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Background Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia. Methods A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. Results In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, − 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2 = 101–200. Conclusions Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. Trial registration ClinicalTrials.gov, NCT04345614. Submitted on 7 April 2020. Graphical abstract

Background: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. Methods: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and encroachment of prohibited medications as standard of care, the trial was stopped early. Results: The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2 £200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P=0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P=0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P=0.0165). Similar trends were noted in patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤100. Serious adverse events occurred less frequently in patients treated with Auxora vs. placebo. Conclusions: Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in combination with corticosteroids and other immunomodulatory agents are warranted.Trial registration: NCT04345614

Store-operated Ca(2+) entry (SOCE) mediated by calcium release-activated calcium (CRAC) channels contributes to calcium signaling. The resulting intracellular calcium increases activate calcineurin, which in turn activates immune transcription factor nuclear factor of activated T cells (NFAT). Microglia contain CRAC channels, but little is known whether these channels play a role in acute brain insults. We studied a novel CRAC channel inhibitor to explore the therapeutic potential of this compound in microglia-mediated injury. Cultured microglial BV2 cells were activated by Toll-like receptor agonists or IFNγ. Some cultures were treated with a novel CRAC channel inhibitor (CM-EX-137). Western blots revealed the presence of CRAC channel proteins STIM1 and Orai1 in BV2 cells. CM-EX-137 decreased nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in activated microglia and reduced agonist-induced intracellular calcium accumulation in microglia, while suppressing inflammatory transcription factors nuclear factor kappa B (NF-κB) and nuclear factor of activated T cells (NFAT). Male C57/BL6 mice exposed to experimental brain trauma and treated with CM-EX-137 had decreased lesion size, brain hemorrhage, and improved neurological deficits with decreased microglial activation, iNOS and Orai1 and STIM1 levels. We suggest a novel anti-inflammatory approach for managing acute brain injury. Our observations also shed light on new calcium signaling pathways not described previously in brain injury models.

Background Existing scoring systems to predict mortality in acute pancreatitis may not be directly applicable to the emergency department (ED). The objective of this study was to derive and validate the ED-SAS, a simple scoring score using variables readily available in the ED to predict mortality in patients with acute pancreatitis. Methods This retrospective observational study was performed based on patient data collected from electronic health records across 2 independent health systems; 1 was used for the derivation cohort and the other for the validation cohort. Adult patients who were eligible presented to the ED, required hospital admission, and had a confirmed diagnosis of acute pancreatitis. Patients with chronic or recurrent episodes of pancreatitis were excluded. The primary outcome was 30-day mortality. Analyses tested and derived candidate variables to establish a prediction score, which was subsequently applied to the validation cohort to assess odds ratios for the primary and secondary outcomes. Results The derivation cohort included 599 patients, and the validation cohort 2011 patients. Thirty-day mortality was 4.2 and 3.9%, respectively. From the derivation cohort, 3 variables were established for use in the predictive scoring score: ≥2 systemic inflammatory response syndrome (SIRS) criteria, age > 60 years, and SpO2 Conclusion An ED-SAS score that incorporates SpO2, age, and SIRS measurements, all of which are available in the ED, provides a rapid method for predicting 30-day mortality in acute pancreatitis.

Purpose: Calcium release-activated calcium (CRAC) channels activate microglia via store-operated Ca 2+ entry. We previously reported that the specific CRAC channel inhibitor (CM-EX-137) had neuroprotective effects in a model of experimental stroke due to suppression of microglial activation in male mice. However, it is well known that sex differences can influence stroke outcome as well as immune responses. Whether CRAC channel inhibition in female mice is similarly neuroprotective is unknown. The purpose of this study is to determine whether female mice respond similarly CRAC channel inhibition in a stroke model Subjects and Methods: C57/BL6 female mice, aged 2 months were subjected to distal middle cerebral artery occlusion (dMCAO) were treated with CM-EX-137 (5mg/kg IP; dMCAO-CM) or vehicle control (dMCAO-vehicle) daily for 3d. Stroke surgeries were carried out during the same phase of the estrus cycle (diestrus) to avoid potential confounds due to varying estrogen levels. These groups were also compared to sham groups. CM-EX-137 was injected immediately after occlusion and at 24 & 48h. Brains were extracted 3d post dMCAO. Neurological functions were evaluated before surgery, and 1 & 3d later. Lesion size was estimated from cresyl violet stains. Microglia and astrocyte activation were assessed using immunohistochemistry. Results: Neurological function at both 24 and 72 h post ischemia were significantly improved in dMCAO-CM group, compared with dMCAO-vehicle group (n=7/group; p Conclusion: CRAC channel inhibition reduce inflammatory responses and improve neurological outcome following experimental stroke in female animals. These results are in line with those that we observed in male mice. Thus, CRAC channel inhibition seems to be similarly effective and anti-inflammatory in both genders in a stroke model.

