Predialysis Chronic Renal Failure Patients Research Articles

Importance of Diastolic Dysfunction and Nt-ProBNP Measurement for Identification of Volume Load in Predialysis Chronic Renal Failure Patients

Importance of Diastolic Dysfunction and Nt-ProBNP Measurement for Identification of Volume Load in Predialysis Chronic Renal Failure Patients

Spiritual Benson Relaxation in Pre-Dialysis Chronic Kidney Failure Patients with Anxiety Problems: Case Study

Background: Chronic kidney failure patients say they are worried because they see the intervals flowing blood, costs incurred each time undergoing therapy, anxiety because invasive measures will be carried out, and uncertainty about recovery. This case study aims to carry out nursing care for patients with Pre-Dialysis Chronic Renal Failure Patients with anxiety nursing problems at Islamic Hospital Surabaya A.Yani. Methods: This type of research uses qualitative methods with a case study approach. The subjects were 1 Pre Dialysis Chronic Renal Failure patient with nursing problems for three interventions (1 time a day for 10-15 minutes) with data collection methods including assessment, determining diagnosis, making interventions, implementation, and evaluation. Results: Results of a case study of the Spiritual Application of Benson Relaxation in Pre-Dialysis Chronic Kidney Failure Patients at Rumah Sakit Islam Surabaya A.Yani with anxiety nursing problems three times. After carrying out nursing actions 3 x Pre-Hemodialysis Interventions in Chronic Kidney Failure patients, anxiety nursing problems can be resolved. Patients experience changes from initially having an Anxiety score of 78 (anxiety ) to 40 (not anxious). Conclusion: Therapy Spiritual Benson Relaxation effectively reduces anxiety, so it can be used as an alternative to reduce anxiety in patients with chronic kidney failure and for room nurses to be able to implement independent actions by implementing quick response actions so that patients can achieve optimal action.

Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

We assessed the cerebrovascular CO2 reactivity (CO2R) in chronic renal failure (CRF) patients without diabetes mellitus (DM), uncontrolled hypertension, peripheral vascular disease, or neurological disease under isoflurane-nitrous oxide anesthesia. Forty-nine patients undergoing surgery, including 36 CRF patients (30 receiving dialysis and six pre-dialysis patients) and 13 patients without CRF (controls). Middle cerebral artery flow velocity (VMCA) was measured by transcranial Doppler ultrasonography at an end-tidal CO2 of 35 to 45mmHg. CO2R was calculated as an absolute value (change in VMCA per mmHg PaCO2) and a relative value (absolute CO2R/baseline VMCA×100). Factors associated with CO2R were evaluated simultaneously. Despite no significant differences in the absolute and relative values of CO2R between the CRF (mean 2.5cm/s/mmHg; median 5.0%/mmHg) and control (2.4cm/s/mmHg; 5.0%/mmHg) groups, blood urea nitrogen (BUN) concentrations in the CRF group correlated inversely with both absolute and relative CO2R. BUN concentration was higher (mean 72 versus 53mg/dl, p=0.006) and relative CO2R was lower (mean 2.6 versus 5.7%/mmHg, p=0.011) in patients with pre-dialysis CRF (n=6) versus CRF patients receiving dialysis (n=30). CO2R in CRF patients was not significantly different from that in controls. However, in CRF patients with high BUN concentrations, CO2R might be impaired, leading to reduced cerebrovascular reserve capacity. Because DM is a major cause of CRF and we excluded DM patients, our results might not be applicable to patients with DM-induced CRF.

The relationship between malnutrition subgroups and volume parameters in pre-dialysis patients.

