Are we taking proper care of living donors? A follow-up study of living kidney donors in Poland and further management proposal.

OBJECTIVE: The first kidney transplantation was performed in Poland in 1966. Since that time approximately 11,000 patients have undergone the procedure, but most of them have received the kidney from deceased donors; only 342 procedures utilized living donors (LD; 2.7%). The aim of this study was to review the results of a LD follow-up in Poland. PATIENTS AND METHODS: A questionnaire was sent to 11 centers that had performed 197 LD kidney transplantations during the last 10 years. The donors, who were all genetically or emotionally related, were 23 to 61 years old. No donor showed an abnormality regarding cardiovascular function or metabolic abnormalities. RESULTS: The 6 centers that responded reported data on 118 donors. In 2 centers no donor follow-up was available. Eleven of 118 donors did not attend the control visits. Follow-up of the remaining donors ranged from 2 to 8 years. Four donors died at 4 to 5 years after nephrectomy due to cerebral hemorrhage, brain tumor, stomach cancer, or car accident. The overall mean serum creatinine had increased from 0.8 to 1.25 mg/dL, but 2 patients displayed a value >2 mg/dL. The calculated creatinine clearance (MDRD formula) had decreased from 95 to 65 mL/min (P < .05). In 3 donors proteinuria (>0.6 g/24 h) was observed at 3 to 5 years after donation. Of 3 patients who experienced mild hypertension, 2 required treatment. The remaining donors showed normal blood pressures. CONCLUSIONS: Since 2007, when the Living Donor Registry was introduced by law, transplant centers have been obliged to report data on each LD procedure together with follow-up data. All donors are life-insured (by Alianz SA) for 3 months from the time of transplantation. Stepwise interventional reno- and cardioprotection programs have been introduced after nephrectomy for LD, especially those with metabolic abnormalities at the time of donation.

The assessment of residual kidney function after living donor nephrectomy.

BACKGROUND: The number of patients on the waiting list for kidney transplantation is increasing as a result of the cadaveric donor shortage. One way to expand the pool is living donor transplantation. However, only 2% of kidney transplants in Poland come from living-related donors. AIM: We sought to assess residual renal function, incidence of hypertension, and proteinuria among living kidney donors. PATIENTS AND METHODS: Between 2004 and 2007, we performed 46 living donor open nephrectomies. The mean age of the kidney donor was 39 years (range, 25-57). The donors were predominantly females (61%). Mean hospitalization time was 8 days (range, 4-22). Nine donors did not report for follow-up visits. The observation periods ranged from 1 to 24 months. Physical examination, blood and urine tests, as well as ultrasound scans were performed before nephrectomy and at every follow-up visit (1, 3, 12, and 24 months post operatively). RESULTS: Mean creatinine concentration was higher at 3 months after nephrectomy than preoperatively (P < .05). Mean creatinine clearance according to Cockroft-Gault formula and mean creatinine clearance according to abbreviated modification of diet in renal disease equation (aMDRD) decreased after donation by 30% (P < .05). No cases of proteinuria were observed. Hypertension occurred in 1 donor (2.7%). CONCLUSION: Living kidney donation resulted in a reduced creatinine clearance in the donor. Follow-up of living kidney donors is essential to determine risk factors for deterioration of residual kidney function.

Chlamydia pneumoniae infection in patients after kidney transplantation treated with spiramycin.

INTRODUCTION: Previous research has pointed to a role of Chlamydia pneumoniae infection in the development of chronic renal allograft dysfunction, chronic liver rejection, and vasculopathy in the transplanted heart. The aim of this study was to evaluate the presence of C. pneumoniae prior to and after kidney transplantation as well as to determine the role of spiramycin therapy among kidney transplant recipients. MATERIALS AND METHODS: The study group consisted of 50 patients (25 pairs) who received kidney transplants from cadaveric donors. One of the 2 kidneys from a donor was transplanted to a patient randomized to spiramycin (2 x 3 million U/d orally for 3 months; group S) and the other to a patient assigned as control (group C). Markers of infection were assessed on day 1 posttransplantation and 3 months later (average, 94 days). All 50 patients were examined for the presence of bacterial DNA in peripheral blood leukocytes using real-time polymerase chain reaction (PCR) and for titers of serum anti C. pneumoniae immunoglobulin (IgG) and IgA antibodies using microimmunofluorescence (MIF). C. pneumoniae infection was diagnosed by the presence of C. pneumoniae DNA in peripheral blood leukocytes or positive antibodies of both classes. RESULTS: C. pneumoniae infection was initially diagnosed in 14 patients among group S and 8 patients among group C (P = not significant [ns]) and after 3 months in 12 and 9 patients, respectively (P = ns). Conversion from positive to negative C. pneumoniae status occured in 7 patients among group S and 1 patient among group C (P = .04). Conversion from negative to positive C. pneumoniae status occured in 5 patients from group S and 2 patients from group C (P = ns). CONCLUSIONS: These results suggest a possible role for spiramycin treatment of C pneumoniae infection in kidney allograft recipients. C. pneumoniae infection diagnosis and treatment should be considered to be routine for every patient awaiting transplantation.