INTRODUCTION: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications in patients with COVID-19 D-dimer levels have been correlated with disease severity and risk of mortality in patients with COVID-19 The effect of CRAC channel inhibition on D-dimer levels was investigated METHODS: The safety and efficacy results of a randomized, controlled, open-label study comparing Auxora, a novel, intravenously administered CRAC channel inhibitor, to standard of care (SOC) in adults with severe/critical COVID-19 pneumonia have been previously reported In this study, D-dimer levels were recorded at baseline and every 48 hours thereafter Shortages of Personal Protective Equipment for laboratory personnel at 2 sites and restrictions in shipments of blood samples containing SARS-CoV2 at one site prevented laboratory personnel from drawing blood at times outlined in the protocol Consequently, a limited number of patients had blood samples drawn prior to randomization RESULTS: In total, 17 patients with severe COVID-19 pneumonia were randomized to Auxora and 9 to SOC All patients received anticoagulation according to SOC Over the course of this study, D-dimer levels decreased in patients receiving Auxora but increased in those receiving SOC From baseline to 48 hours, the median change was -0 24 μg/ mL for patients receiving Auxora (n=10) and 0 63 μg/mL in patients receiving SOC (n=8), and from baseline to 96 hours the median change was -0 85 μg/mL (n=6) and 0 07 μg/mL (n=3), respectively Two patients receiving SOC developed femoral deep vein thrombosis No patients receiving Auxora developed thromboembolic disease In the 30 days postrandomization, 2 patients receiving Auxora and 2 receiving SOC died due to respiratory failure, all of whom experienced >100% increase in D-Dimer levels in the first 48 hours CONCLUSIONS: Auxora demonstrated improved D-dimer levels as early as 48 hours and as previously reported, a favorable safety profile and improved clinical outcomes Results from this study suggest that a >100% increase in D-dimer levels in the first 48 hours may identify patients with severe COVID-19 at risk for mortality from respiratory failure

Purpose: Inflammatory responses after ischemic stroke contribute to worsening of ischemic brain injury. Calcium release-activated calcium (CRAC) channels are known to be involved in the activation of immune responses in microglia, and have been studied indirectly through non-specific calcineurin inhibitors such as cyclosporine and FK506. Since these compounds have many off-target effects and unacceptable side effects, we studied a novel CRAC channel inhibitor which is specific to the CRAC channel and appears safe in preclinical studies in anticipation of human clinical trials for other indications. We explored whether this inhibitor might improve outcome in experimental stroke by inhibiting microglial activation. Subjects and Methods: 2-3 month old C57/BL6 male mice, were exposed to transient middle cerebral artery occlusion (tMCAO, filament model) for 2h followed by reperfusion. Some were treated with the CRAC channel inhibitor (CM-EX-137, 5mg/kg IP; tMCAO-CM) or vehicle control (tMCAO) daily beginning immediately after occlusion and the following two days. Brains were collected 3d post-stroke. Neurological function was evaluated using a Bederson score, elevated body swing test, adhesive removal test, and corner test at baseline, at 3, 24 and 72 h. Relative cerebral blood flow (rCBF) was studied in some mice using laser Doppler flowmetry. Ischemic lesion size was evaluated by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Microglial/monocyte activation was assessed by isolectin B4 histochemistry. Results: A total of 18 mice were studied (tMCAO-CM: 8; tMCAO: 8, sham:2). rCBF was no different between experimental groups, and is consistent with the notion that the compound should not alter blood flow. Neurological function at 1 & 3d after ischemia was significantly improved in tMCAO-CM group compared to tMCAO (p Conclusion: CRAC channel inhibition protects against experimental stroke by decreasing lesion size, improving neurological outcomes and decreasing microglial activation.