There are two types of malnutrition in patients with chronic renal failure (CRF); type 1 and type 2. The aim of this study was to investigate the relationship between malnutrition and inflammation and also the relationship between malnutrition and volume status. Ninety-four pre-dialysis CRF patients were included in the study. Nutritional status of the patients was calculated using the subjective global assessment. Scores of 1-5 were given according to the severity of the symptoms and physical examination findings. Serum inflammation markers [high-sensitive C-reactive protein (hs-CRP), interleukin-1β, interleukin-6 and tumor necrosis factor-alfa] and nutrition parameters (albumin, pre-albumin, transferrin, fetuin-A, insulin like growth factor-1 and insulin-like growth factor-binding protein-3)] were measured in all the patients. Serum N-terminal pro-brain natriuretic peptide levels and echocardiography were performed to evaluate the volume status of the patients. The mean age of the patients was 59.6±13.3 years, the mean malnutrition score was 17.2±6.01, the mean and the median of hs-CRP levels were 18.5±40.7 and 5.6 mg/L, respectively, the mean albumin level was 3.46±0.48 and the mean creatinine clearance was 23.7±13.5 mL/min. A positive correlation between malnutrition scores with inflammation and volume parameters was found in the bivariate and multivariate analysis. In the multiple regression analysis, volume parameters proved to be the most important factors influencing malnutrition scores. Thus, the elimination of volume excess would ameliorate both inflammation and malnutrition. This hypothesis needs to be supported or proved with prospective studies.

Biochemical evaluation of renal osteodystrophy in uraemic patients

Background/aim Renal osteodystrophy is a multifactorial disorder of bone remodelling that develops in patients with chronic renal failure (CRF). Biochemical markers of bone turnover have been proposed for the noninvasive diagnosis of renal osteodystrophy. The purpose of this study was to evaluate intact parathyroid hormone (iPTH) and some markers of bone disease in predialysis (preD) and haemodialysis (HD) CRF patients and correlate them with bone mineral density (BMD). Patients and methods Several biochemical markers were measured in the serum of 74 CRF patients (38 preD patients and 36 patients on regular HD). In addition, 30 healthy volunteers were included as controls. BMD of all patients was measured by means of calcaneal ultrasonography. Results BMD was measured by means of ultrasound. BMD was significantly decreased in both patient groups when compared with controls. Also, it was significantly lower in patients with osteoporosis than in those with osteopenia. iPTH, total alkaline phosphatase (ALP) and osteocalcin (OC) levels were significantly elevated in both patient groups when compared with controls. Ionized calcium (Ca 2+ ), free carnitine and insulin-like growth factor-1 (IGF-1) levels were significantly decreased in patients compared with controls. There was a significant inverse correlation of BMD with iPTH, ALP and OC and a significant positive correlation with Ca 2+ and IGF-1 in HD patients. PreD patients showed significant inverse correlation of BMD with iPTH and ALP and significant positive correlation with Ca 2+ . Conclusion The results of the present study suggested that ultrasound is a useful method for evaluating BMD and provides information about diverse regional skeletal changes in CRF patients. iPTH, ALP, OC and Ca 2+ can predict renal osteodystrophy in preD and HD CRF patients. PreD and HD CRF patients often have low serum concentrations of free carnitine and IGF-1.

Hepatocyte Growth Factor in Saliva of Patients with Renal Failure and Periodontal Disease

Background: Hepatocyte growth factor (HGF), endogenous cytokine with pleiotropic repairing and regeneration properties in relation to most tissues and organs, contributes to the progression of periodontal disease (PD). Furthermore, PD is a significant health problem in patients with chronic renal failure (CRF). The role of HGF in the development of PD in this specific population was not a subject of research so far. Material and methods: The following groups were enrolled in the study: (1) 26 chronic hemodialysis (HD) subjects, (2) 26 patients treated by continuous ambulatory peritoneal dialysis (CAPD), (3) 28 predialysis CRF patients, (4) 26 subjects with advanced PD (without coexisting diseases), and (5) 20 healthy subjects without PDs. HGF level in saliva was measured using the immunoenzymatic method. Gingival index, papillary bleeding index, plaque index, and the loss of clinical attachment level were evaluated. Results: The HGF level in saliva of HD patients was twice higher than in that of subjects with healthy periodontium. Direct relationships between proper HGF level in saliva and the indices GI, PBI, and PI in CAPD-treated patients and with more severe PD were shown. It was found that PD is most advanced in HD patients, moderately in CAPD-treated patients and to the smallest extent in predialysis CRF patients. Conclusions: The HGF level in mixed saliva is the index of PD progression in subjects without renal failure and in CAPD-treated patients. PD is common in renal failure patients and is a significant problem concerning general health status.

