Impaired leukocytes autophagy in chronic kidney disease patients.

BACKGROUND: Proteins and cytoplasmic organelles undergo degradation and recycling via autophagy; its role in patients with chronic kidney disease (CKD) is still unclear. We hypothesize that impaired kidney function causes autophagy activation failure. METHODS: We included 60 patients with stage 5 CKD and 30 age- and sex-matched healthy subjects as controls. Patients with conditions that could affect autophagy were excluded. Leukocytes were isolated and analyzed from peripheral blood samples collected after overnight fasting and 2 h after breakfast. RESULTS: Overnight fasting induced conversion of microtubule-associated protein-1 light chain 3 I to II (γLC3) and increased mRNA levels of the autophagy-related gene 5 (Atg5) and Beclin-1 in healthy subjects, which were nearly absent in CKD patients (p = 0.0001). Moreover, no significant difference in autophagy activation was observed between CKD patients with or without hemodialysis. Correlation studies showed that γLC3 was negatively associated with the left atrium size. Changes in Atg5 transcript levels were negatively associated with the left ventricular end-diastolic diameter, and changes in Beclin-1 transcript levels were negatively associated with the mitral inflow E- and A-wave sizes. CONCLUSION: These data suggest that CKD patients have impaired autophagy activation, which cannot be reversed with hemodialysis and is closely related to their cardiac abnormalities.

Successful treatment of autoimmune thrombocytopenic purpura with rituximab in a dialysis patient with systemic lupus erythematosus.

Autoimmune thrombocytopenic purpura (ATP) in systemic lupus erythematosus involves autoantibody mediated destruction of platelets. In dialysis patients with refractory ATP which is unresponsive to corticosteroid and immunosuppressive agents, the management is difficult. B cell targeted therapy with rituximab has emerged as a promising agent by reducing the levels of pathogenic autoantibodies. However, its safety and efficacy in dialysis patients are uncertain. In this report, we described a dialysis patient with refractory lupus-related ATP, whose platelet counts responded only to rituximab. Furthermore, no severe side effects were noted during the treatment period, suggesting that rituximab can be administered safely in dialysis patients.

Type B aortic dissection with early presentation mimicking acute pyelonephritis.

Aortic dissection is a life-threatening illness requiring early diagnosis and treatment. Uncommon early presentations mimicking various illnesses can delay diagnosis. This case study describes a 44-year-old woman with type B aortic dissection initially presenting as acute pyelonephritis (APN). Early clinical manifestations were sudden onset of left flank pain, fever, hematuria and pyuria, and following admission, severe abdominal pain, nausea, vomiting, reduced urine output and renal function deterioration. Abdominal computed tomography showed type B aortic dissection complicated with a small bowel infarct, ischemic ascending colon and left renal infarct. Emergency surgical interventions of small bowel resection, ileoduodenostomy and cholecystectomy were performed; a second laparotomy was subsequently performed for anastomosis leakage. The patient died due to septic shock with multiorgan failure. Aortic dissection initially mimicking APN is rare. Accurate early diagnosis of aortic dissection with indeterminate presentation is crucial. Early surgical intervention for visceral organ ischemia is important to preventing morbidity and mortality.

Aristolochic acid-related nephropathy associated with the popular Chinese herb Xi Xin.

Chinese herbs nephropathy is known as a subacute interstitial nephritis attributed to aristolochic acid. This work describes the case of a 49-year-old male who displayed subacute renal failure induced by ingestion of herbal powder containing Xi Xin, which includes aristolochic acid. Since Xi Xin is a common ingredient in traditional formulae, care needs to be taken in the future to identify the aristolochic acid concentration of different components of Xi Xin. Xi Xin containing aristolochic acid should be forbidden for use in remedies in order to prevent the harmful effects of aristolochic acid.

Clinical distinction and evaluation of leptospirosis in Taiwan--a case-control study.

