Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dL

BACKGROUND: Left ventricular hypertrophy (LVH) frequently complicates chronic renal insufficiency. Anemia is also common in these patients and may contribute to LVH. METHODS: We conducted an open-label interventional trial to evaluate the effect of recombinant erythropoietin (rhEPO) on left ventricular mass index (LVMI) in anemic patients with renal insufficiency. Adults with creatinine clearance 10 to 30 mL/min (nondiabetics) or 20 to 40 mL/min (diabetics) were recruited, and rhEPO was given to those with anemia (hemoglobin level <10 g/dL). Baseline and 6-month LVMI and LVH (LVMI >130 g/m(2) in men and >100 g/m(2) in women), hemoglobin levels, creatinine clearance, blood pressure, medications, and medical history were obtained. Forty anemic and 61 nonanemic control subjects were enrolled. RESULTS: Overall, the prevalence of LVH was 68.3% (95% CI 58.3-77.2), and entry hemoglobin level was the only significant predictor of baseline LVH (adjusted OR 0.69 per g/dL increase in hemoglobin, 95% CI 0.50-0.94). After 6 months, LVMI decreased in anemic patients receiving rhEPO (142 +/- 56 vs. 157 +/- 56 g/m(2)) (P= 0.007), with an increase in hemoglobin (11.3 +/- 1.9 vs. 9.1 +/- 0.7 g/dL) (P= 0.001). There were no changes in LVMI or hemoglobin level among controls. After adjusting for confounders and change in hemoglobin, receipt of rhEPO was associated with a significant reduction in LVMI (P= 0.01). CONCLUSION: Treatment with rhEPO was not independently associated with significant changes in blood pressure or renal function. LVH is a common finding in chronic renal insufficiency and is associated with lower hemoglobin levels. Treatment with rhEPO may decrease LVH in patients with severe renal insufficiency and anemia.     

Erythropoietin and anemia in the progression of Balkan endemic nephropathy and other renal diseases

We have investigated anemia in patients at different stages of the evolution of three chronic renal diseases: Balkan endemic nephropathy (BEN), chronic pyelonephritis (PN) and chronic glomerulonephritis (GN). A total of 88 patients with creatinine clearances from 9 to 118 ml/min and hemoglobin concentrations from 70 to 160 g/l were studied with regard to the relationship, if any, between erythropoietin production and the type and stage of nephropathy. Anemia in BEN was a particular focus of interest since it had been stated that in BEN, anemia precedes renal failure. Our data neither prove nor disprove this statement. A significant positive correlation between creatinine clearance and hemoglobin concentration was found in all three nephropathies, indicating that in the patients studied the severity of anemia increased with the impairment of renal function regardless of the underlying disease. Serum levels of immunoreactive erythropoietin were in the normal range in 54 patients, moderately increased in 20 and slightly decreased in 14. The erythropoietin level appears to be unrelated to the stage of renal failure or the type of nephropathy. The only exception was the subgroup where the patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher parameters of red blood cell concentration than the patients from the same subgroup with tubulointerstitial nephropathies. In patients with severe renal failure and anemia, serum erythropoietin levels were inappropriately low for the degree of anemia, indicating that erythropoietin plays a role in the pathogenesis of the anemia.     

Epidemiology of anemia associated with chronic renal insufficiency

Several recently published reports have advanced our understanding of the epidemiology of anemia associated with chronic renal insufficiency. Anemia is commonly observed among subjects with chronic renal insufficiency. In comparison with subjects with preserved renal function, a significant decrease in hemoglobin could be detected in subjects with more modest degrees of renal insufficiency than was previously realized. Some of this undoubtedly reflects a decrease in renal production of erythropoietin, but these subjects may also suffer concomitant 'anemia of chronic disease'. Anemia is more likely not only among those with worse renal insufficiency, but also among black subjects, those with relative iron deficiency and those with lower serum albumin. Compared with those with preserved renal function, a significant decrease in hemoglobin could be detected in men at higher estimated creatinine clearance levels than in women; and at any given creatinine clearance, the decrease in hemoglobin is greater in men than in women. In the US, 800000 adults were estimated to suffer chronic renal insufficiency associated anemia, defined as hemoglobin level below 11 g/dl. As detailed in the present review, several methodological issues should be kept in mind when interpreting the literature. Further studies are needed to define the clinical implications of this common condition and to determine the most appropriate therapeutic response.     