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.

Significance of urodynamic assessment of lower urinary tract in dialysis patients before renal transplantation.

INTRODUCTION: Some dialyzed patients suffer from lower urinary tract (LUT) anatomic and functional disturbances. Complete LUT assessment should be performed to decide whether they can be included on the waiting list, because such disorders, if not diagnosed and properly treated before transplant, may lead to graft loss. PATIENTS AND METHODS: Based on data in the medical records of 4170 dialysis patients, 535 were selected for further investigation: 265 patients after undergoing urethrocystography or urethrocystoscopy, were included on the waiting list for transplantation and 145 patients underwent nephroureterectomy owing to reflux, nephrolithiasis, polycystic renal disease, or hydronephrosis. Five patients with urethral or bladder neck stricture underwent urethral dilation or bladder neck incision. These patients were also ultimately listed for transplantation. Twenty-two patients, with serious LUT disease were qualified for kidney transplantation after extra-anatomic urine outflow. Ninety-eight patients underwent a urodynamic study (URD) to assess LUT disturbances. RESULTS: Of 535 studied patients, 460 (86%), including those who underwent surgical or pharmacologic treatment, were ultimately listed for kidney transplantation. Out of 98 patients who underwent a URD, 45 (46%) were included for kidney transplantation, and 47 for transplantation with atypical urinary outflow. Six patients were excluded from transplantation owing to refusal of investigations or serious contraindications. CONCLUSIONS: All potential kidney recipients should undergo proper evaluation of the LUT before being qualified for kidney transplantation. This study allows selection of patients who should undergo surgical and/or pharmacologic treatment before transplantation.

Significant increase in the isolation of glycopeptide-resistant enterococci from patients hospitalized in the transplant surgery ward in 2004-2005.

Enterococci despite their low pathogenicity are the third cause of hospital infections. Enterococci resistant to glycopeptides present special risks. The aim of this work was to determine the frequency of isolates of all enterococci versus enterococci resistant to glycopeptides from patients in the Transplant Surgery Ward. Moreover, vancomycin-resistant enterococci (VRE) were characterized with respect to the type of van and ddl genes as well as vancomycin and teicoplanin MIC values. Among 160 enterococcal strains isolated in 2004, only 2 were resistant to glycopeptides (1.3%). In 2005, among 244 enterococci, 44 strains were resistant (18%). All resistant strains were Enterococcus faecium, as confirmed by detection of the ddl gene specific for E. faecium. Moreover, among all enterococci isolated from these patients, E. faecium dominated (over 50% in 5 subsequent years). All examined VRE possessed VanA type of resistance with high vancomycin and teicoplanin MIC values. All of them possessed the vanA ligase gene. The investigated VRE were characterized by high resistance to most antibiotics: penicillin and amoxicillin, rifampicin, ciprofloxacin, and high concentrations of streptomycin, but susceptible to linezolid and quinupristine/dalfopristine. Strains differed in their susceptibility to tetracycline, nitrofurantoin, and high concentrations of gentamicin.

Occurrence of glycopeptide-resistant enterococci in transplant medicine internal wards in 2001-2005.

The appearance of vancomycin-resistant enterococci (VRE) has caused serious therapeutic problems. In Poland, the frequency of VRE isolation is lower than in the United States or some other European countries. The aim of our work was to analyze the occurrence and characterization of VRE isolated from patients of 2 transplant medicine wards. These wards contained liver or kidney transplant patients. This study examined 5 years, including 235 to 313 enterococcal isolates per year. In 2001-2002, none of the isolated enterococci was confirmed as VRE, which appeared in 2003 (11 strains) and continued on a similar level (from 4% to 6%) in the next 2 years. Among all isolated enterococci, Enterococcus faecalis predominated. In 2003 and 2004, the numbers of E. faecium and E. faecalis among isolated VRE strains were similar, but in 2005, we observed significant predominance of E. faecium. Among VRE strains examined by polymerase chain reaction for the presence of vanA, vanB, vanD, vanE, and vanG ligases, only vanA was found in all cases. The examined strains represented several patterns of resistance to other antibiotics.

