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PubMed2004

Kidney-bone, bone-kidney, and cell-cell communications in renal osteodystrophy.

The relationship between bone and the kidney in renal osteodystrophy is a complex interplay of kidney to bone connections, bone to kidney connections, and cell to cell connections. In addition, such interactions have a profound effect on the vasculature. In this review, we discuss the role of the bone morphogenetic proteins (BMPs) in the skeleton, kidney, and vasculature. In addition, we propose that deficiencies of these BMPs seen in chronic kidney disease (CKD) result in decreased bone remodeling and a compensatory secondary hyperparathyroidism (high turnover state). Treatment of the hyperparathyroidism blocks this compensatory arm and thus decreased bone remodeling occurs (low turnover). We review animal models of CKD in which treatment with BMP-7 resulted in normalization of both high and low turnover states. Finally, we discuss vascular calcification as it relates to bone metabolism. We discuss the roles of BMP-7 and 2 other bone regulatory proteins, osteoprotegerin (OPG) and alpha2-HS glycoprotein (AHSG, human fetuin), in the human vasculature and their implications for vascular calcification.

Bone Morphogenetic Proteins↗

PubMed2005

Safety and efficacy of atorvastatin in patients with severe renal dysfunction.

OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. CONCLUSION: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Aged↗

PubMed2026

Assay-dependent variability in peptide biomarker quantification: experimental evidence from renalase in chronic kidney disease.

BACKGROUND: Renalase is a promising biomarker for kidney disease, but published levels vary widely between studies. We hypothesised that variability in commercial enzyme-linked immunosorbent assays (ELISAs) kits and matrix effects (serum vs plasma) drive these inconsistencies. METHODS: Paired serum and plasma samples from 56 participants (28 chronic kidney disease (CKD) stages 2-5, 28 healthy controls) were tested using three commercial renalase ELISAs (BTLAB, Cloud-Clone, EIAab). We assessed intra-assay precision, inter-assay agreement (Spearman's rank correlation and Bland-Altman analysis on log10-transformed values), matrix effects, and associations with estimated glomerular filtration rate (eGFR). Diagnostic performance was evaluated by Receiver operating characteristic (ROC) analysis. RESULTS: Inter-assay renalase concentrations differed markedly (up to orders of magnitude), with weak inter-assay correlations (r ≤ 0.25). Bland-Altman analyses revealed large, systematic biases between kits. Only the BTLAB assay showed consistent serum/plasma agreement, a significant correlation with eGFR (ρ ≈ 0.32-0.42, p < 0.05), and moderate discriminatory performance for CKD in serum (AUC = 0.70) and plasma (AUC = 0.68). Cloud-Clone and EIAab produced divergent results and strong matrix-dependent biases. CONCLUSIONS: Observed variability among commercial ELISA platforms may compromise comparability between studies. Harmonisation, standardised reference materials, and cross-validation are necessary before renalase assays can be used reliably in clinical practice.

Humans↗

PubMed2006

Effects of correction of metabolic acidosis on blood urea and bone metabolism in patients with mild to moderate chronic kidney disease: a prospective randomized single blind controlled trial.

BACKGROUND: There are no controlled trials on the efficacy of oral bicarbonate therapy in patients with mild to moderate chronic kidney disease (CKD). This prospective randomized controlled study was done to evaluate the effects of correction of metabolic acidosis on renal functions and bone metabolism in this group of patients. PATIENTS AND METHODS: Forty patients were randomized to treatment with oral bicarbonate or placebo for a period of 3 months. Investigations at baseline included venous pH, bicarbonate, renal functions, serum iPTH, and bone radiology. The treatment group (Group B) received daily oral sodium bicarbonate therapy at a dose of 1.2 mEq/kg of body weight. Their venous blood pH and bicarbonate levels were estimated weekly to keep blood pH near 7.36 and bicarbonate at 22-26 mEq/L by adjusting the dose of sodium bicarbonate. At the end of 3 months, all the tests were repeated in both groups. RESULTS: After oral bicarbonate therapy (OBT), there was a significant decline in the rise of blood urea level in Group B associated with a sense of well-being in 50% patients. The rise in parathormone (PTH) was six times the baseline value in Group A and only 1.5 times baseline value in Group B, although not statistically significant. There was no significant change in total calcium, phosphorus, alkaline phosphatase, creatinine, total protein, or albumin levels. CONCLUSION: Correction of metabolic acidosis in patients with moderate CKD attenuates the rise in blood urea and PTH, which might prevent the deleterious long-term consequences of secondary hyperparathyroidism.

