Nondialyzed Chronic Renal Failure 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.

Drug Treatment in Non-Dialysed Chronic Renal Failure Patients in Senegal (West Africa)

Drug Treatment in Non-Dialysed Chronic Renal Failure Patients in Senegal (West Africa)

Pseudoporphyria Associated with Nonhemodialyzed Renal Insufficiency, Successfully Treated with Oral N-Acetylcysteine

Pseudoporphyria (PP) is a relatively rare, photodistributed bullous dermatosis that resembles porphyria cutanea tarda (PCT), but it is not accompanied by porphyrin abnormalities in the serum, urine, or stool. It was initially described in renal failure patients on dialysis. Thereafter, it has been associated with several aetiological factors. We report a case of PP in a 67-year-old woman with mild renal failure, successfully treated with N-acetylcysteine. This is the second reported case of PP developing in nondialyzed chronic renal failure. Such cases support the view that renal impairment itself may play a more important aetiological role in developing PP than it was originally considered.

Étude prospective observationnelle des hyperkaliémies secondaires aux inhibiteurs de l’enzyme de conversion chez des patients ayant une maladie rénale chronique hospitalisés

ObjectiveTo study the incidence and risk factors of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with hypertension and preexisting chronic renal failure. MethodologyTwo-months prospective observational study was used including all hospitalized patients older than 18 years with a history of hypertension, non-dialyzed chronic renal failure and who had angiotensin converting enzyme prescription at the time of the admission. Hyperkalemia greater than or equal to 5mmol/L was detected in these patients. The studied variables were demographic, clinical, biological and therapeutic. ResultsEight patients, among 27 included, had a hyperkalemia (2963 %). They were 73±15 years old. Factors that predispose to hyperkalemia were present in all patients. Hyperkalemia was associated in six cases with decompensation of renal function. The age was associated with hyperkalaemia in patients treated with angiotensin converting enzyme inhibitors (RC=1.21; IC95 1,11-1,46; P=0,021). Diabetes is a possible risk factor (OR=59 021 et, 95 0.93 to 2410, P=0.053). Compared with patients who did not develop hyperkalemia, the occurrence of hyperkalemia in patients included was associated with a longer duration of hospitalization (OR=130, 95 112 to 160, P=0. 022). ConclusionThe prescription of angiotensin converting enzyme inhibitors in the elderly with chronic renal failure and diabetes requires careful monitoring of serum potassium.

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.

A new approach to the evaluation of hyperphosphatemia in chronic kidney disease

Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.

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.

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.

Aberrant Activation of the TNF‐α System and Production of Fas and Scavenger Receptors on Monocytes in Patients With End‐stage Renal Disease

Ten patients with nondialyzed chronic renal failure (CRF), 14 receiving continuous ambulatory peritoneal dialysis (CAPD), 16 receiving hemodialysis (HD), and 10 normal controls (NC), were evaluated. Levels of Fas antigen (CD95), scavenger receptors (CD36 and CD68), and tumor necrosis factor-receptor 2 (CD120b) on monocytes were measured using flow cytometry. All patients showed lymphocytopenia, and monocyte counts were decreased in those with CRF. Fas levels were higher in patients receiving HD than the others, and were higher in the CRF and CAPD groups than in controls. CD120b levels were similar to those of Fas. Monocyte CD36 levels in the dialysis groups were significantly higher than in the CRF and NC groups. CD68 was also significantly elevated in HD patients. Fas levels were positively correlated with those of CD120b and CD68. The patient groups showed higher levels of apoptotic markers and scavenger receptors, combined with activation of the TNF-alpha system, especially in patients receiving HD.

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.