Comparison of cystatin C, creatinine and creatinine clearance vs. GFR for detection of renal failure in renal transplant patients

BACKGROUND: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients. METHODS: In a 60-subject cohort (40 +/- 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut-off (60 and 90 mL/min/1.73 m2). RESULTS: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m2 were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different. CONCLUSIONS: This study provides cut-off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.     

Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial

BACKGROUND: Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia. METHODS: We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to <9 g/dL. The primary end point was a composite of doubling of creatinine, renal replacement, or death. RESULTS: Eighty-eight patients were randomized (early treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5 months. During follow-up, 13 versus 23 patients reached the primary end point in the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar regardless of the baseline hemoglobin and proteinuria. No patients had any severe adverse events. CONCLUSION: Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy.     

Creatinine clearance and risk of early mortality in patients undergoing coronary artery bypass grafting

OBJECTIVES: We sought to evaluate renal function assessed on the basis of calculated creatinine clearance as a predictor of early mortality and postoperative complications in patients undergoing coronary artery bypass grafting and to assess whether calculated creatinine clearance is superior to serum creatinine concentration in predicting early death postoperatively. METHODS: Six thousand seven hundred eleven consecutive patients without dialysis-dependent renal insufficiency undergoing a first isolated coronary artery bypass grafting were included. Preoperative serum creatinine concentrations and creatinine clearance calculated by using the Cockroft-Gault formula were related to mortality within 30 days postoperatively. RESULTS: There were 136 early deaths. After adjustment for age and other confounders in multivariate analyses, moderate (calculated creatinine clearance 30-60 mL/min) and severe (calculated creatinine clearance < 30 mL/min) renal insufficiency predicted early mortality (odds ratio of 2.4 [95% confidence interval, 1.2-4.8] and odds ratio of 4.8 [95% confidence interval], 1.6-13.9, respectively) compared with normal (calculated creatinine clearance > or = 90 mL/min) renal function. The area under the receiver operating characteristic curve for calculated creatinine clearance and serum creatinine concentration was 0.71 and 0.62, respectively, yielding a difference of 0.08 (P = .0004). No increased risk of mediastinitis or bleeding was observed in patients with renal insufficiency. CONCLUSION: Moderate and severe renal insufficiency independently increase the risk of early death after coronary artery bypass grafting. Our results indicate that calculated creatinine clearance is a better predictor of early mortality postoperatively than serum creatinine concentration.     

Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency

The relative importance of erythropoietin (Ep) and inhibition of erythropoiesis in the anemia of chronic renal insufficiency has been investigated. Sixty patients with varying degrees of renal insufficiency, 40 normal subjects and 40 patients with anemia and normal renal function, were studied. Erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell colony formation were assayed in fetal mouse liver and human bone marrow cultures, respectively. Erythropoietin was measured by radioimmunoassay. Hematocrit and plasma creatinine concentration correlated with the degree of serum inhibition of CFU-E formation (r = 0.69, P less than 0.001, and r = 0.62, P less than 0.001, respectively). Serum erythropoietin levels in patients with renal insufficiency (34.4 +/- 6.7 mU/ml) were slightly higher than normal values (23.1 +/- 0.98 mU/ml), but showed no relationship to plasma creatinine, hematocrit, or inhibition of CFU-E formation. In contrast, serum erythropoietin concentrations increased exponentially as the hematocrit decreased below 32% (r = 0.61, P less than 0.001), and CFU-E formation was stimulated by serum in anemia patients with normal renal function. Studies of granulopoiesis showed uremic sera supported in vitro CFU-GM growth more efficiently than sera from normal subjects. These results suggest that inhibition of erythroid, but not granulocytic, progenitor cell formation, in addition to a relative erythropoietin deficiency, are the primary factors responsible for the anemia of chronic renal failure.     