BACKGROUND: Leptospirosis is the most widespread zoonosis. Leptospirosis remains underreported in Taiwan because of ignorance and the broad spectrum of clinical manifestations. Acute renal failure (ARF) is a prominent feature of leptospirosis. This investigation conducted a case-control study to obtain information to distinguish leptospirosis from other conditions with similar presentations. METHODS: Leptospirosis surveillance was performed at Chang Gung Memorial Hospital, Taiwan, between September 2000 and December 2001. Suspected clinical cases were included in the sample and investigated. Diagnosis was confirmed with four-fold or greater increase of microscopic agglutination test (MAT) titer in paired sera; positive immunoglobulin M (IgM) dipstick with single MAT > or =400; or isolation of leptospira. Cases were classified as excluded based on confirmed etiology other than leptospirosis or negative paired serologic test. RESULTS: Twenty-two confirmed cases and 21 excluded cases of leptospirosis were identified from among 169 suspected cases. An outbreak was observed during the flooding from Typhoon Nali. L. shermani, the most common serovar in Taiwan, was identified in 78.5% of confirmed cases. In the confirmed group, mean age was 44 +/- 14.5 (21-66) yrs similar to that of the excluded group, with male predominance (86.4 vs. 57.1%, p<0.05). The most common presentations in the confirmed group were fever (95.5%), ARF (86.4%), myalgia (72.7%) and jaundice (63.6%). Ten patients were infected through occupational or recreational exposure, and in six patients, the infection was associated with flooding. The most distinct presentations of leptospirosis cases compared with excluded cases were increased incidence of hemorrhagic diathesis (odds ratio (OR): 10, p=0.04), myalgia (OR: 8.0, p=0.02), bilateral enlarged kidneys (OR: 7.5, p=0.0004), risk factor exposure (OR: 6.9, p=0.005), sterile pyuria (OR: 6.3, p=0.017), hypokalemia (OR: 5.0, p=0.035) and thrombocytopenia (OR: 4.8, p=0.04). Hospitalization days correlated well with levels of peak creatinine (Cr) (p=0.0362) and platelet nadir (p=0.0039) reached. Penicillin treatment was followed by rapid symptoms and renal function improvement. CONCLUSIONS: Prompt recognition of the characteristic presentations of leptospirosis, followed by timely antibiotic treatment, can dramatically save the patients even with severe multiple organ damage.

Ultrapure dialysate improves iron utilization and erythropoietin response in chronic hemodialysis patients - a prospective cross-over study.

BACKGROUND: The impact of ultrapure dialysis on dialysate-related chronic inflammatory status and anemia in uremic patients on maintenance hemodialysis (HD) remains uncertain. We evaluated ultrapure dialysate effects on erythropoietin (EPO) response and inflammatory status in a prospective, randomized, cross-over study. METHODS: Thirty-four HD patients were divided into two groups. One group was treated with conventional dialysate and the other group with ultrapure dialysate for 6 months and crossed over for another 6 months. Bacteria growth and dialysate endotoxin were examined. Parameters including C-reactive protein (CRP), recombinant human erythropoietin (rHuEPO) dose, ferritin, iron saturation and serum albumin were measured at the start, and at 6 and 12 months. RESULTS: The endotoxin levels reduced significantly in the ultrapure dialysate by adding a dialysate ultrafilter. After a 6-month treatment with ultrapure dialysate, there were statistically significant differences in the systemic inflammation markers between both groups. Changing from conventional to ultrapure dialysis fluid significantly reduced CRP (7.01 +/- 5.059 to 4.461 +/- 3.754 mg/L, p<0.05), and resulted in reduced rHuEPO doses (12500 +/- 7060 to 10440 +/- 7050 U/month, p<0.05). Continuous conventional dialysate use was not associated with significant alternations in CRP (from 5.849 +/- 7.744 to 6.187 +/- 7.997 mg/L, p=0.456) and rHuEPO dose (14060 +/- 6210 to 15060 +/- 7250U/month, p>0.05). The ferritin level reduced significantly (422 +/- 183 to 272 +/- 162 mcg/L, p<0.05) in the ultrapure dialysate group. After another 6-month cross-over, the study parameters were reversed among the two groups indicating the beneficial effect of ultrapure dialysis. CONCLUSIONS: Through endotoxin reduction in conventional dialysate, ultrapure dialysis in dialysis patients manifested a reduced inflammatory parameter, reduced rHuEPO dose and improved iron utilization; and therefore, could be beneficial in anemia treatment.

