Phase Of Chronic Renal Failure Research Articles

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

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

Dysnatremia in Renal Failure.

Proximal salt reabsorption in the hypertrophied tubules in the early phase of chronic renal failure (CRF) would be diminished according to the inhibited expression of proximal salt-transporting molecules, which may be facilitated by the inhibition of Na-K-ATPase expression. Results from animal models suggest that patients with early-phase CRF would easily develop hyponatremia and, in contrast, patients showing developed CRF would be more likely to show dehydration or hypernatremia. Several large-scale studies of individuals with chronic kidney disease (CKD) revealed that hyponatremia is much more common than hypernatremia in patients with earlier stages of CKD. However, patients with end-stage renal disease (ESRD) more frequently show hypernatremia than hyponatremia. These clinical trends in CKD and CRF patients are in agreement with the results of animal experiments, suggesting that salt loss might be a principal pathological setting in the early stages of CKD and that water loss could overcome the salt loss in ESRD.

Procena kvaliteta života u nezi bolesnika na hemodijalizi

According to the World Health Organization, Health Related Quality of Life, HRQoL, is defined as patient's individual assessment of how much disease and applied therapy affect his physical, social or emotional feeling of 'well being'. Increasing the quality of life is the primary goal of medical and nursing care in the terminal phase of renal insufficiency, and one of the most suitable indicators of efficiency in evaluating individual care, since both, the concept of quality of life and nursing care, doctrinally represent a holistic approach in the treatment of patients. Since 1994, a standardized questionnaire has been used to assess the quality of life of patients treated with repeated hemodialysis, KDQOL - SF (Kidney Disease Quality of Life questionnaire, Short form), composed of general SF - 36 questionnaire, which is specifically supplemented with several items specifically addressing the health problems of patients on hemodialysis. Improving the quality of life and individual adjustment of the dialysis procedure to each patient individually, represent the basis of good clinical practice and appropriate treatment of patients in the final phase of chronic renal failure.

Pharmacotherapy of Ischemia-Reperfusion Injury of Transplanted Kidneys in Children: Comparative Study

Background. Prevention of ischemia-reperfusion injury of the allograft (IRIA) is an urgent problem in transplantology, which largely determines the prognosis for both the transplanted organ and the patient as a whole. Objective. Our aim was to study the effectiveness of eculizumab in comparison with plasmapheresis during induction immunosuppressive therapy in kidney transplantation in children. Methods. The retrospective study includes children with terminal phase of chronic renal failure who have received kidney transplants from either a living relative or deceased donor. The age of patients is from 1 year to 18 years. Induction immunosuppression in both groups was performed with alemtuzumab. Group 1 (main) included children who were treated with eculizumab to prevent IRIA, Group 2 (comparison) included children who were treated with plasmapheresis for the same purpose. The comparative analysis was carried out according to the following criteria: the rate of blood creatinine subnormalization (in days), the rate of glomerular filtration (in ml/min) 30 days after the operation; daily protein excretion (mg/24 h) 30 days after organ transplantation; morphological characteristics of renal biopsy samples by Banff 30 days after surgery. Results. During the comparative analysis from December 2012 to November 2016, eculizumab was administered to 32 patients, 24 patients underwent plasmapheresis. In Group 1, blood creatinine normalized almost 4 days earlier than in Group 2 (p=0.0049); the glomerular filtration rate in Group 1 was 4.5 times higher than in Group 2 (p=0.0018). Daily proteinuria in Group 1 was 4 times lower than in Group 2 (p=0.0019). Conclusion . The carried out study showed better indices of renal allograft function when using eculizumab in comparison with plasmapheresis: consequently, eculizumab more effectively suppresses IRIA than plasmapheresis.

Survival during renal replacement therapy of patients previously treated with a very low-protein diet supplemented with ketoacids : the Italian experience.

