Stage Renal Failure Research Articles

Plasma and erythrocyte relationship of catecholamines in hemodialysis patients.

The function of the autonomic nervous system is based on reciprocal interaction between the sympathetic and parasympathetic parts, most frequently in the form of antagonistic action on target organs. The main mediators of the sympathetic nervous system in the effectors part are catecholamines (CA), which are involved in various physiological processes. Moreover, CA also has a profound effect on the kidneys, being factors that impact on renal haemodynamics, and have been reported to be altered in pathological disorders, e.g. extracellular volume expression, hypertension and cardiovascular complications. The increased sympathetic nerve activity, at least in part, can explain the raised in plasma CA observed in chronic kidney diseases. Furthermore, plasma CA levels in ureamic patients cannot be considered a reliable index of sympathetic activity, due to existence of many factors which may affect their values. In addition, CA released into the circulation, as one of many substances, may penetrate across the cellular membranes of erytrocytes (RBC). Taking these observations together, the aim of the presented study was to investigate for the first time the plasma and erythrocyte relationship of catecholamines in haemodialysis. The studies were performed among 37 haemodialysed patients who were inhabitants of the Lublin commune. Plasma and intracellular concentration of CA were measured prior to and following haemodialysis by high performance liquid chromatography with electrochemical detection. The results suggest that RBC are able to accumulate CA at the stage of terminal renal failure; in addition, the levels of adrenaline and dopamine in RBC depend on the accumulation of urea in plasma. It was also found that the dynamic changes in concentration of RBC adrenaline are an independent predictor of mortality in haemodialysis patients.

PENATALAKSANAAN DIET PADA NEFROPATI DIABETIK

One of the complication of diabetes mellitus is nephropathy diabetic, if this situation is not cured properly it tends to develop the end stage of renal failure. The objectives of this diet management in patients with nephropathy diabetic are to reduce progression of renal damage, maintain the nutritional status of the patient, control blood glucose, lipid serum and maintain electrolyte and fluid balance. Nutrient requirement of nephropathy diabetic patients should contain: protein 0.8 g/kg/body weigh/day. But if patients suffered of end stage of renal failure 0.8 g/kg body weigh/day, in the case of dialysis the protein need is 1-1.2g/kg body weigh/day. For energy requirement they need 35 kcal/kg body weigh/day, with the carbohydrate 60% from total energy need, fat should be 30% total energy need contain poly unsaturated fatty acid and mono unsaturated fatty acid. For mineral, natrium (Na) is needed 1000-3000 mg/day, whereas kalium (K) is 40-70 mEq/day (1600-2800mg/day). In conclusion, diet management is taking an important role to delay the progression of being end stage renal failure. Keywords : nefropati diabetik, gagal ganjal terminal

Serum total p-cresylsulfate level is associated with abnormal QTc interval in stable angina patients with early stage of renal failure

Backgroundp-Cresylsulfate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. Furthermore, the association among serum total PCS, major adverse cardiovascular events, and all-cause mortality were also found in previous studies. However, little is known about the relationship between total PCS level and prolonged QT interval. We assessed whether serum total PCS level is related with prolonged QT interval by measuring 12-lead electrocardiogram (ECG) recording in stable angina patients with early stage of renal failure. MethodsSerum total PCS concentrations were measured by using the Ultra Performance LC System in 154 consecutive stable angina patients. A 12-lead ECG recording was obtained from each subject. ResultsPatients with abnormal corrected QT (QTc) interval have higher median serum total PCS levels than patients with normal QTc interval. Statistically significant associations were observed between the serum total PCS levels and the QTc interval (r=0.217, P=0.007). Using multivariate and trend analyses, serum total PCS level was independently associated with QTc prolongation. ConclusionsThis study indicates that serum total PCS levels are significantly higher in the presence of abnormal QTc interval and are associated with the QTc prolongation. Whether total PCS plays a role in the pathogenesis of QTc prolongation requires future investigation.

Effect of erythropoietin on free radical oxidation and glycoprotein expression in platelets under conditions of chronic renal failure.

