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BACKGROUND: Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia. METHODS: In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0–10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set. RESULTS: Of 564 eligible participants randomized to receive tenapanor (n=423) or sevelamer carbonate (n=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (n=128) or placebo (n=127) during the randomized withdrawal period. In the efficacy analysis set (n=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was −1.4 mg/dl (P

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of β-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 ( n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly ( P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate ( P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 ( n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB ( r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Background and Aims Tenapanor, a first-in-class, phosphate absorption inhibitor blocks the paracellular absorption of phosphate in the GI tract by local inhibition of the sodium-hydrogen exchanger (NHE3). It therefore provides a novel, non-binder approach for managing hyperphosphatemia. Tenapanor is dosed as one small pill twice daily. In three pivotal trials, tenapanor met its primary phosphorus-lowering outcome. This report evaluates long-term safety data from the longest of these trials. Method This 52-week study consisted of a 26-week, open-label, randomized treatment period with a 12-week placebo-controlled randomized withdrawal period, followed by a 14-week open label safety extension period. Maintenance dialysis patients with serum phosphorus ≥ 6.0 mg/dL and a 1.5 mg/dL increase in serum phosphorus following phosphate binder washout were randomized 3:1 to receive tenapanor 30 mg twice daily or sevelamer carbonate, dosed per package insert. At end of the randomized treatment period all patients in the tenapanor arm were re-randomized 1:1 to either tenapanor or placebo for the randomized withdrawal period followed by tenapanor for the safety extension period. Sevelamer was used as a safety control for comparisons of serious adverse events/hospitalizations to tenapanor. Results Tenapanor was generally well tolerated, with diarrhea the only adverse event reported by >5% of patients during the randomized treatment period. Diarrhea was typically mild-to-moderate in severity, transient, and occurred more commonly during the randomized treatment period than the randomized withdrawal or safety extension periods. Rates of serious adverse events leading to hospitalization were higher in patients treated with sevelamer than tenapanor (35.8% vs 24.6%). The highest reported percentages of serious adverse events were infections and infestations (16.1% vs 9.3%) cardiac disorders (8.0% vs 5.7%), respiratory, thoracic and mediastinal disorders (8.8% vs 5.5%), and metabolism and nutritional disorders (7.3% vs 3.6%) for sevelamer and tenapanor, respectively. Adverse events leading to death were higher in patients treated with sevelamer than tenapanor (3.6% vs 2.9%). Conclusion Among maintenance dialysis patients with hyperphosphatemia, tenapanor, a novel, non-binder, phosphate absorption inhibitor that blocks paracellular absorption of phosphorus with a one tablet twice daily dose, has an acceptable safety profile, and, if approved, may offer a new approach to the treatment of hyperphosphatemia.

Malnutrition is prevalent in end-stage renal disease (ESRD) patients treated with hemodialysis (HD) and peritoneal dialysis (PD). In addition, there is increased incidence of morbidity in this group. Evaluation of nutritional status is important. Application of body composition in the ESRD population to evaluate body compartments and to assess nutritional health has become more common in clinical practice. Neutron activation analysis (NAA) may provide data on metabolically active tissue by quantification of total body potassium (TBK) for body cell mass and assessment of protein by total body nitrogen (TBN). This method may be able to detect changes in body composition before clinical signs of malnutrition are apparent. Ten HD (5 male and 5 female) and 10 PD patients (7 male and 3 female) were evaluated by NAA, TBK, and isotope dilution. Female PD patients had an increased total body water (TBW) and increased intracellular water compared to HD females. Albumin was lower in PD women. There was no significant difference between PD men and laboratory controls in TBW, extracellular water, and TBN. The clinical application of body composition methods for evaluation of dialysis patients by serial assessment and for development of a bedside tool needs further study.

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814

Objective: To evaluate percentage body fat in hemodialysis (HD) and peritoneal dialysis (PD) patients. Design: A prospective study of 20 HD patients and 20 PD patients. Setting: Sol Goldman Renal Therapy Center, Lenox Hill Hospital, New York, NY; Baumritter Kidney Center Albert Einstein College of Medicine, Bronx, NY; Body Composition Unit, St Luke's Roosevelt Hospital, Columbia University, New York, NY. Patients: Twenty HD (10 men, 10 women) patients, mean age 41.8 ± 2.4 years and 20 PD (12 men, 8 women) patients, mean age 48.6 years ± 3.0 years. Intervention: This is a noninterventional study. Patients signed consent to undergo dual-energy x-ray absorptiometry, total body potassium counting bioelectrical impedance analysis, total body water determination, and anthropmetric evaluation. Main outcome measures: Present and compare percentage body fat between HD and PD patients as determined by the methods used. Results: Percentage fat is not different between HD and PD patients. Differences in absolute values of percent fat between techniques exist. Conclusion: HD patients and PD patients may be evaluated by the methods of body composition used. Percentage body fat will vary among techniques; therefore the same method should be used to follow a patient over time.

