Citrate anticoagulation during post-dilution hemodiafiltration with a high cut-off (Theralite) membrane

Citrate anticoagulation has not yet been described for hemodiafiltration (HDF) with high cut-off (HCO) membranes, which can be used in the treatment of cast nephropathy secondary to multiple myeloma. A 57-year-old male patient with multiple myeloma and acute renal failure was treated with HDF using a HCO membrane (Theralite) each or every other day. Due to thrombocytopenia, citrate anticoagulation was done for the first 7 h, and anticoagulant-free HDF was performed for the last hour to avoid citrate accumulation. Magnesium, phosphate, and albumin were measured after 3, 6, and 8 h, and were replaced as necessary. Thirty-two post-dilution HDF procedures (8 h each, infusate 24 L) were performed with blood flow at 300-330 mL/h; sodium citrate 4% was infused at 300 mL/h and 1 mol/L calcium chloride was infused at a mean rate of 14.6 ± 1.1 mL/h. Calcium-free dialysate/infusate was used. Ionized calcium was stable (1.10 ± 0.06 before and 1.08 ± 0.06 mmol/L after HDF). Magnesium was stable (0.67 ± 0.12 before and 0.68 ± 0.05 mmol/L after HDF), with an average 390 ± 180 mg per procedure, substituted orally. There was no metabolic alkalosis or hypernatremia after the procedures, and no significant clotting was noted. The total/ionized calcium ratio (1.87 ± 0.22 before vs. 1.56 ± 0.20 after 6 h) and the corrected/ionized calcium ratio (2.02 ± 0.21 before vs. 1.88 ± 0.27 after 6 h) decreased during HDF, indicating no citrate accumulation. Citrate anticoagulation was effectively performed during 8 h of HCO membrane HDF. There were no side effects of citrate anticoagulation, nor were any signs of citrate accumulation noted.     

Phosphate kinetics during different dialysis modalities

BACKGROUND: An abnormal serum phosphate concentration is common in acute renal failure patients, with a reported incidence of 65-80%. Phosphate removal and kinetics during intermittent hemodialysis (IHD) have been investigated, but there is no information on its kinetics during slow low-efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT). METHODS: Eight IHD, 8 SLED, and 10 continuous venovenous hemofiltration (CVVH) patients with a residual renal clearance of <4.0 ml/min were studied during a single treatment to evaluate phosphate removal and kinetics. CVVH was studied the first 24 h after initiation. Dialysis/replacement fluid contained no phosphate. Kt/V, clearance of urea (Ku), inorganic phosphate (Kp) and solute removal was determined by direct dialysate quantification (DDQ). RESULTS: Kp recorded with the three techniques were: IHD, 126.9 +/- 18.4 ml/min; SLED, 58.0 +/- 15.8 ml/min, and CVVH, 31.5 +/- 6.0 ml/min. However, in shorter dialysis treatment the total removal of phosphate was significantly lower than in longer dialysis (IHD, 29.9 +/- 7.7 mmol; SLED, 37.6 +/- 9.6 mmol; CVVH, 66.7 +/- 18.9 mmol, p = 0.001). The duration of treatment is the only factor determining phosphate removal (r = 0.7, p < 0.0001 by linear correlation model). Like IHD, phosphate kinetics during SLED could not be explained by the two-pool kinetic model, and the rebound of phosphate extended beyond 1 h after dialysis. Rebound, however, is less marked than in short dialysis. CONCLUSION: These results are reliable evidence about amount of phosphate removal and behavior of intradialytic phosphate kinetics in renal failure patients undergoing different dialysis modalities. These data will help clinicians plan phosphate supplementation and treatment intensity.     

