Elderly dialysis patients: analysis of factors affecting long-term survival in 4-year prospective observation

Purpose

To assess factors influencing the long-term survival of elderly dialysis patients.

Methods

The study group consisted of 51 prevalent dialysis patients aged over 70?years (32 F and 19?M, all caucasians), who had been on a chronic hemodialysis (27) or peritoneal dialysis program (24) for at least 2?months; median age was 77?years, median time on dialysis before inclusion was 16?months, and median residual diuresis was 600?ml. The patients were prospectively followed up to 4?years, and an analysis of factors affecting survival was performed.

Results

Thirteen patients from the initial cohort of 51 (25.5?%) survived the whole 48-month observation period: 10 HD patients (37?%) and 3 PD patients (12.5?%). Annual mortality rate was 28.2?%: 37.4?% on PD vs. 20.9?% on HD. The dialysis modality had a significant impact on patients?? survival (p?=?0.049; Cox F-test). The independent mortality risk factors in the Cox proportional hazard regression model were higher plasma pro-atrial natriuretic peptide (pro-ANP) (p?=?0.006), lower residual diuresis (p?=?0.048), and lower systolic blood pressure (BP) value (p?=?0.039).

Conclusions

Paramount for the survival of the elderly on dialysis is adequate extracellular volume control. Residual renal function is a protective factor for the survival of elderly HD patients. This observation is novel, not previously reported in an elderly dialysis population.     

Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.

OBJECTIVE: Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory. METHODS: This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT. RESULTS: Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls. CONCLUSION: SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.     

The Influence of Recombinant Human Erythropoietin on Tumor Necrosis Factor α and Interleukin-10 Production by Whole Blood Cell Cultures in Hemodialysis Patients

Abstract: Impaired immunological response in hemodialysis (HD) patients, which leads to inappropriate cytokine production, is partially caused by the hyperstimulation of both T lymphocytes and monocytes/macrophages. Recent data suggest that human recombinant erythropoietin (rhEPO) may have an immunological action. The goal of our study was to estimate the influence of rhEPO treatment on the production of the inflammatory cytokine tumor necrosis factor α (TNFα) and antiinflammatory cytokin interleukin-10 (IL-10) in 10 HD patients receiving rhEPO for 6 months. The levels of cytokines were measured in the in vitro cultures of whole blood. The level of IL-10 increased in all treated patients during the therapy, and it was accompanied by a transitory decrease of TNFα. The results of our studies suggest that rhEPO may reduce the inflammatory process by decreasing production of TNF α and increasing production of IL-10.     

Effect of the transdermal low-level laser therapy on endothelial function

The effect of low-level laser therapy (LLLT) on the cardiovascular system is not fully established. Since the endothelium is an important endocrine element, establishing the mechanisms of LLLT action is an important issue.The aim of the study was to evaluate the effect of transdermal LLLT on endothelial function.In this study, healthy volunteers (n?=?40, age?=?20–40 years) were enrolled. N?=?30 (14 female, 16 male, mean age 30?±?5 years) constituted the laser-irradiated group (LG). The remaining 10 subjects (6 women, 4 men, mean age 28?±?5 years) constituted the control group (CG). Participants were subjected to LLLT once a day for three consecutive days. Blood for biochemical assessments was drawn before the first irradiation and 24 h after the last session. In the LG, transdermal illumination of radial artery was conducted (a semiconductor laser λ?=?808 nm, irradiation 50 mW, energy density 1.6 W/cm² and a dose 20 J/day, a total dose of 60 J). Biochemical parameters (reflecting angiogenesis: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiostatin; antioxidative status: glutathione (GSH) and the nitric oxide metabolic pathway: symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA) and l-arginine) were assessed. In the LG, a significant increase in GSH levels and considerable decrease in angiostatin concentration following the LLLT were observed. No significant differences in levels of the VEGF, FGF, SDMA, ADMA were observed.LLLT modifies vascular endothelial function by increasing its antioxidant and angiogenic potential. We found no significant differences in levels of the nitric oxide pathway metabolites within 24 h following the LLLT irradiation.     