Monitoring the content of reticulocyte hemoglobin (CHr) as the progression of anemia in nondialysis chronic renal failure (CRF) patients

BACKGROUND: We previously showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status in chronic dialysis patients with erythrocytopoiesis. The CHr was significantly correlated with conventional parameters of iron deficiency in dialysis patients. We attempted to utilize the measurement of CHr levels to monitor iron status and clarify the changes in iron levels that occur as renal anemia progresses in patients with chronic renal failure (CRF). METHODS: We measured CHr, iron parameters, and the intrinsic erythropoietin (EPO) concentration in nondialysis CRF patients who visited our outpatient clinic (n=211). Iron deficiency was defined according to the transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). RESULTS: The mean CHr value of the nondialysis CRF patients (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not significantly different from that of the dialysis patients. Significant correlations were found between CHr and ferritin levels (r=0.042, p<0.0403) and CHr and TSAT levels (r=0.040, p<0.0157). A positive correlation was observed between the CHr and serum creatinine levels. Nondialysis CRF patients treated with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower CHr levels, compared with those of other patients who received less than 24,000 U/month. CONCLUSION: CHr is an easily measurable and trustworthy marker of iron status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and thus, the CHr value could likely provide useful information regarding the need for iron supplementation.     

Factor Deficiency in the Anemia of Renal Transplant Patients With Grade III-IV Chronic Kidney Disease: Baseline Results of the ARES Study

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: ≤60 and >15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 μg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin ≤13 g/dL (men) or ≤12 g/dL (women) and/or use of erythropoietin (EPO). Anemic patients (59.4%) had less sideremia (73.4 vs 81.2 μg/dL; P = .008), but no significant differences were observed for transferrin saturation index (25.9% vs 25.5%), ferritin (167 vs 171 ng/mL), iron insufficiency (26.5% vs 36.2%), pronounced ferropenia (20.4% vs 20.1%), folic acid (7.5 vs 6.6 ng/mL), or vitamin B12 (486 vs 530 pg/mL). Treatment with oral or intravenous iron was much more frequent in anemic patients (31.6% vs 9.9%; P < .001). The logistic regression analysis of factors associated with anemia revealed that renal function and the use of angiotensin-converting enzyme (ACE) inhibitors were significant but not the degree of iron deficiency. In conclusion, iron deficiency in renal transplant patients with chronic nephropathy is frequent and insufficiently treated. Although it may be an aggravating factor, it was not shown to be a determining factor for the presence or absence of anemia in the patients as a group.     

Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients

Sirolimus, being nonnephrotoxic, is a viable alternative in patients who develop renal insufficiency caused by calcineurin inhibitors (CIs). The aim of this study is to determine whether there is improvement in renal function in liver transplant recipients after switching to sirolimus-based immunosuppression. In this retrospective review, patients who were more than 3 years posttransplantation were selected. Patients who had proteinuria (protein > 300 mg/24 hr), those administered any other nephrotoxic agents, and those with a creatinine clearance (CCr) less than 20 mL/min were excluded. Renal insufficiency was defined as mild (CCr > 70 mL/min), moderate (CCr, 40 to 70 mL/min), or severe (CCr, 20 to 40 mL/min). In the 16 patients studied; there was significant improvement in serum blood urea nitrogen (36 mg/dL; range, 19 to 53 mg/dL; to 25 mg/dL; range, 10 to 37 mg/dL; P = .002) and serum creatinine levels (median, 1.95 mg/dL; range, 1.3 to 2.8 mg/dL; to 1.5 mg/dL; range, 1.0 to 2.4 mg/dL; P = .001) 6 months after switching to sirolimus therapy. There also was a trend in improvement in CCr from 43 mL min (range, 24 to 68 mL/min) to 49 mL/min (range, 22 to 152 mL/min). Among 9 patients with moderate renal insufficiency, 2 patients improved to mild renal insufficiency, 4 patients remained unchanged, and 3 patients deteriorated to severe renal insufficiency. Among 7 patients with severe renal insufficiency, 1 patient improved to mild renal insufficiency, 4 patients improved to moderate renal insufficiency, and 2 patients remained unchanged. No patient developed cellular rejection or other graft-related complications. In liver transplant recipients with chronic renal insufficiency, conversion to sirolimus-based immunosuppression allows complete withdrawal of CIs, leading to some improvement in renal function. (Liver Transpl 2003;9:126-129.)     