Preoperative 24-hour urine amount as an independent predictor of renal outcome in poor cardiac function patients after coronary artery bypass grafting.

PURPOSE: To investigate the incidence and the main pre-operative risk factors for the development of acute renal failure (ARF) in triple vessels coronary artery bypass grafting (CABG) with special reference to a subset of patients with poor cardiac function (ejection fraction <50%). PATIENTS: The study included the patients (n = 66) requiring CABG from January 1, 1995 to January 1, 2002 in a medical center. RESULTS: A high percentage (84.8%) of patients developed ARF and 57.6% of patients received hemodialysis (HD). Preoperative variables significantly associated with the development of ARF included increased age, increased preoperative serum creatinine, decreased preoperative 24-hour urine output and accepted emergent CABG. By the logistic multivariate regression model, increased age (OR = 1.16), preoperative serum creatinine (OR = 3.58,), decreased preoperative 24-hour urine amount (OR = 0.99,) and emergent CABG (OR = 2.01) were independently associated with ARF. As for the need for HD, those factors including, preoperative serum creatinine (2.11 +/- 1.13 v 3.08 +/- 1.67 mg/dL) and preoperative 24-hour urine output (1358.6 +/- 745.9 v 755.2 +/- 572.1 mL/day) were significantly associated with requirement of dialysis. Using multivariate logistic regression, the significant risk factors independently associated with dialysis were preoperative serum creatinine (OR = 1.34) and preoperative 24-hour urine output (OR = 0.99). Patients with non- oliguric renal failure had significantly greater chance of recovering their renal function after cardiac surgery compared to those with oliguria (36.9% v 10.0%, P <.05). CONCLUSION: Preoperative 24-hour urine amount and pre-operative serum creatinine can provide valuable information for predicting the likelihood of developing acute renal failure and requiring dialysis in this subgroup of patients.

Low dose intravenous ascorbic acid for erythropoietin-hyporesponsive anemia in diabetic hemodialysis patients with iron overload.

BACKGROUND: Recent report demonstrates that inadequate iron mobilization and defective iron utilization may cause recombinant erythropoieitin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. The effect of intravenous ascorbic acid (IVAA) in HD patients selected on the basis of iron overload and EPO resistance also has been proven. However, it is uncertain whether IVAA still works in diabetic ESRD patients with hyperferritinemia. Therefore, the aim of this study focusing on diabetic ESRD patients was to analyze the potential effect of low dose IVAA on improvement of anemia and erythropoiesis-related parameters when compared with control period. PATIENTS AND METHOD: This study consisted of 22 chronic hemodialysis patients with type II diabetes in a single dialysis unit. In studies of this type, all eligible patients are followed up, but the primary comparison is still between different sequentially treatment including control period and post-IVAA period in same patients. IVAA patients received ascorbic acid, 100 mg each administered intravenously three times per week for eight weeks of treatment and four months of post-treatment follow-up. RESULTS: The demographic characteristics of 22 diabetic uremic patients show that mean age is 63.6 +/- 10.2 years old. The ratio of sex (M/F) = 10/12. Mean duration of HD is 46.7 +/- 33.2 months. As for the urea kinetic study between these two periods including KT/V, nPCR, and URR, there is no significantly different. As for anemia-related parameters, Hb and Hct increased significantly in post-IVAA period after 3 months compared with control period, while MCV did not increase significantly. Serum ferritin significantly decreased at study completion. The same situation is for iron. As for TS, it significantly increased at one month and further markedly increased at subsequent three months. CONCLUSION: This study has demonstrated that short-term low dose IVAA therapy can facilitate iron release from reticuloendothelial system but also increase iron utilization in diabetic hemodialysis patients with iron overload. Therefore, IVAA is a potential adjuvant therapy to treat erythropoeitin-hyporesponsive anemia in iron-overloaded patients.