A short-term open prospective study examined 62 patients at the terminal stage of chronic renal failure. The experimental group received erythropoietin in a total dose of about 40,000 U. The expression of glycoproteins IIb-IIIa, IIb, and Ib was enhanced, the content of LPO products was elevated, and SOD and catalase activities were reduced in platelets from patients with chronic renal failure. Administration of erythropoietin partially restored free radical oxidation and expression of glycoproteins IIb-IIIa, IIb, and Ib in platelets. A significant correlation was revealed between the expression of platelet receptors on the one hand, and content of LPO products and SOD and catalase activities, on the other hand.

Natural killer (NK) cells but not NK T cells attenuate renal fibrosis after acute kidney injury (AKI). (IRC8P.480)

Abstract Renal fibrosis is the common pathway of various kidney diseases that lead to progressive renal failure and end stage renal disease. NK and NK T cells have been linked to regulating fibrosis in several different organ systems. However, there is debate as to whether they are pro-fibrotic or anti-fibrotic. To determine their role in renal fibrosis, mice were administered PK136 mAb (200μg i.p), which depletes both NK and NKT cells, twice weekly for 14 days starting 5 days after 26 minutes of unilateral kidney ischemia-reperfusion (uIRI) or folic acid (250 mg/kg, i.p.). In both models, compared to IgG-treated mice, kidneys of mice treated with PK136 had increased fibrosis as assessed by Masson’s Trichrome and mRNA expression of collagen 1 and α-SMA. This suggests that NK/NKT depletion increases extracellular matrix deposition and myofibroblast number. This may be due to changes in the kidney microenvironment as kidneys of PK136-depleted mice had decreased expression of IFN-γ and increased expression of IL-10 and TGF-β compared to IgG-treated mice. We next subjected Jα18-/- and CD1d-/- mice to unilateral IRI to determine the specific role of NKT cells in renal fibrosis. Compared to wild-type mice, Jα18-/- and CD1d-/- mice subjected to uIRI demonstrated no increase in fibrosis, thus we conclude that the that NK but not NKT cells attenuate renal fibrosis after AKI. Further investigation will focus on determining the mechanism by which NK cells regulate fibrosis within the kidney.

Pleiotropic functions of TIMP-1 in patients with chronic kidney disease

Sir, We have read with great interest a recent in-depth review by Christian Ries [1], giving a picture of multiple activities of a tissue inhibitor of metalloproteinases (TIMP)-1 and revealing its complex cytokine impact on various cell functions. The pleiotropic role of TIMP-1 results from both metalloproteinase (MMP)-dependent and MMP-independent actions, creating a tool for the control of such diverse phenomena as apoptosis, cell differentiation or uncontrolled cell migration, resulting in metastases. In addition to a detailed theoretical background, the author has described the clinical implications of TIMP-1 activity, including cancer and cardiovascular disease. In our opinion, chronic kidney disease (CKD) is also worth mentioning among those examples. CKD, with its irreversible progressive clinical course and multiple complications, seems an ideal example of TIMP-1 multifaceted activity, influencing chronic inflammation, impaired immunity, enhanced apoptosis and cardiovascular comorbidity. Our recent investigation has concentrated on various aspects of MMP and the role of TIMP-1 in the course of CKD in the pediatric population. We have shown that the increase of serum TIMP-1 concentrations in CKD children appears only in the late stages of renal failure and is delayed in comparison to the early rise of MMP values, being an anti-fibrotic response to extracellular matrix accumulation [2]. Moreover, TIMP-1 was the best predictor of TGFbeta1, a hallmark of fibrosis, a fact that is concordant with the tight TIMP–MMP–TGFbeta1 connections described by Ries [1]. Another interesting aspect of TIMP-1 activity is its anti-apoptotic function, realized by both direct, receptor-mediated, and indirect, by MMP inhibition, pathways [1]. Enhanced apoptosis is one of the key elements in the course of chronic kidney disease, additionally aggravated by the commencement of dialysis. Indeed, our investigation has revealed increased MMP/TIMP concentrations in chronically dialyzed children versus controls [3]. The additional discrepancy between dialysis modalities, most evident in the case of TIMP-1, has strengthened the suggestion that hemodialysis triggers apoptosis and reciprocal anti-apoptotic protection to greater extent than peritoneal dialysis. We have also noticed the statistically significant correlations between markers of matrix turnover and apoptosis [3]. In addition, regression analysis has shown that TIMP-1 was more accurate than TIMP-2, MMP-2, or MMP-9 in the prediction of the well-established apoptotic markers, sFas and sFasL [3]. The abovementioned MMP overactivity and MMP/TIMP imbalance disrupts the integrity of the extracellular matrix in the course of CKD. The subsequent tissue remodeling, together with cell damage and matrix accumulation, gives way to atherosclerosis, renal fibrosis and aggravated cell migration to sites of inflammation. In particular, cells losing their anchorage due to proteolytic overactivity, if not eliminated by anoikis, gain the ability for uncontrolled migration and further metastatic spread. The hallmark of anoikis activity is E-cadherin, released in a circulating form from destroyed cell–cell junctions, and easing epithelial-to-mesenchymal transition (EMT). We have shown for the first time significant correlations between this marker and MMP/TIMP in CKD children, particularly in those on chronic dialysis [4]. Moreover, on regression analysis, TIMP-1 has turned out to be the best predictor of E-cadherin among examined MMPs, TIMPs, and apoptotic indexes [4]. The last intriguing aspect of TIMP-1 activity in the CKD population is its functional similarity with heat shock proteins (HSP). HSP are classified as damage-associated molecular patterns (DAMP), highly conserved in their structure throughout species. Likewise, TIMPs appear in all mammals [1]. They all influence the immune system by activating (HSP) or inhibiting (TIMP-1) nuclear factor (NF)κB. We have revealed for the first time the significant correlations between HSP and MMP/TIMP both in pre-dialysis children and in those on chronic dialysis [2, 5]. Moreover, we discovered that TIMP-1 was the most valuable predictor of various HSP (Hsp27, Hsp90alpha, anti-Hsp60), suggesting that they share some common features, and that TIMP-1 may, under the circumstances, behave like a stress protein. However, this hypothesis requires further in-depth investigation.

