Non-traditional cardiovascular disease risk factors in end-stage renal disease: oxidate stress and hyperhomocysteinemia

Studies in experimental animals have shown that oxidative stress and hyperhomocyst(e)inemia culminate in abnormal vascular and endothelial regulation, functional nitric oxide deficiency, vascular hypertrophy, and atherosclerosis. Oxidative stress is accompanied by increased advanced glycation endproducts and oxidized low density lipoproteins. Studies of patients with end-stage renal disease provide extensive indirect, evidence of increased oxidative stress and more than ninety percent are hyperhomocyt(e)inemic. Presently, only uncontrolled or observational studies are available to assess the effects of anti-oxidant therapy for oxidative stress or folate therapy for hyperhomocyst(e)inemia in these patients. Promising developments include the reports of beneficial effects of a vitamin E coated dialyzer, and the reduction in homocyst(e)ine levels in patients with end-stage renal disease given an intravenous folate metabolite. However, there is presently no therapy available to reverse fully oxidative stress or hyperhomocyst(e)inemia. Therefore, the causative role of these nontraditional risk factors of cardiovascular disease remains untested.     

Adenomatous colonic polyps are rare in ulcerative colitis

BACKGROUND: Uncertainty exists as to whether dysplastic polyps in ulcerative colitis should always be managed as dysplasia-associated lesions/masses requiring colectomy, or whether some can be managed by polypectomy. The prevalence of non-inflammatory polyps in ulcerative colitis is unknown. AIM: To compare dysplastic polyp occurrence in patients with ulcerative colitis and in patients without inflammatory bowel disease. METHODS: The clinical, endoscopic and histological records of 150 ulcerative colitis patients (median disease duration, 10 years; 57% with pancolitis) undergoing colonoscopy were scrutinized for any polyp history. Two hundred and five patients undergoing colonoscopy for altered bowel habit, but without features suggestive of polyp presence, were used as a control group. Immunohistochemical staining of flat and polypoid mucosa for p16, beta-catenin, p53 and cyclo-oxygenase-2 was compared in the two groups. RESULTS: Only six (4%) ulcerative colitis patients had ever had dysplastic polyps. Two had single adenomatous polyps proximal to the colitis segment. Of the four patients with dysplastic polyps within colitic mucosa, two were treated endoscopically, but in two the lesions were considered to be dysplasia-associated lesions/masses and colectomy was advised. In contrast, 24 controls had at least one adenomatous polyp (chi(2) = 6.7, P < 0.01). Ten (6.7%) ulcerative colitis patients and 24 (12%) control patients had metaplastic polyps (N.S.). Immunohistochemical staining was not discriminatory. CONCLUSION: Despite the increased cancer risk in long-standing ulcerative colitis, adenomatous polyps arise less frequently in ulcerative colitis patients than in patients without ulcerative colitis.     

Early Posttransplant Nephrotic Range Proteinuria as a Presenting Feature of Minimal Change Disease and Acute T Cell–mediated Rejection

Early-onset nephrotic range proteinuria is an extremely rare presentation of an acute rejection episode. Herein, we have reported a patient who developed nephrotic range proteinuria 7 days after receiving a renal allograft from his sister despite minor changes in serum creatinine levels. A kidney biopsy spcimen revealed a T cell–mediated acute rejection process concomitant with minimal change disease (MCD). Proteinuria and renal dysfunction improved dramatically in response to corticosteroids. The possibility of acute cellular rejection and coexisting MCD should be considered in patients with early posttransplantation nephrosis and normal serum creatinine levels. The coexistence of these entities provides support for the role of T cells in the pathogenesis of MCD.     

