Vascular response to vasoactive agents in dialysed patients with chronic renal failure with and without diabetes mellitus

Using a muscle bath technique the vascular response to KCl,noradrenaline, angiotensin II, acetylcholine, and sodium nitroprussidewere evaluated in 13 patients with diabetes mellitus (DM group)and 15 non-diabetic (non-DM group) chronic renal failure patientstreated with haemodialysis. There were no differences in age,duration of haemodialysis, blood pressure and the levels ofplasma renin activity, noradrenaline, and parathyroid hormonebetween groups. After informed consent was obtained, a smallpiece of forearm vein was resected during the blood access surgery.The ring preparation of the blood vessel was sustained in themuscle bath filled with Krebs-Henseleit solution and the isometrictension development was recorded. All drugs produced concentrationdependent responses in the ring preparations of both groups.Although there were no significant differences in E_max valuesfor KCl-and angiotensin-II-induced contractions between groups,the value for noradrenaline in the DM group was significantlyless than that in the non-DM group. Sodium nitroprusside completelyrelaxed the ring preparation precontracted by 10^–5 M noradrenaline.However, the response to acetylcholine in the DM group was significantlyweaker than that in the non-DM group. These results suggesta reduced vascular response to noradrenaline and acetylcholinein dialysed diabetic renal failure patients, which may relateto the autonomic nervous system dysfunction.     

Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients

INTRODUCTION: Fibroblast growth factor (FGF) 23 is a recently identified circulating factor that regulates phosphate (Pi) metabolism. Since the derangement of Pi control is an important risk factor for vascular calcification, we investigated the importance of plasma FGF-23 in the development of vascular calcification in the aorta and peripheral artery in hemodialysis patients with and without diabetes mellitus (DM). METHODS: Male hemodialysis patients with DM (n=32) and without DM (n=56) were examined. Plasma samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Roentgenography of the aorta and hand artery was performed, and visible vascular calcification was evaluated by one examiner, who was blinded to the patient characteristics. RESULTS: In the 56 non-DM hemodialysis patients, vascular calcification was found in the hand artery in 5 patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and 21 (65.6%) had vascular calcification of the hand artery and aorta, respectively. Multiple regression analyses performed separately in the non-DM and DM patients showed that the plasma FGF-23 level, CaxPi product, and body weight are independent factors significantly associated with hand-artery calcification and that diastolic blood pressure is associated with aorta calcification in non-DM patients. In DM patients, the plasma FGF-23 level and hemodialysis duration emerged as independent factors associated with hand-artery calcification and diastolic blood pressure was associated with aorta calcification. The independent association of the plasma FGF-23 level with hand-artery calcification was retained in both non-DM and DM patients when adjusted for the CaxPi product. CONCLUSION: Our findings show that the plasma FGF-23 level is an independent factor negatively associated with peripheral vascular calcification in the hand artery, but not in the aorta, in both male non-DM and DM hemodialysis patients, even when adjusted for the CaxPi product. This study raises the possibility that the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial calcification in male hemodialysis patients, independent of its regulatory effect on Pi metabolism.     

Hypotension during hemodialysis results from an impairment of arteriolar tone and left ventricular function

