Ali K. Abu-Alfa

Superiority of Icodextrin Compared with 4.25% Dextrose for Peritoneal Ultrafiltration

Several clinical observations suggest the superiority of icodextrin compared with 4.25% dextrose in optimizing peritoneal ultrafiltration (UF), but no rigorous controlled evaluation has hitherto been performed. For comparing icodextrin and 4.25% dextrose during the long dwell of automated peritoneal dialysis, a multicenter, randomized, double-blind trial was conducted in 92 patients (control, 45; icodextrin, 47) with 4-h dialysate to plasma ratio creatinine >0.70 and D/D(0) glucose <0.34. Long-dwell net UF and the UF efficiency ratio (net UF volume per gram of dialysate carbohydrate absorbed) were determined at baseline, week 1, and week 2. The control and treatment groups were comparable at baseline (all patients using 4.25% dextrose for the long dwell) with regard to mean (+/-SEM) net UF (201.7 +/- 103.1 versus 141.6 +/- 75.4 ml, respectively; P = 0.637) and the percentage of patients with negative net UF (control, 37.8%; treatment, 42.6%; P = 0.641). During the study period, net UF was unchanged from baseline in the control group but increased significantly (P < 0.001) in the icodextrin group from 141.6 +/- 75.4 to 505.8 +/- 46.8 ml at week 1 and 540.2 +/- 46.8 ml at week 2. In the icodextrin group, the incidence of negative net UF was significantly lower (P < 0.0001) than in the control group. Findings were similar for UF efficiency ratio. Rash was reported significantly more often in the icodextrin group. This study showed that in high-average and high transporters, icodextrin is superior to 4.25% dextrose for long-dwell fluid and solute removal.

Immunochemical characterization of Na+/H+exchanger isoform NHE4

Mammalian Na+/H+exchangers (NHEs) are a family of transport proteins (NHE1-NHE5). To date, the cellular and subcellular localization of NHE4 has not been characterized using immunochemical techniques. We purified a fusion protein containing a portion of rat NHE4 (amino acids 565-675) to use as immunogen. A monoclonal antibody (11H11) was selected by ELISA. It reacted specifically with both the fusion protein and to a 60- to 65-kDa polypeptide expressed in NHE4-transfected LAP1 cells. By Western blot analysis, NHE4 was identified as a 65- to 70-kDa protein that was expressed most abundantly in stomach and in multiple additional epithelial and nonepithelial rat tissues including skeletal muscle, heart, kidney, uterus, and liver. Subcellular localization of NHE4 in the kidney was evaluated by Western blot analysis of membrane fractions isolated by Percoll gradient centrifugation. NHE4 was found to cofractionate with the basolateral markers NHE1 and Na+-K+-ATPase rather than the luminal marker γ-glutamyl transferase. In stomach, NHE4 was detected by immunoperoxidase labeling on the basolateral membrane of cells at the base of the gastric gland. We conclude that NHE4 is a 65- to 70-kDa protein with a broad tissue distribution. In two types of epithelial cells, kidney and stomach, NHE4 is localized to the basolateral membrane.

Nephrogenic Systemic Fibrosis and Gadolinium-Based Contrast Agents

The strong association between nephrogenic systemic fibrosis (NSF) and exposure to gadolinium-based contrast agents (GBCAs) has greatly affected the care of patients with kidney disease. NSF has been reported in patients with ESRD, CKD, and acute kidney injury (AKI). The majority of cases have occurred in patients with ESRD, but about 20% have been reported in patients with AKI or CKD stages 4 and 5. There is also a risk difference among GBCAs, with the Food and Drug Administration contraindicating 3 linear agents in patients at risk. Given the significant morbidity and mortality of NSF, it is imperative to identify individuals at risk. Although there are no data to support a role for hemodialysis (HD) in reducing the risk for NSF after administration of GBCAs, immediate HD is still recommended within 2 hours. Patients maintained on peritoneal dialysis seem to be at high risk and immediate HD is also recommended. However, this is not the current recommendation for CKD stages 4 and 5, especially with suspected lower risk of noncontraindicated agents. Individualized assessment is important and especially in those patients close to dialysis initiation. Instituting policies is important to address the imaging needs of patients with CKD and AKI while ensuring a balance between benefits and risks.