Association of increased active PTH(1–84) fraction with decreased GFR and serum Ca in predialysis CRF patients: modulation by serum 25-OH-D

As the serum calcium and glomerular filtration rate decreased, the proportion of active PTH(1-84) molecules in PTH immunoreactivity increased in serum from predialysis uremic patients, particularly those with vitamin D insufficiency. The PTH(1-84) fraction was altered in predialysis patients with chronic renal failure (CRF). Serum PTH in predialysis CRF patients without any medication was measured by PTH(1-84)-specific whole PTH assay and intact PTH assay cross-reacting with N-truncated PTH. In CRF patients, the glomerular filtration rate (GFR) correlated positively with serum Ca and 1,25-dihydroxyvitamin D (1,25(OH)(2)D), and inversely with serum Pi, log intact PTH, and log whole PTH. In multiple regression analysis, including age, gender, body mass index, GFR, Ca, and Pi and 1,25(OH)(2)D as independent variables, serum Ca and GFR associated significantly with serum log whole PTH and intact PTH. Serum log whole PTH/intact PTH ratio, which increased as serum Ca and GFR decreased, retained a negative correlation in those with serum 25-hydroxyvitamin D levels below 20 ng/ml, but not in those above 20 ng/ml. The ratio also correlated positively with serum log tartrate-resistant acid-phosphatase-5b, log cross-linked N-telopeptide of type-I collagen, and log bone alkaline-phosphatase. As GFR declined with suppression of serum Ca, the proportion of active PTH molecules increased in predialysis CRF patients, particularly those with vitamin D insufficiency.

Elevation of Pro-Inflammatory Cytokines, C-Reactive Protein and Cardiac Troponin T in Chronic Renal Failure Patients on Dialysis

Chronic renal failure (CRF) patients suffer from a chronic inflammation. They are at increased risk of cardiovascular disease. In order to investigate this inflammatory process and cardiovascular risk factors associated with haemodialysis (HD) and peritoneal dialysis (PD), we compared serum/plasma pro-inflammatory cytokines, C-reactive protein (CRP), and cardiac troponin T (cTnT) of 146 CRF patients treated or not treated with PD or HD. Serum cytokines and CRP as well as plasma cTnT were measured by enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and electrochemiluminescence immunoassay, respectively. Results indicated that serum interleukin (IL)-18 concentrations were significantly higher in PD and low creatinine clearance pre-dialysis CRF (LCC) patients than HD patients (both p < 0.05). IL-6 and tumour necrosis factor (TNF)-α concentrations were significantly higher in PD patients than LCC patients (both p < 0.01). Serum hsCRP and plasma cTnT in HD were significantly higher than LCC (both p < 0.01). The elevation of pro-inflammatory cytokines should play an important role in the chronic inflammation and increased cardiovascular risk of CRF patients on dialysis. We are evaluating further the diagnostic and prognostic applications of pro-inflammatory cytokines and biochemical inflammatory markers for these patients.

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.

Health-Related Quality of Life of Predialysis Patients with Chronic Renal Failure

Background: Health-related quality of life (HQOL) of predialysis patients with chronic renal failure (CRF) has received less attention than that of dialysis patients. We investigated changes in SF-36 over 1 year and examined associations between clinical parameters and SF-36 in predialysis CRF patients. Methods: Subjects were 471 predialysis CRF patients. SF-36 and clinical parameters were measured every 8 weeks for 48 weeks. Of the 471 subjects, 294 underwent one or more follow-ups. We analyzed the pooled dataset of the 294 CRF patients and 2002 subjects from Japanese general population using analysis of covariance. Results: After adjustment for age and sex, the 1-year declines in SF-36 domains were significantly greater in the predialysis patients than in the general population. For a 10% decline in hematocrit from the baseline survey value, the decline in vitality of SF-36 was 4.5 points (p = 0.003), while for a 10% increase in serum creatinine from the baseline survey value, respective declines in physical functioning, role-physical and mental health were 1.2 (p = 0.004), 1.9 (p = 0.035), and 1.0 points (p = 0.008). Conclusion: Among these predialysis CRF patients, the decline in HQOL was faster than that in the general population, and was associated with an increase in serum creatinine and decline in hematocrit.