Update on Postdialysis Rebound by a New Technology in Hemodialysis

After dialysis ends, urea continued movement causes rebound postdialysis, with values at about 20%. New techniques have been incorporated into hemodialysis, but their relationship with rebound has not yet been studied. This study aimed to quantify urea rebound at 30‐min postdialysis during sessions using polysulfone filters and high‐flow versus online hemodiafiltration, and to define its correlation with body composition measured by bioimpedance by a cross‐sectional study with 69 patients (December 2015 to January 2016). Mean urea rebound was 24.39, which was positively associated with recirculation, Kt/V or hypotension, and showed a negative relationship with online hemodiafiltration. It was not associated with different body composition compartments. To conclude, postdialysis urea rebound remained high with polysulfone dialyzers and low dialysis doses. Online hemodiafiltration could improve postdialysis urea rebound. Different body composition compartments were not related to rebound.     

A case report of pediatric fulminant hepatitis treated with plasma diafiltration

Plasma diafiltration (PDF) is blood purification therapy in which simple plasma exchange is performed with a membrane plasma separator while dialysate flows outside the hollow fibers. A 14-year-old boy with fulminant hepatitis underwent two sessions of PDF and one session of hemodiafiltration. We infused filtered replacement fluid for artificial kidneys at a dialysate flow rate of 600 mL/h and a replacement flow rate of 450 mL/h. We infused fresh frozen plasma (1200 mL) and 25% albumin solution (50 mL) intravenously over 8 h. Each PDF session lasted 8 h. The patient's total bilirubin, interleukin-18, and cystatin C levels decreased with treatment, and he recovered from hepatic failure. PDF may be an extremely useful blood purification therapy for pediatric fulminant hepatitis in terms of both medical economics and cytokine removal.     

Evaluation of pre- and postdilutional on-line hemodiafiltration adequacy by partial dialysate quantification and on-line urea monitor.

On-line highflux hemodiafiltration (HDF) is a clinically interesting and effective mode of renal replacement therapy, which offers the possibility to obtain an increased removal of both small and large solutes. The fundamental role of urea kinetic monitoring to assess dialysis adequacy in conventional hemodialysis has been widely studied. Both direct measurement of the urea removed by the modified direct dialysate quantitation (mDDQ) based on partial dialysate collection (PDC) and dialysate-based urea kinetic modeling (DUKM) using urea monitor have been advocated. The validity of this assessment tool in the patients with on-line HDF remained unclear. The aims of this investigation were (1) to compare the delivered Kt/V, urea mass removal (UMR), solute removal index (SRI) and normalized protein catabolic rate (nPCR) between pre- and postdilutional high-flux HDF; (2) to verify and compare the efficiency of pre- and postdilutional HDF using DUKM with on-line dialysate urea sensor, and mDDQ with partial dialysate collection. During both mode of HDF, the paired analysis urea removed and Kt/V showed no significant difference. Using mDDQ, mean values for predilutional mode were as follows: Kt/V 1.53 +/- 0.01 UMR, 16.8 +/- 0.3 g/session; urea clearance 178 +/- 18 ml/min; SRI 75.5 +/- 7.7%; urea distribution volume (V) 28.3 +/- 1.2 liters; nPCR 1.34 +/- 0.18 g/kg/day; on the other hand, mean values for postdilutional mode were Kt/V 1.58 +/- 0.01; UMR 17.10 +/- 0.28 g/session; urea clearance 184 +/- 21 ml/min; SRI 77.2 +/- 3.5%; urea distribution volume, 27.8 +/- 1.5 liters; nPCR 1.34 +/- 0.19 g/kg/day. The mean value of urea generation rate was 5.82 +/- 1.12 mg/min during HDF. Our results showed that dialysis adequacy was achieved with both high-volume predilutional HDF and postdilutional HDF. These two modes of HDF provided similar and adequate small solute clearance. In addition, we found that on-line analysis of urea kinetics is a reliable tool for quantifying and assuring delivery of adequate dialysis.     

