Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

LUMINAL BACTERIAL OVERGROWTH AND INTESTINAL TRANSLOCATION IN PIGS GIVEN EITHER CYCLOSPORINE-A OR 15-DEOXYSPERGUALIN AFTER SMALL-BOWEL TRANSPLANTATION

Objective: To examine the effects of two immunosuppressant regimens on composition of the bowel flora and rate of translocation after transplantation of the small bowel in pigs. Design: Randomised controlled study. Setting: University hospital, Italy. Material: 35 female Large White pigs. Interventions: 9 Animals were not operated on (normal controls). 19 Animals underwent total orthotopic small bowel allotransplantation and were then randomised to receive: group A (n = 8) cyclosporin A 25 mg/kg subcutaneously and cephazalin 2 g intramuscularly daily; group B (n = 6) 15-deoxyspergualin (15-dos) 3 mg/kg for 7 days then 1.5 mg/kg, cephazolin 2 g intramuscularly daily for 4 days then selective intestinal decontamination with colistin 1.5 million U, tobramycin 100 mg, vancomycin 1 g, and nystatin 500000 U daily; and group C (n = 5) cephazolin 2 g intramuscularly daily for 8 days. A further group (D, n = 7) underwent orthotopic autotransplantation and received the same antibiotic and selective decontamination regimens as group B. Animals in group C were killed on day 8, and the rest on day 29. Main outcome measures: Signs of rejection, graft versus host disease, luminal overgrowth, and evidence of translocation to mesenteric lymph nodes. Results: All animals in group C, and 2 in group B, showed signs of acute rejection. There was a significant overgrowth of both aerobic and anaerobic bacteria in all 3 groups after allotransplantation compared with normal controls. Bacterial translocation was similar in autografted and allotransplanted animals. Mesenteric lymph nodes were colonised in 4/9 controls, 7/8 in group A, 4/4 in group B, 5/5 in group C, and 7/7 in group D. Conclusion: Neither cyclosporin A nor 15-dos prevented luminal overgrowth or bacterial translocation to mesenteric nodes up to one month after operation. The rate of translocation was similar in autotransplantation and allotransplantation, suggesting that non-immunological factors (for example, denervation and interruption of lymphatics) may have a role in these alterations

PARENTERAL ANTIBIOTICS AND SELECTIVE INTESTINAL DECONTAMINATION DO NOT PREVENT ENTERIC BACTERIAL OVERGROWTH OR TRANSLOCATION OBSERVED IN A SWINE MODEL OF SMALL-BOWEL TRANSPLANTATION

Alterations in the luminal microflora and increased intestinal translocation have been reported to occur following experimental and clinical small bowel transplantation (SET). Selective intestinal decontamination (SID) has been used to prevent luminal overgrowth and bacterial translocation. Despite the wide use of SID in clinical SET, there are no data supporting its usefulness in this situation. Thus, the aim of this investigation was to examine the effects of cyclosporine A (CSA) and SID upon bacterial overgrowth and translocation in a swine model of SET. Nineteen Large White female pigs weighing 30 +/- 2 kg underwent a total orthotopic SET and were randomly allocated to one of the following experimental groups as follows: Group 1 (No. 8) CSA 25 mg/kg body weight (b.w.)/day administered subcutaneously and Cefazolin 2 g/day im. Group 2 (No. 6) received the identical immunosuppression but the Cefazolin 2 g/day im was discontinued on the 5th Postoperative Day (pod) and switched to a SID regimen consisting of Vancomycin, 1 g, Nystatin, 500,000 IU, Colistin, 1,500,000 IU, and Tobramycin, 100 mg, given through a gastrostomy tube. Group 3 (No. 5) received no immunosuppression but antibiotic consisting of Cefazolin 2 g im/day. Group 4 (No. 7) underwent a small bowel autotransplantation. Group 4 received SID as in group 2 but no immunosuppression was given, Finally, 17 normal animals were sham-operated and were used as normal controls (N group). The animals in groups 1, 2, and 4 were sacrificed on the 29th pod. Those in group 3 were sacrificed on the 7th pod. Samples from graft, native bowel, liver, kidney, skin, and lungs were processed for histologic evaluation. Moreover, samples from the graft (proximal, middle, and distal) and adjacent mesenteric lymph nodes were harvested aseptically and cultured for both aerobes as well as for anaerobes. Significant increases in the number of aerobes and anaerobes were found in the proximal graft of all groups studied compared to the normal controls. The rate of intestinal translocation was 19% in the normal controls and increased to 88, 83, 100, and 100% in groups 1, 2, 3, and 4, respectively. Based upon these data, it can be concluded that SID is no better than a parenteral antibiotic regimen at preventing bacterial overgrowth following SET. Moreover, neither therapy reduces the high rate of bacterial translocation to mesenteric nodes seen in arrivals following experimental SET. (C) 1995 Academic Press, Inc