Angiotensin-converting enzyme inhibitor therapy in chronic hemodialysis patients: Any evidence of erythropoietin resistance?

Exacerbation of anemia associated with angiotensin-converting enzyme (ACE) inhibitor therapy has been noted to occur in patients with chronic renal failure, end-stage renal disease, and renal transplantation. Angiotensin-converting enzyme inhibitors appear to cause anemia through induction of decreased red blood cell production. There are data suggesting that ACE inhibitors may impair erythropoiesis via either suppression of angiotensin-mediated erythropoietin (EPO) production or bone marrow response to EPO. Patients on chronic hemodialysis receive recombinant human EPO (rHuEPO) for therapy of anemia and may also receive an ACE inhibitor for hypertension or congestive heart failure. We undertook a retrospective study to evaluate whether patients treated with ACE inhibitors developed a more severe anemia or required a higher dose of rHuEPO to maintain a similar hematocrit. Ninety-five of 108 chronic hemodialysis patients met study criteria (hemodialysis for 4 months and no treatment with an ACE inhibitor for at least 4 months = group 1; therapy with an ACE inhibitor for at least 4 months = group 2). Forty-eight patients (group 1, n = 24; group 2, n = 24) were available for analysis after exclusion for a variety of factors. There was no difference between the two groups in terms of baseline characteristics, number of blood transfusions or hospital days, or other laboratory parameters. There was no statistically significant difference in average hematocrit between group 1 (33.5% +/- 3.9%) and group 2 (32.6% +/- 1.6%). Similarly, no significant difference was observed for the average rHuEPO dose/treatment between group 1 (3,272 +/- 1,532 IU/treatment; 50.69 +/- 26.94 IU/kg/treatment) and group 2 (3,401 +/- 1,009 IU/treatment; 52.87 +/- 19.38 IU/kg/treatment). These results suggest that ACE inhibitors do not significantly induce more severe anemia or alter rHuEPO response in chronic hemodialysis patients.

Observations on HIV-associated Renal disease in the era of highly active antiretroviral therapy

Background: Renal disease in patients infected with HIV has evolved to include several lesions, including HIV‐associated nephropathy (HIV‐AN), which can promote progressive loss of renal function. Although angiotensin‐converting enzyme inhibitors and corticosteroids are beneficial in selected patients, the effect of highly active antiretroviral therapy (HAART) on renal function is currently being explored. Methods: We undertook a retrospective study to determine the types of renal lesions present in patients infected with HIV with renal insufficiency and/or proteinuria during the era of HAART availability and the effect of HAART on renal outcomes in these patients. Patients with HIV infection referred to the renal clinic from July 1996 through December 2000 were evaluated. Patient characteristics and data were collected including CD4 count, viral load, serum creatinine, blood pressure, proteinuria, renal ultrasound, and biopsy results, and treatment with HAART. Study endpoints were doubling of serum creatinine, initiation of dialysis, or death. Results: Twenty‐three patients met study criteria, 13 received HAART, and 10 did not. Baseline characteristics were similar except for renal function parameters, viral loads, and CD4 counts. A variety of lesions were noted on 12 renal biopsies. A clinical diagnosis of HIV‐AN was made in the other 11 patients. Only 2 patients receiving HAART before renal evaluation were noted to have HIV‐AN. In the HAART group, none of the patients, including those with HIV‐AN, developed a doubling of serum creatinine. In the non‐HAART group, all patients manifested a doubling of serum creatinine, 2 patients died, and 8 patients required dialysis. Conclusions: A variety of renal lesions are noted in patients infected with HIV during the HAART era. Patients who received HAART maintained stable renal function, whereas patients who did not required dialysis therapy or died with advanced renal failure. It seems that HAART may improve renal outcomes in patients with HIV and renal disease.