Heat stroke with multiple organ failure treated with cold hemodialysis and cold continuous hemodiafiltration: a case report

A 23-year-old comatose man was presented in the emergency room. He had been working inside a building under construction on a hot summer's day. His core body temperature was 42.1 degrees C and he was diagnosed with heat stroke. Urgent cooling procedures, including applying cold vapor to the patient's skin, a gastric lavage with cold water and an intravenous cold saline infusion, were not completely successful and his body temperature remained above 40 degrees C. Because his high temperature was refractory to conventional cooling procedures and we suspected that acute renal failure (ARF) by rhabdomyolysis would develop, we applied hemodialysis (HD) using cold dialysate (initially 30 degrees C and later 35 degrees C), followed by continuous hemodiafiltration (CHDF) with cold dialysate (35 degrees C) at a high flow rate of 18,000 mL per hour. The patient's body temperature fell below 38.0 degrees C within 3 h and was kept below 38.0 degrees C. Continuous hemodiafiltration was continued for one week. During the first week, the patient suffered from multiple organ failure (MOF) involving renal failure, as well as the failure of heart, liver, lung, and central nervous systems. Disseminated intravascular coagulation also developed. However, by virtue of cold CHDF, he almost recovered 3 weeks after the onset, except for remaining mild liver and renal dysfunction. In severe heat stroke, cold HD and high flow, cold CHDF should be a therapeutic choice for cooling and treatment of MOF. Considering mild liver and renal dysfunction still remained, this case suggested these procedures should be initiated at the very beginning of the treatment of severe heat stroke.     

Valoración de la influencia de la superficie de la membrana y el flujo sanguíneo en dializadores de medio cut-off

IntroductionRecently, a new class of dialyzers, medium cut-off membranes (MCO), designed to improve the permeability, which could provide an efficacy similar to hemodiafiltration, have been incorporated into our therapeutic possibilities. To increase the knowledge about its use, the objective of the study was to evaluate the effect of the surface and blood flow (Qb) on the depurative efficacy in the MCO membranes.Material and methodsWe included 19 patients in the hemodialysis. Each patient received 6 sessions, in which the membrane surface was varied, from 1.7 to 2.0 m², and/or the Qb (300, 350, 400 or 450 mL/min). In each session, different solutes were determined at the beginning and end of dialysis.ResultsThe surface change of the dialyzer did not show significant differences in the removal of small or large molecules, without changes in albumin loss. The increase in Qb was accompanied by an increase in clearance of small molecules, without showing differences in the percentage reduction of β₂-microglobulin, myoglobin, prolactin, α₁-microglobulin and α₁-acid glycoprotein, except for some comparison with Qb 450 mL/min. There were also no differences in the loss of albumin in the dialysis fluid, less than 2.5 g in all situations.ConclusionThe increase of the surface area from 1.7 to 2.0 m² in the MCO dialyzer has not meant a greater depurative effectiveness. In these dialyzers the increase of Qb does not seem to be as determinant as in hemodiafiltration except for the clearance of small molecules.     

Efficacy of Series Double Continuous Hemodiafiltration Using Two Polymethyl Methacrylate Membrane Hemofilters for Patients With Hypercytokinemia

Continuous hemodiafiltration using a hemofilter made from a membrane with cytokine adsorption properties is thought to be effective to remove cytokines in septic patients. In order to enhance cytokine removal capacity by increasing adsorption area, we devised a double polymethyl methacrylate continuous hemodiafiltration method, which involves serial connection of two polymethyl methacrylate membrane hemofilters, and we report clinical efficacy with this method. Of 74 patients who underwent continuous hemodiafiltration and had interleukin‐6 blood levels measured during their ICU stay between March 2010 and June 2012, 13 patients with hypercytokinemia (interleukin‐6 blood level >900 pg/mL) underwent series double continuous hemodiafiltration to be treated for hypercytokinemia. Cytokine reduction rate and clinical efficacy were compared between those 13 patients and those with a similar pathological condition who underwent continuous hemodiafiltration using the single polymethyl methacrylate membrane hemofilter. Interleukin‐6 blood levels 6 h after continuous hemodiafiltration initiation increased in the single continuous hemodiafiltration group from 17040 ± 33660 pg/mL to 26290 ± 66250 pg/mL; however, interleukin‐6 blood level significantly decreased in the series double continuous hemodiafiltration group from 20220 ± 29120 pg/mL to 6790 ± 10820 pg/mL. Interleukin‐6 reduction rate during the period between initiation and 6 h after initiation of continuous hemodiafiltration was significantly higher in the series double continuous hemodiafiltration group(63.5 ± 38.9%) compared to that of the single continuous hemodiafiltration group (–342 ± 1306%)(P = 0.039). Series double continuous hemodiafiltration using two polymethyl methacrylate hemofilters with cytokine adsorbing capacity is effective to remove cytokine in hypercytokinemic septic patients.     