Non-small-bowel lesions detected by capsule endoscopy in patients with obscure GI bleeding

BACKGROUND: Approximately two thirds of patients undergoing capsule endoscopy for obscure GI bleeding will have an abnormality found in the small intestine. This report describes 9 patients (4 men, 5 women) of 140 with obscure bleeding in whom a source of their blood loss was found in the stomach or the colon at capsule endoscopy. METHODS: A review was made of a prospective database of 140 consecutive patients undergoing capsule endoscopy for obscure GI bleeding at a single center. Patients with a definite or likely cause of bleeding within reach of conventional upper or lower GI endoscopy were identified. RESULTS: Three patients had gastric antral vascular ectasia and another an inflamed pyloric canal polyp. Two patients had actively bleeding cecal carcinoma, missed at previous colonoscopies. Two others had bleeding cecal angiodysplasia. The final patient had severe nonspecific cecal inflammation. The identification of these lesions was aided by the suspected blood indicator. All patients underwent endoscopic therapy or surgery for their non-small-bowel lesions. CONCLUSIONS: Like push enteroscopy, capsule endoscopy also can identify lesions within reach of conventional endoscopy and colonoscopy. These subsequently can be treated successfully. The reasons why these lesions have been missed are unclear.     

Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium

AIMS: Mycophenolate mofetil is an effective therapy for lupus nephritis (LN) and other glomerulonephritis (GN). However, gastrointestinal (GI) complications can limit its use. Enteric-coated mycophenolate sodium (EC-MPS) has been designed to reduce GI adverse events, but it has not been fully investigated in the treatment of GN. METHODS: Patients with LN and primary GN who had received EC-MPS were studied for effects on renal function. RESULTS: 30 subjects (17 LN, 13 primary GN) were studied. EC-MPS decreased proteinuria in both LN and GN. In LN, 16 patients had EC-MPS as induction therapy. Of these, 8 patients achieved complete remission (CR), 4 had partial remission (PR) and 1 improved renal function. In primary GN, CR was achieved in 4 out of 5 with minimal change disease, but only 1 did not relapse. PR was achieved in 1 of 4 patients with membranous glomerulopathy, 2 out of 2 patients with focal segmental glomerulosclerosis and 1 out of 2 patients with IgA nephropathy. Infections, anemia and alopecia were observed, but no patient had GI side effects. CONCLUSIONS: EC-MPS is effective in LN, but not as effective in primary GN. The risk of GI side effects appears to be low, but other side effects can still occur.     

Double-Filtration Plasmapheresis Plus Low-Dose Anti-thymocyte Globulin and Tacrolimus in Asian Living-Donor Kidney Transplantation With Donor-Specific Anti-HLA Antibody

BackgroundPretransplant desensitization protocols, including plasmapheresis, intravenous immunoglobulin, induction antibody therapy, and intensive maintenance immunosuppression, are generally employed in kidney transplant recipients who have positive status for donor-specific anti-HLA antibody (DSA). To avoid serious infectious complications, the authors designed a novel low-dose protocol in Thai patients undergoing DSA+ living-related kidney transplantation (LRKT).MethodsA retrospective cohort study of the patients who underwent DSA+ LRKT was conducted. The novel protocol consisted of 3 to 5 sessions of pretransplant double-filtration plasmapheresis (DFPP) with or without low-dose intravenous immunoglobulin together with low-dose anti-thymocyte globulin (ATG) induction (1-1.5 mg/kg/d for 3-4 days) and low-dose tacrolimus (Tac) (trough level 5-10 ng/mL), mycophenolate, and prednisolone.ResultsThe study included 17 patients. The lymphocyte crossmatch via complement-dependent cytotoxicity was negative in 12 patients and positive for B cell immunoglobulin M in 5 patients. The novel desensitization protocol resulted in a decrease of at least 50% of DSA mean fluorescence intensity from baseline (from 4320 ± 549 before DFPP to 1601 ± 350 before transplantation, P < .005) and successful kidney transplantation with good allograft function in all cases. Early DSA rebound was observed in 3 patients after transplantation, and kidney biopsy revealed subclinical antibody-mediated rejection in 1 patient and diffuse C4d staining without cell infiltration in 2 patients. There were good long-term outcomes in patient and graft survival (100% and 94.1%, respectively). Only 1 allograft loss occurred because of nonadherence. The majority of patients have stable allograft function with serum creatinine less than 1.5 mg/dL. However, infections, including CMV and other organisms, were commonly observed.ConclusionsDesensitization protocol with DFPP, low-dose ATG, and Tac provides excellent outcomes in living donor kidney transplantation in highly sensitized Asian populations.