In the course of chronic renal failure, low protein-diets allow better control of metabolic disorders and may delay the start of renal replacement therapy (RRT). However, concerns exist that a very low protein diet supplemented with ketoacids (sVLPD) worsens survival after starting RRT. To evaluate whether a prolonged sVLPD regimen may affect all-cause mortality during the following RRT period, we studied time to all-cause death during RRT in patients previously followed in renal clinics either treated with sVLPD (sVLPD group, n =184, age 67±18 yrs) or not (CKD group, n =334, age 66±14 yrs). A Control group including 9,092 patients (age 66±14 yrs) was selected from the Italian dialysis & transplantation registry (RIDT). In sVLPD, CKD and Control groups, the prevalence of an history of cardiovascular disease was 41, 31, 25% and of diabetes was 18%, 31%, 17%, respectively; the median follow-up time in RRT (36, 32, 36 months) did not differ among groups.Cumulative survival was similar in sVLPD and CKD groups ( p =0.638), but significantly higher than in the Control group (Long-rank test, 20,62; p p =0.0001) in sVLPD and 0.65 [0.53−0.80] ( p =0.001) in CKD group. Due to age interaction with survival in sVLPD ( p =0.024), HRs for death reduced to 0.34 [0.16−0.73] and 0.58 [0.37−0.92] in sVLPD and CKD pts In conclusion, prescription of sVLPD during the conservative phase of chronic renal failure does not worsen, or even improves, survival after starting RRT. This survival advantage is more evident in patients younger than 70 years.

Correlation between dialysis solution type and cardiovascular morbidity rate in patients undergoing continuous ambulatory peritoneal dialysis

Peritoneal dialysis (PD) patients have an increased risk for cardiovascular diseases. The aim of the study was to evaluate the cardiovascular changes in patients undergoing chronic PD and the eventual existing differences depending on biocompatibility of dialysis solutions. After 3 +/- 2 years of starting PD, 21 PD patients on the treatment with bioincompatible dialysis solutions (conventional glucose- based solutions: PDP-1), average age 47.43 +/- 12.87 years, and 21 PD patients on the treatment with biocompatible dialysis solutions (neutral solutions with lower level of glucose degradation products, lower concentration of Ca2+ and neutral pH: PDP-2), average age 68.62 +/- 13.98 years, participated in the longitudinal study. The average number of episodes of peritonitis was similar in both groups: 1 episode per 36 months of the treatment. The control group included 21 patients with preterminal phase of chronic renal failure (Glomerular Filtration Rate: 22.19 +/- 10.73 ml/min), average age 65.29 +/- 13.74 years. All the patients underwent transthoracal echocardiography (in order to detect: eject fraction (EF), left ventricular hypertrophy (LVH), and valvular calcification (VC) and B-mode ultrasonography of common carotid artery (CCA): IMT, lumen narrowing, and plaque detection. The values of EF were: in PDP-1 group 62.05 +/- 5.65%, in PDP-2 group 53.43 +/- 7.47%, and in the control group 56.71 +/- 8.12% (Bonferroni test, p = 0.001). The recorded LVH was: in PDP-1 group in 47.6% of the patients; in PDP-2 group in 61.9% of the patients; and in control the group in 52.4% (chi2 test; p = 0.639). The detected VC was: in PDP-1 in 52.4% of the patients, in PDP-2 group in 42.9% of the patients, and in the control group in 23.8% of the patients (chi2 test; p = 0.776). The IMT was: in PDP-1 group 1.26 +/- 0.54 mm, in PDP-2 group 1.23 +/- 0.32, and in the control group 1.25 +/- 0.27 mm (Bonferroni test; p = 0.981). An average lumen narrowing was: in PDP-1 group 13.78 +/- 18.26%, in PDP-2 group 18.57 +/- 22.98%, and in the control group 25.00 +/- 28.02% (Kruskal Wallis test; p = 0.413). Calcified plaques of CCA were detected in PDP-1 group in 61.9% of the patients, in PDP-2 group in 85.7%, of the patients and p = 0.159). Generally, PD had a significant influence on cardiovascular morbidity in the treated patients, especially on the left ventricular function and peripheral atherosclerosis. The age of the patients had more influence on acceleration of atherosclerosis than the length of dialysis or biocompatibility of dialysis solutions.

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 +/- 10.8 years; serum creatinine 2.7 +/- 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)(2)D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)(2)D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = -0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)(2)D (beta = 0.434) was a significant predictor of decreases in total and trabecular BMD (R (2) = 0.188, P < 0.01; and R (2) = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)(2)D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.