There exists an imperative to monitor changes in body composition in all dialysis patients on a regular basis to avoid overt malnutrition. In this regard, the absolute measurement of the fat-free mass assessment may not be as crucial as the serial measurement of fat-free mass with the same modality. A significant difference in measured fat and fat-free mass should be expected if different techniques are employed. Therefore, when attempting to monitor patients over time or to assess the effects of changes in therapeutic regimens, a single methodology should be employed. Our data validate the use of BIA in the stable PD patient, indicating that BIA can predict the DXA results. Considering the ease with whichBIA measurements can be obtained and the lack of dependency on operator interpretation, BIA is an ideal technique for use in the clinical setting. The applicability of this technique for use in monitoring longitudinal changes in body composition has, in fact, been well established (25,30,31). BIA appears to be an excellent method for routine fat-free mass measurement in dialysis patients. In as much as malnutrition continues to remain a significant problem in PD patients, measuring and monitoring body composition is strongly recommended.

Purpose: Provision of lifelong angioaccess for hemodialysis generally requires multiple procedures. To extend the availability of each extremity as an access site, we have used the transposed basilic vein for fistula construction since 1988. Our purpose is to present our initial experience, with follow-up of 30 months. Methods: We have used the transposed proximal basilic vein in 65 procedures to construct an autogenous arteriovenous fistula (AVF) to the brachial artery in 58 patients without suitable superficial venous anatomy. There were 25 males and 33 females, with a mean age of 47 years (range 10 to 77). The basilic vein transposition was the initial angioaccess procedure in only 25% of cases and secondary in 75%. Three additional patients underwent exploration of an inadequate basilic vein with subsequent prosthetic grafting. Results: There were no operative deaths. Two postoperative complications included a wound infection and a transient steal syndrome. The actuarial life-table patency rate for all successfully completed AVFs was 49% at 30 months. Late revisions with continued patency were required in 11 cases, including repair of a focal stenosis in six, pseudoaneurysm resection in two, and thrombectomy in one. Sixty-seven percent of patients who required subsequent prosthetic grafting for a failed basilic vein AVF had an ipsilateral procedure. Patient preference for the opposite arm was the usual indication for contralateral grafting in the remainder. Conclusion: The transposed basilic vein AVF was technically feasible in 95% of cases, can frequently be performed in patients with multiple previous access procedures, does not compromise the arm for future prosthetic grafting, and has a long-term patency rate that is comparable to more traditional autologous AVFs. This underused procedure should be considered before placement of polytetrafluoroethylene graft for long-term angioaccess. (J VASC SURG 1993;18:391-7.)

Branched-chain amino acid in chronic renal failure patients: Respiratory and sleep effects. Sleep disorders, including a high incidence of sleep apnea, have been recognized as a significant problem in chronic renal failure (CRF) patients. In a preliminary study, we examined CRF patients on maintenance hemodialysis for three nights; one control night, and thereafter randomized to infusion of saline (placebo) for one night and 4% branch-chain amino acid (BCAA) solution for one night. Polysomnographic and respiratory data [respiratory rate, oxygen saturation and end-tidal CO2 (ETCO2)] was recorded continuously throughout the nights and data from each hour compared with baseline (awake) values. The patients studied were characterized by reduced sleep quality and decreased amount of rapid eye movement (REM) sleep. The BCAA infusion was associated with a return of REM sleep to normal and a significant decrease in ETCO2 during both REM and non-REM sleep (P < 0.05). Our findings demonstrate respiratory stimulation during sleep with infusion of BCAA; this stimulatory effect on respiration (in contrast to many respiratory stimulants) is associated with an increased amount of REM sleep.

