Maciej Kosieradzki

Ischemia/Reperfusion Injury in Kidney Transplantation: Mechanisms and Prevention

Ischemia has been an inevitable event accompanying kidney transplantation. Ischemic changes start with brain death, which is associated with severe hemodynamic disturbances: increasing intracranial pressure results in bradycardia and decreased cardiac output; the Cushing reflex causes tachycardia and increased blood pressure; and after a short period of stabilization, systemic vascular resistance declines with hypotension leading to cardiac arrest. Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that all of these changes-the early innate response and the ischemic tissue damage-play roles in the development of adaptive responses, which in turn may lead to an acute font of kidney rejection. Hypothermic kidney storage of various durations before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion. Reperfusion injury, the effector phase of ischemic injury, develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy, and necrosis; the fate of the organ depends on whether cell death or regeneration prevails. The whole process has been described as the ischemia-reperfusion (I-R) injury. It has a profound influence on not only the early but also the late function of a transplanted kidney. Prevention of I-R injury should be started before organ recovery by donor pretreatment. The organ shortage has become one of the most important factors limiting extension of deceased donor kidney transplantation worldwide. It has caused increasing use of suboptimal deceased donors (high risk, extended criteria [ECD], marginal donors) and uncontrolled non-heart-beating (NHBD) donors. Kidneys from such donors are exposed to much greater ischemic damage before recovery and show reduced chances for proper early as well as long-term function. Storage of kidneys, especially those recovered from ECD (or NHBD) donors, should use machine perfusion.

Machine Perfusion Preservation Improves Renal Allograft Survival

Machine perfusion (MP) has been used as the kidney preservation method in our center for over 10 years. The first, small (n = 74) prospective, single‐blinded randomized study comparing MP and Cold Storage (CS) showed that the incidence of delayed graft function was higher after CS. There have been no reports in the literature on the effect of storage modality on long‐term function of renal allografts. This paper presents an analysis of long‐term results of renal transplantation in 415 patients operated on between 1994 and 1999. Of those, 227 kidneys were MP‐stored prior to KTx. The control group consisted of 188 CS kidney transplants. Kidneys were not randomized to MP or to CS. Donor demographics, medical and biochemical data, cold ischemia time, HLA match and recipient data were collected. Standard triple‐drug immunosuppression was administered to both groups. Mortality, graft survival and incidence of return to hemodialysis treatment were analyzed. Despite longer cold ischemia time and poorer donor hemodynamics in MP group, 5‐year Kaplan‐Meier graft survival was better in MP‐stored than in CS‐stored kidneys (68.2% vs. 54.2%, p = 0.02). Conclusion: In this nonrandomized analysis, kidney storage by MP improved graft survival and reduced the number of patients who returned to dialysis.

The Objective of Psychological Evaluation in the Process of Qualifying Candidates for Bariatric Surgery

Psychosocial and behavioral variables play an important role in both the development and treatment of obesity. Therefore, in the process of qualifying the patient for bariatric surgery, it is necessary to professionally evaluate his/her psychological state. Such evaluation is very helpful in the identification of factors potentially disturbing the effectiveness of the treatment. Clinical interviews with a group of 80 patients were conducted by a psychologist in the pre- and post-surgical period. The qualitative analysis of the interviews led to the identification of the major elements which should become the object of psychological evaluation in the process of qualifying patients for bariatric surgery. Conducting a clinical interview comprising these elements allows one to evaluate their potential influence on the process of surgical treatment of obesity and to provide optimal psychological support for the patient before and after the surgery.

Surgical complications observed in simultaneous pancreas-kidney transplantation : Thirteen years of experience of one center

SIMULTANEOUS pancreas and kidney transplantation (SPKTx) is the procedure of choice for a majority of transplant candidates with end-stage renal disease and diabetes mellitus. Recent evidence supports its benefits on the maintenance of normoglycemia and the arrest or even possibily of reversal of diabetic complications, such as vasculopathy, nephropathy, and neuropathy. However, pancreas transplant has been associated with the highest surgical complication rate of all the routinely performed organ transplant procedures. A significant number of pancreas grafts are lost early post-transplant secondary to surgical complications. Over the last decade, the operative procedure has been refined and immunosuppressive regiments have improved such that 1-year graft survival routinely exceeds 75%. The purpose of this study was to assess our improved results and to determine other risk factors that may help us decrease the complication rate further.

