Coronary revascularization in uremic diabetic patients under chronic hemodialysis

Coronary heart disease is the main cause of mortality among uremic patients on chronic hemodialysis (CHD) and is the determinant of the outcome in these cases after renal transplantation, especially in diabetics. In this study we report our experience with two uremic diabetics on CHD with severe coronary artery lesions in whom aortocoronary bypass was performed before renal transplantation. The outcome in the two patients, after 30 and 55 months respectively indicates successful results. We discuss the necessity to perform coronariography in all the high risk patients on CHD, such as diabetics and elderly before planning renal transplantation and achieve aortocoronary bypass surgery in those with severe coronary disease. The technics and difficulties of the surgery in uremics are also analized.     

Effect of hemodialysis and hemodiafiltration on uremic neuropathy.

This study was undertaken to compare the effect of 1 year hemodialysis (HD) or hemodiafiltration (HDF) treatment on peripheral neuropathy. Thus 21 of 42 patients on chronic HD (1-1.3 m2 cuprophane dialyzer, Qb 300 ml/min) were switched to HDF (1.3 m2 polysulfone dialyzer, Qb 400 ml/min, substitution volume 9-13 liters, ultrafiltration rate 60-70 ml/min), while the remaining patients were considered as a control group. Treatment time was scheduled both in HD and HDF to maintain adequate BUN levels in relation to protein catabolic rate. However, HDF provided a significantly greater weekly inulin (MW 5,000) clearance than HD (5.8 +/- 1.2 vs. 1.6 +/- 0.2 ml/min; p less than 0.001). HD and HDF groups were comparable for age, time on dialysis and starting electroneurographic parameters, which were on average within the normal range. After 1 year follow-up, creatinine, hematocrit, calcium, phosphate, PTH, BUN, protein catabolic rate and residual GFR were comparable in the two groups, whereas beta 2-microglobulin was significantly reduced in HDF patients (29 +/- 6.7 vs. 38.8 +/- 13.9 mg/l in HD patients, p less than 0.01). During the 1-year treatment, electroneurographic parameters did not change in HDF patients, whereas a significant decrease of ulnar motor nerve conduction velocity, ulnar muscle action potential amplitudes, median sensory nerve conduction velocity and peroneal muscle action potential amplitudes was detected in HD patients. We conclude that HDF might prevent the worsening of the electroneurographic indices occurring during chronic HD treatment, as it provides a more effective removal of middle and larger molecules than HD. The use of a more biocompatible membrane in HDF might further contribute to this favorable effect on uremic neuropathy.     

Alterations of granulopoiesis in chronic uremic patients treated with intermittent hemodialysis

Granulocyte-macrophage progenitor cells (CFU-GM), leukocyte colony-stimulating activity (CSA), granuloblast differentiation and proliferation and the effect of uremic serum on the in vitro growth of normal CFU-GM have been studied in 8 chronic uremic patients treated with intermittent hemodialysis three times a week. The studies were performed in the postabsorptive state twice in each patient, that is at the longest and shortest dialytic interval. CFU-GM growth in agar and leukocyte CSA did not differ significantly from the normal level in uremic subjects. The granulocytic and macrophagic differentiation in a liquid culture system was significantly reduced in uremic patients, notwithstanding the appearance of high numbers of undifferentiated blastic cells. The serum of uremic patients had no effect on normal CFU-GM and leukocyte CSA.     

Changes in heart rate variability in chronic uremic patients during ultrafiltration and hemodialysis

BACKGROUND: The analysis of heart rate variability (HRV) is a useful tool to evaluate cardiac autonomic modulation, which is frequently impaired in chronic uremia. AIMS: The aim of this study was to evaluate HRV in chronic uremics and to separately investigate the acute changes induced by volume depletion and solute removal during a hemodialysis session. METHODS: Fourteen uremic patients (8 males and 6 females, aged 50 +/- 15 years) on maintenance hemodialysis and 14 sex- and age-matched healthy controls were studied. Both groups underwent ambulatory electrocardiogram monitoring to evaluate the HRV time and frequency domain indices. The hemodialysis session was performed by 1 h of high-rate isolated ultrafiltration followed by 3 h of bicarbonate diffusive procedure. RESULTS: In uremic patients, the overall variability in the frequency [low-frequency power (LF): 505 +/- 473, vs. 1,446 +/- 654; high-frequency power (HF): 133 +/- 162 vs. 512 +/- 417; p < 0.001] and time domain indices (standard deviation of normal R-R intervals: 101.9 +/- 33.3 vs. 181.7 +/- 44.1 ms; p < 0.001) was markedly reduced compared to controls, whereas mean heart rate (83 +/- 12.4 vs. 60.9 +/- 8.8 bpm; p < 0.001) and LF/HF ratio (5.8 +/- 3.5 vs. 2.2 +/- 0.8; p < 0.001) were increased. Isolated ultrafiltration produced a marked further decrease in HRV indices, but the subsequent diffusive hemodialysis procedure, with a low ultrafiltration rate, made HRV increase again. CONCLUSIONS: Chronic uremics showed abnormal autonomic modulation with sympathetic-vagal imbalance. The unbalanced hypersympathetic response to body fluid depletion is related to the ultrafiltration rate. Low interdialytic weight gain and a low ultrafiltration rate, associated with adequate hemodialysis, should be the preferable strategy for uremic patients with autonomic dysfunction.     

Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients undergoing hemodialysis

carnitine concentrations were measured in the plasma and adipose tissue of seven chronically uremic and hyperlipidemic patients undergoing hemodialysis. Plasma levels of carnitine had dropped by the end of dialysis. The clearance of free carnitine was greater than that of acylcarnitine. Fasting plasma free carnitine, long-chain acylcarnitine, d-β-hydroxybutyrate and free fatty acid concentrations were normal but short-chain acylcarnitine values were elevated. In adipose tissue, total carnitine concentrations were normal but long-chain acylcarnitine concentrations were increased. These findings may indicate a hypermetabolic state in which the acute removal of carnitine during hemodialysis may lead to a critical shortage of this substance.     

Electrical spinal cord stimulation in the long-term treatment of chronic painful diabetic neuropathy.

AIMS: Electrical spinal cord stimulation (ESCS) is a technique for the management of chronic painful diabetic neuropathy (CPDN) affecting the lower limbs. We assessed the efficacy and complication rate of ESCS implanted at least 7 years previously in eight patients. METHODS: After a trial period of percutaneous stimulation, eight male patients had been implanted with a permanent system. Mean age at implantation was 53.5 years and all patients were insulin treated with stage 3 severe disabling CPDN of at least 1 year's duration. The ESCS was removed from one patient at 4 months because of system failure and one patient died 2 months after implantation from a myocardial infarction. RESULTS: Six patients were reviewed a mean of 3.3 years post-implantation. With the stimulator off, McGill pain questionnaire (MPQ) scores (a measure of the quality and severity of pain) were similar to MPQ scores prior to ESCS insertion. Pain scores (visual analogue scale) were measured with the stimulator off and on, respectively: background pain [74.5 (63-79) mm vs. 25 (17-33) mm, median (interquartile range), P = 0.03), peak pain (85 (80-92) mm vs. 19 (11-47) mm, P = 0.03]. There were two further cardiovascular deaths (these patients had continued pain relief) and the four surviving patients were reassessed at 7.5 (range 7-8.5) years: background pain [73 (65-77) mm vs. 33 (28-36) mm, median (interquartile range)], peak pain [86 (81-94) mm vs. 42 (31-53) mm]. Late complications (> 6 months post-insertion) occurred in two patients; electrode damage secondary to trauma requiring replacement (n = 1), and skin peeling under the transmitter site (n = 1). One patient had a second electrode implanted in the cervical region which relieved typical neuropathic hand pains. CONCLUSIONS: ESCS can continue to provide significant pain relief over a prolonged period of time with little associated morbidity.     

血液透析患者冠心病介入治疗可行性初探

目的　探讨尿毒症血液透析患者进行冠状动脉造影及介入治疗的可行性及近期疗效。方法　对 3例频发心绞痛的血液透析患者在适当水化和强化透析基础上 ,应用非离子型造影剂行冠状动脉造影术。结果　单支病变 2例 ,双支 (多处 )病变 1例。分别于造影后 4～ 7日行支架置入术 ,成功置入 1～ 4个支架。术后临床随访 12～ 18个月 ,患者心绞痛症状明显缓解或消失 ,肾功能无恶化。结论　对血液透析患者行冠状动脉造影及介入治疗是安全可行的。     

Relation between asymmetrical hypertrophy of the interventricular septum and plasma levels of catecholamines in normotensive chronic uremic patients undergoing hemodialysis treatment

Sympathetic-adrenergic activity has been evaluated in 23 chronic uremic, normotensive patients on regular hemodialysis, 7 of which (30.4%) with M-mode and bidimensional echocardiographic finding of asymmetric septal hypertrophy. The sympathetic function has been assessed by measuring arterial plasma norepinephrine and epinephrine levels before and after postural activation, just before and after dialysis. After dialysis, standing caused a significant increase of plasma norepinephrine levels in patients with asymmetric septal hypertrophy in comparison with patients without asymmetric septal hypertrophy and with the control non uremic group. Moreover, a significant decrease in blood pressure and a sharp heart rate increase were noted in the patients without asymmetric septal hypertrophy, whereas mean blood pressure and heart rate were unchanged in the patients with asymmetric septal hypertrophy. These results suggest that increased plasma norepinephrine concentration may have a role in the development of interventricular septal hypertrophy.     

Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure.

AIMS: An erythropoietin (EPO)-deficient anaemia is recognized in Type 1 diabetic patients with early nephropathy and symptomatic autonomic neuropathy (DN). The aim of this study was to determine whether the EPO response to hypoxia was deficient in order to clarify the mechanisms involved in this process. METHODS: Five Type 1 diabetic patients DN (age 39 (28-48) years (mean (range))) with EPO-deficient anaemia (haemoglobin, Hb 10.6 (9.5-12.0) g/dl, EPO 5.0 (3.2-6.5) IU/l) and early diabetic nephropathy (persistent proteinuria 1161.6 (130-2835) mg/day, serum creatinine 97.6 (63-123) micromol/l)) were compared with nine normal subjects (age 31 (24-39) years, Hb 13.4 (11.8-15.7) g/dl, EPO 7.6 (5.6-10.3) IU/l) and four patients with non-diabetic advanced chronic renal failure RF (proteinuria 2157.5 (571-4578) mg/day, serum creatinine 490.2 (406-659) micromol/l, Hb 10.3 (9.0-11.3) g/dl, EPO 4.6 (2.9-8.5) IU/l). The subjects were exposed to 6 h of hypoxia (inspired oxygen 11.6-12.6%) by breathing a gas mixture via a hood. Hourly serum EPO levels were measured. RESULTS: All groups showed a rise in EPO production after 2 h. The diabetic DN group achieved a similar maximal response to the normal subjects at 6 h (EPO 17.3 +/-5.4 vs. 17.8 +/-7.9 IU/l). The renal failure patients mounted an EPO response to hypoxia but at lower EPO levels. CONCLUSIONS: Although the DN patients have inappropriately low EPO levels for the severity of their anaemia, they can mount an appropriate EPO response to moderate hypoxia. The mechanism underlying the EPO-deficient anaemia present in some diabetic patients remains unclear.     

Intravenous iron alone for the treatment of anemia in patients with chronic heart failure.

OBJECTIVES: This study was undertaken to assess the hematologic, clinical, and biochemical response to intravenous iron in patients with chronic heart failure (CHF) and anemia. BACKGROUND: Anemia is common in patients with CHF and is associated with higher morbidity and mortality. The combination of erythropoietin (EPO) and iron increases hemoglobin (Hb) and improves symptoms and exercise capacity in anemic CHF patients. It is not known whether intravenous iron alone is an effective treatment for anemia associated with CHF. METHODS: Sixteen anemic patients (Hb < or =12 g/dl) with stable CHF (age 68.3 +/- 11.5 years, 12 men, 9 participants New York Heart Association [NYHA] functional class II and the remainder class III, left ventricular ejection fraction 26 +/- 13%) received a maximum of 1 g of iron sucrose by bolus intravenous injections over a 12-day treatment phase in an outpatient setting. Mean follow-up was 92 +/- 6 days. RESULTS: Hemoglobin rose from 11.2 +/- 0.7 to 12.6 +/- 1.2 g/dl (p = 0.0007), Minnesota Living with Heart Failure (MLHF) score fell (denoting improvement) from 33 +/- 19 to 19 +/- 14 (p = 0.02), 6-min walk distance increased from 242 +/- 78 m to 286 +/- 72 m (p = 0.01), and all patients recorded NYHA class II at study end (p < 0.02). Changes in MLHF score and 6-min walk distance related closely to changes in Hb (r = 0.76, p = 0.002; r = 0.56, p = 0.03, respectively). Of all baseline measurements, only iron and transferrin saturation correlated with increases in Hb (r = 0.60, p = 0.02; r = 0.60, p = 0.01, respectively). There were no adverse events relating to drug administration or during follow-up. CONCLUSIONS: Intravenous iron sucrose, when used without concomitant EPO, is a simple and safe therapy that increases Hb, reduces symptoms, and improves exercise capacity in anemic patients with CHF. Further assessment of its efficacy should be made in a multicenter, randomized, placebo-controlled trial.     

