J. Pazik

Successful Pregnancy Outcome after In Vitro Fertilization in a Kidney Graft Recipient: A Case Report and Literature Review

BACKGROUND Successful spontaneous pregnancy in a kidney graft recipient is regarded as a sign of full recovery. The crucial factors determining positive outcome are optimizing time of conception and multidisciplinary team care. However, there are only a few reports dealing with in vitro fertilization (IVF) outcomes in organ recipients. CASE REPORT A 34-year-old living donor kidney recipient with primary infertility due to bilateral tubal obstruction was referred to our clinic. Transfer of 2 embryos was conducted after a long stimulation protocol with GnRH and rFSH, and a viable singleton pregnancy was confirmed by subsequent ultrasound examination. Pregnancy complications were: chronic hypertension, fetal intrauterine growth restriction, and severe anemia requiring blood transfusions and erythropoietin treatment. In the 34th week of gestation the patient presented with worsening of blood pressure control. A male newborn, 1810 grams weight and 10 points Apgar score was delivered by cesarean section. Although our patient was qualified for the IVF program with signs of suboptimal graft function, it was stable during the ovarian stimulation protocol. Fortunately, in the second half of the pregnancy only mild creatinine rise and proteinuria <1 g/day were observed. CONCLUSIONS IVF may be a good treatment option in female kidney graft recipients. It does not necessarily lead to graft function deterioration and it provides multidisciplinary specialized care, allowing for delivery of a healthy newborn.

A Threat of the Klebsiella Pneumoniae Carbapenemase–Producing Strains Among Transplant Recipients

BACKGROUND Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased therapeutic failure and mortality. Our laboratory recognized several strains producing KPC, most of which originated from transplantation ward patients. MATERIALS AND METHODS All strains of K pneumoniae resistant to at least 1 carbapenem isolated in 2010 were examined for KPC production by disc diffusion and then verified by molecular methods. RESULTS All positive strains originated from 7 patients. Six of them were from transplantation wards. None of the KPC-producing strains was isolated from the patients blood. CONCLUSIONS A quick, accurate diagnosis of KPC-producing strains enabled immediate isolation of carriers or infected persons. Isolation prevented spread of dangerous strains among immunocompromised patients and reduced the possibility of serious infections.

Human herpesvirus-6 in renal transplant recipients: Potential risk factors for the development of human herpesvirus-6 seroconversion

Herpesviruses, including human herpesvirus-6 (HHV-6), reactivate and have the potential to be pathogenic in immunocompromised patients. Little information is available regarding the correlation between immunosuppressive therapy and HHV-6 seroconversion after organ transplantation. Serum samples obtained from 120 kidney and kidney/pancreas transplant recipients were tested to explore the potential risk factors for developing HHV-6 infection including types of immunosuppression and induction/rejection therapy. Stored serum samples obtained prior to and at the 2nd, 4th, 12th and 48th weeks after transplantation were tested for anti-HHV-6 immunoglobulin (Ig)M antibodies using indirect immunofluorescence assay. Prior to transplantation and 48 weeks after transplantation the sera were additionally tested for anti-HHV-6 IgG using enzyme-linked immunoassay. Ninety-one percent of 120 recipients were HHV-6 IgG-positive before transplantation. One hundred seven of 120 patients were anti-HHV-6 IgM-negative before transplantation. Primary/secondary HHV-6 seroconversion occurred in sera of 46.6% of these 107 patients. HHV-6 seroconversion most frequently occurred 2 to 4 weeks after transplantation. There was no significant relationship between HHV-6 seroconversion and the treatment with methylprednisolone (MP). The incidence of HHV-6 seroconversion was significantly higher in subjects who were treated with the regimens including Daclizumab or Sirolimus as compared with those who were on other protocols. HHV-6 seropositivity in the Polish population of organ transplant recipients is very high. We demonstrated a trend toward association of HHV-6 seroconversion with type of immunosuppressive therapy.

Pregnancy after kidney and liver transplantation: its outcome and effect on the graft, mother, and neonate.