ASAIO 52nd annual conference, Chicago, Illinois, June 8–10, 2006

ASAIO 52nd annual conference, Chicago, Illinois, June 8–10, 2006

In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients

The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients. Our clinical study has been designed as a randomized double-blind placebo controlled study. A total of 55 chronic kidney disease (CKD) patients at stages 3 and 4 (mean creatinine clearance 45 ml/min, range 15-60) were randomly assigned to receive simvastatin 40 mg/day or placebo, added to their ongoing treatment, for 6 months. Blood samples were obtained at baseline, and after 3 and 6 months of observation for the determination of lipids, inflammatory markers and renal function. For the in vitro studies, the effect of increasing doses of simvastatin on cytokine production [namely interleukin (IL)-6 and IL-8] in human cultured monocytes from 10 healthy subjects (HS) and 15 CKD patients stimulated by lipopolysaccharide (LPS) was investigated. A significant reduction in total cholesterol from 221+/-44 mg/dl to 184+/-41 mg/dl (3 months) and to 186+/-39 mg/dl (6 months) (P<0.02) and low-density lipoprotein cholesterol from 139+/-40 mg/dl to 104+/-29 mg/dl (3 months) and to 100+/-31 mg/dl (6 months) (P<0.001) was observed in the 28 patients treated with simvastatin. In this group, C-reactive protein (CRP) levels significantly decreased from 2.6 mg/l [interquartile range (IQR 4.9)] to 2.0 mg/l (IQR 1.9) (P = 0.03) at 6 months (P<0.05). A parallel reduction of IL-6 levels from 5.1 pg/ml (IQR 3.8) to 3.5 pg/ml (IQR 3.1) (P = 0.001) at 6 months was also observed. No significant reduction in inflammatory markers [CRP from 5.1 mg/l (IQR 1.9) to 5.4 mg/l (IQR 1.3) (P = NS) at 6 months] or plasma lipids [LDL-cholesterol from 127+/-32 mg/dl to 131+/-21 mg/dl (6 months)] was observed in the 27 patients of the placebo group. In the in vitro studies, the average value for cell-associated IL-6 and IL-8 was higher in CKD (155+/-95 pg/ml monocytes for IL-6 and 722+/-921 pg/ml monocytes for IL-8) vs HS (137+/-87 pg/ml monocytes and 186+/-125 pg/ml monocytes) (P<0.01) and was not affected by simvastatin alone. LPS resulted in a significant increase in cytokine production (IL-6: 1954+/-321 pg/ml monocytes for CKD and 1451+/-237 pg/ml monocytes for HS; P<0.001); the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups. These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.

Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients

Intravenous iron is a recognized therapy of anaemia in chronic haemodialyzed patients, especially in those receiving erythropoietin (Epo), while its role in the anaemia of pre-dialyzed chronic renal failure (CRF) patients is much less clear. This study attempted to evaluate the effects of intravenous iron in anaemic pre-dialyzed patients. Sixty anaemic (haemoglobin<11 g/dl) non-diabetic patients with moderate CRF [32 males, 28 females; mean age 52.2+/-12.5 years; mean glomerular filtration rate 36.2+/-5.2 ml/min], without iron deficiency, iron overload or inflammation, without concomitant erythropoietin treatment and without any previous iron therapy were enrolled. Intravenous iron was administered as iron sucrose, 200 mg elemental iron per month for 12 months, with 1 month pre-study survey and 1 month follow-up after the last iron dose. Intravenous iron supplementation was associated with a significant increase in haemoglobin (from 9.7+/-1.1 at the baseline to 11.3+/-2.5 g/dl after 12 months, a mean increase of 1.6 g/dl), a further 36% of patients reaching the target haemoglobin of 10 g/dl. There was a significant increase in serum iron from 73.9+/-17.2 to 101.8+/-12.2 microg/dl, in serum ferritin from 98.0 (24.8-139.0) to 442.5 (86.0-496.0) microg/l and in transferrin saturation from 21.6+/-2.6 to 33.6+/-3.2%. No worsening of renal function, no increase in blood pressure and no other side effects were noted. Intravenous iron therapy in pre-dialysis patients with no Epo seems often to ameliorate the anaemia, avoiding the necessity of Epo or blood transfusions in one-third of pre-dialyzed non-diabetic patients. Intravenous iron supplementation appears to be an effective and safe treatment for anaemia in pre-dialysis CRF patients.