AIMS: Hypotensive episodes are a major complication of hemodialysis. Hypotension during dialysis could be directly related to a reduction in blood volume or to a decrease in cardiovascular activation as a response to decreased cardiac filling. A decreased cardiovascular activation could be due to patient-related or to dialysis-related factors. In order to study the isolated effect of a reduction in filling pressure, lower body negative pressure (LBNP) causes activation of the cardiovascular reactivity with a decrease in cardiac filling, but without the influence of the dialysis procedure that could affect cardiovascular reactivity. METHODS: We studied the relationship between relative blood volume (RBV), central venous pressure (CVP), systolic arterial pressure, heart rate, stroke volume index (SI), and total peripheral resistance index (TPRI) during a combined dialysis/ultrafiltration and during LBNP to -40 mmHg in 21 hemodialysis patients with a high incidence of hypotension. Systolic arterial pressure, heart rate, SI and TPRI were measured by Finapres. CVP was measured after cannulation of the jugular vein. During dialysis RBV was measured by a blood volume monitor (BVM). In order to study the conditions in which hypotension occurred after dialysis, we divided the patients into 2 groups: hypotensive (H) and non-hypotensive (NH) during dialysis. RESULTS: Baseline levels did not show any significant differences. During dialysis systolic arterial pressure declined gradually in the H group from 30 minutes before the onset of hypotension. There was a similar decrease of RBV and increase of heart rate in both groups with a large interindividual variation. At hypotension, H patients showed a significantly smaller increase in TPRI as compared to NH patients. The reduction in SI tended to be greater at hypotension, while CVP decreased to a similar extent in both groups. Moreover, during LBNP, a similar reduction in CVP resulted in a much smaller decrease in SI. Systolic arterial pressure was only slightly lowered due to a much greater increase in TPRI. CONCLUSION: We conclude that dialysis-related hypotension in our patient group did not result from an inability to maintain blood volume or from decreased cardiac filling. Hypotension appeared to result from the inability to adequately increase arteriolar tone and a reduction in left ventricular function. Both vascular tone and left ventricular function appeared to be impaired by the dialysis procedure.     

Which components of malnutrition–inflammation–atherosclerosis syndrome are more common in haemodialysis patients with diabetic nephropathy?

Aim:   Malnutrition–inflammation–atherosclerosis syndrome (MIA) in haemodialysis (HD) patients is a common clinical condition characterized by increased mortality rate. The aim of this study was to analyze the frequency of MIA components in a selected population of HD patients with and without diabetic nephropathy.
Methods:   The frequency of MIA components was analysed in 49 patients with an over 10-year history of diabetes before initiation of HD (DM group) and 49 non-diabetic HD patients (non-DM group).
Results:   The chance for occurrence of atherosclerosis (odds ratio = 3.26) was markedly higher in DM than non-DM subjects. The most frequent MIA component in DM and non-DM subjects was atherosclerosis (67.3% and 40.8%, respectively). Atherosclerosis frequently coexisted with inflammation in both groups (51.5% in DM and 20.0% in non-DM) and less frequently with malnutrition. The frequency of inflammation was only slightly higher in DM, while of malnutrition was similar. Patients with atherosclerosis in the DM group had significantly higher serum concentrations of interleukin-6 than the ones in the non-DM group: 11 (6–24) versus 5 (2–9) pg/mL, respectively ( P  = 0.002).
Conclusions:   We can conclude that: (i) atherosclerosis is more common in HD patients with diabetic nephropathy; and (ii) this fact may explain the poor outcome of these patients and indicates the challenge in diagnostic and therapeutic management.     

Optimal hematocrit based on regional cerebral blood flow in hemodialysis patients with diabetic nephropathy

Background. The optimal hematocrit (Hct_opt) in hemodialysis (HD) patients has yet to be determined based on the etiology and complications of their endstage renal disease (ESRD). To investigate this problem, we compared regional cerebral oxygen supply (rCOS) in diabetic (DM group) and non-diabetic HD patients (non-DM group) with data from subjects without renal disease or DM (control group). Methods. Regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography (SPECT) by the N-isopropyl-p-[¹²³I]-iodoamphetamine (¹²³I-IMP)-autoradiographic (ARG) method, and both the O₂ content (O₂CT) of arterial blood and hematocrit (Hct) were evaluated. Using the regression lines of rCBF vs Hct and O₂CT vs Hct, we established a convex curve between rCOS and Hct. The peak of the curve indicates the maximum rCOS (rCOS_max) and Hct_opt for rCOS_max. Results. The rCBF in both the DM and non-DM groups was lower than that of the control group at the same Hct level, and the DM group had the lowest values. The rCOS_max values in the DM and non-DM groups were nearly equal, but both were lower than in controls. The Hct_opt in the DM group was lower than that in the non-DM group by 6.3% - 3.3%. Conclusions. Although the difference in Hct_opt values in the DM and non-DM groups was 6.3%, the rCOS_max values in both groups were nearly equal. This suggests that differences in the Hct_opt may depend on complications or causes of ESRD. The optimal Hct in the DM group was 22.6% - 1.9%, and that for the non-DM group was 29.0% - 1.8%.     

