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Background and study aims The successful eradication rates with standard clarithromycin-based triple therapy are declining concerning the high antibiotic resistance rate and adverse drug reactions . This study aims to evaluate the effect of adding 1,25-hydroxyvitamin D3 on the eradication rates of the standard clarithromycin-based triple therapy for Helicobacter pylori infection. Patients and methods This is a randomized prospective comparative study of 150 patients diagnosed with H. pylori gastritis using magnifying narrow-band imaging endoscopy and supported by a stool antigen test. Patients were divided into two groups: group A ( n = 75) treated with amoxicillin , clarithromycin , and esomeprazole for 2 weeks; group B ( n = 75) treated with 1,25-hydroxyvitamin D3 for 1 month plus amoxicillin, clarithromycin, and esomeprazole for 2 weeks. The H. pylori eradication rates were assessed using stool antigen test conducted 4 weeks after the end of therapy. Furthermore, the H. pylori eradication rates were assessed with per-protocol (PP) and intention-to-treat (ITT) analyses. Results The current results showed that H. pylori eradication was achieved in 46 of 62 (74.19%) and 46 of 75 (61.33%) patients via PP and ITT analyses, respectively, in group A. However, eradication was achieved in 60 of 68 (88.23%) and 60 of 75 (80%) patients via PP and ITT analyses, respectively, in group B. Therefore, the H. pylori eradication rates in the group where vitamin D3 was added to the clarithromycin-based triple therapy were significantly higher than in the other groups ( p = 0.012 and p = 0.029 in ITT and PP analyses, respectively). Conclusions Adding vitamin D3 to the standard clarithromycin-based triple therapy could provide an additional advantage to achieve significantly higher eradication rates for H. pylori infection.

Combination of Intravenous benzodiazepines with opiates appears to be essential in order to guarantee high quality of moderate sedation during colonoscopy. Diphenhydramine is recommended for endoscopic procedures in difficult-to-sedate patients However, the studies supporting its use have yielded conflicting results.To assess the value of adding diphenhydramine hydrochloride before initiation of moderate sedation with midazolam and pethidine for Improving Quality of Sedation during colonoscopy.We conducted a prospective, randomized, double-blind, placebo-controlled study of 150 Patients undergoing diagnostic colonoscopy. Of 150 patients, data were analyzed for 100 patients randomized into two groups: Diphenhydramine group (n = 53) received 50 mg of diphenhydramine intravenously before initiation of moderate sedation with pethidine and midazolam while in placebo group (n = 47) received placebo in addition to pethidine and midazolam. Amount of pethidine and midazolam used and Quality of sedation were assessed.The mean doses of pethidine was significantly higher in placebo group as compared to diphenhydramine group (69.9 ± 35.4 mg vs 61.2 ± 21.0 mg, p 0.01) However, no significant difference between the two groups regarding midazolam mean dose (4.9.±2.1 mg vs 4.8 ± 2.0 mg,p = 0.786). More patients in diphenhydramine group were being very satisfied with the procedure as compared to those in placebo group (88.67% vs 59.57%,p 0.001).Furthermore more endoscopist in diphenhydramine group were being very satisfied with the procedure as compared to those in placebo group (77.35% vs 51.06%,p 0.001).Intravenous diphenhydramine hydrochloride given before initiation of midazolam and pethidine offers a significant Improvement of Quality of moderate Sedation during colonoscopy without increasing the number of sedation related complications.

BACKGROUND: Current anemia therapies for patients with non–dialysis-dependent CKD may require injection and medical visits. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis and improves iron homeostasis. METHODS: In this double-blind phase 3 study, we randomized patients with non–dialysis-dependent CKD stages 3–5 and hemoglobin

Background/Aim Many studies have investigated risk factors other than antibiotic resistance linked to Helicobacter pylori (H. pylori) eradication failure. The aim of this study was to study the effect of serum levels of 25-hydroxy-vitamin D (25[OH]D) on eradication rates of H. pylori infection. Methods This study included 150 patients diagnosed with H. pylori gastritis using magnifying narrow-band imaging endoscopy supported by stool antigen test. Serum 25-OH vitamin D levels were measured via the Enzyme-Linked Immune Sorbent assay (ELISA) method before starting eradication therapy of H. pylori infection. All patients were treated with clarithromycin-based triple therapy for 14 days. H. pylori eradication was determined via a stool antigen test performed 4 weeks after the end of therapy. According to the serum level of 25-OH vitamin D levels, the patients were divided into two groups: group I (sufficient) had a vitamin D level of ≥20 ng/mL, while group II (deficient) had a vitamin D level of