Acidosis↗

PubMed2003

The effect of erythropoietin therapy and hemoglobin levels on the immune response to Engerix-B vaccination in chronic kidney disease.

BACKGROUND: Patients undergoing chronic hemodialysis have an increased risk of acquiring hepatitis B infection. Only 43-66% of dialysis patients develop effective anti-HBs titers after vaccination. AIM: To evaluate the effect of recombinant erythropoietin (rEPO) therapy and basal hemoglobin levels on the outcome of the immune response to four doses of IM 40 microg Engerix-B vaccination in hemodialysis and chronic kidney disease (CKD) patients before starting replacement therapy. SUBJECTS AND METHODS: One hundred and three patients were included in the study: 34 hemodialysis patients treated with rEPO (Group A), 36 predialytic patients who did not treated with rEPO (Group B) and 33 predialytic patients treated with rEPO (Group C). Plasma creatinine in predialytic patients was 2-7 mg/dL. All patients' HBsAg and anti-HBs antibodies were negative. Patients were immunized with IM 40 microg Engerix-B at 0, 1, 3, and 6 months. Anti-HBs titers were measured at 7th month. RESULTS: Eighty seven point one percent of patients from group C developed protective anti-HBs titers compared with 69.4% from group B and 44.1% from group A (p = 0.001). Patients from all groups with baseline hemoglobin levels above 11 gr/dL developed protective anti-HBs titers significantly more than patients with baseline hemoglobin levels below 11 gr/dL (p < 0.05). CONCLUSION: Predialytic patients treated with rEPO and with hemoglobin levels higher than 11 gr/dL had significantly better immune response outcomes to Engerix-B vaccination. Immunization against hepatitis B infection should be considered at early stages of CKD prior to the deterioration in kidney functions and the development of renal anemia.

Aged↗

PubMed2004

Electrophysiological abnormalities in upper extremities after brachiocephalic A-V fistulas construction in predialysis patients.

BACKGROUND: Peripheral neuropathy is considered a common complication in patients suffering from advanced chronic kidney disease (CKD). Superimposed peripheral multiple neuropathies may complicate arteriovenous (A-V) fistulas construction. AIM: To evaluate, prospectively, the influence of brachiocephalic A-V fistulas construction on the peripheral nerves of the same extremity and to characterize the patients at risk for developing ischemic and neurological complications. PATIENTS AND METHODS: Twenty patients suffering from advanced CKD were enrolled in the study: 10 diabetic and 10 non-diabetic patients. All patients underwent electrophysiological evaluation one week before, 3 weeks and 3 months after surgery. Median, ulnar and radial nerves were studied. RESULTS: In non-diabetic patients MNCV was normal before and after surgery, but were significantly lower and reduced progressively and significantly after surgery in diabetic patients (p< or =0.02). In both non-diabetic and diabetic patients SNCV was reduced, but were significantly lower in diabetic patients before and after surgery (p< or =0.03). In diabetic patients it reduced progressively and significantly after surgery (p<0.01). Thirty percent of patients developed local edema and significant decrease of CMAP of median nerve three weeks after surgery (p=0.02) with complete resolution at three months. CONCLUSION: Diabetic uremic patients are at increased risk to develop disabling neurological complications after the construction of A-V fistulas. Diabetes was the only predictive risk factor for developing these complications. Prevention requires careful preoperative electrophysiological evaluation and postoperative follow-up.

Adult↗

PubMed2002

Erythropoietin therapy may retard progression in chronic renal transplant dysfunction.