Partnership for Transplantation: A New Initiative to Increase Deceased Organ Donation in Poland

Despite the long-standing history of transplantation, the shortage of organs has remained its most restrictive factor. In 2010, the number of actual deceased organ donors in Poland was 13.5/million population (pmp). However, a huge difference in organ recovery rates is evident between various regions, eg, 32 pmp, in western Pomerania compared with 1-3 pmp in southern districts. A substantial number of patients who die while awaiting organ transplantations could be saved were effective programs able to overcome barriers in deceased organ donation. Such programs, eg, the European Donor Hospital Education Program, Donor Action, European Training Program on Organ Donation, United States Collaborative in Donation were introduced several years ago, but after transient improvements there has not been real progress. A new comprehensive program-Regional Partnership for Transplantation-was initiated a year ago in 4 districts of southern Poland by the Polish Union for Transplantation Medicine. The letter of intent to activate the donation program was signed by the local administration, the president of the local medical school, president of the Physicians Chamber, transplant centers, the Polish Union for Transplantation, and the Polish Transplant Coordinating Center. The plan of action included training of in-hospital coordinators, visits to all regional hospitals in company of a representative of the hospital founding body, examination of the real donation pool and the need for participation in a donation program training and education of the hospital staff in legal and organizational aspects of donation, brain death recognition, and various aspects of donor care. In addition, the program included communication skills workshops for intensive care unit physicians (with participation of 2 actors, an experienced anesthesiologist, and a psychologist), lectures for high school and university students and for hospital chaplains as well as alumni of higher seminaries. The preliminary results (after the first year) showed 40%-70% increases in activity of the local hospitals in the organ donation process.

Detrimental Effect of Aprotinin Ban on Amount of Blood Loss During Liver Transplantation: Single-Center Experience

BACKGROUND Aprotinin, a plasmin inhibitor, had been used for reduction of intraoperative bleeding caused by hyperfibrinolysis during extensive surgery. Prophylaxis with aprotinin to limit blood loss during orthotopic liver transplantation (OLT) had been widely applied until the drug was weaned off the therapeutic list for severe complications. We compared the need for blood and blood products transfusion in patients undergoing OLT with and without the use of aprotinin. MATERIALS AND METHODS A retrospective analysis was performed on 150 patients, who underwent OLT between March 2004 and August 2008 and were divided into 2 groups: the APRO group (n = 111) after induction of anesthesia was given a bolus of 500 kIU of aprotinin in a 30-minutes infusion followed by 140 kIU/h till the end of the OLT in which aprotinin was not administered, and the NON-APRO group (n = 39). RESULTS Patients from the NON-APRO group needed significantly more units of packed red blood cells (PRBC) than the APRO group (5.53 ± 4.89 vs 3.99 ± 3.58 units; P = .037). Avoidance of aprotinin administration (β = 1.408), Child-Pugh score (β = 0.519), and duration of anhepatic phase (β = 0.03) affected the volume of transfused blood according to multiple regression analysis (P < .05). CONCLUSIONS Our study confirmed the important prophylactic role aprotinin used to have during OLT in limiting the need for blood transfusions. Further research and progress in methods of blood loss minimization and monitoring of hemostasis are needed to warrant safe liver transplantation.

Obesity and Pelvic Floor Disorders: A Review of the Literature

Overweight and obesity are becoming a worldwide health problem associated with numerous co-morbidities. National costs of obesity and pelvic flor disorders have been rising since the 1950s across the world. Obesity is thought to have a very strong effect on pelvic floor disorders, and, considering the high prevalence of both problems worldwide, it is of utmost importance to evaluate the association between these pathologies as well as the impact of obesity on treatment efficacy. This review is based on a selection of reports in the literature (PubMed search), including guidelines and Cochrane reviews. Obesity seems to be a well-documented risk factor for lower urinary tract symptoms (LUTS) and is a predictor of exacerbation of stress urinary incontinence (SUI) and overactive bladder (OAB). Weight loss is also associated with improvement or resolution of SUI and OAB. In the case of pelvic organ prolapse (POP), weight loss is associated with improvement in quality of life. Although obesity is associated with POP in general, the exact role of obesity in symptomatic POP remains uncertain. While outcomes of anti-incontinence surgery among obese women are similar to those in non-obese women, postoperative urge incontinence is more likely to occur. It seems that obesity is not a risk factor for postoperative complications or short-term efficacy of POP surgical treatment. Long-term effects are still uncertain. Obesity is a strong risk factor for LUTS, but in most cases it does not affect efficacy of operative treatment. It may be associated with some post-operative complications. Weight loss in many cases allows avoiding surgical intervention.