The neutrophil gelatinase-associated lipocalin (NGAL) has been emerging as a novel biomarker of acute kidney injury while its value in lupus nephritis is uncertain. The aim of this study was to assess urinary NGAL levels as a marker for disease activity in patients with lupus nephritis.This study included 70 systemic lupus erythematosus (SLE) patients; 50 with active lupus nephritis (LN) and 20 without as well as 20 matched controls. The neutrophil gelatinase-associated lipocalin (NGAL) in both serum and urine samples was measured by enzyme-linked immunosorbent assay (ELISA). Patients with active LN received standard treatment then assessed for response as well as the value of urinary NGAL (uNGAL). Our results revealed that, The SLE patients with or without LN had an elevated urinary NGAL as compared to controls (p 0.000) and the mean of uNGAL was (20.67 ± 5.34),(10.63 ± 3.53),(5.65 ± 2.49) respectively. Furthermore,Urinary NGAL levels in LN patients were significantly higher than those in non-LN patients (P 0.0001). In the ROC curve analysis , the diagnostic performance of uNGAL for discriminating patients with nephritis from those without nephritis showed that the best cutoff value was 13.66 ng/ml ,sensitivity 92%,specificity 75%,area undercurve (0.959) and (P 0.0001). Measurement of urinary NGAL levels showed an excellent diagnostic performance for discriminating patients with LN from SLE without nephritis.

Background and Aim Visceral fat is an important endocrine organ that secretes different bioactive substances such as adipocytokines. The aim of this study was to investigate the adiponectin level changes among patients with erosive gastroesophageal reflux disease (GERD)and its consequence on pathogenesis. Methods In this study, 150 subjects were selected and divided into four groups: Group І (n = 40) were healthy individuals with an average body mass index and had no gastrointestinal tract symptoms; Group ІІ (n = 50) were patients with mild to moderate erosive esophagitis; Group ІІІ (n = 40) were patients with severe erosive esophagitis; and finally, Group ІV (n = 20) were patients with Barrett's esophagus. Upper gastrointestinal endoscopy was performed for Groups II, III, and IV only, and histopathological assessment was conducted for the suspicious cases of Barrett's esophagus. The measurement of serum adiponectin was performed for all groups using the ELISA test. Results Our results revealed that the serum level of adiponectin was significantly lower in patients with different grades of GERD as well Barrett's esophagus as compared to healthy controls (P-value < 0.001). Additionally, the serum level of adiponectin was correlated with different grades of GERD as the highest level of the adiponectin was found in the control group (11.05 ± 2.58) followed by mild to moderate GERD (6.39 ± 1.64) and then severe GERD (2.42 ± 1.00); finally, the lowest level was detected in the Barrett's esophagus group (1.99 ± 0.47). Our study showed significant correlation between body mass index, waist circumference, and waist-hip ratio on one hand and serum adiponectin level on the other hand, with a statistically significant difference (P-value < 0.001). The best cut-off value for serum adiponectin was 7.7 (μg/mL), with a sensitivity of 91.8% and specificity of 97.5%. Conclusions Low serum adiponectin level appears to be associated with an increased risk of erosive esophagitis, and visceral fat accumulation is related to the impaired secretion of adiponectin, which may have an influence on the pathogenesis of GERD.

Background/Aim: Several treatment options have been developed for portal hypertensive gastropathy (PHG); medications and endoscopic management. The aim of this study was to evaluate the efficacy and safety of argon plasma coagulation (APC) versus Carvedilol in treatment of a cohort of Egyptian patients with severe PHG. Methods: A total of 130 patients with severe PHG were enrolled; 10 patients were excluded due to death and failure to complete the treatment sessions accordingly, 120 patients were included. Patients were divided into 2 groups: Group A (n = 52) treated with APC; Group B (n = 68) treated with oral Carvedilol. Success was defined as stabilization of hemoglobin (Hb) over 100 g/dL or Hb increase >10% from pretreatment level and reduction of blood transfusion requirements over the following 3 months after the start of therapy. Upper gastrointestinal endoscopy was performed to assess the degree and site of PHG. APC was conducted to areas with mucosal ectatic vascular lesions. Results: PHG was mostly fundic (36.35%) in APC group and (36.76%) in Carvedilol group (p = 0.56). Throughout follow-up period, there was significant increase in Hb level, serum iron, and serum ferritin with a significant decrease in total iron-binding capacity (TIBC) in APC group as compared to Carvedilol group (p < 0.001). Additionally, there was gradual increase in the mean Hb, serum iron, and serum ferritin and gradual decrease of TIBC in Carvedilol group. Accordingly, there was an overall improvement of iron deficiency anemia (IDA) in both groups; however, it was significantly better in APC group than in Carvedilol group. No major adverse events were detected in both the groups. Conclusion: APC significantly improves IDA and decreases transfusion requirements in patients with severe PHG as compared to oral Carvedilol with small risk of adverse events. Furthermore, the combination of APC and Carvedilol unless contraindicated could have a synergistic effect in controlling severe PHG.

