Michael R. Rudnick

Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients

The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.

Effects of Recombinant Human Erythropoietin on Renal Function in Chronic Renal Failure Predialysis Patients

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.

Contrast-Induced Nephropathy: What Are the True Clinical Consequences?

BACKGROUND AND OBJECTIVES Observational studies have demonstrated that short- and long-term mortality is increased in patients who develop contrast-induced nephropathy (CIN). The more clinically relevant questions, and the objectives of this review, are whether CIN is causally related to mortality, and to what extent could mortality in patients undergoing contrast procedures be reduced by preventing CIN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A literature review was conducted, focusing on observational studies that assessed factors associated with mortality in patients with CIN. RESULTS The deaths of some patients with CIN are complicated by factors that cannot be directly related to CIN, such as liver disease, sepsis, respiratory failure, bleeding, etc. However, it is plausible that CIN contributes to cardiovascular causes of death in patients with CIN. CONCLUSIONS At the very least, CIN is a marker for increased mortality. More carefully designed prospective studies are needed to fully elucidate the relationship between CIN and death. In the absence of data disproving a causal relationship between CIN and death in all subgroups, reducing its incidence should remain a goal in clinical practice as well as a target for future research.

Nephrotoxicity of iodixanol versus iopamidol in patients with chronic kidney disease and diabetes mellitus undergoing coronary angiographic procedures

BACKGROUND The choice of radiographic contrast media for use in patients at increased risk of contrast-induced nephropathy (CIN) is of ongoing interest. METHODS The current study is a prospective, multicenter, randomized, double-blind design comparing the renal effects of the non-ionic, iso-osmolal agent, iodixanol, versus the non-ionic, low-osmolal agent, iopamidol, in 526 subjects with impaired baseline renal function (chronic kidney disease) and diabetes mellitus undergoing diagnostic and/or therapeutic coronary angiographic procedures. The co-primary end points were the peak increase in serum creatinine (SCr) and the incidence of CIN (increase > or =0.5 mg/dL) in SCr from baseline within 3 days of receiving contrast media. RESULTS In 418 evaluable subjects with complete postcontrast media SCr data, the median peak increase in SCr in the iodixanol arm was 0.10 mg/dL, whereas in the iopamidol arm, the median peak increase was 0.09 mg/dL (P = .13). The overall CIN incidence was 10.5% (11.2% % in the iodixanol arm and 9.8% in the iopamidol arm, P = .7). The volume of contrast media, volume of saline administered, frequency of coronary interventional procedures, and severity of baseline kidney disease and of diabetes mellitus were similar between treatments. CONCLUSIONS In the present study, the overall rate of CIN in patients with chronic kidney disease and DM undergoing coronary angiographic procedures was 10.5%. There was no significant difference between iodixanol and iopamidol in either peak increase in SCr or risk of CIN.

Multicenter trial of ionic versus nonionic contrast media for cardiac angiography

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Clinical significance and preventive strategies for contrast-induced nephropathy.

Purpose of reviewContrast-induced nephropathy continues to be a common cause of in-hospital acute kidney injury. Published studies on pathogenesis, clinical significance, diagnosis, and preventive measures have dramatically increased significantly in the past several years. This review will focus on new developments in contrast-induced nephropathy. Recent findingsStudies on the clinical significance of contrast-induced nephropathy are reviewed along with initial reports of biomarkers in diagnosing this complication of iodinated contrast administration. Emerging literature on the relative nephrotoxicity of iso-osmolar versus low-osmolar contrast media and the value of bicarbonate hydration are discussed. More recent preventive measures using prostacyclin, ‘statins’, and erythropoietin are also reviewed. SummaryContrast-induced nephropathy is an increasing cause of acute kidney injury and is associated with significant mortality and morbidity. Future developments in this field will focus on refining the clinical significance of this complication, earlier diagnosis with biomarkers, clarifying the role for bicarbonate and iso-osmolar contrast agents as preventive strategies, and the introduction of new prophylactic techniques on the basis of an improved understanding of pathogenesis at the cellular level.

Contrast-Induced Nephropathy: Is the Picture any Clearer?