Management of intra-abdominal hypertension in patients with severe acute pancreatitis with continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter

To evaluate, with a prospective observational study, whether continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA-CHDF) is effective for prevention and treatment of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on patients with severe acute pancreatitis (SAP). The study was carried out in the general intensive care unit (ICU) of a university hospital. Seventeen consecutive patients with SAP were treated in the intensive care unit and underwent PMMA-CHDF whether or not they had renal failure. Blood level of interleukin (IL)-6, as an indicator of cytokine network activation, and intra-abdominal pressure (IAP) were measured daily to investigate their time-course of changes and the correlation between the two. The blood level of IL-6 was high at 1350+/-1540 pg/mL on admission to the ICU. However, it significantly decreased to 679+/-594 pg/mL 24 h after initiation of PMMA-CHDF (P<0.05), and thereafter decreased rapidly. Mean intra-abdominal pressure (IAP) on admission was high, at 14.6+/-5.3 mm Hg, with an IAP of 20 mm Hg or over in 2 of 17 patients, showing that they had already developed IAH. The IAP was significantly lower (P<0.05) 24 h after initiation of PMMA-CHDF, and subsequently decreased. There was a significant positive correlation between blood level of IL-6 and IAP, suggesting that PMMA-CHDF improved vascular permeability through elimination of cytokines, and that it thereby decreased interstitial edema to lower IAP. Sixteen of the 17 patients were discharged from the hospital in remission from SAP without development of complications. Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter appears to be effective for prevention and treatment of IAH in patients with SAP through the removal of causative cytokines of hyperpermeability.     

Biochemical markers of ischaemia for the early identification of acute myocardial infarction without St segment elevation

Blood was collected on admission and after 1-2 h in 130 consecutive patients admitted with typical chest pain in order to assess the capacity of myoglobin, fatty-acid-binding protein (FABP), CK-MB mass, and troponin I (TnI) in the early identification of acute myocardial infarction (AMI) without ST elevation. Using the maximum value within 6 h of onset of symptoms, AMI was detected with a 90-95% sensitivity and a 81-94% specificity by FABP at a cut-off level 8-12 midrog/l, or 81-86% and 89-93%, respectively, by myoglobin at a cut-off level 70-90 microg/l. CK-MB mass and TnI had low sensitivity, albeit very high specificity. As almost all AMI patients were identified within 6 h, serial measurements of FABP or myoglobin ruled out AMI with a very high degree of certainty. Due to the low prevalence of AMI (16%), the positive predictive values were modest (47-73%), yet increasing the probability of AMI by a factor 3-4. Myoglobin and FABP are very useful markers in the early triage of chest pain patients.     

Arteriovenous hemodiafiltration associated with continuous arteriovenous hemofiltration: a combined therapy for acute renal failure in the hypercatabolic patient