BACKGROUND: Recent data suggests that erythropoietin therapy may actually retard the progression of chronic kidney disease (CKD). Transplant recipients with evidence of chronic allograft dysfunction could respond in a similar manner to erythropoietin. METHODS: We evaluated 166 individuals who initiated erythropoietin therapy after at least 18 days of transplant function. One hundred and nine individuals received erythropoietin between days 18 and 294 of transplant function (group 1-early epoietin alfa) while 57 individuals received erythropoietin on or after day 294 of transplant function (group 2-late epoietin alfa). The slope of serum creatinine (Scr) (Deltaslope Scr) prior to and following the start of erythropoietin therapy and calculated glomerular filtration rates (GFR) were used to assess renal function over time. RESULTS: The average haematocrit rose 6.6% in group 1 patients and 2.1% in group 2 patients during the first 100 days of erythropoietin therapy. The Deltaslope Scr was not significantly altered in group 1 patients. However, for group 2 individuals who continued to have graft function (n=35), the Deltaslope Scr became negative during erythropoietin treatment. This indicated a deceleration in the rate of loss of renal function (day 200 Deltaslope Scr -0.0033, P=0.00091; day 300 Deltaslope Scr -0.0014, P=0.05; day 400 Deltaslope Scr -0.0066, N.S., P=0.066). GFR remained stable in both cohorts. Finally, group 2-late epoietin alfa patients treated with erythropoietin demonstrated a marked trend towards longer graft survival than a group of similar control patients (N.S., P=0.064). CONCLUSIONS: The data in a group of renal transplant recipients with chronic allograft dysfunction reinforce data from the CKD realm suggesting that erythropoietin may be of benefit in slowing the rate of loss of function over time. However, this renal response is not evident in all patients. Prospective studies of erythropoietin or erythropoietin-like medications are warranted in this population to better discriminate those who may respond well to administration of these drugs.

Adult↗

PubMed2002

Clinical factors influencing sensitivity and response to epoetin.

In patients with chronic kidney disease (CKD), sensitivity to recombinant human erythropoietin (r-HuEPO, epoetin) is of clinical and economic importance. Insight into factors that influence sensitivity and response to epoetin is essential for the adequate management of anaemia. Some factors influencing response to epoetin, such as gender, age, length of time on dialysis, type of dialysis and co-morbidities such as haemoglobinopathy, are not susceptible to clinical intervention. However, many other factors can be controlled. Iron deficiency is the most common factor that limits the response to epoetin. Adequate monitoring of iron status and iron supplementation in patients with CKD will result in a more efficient epoetin response. Increased dialysis dose is associated with improvements in haemoglobin outcome and reduced requirements for epoetin. Dialysis water quality (both chemical and biological) is also important in determining the response to epoetin; 'ultrapure' water reduces epoetin requirements. Some patients, despite adequate epoetin and iron therapy, still have epoetin resistance (low haemoglobin and/or high epoetin requirements). Raised C-reactive protein and/or low albumin may reflect long-standing inflammatory pathology and indicate a need for investigation.

Aging↗

PubMed2002

Hyperphosphataemia as a cardiovascular risk factor -- how to manage the problem.