Anti-renin-angiotensin-system drugs and development of anemia in chronic kidney disease

BACKGROUND: A variable inhibition of erythropoiesis has been reported in uremic patients with renal anemia receiving anti-renin-angiotensin-system (RAS) drugs (angiotensin-converting-enzyme inhibitors, and angiotensin-receptor-antagonists). The time to development of renal anemia before dialysis is still unknown. METHODS: A retrospective cohort study (1 to 15 years) on records of 327 out-patients (217 males, 110 females) without anemia and with chronic renal insufficiency (creatinine clearance 16 to 75 mL/min) was conducted to estimate the time to development of renal anemia (Hb < 11.5 g/dL in females and Hb < 12.5 g/dL in men), and the time to decrease of Hb by 1 and 2 g/dL or more, irrespective of anemia development. Two treatment groups were analyzed: 142 patients with, and 185 without anti-RAS drugs. RESULTS: Median survival time to development of anemia was 81 months, 59 months to the loss of Hb > 1 g/dL, and 94 months for the loss of Hb > 2 g/dL. Anemia developed significantly earlier in patients with initial Ccr < 40 mL/min and in those with initial Hb < 14 g/dL. In the multivariate analysis (Cox model), male gender, Ccr < 40 mL/min, and Hb < 14 g/dL, in increasing order of relative risk, significantly contributed to prediction of anemia development without any influence of the treatment with anti-RAS drugs. The same results were obtained considering survival to the loss of either Hb > 1 g/dL or Hb > 2 g/dL. CONCLUSIONS: Development of renal anemia in mild to severe chronic kidney disease is not influenced by treatment with anti-RAS drugs.     

A Retrospective Assessment of Pre-Treatment Variables on the Response to Darbepoetin Alfa After Renal Transplantation

This retrospective review assesses the efficacy of darbepoetin alfa for treating anemia after renal transplantation. Patients were evaluated over a 12-week period, and efficacy was based on achieving hemoglobin >12 g/dL. Thirty-six patients were analyzed (53% male, 53% cadaveric allografts, median age 42.5 years). Baseline creatinine clearance ranged from approximately 15 to >100 mL/min. Most patients initiated darbepoetin alfa <3 months (50%) or >12 months (44%) after transplantation, 19% were previously receiving recombinant human erythropoietin (rHuEPO), and 47% were on concomitant ACE inhibitors. The majority of patients received either tacrolimus- (53%) or cyclosporine- (44%) based immunosuppression. Overall, 29 (81%) patients achieved the hemoglobin target with a mean time to response of 4.4 weeks. Neither the time to anemia onset, previous rHuEPO therapy, concomitant ACE inhibitor, allograft source, immunosuppressive regimen, nor degree of renal function affected the proportion of patients achieving the hemoglobin target, time to response or darbepoetin alfa dose requirement. Patients with anemia >12 months post-transplantation or on concomitant ACE inhibitors required a significantly longer duration of therapy. No adverse events associated with darbepoetin alfa therapy were detected. These results demonstrate that darbepoetin alfa is a safe and effective treatment for anemia in renal transplant recipients.     

