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Effects of Simultaneous KP transplantation VS KD single in type 2 diabetics: seven years follow-up

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Enteropatia Diabetica nel Trapianto Rene-Pancreas vs Rene Singolo: follow-up di 7 anni

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Effects of Simultaneous KP transplantation VS KD single in type 2 diabetics: seven years follow-up

  1. 1. Università Vita-Salute San RaffaeleEffects of Simultaneous Kidney-Pancreas and Kidney Alone Transplantation on Diabetic Enteropathy: a 7-year Follow-up Study Scuola di Specializzazione Chirurgia dell’Apparato Digerente Direttore Prof. Carlo Staudacher Diploma di Specializzazione del Dott.: Francesco LUPARINI matr. 001443
  2. 2. Background• DEFINITION: All gastrointestinal disorders associated with hyperglycaemia• EPIDEMIOLOGY: Ranging from 20-76% Janatuinen (1993) Scan J Gastroenterol; Bytzer (2001) Arch Intern Med. ; Feldman (1983) Ann Intern Med; Maleki (2000) Arch Intern Med• ETIOLOGY: Autonomic Neuropathy and Vasculopathy. Bjornsson (1994) Scand J. Gastroenterol ; Koch (1999) Dig Dis Sci• SYMPTOMS: • Upper GI: Early satiety; Nausea; Vomiting; Heartburn ; Dysphagia; Gastroparesis. • Lower GI: Constipation; Abdominal Pain; Diarrhea; Fecal incontinence.• DIAGNOSIS IMAGING: Esophageal Manometry; Electrogastrography; Gastric Emptying Scintigraphy; Anorectal Manometry; Defecography; Electromiography• THERAPY: only symptomatic and poorly effective Francesco Luparini MD
  3. 3. Aims of the Study1) To evaluate the effects of Kidney-Pancreas Transplantation (KP) or Kidney Alone (KD) through: - Laboratory/Blood Pressure values - Specimen of rectal mucosa - Gastrointestinal symptoms/fecal incontinence2) To correlate biochemical,functional and microscopic data in Kidney-Pancreas or Kidney transplantation toward Diabetic Enteropathy Francesco Luparini MD
  4. 4. Patients• Patients: Type 1 Diabetic undergoing renalsubstitutive therapy• Observation Period: 06/2000 – 06/2010• Follow-up: 7 years (mean) Francesco Luparini MD
  5. 5. MethodsEvaluation during Recovery: Haematic samples for biochemical, metabolic values and plasma sample for Ghrelin Elisa assay Interview-based Questionnaire consisting of 15 items (GSRS; Rating Scale for Gastrointestinal Symptoms) Svedlund (1988) Dig Dis Sci Anorectal Manometry Rectal mucosa biopsies for optical and electronic microscopy Francesco Luparini MD
  6. 6. Patients’ Characteristics I Baseline KP (n=26) KD (n=20)Age (yrs)* 37.3±3.7 Age (yrs)* 43.4±7.0Duration of Diabetes (yrs) 27.6 ±6.2 Duration of Diabetes (yrs) 31.3±12.7HbA1c (%) 8.3±1.7 HbA1c (%) 8.5±1.6Gender (male/female) 17/9 Gender (male/female) 13/7Time of Dialysis (months) 53.4±30.2 Time of Dialysis (months) 43.8±25.9Laser-treated Retinopathy (%) 72% Laser-treated Retinopathy (%) 61%Kidney Warm Ischemia (min) 40.0±19.6 Kidney Warm Ischemia (min) 45.2±21.3Kidney Cold Ischemia (h) 7.0±4.6 Kidney Cold Ischemia (h) 7.6±9.5BMI 22.9±2.3 BMI 23.7±3.1Creatinine (mg/dl) 8.4±2.6 Creatinine (mg/dl) 8.7±2.5eGFR (ml/min/1.73m2) 7.9±2.9 eGFR (ml/min/1.73m2) 7.0±2.4 yrs= years ; Hb1Ac=Glycated hemoglobin; min= minutes BMI= body mass index; * p= 0.004 Francesco Luparini MD
  7. 7. Patients’ Characteristics II Baseline KP (n=26) KD (n=20)BUN (mg/dl) 142.0±44.0 BUN (mg/dl) 147.1±51.8Uric Acid (mg/dl) 6.9±1.3 Uric Acid (mg/dl) 6.7±1.5EIR (UI/die) 37.4±11.0 EIR (UI/die) 39.1±17.2Systolic BP 143.5±12.9 Systolic BP 146.3±18.7Diastolic BP 83.7±8.3 Diastolic BP 82.8±8.5TG (mg/dl) 162.5±92.7 TG (mg/dl) 191.7±119.2Chol (mg/dl) 201.0±45.7 Chol (mg/dl) 198.4±50.3LDL (mg/dl) 116.3±40.3 LDL (mg/dl) 109.7±37.1HDL (mg/dl) 48.1±14.4 HDL (mg/dl) 47.9±12.1eGFR= glomerular filtration rate; BUN= blood urea nitrogen;EIR= exogen insulin requirement; UI= international unit; BP= blood pressure; TG= Tryglicerids;Chol= cholesterol; LDL= low density lipoprotein; HDL= high density lipoprotein Francesco Luparini MD