Systematic Barriers to the Effective Delivery of Home Dialysis in the United States: A Report From the Public Policy/Advocacy Committee of the North American Chapter of the International Society for Peritoneal Dialysis

Home dialysis, currently underused in the United States compared with other industrialized countries, likely will benefit from the newly implemented US prospective payment system. Not only is home dialysis less expensive from the standpoint of pure dialysis costs, but overall health system costs may be decreased by more subtle benefits, such as reduced transportation. However, many systematic barriers exist to the successful delivery of home dialysis. We organized these barriers into the categories of educational barriers (patient and providers), governmental/regulatory barriers (state and federal), and barriers specifically related to the philosophies and business practices of dialysis providers (eg, staffing, pharmacies, supplies, space, continuous quality improvement practices, and independence). All stakeholders share the goal of delivering home dialysis therapies in the most cost- and clinically effective and least problematic manner. Identification and recognition of such barriers is the first step. In addition, we have suggested action plans to stimulate the kidney community to find even better solutions so that collectively we may overcome these barriers.

Ace inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

The Impact of NSF on the Care of Patients With Kidney Disease

The association of nephrogenic systemic fibrosis (NSF) with the use of gadolinium-based magnetic resonance contrast agents (GBMCAs) has greatly affected the care of patients with kidney disease. Nephrogenic systemic fibrosis has been reported in patients with end-stage renal disease, chronic kidney disease (CKD) and acute kidney injury. The majority of cases have occurred in patients with end-stage renal disease, but cases of NSF have been reported in CKD patients with glomerular filtration rates less than 30 mL/min/1.73 m(2). Odds ratios have ranged between 8.97 and 32.5 among patients exposed to GBMCAs. Given the significant morbidity, disability, and mortality associated with NSF, it is imperative to properly and preemptively identify those patients at risk. Patients with end-stage renal disease seem to be at highest risk, particularly those maintained on peritoneal dialysis (PD). Although there are no data to support a role for hemodialysis in reducing the risk for NSF after the administration of GBMCAs, hemodialysis is recommended within 2 to 3 hours. Patients maintained on PD and those with CKD present a challenge, as they do not typically have vascular access for hemodialysis, yet the clearance of GBMCAs is very low, and it may be prudent to consider hemodialysis especially for PD patients. Gadolinium-based magnetic resonance contrast agents are removed by dialysis, with estimates that about 99% of a dose is removed after 3 to 4 sessions of hemodialysis. The elimination half-life averaged 9 hours in patients with stage 4 CKD (glomerular filtration rate <30 mL/min/1.73 m(2)) compared with 1.5 hours in those with normal glomerular filtration rates. This prolonged elimination and longer exposure may be important factors in predisposing to NSF.

Gadolinium-based contrast agents and nephrogenic systemic fibrosis: why did it happen and what have we learned?

This article addresses two questions about gadolinium‐based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF): “Why did it happen” and “What have we learned”? It reviews the events leading to the discovery of an association between NSF and GBCAs. Various factors are elucidated that contributed to the delay between the time when GBCA came into widespread clinical use and a link was made with NSF, including use in renal‐compromised patients, high‐dose magnetic resonance angiography (MRA), lack of documentation and adequate databases, policy and regulatory changes, and an absence of scientific evidence. The authors conclude that the overriding cause was lack of awareness. J. Magn. Reson. Imaging 2009;30:1236–1239.

Successful use of intraperitoneal daptomycin in the treatment of vancomycin-resistant enterococcus peritonitis.

Peritoneal dialysis-associated peritonitis from such resistant organisms as vancomycin-resistant enterococci increasingly is occurring and is challenging to treat. We describe 2 cases of vancomycin-resistant entercoccus peritonitis successfully treated with intraperitoneal daptomycin. Both patients were on automated peritoneal dialysis therapy with culture-positive vancomycin-resistant Enterococcus faecium peritonitis and were treated with 10 to 14 days of intraperitoneal daptomycin given every 4 hours through manual peritoneal dialysate exchanges. Despite the known degradation in dextrose solutions, intraperitoneal daptomycin was effective in clearing both infections. Neither patient experienced a relapse or repeated peritonitis. Additional studies of dosing and pharmacokinetics of intraperitoneal daptomycin in the treatment of patients with vancomycin-resistant enterococcus peritonitis are needed.