Intraoperative blood flow measurements in organ allografts can predict postoperative function.

A reliable method to recognize the extent of ischemia/reperfusion injury in transplantation is needed in order to tailor the immunosuppressive scheme to the needs of a damaged organ. This study sought to assess the correlation between the total and the parenchymal blood flow into a transplanted kidney (n = 71) or liver (n = 15) shortly after revascularization with the early function of the organ after transplantation. The total blood flow in the renal artery in kidney recipients or in the hepatic artery and portal vein in liver recipients was measured by an electromagnetic flowmeter. The parenchymal blood flow (in several parts of the transplanted organ) was assessed using a laser-Doppler flowmeter. Two measurements were always taken after revascularization (5 to 60 minutes apart). Vascular resistance (VR) as calculated by the difference between the mean arterial pressure (MAP) and the central venous pressure (CVP) was correlated with immediate kidney or liver function parameters. Neither total renal blood flow (RBF) nor VR was different between the immediate function (IF) and delayed graft function (DGF) groups of kidney transplant patients. However, the cortical (parenchymal) blood flow was significantly greater in the IF than the DGF group at 5 minutes: 29.98 +/- 6.13 mL/min/100 g vs 23.56 +/- 6.46 mL/min/100 g (P < .001). The difference was even more significant at 35 minutes: 33.94 +/- 7.47 mL/min/100 g vs 15.47 +/- 3.34 mL/min/100 g (P < .0001). Among liver transplant patients, the results suggested a correlation between hepatic arterial blood flow and early graft viability and function. The most reliable predictor of early graft function was the portal blood flow, which correlated with the volume of secreted bile as well as the bilirubin, and transaminase levels and coagulation profile. Further studies must confirm the value of measurements of total and parenchymal blood flow in organ transplant recipients.

Long-term results of kidney transplantation from HCV-positive donors.

BACKGROUND: Due to the shortage of organs for transplantation, procurement of kidneys from marginal donors is inevitable. Not infrequently, these donors are infected with hepatitis C virus (HCV). AIM: We sought to determine the effect of transplanting kidneys from anti-HCV-positive donors to anti-HCV-positive recipients. PATIENTS AND METHODS: Among 765 procedures between 1994 and 2006, 259 kidney recipients were anti-HCV-positive, including 60 who received kidneys from anti-HCV-positive donors (HCV(+)/HCV(+) group) and the others, from seronegative donors (HCV(-)/HCV(+) group). The control group of 506 seronegative recipients received kidneys from seronegative donors (HCV(-)/HCV(-) group). All kidneys from anti-HCV-positive donors were preserved with machine perfusion. We investigated recipient liver function tests (LFTs; alanine aminotrasferase, aspartate aminotransferase; alkaline phosphatase, and bilirubin), graft survival, and patient survival. RESULTS: No significant difference was observed between the groups among the biochemistry results (LFTs, creatinine at 5 years). No significant differences, were observed in patient survival, graft survival, or number of patients returning to dialysis. CONCLUSION: Transplantation of kidneys from HCV-positive donors to HCV-positive recipients did not influence long-term liver function, or long-term renal allograft function. This strategy enhances the availability of transplantation as means of end-stage renal disease treatment.

Surgical site infections in liver recipients in the early posttransplantation period: etiological agents and susceptibility profiles.

OBJECTIVE: This study evaluated the frequency of microbial isolates and their susceptibility profiles from cultures at the surgical site of 83 liver recipients in the early posttransplantation period. PATIENTS AND METHODS: We prospectively collected microbiologic culture data on 83 adult patients undergoing orthotopic liver transplantation (OLT) using standard procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was performed by the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: All patients were followed prospectively for the first 4 weeks after surgery. Among 284 microbial isolates from clinical surgical site samples in 80 liver recipients, cultures were positive in 110 samples. The most commonly isolated species were: Gram-positive cocci (n = 222 isolates, 78%) with dominance of methicillin-resistant coagulase-negative staphylococci (MRCNS; 42%) and high-level aminoglycoside-resistant enterococci (HLAR strains; 24.3%). Gram-negative bacteria were identified in 21.5% of positive cultures, including 30 strains (24%) from the Enterobacteriaceae family, with 13.3% of extended spectrum beta-lactamase producers [ESBL(+)]. Significant differences (P = .0012) were observed during the analysis of changes in the occurrence of Gram-positive bacteria isolated from the surgical site in the first week versus the second to the end of the fourth week. CONCLUSION: Gram-positive bacteria predominated as 78% of isolates.