Assessment of kidney function in the elderly: a population-based study

Chronic kidney disease (CKD) affects all age groups, and its prevalence has increased during recent years. CKD is divided into six stages, according to the renal function of patients: 1. Normal renal function without kidney damage; 2. Kidney damage with normal renal function; 3. Mild renal insufficiency; 4. Moderate renal insufficiency or lab tests failure; 5. Severe renal insufficiency or clinical failure; 6. End stage of chronic renal failure. This study was intended to assess renal function in elderly patients and identifying the presence of factors associated with those changes. A cross-sectional population-based study was performed. Elderly patients were surveyed between September 2010 and May 2011. Kidney function was assessed by determining of serum creatinine, and estimation of the glomerular filtration rate by the CKD-EPI equation. In all, 822 elderly were surveyed; 61.6% were women; 92.2% were Caucasian; and most (61.0%) were aged between 60 and 69 years. With regard to the glomerular filtration rate, 26.2% had a normal rate; 60.2% showed a slight decrease; 13.0% a moderate decrease; 0.5% severe kidney function decline; and 0.1% extreme fall. Increasing age was associated with kidney damage by decreased glomerular filtration rate (p < 0.001). In addition, obesity, hypertension and smoking were factors independently associated with reduced glomerular filtration rates. This study found that the great majority of the surveyed elderly had some mild kidney damage, and 13.6% showed moderate to severe dysfunction.

Heart function disturbances in chronic kidney disease - echocardiographic indices.