Changes in parathyroid hormone in diabetic patients on long-term hemodialysis

Changes in parathyroid hormone (PTH) and osteocalcin over 3 years were studied in hemodialyzed patients with diabetic nephropathy (HD/DM) and hemodialyzed patients without diabetes (HD/non-DM). In HD/DM patients, concentrations of the carboxyl terminal regions of PTH and osteocalcin in the serum did not change significantly, but in HD/non-DM patients, both concentrations increased significantly. In patients in both groups, the mean concentration of the mid-region of PTH increased significantly. Secondary hyperparathyroidism in HD/DM develops slower than in HD/non-DM.     

Paraoxonase (Pon1) Q192R polymorphism and serum Pon1 activity in diabetic patients on maintenance hemodialysis

Patients with diabetic nephropathy have an increased risk of coronary heart disease (CHD). Paraoxonase (Pon1) is a high-density lipoprotein- (HDL) associated enzyme that protects low-density lipoprotein from oxidation and also protects against atherosclerosis. We investigated the relationship of serum Pon1 activity, Pon1 Q192R polymorphism and HDL-C level to type 2 diabetes mellitus (DM) in patients on maintenance hemodialysis (HD). DM patients (n = 56, F/M = 17/39, aged 64.5 +/- 7.5 years) and non-DM patients (n = 89, F/M = 28/61, aged 62.7 +/- 8.3 years) under HD were included in this study. Salt-stimulated serum Pon1 activities were measured using paraoxon as a substrate. Pon1 Q192R polymorphism was detected by the mutagenically separated polymerase chain reaction. DM patients on HD had significantly lower HDL-C levels and serum Pon1 activities than non-DM patients on HD (657 +/- 277 vs. 763 +/- 257 IU/l, p < 0.01). The distribution of Pon1 Q 192R genotypes in all subjects did not differ from that predicted from the Hardy-Weinberg equilibrium. Serum Pon1 activities in both DM and non-DM patients on HD were regulated by Pon1 Q192R polymorphism: RR > QR > QQ. However, the reduced Pon1 activities in DM patients on HD were related to DM independent of the Pon1 genotype: reduced Pon1 activity was related to DM in RR carriers. Serum Pon1 activities were positively correlated with HDL-C levels. The association between HDL-C and DM in hemodialyzed patients was independent of Pon1 activity as assessed by an analysis of variance. But the relation between Pon1 activity and DM was modified by HDL-C levels: significantly when HDL-C was below 50 mg/dl, but not significantly when HDL-C was above 50 mg/dl. The results of a logistic regression analysis show that reduced serum Pon1 activities and low HDL-C levels were additively associated with DM. In conclusion, Pon1 status and HDL levels are independently associated with DM in patients on hemodialysis and may contribute to the increased risk of CHD in diabetic nephropathy.     

Results of Kidney Transplantation for Diabetic Nephropathy: A Single-Center Experience

In Japan, diabetic nephropathy accounted for 16,225 (43.7%) of the 38,473 patients who began hemodialysis in 2010 and the number increases year by year. In 1991, we started a kidney transplantation program for patients with diabetic nephropathy in our institution, and the ratio of patients who underwent kidney transplantation for diabetic nephropathy traces the course of increase. Among the 516 patients who underwent primary kidney transplantation in our institution from January 1991 to February 2013, we divided them into 2 groups. One group was the diabetes mellitus (DM) group, which included patients with primary disease of diabetic nephropathy, and the other group was the non-DM group. The DM group included 50 patients, and in our institution the ratio traces the course to increase. There was no significant difference for the 1-year and 5-year patient survival rates and graft survival rates between the DM group and the non-DM group. Moreover, the rate of acute rejection in the 2 groups was not significantly different. Furthermore, when we investigated the causes of death in the 2 groups, there was no significant difference with the mortality of cases due to heart vascular disease in the DM group and the non-DM group. Also, no case in which the graft lost function due to recurrence of diabetic nephropathy was observed. Although the early outcome of kidney transplantation for diabetic nephropathy in our institution did not have inferiority in comparison with kidney transplantation for the other primary disease, we think that careful diabetic control after kidney transplantation is required for long-term outcome.     