Inflammatory responses following ischemia can worsen neurological outcome, and represent a potential target for therapeutic intervention. Store-operated Ca 2+ entry (SOCE) mediated by CRAC channels contribute to calcium signaling in immune cells. CRAC channels consist of the endoplasmic reticulum resident Ca 2+ -sensing protein stromal interaction molecule 1 (STIM1) and the calcium channel protein ORAI1 located in the plasma membrane. Prolonged Ca 2+ entry through CRAC channels activates, via calcineurin, nuclear factor of activated T cells (NFAT), involved in T cell proliferation and cytokine expression. Microglia mediate inflammation in the injured brain, but little is known about the role of CRAC channels in this process. We studied novel CRAC channel inhibitors to explore their therapeutic potential in microglia-mediated injury. A neuron cell line (Neuro-2A, N-2A) was cultured alone or with microglial BV2 cells then exposed to 2h oxygen glucose deprivation (OGD). Some cultures were treated with a novel CRAC channel inhibitor. Toll-like receptor (TLR) -3, -4 agonists or IFNγ were also used to activate microglia. Western blots revealed the presence of CRAC channel proteins STIM1 and ORAI1 in microglia. CRAC channel inhibition decreased NO release and inflammatory proteins iNOS and COX-2 expression in activated microglia, but did not affect STIM1 or ORAI1 expression. CRAC channel inhibitors also reduced agonist induced intracellular calcium accumulation in BV2 cells. Agonists also activated JNK1/2 kinase, NFAT, NF-κB, CREB & STAT1 in microglia, but only JNK1/2 kinase & NFAT were attenuated by inhibitor. OGD decreased N2A neuronal cell viability, further exacerbated by BV2 cells, but neuronal cells were protected by CRAC channel inhibition (n=5, *p

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase–associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase–associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusions Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department.

Enteric-coated mycophenolate sodium (MPS) has been developed to help circumvent the upper gastrointestinal side-effects of mycophenolic acid by facilitating drug release in the small intestine. Many questions regarding the side-effect profile of MPS remain. Therefore, the purpose of this study is to review a single-center’s experience with mycophenolate mofetil (MMF) and MPS. Methods: This retrospective, sequential cohort analysis of de novo renal and pancreas transplants (n = 198) compared MMF 500 mg b.i.d. to MPS 360 mg b.i.d. in conjunction with antibody induction, tacrolimus, and steroids. Results: There were fewer adverse event driven drug manipulations in the MPS group at 90 d (4% MPS vs. 17% MMF) and 180 d (10% MPS vs. 24% MMF, p = 0.006, log-rank) after transplantation. There was a trend toward fewer GI-related hospital admissions in the MPS arm (7% MPS vs. 13% MMF, p = 0.18). Allograft outcomes including patient survival, graft survival, acute rejection, serum creatinine, and infection were similar. Conclusion: This single-center, sequential cohort study demonstrates that MPS is associated with fewer adverse event driven drug manipulations while maintaining similar safety and allograft outcomes.

Background. End-stage renal disease (ESRD) patients are prescribed numerous medications. The United States Renal Data System (USRDS) reported on medication prescribing patterns in 1998. Since then, several new medications, treatment guidelines and recommendations have been introduced. The objective was to analyse and compare haemodialysis (HD) patient medication prescribing patterns between the Dialysis Clinic, Inc. (DCI) database and the USRDS report. Methods. Point-prevalent (01/01/03) medication use data from the DCI national database was obtained. Data collected included patient demographics, reason for and duration of ESRD, and medication listed on profile. All medications were classified similar to the USRDS and by where taken (clinic vs home). Medication prescribing patterns were compared between DCI and USRDS databases. Comparisons between age groups (

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

article i nfo Objective. The purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malig- nant pelvis masses in Asian women. Methods. This was a prospective, multicenter (n=6) study with patients from six Asian countries. Pa- tients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, posi- tive predictive value (PPV) and negative predictive value (NPV). Results. A total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensi- tivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk. Conclusion. ROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.

Patients on peritoneal dialysis experience inflammation associated with advanced chronic kidney disease and the therapy itself. An important consequence of the inflammation may be acceleration of the rate of decline in residual renal function. The decline in residual renal function has been associated with an increased mortality for patients in this population. Bardoxolone methyl is a synthetic triterpenoid. To date, the effects of bardoxolone methyl on kidney function in humans have been studied in patients with type 2 diabetes mellitus. A large-scale event-driven study of bardoxolone methyl in patients with type 2 diabetes mellitus with stage 4 chronic kidney disease is underway. The safety of bardoxolone methyl has not been evaluated in patients with more advanced (stage 5) chronic kidney disease or patients on dialysis. This report describes a proposed double blind, prospective evaluation of bardoxolone methyl in patients with type 2 diabetes mellitus receiving peritoneal dialysis. In addition to assessing the safety of bardoxolone methyl in this population, the study will evaluate the effect of bardoxolone methyl on residual renal function over 6 months as compared to placebo.