Improvement of clinical outcome by early nephrology referral in type II diabetics on hemodialysis.

OBJECTIVES: To evaluate the influence of early nephrology referral on clinical outcome in type II diabetes mellitus patients on maintenance hemodialysis dialysis. PATIENTS AND METHODS: This study retrospectively analyzed the type II diabetic patients entering our PD program from February 1988 to June 2001. Patients who were presented to a nephrologist more than 6 months before starting dialysis were defined as early referral (ER). Patients were considered late referral (LR) if they were transferred to the nephrology department within 6 months before initial dialysis. RESULTS: Hundred and fifteen type II diabetic patients receiving HD for at least 3 months were enrolled in this study. Sixteen of the 53 patients (46.1%) were in the ER group and 62 of the 115 (53.9%) were in the LR group. In univariate analysis by Cox proportional hazards mode, the early referral (Exp (Coef) = 0.423, p < 0.01), good glycemic control (Exp (Coef) = 0.16, p < 0.05), and age at dialysis (Exp (Coef) = 1.026, p < 0.05 (had significantly influenced the patient survival. The residual renal function in the ER group, estimated by creatinine clearance (Ccr), significantly exceeded that of the LR group (ER vs. LR: 4.46 +/- 1.56 vs. 2.51 +/- 1.70 mL/min, p < 0.001). The patients with early referral had significantly better survival (p < 0.05). Five-year survival improved significantly in the early referral group compared to the late referral group (ER: 72.4%; LR: 35.2%, p < 0.05). CONCLUSIONS: We demonstrate that the time of referral before starting dialysis is a predictor of survival for type II diabetics on HD. Patients with early referral are associated with longer survival. The beneficial effect might be associated with the timely initiation of the chronic HD program. These results suggest that early referral before dialysis is important in determining the long-term prognosis in type II diabetics on HD.

Refractory hypertension and anemia in end-stage renal disease: an unusual manifestation of Kimura's disease.

Hypertension and anemia are common in uremic patients. This article describes a 35-year-old uremic Taiwanese who was admitted to our hospital with refractory hypertension and refractory anemia following chronic hemodialysis for more than two years. He was diagnosed with Kimura's disease finally. Refractory hypertension and refractory anemia were noted over two years before an enlarged inguinal lymph node was observed. The symptoms lead to the diagnosis of Kimura's disease. Unlike most cases, refractory hypertension and refractory anemia were first noted before the inguinal mass and eosinophilia were presented. The inflammatory parameters increased when the disease was active. Steroid treatment was conducted, and the symptoms including hypertension and anemia promptly decreased. To the authors' knowledge, this case is for first one in which Kimura's disease has induced refractory hypertension and anemia in an ESRD patient and in which these symptoms rapidly subsided following steroid treatment. The activity of Kimura's disease is closely related refractory hypertension, suggesting that inflammation may be involved in refractory hypertension and anemia in a dialytic patient with Kimura's disease.

LV mass index significantly impacts on patient and renal outcomes in patients with coronary artery bypass grafting and poor left-ventricular function.