To increase the efficiency of continuous arteriovenous hemofiltration (CAVH) in cases of severe catabolism, we used a modified CAVH treatment, called arteriovenous hemodiafiltration (AVHDF), in 4 patients. The transport of solutes was increased by providing the infusion of a counter current flow of urea-free solutions in the UF compartment of a standard CAVH circuit. Patients were treated with standard CAVH and, when a more efficient treatment was required, intermittent daily sessions of AVHDF were performed using the same filter and lines. The urea kinetic study enabled the calculation of the time needed to perform AVHDF, in addition to standard CAVH, to maintain the blood urea nitrogen (BUN) level under control. A dialysate flow rate of 300 ml/min made it possible to increase the urea nitrogen mass transfer rate from 10 to 65 mg/min and the clearance from 10.5 to 37.5 ml/min. The addition of AVHDF to CAVH enabled the control of BUN levels in the 4 patients affected by acute renal failure and a severe catabolic state. The technique is simple, does not require additional devices, and maintains the advantages of CAVH providing a better efficiency in terms of solute removal.     

Double-chamber on-line hemodiafiltration: a novel technique with intra-treatment monitoring of dialysate ultrafilter integrity

On-line hemodiafiltration is a technique that relies on the re-injection of pyrogen-free substitution fluid obtained by cold filtration of dialysate. Therefore, safety of this treatment modality depends on the quality of dialysate and, mainly, on the integrity of the ultrafilter(s) employed. Double-chamber on-line hemodiafiltration is a new technique where re-infusion takes place inside the dialyser by means of dialysate backfiltration. The peculiar geometry of the dialyser allows intra-treatment assessment of its fibre integrity. In this paper, we tested feasibility and safety of this new modality of on-line treatment. The extracorporeal blood and infusate pressure values resulted well inside the safety range. Blood urea clearances and beta(2) removal were consistent with the figures usually found in standard hemodiafiltration. Whole blood production of cytokines was similar when blood was exposed to saline or infusate, both values being comparable to the spontaneous whole blood cytokine release. The on-line dialyser fibre integrity check showed a great sensitivity even for minimal dialyser damage. We conclude that double-chamber on-line hemodiafiltration is a feasible and safe procedure. Our preliminary results encourage the undertaking of multicentre, prospective, randomised studies.     

Renal granulomatoses: a retrospective study of 40 cases and review of the literature

Renal granulomatoses represent 0.5%-0.9% of nephropathies examined by renal biopsies. Granulomas can be isolated to the kidney or associated with other tissue involvement. We describe 40 consecutive patients with renal granulomatoses, associated with pauci-immune crescentic glomerulonephritis in 2 patients and with vasculitis in another, seen in northeastern Paris hospitals between January 1991 and February 2004. The criterion for inclusion was the presence of 1 or more epithelioid granulomas in the renal interstitium. Our population of 25 men and 15 women had a median age of 53 years. All patients suffered from renal insufficiency with median creatininemia of 236.8 micromol/L (range, 124-805 micromol/L), associated with hypertension (25%), median proteinuria of 0.6 g/24 h (range, 0.08-3.00 g/24 h), microscopic hematuria (15%) and leukocyturia (22.5%). Histologic examination of extrarenal specimens detected granulomas in 82.4% of the bronchial biopsies taken, and in 100% of the 2 skin biopsies, the 2 lymph-node biopsies, and the liver and colon biopsies. The following etiologies were retained: sarcoidosis for 20 (50%) patients, drug-induced for 7 (17.5%), tuberculosis for 3 (7.5%), Wegener granulomatosis for 2 (5%), and leprosy, Mycobacterium avium infection, and Crohn disease for 1 (2.5%) patient each. No etiology could be identified for 5 (12.5%) patients. Treatment must be adapted to the etiology of each case. The renal outcome after treatment was generally favorable, with the estimated median creatinine clearance increasing from 26 mL/min (range, 5.4-80.0 mL/min) to 46.5 mL/min (range, 0-118 mL/min) after a median follow-up of 35.5 months (range, 3-158 mo). Nonetheless, 32 patients had persistent renal insufficiency; 1 required hemodialysis and another underwent renal transplantation. Sarcoidosis and medications are the most common causes of renal granulomatosis. Idiopathic and drug-induced forms do not relapse after treatment discontinuation, and remission persists at long-term follow-up.     