IntroductionIn chronic kidney disease (CKD) patients left ventricular (LV) diastolic dysfunction occurs frequently and is associated with heart failure (HF) and higher mortality. Left ventricular systolic dysfunction is associated with coronary artery disease (CAD) and is a major determinant of prognosis. The aim of this study was to assess indices of LV diastolic dysfunction in CKD patients.Material and methodsStudy included 118 CKD patients. All patients underwent transthoracic echocardiography. Diastolic function based on E and A, E/A ratio and pulmonary vein flow velocities as well as EF%, deceleration time, RA, LA volume were assessed. In dialysis patients examination was carried out before and after dialysis.ResultsIn CKD patients the stage of renal failure was associated with the significant increase in LV mass (268.0 ±47.6 CKD I/II vs. 432.7 ±122.4 CKD V/dialysis, p < 0.0001), systolic LV (37.3 ±4.5 vs. 51.2 ±8.9, p < 0.0001) and diastolic LV (CKD I–II 44.7 ±4.1 vs. CKD III 48.5 ±6.7 vs. CKD IV 47.1 ±5.6; p = 0.004) dimensions and in the size of the LA (40.4 ±2.0 vs. 41.9 ±2.7 vs. 42.3 ±3.2 vs. 44.8 ±3.1; p < 0.0001). The increase the E/E’ ratio between groups of patients (6.7 ±1.5 vs. 8.9 ±2.4 vs. 11.5 ±4.0 vs. 13.5 ±5.0; p < 0.0001) was seen in this study. The reduction in deceleration time (247.2 ±34.5 in CKD I/II vs. 197.4 ±61.0 in CKD IV, p = 0.0005) along with the decrease in estimated glomerular filtration rate was also observed in this study.ConclusionsEarly identification of factors involved is necessary to prevent this devastating process. Many indexes of contractility are used and each of them has imperfections. It seems that TVI, E, E/A and E/E’ are good instruments for the early detection of left ventricular hypertrophy and diastolic dysfunction.

VACCINATION OF CHILDREN WITH CHRONIC RENAL FAILURE IN PRE- AND POSTTRANSPLANTATION PERIODS

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в

Exploration of novel predictive markers in rat plasma of the early stages of chronic renal failure

To identify blood markers for early stages of chronic kidney disease (CKD), blood samples were collected from rats with adenine-induced CKD over 28 days. Plasma samples were subjected to metabolomic profiling by liquid chromatography-mass spectrometry, followed by multivariate analyses. In addition to already-identified uremic toxins, we found that plasma concentrations of N6-succinyl adenosine, lysophosphatidylethanolamine 20:4, and glycocholic acid were altered, and that these changes during early CKD were more sensitive markers than creatinine concentration, a universal indicator of renal dysfunction. Moreover, the increase in plasma indoxyl sulfate concentration occurred earlier than increases in phenyl sulfate and p-cresol sulfate. These novel metabolites may serve as biomarkers in identifying early stage CKD.

Does the Osteoporosis Dose of Denosumab Really Cause Clinically Significant Hypocalcaemia in CKD 4 and 5

Denosumab is a potent novel antiresorptive agent for treatment of osteoporosis with unique mechanism of action . It is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Initially denosumab appeared particularly promising for patients with advanced stages of renal failure but over the past two years several publications questioned that, reporting adverse effects and especially severe hypocalcaemia. Aim of the Study: to investigate further the effect of the osteoporosis dose of denosumab on serum calcium levels in patients with CKD 4 and CKD 5. Methods: This retrospective outpatient study included 17 females with CKD 4 and 5 who received a single or a multiple (at 6 months intervals) 60-mg subcutaneous dose of denosumab. Adjusted serum Calcium was measured prior to the dose and at various points of time after that. Results: Only two of the subjects developed clinically significant hypocalcaemia. Both of them were clearly inadequately supplemented with calcium and vitamin D. Conclusion: The results from the current study along with a critical analysis of the previous publications reveal that the vast majority of the previous reports were based on inadequately supplemented with calcium and vitamin D patients and that severe hypocalcaemia is unlikely in appropriately supplemented subjects, especially in the CKD 4 subgroup. However, due to the scarcity of data further research is warranted, Original Research Article British Journal of Medicine & Medical Research, 4(2): 649-659, 2014 650 especially in the CKD 5 subgroup. In the mean time more cautious approach rather than a blanket ban on denosumab appears to be the most appropriate policy in these two populations.

Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus

Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.

Is IL-33 useful to detect early stage of renal failure?

IL-33 is a proinflammatory cytokine that is a member of IL-1 family. Previously the effect of IL-33 on kidney injury is showed in animal models. In this study, we searched if we can use IL-33 to show the early stage of kidney injury in diabetic patients. Three groups are identified: 26 patients in Group 1: Healthy group, that do not have any chronic diseases and not taking any medication; 42 patients in Group 2: DM (diabetes mellitus) group without any known kidney disease and with normal kidney functions; 32 patients in Group 3: DM + MA (microalbuminuria) group that are assumed to have nephropathy. IL-33 level of DM patient group is greater than healthy group; also IL-33 level of DM + MA patient group is greater than healthy group; but there is not any difference between DM and DM + MA group. The increase in IL-33 levels in diabetic nephropathy is not associated with kidney injury but the increase could be resulting because of diabetes. So IL-33 cannot be used in early recognition of diabetic nephropathy.