5-HT2A Receptor Induces ERK Phosphorylation and Proliferation through ADAM-17 Tumor Necrosis Factor-α-converting Enzyme (TACE) Activation and Heparin-bound Epidermal Growth Factor-like Growth Factor (HB-EGF) Shedding in Mesangial Cells

In this study, we present multiple lines of evidence to support a critical role for heparin-bound EGF (epidermal growth factor)-like growth factor (HB-EGF) and tumor necrosis factor-alpha-converting enzyme (TACE) (ADAM17) in the transactivation of EGF receptor (EGFR), ERK phosphorylation, and cellular proliferation induced by the 5-HT(2A) receptor in renal mesangial cells. 5-hydroxy-tryptamine (5-HT) resulted in rapid activation of TACE, HB-EGF shedding, EGFR activation, ERK phosphorylation, and longer term increases in DNA content in mesangial cells. ERK phosphorylation was attenuated by 1) neutralizing EGFR antibodies and the EGFR kinase inhibitor, AG1478, 2) neutralizing HB-EGF, but not amphiregulin, antibodies, heparin, or CM197, and 3) pharmacological inhibitors of matrix-degrading metalloproteinases or TACE small interfering RNA. Exogenously administered HB-EGF stimulated ERK phosphorylation. Additionally, TACE was co-immunoprecipitated with HB-EGF. Small interfering RNA against TACE also blocked 5-HT-induced increases in ERK phosphorylation, HB-EGF shedding, and DNA content. In aggregate, this work supports a pathway map that can be depicted as follows: 5-HT --> 5-HT(2A) receptor --> TACE --> HB-EGF shedding --> EGFR --> ERK --> increased DNA content. To our knowledge, this is the first time that TACE has been implicated in 5-HT-induced EGFR transactivation or in proliferation induced by a G protein-coupled receptor in native cells in culture.

Microfocus Computed Tomography Analysis of Early Changes in Bone Microstructure in Rats with Chronic Renal Failure

Background/Aims: Little is known about the microstructural changes in bone tissue in the early phase of chronic renal failure (CRF). In this study, we analyzed the bone tissue in a rat model of early CRF using a high-resolution X-ray tomographic system, i.e. microfocus computed tomography (MXCT), which is capable of detecting microscopic structural changes in bone tissue. Methods: CRF rats were created by 7/8 nephrectomy by ligation of the renal artery branches, and were sacrificed 24 weeks after surgery. MXCT and bone mineral densitometry by single-energy X-ray absorptiometry (SXA) were performed using extracted bone samples. Images obtained by MXCT were further analyzed by node-strut morphometry. Results: Biochemical analysis confirmed that CRF was induced in 7/8-renal artery-ligated rats. MXCT demonstrated a significant decrease in trabecular bone in uremic rats, whereas SXA was unable to detect the difference. The node-strut method revealed decreased trabecular connectivity, with little change in the thickness of the trabecular bone in uremic rats. Conclusion: MXCT was able to detect significant changes in trabecular bone at an early stage of renal failure. The observed structural changes differed from those found in long-term dialysis patients. MXCT is a practical and promising device used for the non-invasive evaluation of early bone changes in uremic patients.

Exploring the pathways leading from disadvantage to end-stage renal disease for Indigenous Australians