A patient receiving adoptive immunotherapy with recombinant interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells for metastatic melanoma developed acute renal insufficiency out of proportion to the decrease in her renal perfusion after 4 days of receiving IL-2. On the 8th day of IL-2 and the 3rd day of LAK cell infusion she expired suddenly from an acute intra-abdominal hemorrhage due to rupture of a metastasis. Postmortem examination of the kidneys showed an interstitial infiltrate consisting largely of lymphocytes and concomitant tubulitis. Immunoperoxidase staining of the infiltrating cells with a panel of lymphocyte-specific monoclonal antibodies showed the majority of cells to be T lymphocytes (70-75%), with a more focal infiltrate of B lymphocytes (25-30%) and rare monocytes, granulocytes and natural killer cells. This patient represents the first reported case of acute interstitial nephritis associated with IL-2 immunotherapy. Our finding is consistent with the hypothesis that the acute renal failure that accompanies this therapy may sometimes be due to intrinsic renal disease as well as the usual pre-renal failure. Nephritis may be caused by IL-2-mediated effects on lymphocytes, resulting in renal parenchymal infiltration.

Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been effective in treating some advanced malignancies in animals and humans. One complication of this treatment is a reversible, oliguric, acute renal failure, which has been ascribed to renal hypoperfusion and resultant prerenal azotemia. We serially studied renal function in 10 patients receiving high-dose regimens of recombinant interleukin-2 (rIL-2) to attempt to delineate further the nature of the renal dysfunction caused by IL-2 treatment. Renal plasma flow was computed from iodine 131 (I-131 Hippuran; Mediphysics, Paramus, NJ) orthoiodohippurate, excretion curves, and glomerular filtration rate (GFR) was determined by creatinine clearance. Studies done prior to and on day 4 of treatment showed that GFR fell in nine of 10 patients, with a mean decrease of 43% +/- 8%, and renal plasma flow fell in five of the 10 patients with a mean decrease of 5% +/- 10%. The average pretherapy filtration fraction was calculated to be 23% +/- 1% and after 4 days of treatment, decreased to a mean value of 15 +/- 2%. The BUN to creatinine ratio also declined in all patients. These findings collectively suggest that IL-2 nephrotoxicity may result from an intrarenal defect in addition to the previously described prerenal azotemia. Additionally, radionuclide studies of renal function are a reliable and reproducible noninvasive method of assessing these changes in renal function.

In 1997, the Health Care Financing Administration Hematocrit Measurement Audit (HMA) program initiated use of a 3-month rolling average hematocrit (Hct) level for reimbursement of epoetin claims in hemodialysis patients, with denial of payment when this value exceeded 36.5%. This study evaluated the impact of the HMA program on anemia-related outcomes in hemodialysis patients. An observational, retrospective study of 987 hemodialysis patients from 11 dialysis centers in the United States was performed, collecting data between October 1996 and December 1997. Centers were selected from a pool of nearly all facilities in the United States, which during May 1997 satisfied one of two criteria: greater than 75% of patients at the facility had mean Hct level ofor =33% (Group A) or fewer than 50% of patients at the facility had mean Hct level ofor =33% (Group B). Each facility maintained its own anemia management practices without specific anemia management interventions as part of this study. Hct level, hemoglobin (Hb) level, and epoetin dose were analyzed to compare the pre-HMA period (October 1996 to May 1997) to the HMA period (June to December 1997) and/or for each of the five quarters of the study period. The primary study endpoint was the percentage of patients with Hct levels ofor =33% during each study quarter. The mean Hct level at baseline was 34% in Group A and 33.4% in Group B (p = 0.01). Hct levels, which were increasing before implementation of the HMA program, decreased during the HMA period (p0.001 and p = 0.013 in Groups A and B, respectively). The percentage of patients in Groups A and B with mean quarterly Hct levels ofor =33% decreased during the last quarter of the HMA implementation period compared to the quarter immediately preceding the start of the HMA program (p0.001 for both comparisons). Changes in Hb levels were similar to those seen in Hct levels. The mean epoetin dose administered decreased from 13,090 U/week at the start of the study to 11,884 U/week immediately before the HMA program took effect (p0.05). The HMA program adversely affected anemia treatment outcomes, regardless of whether dialysis units before HMA implementation had50% of patients with a Hct level ofor =33% or had75% of patients with a Hct level ofor =33%. The decline in mean weekly dose of epoetin was likely a result of withholding doses out of concern among providers about risk of reimbursement denial.

Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran.BackgroundParenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.MethodsThis multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.ResultsA total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.ConclusionSFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.

