Eculizumab for salvage treatment of refractory antibody-mediated rejection in kidney transplant patients: case reports.

Antibody-mediated rejection (AMR) in a group of preoperatively desensitized patients may follow a dreadful course and result in loss of the transplanted kidney. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD 20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present two cases of acute-onset AMR in preoperatively desensitized patients. Eculizumab was used as a salvage agent in addition to conventional therapy. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss.

Fetuin-A, inflammation, and coronary artery calcification in hemodialysis patients.

Hemodialysis patients have extremely increased cardiovascular mortality. Vascular calcification, inflammation, and low serum fetuin-A levels are implicated for increased mortality. In this study, relationship between coronary artery calcification, inflammation, and serum fetuin-A levels were investigated. Seventy-eight hemodialysis patients (38 male, 40 female, mean age: 52±14.5 years) were included. All patients were on dialysis for more than 6 months. Coronary artery calcium scores (CACS) are determined by electron-beam computed tomography. Serum CRP, IL-1ß, IL-6, TNF-α, and serum fetuin-A levels were measured. Mean CACS value was 488.5±94.5. Serum fetuin-A levels were negatively correlated with CACS (r:-0.30, P=0.009). Patients are divided into two groups according to total CACS value; group 1 (CACS<10), group 2 (CACS≥10). There was a statistically significance difference in fetuin-A levels between CACS group 1 and group 2 (P=0.001). In this study, serum fetuin-A levels were associated with total CACS. This Fetuin-A may play a role in increased mortality in this group of patients via facilitating CAC.

Comparison of nutritional status in hemodialysis patients with and without failed renal allografts.

BACKGROUND: The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aimed to compare the nutritional status and its relation with inflammation in patients on HD with and without previous kidney transplantation. METHODS: Forty-three patients with failed renal allografts (27 males; mean age 36±9 yr) and 40 never transplanted HD patients (24 males; mean age 39±9 yr) were included in the study. Body weight, triceps (TSF), biceps (BSF), subscapular (SSSF), and suprailiac skinfold thicknesses (SISF); mid-arm, mid-arm muscle, hip and waist circumferences; as well as body mass indices (BMIs) were determined as anthropometric parameters. Moreover, biochemical markers of nutritional status, including serum cholesterol and albumin as well as high-sensitive C-reactive protein (hs-CRP), as a marker of inflammation, were measured. Associations among these variables were analyzed. RESULTS: There were no significant differences considering age, gender or duration of renal replacement therapy between the two groups. The TSF (p<0.0001), BSF (p=0.005), SSSF (p=0.001), SISF (p<0.0001) skinfold thicknesses; mid-arm (p=0.003) and mid-arm muscle circumferences (p=0.037) and BMIs (p=0.001) of the patients with failed renal allografts were significantly lower than those of the never transplanted HD patients. Waist circumference was significantly lower as well (p=0.028). Patients with failed transplants were characterized by lower serum albumin (p<0.0001) and higher hs-CRP levels (p=0.001) as compared with never transplanted HD patients. CONCLUSIONS: This study confirms the concept that retained failed allografts may induce chronic inflammation in chronic HD patients which may result in a worse nutritional status.

Endothelial dysfunction in peritoneal dialysis patients with and without failed renal transplants.

BACKGROUND: Endothelial dysfunction (ED) is a common, early abnormality that predisposes patients to develop atherosclerosis and cardiovascular events; inflammation is associated with atherosclerosis and malnutrition. Patients with failed transplants are usually complicated by inflammation; however, ED in this group of patients has not been well defined. In this cross-sectional study, we sought to investigate ED among naïve peritoneal dialysis (nPD) patients who were never transplanted as well as patients with failed renal transplants who were re-starting peritoneal dialysis (fTxPD). METHODS: Twenty-five nPD patients (15 female/10 males; mean age, 44 +/- 11 years), and 12 fTxPD patients (4 males; mean age, 37 +/- 10 years) were included in the study. Coronary flow reserve (CFR) measurements were used to evaluate ED. Serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin, and intact parathyroid hormone (iPTH) were measured. Also, highly sensitive C-reactive protein (hs-CRP) levels and weekly Kt/V were determined as possible confounding factors. Results were compared between the 2 groups. RESULTS: There were no significant differences regarding age, gender, mean systolic and diastolic blood pressures, or smoking status. Mean duration on PD, peritoneal transport characteristics, PD modality and doses, frequency of peritonitis episodes, as well as serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin and iPTH levels were similar between the 2 groups. Weekly Kt/V of both groups were similar as well. However, hs-CRP levels were significantly higher (34 +/- 52 vs 6.7 +/- 7.5 mg/L; P = .017) and CFR significantly lower among patients with fTxPD compared with nPD patients (1.52 +/- 0.20 vs 1.91 +/- 0.53; P = .022). CONCLUSION: ED was more prominent among patients with failed transplants than nPD cases, suggesting that the failed allograft may be responsible for this abnormality.

Association between chronic hepatitis C infection and coronary flow reserve in dialysis patients with failed renal allografts.

BACKGROUND: Hepatitis C infection occurs frequently among patients with end-stage renal disease and increases the risk of atherosclerotic cardiovascular diseases. Endothelial dysfunction (ED) is an early event in the pathogenesis of atherosclerosis. It has been reported among patients treated with hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation. The aim of the present study was to evaluate effects of chronic hepatitis C infection on ED in patients with failed renal transplants. METHODS: Twenty-six nondiabetic, anti-hepatitis C virus (HCV)-positive (15 females, mean age: 38 +/- 8 years) and 26 anti-HCV-negative patients (15 females, mean age: 36 +/- 5 years), all of whom had returned to PD or HD after renal transplant failure were studied to assess coronary flow reserve (CFR) by transthoracic Doppler echocardiography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured as markers of chronic inflammation. CFR recordings and intima-media thickness measurements were performed using the Vivid 7 echocardiography device. RESULTS: Demographic and clinical characteristics of patients were similar between the two groups. Serum hs-CRP levels were significantly higher among HCV-positive patients versus HCV-negative counterparts. HCV-positive patients showed lower CFR measurement than HCV-negative ones. Also, a negative correlation was observed between serum hs-CRP levels and CFR values. CONCLUSION: CFR values are worse among anti-HCV-positive patients with failed renal transplants compared with anti-HCV-negative subjects. Graft dysfunction per se may aggravate a proinflammatory states thereby inducing ED. Furthermore, the presence of HCV is a greater trigger of ED among patients with renal failed grafts.