Percutaneous nephrolithotomy requiring multiple tracts: comparison of morbidity with single-tract procedures

PURPOSE: To compare the morbidity of percutaneous nephrolithotomy (PCNL) requiring multiple percutaneous tracts with that of procedures requiring a single tract for calculus clearance. PATIENTS AND METHODS: Data from 20 patients undergoing PCNL through two or more percutaneous renal tracts over a 1-year period were compared with a contemporary cohort of 20 patients undergoing PCNL requiring a single tract. The mean stone size was 2157 mm(2) v 423 mm(2) (P < 0.0001), the baseline serum creatinine concentration was 1.67 mg/dL v 1.13 mg/dL (P < 0.05), and the baseline hemoglobin concentration was 11.8 g/dL v 13.4 g/dL (P < 0.05) in the multiple- and single-tract groups, respectively. RESULTS: All single-tract and 95% of multiple-tract patients were rendered stone free. The mean drop in hemoglobin was similar in the two groups (2.3 g/dL for single tract v 2.1 g/dL for multiple tracts; P = 0.55). Complications occurred in two patients in each group. Four multiple-tract patients required blood transfusion. The need for transfusion correlated with lower preoperative hemoglobin and higher preoperative serum creatinine. There was a significant rise in serum creatinine (1.67 mg/dL to 1.91 mg/dL; P < 0.05) and drop in creatinine clearance (76.9 mL/min to 67.2 mL/min; P < 0.05) in the multiple-tract group; this was more pronounced in patients with existing renal insufficiency. No significant change in renal function was seen in the single-tract group. CONCLUSIONS: Monotherapy with PCNL utilizing multiple percutaneous tracts is highly effective in the treatment of staghorn and other large-volume renal calculi. Blood loss and complication rates with such an aggressive approach are comparable to those of PCNL incorporating a single percutaneous tract for more straightforward calculi.     

Anemia Is a Predictor of Outcome in Heart Transplant Recipients

Background

Cardiovascular disease and kidney disease share similar characteristics. It has been recently recognized that many patients with cardiovascular disease have anemia, which often is associated with kidney dysfunction. Even the term “cardiorenal anemia syndrome” was endorsed to stress the dangerous association.

Objective

To assess the prevalence of anemia in relation to chronic kidney disease in 160 patients after orthotopic heart transplantation.

Results

According to the World Health Organization definition of anemia (hemoglobin concentration <13 g/dL in males and <12 g/dL in females), 41% of our patients had anemia. Patients with anemia exhibited a significantly lower mean (SD) glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease formula vs the Cockcroft-Gault formula: 44.46 (26.84) mL/min vs 62.70 (24.15) mL/min and 48.93 (27.80) mL/min vs 72.11 (29.76) mL/min, respectively (P < .001). In addition, they demonstrated lower creatinine clearance, red blood cell count, hemoglobin concentration, and ejection fraction and significantly higher creatinine and N-terminal probrain natriuretic peptide concentrations. Presence of anemia was associated with time since transplantation, GFR, creatinine clearance, N-terminal probrain natriuretic peptide and cholesterol concentrations, and ejection fraction. At multiple regression analysis, the only predictor of anemia was kidney function (GFR or creatinine clearance), which accounts for 22% of the variation. Type of immunosuppression regimen (calcineurin inhibitors vs mammalian target of rapamycin) did not seem to affect prevalence of anemia in the study population.

Conclusions

The prevalence of anemia is relatively high in heart allograft recipients and is not adequately treated. In patients with cardiovascular disease, GFR should be estimated because renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality. Chronic heart failure is also more common in patients with anemia.     