Feasibility study: watchful waiting for localized low to intermediate grade prostate carcinoma with selective delayed intervention based on prostate specific antigen, histological and/or clinical progression

PURPOSE: We assessed the feasibility of a watchful waiting protocol with selective delayed intervention using clinical, prostate specific antigen (PSA) or histological progression as treatment indications for clinically localized prostate cancer. MATERIALS AND METHODS: In this prospective, single arm cohort study patients with favorable clinical parameters (stage T1b to T2b N0M0, Gleason score 7 or less and PSA 15 ng./ml. or less) are conservatively treated with watchful waiting. When a patient meets disease progression criteria, arbitrarily defined by the 3 parameters of the rate of PSA increase, clinical progression or histological upgrade on repeat prostate biopsy, appropriate treatment is implemented. Patients are followed every 3 months for the first 2 years and every 6 months thereafter. Serum PSA measurement and digital rectal examination are done at each visit and repeat prostate biopsy is performed 18 months after study enrollment. RESULTS: Since November 1995, the study has accrued 206 patients with a median followup of 29 months (range 2 to 66). Of these men 137 remain on the surveillance protocol with no disease progression, while 69 were withdrawn from study for various reasons. There was clinical, PSA and histological progression in 16, 15 and 5 cases, respectively. The estimated actuarial probability of remaining on the surveillance protocol was 67% at 2 years and 48% at 4. The probability of remaining progression-free was 81% and 67% at 2 and 4 years, respectively. CONCLUSIONS: A policy of watchful waiting with selectively delayed intervention based on predefined criteria of disease progression is feasible. This strategy offers the benefit of an individualized approach based on the demonstrated risk of clinical or biochemical progression with time and, thus, it may decrease the burden of therapy in patients with indolent disease, while providing definitive therapy for those with biologically active disease.     

Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography.

Sir, Neutrophil gelatinase-associated lipocalin (NGAL), a memberof the lipocalin family, is readily excreted and detected inurine, due to its small molecular size (25 kDa) and resistanceto degradation. NGAL is highly accumulated in the human kidneycortical tubules, blood and urine, after nephrotoxic and ischaemicinjuries [1]. Thus, NGAL might represent an early, sensitive,non-invasive biomarker for acute renal injury [2], and urinaryNGAL might serve as an early marker for ischaemic renal injuryin children after cardiopulmonary bypass [3]. On the other hand,serum cystatin C was proposed as a new marker of glomerularfiltration rate (GFR), even in chronic kidney disease [4]. CystatinC has a low molecular weight (13 kDa) and is freely filtered     

Persistent downregulation of calcium-sensing receptor mRNA in rat parathyroids when severe secondary hyperparathyroidism is reversed by an isogenic kidney transplantation

Experimental severe secondary hyperparathyroidism (HPT) is reversed within 1 wk after reversal of uremia by an isogenic kidney transplantation (KT) in the uremic rats. Abnormal parathyroid hormone (PTH) secretion in uremia is related to downregulation of CaR and vitamin D receptor (VDR) in the parathyroid glands (PG). The aim of this investigation was to examine the expression of CaR and VDR genes after reversal of uremia and HPT in KT rats. 5/6 nephrectomized rats were kept on a normal or high-phosphorus (hP) diet for 8 wk to induce severe HPT (n = 8 in each group). In another group of seven uremic hP rats, uremia was reversed by an isogenic KT and PG were harvested within 1 wk posttransplant. Plasma urea, creatinine, total calcium, phosphorus, and PTH levels were measured. Parathyroid CaR and VDR mRNA were measured by quantitative PCR. Uremic hP rats had significantly elevated levels of creatinine, urea, and phosphorus (P < 0.001) and developed significant hypocalcemia (plasma calcium 1.83 +/- 0.2 mmol/L; P < 0.001) compared with normal control rats. After KT, the levels were normalized from day 3 to 7: creatinine from 0.117 +/- 0.016 to 0.050 +/- 0.002 mmol/L; urea from 23 +/- 4 to 7 +/- 0.3 mmol/L; phosphorus from 3.9 +/- 0.6 to 1.5 +/- 0.06 mmol/L; calcium from 1.8 +/- 0.2 to 2.5 +/- 0.02 mmol/L. Plasma PTH levels fell from 849 +/- 224 to a normal level of 38 +/- 9 pg/ml (P < 0.01). In uremic rats on a standard diet, CaR mRNA was similar to that of normal control rats, whereas VDR mRNA was significantly decreased. In uremic rats kept on hP diet, CaR mRNA was significantly decreased to 26 +/- 7% of control rats (P = 0.01) and VDR mRNA reduced to 36 +/- 11% (P < 0.01). In KT, previously hP uremic rats, both CaR mRNA and VDR mRNA remained severely reduced (CaR, 39 +/- 7%; VDR, 9 +/- 3%; P < 0.01) compared with normal rats. In conclusion, circulating plasma PTH levels normalized rapidly after KT, despite persisting downregulation of CaR and VDR gene expression. This indicates that upregulation of CaR mRNA and VDR mRNA is not necessary to induce the rapid normalization of PTH secretion from hyperplastic parathyroid glands.     

