Charles J. Diskin

Is Systemic Heparin a Risk Factor for Catheter-Related Sepsis in Dialysis Patients?

Background: Biofilms are dense aggregates of surface adherent microorganisms embedded in a polysaccharide matrix. Intravenous iron and heparin are thought to promote the formation of biofilm. Both are commonly employed during hemodialysis treatments which might affect the incidence of catheter-related sepsis. Methods: 559 patients who underwent hemodialysis treatment with a catheter were reviewed. Episodes of sepsis were analyzed for the use of systemic heparin and intravenous iron as well as all other risk factors for sepsis. Results: Sepsis developed in 141 of the 796 catheters. Analysis of variance revealed that the number of days that the catheter remained in place was the most significant variable (p < 0.0001) associated with catheter-related sepsis along with multiple other variables, but a Cox proportional hazards analysis revealed that only the two biofilm risk factors (intravenous iron [p < 0.001], and mid-treatment bolus of heparin [p = 0.046]) along with previously reported factor of a depressed serum albumin (p = 0.001) are of significance. Conclusion: In addition to duration of catheter use, we found three significant risk factors for sepsis and two of those three have been associated with the development of biofilm.

Towards an understanding of oedema.

Sometime during the reign of Tiberius (25-50 AD) Celsus wrote: A chronic malady may develop in patients who collect water under their skin. The Greeks call this hydrops. There are three species: 1. Sometimes the belly is tense. The Greeks call this tympanites. 2. Sometimes the body is rendered uneven by swellings arising here and there and all over. The Greeks call this hyposarka. 3. Sometimes, the water is all drawn within and is called ascites.1 Oedema has been recognised almost since the earliest recordings of medical history. Even the ancient Egyptians seem to have had a hieroglyphic for “water under the skin.” In the description of case number four in the Edwin Smith papyrus the hieroglyphic appears to be similar to the one used for water that floods from the Nile.2 This ancient familiarity, however, has not yet led to a complete understanding of oedema, and sometimes its treatment remains imperfect. None the less, an improved understanding of the pathophysiology and biophysics of oedema will allow most doctors to develop a more rational approach to treating it. #### Summary points Fig 1 Child with periorbital oedema This article is based mostly on our own research and clinical experience. When Bright first described the retention of water and waste by diseased kidneys3 he was deliberately vague about whether he was describing one disease or two since he could not …

Can acidosis and hyperphosphataemia result in increased erythropoietin dosing in haemodialysis patients

Aim:  To evaluate whether factors such as acidosis and hyperphosphataemia that might cause an increased oxygen delivery to tissues could result in increased dosing requirements for intravenous erythropoietin (EPO) administration given to haemodialysis patients.

Pharmacokinetics and Dialyzability of Sulindac and Metabolites in Patients with End-Stage Renal Failure

Sulindac was administered as a single 300‐mg oral dose to six patients with end‐stage renal failure and six normal subjects. Plasma concentrations of sulindac and its sulfide and sulfone metabolites were examined over a 48‐hour period. As determined by ultrafiltration methods at 37°C, the percentage free of sulindac and sulindac sulfide in plasma was greater, respectively, in the patients with renal failure (10.50 ± 2.42 and 9.96 ± 1.21) than in the normal subjects (6.78 ± 0.45 and 6.01 ± 0.37). Free sulindac plasma concentrations were not different between the two groups. However, sulindac sulfide, total and free, plasma concentrations were substantially decreased in the group with renal failure. Total area under the curve (AUC) of the sulfide metabolite was 18% in the normal subjects and the free AUC was 29%. In patients with renal failure, the apparent half‐lives of sulindac (1.98 ± 0.76 hours) and sulindac sulfide (15.6 ± 5.8 hours) were not different from those of normal subjects. Sulindac sulfone half‐life was highly variable and longer in the patient group. Studies of dialysis clearance showed that sulindac and its metabolites are poorly dialyzed. A 4‐hour dialysis period increased the plasma binding of both sulindac and sulindac sulfide in the patient group. Based on the decreased plasma concentration of the active sulindac sulfide metabolite in the patient group, dosage adjustments may be required in patients with end‐stage renal failure.

Understanding the pathophysiology of hemodialysis access problems as a prelude to developing innovative therapies

Maintenance of a functioning vascular access for hemodialysis is a major challenge for nephrologists, vascular surgeons and—most importantly—the patients themselves. Greater insight into the pathophysiology of access thrombosis, stenosis, aneurysm formation, fistula maturation failure and catheter infection will aid the development of innovative ways to prevent and treat these complications. According to the results of observational studies, agents that decrease the release of inflammatory mediators, improve endothelial function, and inhibit the migration and proliferation of vascular smooth-muscle cells might improve the maturation and survival of native hemodialysis fistulas and synthetic hemodialysis grafts by reducing the risks of thrombosis and stenosis. Currently available drugs that interfere with metalloproteinases could prevent the formation of aneurysms, and bacterial quorum sensing offers a promising target for the prevention of biofilm infection in hemodialysis catheters.

A Hypothesis: Can Erythropoietin Administration Affect the Severity of Retinopathy in Diabetic Patients With Renal Failure?