Simultaneous pancreas-kidney transplantation: analysis of donor factors

There are no urgent indications for simultaneous pancreas-kidney transplantation. So our policy is to harvest only a pancreas in good biologic condition. The criteria for acceptance of a pancreas donor are: age 15 to 40 years, ICU stay < 7 days, no clinical signs of infection, negative virologic status, no history of hypotension or cardiac arrest, serum amylase elevation below three times normal values, controllable hyperglycemia, no history of pancreatic disease, no history of abdominal trauma damaging the organ, no history of alcohol addiction, BMI < 25, no functional or anatomical lesions of the kidneys, and expected ischemia time less than 12 hours. The proper selection of a pancreas donor allows one to achieve good insulin secretion immediately after transplantation. In 2000 to 2002 all 20 pancreases transplanted at transplant center displayed immediate secretory function after transplantation.

Improvement of Graft Function following Roux-en-Y Gastric Bypass Surgery in a Morbidly Obese Kidney Recipient: A Case Report and Literature Review

BACKGROUND Transplantation is the best and approved method of renal replacement therapy. Graft function depends not only on proper regulation of immune processes but also on the optimal control of chronic diseases. The obesity epidemic involves the healthy population and organ recipients equally. Obesity and metabolic syndrome lead to a number of disorders exerting adverse effects on the transplanted organ. CASE REPORT We report a case of a kidney recipient, 12 years after transplantation, with chronic graft failure (serum creatinine level 2.1 mg/dl, GFR 31 ml/min/1.73 m(2)), morbid obesity (weight 139.8 kg, BMI 46.2 kg/m(2), excess body mass 73.1 kg), hypertension, poorly controlled type 1 diabetes (HbA1c 8.8%), and ischemic heart disease. The cause of chronic kidney disease was diabetic nephropathy. The patient was the first Polish kidney recipient referred for bariatric gastric bypass surgery (GB). Directly after surgery, transient creatinine elevation (4.7 mg/dl) was noted. There was no reduction in diuresis. Desired weight loss was achieved within 12 months after surgery (body mass 81.9, BMI 27.1 kg/m(2), percentage loss of excess weight 86.9%) with improved graft function (serum creatinine level 1.3 mg/dl, GFR 45.1 ml/min/1.73 m(2)) and reduction of daily insulin requirement from 74 to 40 units. The severity of hypertension and ischemic heart disease diminished as well. CONCLUSIONS Metabolic surgery is the best treatment of obesity and may contribute to post-transplantation care if weight gain is observed, as a result of the interaction of many factors leading to deterioration of renal graft function.

Attitude of Healthcare Professionals: A Major Limiting Factor in Organ Donation from Brain-Dead Donors

Public attitude toward deceased donor organ recovery in Poland is quite positive, with only 15% opposing to donation of their own organs, yet actual donation rate is only 16/pmp. Moreover, donation rate varies greatly (from 5 to 28 pmp) in different regions of the country. To identify the barriers of organ donation, we surveyed 587 physicians involved in brain death diagnosis from regions with low (LDR) and high donation rates (HDR). Physicians from LDR were twice more reluctant to start diagnostic procedure when clinical signs of brain death were present (14% versus 5.5% physicians from HDR who would not diagnose death, resp.). Twenty-five percent of LDR physicians (as opposed to 12% of physicians from HDR) would either continue with intensive therapy or confirm brain death and limit to the so-called minimal therapy. Only 32% of LDR physicians would proceed with brain death diagnosis regardless of organ donation, compared to 67% in HDR. When donation was not an option, mechanical ventilation would be continued more often in LDR regions (43% versus 26.7%; P < 0.01). In conclusion, low donation activity seems to be mostly due to medical staff attitude.