  8. 8. Biochemistry KP KD * * p<0.01 vs. all * * p<0.01 vs. all Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n=26) (n=25) (n=22) Francesco Luparini MD (n=20) (n=15) (n=8)
  9. 9. Biochemistry KP KD * * * p<0.01 vs. all * p<0.01 vs. all * * * p<0.01 vs. all * p<0.01 vs. all Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n=26) (n=26) (n=23) (n=20) (n=14) (n=12) Francesco Luparini MD
  10. 10. Biochemistry KP KD p=0.03 p<0.01 Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n=24) (n=24) (n=22) Francesco Luparini MD(n=17) (n=16) (n=9)
  11. 11. Biochemistry KP KDBasal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n=22) (n=22) (n=20) Francesco Luparini MD (n=17) (n=17) (n=10)
  12. 12. Biochemistry KP KD p= 0.02 p< 0.001 p= 0.01 p< 0.001Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n=11) (n=7) (n=2) (n=10) (n=6) (n=2) Francesco Luparini MD
  13. 13. Blood pressure KP KD * * p<0.01 vs. all * * p<0.01 vs. all Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n=25) (n=25) (n=22) (n=17) (n=16) (n=9) Francesco Luparini MD
  14. 14. GSRS questionnaire KP KD p=0.03 Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD
  15. 15. GSRS questionnaire KP KD Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD
  16. 16. GSRS questionnaire KP KD Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD
  17. 17. Anorectal Manometry KP KD p=0.06 Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD Normal value: 55-120 mmHg Corsetti, Passeretti (2009) Colorectal Disease
  18. 18. Anorectal Manometry KP KD p=0.01 Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD Normal value: 160-370 mmHg Corsetti, Passeretti (2009) Colorectal Disease
  19. 19. Anorectal Manometry KP KD Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD Normal value: <100 ml Corsetti, Passeretti (2009) Colorectal Disease
  20. 20. Anorectal Manometry KP KD p=0.01 Basal 2 yrs 7 yrs Basal 2 yrs 7 yrs(n: 18) (pts:13) (pts:10) (pts: 10) (pts:8) (pts:4) Francesco Luparini MD Normal value: 100-180 ml Corsetti, Passeretti (2009) Colorectal Disease
  21. 21. Pathology H&E CD31 S100 Serotonin Glycentin PYY SomatostatinKP pre-txKP 2 yearsKP 7 yearsKD pre-txKD 2 yearsKD 7 years Original magnification 20x Francesco Luparini MD
  22. 22. PathologyKP KD Francesco Luparini MD
  23. 23. PathologyKP KD Francesco Luparini MD
  24. 24. KP KDPathology: Ki67 Pre-tx Pre-tx 2 years 2 yearsControlOriginal magnification 40x 7 years Luparini MD Francesco 7 years
  25. 25. Pathology: Crypt of Lieberkühn KP KD p <0.01p <0.01 p <0.05 Francesco Luparini MD
  26. 26. KP KDEM:Endothelium and Vases Pre-Tx Pre-Tx 2 years 2 yearsControl 7 years Francesco Luparini MD 7 years
  27. 27. EM: Endothelial Cells KP KDp < 0.05 Francesco Luparini MD
  28. 28. EM: Endothelial CellsKP KD Francesco Luparini MD
  29. 29. KP KDEM:Mucosal Nerves Pre-Tx Pre-Tx 2 years 2 years Control 7 years Luparini MD Francesco 7 years
  30. 30. EM: Mucosal NervesKP KD p <0.01 p <0.05 * * * p <0.05 p <0.01 p <0.05 Francesco Luparini MD
  31. 31. KP KDEM:Schwann Cells Pre-Tx Pre-Tx 2 years 2 years Control Francesco Luparini MD 7 years 7 years
  32. 32. EM: Schwann CellsKP KD Francesco Luparini MD
  33. 33. Overview IMPROVE STABLE WORSEN Ghrelin KP- KD Glycemia KP KDBiochemical Creat. & Uremia KP KP-KD TG KP KD B. Pressure KP KDClinical Abd. Pain Diarrhoea KP KP KD KP-KD Immunohist. KP-KD Ki-67 KP KDMicroscopy Endothelium KP-KD Nerves Vesicles KP KP KD Schwann KP-KD Resting KP KDAnorectal Contraction KP KDManometry Reflex KPKP KP KD KD Urgency Francesco Luparini MD
  34. 34. Conclusions KP tx, but not KD, improves diabetic enteropathy• Effect on Biochemistry: improves glycemic and TG profile• Effect on Symptoms: reduces abdominal pain• Effect on Manometry: stabilises continence• Effect on Ultrastructures: improves mitosis, nerves vesicles, endothelial and Schwann cells Further studies are requested to confirm our observation in larger pool of kidney–pancreas recipients Francesco Luparini MD

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