Anemia and iron deficiencies among long-term renal transplant recipients

Iron deficiency anemia after renal transplantation has not been systematically investigated. The prevalence of anemia and the indicators of iron deficiency among 438 renal transplant recipients were examined. Anemia was present in 39.7% of the patients. The prevalence of iron deficiencies, as indicated by a percentage of hypochromic red blood cells (HRBC) of >or=2.5%, was 20.1%. The majority of severely anemic patients exhibited HRBC values in the upper quartile. Positive associations of hemoglobin levels with creatinine clearance, serum transferrin levels, male gender, transferrin saturation (TSAT), polycystic kidney disease, and age were observed. Negative associations with erythropoietin therapy, use of azathioprine, serum ferritin levels, and body mass index were observed. The risk for anemia was closely related to the highest quartile of HRBC percentages (odds ratio, 2.35; 95% confidence interval, 1.48 to 3.75; P = 0.00029), whereas ferritin levels and TSAT conferred no risk for anemia. Therefore, assessment of the HRBC proportion is superior to decreased ferritin and decreased TSAT measurements for the diagnosis of iron deficiencies among renal transplant recipients.     

The relationship of hepcidin level with renal anemia and micro ? inflammation status in peritoneal dialysis patients

ObjectiveTo observe the level of serum hepcidin and the relationship of hepcidin with renal anemia and micro - inflammation state in peritoneal dialysis(PD) patients. MethodsSerum hepcidin, interleukin-6(IL-6), soluble transferrin receptor (sTfR) and erythropoietin (EPO) were measured in 50 PD patients with anemia, 30 PD patients without anemia and 40 cases of normal control by ELISA. The indexes of blood routine examination, biochemistry and iron metabolism were also detected at the same time. ResultsThe level of hepcidin in PD patients was significantly higher than that in normal control[(103.65±43.6) μg/L vs (56.39±35.7) μg/L，P＜0.05]. Furthermore, the level of hepcidin in PD patients with anemia was higher than that in PD patients without anemia [(122.67±36.6) μg/L vs (83.65±26.4) μg/L，P＜0.05]. The results of correlation analysis showed that serum IL-6, sTfR, EPO and ferritin were positively correlated with hepcidin(R ＝0.821, 0.742, 0.711, 0.531，all P＜0.05 ), while creatinine clearance of residual kidney in 24 hours and hemoglobin were negatively correlated with hepcidin(R ＝-0.533, -0.685，all P＜0.05 ). ConclusionsThe higher level of hepcidin in PD patients is related with the residual renal function and the micro-inflammatory state. The higher level of hepcidin may induce the iron metabolism imbalance, and then influence the state of renal anemia. The adjustment of hepcidin may provide clinical research value of improving renal anemia and micro-inflammatory state in PD patients.     

Influence of renal function on serum and urinary heart fatty acid-binding protein levels.

BACKGROUND: Serum heart fatty acid-binding protein (H-FABP) has been reported to be a sensitive and early indicator of myocardial damage. However, circulating H-FABP may be cleared considerably from kidney, similar to that found for myoglobin. Therefore, the possibility exists that any change in renal function affects serum H-FABP concentration, and thus leads to erroneous interpretation. To evaluate the influence of renal function on H-FABP levels, we conducted a prospective study. METHODS: Nineteen patients undergoing isolated primary coronary artery bypass grafting were enrolled in this study. The patients were classified by the preoperative creatinine clearance into two groups: the control group (n=12); patients with creatinine clearance of 40 mL/min or greater, and the renal dysfunction group (n=7); patients with creatinine clearance of less than 40 mL/min. Serum H-FABP, CK-MB, troponin-T and urinary H-FABP levels were measured perioperatively. RESULTS: None of the patients had perioperative myocardial infarction. No significant differences were found in CK-MB and troponin-T levels between the groups. The renal dysfunction group resulted in significantly (p<0.05) higher serum H-FABP levels and lower urinary H-FABP levels than those in the control group, postoperatively. The creatinine clearance correlated inversely with the peak levels of serum H-FABP (r=-0.75, p=0.0001) and correlated with the peak levels of urinary H-FABP (r=0.64, p=0.003). CONCLUSIONS: The results indicate that the kidneys play an important role in the clearance of serum H-FABP. Thus, caution must be taken in interpreting this marker for myocardial damage during cardiac surgery in patients with renal dysfunction.     