Background/Aim Many studies have investigated risk factors other than antibiotic resistance linked to Helicobacter pylori (H. pylori) eradication failure. The aim of this study was to study the effect of serum levels of 25‐hydroxy‐vitamin D (25[OH]D) on eradication rates of H. pylori infection. Methods This study included 150 patients diagnosed with H. pylori gastritis using magnifying narrow‐band imaging endoscopy supported by stool antigen test. Serum 25‐OH vitamin D levels were measured via the Enzyme‐Linked Immune Sorbent assay (ELISA) method before starting eradication therapy of H. pylori infection. All patients were treated with clarithromycin‐based triple therapy for 14 days. H. pylori eradication was determined via a stool antigen test performed 4 weeks after the end of therapy. According to the serum level of 25‐OH vitamin D levels, the patients were divided into two groups: group I (sufficient) had a vitamin D level of ≥20 ng/mL, while group II (deficient) had a vitamin D level of

Background Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia. Methods In this multicenter, two-stage, double-blind, phase 3 trial, we randomly assigned 753 patients with hyperkalemia to receive either ZS-9 (at a dose of 1.25 g, 2.5 g, 5 g, or 10 g) or placebo three times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14. The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours. Results At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6 mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively (P

Objectives: Peribulbar anesthesia is associated with delayed and/or incomplete orbital akinesia compared with retrobulbar anesthesia. This study examined the effects of adding rocuronium 5 mg to two different concentrations of lidocaine-bupivacaine mixture on onset time of orbital and eyelid akinesia in patients undergoing cataract surgery. Methods: In a double-blind study, 90 patients were equally randomized to receive a mixture of 0.5 ml normal saline, 4 ml lidocaine 2%, and 4 ml bupivacaine 0.5% (group I), a mixture of rocuronium 0.5 ml (5 mg), 4 ml lidocaine 2%, and 4 ml bupivacaine 0.5% (group II), or a mixture of rocuronium 0.5 ml (5 mg), 4 ml lidocaine 1%, and 4 ml bupivacaine 0.25% (group III). Orbital akinesia was assessed on a 0-8 score (0 = no movement, 8 = normal) at 2 min intervals for 10 min. Time to adequate anesthesia was also recorded. Results are presented as mean±SD. Results: Ocular movement score decreased during the assessment period in all groups. However, at 2 min after block administration, the score decreased to 4±2 (95% CI 3,5) in groups II and III compared with 5±2 (95% CI 4,6) in group I (P

Objective To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti–double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

Risk of hyperkalemia (HK) limits the use of RAAS inhibitors (RAASi) in pts with congestive heart failure (CHF), chronic kidney disease (CKD), or diabetes. ZS-9, a nonabsorbed cation exchanger designed to preferentially entrap K + in the GI tract, significantly reduced serum K + vs placebo (PBO) over 48 hours with low rates of adverse events in CKD patients with hyperkalemia. A pre-specified subgroup analysis was conducted with CHF patients from a large Phase 3 trial of ZS-9 for HK. Pts (N=753) with K + 5.0-6.5 mmol/L were randomized (1:1:1:1:1) to ZS-9 (1.25, 2.5, 5 or 10 g) or PBO orally 3х daily for 48 hr (acute phase). At the end of this phase, pts with K + 3.5-5.0 mmol/L (n=542) were randomized 1:1 to the same ZS-9 acute phase dose or PBO once daily (QD) on Days 3-15 (extended phase); patients initially on PBO were randomized to 1.25 or 2.5g ZS-9 QD. RAASi were kept constant during the study. Serum K + in CHF pts treated with the highest ZS-9 dose (10g) was compared to PBO with an unpaired t-test. Among 753 pts, 300 (40%) had CHF at baseline (per investigator assessment), of whom 72% were on RAASi. Mean baseline K + was 5.3 mmol/L in the CHF pts. CHF pts who entered the Extended Phase (n=204) either remained on ZS-9 10g (n=26) or switched to PBO (n=23). The extended phase baseline K + was similar between groups (4.4 vs 4.5 mmol/L) and to the overall group (4.5 mmol/L ZS-9 [n=63] vs 4.4 mmol/L PBO [n=61]). On Day 15, mean K + for CHF patients on ZS-9 10g was 4.5 mmol/L vs 5.0 mmol/L for PBO (P=0.002; Fig). ZS-9 10g once daily maintained mean serum K +

Introduction: RAAS inhibitors (RAASi) are limited by hyperkalemia (HK; serum K + >5.0 mEq/L), a mortality risk factor in patients (pts) with heart failure (HF) and chronic kidney disease (CKD). Sodium zirconium cyclosilicate (ZS-9) is a nonabsorbed cation exchanger that selectively traps potassium (K + ) in the gut. ZS-9 was well tolerated and acutely reduced and maintained K + in HK pts in a Phase 3 study. We report acute phase efficacy of ZS-9 vs placebo (PBO) across prespecified subgroups of baseline (BL) K + , eGFR, HF, CKD, diabetes mellitus (DM), and RAASi use. Methods: Pts (N=753) with serum K+ 5.0-6.5 mEq/L were randomized (1:1:1:1:1) to ZS-9 (1.25, 2.5, 5 or 10g) or PBO orally 3X/day for 48 hr, after which pts with K + ≤4.9 mEq/L (n=542) were switched to ZS-9 or PBO 1x/day on Days 3-14. RAASi was kept constant. Mean serum K + (95% CIs) was recorded at BL and 48 hr. Differences between groups were compared by unpaired t-test. Results: Prevalence of subgroups were CKD 60%, HF 41% and DM 58%; 2/3 of pts were on RAASi. ZS-9 10g (n=158) vs PBO (n=143) is presented. Mean BL K + was 5.3 mEq/L in both groups. Mean change in K + at 48 hr was -0.73 mEq/L and -0.25 mEq/L in ZS-9 10g and PBO groups, respectively (p Pts with starting K + >5.5 mEq/L had the largest decline in K + with 10g ZS-9 (-1.1 mEq/L vs -0.4 mEq/L PBO; p Conclusions: ZS-9 was well tolerated and achieved normokalemia in all prespecified subgroups of HK pts with CKD, HF, DM and on RAASi and may potentially permit optimal cardiorenal protection by life-saving RAASi.

