/ml, and after HD (T240): 2,401.6 ± 756.4 and 648.3 ± 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 ± 472.9 and 165.6 ± 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 ± 241.5 and 217.6 ± 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 ± 21.3 vs. 42.1 ± 18.9 ng/ml and 187.9 ± 66.9 vs. 198.8 ± 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 ± 54.6 and 453.2 ± 231.1 ng/ml in patients prior to HD, 118.7 ± 66.2 and 350.8 ± 114.8 ng/ml during the HD session and then 132.3 ± 61.1 and 368.3 ± 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). Conclusions: The increased circulating TNF-α receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.

크레메진의 만성신부전증 환자 투석도입 지연효과에 대한 최대지불의사액(willingness-to-pay) 추청

To assess the economic value of pharmaceutical therapy with Kremezin, we investigated the maximum amount of willingness-to-pay (WTP) of patients with chronic renal failure (CRF) for a hypothetical effect of Kremezin in delaying the initiation of dialysis treatments. A face-to-face survey was carried out in a sample of 141 CRF patients from 2 dialysis centers, composed of 82 hemodialysis patients, 38 peritoneal dialysis patients, and 21 non-dialysis CRF patients. Using a bidding game method with a starting point of 320,000 Won, which is the average monthly out-of-pocket payment for dialysis treatment, we asked the study subjects how much they would pay per month to receive Kremezin therapy. The mean out-of-pocket monthly WTP for Kremezin was 310,000, 430,000, and 520,000 Won (p<0.05, repeated one-way ANOVA)) when Kremezin delays the initiation of dialysis treatments by 1, 2, and 4 years. Significant correlation between the respondent's WTP and income <TEX>$(r=0.266{\sim}0.368,\;p<0.05)$</TEX> confirmed the construct validity of the WTP instrument. Regression results showed that patients with a higher education, with diabetes as a major causes of CRF, and undergoing hemodialysis treatments tended to express higher WTP for Kremezin. The economic value of WTP from the perspective of patients varied from 310,000 to 520,000 Won depending on the effect size of Kremezin. The mean WTP was higher than 32,000 Won, only when the hypothetical effect of Kremezin in delaying the initiation of dialysis is for 2 years. This implies that Kremezin might be the preferred choice of therapy by CRF patients if it delays the initiation of dialysis treatment for at least 2 years.

Sleep-Disordered Breathing in Nondialyzed Patients with Chronic Renal Failure

The prevalence and significance of sleep-disordered breathing (SDB) in dialysis-independent chronic renal failure (CRF) remains unknown. We studied the presence of SDB in nondialyzed CRF patients. Diagnostic polysomnography was performed in consecutive stable nondialyzed CRF patients. Inclusion criteria were age <or=70 years, absence of systolic dysfunction or history of pulmonary edema, FEV(1) > 70% pr, absence of neurologic disease or hypothyroidism, and calculated creatinine clearance <40 ml/min. Thirty-five patients (19 male, 16 female) were studied. An apnea-hypopnea index (AHI) >or=5/h was present in 54.3% (almost exclusively obstructive events). AHI correlated with urea (r = 0.35, p = 0.037), age (r = 0.379, p = 0.025), and body mass index (BMI) (r = 0.351, p = 0.038), but not with creatinine clearance. AHI or SDB were unrelated to gender. In nondiabetics (n = 25), AHI correlated with urea (r = 0.608, p = 0.001) and creatinine clearance (r = -0.50, p = 0.012). Nondiabetics with severe CRF (calculated GFR < 15 ml/min/1.73 m(2)) had a significantly higher AHI compared with less severe CRF. Restless legs syndrome (RLS) was present in 37.1% and periodic limb movements in 28.6%. Daytime sleepiness was not associated with respiratory events, but was more common in patients with RLS. The prevalence of SDB and RLS is high in dialysis-independent CRF. SDB weakly correlates with indices of kidney function and this association becomes stronger in nondiabetics.

Comparison of Effect of Vitamin E-Coated Dialyzer and Oral Vitamin E on Hemodialysis-Induced Cu/Zn-Superoxide Dismutase

Background: We reported earlier that production of Cu/Zn-superoxide dismutase (SOD) increases markedly in hemodialysis patients but not in non-dialyzed chronic renal failure (CRF) patients. In this study, we compared the antioxidant effects of oral vitamin E supplementation (VE-PO) and vitamin E coating of a dialyzer (VE-BMD) by measuring increased Cu/Zn-SOD in hemodialysis patients. Methods: 31 hemodialysis patients were divided into two groups: 16 hemodialysis patients underwent usual dialysis with vitamin E supplementation 600 mg/day while 15 others were dialyzed using vitamin E-coated membrane for 6 months. Total plasma SOD activity was determined by NBT method, plasma Cu/Zn-SOD contents by ELISA and Cu/Zn-SOD mRNA in leukocytes by RT-PCR. Results: VE-PO and VE-BMD showed almost comparable effects on Cu/Zn-SOD contents and its mRNA levels in hemodialysis patients. VE-PO resulted in a progressive decrease of Cu/Zn-SOD content (p < 0.001). A comparable progressive decrease was observed also in VE-BMD (p < 0.0001). Both VE-PO and VE-BMD resulted in a progressive decrease of Cu/Zn-SOD mRNA (p < 0.01), which reached the level of non-dialyzed CRF patients.