Hyperphosphataemia is a frequent and important cardiovascular risk factor in patients with chronic kidney disease (CKD). High phosphate levels may influence vascular calcifications by two separate mechanisms: by worsening secondary hyperparathyroidism, which in turn facilitates calcification, and by promoting calcium phosphate deposition in pre-formed endothelial plaques and in the arterial wall. Recent studies have shown that hyperphosphataemia induces the proliferation and differentiation of endothelial vascular cells into osteoblast-like cells, promoting vascular calcification. High phosphate levels also increase the risk of mortality in patients with CKD. To reduce the negative impact of high phosphate, serum phosphate levels should be <5 mg/dl and serum calcium <10 mg/dl. This allows the calcium x phosphate product to be maintained at < or =50 mg(2)/dl(2), reducing the risk of vascular, valvular, and extraskeletal calcification. A multiple-factor approach can be used to reduce serum phosphate: (i). decrease bone resorption by maintaining adequate serum parathyroid hormone levels; (ii). reduce phosphorous intake in the diet, (iii). use phosphate binders efficiently; and (iv). avoid under-dialysis. The patient's diet should be high in nutrition but with the lowest possible phosphorous content. Doses of phosphate binders should be tailored to individual dietary habits and must be taken during meals in a dose proportional to the phosphorous content of the meal. Because of the risk of increased extraskeletal calcification, calcium-containing phosphate-binder intake should not exceed 2-3 g/day. Sevelamer hydrochloride, a non-calcium and non-aluminium phosphate binder with a potency similar to that of calcium salts has shown beneficial effects on lipid profiles. Better control of serum phosphate is achieved in patients on continuous ambulatory peritoneal dialysis than in those on haemodialysis. Removal of phosphate is directly correlated with duration and frequency of dialysis sessions. Thus, it is advisable not to reduce the duration of dialysis sessions to <4 h three times per week.

Calcinosis↗

PubMed2002

Treatment of secondary hyperparathyroidism with vitamin D derivatives and calcimimetics before and after start of dialysis.

Chronic renal failure is almost always associated with secondary uraemic hyperparathyroidism. Action should be taken as early as possible to avoid it or reduce its severity in patients with chronic kidney disease (CKD). Over the last decade, the most effective way of achieving this has been defined as therapy with active vitamin D derivatives. However, the so-called 'non-hypercalcaemic' vitamin D derivatives, which are said to be superior, have not met our expectations so far. In contrast, calcimimetic agents, the new class of compounds that act specifically on the calcium-sensing receptor, are very promising for the treatment and prevention of hyperparathyroidism. CKD is associated with disturbances in calcium, phosphate, and vitamin D metabolism that occur early in the course of renal disease. In most patients, these disturbances lead to secondary hyperparathyroidism and osteitis fibrosa or associated, more complex, skeletal lesions. Here, we focus on recent advances in the prevention and treatment of secondary hyperparathyroidism by vitamin D derivatives and by calcimimetic agents.

Aniline Compounds↗

PubMed2002

Prevalence and socio-economic aspects of chronic kidney disease.

The incidence and prevalence of end-stage renal disease (ESRD) are rising in Europe, the USA, and Japan. Prevalence is rising more steeply than incidence, due mostly to improved efficiency of treatment -patients are surviving longer. Hypertension and diabetes, the main causes of progression from chronic kidney disease (CKD) to ESRD, are becoming more frequent in the general population and make a large contribution to the rising incidence of ESRD. More effective therapies for other conditions have introduced new complications for patients with CKD, thereby also increasing the incidence of ESRD. Increased survival in the general population is reflected in the greater number of elderly people requiring care for ESRD. ESRD is a great economic burden and one that will increase as the incidence and prevalence of the disease increase. This needs to be considered when planning treatment. Prevention and early treatment of hypertension and diabetes will have the greatest impact on the future prevalence of ESRD and the costs associated with its treatment.

Chronic Disease↗

PubMed2005

Inflammation and resistance to erythropoiesis-stimulating agents--what do we know and what needs to be clarified?

Resistance to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) can be associated with evidence of enhanced systemic inflammatory responses. This review considers the inflammatory mechanisms thought to be involved in the development and aetiology of anaemia of CKD that may help our understanding and management of patients with ESA resistance. The potential role of nutritional support and of anti-inflammatory therapies in managing resistance to ESA therapy is discussed and explored.

Anemia↗

PubMed2004

Patient referral is influenced by dialysis centre structure in the Diamant Alpin Dialysis cohort study.