Perceived health-related quality of life and comorbidity in diabetic patients starting dialysis (CALVIDIA study)

BACKGROUND: Diabetes mellitus (DM) is a widespread prevalent illness, currently the main cause of end-stage renal disease (ESRD). MATERIAL AND METHODS: In a longitudinal, prospective study we compared two cohorts of patients starting dialysis therapy, diabetic and non-diabetic ESRD patients. Perceived health was measured by the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire, functional status by the Karnofsky scale and comorbidity by the Charlson age-comorbidity index. A broad spectrum of variables in relation to diabetes, ESRD, comorbidity and renal replacement therapy (RRT) were studied, as well as the distribution of comorbidity frequencies at dialysis start. RESULTS: Thirty-four Spanish centers included 232 diabetic patients, 43 type 1 and 189 type 2, mean diabetes duration 18 +/- 9 yrs, and five centers included 121 non-diabetic patients. Out of the 232 diabetic patients, 187 patients (81%) started hemodialysis (HD) and 45 patients (19%) started peritoneal dialysis (PD) (vs. 82% and 18%, respectively in non-diabetic patients). Transient vascular access (VA) for starting RRT was required in 54% of the diabetic patients vs. 53% in the nondiabetic patients. When both study groups were compared, diabetic patients required antihypertensive drugs more frequently than non-diabetic patients and showed higher systolic blood pressure (BP), as well as higher cardiovascular (CV) complication incidences, poorer SF-36 physical component summary scores and mental component summary scores and worse Karnofsky scale scores, with the Charlson age-comorbidity score being higher. CONCLUSION: Diabetic patients starting dialysis in Spain are more often type 2 diabetics, have worse perceived health-related quality of life (HRQoL) in relation to non-diabetic patients, worse functional status and higher incidences of prognostic mortality markers.     

The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter Clinic Study

Purpose: It is well established that diabetic peritoneal dialysis (PD) patients have a higher mortality rate than the other PD population. This study was designed to determine the overall predictors of survival and compared mortality and morbidity between diabetic and non-diabetic Turkish PD patients. Methods: We conducted a multicenter retrospective study with 915 PD patients [217 had diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis episodes and ultrafiltration failure during the follow-up period were recorded. Results: DM patients were older and had more co-morbidities than non-DM patients. Peritonitis rates were higher in DM patients (one episode per 35.9 patient months) compared to non-DM patients (one episode per 41.5 patient months) (p?p?=?0.022), age (HR 1.03, p?p?p?=?0.038), peripheral artery disease (HR 1.83, p?=?0.025) and amputation (HR 4.1, p?=?0.009) at baseline were significant predictors of overall mortality. Conclusions: Patient survival is lower in diabetic compared to non-diabetic patients on PD. Peritonitis rates were also higher in diabetic PD patients. DM, older age, albumin level and cardiovascular co-morbidities are predictors of mortality     

Hemodynamic and volume changes by ultrafiltration in refractory edema of diabetic nephrotic syndrome with severe renal insufficiency

Effects of ultrafiltration (UF) were examined in 6 diabetic nephrotics having refractory edema. Plasma volume (PV) was 139% of the normal control before and significantly reduced to 125% N after UF (p less than 0.05). Average reduction of PV was 0.3 l, while that of body weight was 4.4 kg. This means that UF induces mainly the reduction of extracellular fluid volume with very little effect on blood volume due to high intravascular refilling. Hemodynamically, cardiac index decreased and total peripheral resistance index (TPRI) remained unchanged according to the decrease of mean blood pressure (MBP). Change in MBP was linearly correlated to that in TPRI. The present study indicates that UF leads to interstitial fluid volume depletion and blood pressure reduction in diabetic nephrotics with severe renal insufficiency. Clinically, UF is a temporary relief from a life-threatening generalized edema in these patients, although neither the progress of renal dysfunction or the recurrence of nephrotic syndrome can be prevented.     

Differences in heart rate variability parameters during the post-dialytic period in type II diabetic and non-diabetic ESRD patients.