Bacteria isolated from bile samples of liver recipients in the early period after transplantation: epidemiology and susceptibility of the bacterial strains.

OBJECTIVE: We estimated the frequency and susceptibility to antibacterial agents of bacterial isolates from bile samples obtained from 83 liver recipients in the early period after transplantation. PATIENTS AND METHODS: We prospectively collected data on 83 adult patients undergoing orthotopic liver transplantation (OLT), including bile samples taken during the first 30 days after OLT from adult liver recipients suspected to have bile infections. The isolation/identification of cultured bacteria was performed according to standard microbiological procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: Among 210 bile samples obtained from 79 liver recipients, bacterial cultures were positive in 110 samples from 59 (75%) recipients yielding 156 bacterial strains. The most commonly isolated species were as follows: gram-positive cocci (109 isolates) with dominance of coagulase-negative staphylococci (52%) and enterococci (36%); and gram-negative bacteria, 21 strains from the Enterobacteriaceae family and 14 of non-fermenting rods. We identified some multidrug-resistant (MDR) bacterial strains. In the first week after OLT, we investigated samples from 59 patients, yielding 36 bacterial strains. From the second to the end of the fourth week after OLT, 120 bacterial strains were isolated from 65 recipients. CONCLUSION: Gram-positive bacteria comprised 68.5%. The dominance of MDR gram-positive bacteria may be related to selection by perioperative antibiotic prophylaxis.

Detection of Clostridium difficile in stool samples from patients in the early period after liver transplantation.

OBJECTIVE: We examined the frequency of detection of Clostridium difficile (CD) toxins compared with the recovery of C. difficile in stool specimen cultures among orthotopic liver transplant (OLT) patients with nosocomial diarrhea in the early period. MATERIALS AND METHODS: The study included stool samples obtained during the first 30 days after OLT in adults who were suspected of CD-associated diseases. The identification of cultured CD strains was performed by standard microbiological methods. The presence of CD toxins was assayed using a commercial immunoassay. RESULTS: All patients were followed prospectively for CD infections from the date of OLT for the first 4 weeks after surgery. Among 54 samples, 16.7% were culture-positive for CD. CD toxins were tested on 54 samples, yielding 63% toxin-positive samples and 30% toxin- and culture-negative results. In the first week after OLT, samples from 19 patients were subjected to CD investigation. Among 19 samples positive for toxin, 52.6% of all samples were culture-negative. We analyzed 35 samples from the second to the fourth week after OLT in 31 recipients. Among 35 samples, 68.6% and 25.7% were positive for CD toxin and for culture, while 20% of samples were negative for toxin and culture. CONCLUSION: In our study, 63% of samples were toxin-positive with 16.7% yielding growth of CD and 30% being negative for toxins and cultures.

Etiological agents of bacteremia in the early period after liver transplantation.

Bacteremia is one of the major infections in orthotopic liver transplantation (OLT). The study of 83 adults who underwent OLT from 2001 to 2004, included patients followed prospectively from the day of transplantation to 4 weeks after the procedure by bacteriological cultures. The microorganisms were investigated according to standard National Committee for Clinical Laboratory Standards (NCCLS) procedures. Blood samples were examined in 59 recipients (71.1%) before and in 76 patients (91.6%) during the month after transplantation. Among 249 investigated samples, 96 were positive, as cultured from 19 recipients before OLT and 48 patients afterward. The most common were Gram-positive cocci (n = 71) and coagulase-negative staphylococci (n = 52), including methicillin-resistant coagulase-negative staphylococci (MRCNS). Enterococcus spp. occurred in 9 isolates (high-level aminoglycoside-resistant enterococci [HLAR] strains were cultured). We cultured the Enterobacteriaceae family (n = 16 isolates) and (n = 15 isolates), Gram-negative nonfermenting rods some of which were extended spectrum beta-lactamase producing [ESBL(+)] strains. The predominance of Gram-positive cocci was caused by CNS, and the use of prophylaxis to reduce Gram-negative bacteria. The increased rate of isolation of bacteria with multidrug resistance (MDR) to antimicrobial agents may be due to their frequent use for prophylaxis of bacterial infections in OLT. These MDR bacterial strains caused severe BSI after OLT.

Early hyperglycemia after allogenic kidney transplantation.