Animal studies indicate that insulin resistance and glucose intolerance leading to dyslipidemia in uremic rats are associated with increased cytosolic calcium ([Ca++ i]). The resistance and intolerance are reversed with verapamil, but recur after its discontinuation. This finding suggests that hyperparathyroid-induced [Ca ++ i] increase is responsible for the metabolic derangement. We retrospectively examined, over a 12-year period, the effects of factors that lower [Ca ++ i] on total serum cholesterol and triglycerides in 332 hemodialysis (HD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on morbidity and mortality outcomes related to atherosclerotic vascular disease. Patients with diabetes mellitus were excluded, because their dyslipidemia and vascular disease are mediated via a different mechanism. Four groups emerged: group I [high parathormone (PTH) in the absence of calcium channel blockers (CCBs), n = 107], representing the highest [Ca++ i]; group II (high PTH in the presence of CCBs, n = 76) and group III (lower PTH in the absence of CCBs, n = 66), representing intermediate [Ca ++ i]; and group IV (lower PTH in the presence of CCBs, n = 83) representing the lowest [Ca ++ i]. The theoretically lower [Ca ++ i] was achieved via CCB therapy or lower PTH, or both. The mean serum cholesterol in group I was 322 ± 24 mg/dL and the level of triglycerides was 398 ± 34 mg/dL. Group II had mean serum cholesterol of 196 ± 16 mg/dL and triglycerides of 157 ± 17 mg/dL. Group III had a mean serum cholesterol of 202 ± 19 mg/dL and triglycerides of 160 ± 15 mg/dL. Group IV had a mean serum cholesterol of 183 ± 9 mg/dL and triglycerides of 94 ± 6 mg/dL. The differences in cholesterol and triglyceride levels among four groups were significant (p < 0.001) by one-way analysis of variance (ANOVA). The incidence of cardiovascular morbidity and mortality events was 61% in group I, 24% in group II, 28% in group III, and 18% in group IV (χ 2 = 47.7, p < 0.001). We conclude that, in non diabetic HD patients, hyperparathyroidism, especially in the absence of CCBs, is associated with severe dyslipidemia and increased risk of cardiovascular morbidity and mortality. Dyslipidemia may be related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++ i]. Lowering [Ca++ i] by decreasing PTH or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long-term cardiovascular morbidity and mortality. Prospective randomized studies, with actual measurement of [Ca ++ i], are needed to verify the results of this study.

The outcome of patients with acute renal failure (ARF) due to acute tubular necrosis (ATN) was evaluated in this study. Two hundred and twenty-two patients with a mean age of 55.1+/-17.7 years (range 19-97 years; male 153, female 69) who developed ATN in the period from July 1991 through January 1997 were studied. Patients were divided into four groups according to their APACHE II scores at the time of the diagnosis of ATN. Group I included patients with an APACHE II score of 14 or less (n = 70), Group II with a score of 15-18 (n = 52), Group III with a score of 19-23 (n = 58), and group IV with a score of 24 or above (n = 42). The mean APACHE II score for each of the four study groups was 11+/-0.4, 16+/-0.2, 20+/-0.2, and 29+/-0.7, respectively. Patient survival was evaluated by the Kaplan-Meier analysis with censorship at 12 months. Survival rates at 180 days were 67%, 47%, 39%, and zero%, for group I through IV respectively, chi2 = 27.99, p 365, 120, 31, and 11 days, for groups I through IV, respectively. For patients with oliguria (n = 88) survival at 180 days was 23% vs. 58% for patients without oliguria (n = 134), p 365 d, respectively. Finally, 6 months survival in patients with one (kidney only), two, three, and four organ failure was 76, 30, 11, and zero percent, respectively, p = 0.0001, median survival >365, 16, 11, and 12 days, respectively. We conclude that the use of the APACHE II score for the stratification of the severity of illness could be of clinical utility in predicting mortality in patients with ATN. Other predictors of poor prognosis include the need for dialysis, the presence of oliguria, the need for mechanical ventilation, the presence of sepsis, and the number of failed organs.