Indigenous Australians are disadvantaged, relative to other Australians, over a range of socio-economic and health measures. The age- and sex-adjusted incidence of end-stage renal disease (ESRD)—the irreversible preterminal phase of chronic renal failure—is almost nine times higher amongst Indigenous than it is amongst non-indigenous Australians. A striking gradient exists from urban to remote regions, where the standardised ESRD incidence is from 20 to more than 30 times the national incidence. We discuss the profound impact of renal disease on Indigenous Australians and their communities. We explore the linkages between disadvantage, often accompanied by geographic isolation, and both the initiation of renal disease, and its progression to ESRD. Purported explanations for the excess burden of renal disease in indigenous populations can be categorised as: (1) primary renal disease explanations; (2) genetic explanations; (3) early development explanations; and (4) socio-economic explanations. We discuss the strengths and weaknesses of these explanations and suggest a new hypothesis which integrates the existing evidence. We use this hypothesis to illuminate the pathways between disadvantage and the human biological processes which culminate in ESRD, and to propose prevention strategies across the life-course of Indigenous Australians to reduce their ESRD risk. Our hypothesis is likely to be relevant to an understanding of patterns of renal disease in other high-risk populations, particularly indigenous people in the developed world and people in developing countries. Furthermore, analogous pathways might be relevant to other chronic diseases, such as diabetes and cardiovascular disease. If we are able to confirm the various pathways from disadvantage to human biology, we will be better placed to advocate evidence-based interventions, both within and beyond the scope of the health-care system, to address the excess burden of renal and other chronic diseases among affected populations.

Angiographical severity of coronary atherosclerosis predicts death in the first year of hemodialysis.

Cardiac deaths and events tend to cluster within the early-phase after starting dialysis. Our goal is to clarify the influence of severity of coronary atherosclerosis on early-phase death after starting hemodialysis (HD) therapy. Eighty-three consecutive patients [mean age 62 years; male/female 64/19; diabetic nephropathy in 50 (54%)] with end-stage renal disease who admitted to our hospital to initiate regular HD treatment, and then received coronary angiography within 3 months after first dialysis therapy, were eligible for this study. Angiographical severity of coronary atherosclerosis was scored by numerically using Gensini scoring system. The patients who died within one year from starting HD were compared with those who survived as control by means of logistic regression analysis. Of 83 patients, 12 (14%) died less than one year after starting dialysis therapy. Of these 12 patients, nine died for cardiac causes. Confirmed predictors of death from cardiac cause were older age (>70 years), lower mean blood pressure (<100 mmHg), presence of ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), chronic heart failure (CHF), poor cardiac function, abnormal wall motion of left ventricule (LV) and angiographical severity of coronary atherosclerosis by univariate model. Adjusting for confounding variables by multivariate model, only severity of coronary atherosclerosis (Gensini score >40 points) had a powerful influence, increasing risk for cardiac cause of early-phase death by about 17 times. Severity of coronary atherosclerosis predicts death in the first year of HD. These findings suggest that the strategy for prevention of coronary atherosclerosis should be instituted during the early phase of chronic renal failure.

Cardiovascular Problems in Peritoneal Dialysis Patients: A Short Overview

cardiogram on starting dialysis. Forty-one percent had concentric left ventricular (LV) hypertrophy, 28% had LV dilatation, and 16% had systolic dysfunction. These results imply that the causes ofLV dysfunction occur in the predialysis phase of chronic renal failure. Two hundred and seventy-five patients had a f ollow-up echo cardiogram 17 months after starting dialysis therapy (12). Now the proportion of those who had a normal echocardiogram was 13%, the proportion with concentric LV hypertrophy was 40%, the proportion with LV dilatation was 26%, and the proportion with systolic dysfunction was 20% (12). In peritoneal dialysis patients, one might expect that blood flow would not increase as much as in hemodialysis patients, because no vascular access is required, and fluctuations in salt and water status are less variable. In 70 patients treated exclusively with peritoneal dialysis, LV cavity volume decreased by 5 mL/m2 during 1 year's follow-up (9). When compared to readings from hemodialysis patients, the differences in the changes in LV volume approached statistical significance (p = 0.06). In 55 normotensive CAPD patients who were on treatment for a mean of 28.8 ± 24.9 months, a high prevalence of left atrial dilatation and left ventricular hypertrophy was found (13). The latter was mainly the result of s eptal thickening. The degree ofventricular hypertrophy in these patients was related to the amount ofhypercirculation and to the quality of blood purification. Abnormal diastolic left ventricular filling in CAPD patients has been found in patients both with and without left ventricular hypertrophy (14,15). In these patients, a disturbed ratio exists between the ventricular rapid filling in protodiastole and the filling owing to atrial contraction, with a greater-thannormal atrial contribution. After init iation ofCAPD therapy, regression as well as progression in left ventricular hypertrophy has been described. Prospective studies did not show a deterioration in left ventricular function up to 2 years after the start of CAPD (16). Others did not observe changes in left ventricular mass, ejection fraction, or left ventricular telediastolic dimension, despite a fall in blood pressure

Renal osteodystrophy and vitamin D derivatives: cellular mechanisms of hyperparathyroidism in uremia.