Citrate anticoagulation for single-needle hemodialysis: safety and efficacy

Single-needle hemodialysis can be the only option in some patients and requires full heparinization. The aim of our retrospective clinical study was to evaluate the safety and efficacy of regional citrate anticoagulation for single-needle hemodialysis. Citrate anticoagulation was performed during 41 single-needle hemodialysis procedures in 24 patients at risk of bleeding, using 4% trisodium citrate, 1 M CaCl2 and calcium-free dialysate. Safety was assessed by the percentage of procedures that were terminated prematurely or changed to another modality due to citrate-related complications and by incidence of important hypocalcemia. Efficacy was evaluated by visually assessing clot formation in the circuit. Five per cent of the procedures were terminated prematurely. Important hypocalcemia was recorded in 34% of the procedures. Anticoagulation was suboptimal in 17% of the procedures, but none of the systems clotted. The median dialyzer assessment grade was excellent. The average protocol parameters were: blood flow 244 +/- 27 mL/min, starting rate of citrate 191 +/- 19 mL/h, starting rate of calcium 6.7 +/- 1.1 mL/h. In the first hour, ionized calcium decreased in 67% of the procedures by 0.08 +/- 0.05 mmol/L. During the entire procedure, ionized calcium decreased in 80% of the cases by 0.17 +/- 0.09 mmol/L. There was a significant, but small increase in sodium (135 +/- 4 vs 137 +/- 4 mmol/L) and no increase in bicarbonate. Citrate anticoagulation during single-needle hemodialysis, according to our protocol, is safe and effective. Close monitoring of ionized calcium is mandatory. The calcium infusion rate should frequently be increased to correct hypocalcemia. The increased starting rate of calcium should be evaluated.     

Establishment of a Blood Purification System for Renal Failure Rats Using Small‐Size Dialyzer Membranes

Hemodialysis techniques for small animals have not been established because no small dialysis apparatus has been available. We recently developed a small‐size dialyzer and established an appropriate blood purification system for small animals. To confirm the appropriate dialysate flow rate, bovine blood was dialyzed for 60 min at a fixed blood flow rate of 1.0 mL/min and variable dialysate flow rates. Blood urea nitrogen and creatinine levels decreased significantly at a dialysate flow rate of 5 mL/min (from 13.7 ± 0.2 to 10.3 ± 1.2 mg/dL and 1.07 ± 0.15 to 0.61 ± 0.12 mg/dL, respectively, P < 0.05). To determine the appropriate in vivo conditions, extracorporeal circulation was performed in anesthetized male Sprague‐Dawley rats at a dialysate flow rate of 0.0 mL/min, for 240 min, and at variable blood flow rates. Extracorporeal circulation was successful at a blood flow rate of 1.0 mL/min, but not 1.5 mL/min. To establish in vivo hemodialysis conditions, we used the animal model of end stage renal failure. Sprague‐Dawley rats were fed a 0.75% adenine‐containing diet for 3 weeks, after which they received hemodialysis for 120 min at a dialysate and blood flow rate of 5.0 and 1.0 mL/min, respectively. There were no significant changes in systolic blood pressure or heart rate during dialysis. Thus, this blood purification system can be safely used for small animals at a dialysate flow rate of 5.0 mL/min and a blood flow rate of 1.0 mL/min. This system provides a basis for further research on hemodialysis therapy.     

Albumin Dialysis Molecular Adsorbents Recirculating System: Impact of Dialysate Albumin Concentration on Detoxification Efficacy