The most commonly used technique for insertion of peritoneal dialysis (PD) catheters is open surgical approach by minilaparotomy. Percutaneous implantation via the peritoneoscopic technique is expanding. Studies have suggested that PD catheters placed peritoneoscopically have longer survival rate than surgically placed ones. However, these studies were not randomized, where the surgical group had more patients who were obese or had prior abdominal surgery, and therefore, the selection of patients may have biased the results. We conducted a prospective randomized study in which patients underwent PD catheter placement by either the surgical or the peritoneoscopic technique. In the period from October 1992 through October 1995, 148 double-cuff, curled-end, swan-neck PD catheters were placed in 148 patients. The outcome of the 76 patients in whom the PD catheters were placed peritoneoscopically was compared with that of the 72 patients in whom the catheters were placed surgically. Early peritonitis episodes (within 2 weeks of catheter placement) occurred in 9 of 72 patients (12.5%) in the surgical group, versus 2 of 76 patients (2.6%) in the peritoneoscopy group (P = 0.02). This higher rate of infection was most likely related to a higher exit site leak in the surgical group (11.1%) as compared with the peritoneoscopy group (1.3%). Moreover, peritoneoscopically placed catheters were found to have better survival (77.5% at 12 months, 63% at 24 months, and 51.3% at 36 months) than those placed surgically (62.5% at 12 months, 41.5% at 24 months, and 36% at 36 months) with P = 0.02, 0.01, and 0.04, respectively. We conclude that peritoneoscopically placed PD catheters have a longer survival rate than surgically placed ones. Furthermore, the rate of exit site leak and early infection is lower in the peritoneoscopic method.

Despite significant progress to decrease its incidence, peritonitis remains the main source of morbidity and treatment failure in patients on continuous ambulatory peritoneal dialysis (CAPD). The majority of cases of peritonitis result from infection with aerobic gram-positive (Staphylococcus epidermidis and Staphylococcus aureus), or gram-negative organisms. Less common organisms that are also reported include anaerobic bacteria, fungi, and mycobacteria, which collectively account for less than 10% of isolates cultured. We report a case of peritoneal dialysis-associated peritonitis, and review the literature on peritonitis caused by Alcaligenes species. Alcaligenes xylosoxidans is a nonfermenting gram-negative rod and opportunistic pathogen that is motile with peritrichous flagella. The clinical features and microbiological data of our case, as well as the other previously reported cases of peritonitis caused by Alcaligenes species show no particular pattern of peritoneal dialysate cell count. However, the rate of recurrence of peritonitis is characteristically high. The cause of such a high rate of recurrence of peritonitis is probably a reflection of the predilection of Alcaligenes species to cause infection in the ‘sicker’ patients, and the almost universal resistance of this species to most antimicrobial agents. We, therefore, recommend that catheter removal be undertaken as early as the identification of the organism is made. Whether patients should be allowed to return to CAPD after recovery is a more difficult question. We suggest that a reevaluation of the patient’s overall status be undertaken, including personal hygiene, exchange technique, presence of diabetes mellitus, malnutrition, and/or other factors that may render the patient more prone to infection with opportunistic pathogens.

Many primary renal diseases are associated with marked proteinuria resistant to immunosuppressive therapy. Short-term treatment with angiotensin converting enzyme (ACE) inhibitors may decrease proteinuria in these patients, but the long-term effect of these agents on urinary protein excretion is not known. We conducted a double-blind, parallel-design, placebo-controlled study of 1 year duration to evaluate the efficacy of the new ACE inhibitor, perindopril, in reducing proteinuria in patients with nephrotic syndrome due to histologically proven membranous and membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Half of the patients treated with perindopril displayed a decrease in urinary protein excretion from 6.1 +/- 1.0 to 1.2 +/- 0.5 g/24 h, and a rise in serum albumin levels. In the placebo group, protein excretion increased modestly and serum albumin level did not change. There was no difference between the responders and nonresponders to perindopril in age, blood pressure, level of creatinine clearance or urinary sodium excretion. However, the degree of proteinuria before treatment with perindopril was significantly (p0.01) higher in the nonresponders. In 3 patients in whom the treatment with perindopril was extended for 18-24 months, urinary protein excretion remained below 1 g/24 h. The data show that perindopril: (1) is an effective agent in the treatment of proteinuria of primary renal diseases; (2) the effect is sustained for up to 2 years if the administration of the drugs is maintained, and (3) this action of perindopril does not depend on the level of sodium intake.

The internal jugular vein is increasingly being used as a temporary route for dual-lumen hemodialysis catheter placement. It is thought to be safer than the subclavian or femoral vein sites. It is important, however, to point out that this route can also be associated with serious complications. Herein we describe a case of right common carotid artery fistula as a complication of the insertion of a polyurethane double-lumen hemodialysis catheter into the right internal jugular vein. A review of the literature on traumatic complications associated with central venous cannulation is also presented.