MRNA Study on Cu/Zn Superoxide Dismutase Induction by Hemodialysis Treatment

Background/Aims: There is little or no controversy about the increased oxidative stress of hemodialysis (HD) patients. Several reports show that the activity of superoxide dismutase (SOD), one of the major endogenous antioxidant enzymes, in plasma is elevated among HD patients. It is still unclear, however, whether this elevation is due to the promotion of SOD production or a decrease in renal excretion of SOD. This study was designed to investigate the cause of the SOD activation in HD patients, and we examined the expression of SOD mRNA levels in leukocytes of patients with chronic renal failure. Methods: The total plasma SOD activity was determined by the nitroblue tetrazolium method, plasma SOD contents by ELISA, and SOD mRNA levels in leukocytes by RT-PCR. Results: Our results demonstrated that contents and mRNA levels of Cu/Zn SOD in HD patients are 4.4 times and 2.0 times, respectively, as large as those in healthy controls. Furthermore, in contrast to nondialyzed chronic renal failure patients, we observed higher concentrations of Cu/Zn SOD in plasma and a more enhanced mRNA expression of Cu/Zn SOD in leukocytes of HD patients. Conclusion: Increased Cu/Zn SOD mRNA reflects enhanced antioxidant capacity of leukocytes and can be a promising oxidative stress marker in HD patients.

Monitoring the Content of Reticulocyte Hemoglobin (CHr) as the Progression of Anemia in Nondialysis Chronic Renal Failure (CRF) Patients

Background: We previously showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status in chronic dialysis patients with erythrocytopoiesis. The CHr was significantly correlated with conventional parameters of iron deficiency in dialysis patients. We attempted to utilize the measurement of CHr levels to monitor iron status and clarify the changes in iron levels that occur as renal anemia progresses in patients with chronic renal failure (CRF). Methods: We measured CHr, iron parameters, and the intrinsic erythropoietin (EPO) concentration in nondialysis CRF patients who visited our outpatient clinic (n = 211). Iron deficiency was defined according to the transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). Results: The mean CHr value of the nondialysis CRF patients (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not significantly different from that of the dialysis patients. Significant correlations were found between CHr and ferritin levels (r = 0.042, p < 0.0403) and CHr and TSAT levels (r = 0.040, p < 0.0157). A positive correlation was observed between the CHr and serum creatinine levels. Nondialysis CRF patients treated with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower CHr levels, compared with those of other patients who received less than 24,000 U/month. Conclusion: CHr is an easily measurable and trustworthy marker of iron status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and thus, the CHr value could likely provide useful information regarding the need for iron supplementation.

Monitoring the Content of Reticulocyte Hemoglobin (CHr) as the Progression of Anemia in Nondialysis Chronic Renal Failure (CRF) Patients

We previously showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status in chronic dialysis patients with erythrocytopoiesis. The CHr was significantly correlated with conventional parameters of iron deficiency in dialysis patients. We attempted to utilize the measurement of CHr levels to monitor iron status and clarify the changes in iron levels that occur as renal anemia progresses in patients with chronic renal failure (CRF).We measured CHr, iron parameters, and the intrinsic erythropoietin (EPO) concentration in nondialysis CRF patients who visited our outpatient clinic (n=211). Iron deficiency was defined according to the transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA).The mean CHr value of the nondialysis CRF patients (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not significantly different from that of the dialysis patients. Significant correlations were found between CHr and ferritin levels (r=0.042, p<0.0403) and CHr and TSAT levels (r=0.040, p<0.0157). A positive correlation was observed between the CHr and serum creatinine levels. Nondialysis CRF patients treated with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower CHr levels, compared with those of other patients who received less than 24,000 U/month.CHr is an easily measurable and trustworthy marker of iron status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and thus, the CHr value could likely provide useful information regarding the need for iron supplementation.

N-methyl-2-pyridone-5-carboxamide: A novel uremic toxin?