BACKGROUND: Heart rate variability parameters were evaluated in 10 healthy subjects, 10 type II diabetic patients and 20 end-stage renal disease (ESRD) patients (11 non-diabetic and nine type II diabetic) undergoing chronic haemodialysis. The study was divided in two phases. METHODS: In the first phase all subjects underwent electrocardiograph (ECG) recording under baseline conditions. In the second phase only ESRD patients underwent haemodialysis and ECG recording. On the day of dialysis and ECG recording the ECG recording was started 1 h before the haemodialysis session (pre-dialytic period), and continued throughout the dialysis (dialytic period), until the morning after (post-dialytic period). RESULTS: Compared with ESRD patients, non-ESRD patients showed the lowest cardiac sympathetic activity. Diabetic patients compared to non-diabetic patients showed a prevalence of cardiac sympathetic activity in the pre-dialytic period (P < 0.01). During the dialytic period in comparison with the pre-dialytic one, a further increase in cardiac sympathetic activity was observed in both diabetic and non-diabetic ESRD patients (P < 0.001). However, in the post-dialysis period the cardiac autonomic nervous system activity remained at the pre-dialytic condition in the diabetic group. In contrast, in the non-diabetic group the cardiac autonomic balance shifted towards a parasympathetic prevalence in the post-dialytic period (P < 0.01). In addition, a significant correlation was found between changes in heart rate variability and changes in plasma urea concentration in the non-diabetic group only (r = 0.65; P < 0.03). CONCLUSIONS: Non-insulin-dependent diabetic uraemic patients undergoing a chronic haemodialysis programme have a severe impairment of heart rate variability. This is probably due to autonomic neuropathy related to the effects of both diabetes and chronic uraemic conditions. In non-diabetic haemodialysis patients uraemia causes similar but reversible changes in heart rate variability compared with the changes caused by diabetes.     

Protective role of extracellular superoxide dismutase in hemodialysis patients

BACKGROUND: The superoxide anion and other oxygen radicals have been implicated in the progression of chronic renal failure, and are removed by extracellular superoxide dismutase (EC-SOD) in the extracellular space on the surface of the endothelium. A single-base substitution of the EC-SOD gene which reduces the binding capability to endothelial cells resulting in an increased serum concentration, has been identified in healthy persons and hemodialysis patients. RESULTS: The proportion of patients with this mutation among hemodialysis patients in each 20 months' duration after the initiation of hemodialysis was retrospectively studied. The percentage of substitution-positive patients declined 80 months after the start of hemodialysis in non-DM patients. In contrast, in DM patients, the rapid decrease was obvious as early as 40 months after the initiation of hemodialysis. By prospective study for 5 years, there were significant differences in the survival rate between patients with and without R213G in DM, but not in non-DM patients. Among those who died, the incidence of ischemic heart disease and cerebrovascular disease in cases with R213G was significantly higher than in cases without R213G. CONCLUSION: These results suggest that the presence of a substitution in the EC-SOD gene at the heparin-binding domain could be a prognostic marker of dialysis patients.     

糖尿病与非糖尿病血液透析患者透析期间心电图变化对照研究

目的 观察伴或不伴糖尿病的维持性血液透析(maintenance hemodialysis,MHD)患者透析期间心电图变化情况.方法 选择新乡市血液净化中心100例MHD患者,分为糖尿病组(41例)和非糖尿病组(59例),分析两组患者血液透析期间心电图变化情况.结果 糖尿病组年龄显著高于非糖尿病组(P＜0.05),透析后总钙水平显著低于非糖尿病组(P＜0.05),透析中心律失常发生率显著高于非糖尿病组(P＜0.05),其中糖尿病组室上性早搏发生率显著高于非糖尿病组(P＜0.05).结论 糖尿病组透中心律失常发生率显著高于非糖尿病组,其中以室上性早搏发生率最明显,与年龄及透析中血钙下降程度相关.     