♦BackgroundPeginesatide is a novel, synthetic, peptide-based pegylated erythropoiesis-stimulating agent that is designed specifically to stimulate the erythropoietin receptor. The purpose of the present study was to assess, for the first time, the efficacy and safety of peginesatide in chronic kidney disease (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin treatment.♦MethodsIn this open-label multicenter study, 59 PD patients with CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide. Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL during the 25 weeks of the study. The primary endpoint was change from baseline in mean hemoglobin values during the evaluation period (weeks 20 – 25).♦ResultsThe mean hemoglobin value during the evaluation period was 11.3 ± 1.07 g/dL, and the mean change from baseline was 0.10 ± 1.15 g/dL (95% confidence limits: –0.24, 0.44 g/dL). During the evaluation period, most patients maintained hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within ±1.0 g/dL of baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients (72.9%) completed the study. Six patients (10.2%) received red blood cell transfusions. The observed adverse event profile was consistent with underlying conditions in the PD patient population. The most common adverse event was peritonitis (20.3%), a complication commonly associated with PD. Four deaths occurred during the study (2 related to septic shock, and 1 each to myocardial ischemia and myasthenia gravis).♦ConclusionsIn this study, once-monthly peginesatide maintained hemoglobin levels in PD patients after conversion from epoetin.

Extrapulmonary tuberculosis is more common in end-stage renal disease than in normal subjects, and it frequently poses both diagnostic and therapeutic challenges. We describe 2 dialysis patients with tuberculosis of the spine (Pott's disease). The 1st patient presented with back and left hip pain, low-grade fever, left-quadriceps weakness, hypoesthesia of the left thigh, and hypoactive left-knee jerk. X-rays of the spine showed only osteophytes. Magnetic resonance imaging showed increased signal intensity of L3 with focal expansion into the spinal canal. A computerized tomography guided biopsy revealed granulomas, and Ziehl-Neelsen stain was positive. Therapy with rifampin, isoniazid, ethambutol, and pyrazinamide caused peripheral neuropathy and optic neuritis. The 2nd patient developed bilateral proximal thigh pain and weakness that progressed to paraplegia. Magnetic resonance imaging showed destructive lesion of L3-5, involving both psoas muscles, prevertebral space, and neural foramina. Ziehl-Neelsen stain of the biopsy specimen was negative, but culture was positive for Mycobacterium tuberculosis. Paraplegia improved only partially after 1 year of therapy. Pott's disease should be suspected in end-stage renal disease patients with back pain and/or neuromuscular complaints, particularly in those who immigrated from Asian and Latin-American countries. Treatment of tuberculosis in dialysis patients may cause significant morbidity.

Two cases of glomerulonephritis associated with non-Hodgkin's lymphoma (NHL) are described. The first patient presented with the nephrotic syndrome and normal renal function, whereas the second suffered from recurrent acute renal failure together with a unique pattern of IgM deposition within glomerular capillaries. Our review of the literature suggests that this association, although rare, has been documented in a sufficient number of cases to show that it is more than coincidental. Whereas the most common renal lesion associated with Hodgkin's disease is minimal change disease, more advanced glomerular changes are found in the patients with NHL. This is reflected in the higher incidence of renal failure in the latter patients. Treatment of the lymphomas has been shown to result in improvement or even cure of the renal disease, although long-term follow-up is rarely available in the reported cases.

Renal function was observed retrospectively in a population of 228 adults who underwent a cardiac allograft at the University of Pittsburgh from June 1980 through June 1987, survived a minimum of one year, and received cyclosporine. Renal function was determined by serial measurement of serum creatinine concentration. Serum creatinine rose from 1.2 +/- 0.0 mg/dl at time of hospital discharge to 2.0 +/- 0.0 mg/dl at two and four years and 3.3 +/- 0.1 mg/dl at seven years. The fall in renal function was biphasic, with a rapid decline (reciprocal creatinine slope -0.018 dl/mg-mo) through 24 months and a slower decline thereafter -0.0036 dl/mg/month). This occurred despite a progressive decrease in cyclosporine levels from 668 +/- 23 ng/ml (whole blood RIA) to 380 +/- 12 ng/ml at seven years. Three of 222 patients (1.6%) developed end-stage renal disease within 18 months of initiation of cyclosporine therapy. Only one additional patient of 26 followed through 54 months (3.8%) developed end-stage disease thereafter. The decline in renal function seen with cyclosporine is rapid in the first 18 months, with a slower but continuing decline seen with later follow up. At least in heart transplantation, the risk of end-stage renal disease is significant, but not prohibitive.

Severe hyperkalemia may be associated with cardiac arrhythmias and often requires emergent intervention including hemodialysis. Sodium zirconium cyclosilicate (ZS-9) is a nonabsorbed cation exchanger designed to specifically trap excess K+ in the gut. Here we report acute-phase efficacy in patients