Does decreased mean platelet volume predict inflammation in chronic renal failure, dialysis, and transplanted patients?

Objectives: Increased platelet activation contributes to cardiovascular mortality in chronic kidney disease patients (CKD). Larger platelets are more active and this increased activity had been suggested as a predictive biomarker for cardiovascular disease. In this study, we aimed to evaluate mean platelet volume (MPV) as an inflammatory marker in a broadened group of CKD patients. Our study is unique in literature as it covers all types of CKD including renal replacement therapies. Materials and methods: 200 patients (50 renal transplanted, 50 hemodialysis, 50 peritoneal dialysis, 50 chronic renal failure stages 3–4) were investigated who were between 18 and 76 years of age. The collected data included demographic properties, platelet count, MPV, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and hemoglobin. All of the patients had at least 12 month of therapy of either renal replacement modality. Results: The mean CRP value was detected statistically significantly higher in hemodialysis (HD) patients compared to the resting three groups of patients (p < 0.01). Mean CRP level was detected significantly higher in the pre-dialysis group compared to transplanted and peritoneal dialysis (PD) patients (p < 0.01). There is no statistically significant difference detected among the mean MPV values of all patient groups (p > 0.05). Conclusions: ESR and CRP were significantly increased in hemodialysis patients compared to the other groups. We did not detect a significant difference among MPV between the groups. ESR was detected lowest in transplanted patients. Transplantation is coming forward as the favorable choice of renal replacement therapy which decreases inflammation.

Effect of Early Stage Kidney Disease on Cardiac Mass: Comparison to Post-Donation Renal Function

Background/Aim: In chronic renal failure the increase in cardiovascular risk is in part related to the high prevalence of left ventricular hypertrophy. The aim of the present monocentric retrospective study was to evaluate the influence of the presence of parenchymal kidney disease on left ventricular geometry in normotensive (arterial pressure <140/90 mm Hg) patients (KD+, n = 50, mean age 39 ± 19 years) with mild to moderate renal failure (stage 2-3 chronic kidney disease). Methods: Left ventricular geometry was estimated by echocardiography and compared to a group of healthy subjects with similarly reduced renal function as a consequence of renal donation (KD-, n = 63, mean age 52 ± 12 years). Results: Subjects with and without kidney disease had similar blood pressure, body mass index and isotopic glomerular filtration rate. Left ventricular mass (LVM) indexed to body surface area was greater in KD+ as compared to KD- subjects and the difference was more pronounced in women than in men. The increase in LVM in KD+ patients was associated with lower albuminemia and hematocrit, and a higher plasma renin activity and aldosterone as compared to KD- subjects. In multivariate analysis, kidney disease emerged as an important determinant of LVM index independently of age, gender and blood pressure. Conclusion: This observation suggests that the presence of kidney disease has an independent amplifying effect on LVM which could be related to volume overload and/or prohypertrophic factors such as aldosterone.

AB0634 Brown tumors in hemodialysis: study of 12 tunisian patients

BackgroundBrown tumors are unusual but serious complications of renal osteodystrophy. This unusual complication of secondary hyperparathyroidism (HPT) is more commonly seen with increased longevity of hemodialysis patients and can be...