Although the clinical features of contrast-induced nephropathy (CIN) have been well described for some time (1,2), during the past 15 yr, interest among physicians on the subject of CIN has dramatically increased. A PubMed search of the phrase “contrast-induced nephropathy” between 1990 and 2007 produced 347 citations. During the past 5 yr alone, there were 290 citations, 159 of which appeared since 2006 (3). Intravascular administration of contrast is widely known to be a common cause of hospital-acquired acute kidney injury (AKI). In 1983, Hou et al. (4) prospectively evaluated 2216 patients with hospital-acquired AKI and found decreased renal perfusion and major surgery to be the leading causes of AKI. Contrast medium (CM) was the next most common cause, accounting for 12% of cases of AKI, and was associated with an in-hospital mortality of 6%. In 1987, Shusterman et al. (5) demonstrated that CM was one of four major factors contributing to hospital acquired AKI (the others being volume depletion, congestive heart failure, and aminoglycosides). The exact risk for CIN is difficult to determine. It is widely known that in patients with normal renal function, even in the presence of diabetes, the risk for CIN is ≤1 to 2% (1). In patients with chronic kidney disease (CKD), it is also well accepted that the risk for CIN is significantly increased and rises in proportion to the severity of underlying renal impairment (1,6,7). Another established observation is that the coupling of CKD and diabetes dramatically increases the risk …

Renal Failure in Patients with Left Ventricular Assist Devices

Implantable left ventricular assist devices (LVADs) are increasingly being used as a bridge to transplantation or as destination therapy in patients with end stage heart failure refractory to conventional medical therapy. A significant number of these patients have associated renal dysfunction before LVAD implantation, which may improve after LVAD placement due to enhanced perfusion. Other patients develop AKI after implantation. LVAD recipients who develop AKI requiring renal replacement therapy in the hospital or who ultimately require long-term outpatient hemodialysis therapy present management challenges with respect to hemodynamics, volume, and dialysis access. This review discusses the mechanics of a continuous-flow LVAD (the HeartMate II), the effects of continuous blood flow on the kidney, renal outcomes of patients after LVAD implantation, dialysis modality selection, vascular access, hemodynamic monitoring during the dialytic procedure, and other issues relevant to caring for these patients.

Low-osmolality contrast media and the risk of contrast-associated nephrotoxicity.

OBJECTIVES. The authors review clinical data, including those from the recent Iohexol Cooperative Group trial, regarding the nephrotoxic potential of low-osmolar versus high-osmolar contrast media. The clinical characteristics and postulated mechanisms of contrast-associated nephrotoxicity are also considered.METHODS. The principal strategy for identifying relevant articles was to search the MEDLINE database using the MeSH heading “contrast media nephrotoxicity.” Articles from 1966 through 1992 that were considered included original research papers as well as reviews. Those articles selected for detailed review documented original research pertaining to use of low-osmolar or high-osmolar agents. Selected abstracts for pertinent society meetings were also used. No attempt was made to be complete in describing the field. Rather, specific articles that selectively address the question of nephrotoxicity related to the osmolar content of contrast media were used for discussion.RESULTS AND CONCLUSIONS. In-vitro and animal studies indicate that renal changes possibly involved in the pathogenesis of contrast-associated nephrotoxicity seem to be ameliorated with low-osmolar contrast media, compared with high-osmolar agents. Several recent clinical trials, as well as a meta-analysis combining 24 randomized studies, suggest that the risk of contrast-associated nephrotoxicity is similarly low with high-osmolar and low-osmolar agents among otherwise stable patients with normal renal function, but that low-osmolar contrast is less nephrotoxic than media with high osmolality in patients with pre-existing renal insufficiency.

How does the nephrologist manage an LVAD patient on chronic maintenance dialysis

1. United States Annual Data Report. Available at: http://www.usrds.org/ 2010/pdf/V2_05.pdf, accessed December 24, 2014 2. Collins AJ, Ma JZ, Ebben J: Impact of hematocrit on morbidity and mortality. Semin Nephrol 20:345–349, 2000 3. Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA: The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339:584–590, 1998 4. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators: Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098, 2006 5. Dr€ ueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A; CREATE Investigators: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355:2071–2084, 2006 6. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R; TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361:2019–2032, 2009 7. FDA safety warnings. Available at: http://www.fda.gov/Drugs/ DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM109375, accessed December 28, 2011 8. USRDS Annual Data Report 2012. Available at: http://www.usrds.org/ 2012/pres/USDialysisBundle_impact_NKFCM2012.pdf, accessed January 8, 2014 9. Yabu JM, Anderson MW, Kim D, Bradbury BD, Lou CD, Petersen J, Rossert J, Chertow GM, Tyan DB: Sensitization from transfusion in patients awaiting primary kidney transplant. Nephrol Dial Transplant 28:2908–2918, 2013