Failure to mount an immune response to CDT appears to be an important mechanism for recurrent diarrhoea [1, 2]. [8]. However, none of the cases reported have CKD. We statement two cases of CKD patients with refractory CDT colitis, treated successfully with Rabbit Polyclonal to RPL22 IVIG. Case Statement 1 A 67-year-old lady with type I diabetes mellitus (DM), diabetic nephropathy and hypertension was admitted to the hospital for assessments regarding diabetic gastroparesis. During her stay, she developed three episodes of sepsis, two due to pneumonia and one urinary tract infection. All these septic episodes were associated with shock, acute-on-chronic kidney disease (background CKD stage 4) and admission to the rigorous therapy unit. During her last septic episode, in March 2007, she developed life-threatening CDT diarrhoea and pseudo-membranous colitis that required aggressive hydration, inotropic support and haemofiltration. The diarrhoea was refractory to two coures of treatment with metronidazole and one of vancomycin. Computerized tomography scan of the stomach and subsequent sigmoidoscopy confirmed severe pseudo-membranous colitis. A total colectomy was considered, but she was deemed unfit for surgery, in view of the underlying sepsis and her acute kidney injury. After liaising with a specialist microbiologist (RC), she was started on IVIG in the form of Intratect? 0.4 g/kg each infusion by five infusions, which resulted in an improvement of symptoms, resolution of diarrhoea (Determine 1) and inflammatory markers. Her acute kidney injury recovered and she became impartial of haemofiltration during the course of therapy. Subsequent stool samples showed clearance of CDT. Open in a separate windows Fig. 1 Patient 1: Stool frequency chart for patient with toxin colitis. Case Statement 2 A 57-year-old man with type 2 DM and CKD stage 3 was admitted with a 4-week history of non-specific symptoms of lethargy, general malaise, nausea, excess weight loss, hypotension and severe cardiac failure. Subsequent investigations confirmed the diagnosis of main amyloidosis on rectal biopsy. He was started on intravenous cefuroxime for chest contamination whilst on chemotherapy, melphalan and dexamethasome. Four days later he developed CDT diarrhoea. His CDT contamination was complicated with acute-on-chronic renal failure, with peak urea and creatinine of 61.5 mmol/L and 347 mol/L respectively. He had a colonoscopy that confirmed pseudo-membranous colitis. His diarrhoea was refractory to two courses of metronidazole and vancomycin. Subsequently, he was started on IVIG (Intratect? 0.4 g/kg each infusion). Two days into his therapy, his diarrhoea started settling and he showed marked symptomatic improvement. Inflammatory markers started to come down and his diarrhoea completely settled after a 3-day course of IVIG therapy. His renal function improved with urea and creatinine of 22.4 mmol/L and 164 mol/L respectively. Regrettably, the patient later died of an unrelated causeventricular tachyarrhythmia secondary to his cardiac amyloid. The treatment of refractory CDT colitis remains controversial. There is some evidence of successful use of IVIG in the treatment of refractory CDT colitis, used as salvage therapy after failure of standard therapy with metronidazole and vancomycin [3C8]. The five most important factors associated with a complicated recurrent CDT disease include increasing age 65, leucocytosis 20 109 cells/L, immunosuppression, hospital acquired contamination and CKD [9]. Complicated DASA-58 CDT disease can be associated with harmful megacolon (disease requiring colectomy) and shock or death. Deficiency of one or more IgG subclasses in patients with renal failure has been implicated as one of the plausible mechanisms, suggesting inhibition of their synthesis in the uraemic state. [10]. At present, no lab provides a diagnostic support to identify poor IgG response to at IgG DASA-58 levels of approximately 1 mg/ml [15]. Thus the neutralizing levels of IgG in the blood are readily achievable with IVIG. However, the precise mechanism of action of IVIG is not clear, as to be effective, IgG anti-toxin must leave the blood circulation and bind to toxins A and B within the colonic lamina propria or lumen [15]. Since our success, two lupus patients with CKD 5, on a chronic haemodialysis programme and immunosuppression, experienced refractory CDT diarrhoea following antibiotic therapy in the Royal Liverpool University DASA-58 or college hospital. They were both treated with metronidazole and vancomycin.