BACKGROUND: A recent report demonstrated that the presence of left ventricular hypertrophy was an independent predictor of mortality in patients with coronary artery bypass grafting (CABG) severely depressed left ventricular function. However, the impact of left ventricle (LV) mass index on the renal and patient outcomes in such patients with CABG has previously not been addressed. The present study thus considers this group of patient and uses LV mass index to assess renal and patient outcomes for these patients. MATERIAL AND METHOD: All patients who arrived at the emergency room with severe cardiac dysfunction (EF < 60%), triple vessel disease, and required CABG and LV hypertrophy (LVH) (LV mass index gamma110 g/m2 in women, gamma134 g/m2 in men) were admitted preoperatively to the intensive care unit (ICU) for supportive intervention from January 1, 1998 to January 1, 2001. Of all LVH patients, 44 underwent CABG, and were divided into two groups according to LV mass index. RESULTS: Of all patients, 72.7% had severe echocardiographic LVH. The echocardiographic data of both dialysis and non-dialysis groups showed no difference with respect to echocardiographic findings. Histories of myocardial infarction were more frequent in the severe LVH group that in the mild LVH group. As for pre-operative systolic blood pressure and diastolic blood pressure, mean systolic and diastolic blood pressure values were significantly lower in the severe LVH group. Ejection fraction was also significantly lower in the severe LVH group than in the mild LVH group. The patients in the severe LVH group were significantly more likely to have received hemodialysis following CABG surgery (62.5% vs. 33.4%, p < 0.05). Mortality was higher in the higher LV mass index group that in the lower LV mass index group (56.2% vs. 25%, p < 0.05). CONCLUSION; Patients with a significantly higher LV mass index usually manifest lower pre-operative blood pressure and poor cardiac function. Consequently, these patients will have a poor renal outcome and higher mortality.

Guillain-Barré syndrome associated with minimal change glomerulopathy and tubular dysfunction - related to acetone-based organic solvent?

A 55-year-old woman presented with Guillain-Barré syndrome, nephrotic syndrome and multiple tubular dysfunction under occupational exposure to an organic solvent, which contained acetone as the principal solvent. In this case, the onset of the nephrotic syndrome and tubular dysfunction coincided with the development of the neurological manifestation. Renal biopsy demonstrated minimal change glomerulopathy with moderate tubulointerstitial nephritis. Several clearance tests that evaluated tubular transport functions revealed multiple tubular defects (including the Na(+)-K(+)-Cl(-) cotransporter of thick ascending limb and distal proton pump). The simultaneous occurrence of Guillain-Barré and nephrotic syndrome has previously been reported. However, both minimal glomerulopathy with multiple tubular dysfunction and progressive peripheral neuropathy under occupational exposure to an organic solvent remain unreported. Herein, we presented a rare association of minimal change nephrotic syndrome, tubular dysfunction with Guillain-Barré syndrome under the risk of exposure to an acetone-based cleansing solution; the case raises our concerns about possible chronic nephrotoxic or neurotoxic effects of common chemical organic solvents.

Improved iron utilization and reduced erythropoietin resistance by on-line hemodiafiltration.

BACKGROUND: Recent investigation has shown that on-line hemodiafiltration (HDF) can reduce the amount of recombinant human erythropoietin (rhEPO) deemed necessary to reach the target hematocrit. The aim of this study was to analyze the potential effect of on-line HDF on rhEPO resistance in relation to iron utilization and anemia-related parameters, when compared to conventional hemodialysis (HD). METHODS: Ninety-two chronic uremic patients were treated with conventional HD and then shifted to on-line HDF. Measurements of various erythropoiesis-related parameters were collected during HD and on-line HDF periods for statistical analysis for erythropoietin resistance. RESULTS: Patients treated with on-line HDF switching from conventional HD significantly contributed to the reduction of EPO dose to reach a higher mean hematocrit level (31.8 +/- 4.4% vs. 29.5 +/- 3.9%, p < 0.001) and a reduction of the serum ferritin level (322.5 +/- 268.4 vs. 544.9 +/- 642.4, p < 0.001). The median EPO/Hct ratio was greater in the HD period (504.6 +/- 310.1) than in the on-line HDF period (307.6 +/- 334.4) (p < 0.001). These results indicated a reduced EPO resistance and improved iron utilization by on-line HDF. By multiple regression analysis, the significant predictors of EPO resistance are ferritin, transferrin, albumin, and TACurea (Time average concentration of urea) in HD treatment. In on-line HDF modality, in addition to ferritin and albumin, the duration of on-line HDF is a negative predictor in EPO resistance. CONCLUSION: When on-line HDF is recommended to chronic dialysis patients, long-term use of this technique provides an efficient means of achieving the goal of an elevated hemoglobulin by reducing EPO resistance, improved iron utilization and may further improve the quality of life.