The optimal method for diagnosing iron deficiency in end-stage renal disease is an area of controversy. This study compared the use of zinc protoporphyrin (ZPP) with the use of conventional tests for determination of iron deficiency when evaluating the need for intravenous iron therapy in hemodialysis patients maintained on erythropoietin (EPO). A baseline survey was performed in all hemodialysis patients at the Baumritter Kidney Center (Bronx, NY), measuring ZPP, ferritin, transferrin saturation (TSAT), mean corpuscular volume, and hematocrit. Patients with ZPP ≥ 90 μmol/mol heme or ferritin less than 100 ng/mL were considered likely to be iron deficient and were treated with 1,000 mg of intravenous iron dextran over 10 hemodialysis treatments. The positive predictive values of ferritin and ZPP for predicting a response to intravenous iron dextran were similar (73% v 83%, respectively; two-tailed, P = 0.48). To determine the sensitivity and specificity of the tests, patients were divided into two groups at the end of the study period: those in whom iron therapy was required (n = 23) (patients treated with intravenous iron dextran who had a 5% increase in hematocrit or a decrease in erythropoietin dose of ≥2,000 U/treatment) and those in whom iron therapy was not required (n = 24) (patients either treated with intravenous iron dextran without a response [n = 9] or patients whose initial ZPP and ferritin levels were not suggestive of iron deficiency and who maintained a stable hematocrit and erythropoietin dose during the study period [n = 15]). Zinc protoporphyrin of ≥90 μmol/mol heme had the best combination of sensitivity and specificity (87% and 83%, respectively) of the tests evaluated, and therefore offered the greatest utility of the tests evaluated for predicting hemodialysis patients who require intravenous iron dextran therapy for iron deficiency.

In patients on continuous ambulatory peritoneal dialysis (CAPD) for more than 6 wk, we measured functional residual capacity (FRC), maximum inspiratory and transdiaphragmatic pressure, diaphragm length, and radius of curvature (roentgenographic methods) as functions of the volume of peritoneal dialysate (PD) instilled within the abdominal cavity. This allowed in vivo characterization of the human diaphragm's force-length relationship. As PD volume increased from zero to 3 L, FRC decreased from 2.41 +/- 0.29 L to 1.93 +/- 0.072 L; mean total diaphragm length index (TDLI) increased from 0.22 +/- 0.01 to 0.28 +/- 0.01, and diaphragm radius of curvature remained unchanged. Respiratory muscle strength increased as a function of dialysate volume, reaching its maximum after the infusion of 3 L PD. In contrast, normal subjects achieved maximal inspiratory muscle force at their normal FRC, with a mean TDLI of 0.26 +/- 0.01 and showed no further increase as the diaphragm lengthened. We conclude that the human diaphragm may be capable of an adaptive rightward shift in its force-length relationship when it is chronically lengthened by CAPD.

Systemic lupus erythematosus (SLE) occurs primarily in women during child-bearing years. The possible influence of pregnancy on the underlying activity of SLE has important implications for this group of patients because of the threat of severe, and even life threatening, exacerbations of disease, and the possibility of a reduced likelihood of a successful outcome for the product of conception. On the basis of previous reports on large series of cases, the relationship between SLE and pregnancy is controversial [1–4]. Furthermore, although renal involvement is a common feature of SLE and is a major source of morbidity and death [5], the influence of pregnancy on lupus nephropathy has not been ascertained. Previous reports on the relationship between lupus nephropathy and pregnancy are difficult to analyze because, in general, few have detailed information on the chronologic sequence of nephropathy and pregnancy, and the type and severity of the underlying renal histopathologic lesion [1–3, 6–11]. Moreover, in some initial reports, current modes of treatment were not available. The present study was undertaken to characterize the clinical course of SLE in patients with lupus nephropathy during pregnancy and postpartum. Because it seemed unlikely that sufficient clinical materials for analysis would be available to any single clinic, or that a prospective study of pregnancy in patients with SLE would be performed in the near future, we conducted a survey of nephrologists with an interest in lupus nephropathy, representing a wide geographic distribution. This analysis is derived from data obtained on 65 pregnancies by 47 patients with SLE reported from 13 centers. All patients manifested clinical signs of lupus nephropathy at some time during the course of their illness, and renal biopsy material was available in 77% of cases. Because lupus nephropathy increases the morbidity associated with SLE, it seems likely that any bias in selection of these cases would favor those with greater severity. In addition, because these cases were obtained from multiple centers, the clinical material used in this analysis tends to reflect the widely divergent attitudes towards SLE and treatment modalities used to treat this disease.