Patients on peritoneal dialysis experience inflammation associated with advanced chronic kidney disease and the therapy itself. An important consequence of the inflammation may be acceleration of the rate of decline in residual renal function. The decline in residual renal function has been associated with an increased mortality for patients in this population. Bardoxolone methyl is a synthetic triterpenoid. To date, the effects of bardoxolone methyl on kidney function in humans have been studied in patients with type 2 diabetes mellitus. A large-scale event-driven study of bardoxolone methyl in patients with type 2 diabetes mellitus with stage 4 chronic kidney disease is underway. The safety of bardoxolone methyl has not been evaluated in patients with more advanced (stage 5) chronic kidney disease or patients on dialysis. This report describes a proposed double blind, prospective evaluation of bardoxolone methyl in patients with type 2 diabetes mellitus receiving peritoneal dialysis. In addition to assessing the safety of bardoxolone methyl in this population, the study will evaluate the effect of bardoxolone methyl on residual renal function over 6 months as compared to placebo.

Enteric-coated mycophenolate sodium (MPS) has been developed to help circumvent the upper gastrointestinal side-effects of mycophenolic acid by facilitating drug release in the small intestine. Many questions regarding the side-effect profile of MPS remain. Therefore, the purpose of this study is to review a single-center's experience with mycophenolate mofetil (MMF) and MPS.This retrospective, sequential cohort analysis of de novo renal and pancreas transplants (n = 198) compared MMF 500 mg b.i.d. to MPS 360 mg b.i.d. in conjunction with antibody induction, tacrolimus, and steroids.There were fewer adverse event driven drug manipulations in the MPS group at 90 d (4% MPS vs. 17% MMF) and 180 d (10% MPS vs. 24% MMF, p = 0.006, log-rank) after transplantation. There was a trend toward fewer GI-related hospital admissions in the MPS arm (7% MPS vs. 13% MMF, p = 0.18). Allograft outcomes including patient survival, graft survival, acute rejection, serum creatinine, and infection were similar.This single-center, sequential cohort study demonstrates that MPS is associated with fewer adverse event driven drug manipulations while maintaining similar safety and allograft outcomes.

Objective The purpose of this study was to develop a risk prediction score for distinguishing benign ovarian mass from malignant tumors using CA-125, human epididymis protein 4 (HE4), ultrasound findings, and menopausal status. The risk prediction score was compared to the risk of malignancy index and risk of ovarian malignancy algorithm (ROMA). Methods This was a prospective, multicenter (n=6) study with patients from six Asian countries. Patients had a pelvic mass upon imaging and were scheduled to undergo surgery. Serum CA-125 and HE4 were measured on preoperative samples, and ultrasound findings were recorded. Regression analysis was performed and a risk prediction model was developed based on the significant factors. A bootstrap technique was applied to assess the validity of the HE4 model. Results A total of 414 women with a pelvic mass were enrolled in the study, of which 328 had documented ultrasound findings. The risk prediction model that contained HE4, menopausal status, and ultrasound findings exhibited the best performance compared to models with CA-125 alone, or a combination of CA-125 and HE4. This model classified 77.2% of women with ovarian cancer as medium or high risk, and 86% of women with benign disease as very-low, low, or medium-low risk. This model exhibited better sensitivity than ROMA, but ROMA exhibited better specificity. Both models performed better than CA-125 alone. Conclusion Combining ultrasound with HE4 can improve the sensitivity for detecting ovarian cancer compared to other algorithms.

Hemodialysis (HD) patients are at risk for medication-related problems. Patient characteristics associated with the number of medication-related problems in HD patients have not been investigated.Patient records were reviewed to identify medical problems, prescribed medications, medication indication(s), and medication-related problems. Medication classes and medication-related problems were compared between patients with and without diabetes mellitus (DM). Correlations were performed to determine whether associations exist between medication-related problems, number of medications, number of medication doses per day, number of comorbid conditions, patient age, and duration of end-stage renal disease while controlling for DM status.Medical records of 133 patients were evaluated. Patients were 60.5 +/- 15.2 years old, prescribed 11.0 +/- 4.2 medications, and had 6.0 +/- 2.3 comorbidities. Medication-related problems were identified in 97.7% of patients. Four hundred seventy-five medication-related problems were identified, averaging 3.6 +/- 1.8 medication-related problems per patient. Patients with DM had more medication-related problems identified than those without DM (303 versus 172 medication-related problems, respectively; P0.05). Medication-related problems correlated positively with number of patient comorbidities (P0.001).Medication-related problems are prevalent in virtually all HD patients. The number of medication-related problems in an individual patient increases as the number of comorbid conditions increases. The most frequent medication-related problems were drug without indication (30.9%), laboratory (27.6%), indication without drug use (17.5%), and dosing errors (15.4%). Patients with DM are at increased risk for medication-related problems. Health care providers taking care of HD patients should be aware of this problem, and efforts to avoid or resolve medication-related problems should be undertaken at all HD clinics.