Cerebral aqueduct block attenuates cardio-renal injuries in post-DOCA-NaCl-hypertensive Dahl R rats

The systemic and/or local effects of the hydrocephalic brain were investigated in DOCA-NaCl-hypertensive Dahl R rats induced by 250 mg kg(-1) DOCA in silicone and 1% saline water. After a 1-week recovery with 0.3% NaCl chow and tap water, one group had the aqueduct of Sylvius blocked with silicone and epoxy materials with a control sham group matching mean blood pressure (BP) and body weight. The 4-week-postsurgery BP on the 0.3% NaCl diet averaged 161±3.2 in the sham group and 146±2.3 mm Hg in the blocked group (P<0.0001). Both groups were then given an 8% NaCl diet and after 4 weeks, the sham group's BP was increased further with markedly increased mortality: 186 mm Hg vs. 154 mm Hg (P<0.0001); 12 sham rats died after 11 weeks, while all the blocked rats survived (P<0.0001). A transient change in plasma Na levels was observed in the blocked group after 48 h on the 8% NaCl diet. At 14 weeks, 0 sham rats survived, compared with 10 out of 16 blocked rats (P<0.0001). After 11 weeks on 8% NaCl, the average tail venous pressure in the sham group was significantly higher than that of the blocked rats (P<0.0001) indicating the end stage of renal and heart failure. The hearts and kidneys weighed significantly more in the sham vs. the blocked rats (P<0.0001 for both groups). These results indicate that the aqueduct block prevents post-DOCA hypertension and cardio-renal injuries, suggesting that centralized third ventricular brain signaling has a role in salt-genetic hypertension.

Severe leptospirosis observed in a man who had just returned from abroad.

Leptospirosis, a re-emerging zoonosis caused by pathogenic Leptospira, has a low incidence in Bulgaria. This paper reports a case of leptospirosis in Pleven, Bulgaria, in which the subject was infected after wading through irrigative canal in northern Greece. Two days later, he had a fever, myalgia and vomiting followed by jaundice, darkness of urine and oliguria. The patient was admitted to Clinic of Infectious Diseases at University Hospital-Pleven after returning to Bulgaria. The history and laboratory findings suggested icterohaemorrhagic leptospirosis. Penicillin G was prescribed and intensive supportive treatment was initiated. Dialysis was performed two hours after admission and was followed by poliuric stage of acute renal failure (peak urine output 16 600 mL/day). Microaglutination test (MAT) for sero-diagnosis was positive (L. hardjo 1:1600, L. icterohaemorrhagiae 1:800). The patient was discharged after sixteen days with improved renal and liver functions. In conclusion, The probability of leptospirosis should not be ignored in patients with fever after returning from abroad. The prompt dialysis and adequate treatment improve prognosis.

Anemia in Chronic Renal Disease: Evaluation of Inflammatory Activity on Erythropoiesis and Iron Metabolism in Patients not Submitted to Dialysis Treatment

Inflammatory activity is one of the factors involved in the physiopathology of anemia in patients with chronic kidney disease (CKD). The majority of studies on anemia, inflammation, and disturbances of iron metabolism have focused on patients in end-stage renal failure and dialysis therapy. However, anemia and inflammation are present in patients in previous stages of renal failure. The objective of this study was to evaluate the possible influence of inflammatory activity on erythropoiesis and iron metabolism in CKD patients without dialytic treatment. 114 CKD adult patients were studied. Patients with anemia (n = 72) were compared with those without anemia (n = 46). Anemic patients were classified as renal anemia (n = 46) or iron deficiency anemia (n = 26). In addition the total group was analyzed according to the degree of renal dysfunction. Iron status, erythropoiesis activity (soluble transferrin receptor and erythropoietin determinations), and inflammatory activity (C-reactive protein, interleukin-6, interleukin-lp, and neopterin determinations) were measured using commercial kits. Reticulocyte hemoglobin content (Ret-Y) was also determined. Interleukin-6, interleukin-li, and neopterin concentrations were higher in the anemic group when compared with those without anemia and controls. There was no difference in C-reactive protein values between CKD with and without anemia, although both of them had showed elevated levels when compared with controls. Ret-Y values were lower in iron deficiency anemia when compared with renal anemia and controls. An inverse correlation between interleukin-6 and hemoglobin (r = -0.4287, p= 0.0002) was observed only in the renal anemia group. It was observed that anemia has a tendency to worsen as renal function deteriorates. Reticulocyte count was lower and neopterin concentrations were higher in more advanced renal failure stages. Inflammatory factors contribute to anemia in renal patients in all stages of renal failure. High levels of neopterin in CKD patients suggest that neopterin contributes to impaired erythropoietin production and anemia in CKD patients.

Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970^s and 80^s. However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.