Background:Before the clinical availability of erythropoietin, diabetic retinopathy was known to stabilize on dialysis. Recently erythropoietin has been shown to be a potent angiogenic factor. Therefore, we chose to examine whether severity and progression of diabetic retinopathy has been accelerated by the administration of recombinant erythropoietin to patients with chronic renal failure. Methods:Records of the patients followed by the Hypertension Nephrology, Dialysis, and Transplantation Clinic, the regional nephrology referral center for Eastern Alabama, from 1982 through 2005 were reviewed. Funduscopic examination at the time of ESRD was ranked according to the proposed international scale for severity of clinical diabetic retinopathy. Forty-five patients from the era before the availability of erythropoietin were matched to 45 patients from 2002 to 2004 who had been given erythropoietin but had similar prevalence of proliferative retinopathy, neuropathy, and years of diabetes before the onset of end-stage renal disease. Progression of retinopathy was compared according to multivariate analysis with 2-tailed Pearson correlation coefficient. Results:There was significantly greater deterioration of retinopathy at 1 year in the patients who had received erythropoietin (P = 0.004). Although the presence of retinopathy at ESRD correlated with known traditional risk factors such as years of diabetes, age, and serum cholesterol, the deterioration of retinopathy after the initiation of hemodialysis correlated only with hematocrit (P = 0.042) and most significantly total dose of erythropoietin (P = 0.001). Conclusions:The prevalence and severity of proliferative retinopathy appear to have increased and are most closely associated with the erythropoietin dosing.

Creatinine and glomerular filtration rate: evolution of an accommodation

This brief review examines the history of the use of creatinine as a measure of renal function. While there are more accurate markers of glomerular filtration, creatinine was chosen for convenience. Since the relationship of creatinine to glomerular filtration depends upon a tenuous balance of counterbalancing factors, practitioners should be alert to situations that alter that balance. While the averaging of variations over time helps to avoid some of the problems with diurnal variations in the past, the present-day reliance upon equations based upon a solitary serum value is likely to amplify those problems in clinical situations when the effect of disease, medications, diet and time of day upon that balance are not considered.

Novel Insights into the Pathobiology of the Vascular Access - Do They Translate into Improved Care?

While recent developments have allowed greater insight into the vascular pathobiology and intimal hyperplasia, very few of these advances have led to improved clinical care of hemodialysis vascular accesses. Indeed the most common procedure for the treatment of access stenosis and thrombosis is the same model for the creation and study of intimal hyperplasia. The evolution of our understanding of vascular thrombosis is reviewed with a current concept that includes a dynamic interplay of the biophysics, chemistry and biology of the blood vessel with the blood and its constituents. Implications for possible future interventions based on these novel concepts are offered, and the significance of improving our understanding of the pathobiology is emphasized.

The Comparative Benefits of the Fractional Excretion of Urea and Sodium in Various Azotemic Oliguric States

Background: The fractional excretion of urea (FeUrea) may result in more reliable in the determination of renal function than sodium in the presence of oliguric azotemia; however, its usefulness remains controversial, perhaps due to an evolving understanding of urea transport within the kidney. Methods: This was a prospective observational study of 100 consecutive patients referred to the nephrology service for azotemic oliguria. Multiple clinical variables were analyzed to determine variables responsible for the differences between the FeUrea and fractional excretion of sodium (FeNa) in the ability to distinguish pre-renal azotemia from intrinsic renal disease. Results: Overall, the FeUrea was more accurate (95 vs. 54%, p < 0.0001), yet both tests accurately detected the presence of intrinsic renal disease (FeNa 75%, FeUrea 85%, p = NS). The FeUrea performed significantly better (98 to 49%, p < 0.0001) in detecting pre-renal azotemia, and that advantage came exclusively in patients taking diuretics (p < 0.0001); however, 4/5 cases incorrectly detected by the FeUrea were correctly detected by the FeNa. All 4 cases had infection. Conclusion: The FeUrea appears more accurate in patients receiving diuretics; however, the FeNa may have an advantage in patients with infection.

Removal of methotrexate by peritoneal dialysis and hemodialysis in a single patient with end-stage renal disease.

Background:Although methotrexate is highly bound to albumin, it is thought to be removed by hemodialysis and not by peritoneal dialysis. We are not aware of any direct comparison in the same patient. Case Report/Methods:A 60-year-old patient on continuous ambulatory peritoneal dialysis was admitted to the East Alabama Medical Center for stomatitis and pancytopenia after being given 10 mg of methotrexate for his rheumatoid arthritis. Measurements of total methotrexate levels were made before, during, and after sequential peritoneal and hemodialysis treatments. Results:We found that the clearance of methotrexate measured in the dialysate was equal in the first hour of dialysis for both types of dialysis, although serum levels were markedly lower in hemodialysis compared to peritoneal dialysis. Conclusion:Methotrexate was cleared by peritoneal dialysis in the first hour of an exchange and was not associated with a rebound in serum levels. Hemodialysis was associated with lower serum levels; however, there was also a significant rebound 2 hours after the procedure ended. Since neither procedure was able to preclude the death of the patient, other more effective means of methotrexate elimination should be employed.