Accelerated atherogenesis is a prominent feature of end-stage renal disease (ESRD).Expression of platelet FcgammaRIIA immunoglobulin G receptor (FcgammaR) was measured in 2 populations: (1) 48 patients with ESRD with a mean age of 50.7 +/- 2.3 (SEM) years and (2) 48 healthy age- and sex-matched controls aged 53.6 +/- 1.6 years.Platelet FcgammaR expression was enhanced significantly in patients with ESRD (mean fluorescence intensity [MFI], 7.88 +/- 0.42 [SEM]; 95% confidence interval [CI], 7.03 to 8.72 versus 5.07 +/- 0.21; 95% CI, 4.64 to 5.49; P0.0001). In patients with ESRD, multivariate analysis showed that hemoglobin level and diastolic blood pressure were related inversely to FCgammaR expression (P = 0.01 and P = 0.03, respectively). Atherosclerotic cardiovascular events (ACVEs) were recorded prospectively for the ESRD cohort. A total of 22 ACVEs, defined as the occurrence of myocardial infarction (10 events), cerebrovascular accident (7 events), and/or a peripheral vascular event (5 events), were observed. In the group with greater receptor expression (MFI7.785; n = 24), 13 of 17 patients (76.5%) experienced at least 1 ACVE, whereas only 4 of 17 patients (23.5%) with low FcgammaR expression (MFI7.785; n = 24) experienced an event (P = 0.007).(1) Uremia is associated with enhanced platelet FcgammaR expression, and (2) patients with greater platelet FcgammaR expression are significantly more likely to experience ACVEs; however, (3) the small sample size is a limitation and our work therefore is a hypothesis-generating pilot study that remains to be confirmed.

Background: The treatment of choice for central venous access device (CVAD) occlusion is intracatheter thrombolysis, which has been reported to reestablish patency in up to 80% of cases. However, these salient results have only been achieved in highly selected CVAD subgroups such as nontunneled devices in adult patients, devices with recent occlusion, and in partially occluded devices through which fluid can still be infused (withdrawal occlusions). Less is known about the success of intracatheter thrombolysis in the broader range of CVAD malfunction encountered in clinical practice, especially in those devices that are totally occluded. Objective: This multiple-center, open-label study was performed to test the hypothesis that a new recombinant urokinase (r-UK, urokinase alfa) is safe and effective in reestablishing patency in a large unselected cohort of occluded CVADs. Methods: Pediatric and adult patients with any type of CVAD occlusion of any duration were treated with 5000 IU/mL intracatheter r-UK. Lumen patency was assessed after 5, 15, and 30 mins; a second dose of r-UK was instilled if the catheter remained occluded after 30 mins. Results: A total of 903 r-UK instillations were performed in 878 patients (age range, 16 days to 96 yrs). Overall, instillation of r-UK successfully restored total catheter patency (all treated lumens) to 75% of CVADs (681 of 902). Patency was restored to at least one occluded lumen in 79% of devices (712 of 902). Patency was restored equally in catheters with total occlusion (76%) as in catheters with only withdrawal occlusion (75%). The median ± sd time to patency was 15 ± 20.8 mins (range, 5–203 mins). Conclusion: The use of a new r-UK, 5000 IU/mL, is safe and effective for the restoration of patency to occluded CVADs.

A renal transplant recipient who developed severe acne 6 months after transplantation is described. Maintenance immunosuppression consisted of cyclosporine A (CsA), azathioprine and prednisone. Tapering the prednisone dose to as low as 5 mg/day, in addition to topical tetracycline, Retin-A cream, and systemic antimicrobial therapy failed to control the progression of the skin lesions. Despite therapy with isotretinoin (Accutane), the lesions continued to progress with nodulocystic transformation (acne conglobata) and isotretinoin was discontinued after 4 months. However, the condition continued to worsen with the development of a systemic illness with daily fever, diaphoresis, and depression. High fever (103 degrees F) with shaking chills prompted hospitalization. Withdrawal of CsA resulted in rapid and continuous improvement of the skin lesions. After 12 months of follow-up, the lesions significantly resolved except for residual areas of scarring. No episodes of acute allograft rejection occurred. In conclusion, we suggest that CsA therapy may be associated with the development of acne. Nodulocystic transformation (acne conglobata) may occur despite the use of isotretinoin. Finally, withdrawal of CsA may lead to resolution of the skin disease and should, therefore, be considered as a therapeutic option for severe and treatment-resistant cases.

Thrombotic microangiopathy (TMA) is more common in HIV-infected individuals than in the normal population. In idiopathic TMA, plasmapheresis with or without prednisone decreases the mortality rate from almost 100 to 10%. Patients with HIV-associated TMA, who do not have AIDS, have a similar favorable outcome when treated with plasmapheresis. However, all 12 patients previously reported with AIDS-associated TMA have died. We report another patient with AIDS-associated TMA, who had a fulminant hospital course and died despite plasmapheresis. None of the reported AIDS-associated TMA patients had evidence of opportunistic infections, sepsis or disseminated malignancies at the time of their death. Since many infections and malignancies can be associated with TMA, it is possible that TMA can be an association of the terminal illness rather than an independent cause of death in AIDS patients. To examine this possibility, we reviewed the charts of all the patients who were hospitalized and died of AIDS at our medical centers from 1987 to 1994. Of the 214 patients reviewed, 15 patients (7%) had evidence of TMA at the time of their death. Seven of the 15 patients (47%) had no direct cause of death other than TMA. The remaining 8 patients had evidence of sepsis and other overwhelming infections. In conclusion, TMA is common in AIDS patients. While HIV-associated TMA has a good prognosis similar to that of idiopathic TMA, AIDS-associated TMA has a grave prognosis. The etiology of the higher mortality in AIDS-associated TMA as compared to HIV-associated TMA remains unclear.