BACKGROUND: Late referral (LR) to the nephrologist of patients with progressing chronic kidney disease (CKD) has numerous deleterious effects and is observed in many countries. The contributing factors associated with LR are controversial and poorly defined. We hypothesized that these factors might be better identified by analysing patients starting dialysis in three distinct European countries within the same area. METHOD: The referral and progression of kidney failure patterns were analysed with demographic, clinical and biological data in 279 non-selected consecutive patients starting dialysis in eight centres of three adjacent regions in France, Italy and Switzerland. RESULTS: Early referral (>6 months before the start of dialysis) was seen in 200 patients (71.6%), intermediate referral (1-6 months) in 42 (15.1%) and LR (<1 month) in 37 (13.3%). However inter-centre variations were between 2 and 19% for LR and 6-50% for combined late and intermediate referral. There were no differences at the national levels, but LR was more frequent in the large city centres than in the private or regional structures, with 31 out of 169 (18.3%), two out of 55 (5.4%) and four out of 55 (7.3%), respectively, of their patients (P<0.01). By multivariate analysis, it appears that, besides the presence of an active cancer and the CKD progression rate, the centre structure and the referring physician (primary care physicians and nephrologists are less responsible for LR than other medical specialists) play a significant role in the practice of LR. CONCLUSIONS: Within a dialysis cohort spread over adjacent regions of three countries, LR has the same global distribution pattern, indicating that different health and social security systems do not play a major role in inducing or preventing this practice. The contributing factors for LR that were identified are the type of the referring physician and the structure of the dialysis unit. Both factors are potential targets for an educational and collaborative approach.

Aged↗

PubMed2004

Sodium ferric gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study.

BACKGROUND: Intravenous (i.v) iron is widely used to treat anaemia in patients with chronic kidney disease (CKD). Although beneficial and usually well tolerated, concerns have been raised about its ability to cause oxidative stress and renal injury. METHODS: To determine if i.v. iron causes oxidative stress [as assessed by plasma and urine malondialdehye (MDA)] and/or renal injury (as assessed by urinary albumin, total protein and enzymuria), we conducted a prospective, four-way randomized crossover, blinded end-point trial in eight patients with CKD. Two widely used doses of sodium ferric gluconate (125 mg infused over 1 h and 250 mg infused over 2 h) were given with or without the antioxidant N-acetylcysteine (NAC), resulting in four treatment dose-antioxidant/placebo combinations in each patient. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, MDA by high performance liquid chromatography, and albuminuria and proteinuria by standard clinical methods. Enzymuria was assessed by measurement of N-acetyl-beta-D-glucosaminidase (NAG) excretion by colorimetric assay. RESULTS: I.v. ferric gluconate infusion at both doses resulted in a marked increase in transferrin saturation and a significant increase in plasma MDA levels. Urinary MDA levels also increased at the higher dose of iron. There was no evidence of acute renal injury, as assessed by albuminuria, proteinuria or enzymuria. Pre-treatment with NAC had no effect on oxidative stress or the above urinary parameters. CONCLUSIONS: I.v. ferric gluconate caused oxidative stress (as reflected by increased MDA), but this was not associated with biochemical manifestations of acute renal injury.

Acetylcysteine↗

PubMed2005

1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism.

BACKGROUND: Calcitriol treatment of secondary hyperparathyroidism (HPT) in chronic kidney disease (CKD) patients can lead to increased serum calcium and phosphorus, which have been associated as risk factors for vascular calcification. Cinacalcet HCl (Sensipar/Mimpara) {(alphaR)-(-)-alpha-methyl-N-[3-[3-(trifluoromethylphenyl)propyl]-1-napthalenemethanamine hydrochloride} lowers serum parathyroid hormone (PTH), calcium, phosphorus and calcium-phosphorous (CaxP) product in stage 5 CKD dialysis patients; however, its effects on vascular calcification are unknown. METHODS: Cinacalcet HCl (10 or 1 mg/kg, p.o. gavage), 1,25-dihydroxyvitamin D(3) (0.1 microg, s.c, calcitriol) or the combination was administered daily for 26 days in a rat model of secondary HPT [5/6 nephrectomy]. After dosing, aortic calcification was determined using the von Kossa staining method. Serum PTH and blood chemistries were determined on days 0, 26 and 0, 14, 26, respectively, prior to and after dosing. RESULTS: Calcitriol-treated rats had moderate to marked aortic calcification, whereas no significant calcification was observed in vehicle- or cinacalcet HCl-only treated groups. Co-administration of cinacalcet HCl with calcitriol did not attenuate the calcitriol-mediated increase in CaxP product or calcitriol-mediated aortic calcification. Both calcitriol and cinacalcet HCl therapy significantly reduced serum PTH levels. Calcitriol significantly elevated serum calcium, serum phosphorous and CaxP product above pretreatment levels, or those seen with vehicle or cinacalcet HCl. Cinacalcet HCl (10 or 1 mg/kg) decreased serum ionized calcium and decreased calcitriol-induced hypercalcaemia. CONCLUSION: Cinacalcet HCl and calcitriol both effectively reduce PTH, albeit via different mechanisms, but unlike calcitriol, cinacalcet HCl did not produce hypercalcaemia, an increased CaxP product or vascular calcification.