Determinants of heart rate variability in chronic hemodialysis patients

To clarify determinants of heart rate variability in hemodialysis patients, we evaluated 187 patients receiving chronic hemodialysis. Ambulatory electrocardiogram was recorded for 24 hours from the beginning of hemodialysis. Standard deviation of the normal RR interval (SDNN) was used as a marker of heart rate variability. Multiple regression analysis was performed to select independent variables associated with SDNN from the following 14 variables: age, sex, body mass index before hemodialysis, presence of ischemic heart disease, diabetic nephropathy as primary renal disease, smoking, duration of hemodialysis, mean blood pressure before hemodialysis, left ventricular mass index and fraction shortening in echocardiography, use of beta blockers, use of angiotensin-converting enzyme inhibitors, hematocrit, and blood urea nitrogen. Older age (P < 0.0001), presence of diabetic nephropathy as primary renal disease (P < 0.0001), lower hematocrit (P = 0.0121), larger body mass index before hemodialysis (P = 0.0133), longer duration of hemodialysis (P = 0.0200), and smoking (P = 0.0350) were associated with reduced SDNN. In hemodialysis patients, SDNN as a marker of cardiac autonomic modulation was associated with hematocrit, body mass index, and duration of hemodialysis, in addition to previously reported variables.     

Diabetic ankle fracture complications: a meta-analysis

IntroductionThis meta-analysis aimed to review complication rates following the treatment of an ankle fracture in diabetic patients and to early detect the subgroup of patients at potential risk in order to minimise this complication rate.MethodsA search of 3 databases was performed for studies published till March 2018. Twelve studies met the eligibility criteria for further statistical analysis. An odds ratio (OR) with a 95% confidence interval (95% CI) for each complication was calculated between the diabetic and non-diabetic groups.ResultsThe overall complication risk after ankle fracture was twice as high in diabetes mellitus (DM) than non-diabetes mellitus (non-DM) patients (OR 1.9, 95%CI: 1.7–2.03). This risk was considerably higher with surgery versus non-surgical treatment (OD 3.7, 95%CI: 2.3–6.2). The risk of infection was 3 times higher in DM than in non-DM patients (OR 3.4, 95%CI: 2.9–9.8). The complication rate was even higher in patients with advanced DM (OR 8.4, 95%CI: 2.9–24.5).ConclusionThis meta-analysis provides evidence that diabetic patients are at a greater risk of complication after an ankle fracture.     

Paradox of advanced glycation end-products in late cardiac biopsies of heart transplant recipients

Background

A pilot study of orthotopic heart transplant (OHT) recipients showed that advanced glycation end-product (AGE) deposits were related to acute rejection episodes among subjects with diabetes mellitus (DM); in contrast, among non-DM patients it was associated with prolonged freedom from coronary artery vasculopathy (CAV). However the number of observations in non-diabetic subjects was low. The aim of the current study was to establish the role of AGEs in late endomyocardial biopsies (EMBs) among a larger group of non-diabetic patients.

Material and Methods

Elective EMBs were performed at 3 years post OHT in 62 subjects with DM, namely, 57 males and 5 females of overall mean age of 50 ± 8 years versus 92 free of DM, including 79 males and 13 females of mean age 51 ± 13 years. We localized AGEs in myocardial paraffin sections using monoclonal mouse anti-AGE antibodies. The presence of AGEs in cardiomyocytes, stromal cells, capillaries, and arterioles was described with a semiquantitative scale.

Results

All-cause deaths, CAV, and CAV-related events were observed in 28% versus 23%, 27% versus 29%, and 15% versus 19% of non-DM versus DM patients (P = NS). The occurrence of AGEs was significantly more frequent among non-DM than DM subjects: cardiocytes, 100% versus 69% (P < .0001); stroma, 54% versus 31% (P = .0037); capillaries, 67% versus 31% (P < .0001); and arterioles, 26% versus 3% (P = .0002; chi-square). Among the DM group, mean EMB score correlated with AGE presence in cardiomyocytes (n = 0.29; P < .05, Spearman test) AGE presence had no impact on survival or CAV development.

Conclusion

AGE presence was more common in late EMB from non-diabetic than diabetic OHT recipients; they had no impact on survival or CAV in non-diabetic patients.     