Hepatitis B vaccination in predialysis chronic renal failure patients a comparison of two vaccination schedules

To improve seroconversion to hepatitis B vaccination, it is recommended that patients suffering with chronic renal failure be vaccinated as soon as dialysis is anticipated. We compared seroconversion rates in 121 predialysis patients with moderate chronic renal failure using either 40 or 20 μg of Engerix B recombinant hepatitis B vaccine administered at 0, 1 and 6 months. Seroconversion was not significantly higher after three doses of 40 μg (67%) compared to 20 μg (57%, p = 0.27). Multivariable analysis using dose of vaccine, eGFR (MDRD equation), calculated creatinine clearance (Cockcroft–Gault), and age as independent continuous variables showed that neither dose nor degree of renal function contributed to seroconversion. Younger age was weakly associated with improved seroconversion ( p = 0.052). Seroconversion was attained in 13% of non-responders after a fourth dose of vaccine.

Dimethylglycine supplementation does not affect plasma homocysteine concentrations in pre-dialysis chronic renal failure patients

Objective: To determine whether daily dimethylglycine supplementation affects plasma homocysteine concentrations. Design and methods: A randomized, blinded, crossover design was used. Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days. Fasting blood samples and 12-h urine samples were collected at baseline and at the end of each treatment period for analysis. Results: No significant differences were observed in plasma homocysteine ( P = 0.624), glycine betaine ( P = 0.452) and methionine ( P = 0.457) concentrations between dimethylglycine and placebo treatments. Conclusion: Daily supplementation with dimethylglycine does not affect plasma homocysteine.

The effect of peritoneal-dialysis on the olfactory function in chronic renal failure patients

Objectives: Patients with chronic renal failure (CRF) show a high prevalence of poor nutritional state and smell plays an important role in nutrition. Despite these facts, only few studies investigated the influence of CRF on the sense of smell. The objectives of the present study were to investigate olfactory function in CRF patient undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: A prospective study of 12 patients all having undergoing CAPD was performed. We performed a case-control study in comparing the CC-SIT scores of CRF patients with age-sex matched healthy controls. And to examine the possible correlations between smell identification test score and various clinical parameters. We analyzed the olfactory function using Cross- Cultural Smell Identification Test (CC-SIT) score. Results: Healthy controls had significantly high CC-SIT scores compared to those of predialysis CRF patients and post-1-month dialysis CRF patients. But no significant differences were observed in CC-SIT score between healthy controls and post-3-month dialysis CRF patients. Healthy controls and post-3-month dialysis CRF patients were significant negative correlation was found between CC-SIT score and age. Conclusion: Removal of uremic toxins by 3 months CAPD can correct olfactory disturbance in this study. Clinical significance of study: Acute removal of uremic toxins by CAPD does not correct olfactory disturbance, but long standing CAPD can correct olfactory disturbance in CRF patient. We are expecting that undernourishment found in CRF patients shall be cured by correcting their sense of olfactory, through long-standing CAPD.