Albumin dialysis with the molecular adsorbent recirculating system (MARS) or single pass albumin dialysis (SPAD) uses human serum albumin (HSA) as an addendum of the dialysate fluid. The purpose of this in vitro study was to evaluate the impact of the dialysate albumin concentration on removal efficacy. Heparinized human plasma (3 L/test) was spiked with creatinine (1000 mg/L), unconjugated bilirubin (100 mg/L), chenodeoxycholic acid (CDCA) (100 mg/L), and diazepam (3 mg/L). The MARS albumin circuit was primed with different amounts of HSA (150, 100, 60, and 40 g). The plasma, albumin, and dialysate flow rates were 200, 200, and 40 mL/min, respectively. Clearances were calculated based on repeated sampling during the experiments, which lasted 480 min. The effective HSA concentrations in the dialysate were 175, 115, 77, and 46 g/L, respectively. They decreased over treatment time to 147, 99, 63, and 41 g/L, respectively, due to surface adsorption. The plasma–HSA concentration remained unchanged over time in all experiments (average 39 g/L). The creatinine clearance was not impacted by dialysate HSA concentration. For the albumin‐bound markers a clear correlation between HSA‐concentration and clearance was demonstrated with the highest clearances for the 100 and 150 g HSA experiments. The 100 g HSA setup appeared to be the one with best cost–benefit ratio, resulting in clearances (after 1 h of treatment) of 31 mL/min creatinine, 0.3 mL/min unconjugated bilirubin, 11 mL/min CDCA, and 35 mL/min diazepam. Low albumin concentrations, such as in SPAD, result in low clearance rates for albumin‐bound substances. The optimal clearances in these experiments were reached with a priming dose of 100 g HSA.     

Hemodynamic responses to converting enzyme inhibition in patients with renal disease

We studied the effects of lisinopril on mean arterial blood pressure (MAP), plasma renin activity (PRA), and renal hemodynamics in nine patients with chronic renal disease and hypertension, before, and after three months of therapy. Lisinopril normalized blood pressure in five of nine patients (responders) and did not in the remaining four (nonresponders). PRA rose after lisinopril (4.8 +/- 2.6 ng/mL/h to 25 +/- 15 ng/mL/h, P less than 0.05) in responders, but not in nonresponders (2.0 +/- 1.4 ng/mL/h to 3.4 +/- 2.9 ng/mL/h). Glomerular filtration rate remained stable in both groups (responders: 43 +/- 11 mL/min to 43 +/- 22 mL/min; nonresponders: 39 +/- 25 mL/min to 32 +/- 21 mL/min). In the responders renal hemodynamics remained stable after lisinopril (renal plasma flow: 223 +/- 80 mL/min to 216 +/- 91 mL/min; filtration fraction: .20 +/- .04 to .20 +/- .05; renal vascular resistance: 386 +/- 179 to 326 +/- 209 units). In the nonresponders, renal plasma flow decreased (228 +/- 141 mL/min to 162 +/- 117 mL/min, P less than 0.005), filtration fraction increased (.19 +/- .08 to .24 +/- .12, P less than 0.05), and renal vascular resistance increased (695 +/- 747 to 1265 +/- 1574 units, P less than 0.05) after chronic lisinopril therapy. We conclude (1) there is a heterogeneous response to lisinopril in patients with chronic renal disease and hypertension, (2) lisinopril monotherapy may result in effective blood pressure control without renal hemodynamic compromise, and (3) an increase in PRA following converting enzyme inhibition may identify those in whom the circulating renin angiotensin system is participating in systemic hypertension and intrarenal hemodynamic changes.     

Effect of compensated renal dysfunction on approved heart failure markers: direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP

Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are markers of heart failure. Although renal dysfunction may increase plasma concentrations, the magnitude of this effect has not been assessed in a head-to-head comparison between the clinically approved tests. We assessed the effect of compensated renal dysfunction on BNP (Triage BNP; Biosite) and NT-proBNP (elecsys proBNP; Roche) in 469 randomly selected stable outpatients after myocardial infarction (MI; Monitoring Trends and Determinants in Cardiovascular Diseases [MONICA] register Augsburg) who were characterized with respect to renal function (glomerular filtration rate [GFR]; Cockroft method) and left ventricular (LV) ejection fraction (EF) and mass (2D echocardiography). BNP and NT-proBNP were elevated in MI patients with LV dysfunction (LVD; EF <35%) compared with MI patients with preserved EF ( >45%; BNP 139+/-27 pg/mL versus 75+/-6; NT-proBNP 816+/-237 pg/mL versus 243+/-20; both P <0.03). Among all MI patients, the prevalence of renal dysfunction (GFR <85 mL/min) was 24%. BNP and NT-proBNP were significantly elevated in MI patients with renal dysfunction (BNP 132+/-17 pg/mL versus 68+/-4 without renal dysfunction; NT-proBNP 535+/-80 pg/mL versus 232+/-19; both P <0.05), and both markers were correlated with GFR in univariate and multivariate analyses (all P <0.01). When binary cut-off values were stratified according to the absence or presence of renal dysfunction (BNP 75 pg/mL and 125 pg/mL, respectively; NT-proBNP 100 pg/mL and 350 pg/mL, respectively), the predictive power of both markers for the detection of LVD increased substantially. BNP and NT-proBNP are almost similarly influenced by mild-to-moderate renal dysfunction. Renal dysfunction is a potential cause of elevated marker concentrations in the absence of LVD, and cut-off concentrations should be stratified according to renal function.     

D-dimer to Rule Out Pulmonary Embolism in Renal Insufficiency

Background

D-dimer levels are often elevated in renal insufficiency. The diagnostic accuracy of D-dimer to rule out pulmonary embolism in patients with renal insufficiency is unclear.

Methods

We evaluated the data of patients presenting to our Emergency Department and receiving computed tomography angiography to rule out pulmonary embolism with measurement of D-dimer and creatinine. Glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula.

Results

There were 1305 patients included; 1067 (82%) had an estimated glomerular filtration rate (eGFR) exceeding 60 mL/min, 209 (16%) 30-60 mL/min, and 29 (2%) <30 mL/min. One hundred fifty-two patients (12%) had D-dimer below 500 μg/L. eGFR (R = −0.1122) correlated significantly with D-dimer (P <.0001). One hundred sixty-nine patients (13%) were found to have pulmonary embolism. Sensitivity of D-dimer for patients with an eGFR >60 mL/min was 96% (confidence interval [CI], 0.93-0.99) and 100% (CI, 100-100) for those with 30-60 mL/min, while specificity decreased significantly with impaired renal function. Area under the curve of the receiver operating characteristic for D-dimer was 0.734 in patients with an eGFR of >60 mL/min, and 0.673 for 30-60 mL/min.

Conclusions

D-dimer levels were elevated in patients with an eGFR <60 mL/min, but proved to be highly sensitive for the exclusion of pulmonary embolism. However, because almost all patients with impaired renal function had elevated D-dimer irrespective of the presence of pulmonary embolism, studies should be performed to determine renal function-adjusted D-dimer cutoffs.     

Chemotherapy with cytosine arabinoside in a child with Burkitt's lymphoma on maintenance hemodialysis and hemofiltration

Summary A case of Burkitt's lymphoma (stage IV) in an 8-year-old boy with end-stage renal failure due to hemolytic uremic syndrom is reported. The boy was treated by maintenance hemodialysis (HD) and hemofiltration (HF). During chemotherapy treatment with continuous cytosine arabinoside (Ara-C) infusion (100 mg/m²/d) for 7 days, concentrations of Ara-C and its metabolite uracil arabinoside (Ara-U) were measured in blood, dialysate, and filtrate. Ara-C levels were always below 200 ng/ml and were only qualitatively detectable in blood, dialysate, and filtrate. Ara-U levels were higher than 200 ng/ml after 18 h treatment and were measured quantitatively. Ara-U clearance during 3 h HD was 92 ml/min and the calculated mass removal 14.7 mg/3 h. In contrast, the Ara-U clearance during 3 h HF was 14 ml/min and the mass removal was 6.7 mg/3 h. Ara-C and Ara-U are eliminated by HD and HF in anuric patients. A continuous infusion of 100 mg Ara-C m²/d during HD or HF treatment did not result in a serum concentration above 200 ng/ml.