Changes in leukocyte subsets: clinical implications for children with chronic renal failure

Increased systemic inflammation and an impaired immune response are features of adult chronic renal failure (CRF). These patients have increased rates of infection, cardiovascular disease, anemia, and malnutrition. We measured inflammatory and immunological markers in a group of children with pre-dialytic CRF. No prior studies have explored these markers even though children with non-dialysed CRF exhibit similar complications to those seen in adults with CRF. Blood was collected from children with mild, moderate, or severe CRF and an age-matched control group. Functional leukocyte subsets were determined using flow cytometry. Circulating levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-10, and tumor necrosis factor-alpha were measured using a flow cytometric bead assay. Children with severe CRF showed significantly reduced total white cell count and absolute neutrophil and lymphocyte counts. Absolute numbers of CD3+/CD45RO+ memory T cells and CD3+/CD45RO+/CD62L+ memory Th2 cells were significantly reduced in all CRF groups versus controls. Children with severe CRF showed increased CD11b expression on neutrophils and monocytes. Some patients showed increases in pro-inflammatory cytokines that were not related to their level of residual renal function. As CD11b expression mediates leukocyte adhesion to vascular endothelium, upregulation may contribute to the increased endothelial dysfunction observed in children with CRF. L-selectin mediates extravasation of leukocytes into tissue and homing of peripheral blood lymphocytes to lymph nodes. The reduction in L-selectin may inhibit these actions and predispose patients to increased infection later in life. This is the first study to comprehensively investigate leukocyte functional molecules and inflammatory cytokine profiles in children with pre-dialytic CRF and provides new immunological evidence for the clinical manifestations associated with the disease.

Significance of 8-hydroxy-2'-deoxyguanosine levels in patients with chronic renal failure.

The aim of this study was to determine the significance of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is known as a marker of oxidative stress in vivo, in patients with chronic renal failure (CRF). Fifty-one non-dialysed CRF patients (29 men and 22 women; mean +/- SD age, 57.8 +/- 12.8 years) who were under dietary therapy for at least 6 months were enrolled in the study. Both serum and urinary 8-OHdG levels were measured by using high-sensitive enzyme-linked immunosorbent assay (ELISA) kits. We examined the relationship between 8-OHdG levels and clinical indices in patients with CRF. As a result, the serum 8-OHdG level was strongly correlated with serum levels of urea nitrogen (UN; r = 0.58; P < 0.0001), creatinine (Cr; r = 0.53; P < 0.0001), and beta2-microglobulin (beta2-MG; r = 0.54; P < 0.0001). Furthermore, the serum 8-OHdG level was inversely correlated with creatinine clearance (Ccr; r = -0.54; P < 0.0001). In contrast, urinary 8-OHdG level was not correlated with any of the clinical parameters. This is the first report of 8-OHdG level determination in patients with CRF. It is suggested that serum 8-OHdG level is not sufficient as a marker of oxidative damage in patients with CRF, and it should be corrected according to the residual renal function to estimate the accurate degree of oxidative stress.

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.

Polymorphonuclear leukocyte rigidity is defective in patients with chronic renal failure.

The purpose of the study was to investigate the rigidity of polymorphonuclear leukocytes (PMNs) in non-dialysed chronic renal failure (CRF) and haemodialysis (HD) patients. PMN rigidity as well as tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) plasma levels were assessed in 10 early-stage CRF, 10 late-stage non-HD, and 10 HD patients, before and during dialysis. In HD patients both cellulose acetate and polysulphone membranes were used. Ten healthy subjects served as controls. Rigidity was tested by counting the deformability in morphologically passive PMNs by the micropipette method. Cytokine levels were measured by enzyme-linked immunosorbent assay. PMN rigidity was significantly increased in end-stage CRF patients regardless of HD but not in early-stage CRF. In HD patients PMN rigidity increased significantly 60 min after initiation of HD. There was an increase of TNF-alpha and IL-1beta levels in end-stage non-HD and HD patients and a further increase at 60 min after initiation of HD. The percentage of morphologically activated PMNs was increased only during dialysis. The nature of the HD membrane had no influence on rigidity, PMN activation, or cytokine production. The results indicate that PMN rigidity is defective in end-stage chronic CRF patients and is further increased 60 min after initiation of HD, regardless of the nature of the HD membrane used. PMN activation, increased TNF-alpha and IL-1beta levels, or a direct PMN impairment may cause the observed cell rigidity.

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Insulin-Like Growth Factor-Binding Protein-6 Levels Are Elevated in Serum of Children with Chronic Renal Failure: A Report of the Southwest Pediatric Nephrology Study Group

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

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.