Parathyroid growth and suppression in renal failure

In advanced uremia, parathyroid hormone (PTH) levels should be controlled at a moderately elevated level in order to promote normal bone turnover. As such, a certain degree of parathyroid hyperplasia has to be accepted. Uremia is associated with parathyroid growth. In experimental studies, proliferation of the parathyroid cells is induced by uremia and further promoted by hypocalcemia, phosphorus retention, and vitamin D deficiency. On the other hand, parathyroid cell proliferation might be arrested by treatment with a low-phosphate diet, vitamin D analogs, or calcimimetics. When established, parathyroid hyperplasia is poorly reversible. There exists no convincing evidence of programmed parathyroid cell death or apoptosis in hyperplastic parathyroid tissue or of involution of parathyroid hyperplasia. However, even considerable parathyroid hyperplasia can be controlled when the functional demand for increased PTH levels is removed by normalization of kidney function. Today, secondary hyperparathyroidism can be controlled in patients with long-term uremia in whom considerable parathyroid hyperplasia is to be expected. PTH levels can be suppressed in most uremic patients and this suppression can be maintained by continuous treatment with phosphate binders, vitamin D analogs, or calcimimetics. Thus modern therapy permits controlled development of parathyroid growth. When nonsuppressible secondary hyperparathyroidism is present, nodular hyperplasia with suppressed expression of the calcium-sensing receptor (CaR) and vitamin D receptor (VDR) has been found in most cases. An altered expression of some autocrine/paracrine factors has been demonstrated in the nodules. The altered quality of the parathyroid mass, and not only the increased parathyroid mass per se, might be responsible for uncontrollable hyperparathyroidism in uremia and after kidney transplantation.     

Very long half‐life plasminogen activator inhibitor type 1 reduces bleeding in a mouse model

OBJECTIVE

To investigate the potential for the future clinical use of a very long half‐life plasminogen activator inhibitor type 1 (VLHL PAI‐1) as a haemostatic agent.

MATERIALS AND METHODS

We developed a VLHL PAI‐1 (half‐life >700 h) recombinant mutant of PAI‐1 and assessed VLHL PAI‐1 for its ability to inhibit fibrinolysis in vitro using human, rabbit, mouse and rat blood. Fibrin clot lysis time, monitored by thromboelastometry, was determined at various concentrations of VLHL PAI‐1. Also, we determined total bleeding time and total blood loss of control, VLHL PAI‐1‐, tissue‐type plasminogen activator (tPA)‐ and tPA + VLHL PAI‐1‐treated mice.

RESULTS

Using a thromboelastometer, mouse blood was most similar to human blood in its coagulation and fibrinolytic characteristics. We evaluated the affect of VLHL PAI‐1 on haemostasis using the mouse model and showed that VLHL PAI‐1 is an effective inhibitor of fibrin clot degradation. It reduced time of bleeding and total blood loss.

CONCLUSION

VLHL PAI‐1 may provide an important physiological mechanism to protect clots from premature dissolution in surgical and trauma settings.