N-methyl-2-pyridone-5-carboxamide (2PY) is one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation. We recently found that serum 2PY concentrations in chronic renal failure (CRF) patients were enhanced to the values, which are potentially toxic. The aim of this study was to determine whether 2PY is an inhibitor of poly(ADP-ribose) polymerase, the nuclear enzyme that is highly involved in variety of physiologic events, including regulation of DNA replication and DNA repair. High-performance liquid chromatography (HPLC) was used to determine 2PY and other NAD catabolite concentrations in serum of: nondialyzed patients; patients chronically hemodialyzed; patients after kidney transplantation; and healthy individuals (control group). Moreover, the effect of nicotinamide and 2PY on poly(ADP-ribose) polymerase (PARP-1) in vitro was studied. The serum nicotinamide, 2PY, and 4PY (N-methyl-4-pyridone-3-carboxamide) concentrations are many times elevated in nondialyzed CRF patients when compared with controls. The direct correlations were found between serum 2PY (as well as 4PY and nicotinamide) concentrations and serum creatinine concentration, and negative correlations between serum concentrations of these compounds and creatinine clearance. The concentration of 2PY decreases considerably after hemodialysis (HD) session, but elevates back 48 hours later. It permanently declines after kidney transplantation. Nicotinamide and 2PY significantly inhibit PARP-1 activity in vitro. Increased serum 2PY concentration, along with a deterioration of kidney function and its toxic properties (significant inhibition of PARP-1 by 2PY), suggest that it could be a novel uremic toxin.

Lipid abnormalities in chronic uremic patients. Response to treatment with gemfibrozil.

Seventy-four patients with end stage renal failure were studied. Forty-six of them were on hemodialysis (HD) while 28 were on continuous ambulatory peritoneal dialysis (CAPD). In addition 56 nondialysis chronic renal failure (NDCRF) patients with various degree of renal failure were also studied. In all groups serum triglyceride concentrations were significantly higher and HDL cholesterol concentrations were significantly lower compared to age- and sex-matched controls. Total and LDL cholesterol were significantly higher in the NDCRF and CAPD patients compared to controls. In 55 patients (20 on HD, 13 on CAPD and 22 NDCRF) with severe hypertriglyceridemia or diminished HDL cholesterol gemfibrozil 300 mg b.i.d. per os was given for 6 months. Drug treatment reduced significantly serum triglycerides in all groups of patients and increased the levels of HDL cholesterol in CAPD patients. Moreover, a statistically significant decrease of the levels of total and LDL cholesterol was noticed in HD and NDCRF patients. During treatment no significant side effects were observed and liver and muscle enzymes remained within normal values.

Increased Salivary Concentration of Human Epidermal Growth Factor in Patients Undergoing CAPD

Epidermal growth factor (EGF) was measured in the saliva of 36 patients with chronic renal failure (CRF) and 29 matched control subjects. Salivary EGF in controls was 0.65 +/- 0.009 nmol/L compared with 0.99 +/- 0.24 nmol/L in nondialyzed CRF patients, 1.15 +/- 0.23 in hemodialyzed patients and 1.96 +/- 0.25 (p less than 0.01, Wilcoxon Rank Sum Test) in CAPD-treated patients. On Sephadex chromatography, the major peak of immunoreactive EGF from patient and control saliva samples coeluted with purified human EGF. We conclude that salivary concentrations of human EGF are significantly elevated in end-stage renal failure, particularly in patients treated by CAPD.

Comparison of Different Parathyroid Hormone Radioimmunoassays in Uremic Patients with Secondary Hyperparathyroidism

Parathyroid hormone (PTH) levels of patients with chronic renal failure (CRF) were measured by three different radioimmunoassays (RIA); RIA for mid-region PTH by antibody CH9 (i-PTH) (1), RIA for intact fragments of PTH (intact PTH) and RIA for C-terminal fragments of PTH (PTH-C). PTH levels were higher in CRF patients undergoing hemodialysis therapy (hemodialysis patients) by all three methods. However, PTH levels measured only by i-PTH assay and intact PTH assay were significantly higher in patients with CRF who were not on dialysis (non-dialyzed CRF patients). PTH levels were above normal when creatinine clearance was below 45 ml/min in the intact PTH assay and 66 ml/min in the i-PTH assay. I-PTH levels were well correlated with the severity of osteitis fibrosa evaluated by the degree of periosteal resorption in the digits of hemodialysis patients. Since special handling of the sample is required for the intact PTH assay, i-PTH assay is the most suitable method for diagnosing secondary hyperparathyroidism in patients with CRF.

Plasma levels of 7B2 (a novel pituitary polypeptide) and its molecular forms in plasma and urine in patients with chronic renal failure: possible degradation by the kidney

Plasma immunoreactive (IR)-7B2 was measured in patients with chronic renal failure (CRF), using a specific radioimmunoassay. The mean (± S.E.M.) concentration of plasma IR-7B2 in CRF patients under hemodialysis (502 ± 36 pg/ml, n = 27) was significantly higher than that in normal subjects (men, 52.9 ± 1.7 pg/ml ( n = 179); women, 55.8 ± 1.3 pg/ml ( n = 198)). Significant correlations between plasma levels of IR-7B2 and those of blood urea nitrogen, creatinine and β 2-microglobulin were evident in non-dialyzed CRF patients. In the analyses of pooled plasma and urine obtained from normal subjects on gel permeation chromatography, a major peak of IR-7B2 was observed at an apparent molecular weight of 20,000 in the plasma, and at a position of a smaller molecular weight in the urine. These results suggest that 7B2 is degraded mainly in the kidney and that measurement of plasma 7B2 may serve as an appropriate tool for assessing renal function.