Elevated creatine kinase (CK) has frequently been described in patients on chronic dialysis, but little is known about its cause and distribution. We, therefore, measured CK in 105 patients on hemodialysis and continuous ambulatory peritoneal dialysis and compared it with biochemical, nutritional, and anthropometric data obtained at the same time. In the entire group, CK was 130.3 +/- (SEM) 15.0 IU/l. Thirty patients had elevated levels of enzyme (greater than 130 IU/l). Isoenzymes determined in patients with elevated CK levels were all more than 97% MM fraction. Men had significantly higher (p less than 0.001) CK values (166.0 +/- 25.8 IU/l) than women (82.4 +/- 9.0 IU/l). Blacks had higher CK values (158.8 +/- 21.7 IU/l; p less than 0.001) than whites (92.6 +/- 12.5 IU/l). Men and blacks had significantly higher weight and midarm muscle circumference than women and whites, respectively. A positive correlation was found between CK and lactic dehydrogenase (p less than 0.001) and between CK and midarm muscle circumference (p less than 0.05), and a negative correlation (p less than 0.01) was found with age. Predialysis and postdialysis CK was measured in 10 patients and did not rise. Three of the patients with elevated CK who have undergone successful renal transplantation showed normalization of CK levels. We conclude that CK is elevated in both hemodialysis and continuous ambulatory peritoneal dialysis patients, particularly in men and blacks, that CK levels are probably related to muscle mass, and that CK declines with advancing age. Although blacks have higher CK values as a whole, normalization of CK values after renal transplantation suggests a contributory role of renal dysfunction.

Ninety-three dialysis units located in the tri-state area were surveyed for the prevalence of priapism. Seventeen of 3,337 male patients experienced an episode of priapism. All of these episodes occurred either during or 2-7 h after dialysis, suggesting a cause-and-effect relationship. The use of heparin during dialysis seemed to play a role in its induction; none of the patients on peritoneal dialysis experienced priapism, and heparin was not used in their exchanges. Eleven of 17 patients also received androgen therapy which might have been a contributing factor. Additional considerations included dialysis-induced hypoxemia and acidosis which have been known to precipitate priapism in patients with sickle cell disease or trait. In our study, 2 of 10 patients, including our case report, were black males with sickle cell trait. The calculated prevalence in the male population is 1:196, and in blacks and Caucasians 1:128 and 1:293, respectively. Except for 2 cases of sickle cell trait in the 10 black males, no particular subpopulation at risk was identified. In view of the absence of a proven etiologic agent and the relatively low prevalence of priapism we do not recommend changes in dialysate, anticoagulant, or the use of androgen therapy.

Hemoglobin variability in epoetin-treated hemodialysis patients. Background Understanding the clinical variability of hemoglobin measurements in epoetin-treated hemodialysis patients is important, particularly when this therapy is aimed at maintaining patient hemoglobin levels within a narrow range, such as the 11 to 12 g/dL range recommended in National Kidney Foundation Kidney Dialysis Outcomes Quality Initiative (NKF-K/DOQI) guidelines. This study examines hemoglobin variability under conditions of standard clinical practice in epoetin-treated hemodialysis patients. Methods We studied 987 hemodialysis patients participating in an observational retrospective study that evaluated anemia management practices from October 1, 1996 to December 31, 1997 at 11 United States dialysis centers that were randomly selected from a pool of nearly all United States dialysis facilities. Each participating facility maintained its own anemia management protocols without specific anemia management recommendations or interventions made as part of this study. Hemoglobin variability was determined by calculating the 1-month and 2- to 6-month rolling average hemoglobin for each patient. The range of mean hemoglobin values that included the middle 50% (25th to 75th percentile), 80% (10th to 90th percentile), and 90% (5th to 95th percentile) of values were determined. The hemoglobin ranges that included 1 standard deviation (SD) (67%) of the study values and 2 SD (95%) of the study values for each time period were calculated. Results The mean hemoglobin was between 10.9 and 11.2 g/dL throughout the study. The hemoglobin range encompassing 50%, 80%, and 90% of values from a single month was 1.7, 3.3, and 4.4 g/dL, respectively. A progressive narrowing in the range of hemoglobin values encompassed by each percentile grouping (i.e., hemoglobin variability) was observed as longer rolling intervals were averaged. The hemoglobin range within the 25th to 75th percentile was 1.7 g/dL using single-month hemoglobin values and 1.1 g/dL using a 6-month rolling average. The range of hemoglobin values that encompassed 90% of patients was 4.4 g/dL using single-month values, 3.7 g/dL using 3-month rolling averages, and 3.2 g/dL using 6-month rolling averages. Fewer than 50% of patients had hemoglobin values within the 1.0 g/dL NKF-K/DOQI recommended range, even when a 6-month rolling average was applied. When hemoglobin values were measured for 1 month, 1 SD was 1.4 g/dL; for the 3-month rolling average, 1 SD was 1.1 g/dL; and for the 4-, 5-, and 6-month rolling averages, 1 SD was 1.0 g/dL. Greater hemoglobin variability correlated with higher mean corpuscular hemoglobin ( P = 0.003) and serum ferritin ( P = 0.047), and inversely correlated with age ( P = 0.006) and serum albumin ( P = 0.0001). Conclusion Substantial variability occurs in hemoglobin values in epoetin-treated hemodialysis patients. The NKF-K/DOQI recommended hemoglobin range appears to be too narrow in clinical practice. Expanding the target range and use of rolling average hemoglobin intervals of 3 to 6 months as a clinical and quality assurance measure avoids clinical variability inherent with the use of isolated hemoglobin values or single-month hemoglobin averages.