BACKGROUND: The aim of the study was to establish the impact of early hyperglycemia on development of diabetes mellitus (DM) in patients after kidney transplantation and to evaluate possible risk factors for post-transplantation DM. We also sought to assess the impact of early hyperglycemia and DM on the renal graft function in the long term (3 year follow-up). MATERIAL/METHODS: 1200 transplant patients from one center, were followed up for 3 years. The rate of chronic rejection, CMV infection, hypertension and dyslipidemia were analyzed. The renal allograft function was examined and pancreatic function peptide C concentration was determined. RESULTS: Early hyperglycemia (within first week after transplantation) was detected in 76 out of 1131 patients (6.7%). In this group within three years observation posttransplantation diabetes mellitus (PTDM) was observed in 57 patients (relative risk 75%). In comparison, transplanted patients with good early glucose control had 8% risk of developing DM within the same period after transplantation. In addition early hyperglycemia predisposed to worse renal graft function and higher proteinuria. The incidence of hypertension as well as the rate of CMV infection was comparable in the DM group and in non-DM patients. PTDM patients had higher values of serum peptide C concentration (p < 0.05), additionally hyperinsulinemia was observed. The kidney allograft function assessed as serum creatinine level was significantly impaired after 3 years in PTDM group compared to non-DM patients. CONCLUSIONS: Our date show the importance of normal glucose concentration in early period after transplantation as predictive factor for diabetes mellitus development and worsening of transplanted organs.

Organ donation in Poland 2006.

Organ transplantation program has been slowly developing over last 30 years. The number of DD (deceased donors) stabilized on the level of approximately 13/million of population. Multiorgan donation has been 45%, due to some problems with donor management. Polish Transplant Coordinating Center POLTRANSPLANT which is responsible for organization of procurement, organ allocation and providing several registries (registry of objections, registry of transplantation, waiting lists of potential organ recipients etc). National data on organ donation and transplantation are each year submitted to the Ministry of Health and the National Transplantation Council which is the Advisory Committee to the Minister.

Insulin resistance in kidney allograft recipients treated with calcineurin inhibitors.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is one of the main complications observed in patients after organ transplantation. The incidence of PTDM in transplant recipients is about 9 times higher than in general population. The reported incidence of PTDM varied throughout the years due to different diagnostic criteria of diabetes mellitus. Nowadays the rate of PTDM amounts to 3-19%. MATERIALS/METHODS: 1270 patients after kidney transplantation, who remained under medical care in the outpatient service at the Transplantation Institute in Warsaw, were taken into consideration. The investigated group comprised 207 patients. 133 of them developed DM that constitutes the incidence of PTDM at 10.5%. RESULTS: In the present study several risk factors that are important for PTDM development were observed: male gender, HLA A3, family history of DM, increased body weight (rather than BMI only), tacrolimus--based immunosuppressive regimen, early hyperglycemia. Patients with PTDM developed hypertension more frequently, had higher serum triglycerides levels in the period before the onset of diabetes. The rate of acute rejection episodes in this group was higher compared with the nondiabetic transplant controls. The PTDM group presented with worse graft function and higher levels of proteinuria in 1-year observation. Tacrolimus--based therapy led to higher peripheral insulin resistance and hyperinsulinemia in comparison to cyclosporine--based regimen. CONCLUSIONS: The proper management of the above described risk factors and the right treatment of PTDM may considerably influence life expectancy rate and quality of life in transplanted patients.

Extreme attitudes toward organ transplantation: how do supporters and opponents of this method of treatment differ in Poland?

BACKGROUND: Many medical professionals share the opinion that the negative social attitudes toward transplantation are the basic cause of the deficit of organ from deceased donors. Although public opinion polls in Poland invariably reveal overall acceptance of transplantation, it is extremely difficult to procure organs. The purpose of this study was to compare the attitudes of supporters and opponents of organ transplantation. MATERIALS AND METHODS: In social psychology, attitude is defined as a relatively stable inclination toward a positive or negative relation to a person or an object. It was assumed that positive attitudes are favorable as regards transplantation, whereas negative attitudes constitute a social obstacle to this method of treatment. The survey conducted between May and August 2002 included a representative sample of 1000 Poles over 15 years of age. The first part of the survey measured the general attitude toward transplantation on a rating scale ranging from "definitely agree" to "definitely disagree." RESULTS: We distinguished two extreme attitudes, ie, supporters and opponents. CONCLUSIONS: The attitudes of supporters were mainly cognitive, whereas the attitudes of opponents were dominated by negative emotions associated with fear of death, psychological trauma, and physical injury which led to avoidance behavior, passive resistance, and selective and biased information processing. Opponents often concealed or belittled their standpoints and were reluctant to discuss transplantation issues. Their behavior was more passive, and their familiarity with the medical and legal aspects of transplantation was relatively poor compared with supporters.