Creatinine clearance in critically ill surgical patients.

Standard tests of renal function (urine output, BUN, and serum creatinine) were compared with creatinine clearance values and with outcome in 131 critically ill surgical patients. There was a strong negative relationship between creatinine clearance and mortality. Of the 23 patients with a severe reduction of creatinine clearance (less than 20 mL/min), 17 died. In contrast, 23 of the 24 patients with a creatinine clearance of 100 mL/min or more survived. Urine output, BUN, and serum creatinine levels correlated poorly with creatinine clearance. A urine output of less than 30 mL/hr, a BUN level greater than 40 mg/dL, and a serum creatinine level greater than 2.0 mg/dL in all instances were associated with reduced creatinine clearances. However, more than half of all the patients with a normal urine output, BUN, or serum creatinine levels also had a reduced creatinine clearance.     

Effect of erythropoietin therapy on red cells filterability and left ventricular mass in predialysis patients

BACKGROUND: Cardiovascular complications are the leading cause of mortality in patients with end-stage renal disease. Left ventricular hypertrophy (LVH) is recognized as an independent risk factor for cardiovascular morbidity and mortality. At the onset of dialysis, more than 70% of the patients with chronic kidney disease have echocardiographic evidence of LVH. Anemia, increased red cells filterability time (RCFT), and blood viscosity are known to induce LVH. AIM: To evaluate, prospectively, the effects of erythropoietin (EPO) therapy for 20 weeks on RCFT and left ventricular mass (LVM). PATIENTS AND METHODS: Twenty uremic and anemic predialysis patients with creatinine clearance test below 35 mL/min were studied. RCFT test and three-dimensional echocardiography were performed at 0, 10, and 20 weeks. RESULTS: EPO therapy for 20 weeks did not adversely affect renal function and did not significantly change the mean blood pressure. It significantly increased the hemoglobin and fibrinogen levels, and decreased RCFT and LVM (p < .01). CONCLUSION: Although correction of anemia can contribute to regression of LVM, we speculate that an increasing number of cells with normalized viscoelastic properties and a direct effect of EPO on erythrocytes and myocardiocytes, through specific receptors, may also play an important role.     

Total dose infusion iron dextran therapy in predialysis chronic renal failure patients

BACKGROUND: Intravenous iron therapy is now the standard modality of iron supplementation in hemodialysis patients, but its role in predialysis chronic renal failure patients is less well established. The efficacy and safety of intravenous iron dextran as a total dose infusion in predialysis chronic renal failure patients, not receiving erythropoietin was assessed in this study. METHODS: Fifty-six predialysis chronic renal failure patients with anemia, not receiving erythropoietin were included in the study, after obtaining informed consent. Hemoglobin, serum creatinine, creatinine clearance rate and serum ferritin were assessed in all the patients at baseline. Iron dextran in a dose of 1 g dissolved in 500 mL normal saline was administered to all patients as a total dose infusion over 6 h after a prior test dose. Patients were kept in hospital under observation for at least 24 h. All the parameters were repeated in all the patients at 12 weeks and in 21 patients at 1 year. RESULTS: The mean hemoglobin (g/dL) in the patients at baseline and at 12 weeks was 8.28 +/- 0.57 and 9.22 +/- 0.44 respectively (p < 0.001). The mean serum ferritin (ng/mL) increased from 29.73 +/- 9.38 at baseline to 218.43 +/- 15.66 at 12 weeks (p < 0.00001). The mean ferritin value in the 21 patients at 1 year was 136.5 +/- 23.4 (p < 0.01). There were no major adverse events and only minor side effects were observed in 4.9% patients. CONCLUSION: Iron dextran as a total dose infusion corrects anemia in predialysis patients and is an effective method to replenish iron stores. The effect on serum ferritin are evident even at 1 year after the total dose infusion.