Nutritional status and dietary manipulation in predialysis chronic renal failure patients

Objective A properly implemented dietary treatment for patients with chronic renal failure (CRF) can correct several metabolic and endocrine disturbances and delay initiation of dialysis, but concerns exist about the risk of malnutrition and protein depletion. The goal of this study is to evaluate nutritional status and its relation to the dietary treatment in patients with advanced CRF. Design Cross-sectional survey. Setting Predialysis outpatient clinic. Patients Seventy patients (43 males, 27 females, 50 ± 12 years) with severe CRF (glomerular filtration rate [GFR] <15 mL/min) being treated with a low-protein (0.6 g/kg/day) diet (LPD) or a very-low-protein (0.3 g/kg/day) diet supplemented with essential amino acids and ketoacids (KAD). Fifty-two healthy subjects with comparable age and sex served as controls. Main outcome measures In all patients and controls, we performed biochemistry, anthropometry, bioelectrical impedance vector analysis (BIVA), and subjective global assessment (SGA), and the patients’ outcomes were also assessed. Results Values of anthropometry and BIVA were similar in patients and controls. SGA scores showed a normal nutritional status (SGA-0) in 50 patients (71.4%) and mild to moderate SGA abnormalities (SGA-1) in 20 patients (28.6%); none had severe malnutrition. The SGA-1 patients differed from the SGA-0 patients by having higher serum urea, lower bicarbonate, and lower renal function (87% of SGA-1 patients had GFR <10 mL/min.). At the same GFR values (6.6 ± 2.3 versus 6.6 ± 2.3 mL/min) SGA-1 patients had lower bicarbonate (21.9 ± 4.3 versus 25.3 ± 2.7 mM, P < .01) and higher serum urea (115 ± 29 versus 82 ± 38 mg/dL, P = .01) and protein intake than SGA-0 patients; SGA-1 score was more prevalent with LPD compared with KAD treatment (45% versus 27%, P < .05). BIVA and anthropometry, serum levels of albumin, prealbumin, insulin-like growth factor–1, hematocrit, and lymphocyte count did not differ between SGA-1 and SGA-0 patients, but the number entering dialysis was higher in the group scoring as SGA-1 compared with SGA-0 (82% versus 47%, P < .05). Conclusions With a planned dietary regimen, severe or overt malnutrition does not occur in predialysis CRF without other serious illnesses. However, some mild to moderate SGA abnormalities were detected in association with a more severe renal insufficiency, a lower serum bicarbonate, a higher serum urea and dietary protein levels and were predictive of poor renal outcome. This study emphasizes the role of proper dietary implementation, correction of metabolic acidosis, and clinical monitoring including SGA in the predialysis conservative care of CRF patients.

The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure.

Several new serum markers for bone metabolism have recently become available and are being applied to clinical practice. Their clinical usefulness in predialysis patients with chronic renal failure (CRF), however, has not yet been determined. Serum levels of three bone formation markers-bone alkaline phosphatase (BAP), osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP)-and three bone resorption markers-type I collagen cross-linked N-telopeptide (NTx), deoxypyridinoline (DPD), and pyridinoline (PYD)-were measured simultaneously in 85 predialysis CRF patients (serum creatinine 3.5 +/- 1.9 mg/dl, 61.0 +/- 10.9 years old, 54 males and 31 females, 36 diabetics and 49 nondiabetics) to examine the relationships between these markers and bone mineral density (BMD) of the distal radius, as measured by peripheral quantitative computed tomography (pQCT). Trabecular BMD, which is strongly affected by bone metabolism, was significantly negatively correlated with each of the bone formation markers (r=-0.341, p=0.0016, for OC; r=-0.314, p=0.0036, for PINP; r=-0.238, p=0.0315, for BAP), but there was no significant correlation between BMD and any of the bone resorption markers. In multivariate regression analyses (adjusted by age, sex, presence of diabetes, glomerular filtration rate, intact parathyroid hormone, calcium, phosphate, and 1,25-dihydroxyvitamin D), OC and PINP were significantly associated with a decrease in BMD, but BAP was not. In conclusion, we demonstrated that in predialysis CRF patients, BMD of the distal radius, particularly of trabecular bone, is associated with serum OC and PINP levels. OC and PINP are suggested to be possible parameters for the clinical evaluation of the effect of bone metabolism on BMD.

Cardiovascular autonomic neuropathy in non-diabetic Nigerian patients with chronic renal failure.