Hemodynamic and volume changes by recombinant human erythropoietin (rHuEPO) in the treatment of anemic hemodialysis patients

Hemodynamic and volume changes induced by recombinant human erythropoietin (rHuEPO) treatment were investigated in 12 chronic hemodialysis patients with refractory anemia. After rHuEPO administration for 49 to 151 days, hematocrit (Ht) significantly improved from 19.4 +/- 2.3 to 30.1 +/- 1.1% (Mean +/- SD). Mean blood pressure (MBP) increased slightly but significantly from 78.8 +/- 13.2 to 88.9 +/- 16.9 mmHg. Hemodynamically, total peripheral resistance index (TPRI) increased significantly from 1,444 +/- 367 to 2,146 +/- 470 dynes.sec.cm-5.m2, while cardiac index (CI) decreased significantly from 4.49 +/- 0.85 to 3.37 +/- 0.60 l/min/m2. Both pulse rate (PR) and stroke volume index (SVI) also decreased significantly, but blood volume (BV) remained unchanged. Plasma renin activity and plasma norepinephrine decreased significantly. There were positive correlations between the change of MBP and that of CI, and between the change in CI and that of BV, respectively (p less than 0.05 or less). In conclusion the improvement of anemia using rHuEPO is hemodynamically associated with an increase in TPRI and a decrease in CI as well. Blood pressure elevation seems to be caused by an inappropriately minor reduction of CI. The contribution of humoral factors is not suggested.     

Uremic autonomic neuropathy studied by spectral analysis of heart rate.

BACKGROUND: There is good evidence that power spectral analysis (PSA) of heart rate variability may provide an insight into the understanding of autonomic disorders. METHODS: We investigated 30 chronic uremic patients who were on periodic bicarbonate hemodialysis by a battery of six cardiovascular autonomic tests (beat-to-beat variations during quiet breathing and deep breathing, heart rate responses to the Valsalva maneuver and standing, blood pressure responses to standing and sustained handgrip) and PSA of heart rate variations. RESULTS: Eleven patients (37%) had an abnormal response to only one parasympathetic test. Twelve patients (40%) had a definite parasympathetic damage, as indicated by at least two abnormal heart rate tests, whereas four (13%) had combined parasympathetic and sympathetic damage. Multivariate analysis of the cardiovascular tests revealed that 19 patients (63%) had moderate-to-severe autonomic neuropathy (AN), and 11 patients exhibited normal autonomic function. Among the symptoms suggestive of autonomic dysfunction, only impotence in males was significantly associated with test-proven AN. The PSA of the heart rate variability demonstrated a good discrimination of low-frequency (LF) and high-frequency (HF) bands (LF, 0.03 to 0.15 Hz; HF, 0.15 to 0.33 Hz) among controls, uremic patients without test-proven AN, and uremic patients with test-proven AN. A significant reduction of the LF value on supine uremic patients without AN suggests that an early sympathetic involvement exists that traditional autonomic tests were unable to detect. CONCLUSIONS: Our study indicates that the current opinion of a major parasympathetic damage in chronic uremic patients on hemodialysis has to be modified in favor of a more widespread autonomic dysfunction involving both the sympathetic and parasympathetic pathways.     

Impairment of ventilatory response to metabolic acidosis in insulin-dependent diabetic patients with advanced nephropathy.

Sudden cardiopulmonary arrest due to a defective respiratory reflex is observed in diabetic patients. Impaired ventilatory response in diabetic patients to acute hypoxia or hypercapnia induced by the inhalation of an artificial gas has been reported. Little is known regarding the respiratory compensatory ability for mild to moderate metabolic acidosis due to renal failure in insulin-dependent diabetic subjects. Arterial blood pH, HCO3-, PaCO2 and PaO2 were measured in 13 insulin-dependent diabetic subjects with advanced nephropathy and in 33 non-diabetic subjects with end-stage renal failure. The diabetic group consisted of six predialysis patients and seven on regular hemodialysis (HD) and the non-diabetic group, ten predialysis patients and 23 on HD. Differences between measured partial arterial pressure of carbon dioxide (PaCO2) and predicted PaCO2 determined from HCO3- were examined. PaCO2 was significantly higher in the diabetic than in non-diabetic group (40.0 +/- 7.4 versus 31.1 +/- 5.1 mmHg, p < 0.05 in predialysis, 42.0 +/- 6.4 versus 36.0 +/- 2.6 mmHg, p < 0.05 in HD), though plasma pH was essentially the same for either. Differences in measured PaCO2 and predicted PaCO2 were significantly larger in the diabetic group than in non-diabetic group. Ventilatory response to uremic acidosis may thus be considered impaired in subjects with advanced diabetic nephropathy.