To our knowledge, there has been no report documenting the spectrum of peritonitis in human immunodeficiency virus (HIV)-infected persons. We therefore analyzed our records to confirm our previous observation of a higher incidence of pseudomonal and fungal peritonitis in a group of HIV antibody-positive (HIV+) patients undergoing continuous ambulatory peritoneal dialysis (CAPD).During a 22-month period, we retrospectively studied 71 patients with end-stage renal disease undergoing CAPD. Of these, seven were HIV+, five were at high risk for HIV infection but antibody-negative, and 59 were at low risk for HIV infection. Organisms isolated in episodes of peritonitis were classified microbiologically as one of the following: gram-positive, non-pseudomonal gram-negative, pseudomonal, fungal, or culture-negative.The total peritonitis rate was higher in both the high-risk (p less than or equal to 0.01) and the HIV+ (p less than or equal to 0.02) groups when compared with that in the low-risk population. These differences were attributable to the following: (1) the high-risk group's two-fold increase in gram-positive infections (p less than or equal to 0.01), and (2) a 24-fold increase in pseudomonal (p less than 0.001) infections and seven-fold increase in fungal (p less than 0.005) infections in the HIV+ group. These infections were invariably associated with catheter loss and frequently resulted in conversion to hemodialysis.We believe that the use of CAPD in HIV+ patients may be limited by this increased occurrence of pseudomonal and fungal peritonitis.

Iodinated radiocontrast agents may cause acute renal failure, particularly in patients with preexisting renal failure, heart failure, or diabetes. The low-osmolality contrast agents cause less hypersensitivity, but substantial nephrotoxicity has not been noted. We report three high-risk patients who developed acute renal failure after one of these new agents, ioxaglate, was administered for coronary arteriography and ventriculography. The renal failure was severe: two of the patients required dialysis. We could find no previously reported cases of acute renal failure associated with ioxaglate. Despite their theoretical advantages, the low-osmolality contrast agents may cause acute renal failure in patients who are at risk and should be used with the same precautions as the conventional agents.

A nineteen year old male subject with Niemann-Pick disease is described. The bone marrow and lymph nodes contained foam cells. The histiocytic lipid inclusions were made up of lamellated multiple membranes with a 45 to 50 A periodicity as seen by the electron microscope. These abnormal cytosomes are considered to be the result of the spatial orientation of complex lipid molecules in relation to water, rather than a degradation of mitochondria or lysosomes. The relationship of Niemann-Pick disease to Gaucher's disease and to Tay-Sachs disease is discussed.

Hemoperfusion has been increasingly used to treat drug intoxication. Although efficient extraction rates have been reported with hemoperfusion devices, simultaneous measurements of drug adsorption on the columns and endogenous clearance rates have not been made. We studied three patients who ingested 12 to 22 g of ethchlorvynol (Placidyl). In each patient saline diuresis was induced, and Amberlite XAD-4 resin hemoperfusion was done. Resin extraction of ethchlorvynol was calculated hourly, and the recovery of drugs from each column was measured. Renal clearance of ethchlorvynol was simultaneously measured. The resin removed 100% of perfused ethchlorvynol measured by gas chromatography. Ethchlorvynol recovery from the columns agreed well with calculated extraction. Renal clearance was 1 to 6 mL/min, and estimated metabolic clearance was 16% to 31% of resin extraction rate. Complications included anemia, thrombocytopenia, hypocalcemia, and pancreatitis. Resin hemoperfusion substantially supplements endogenous clearance of ethchlorvynol and is a valuable therapy in ethchlorvynol intoxication.