To determine the frequency of cardiovascular autonomic neuropathy (CAN), its pattern and clinical predictors in Nigerians with non-diabetic chronic renal failure (CRF). A total of 120 subjects comprising 60 pre-dialysis CRF patients and an equal number of age- and sex-matched healthy controls were studied. Five standard cardiovascular reflex (CVR) tests namely: heart rate response to deep breathing, Valsalva manoevre and posture, as well as blood pressure response to hand grip and posture were used to evaluate the cardiac autonomic functions. A pre-tested questionnaire was administered, with neurological examination and serum biochemical investigations also included in the evaluation. The frequency of CAN in non-diabetic CRF was 65%. Dysfunction of both the parasympathetic and sympathetic divisions of the ANS occurred in CRF patients. Significant impairment in all the heart rate reflex tests (39%) and blood pressure response to the handgrip tests (28%) occurred in patients with CAN. Symptoms of autonomic neuropathy with clinical correlation with CAN included: constipation (60%), hyposialism (51%) and hypohidrosis (33%), whilst those of peripheral neuropathy were: loss of sensation (50%) and numbness (40%). Of the biochemical parameters, serum creatinine and urea had significant correlation with autonomic neuropathy. Autonomic neuropathy is common in Nigerian patients with non-diabetic CRF, especially in those with symptoms of constipation, hypohidrosis, numbness and prickly sensations.

PTH secretion in patients with chronic renal failure assessed by a modified CiCa clamp method: effects of 1-year calcitriol therapy.

Secondary hyperparathyroidism (secondary HPT) in patients with chronic renal failure (CRF) is characterized by parathyroid gland hyperplasia and an intrinsic defect in the recognition of parathyroid hormone (PTH) secretion. Conflicting results have been reported regarding the set point for calcium-regulated PTH release and its modification by calcitriol therapy in hemodialysis patients. Additionally, the effect of calcitriol on the calcium/PTH relationship in predialysis CRF patients with early secondary HPT has not been investigated. Our objective in this controlled study was to investigate the calcium/PTH relationship and to determine the calcium set point in patients with early stages of CRF before and after a 1-year treatment with calcitriol and in normal volunteers. Nine patients with an early stage of CRF (GFR between 20 and 50 ml/min x 1.73 m2 b.s.) aged 35-77 years and 13 healthy volunteers (HV) aged 26-60, years were included in the study. All participants were investigated by sequential lowering and raising of serum calcium levels comprising the following phases: blood-ionized calcium (Ca2+) was lowered by about 0.2 mmol/l (3 steps), steady-state hypocalcemia of Ca2+ 0.2 mmol/l below the baseline (step 4), stop of the infusion for 5 minutes (step 5), Ca2+ was raised to about 0.2 mmol/l above baseline (steps 6 and 7), and a steady state hypercalcemia of Ca2+ 0.2 mmol/l above baseline (step 8). Ionized calcium and intact PTH (iPTH) were measured at 30 time points during 240 minutes. The calcium set point was determined using the classical 4-parameter model. The CiCa clamp test was performed before and after a 1-year treatment with 0.5 microg of calcitriol thrice weekly. No differences in the set point were observed between HV and CRF patients with early secondary HPT. Four of 9 patients responded to calcitriol treatment with a decrease in basal serum iPTH levels ("responders"). There was no difference between renal function (GFR 18 +/- 6 vs. 17 +/- 8 ml/min x 1.73 m2 b.s.), set point (Ca2+ 1.07 +/- 0.13 vs. 1.07 +/- 0.06 mmol/l) and suppressibility of PTH secretion (PTHmin% 7.3 +/- 1.6 vs. 8.2 +/- 2.9) in responders vs non-responders, nor did these values change after treatment with calcitriol. PTHmin% decreased significantly in the whole group after treatment (10.4 +/- 8.5 vs. 7.8 +/- 2.4). Although the calcium set point was not different in predialysis CRF patients with early secondary HPT compared to HV, calcitriol treatment improved the calcium-related suppression of PTH secretion (PTHmin%).