In the early phase of chronic renal failure, physiological concentrations of 1,25(OH)2D in circulation may become insufficient to regulate parathyroid cell function normally. As a result, the set-point of PTH secretion to plasma Ca ion concentration shifts to the right, PTH synthesis becomes enhanced at transcriptional level, and parathyroid cells begin to proliferate. This resistance of the parathyroid cells to the physiological concentration of 1,25(OH)2D may be in part due to the reduction of 1,25(OH)2D receptor density in parathyroid cells. However, the mechanism by which the number of 1,25(OH)2D receptors decreases in parathyroid cells in early renal failure remains to be elucidated.

Testicular function in uremic rats: In vivo assessment of testosterone biogenesis

The mechanism of testosterone (T) production defect in uremic rats has not yet been clearly defined and hypothalamo-hypophyseal impairment as well as primary testicular dysfunction have been suggested. In 42 rats followed monthly after subtotal nephrectomy up to 7.1 ± 0.3 months, we observed a progressive significant decline of T and androstenedione (A) compared to control rats. Two months before the terminal phase of chronic renal failure (CRF), T/A ratio abruptly declined. T and its precursors on the 4-ene pathway, A, progesterone (P) and 17-hydroxyprogesterone were evaluated in pampiniform plexus testicular vein (PPTV) and in peripheral blood (PV) in end stage uremic rats (blood urea > 30 mmol/1, creatinine clearance < 0.5 ml/min). Under basal conditions, all steroids but peripheral P were significantly lower in uremic rats than in controls as well as T/P and A/P ratios. After human chorionic gonadotropin (hCG) stimulation, T concentration in PV and PPTV remained highly significantly lower than in controls whereas T precursor concentrations were partially corrected by hCG administration. T/P ratio remained lower than in controls whereas A/P ratio was not significantly lower than in controls. Those data show a decline in all the steps of T biogenesis in uremic rats in basal conditions. The defect in 17β-hydroxysteroid dehydrogenase evidenced by T/A decrease at the end stage of CRF seems of primary testicular origin as it is not corrected by hCG administration as shown by T/P and A/P ratios in PPTV and in PV.

Serum Alpha-1-Acid Glycoprotein in Chronic Renal Failure

We measured the serum concentration of alpha-1-acid glycoprotein (AAG) in 30 healthy subjects (controls), in 54 patients with various degrees of residual renal function (group I), and in 98 patients in the terminal phase of chronic renal failure (CRF) on both conservative and dialytic therapy (group II). A positive correlation between the logarithm of serum AAG and serum creatinine levels was found in group I. Serum AAG increased significantly when serum creatinine rose above 10 mg/dl. This fact would indicate that a retention of the substance occurs as the renal function falls. The mean serum concentration of AAG was significantly higher in group II patients, with no difference between those on conservative therapy and those on maintenance hemodialysis. However, levels above normal were present in only a minority of cases. We conclude that the serum AAG measurement maintains its diagnostic value as an acute phase reactant also in the terminal phase of CRF.

Lupus nephritis. Clinical and histologic survey.

Introduction Uremia has been cited as a leading cause of death in most reviews1-12of systemic erythematosus (SLE). This has been particularly true since the advent of steroid therapy which has prevented death in the acute toxic phase of the disease, permitting survival and progression to the phase of chronic renal failure.5 Interest with natural history of SLE has been heightened by the recent optimistic reports of Pollak et al.13and Holman,14both of which, contrary to previous opinions,2,3,8,9indicate favorable effects of high dosage steroid therapy. For this reason, we report our clinical and histologic experience. Methods and Material All cases of lupus nephritis from 1951 through mid-1961 at Georgetown University Hospital were reviewed clinically and histologically. The diagnosis was based on the presence of SLE and clinical and/or histologic evidence of renal involvement. After hospital charts were reviewed, the corresponding material, if