Animals↗

PubMed2006

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.

Aged↗

PubMed2006

Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function.

BACKGROUND: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C was proposed as a new endogenous marker of GFR and in our study its diagnostic accuracy was compared with that of other markers of GFR. METHODS: In this study, 164 patients with CKD stages 2-3 (GFR 30-89 ml/min/1.73 m2), who had performed 51Cr-labelled ethylenediaminetetra-acetic acid clearance, were enrolled. In each patient, serum creatinine and serum cystatin C were determined. Creatinine clearance was calculated using the Cockcroft-Gault (C&G) and the modification of diet in renal disease (MDRD) formulas. RESULTS: The mean 51CrEDTA clearance was 57 ml/min/1.73 m2, the mean serum creatinine 149 micromol/l and the mean serum cystatin C 1.74 mg/l. We found significant correlation between 51CrEDTA clearance and serum creatinine (R = -0.666), serum cystatin C (R = -0.792), reciprocal of serum creatinine (R = 0.628), reciprocal of serum cystatin C (R = 0.753) and calculated creatinine clearance from the formulas C&G (R = 0.515) and MDRD formulas (R = 0.716). The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that serum cystatin C had a significantly higher diagnostic accuracy than serum creatinine (P = 0.04) and calculated creatinine clearance from the C&G formula (P < 0.0001), though only in female patients. No difference in diagnostic accuracy was found between serum cystatin C and creatinine clearance calculated from the MDRD formula. CONCLUSIONS: Our results indicate that serum cystatin C is a reliable marker of GFR in patients with mildly to moderately impaired kidney function and has a higher diagnostic accuracy than serum creatinine and calculated creatinine clearance from the C&G formula in female patients.

Adolescent↗

PubMed2006

Effectiveness of weekly darbepoetin alfa in the treatment of anaemia of HIV-infected haemodialysis patients.

BACKGROUND: Anaemia is aggravated by the coexistence of chronic kidney disease (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin alfa effectively alleviates CKD-associated anaemia with less frequent dosing than recombinant human erythropoietin (EPO). The current study aimed to determine the efficacy, safety and cost-effectiveness of darbepoetin alfa compared with erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects receiving haemodialysis. METHODS: An open label, single arm, prospective study of 12 haemodialysis subjects with HIV infection was conducted for a duration of 6 months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to i.v. darbepoetin alfa once weekly. The primary end point was the proportion of patients maintaining haemoglobin (Hb) levels>or=11 g/dl while a weekly dose of darbepoetin alfa was a secondary end point. RESULTS: Darbepoetin alfa, as effectively as EPO-alfa maintained the proportion of the subjects having Hb levels>or=11 g/dl at an average weekly dose of 40.60 microg compared with an equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV infection stage remained the same for each specific patient throughout the study period, including the last 6 months of EPO-alfa therapy. No difference in the incidence of adverse effects was observed after switching from EPO-alfa to darbepoietin alfa. CONCLUSIONS: Lower doses of darbepoetin alfa at extended dosing interval is as safe and effective as EPO-alfa for treating anaemia, suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative to EPO-alfa in the management of anaemia associated with HIV infection in subjects receiving haemodialysis.

Adult↗