The outcome of renal transplantation in 64 patients with end-stage renal disease (ESRD) secondary to lupus nephritis is the subject of this report. The patients were transplanted over a 150-month (12.5-year) period (between July 5, 1979, and January 30, 1992). The study population is predominantly made up of young females (mean age, 34.7 +/- 9 years, n = 54, 81.3%). Fifty-one transplants (79.7%) are cadaveric, and 13 (20.3%) are from living-related donors. Fifty-eight patients (90.6%) had primary (first) allografts, and 6 (9.4%) received a second allograft. Posttransplantation immunosuppression consisted of azathioprine and prednisone (AZA group, n = 22, 34.3%) or AZA, prednisone and cyclosporine (CsA group, n = 42, 65.6%). For all 64 patients combined, the 1-year graft and patient survival rates are 68.8 and 86.5%, respectively, whereas 5-year graft and patient survival rates are 60.9 and 85.9%, respectively. Patients whose immunosuppressive regimen was CsA-based had a 1-year graft survival of 71.5 versus 63.6% in the AZA group. However, this 7.9% difference did not reach statistical significance (p = 0.95). The 5-year graft survival of the CsA-based group was 69.1 versus 45.5% for the AZA group, p0.05. One-year patient survival was 77.3% for the AZA group and 92.9% for the CsA group, p0.05). The data show that patients with ESRD secondary to lupus nephritis can undergo renal transplantation with satisfactory outcome. Immunosuppression based upon CsA improves first-year patient and allograft survival by 15.6 and 7.9%. respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Placement of permanent arteriovenous accesses or of temporary subclavian dual-lumen catheters for hemodialysis can be associated with significant edema of the ipsilateral arm due to venous occlusion. We report an unusual case of marked breast enlargement secondary to hemodialysis arteriovenous fistula, and subclavian vein occlusion proximal to the junction of the mammary vein. To our knowledge, this is a rare complication of hemodialysis accesses. Breast enlargement associated with hemodialysis arteriovenous fistulae, especially in the presence of a history of subclavian vein catheterization, may be indicative of ipsilateral subclavian vein stenosis/thrombosis.

We report case of extrinsic compression of the left brachiocephalic vein by the innominate resulting in massive edema of the arm in a patient with hemodialysis Gore-Tex graft. To our knowledge, such phenomenon has not been previously reported.

Chronic renal failure is associated with structural and functional abnormalities of the exocrine system of the pancreas. Certain data suggest that the excess parathyroid hormone (PTH) in these patients may participate in the genesis of these pancreatic derangements. However, direct evidence that PTH exerts a direct effect on the exocrine pancreatic system is not well documented. The present study examined the effects of the intact molecule (1-84 PTH) and of the amino-terminal fragment (1-34 PTH) of the hormone on the basal output of pure pancreatic juice (PPJ) volume and pancreatic protein secretion in the rat. 1-84 PTH but not 1-34 PTH significantly (p less than 0.01) stimulated the output of PPJ volume without an effect on protein secretion. The magnitude of this stimulatory effect of 1-84 PTH depended on the dose of the hormone administered, and it was related to its biological activity, since inactivation of PTH abolished its action on the output of PPJ volume. The simultaneous administration of the calcium channel blocker, verapamil, reduced but did not abolish the stimulatory effect of PTH on the volume of PPJ output. The data demonstrate that: (1) the ductal cells of the pancreatic acini are targets for PTH and (2) the action of the hormone on these cells is mediated, at least in part, via PTH-induced entry of calcium into the target cells.

Background Increased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD). FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate activation of platelets by collagen and von Willebrand factor. To determine whether expression of FcGammaRIIA impacts platelet reactivity we quantified its expression and platelet reactivity in 33 patients with ESRD who were undergoing hemodialysis. Methods Blood samples were obtained from patients immediately before hemodialysis and before administration of heparin. Platelet expression of FcGammaRIIA and the activation of platelets in response to low concentrations of convulxin (1 ng/ml, selected to mimic effects of collagen), thrombin (1 nM), adenosine diphosphate (ADP, 0.2 uM), or platelet activating factor (PAF, 1 nM) were determined with the use of flow cytometry in samples of whole blood anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa). Results Patients were stratified with respect to the median expression of FcGammaRIIA. Patients with high platelet expression of FcGammaRIIA exhibited 3-fold greater platelet reactivity compared with that in those with low expression in response to convulxin (p < 0.01) and 2-fold greater activation in response to thrombin, ADP, and PAF (p < 0.05 for each). For each agonist, expression of FcGammaRIIA correlated modestly but positively with platelet reactivity. The strongest correlation was with thrombin-induced activation (r = 0.6, p < 0.001). Conclusion Increased platelet reactivity in response to low concentrations of diverse agonists is associated with high expression of FcGammaRIIA and may contribute to an increased risk of thrombosis in patients with ESRD.

Hyperkalemia (HK) limits optimal use of cardioprotective RAAS inhibitors. Treatment of HK with the non-selective cation exchanger sodium polystyrene sulfonate (SPS) has limited efficacy and is associated with adverse effects such as hypocalcemia, hypomagnesemia and colonic necrosis, which are