Questionnaire regarding the knowledge of the rules of organ procurement from cadaveric donors for transplantation directed to the directors of medical institutions in Poland.

We assessed the level of knowledge of organ procurement regulations among the directors of medical institutions in Poland. We also sought to promote the objection form, and the activity of the Central Register of Objections. A questionnaire consisting of 10 questions was sent to 381 random medical health care institution directors countrywide. In 89% of surveyed institutions, the written text of the organ procurement regulations was available and 94% of directors knew the forms of objection, but in 26% of institutions the form was not available and in 14% it was never obtainable. In the medical institutions directors' opinions, the estimated number of objections is 13% of the population in Poland. Organ transplantation is a form of treatment most medical institutions are familiar with, but the matter of donation is not as well known as transplantation, as observed in 48% of questioned institutions.

Increased mRNA expression of transforming growth factor beta in the arterial wall of chronically rejected renal allografts in humans.

INTRODUCTION: Transforming growth factor beta (TGF-beta) has an established role in interstitial damage of renal transplants during chronic rejection (CR). However, its involvement in transplant vasculopathy is not clear. The aim of the study was to assess TGF-beta gene expression in the walls of large-caliber arteries within chronically rejecting renal allografts. We evaluated associations between gene expression of this factor and intimal thickness or clinical data. MATERIAL AND METHODS: Renal artery samples of kidney allografts were obtained from 20 hemodialysis patients with end-stage renal graft disease due to CR, who were undergoing graftectomy. The control group included 32 hemodialysis patients with end-stage renal disease, undergoing nephrectomy due to autosomal dominant polycystic kidney disease (n = 12), chronic pyelonephritis (n = 13), or kidney limited tumor (n = 7). Gene expression of TGF-beta was measured using real-time PCR. RESULTS: TGF-beta mRNA expression was 3.25-fold higher in CR than in control patients (P < .001). Expression of mRNA for this cytokine was not influenced by the following factors: intimal thickness; age; serum cholesterol, triglycerides and glucose; BMI; graft survival; time of dialysis before transplantation; total ischemic time; immunosuppressive regimen; incidence of acute rejection episode; panel reactive antibodies; and period of dialysis before graftectomy. TGF-beta is involved in neointimal formation in CR.

IgA nephropathy in kidney allograft recipients-therapeutic perspective.

INTRODUCTION: A growing number of patients are losing their kidney allografts due to glomerulonephritis. Although posttransplant IgA nephropathy (IgAN) is regarded as benign, it may lead to late allograft loss in a substantial number of patients. The aim of this study was to evaluate the influence of posttransplant IgAN on long-term transplantation outcomes, risk factors for progression of graft dysfunction, and effectiveness of therapeutic interventions. PATIENTS AND METHODS: We evaluated, potential risk factors for accelerated graft loss among 27 kidney allograft recipients with posttransplant IgAN, comparing graft survival in a control group matched for population and transplantation-related parameters. We evaluated the effectiveness of therapeutic interventions regarding immunosuppressive regimen, and hypertension control including angiotensin converting enzyme inhibitor (ACEI) usage with Kaplan-Meier, Cox proportional hazard plots, and log-rank tests in statistical analyses. RESULTS: Compared with the control group, patients with IgAN experienced a 6.57 higher risk for dialysis dependence (P < .01, 95% CI 1.4 to 30.83). The risk for accelerated graft loss in the course of IgAN was associated with graft dysfunction (RR = 2.16 for additional 1 mg/dL of serum creatinine at glomerulonephritis presentation; P < .03, 95% CI 1.2 to 4.36) and intense proteinuria as evidenced by a RR = 4.67 for the presence of the nephrotic syndrome (P < .05, 95% CI 0.95 to 22.8). Immunosuppression enhancement resulted in a significantly decreased risk of dialysis dependence, namely, RR = 4.76 (95% CI 1.12 to 20, P < .04). With ACEI treatment there was a tendency for a 2.8-fold decreased risk of dialysis dependence, without reaching statistical significance (P = .14). CONCLUSIONS: Patients with posttransplant IgAN may benefit from intensifying maintenance immunosuppression, which slows progression to end-stage graft dysfunction.