Novel treatment modalities for painful diabetic neuropathy

Background and aimsPainful diabetic neuropathy significantly affects the quality of life in people with diabetic peripheral neuropathy (DPN). Existing pharmacological agents have limited efficacy and development of tolerance is a limitation.MethodsThe present review focuses on novel pharmacological (systemic and topical) and non-pharmacological modalities for the alleviation of pain in people with DPN. We identified English language articles concerning studies with novel agents (animal or human) targeting symptomatic relief of painful diabetic neuropathy.ResultsThough the pathophysiology of pain in DPN is complex, a better understanding of pain pathways (peripheral and central) have helped to identify potential targets for therapeutic success. Studies of pharmacological agents acting on various aspects of pain pathways including μ-opioid receptor agonist- norepinephrine reuptake inhibitor (MONRI), cannabinoid receptor, dual serotonin-nor-adrenergic (SNRI)-and triple dopamine reuptake inhibitor (SNDRI), purinergic receptors and sodium channel v1.7 blockers have undergone trials in humans and shown to improve pain symptoms and quality of life in people with DPN. A few other investigational agents targeting acetylcholine receptor, vanilloid channel, chemokine signaling, micro-RNA or mesenchymal stem cell based therapies (animal studies) have demonstrated promise in alleviation of pain. Topical agents like high-dose lidocaine, capsaicin, clonidine, amitriptyline and ketamine may benefit refractory neuropathic pain.ConclusionsNovel MONRI, SNRI and cannabinoid receptor agonists have shown some promise for neuropathic pain relief in human trials, but await regulatory approvals. However, most of the novel pharmacological agents (systemic or topical) require appropriately powered placebo-controlled studies for clinical usage in painful diabetic neuropathy.     

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糖尿病肾病(DN)发展到终末期的过程是可以延缓但却是不可逆的。近年国内外报道,肾脏替代治疗人群源于DN逐年增多,美国DN在透析患者中占40%,以2型糖尿病居多[1]。目前我国DN发病率也呈上升趋势,已占透析患者的13.5%,我院统计为8.2%[2]。1充分血液透析延缓糖尿病肾病进展糖尿病导致DN的主要机制是高血糖、高血压、高血脂、内分泌紊乱、血流动力学异常以及微血管结构损害,还包括透析相关因素、遗传因素等[3]。DN早期干预的目的是减慢肾病进展速度,预防高血压和血脂代谢紊乱等导致的心血管并发症。干预重点是在充分透析的基础上控制血糖和…     

Pathophysiology and treatment of diabetic neuropathy

The scope of the present review is to describe epidemiology, classification, symptomatology and treatment of diabetic peripheral somatic neuropathy and autonomic neuropathy. Special attention is paid to the use of local anaesthetic agents in painful diabetic neuropathy. Denervation hypersensitivity is a characteristic of autonomic neuropathy in diabetic patients. The pathophysiology behind this phenomenon is elucidated in this review and most recent studies related to diabetic encephalopathy are reviewed. References for this review were acquired via a MedLine and MedLars literature search. © 1998 John Wiley & Sons, Ltd.     

糖尿病神经病变的诊断和治疗

糖尿病神经病变是指因糖尿病之慢性高血糖状态及其所致各种病理生理改变而导致的神经系统损伤,可累及全身神经系统任何部分,此组病变是糖尿病最常见和最复杂的并发症。超过50%的糖尿病患者有糖尿病神经病变,最常见的是慢性感觉运动性的对称性糖尿病周围神经病变(DPN)和糖尿病自主神经病变(DAN)。糖尿病神经病变对患者的生活质量造成极大影响,如DPN可导致足部溃疡、坏疽,以至截肢,而DAN可累及身体各系统并导致严重后果,尤其是心脏自主神经病变(CAN)的致残率和致死率非常之高。对那些高危糖尿病神经病变患者,运用合适的干预办法可以使溃…     

Microalbuminuria in diabetic subjects with chronic peripheral neuropathy

Fifty-five patients with chronic peripheral neuropathy, 31 with and 24 without retinopathy, had albumin excretion rates determined on 2-h supine urine collections on three occasions by a radioimmunoassay method. Four patients with retinopathy had albustix-positive proteinuria and were excluded from subsequent analysis. Microalbuminuria was found in 20 of the 27 patients with retinopathy compared with 10 of the 24 patients with neuropathy alone. The mean albumin excretion rate (AER) was higher in neuropathic patients with retinopathy than in those patients with neuropathy alone (41.2 +/- 40.3 vs 18.8 +/- 33.2 micrograms/min, P less than 0.01). Multivariate analysis of the data was performed and this revealed a correlation coefficient of R2 = 0.33 (P less than 0.01) for AER as the dependent variable with respect to the independent variables HbA1, systolic blood pressure and known duration of diabetes. There was, however, no significant contribution separately of these individual variables to the regression equation. Microalbuminuria was significantly associated with retinopathy although almost half of the patients with neuropathy alone had microalbuminuria. The association between microalbuminuria and neuropathy even in the absence of retinopathy provides support for a microvascular element in the pathogenesis of diabetic neuropathy.