BACKGROUND The influence of pregnancy on graft function in patients after solid organ transplantation is still uncertain. MATERIAL AND METHODS Our study is based on a group of 78 cases after liver (LTR) and/or renal transplantation (RTR) with 91 deliveries in the past 12 years in the 1st Department of Obstetrics and Gynecology, Warsaw Medical University. We compared duration of pregnancy, mode of delivery, weight of neonates, and graft function. RESULTS Rate of preterm delivery was very high (74% RTR and 43% LTR). The average duration of pregnancy was shorter in the RTR than in the LTR group (34.7 vs. 36.8 p<0.001) with a high rate of cesarean sections (81.4% in RTR and 68.1% in LTR). Birth weight in LTR (2898 g) was higher than in RTR (2248 g) (p<0.0001). Currently, 29 RTR and 38 LTR have preserved graft function. Thus, graft survival in the study group is longer than in the general RTR or LTR population. CONCLUSIONS Pregnancy after kidney or liver transplantation does not seem to increase the risk of graft loss, but is associated with a higher risk of maternal and fetal complications. In our data these complications occur more often in the RTR group.

Arteriolar Hyalinization in Implantation Kidney Biopsies as a Predictor of Graft Function

The shortage of organs suitable for transplantation has caused a constant evolution of donor acceptance criteria, making an implantation biopsy a valuable tool to predict kidney allograft survival. Preimplantation vascular changes may be divided into sclerosis or intimal fibrous thickening or arteriolar hyalinization. Increasing evidence has indicated their impact on graft function. The aim of this study was to evaluate the significance of preimplantation arteriolar hyalinization for the stability of kidney allograft function. Among a prospective cohort study of 53 kidney recipients (implantation: 2006-2007) who showed serum creatinine values between 1 and 2 mg/dL at 3 months after engraftment, the mean observation time was 24 +/- 8.7 months. At the end of the observation, kidney function as defined by the estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFR C-G) was significantly diminished in individuals with preimplantation evidences of arteriolar hyalinization (mean values: 51.2 +/- 14.8 and 62.0 +/- 16.7, respectively; P < .03) or serum creatinine concentrations (1.76 +/- 0.36 vs 1.51 +/- 0.48 mg/dL; P < .09). The negative influence of arteriolar hyalinosis on allograft function was time-dependent; an early satisfactory filtration rate did not preclude progressive kidney dysfunction.

C4d complement split product expression in chronic rejection of renal allograft

Chronic allograft rejection remains the major cause of late renal graft loss. Its pathogenesis is complex, depending on both immunological and nonimmunological factors. An important role in development of chronic rejection is ascribed to an ongoing immunological reaction mainly of the humoral type. C4d complement split product, as a stable fragment of complement degradation activated by antigen-antibody complexes, is considered to be an indicator of humoral activity in allografts. The aim of the present study was to establish a correlation between C4d expression and morphological findings specific for chronic rejection among biopsy specimens from patients with deteriorating graft function versus protocol biopsy specimens versus biopsy specimens of native kidneys with glomerular diseases. C4d deposits in peritubular capillaries and glomeruli were observed in 83% of patients with morphological changes of chronic rejection. No C4d expression was found in the protocol biopsy group. C4d deposits in glomeruli localizations were found in kidneys from patients with glomerulopathies; the pattern of distribution was similar to that for antibodies characteristic for glomerulonephritis. There was a positive correlation between C4d expression and morphological features of chronic rejection. In our opinion, only peritubular capillary localization is specific for a rejection process; glomerular localization is nonspecific and probably secondary to antigen-antibody complex deposition in course of some types of glomerulopathies.

CTX-M and TEM as Predominant Types of Extended Spectrum β-Lactamases Among Serratia marcescens Isolated From Solid Organ Recipients

BACKGROUND Serratia marcescens is an important pathogen in hospital infections since organisms resistant to multiple antimicrobials pose a special threat particularly among transplant patients. The aim of this work was to assess the number of strains producing beta-lactamases with extended spectrum (ESBL) among S. marcescens isolated from our patients. MATERIALS AND METHODS We investigated S. marcescens isolated from 2005 to 2008 for ESBL. The phenotype methods were applied and additionally we chose strains for polymerase chain reactions using primers for the most popular types of ESBL. RESULTS Over the investigated time, 257 patients were infected with S. marcescens with 188 (73%) displaying an ESBL-positive phenotype. A Molecular analysis showed that most of them produced both CTX-M and TEM beta-lactamases. In the last year, the percentage of ESBL-producing strains decreased, but also in the last year, we isolated S. marcescens resistant to carbapenems from three patients. CONCLUSIONS The CTX-M type of ESBL predominated among ESBLs produced by strains of S. marcescens. The appearance of strains resistant to carbapenems is alarming.

Safety and Tolerance of Sodium Mycophenolate in Patients After Renal Transplantation—An Observational Study

BACKGROUND Enteric-coated mycophenolate sodium (EC-MPS) was developed as an alternative agent to mycophenolate mofetil (MMF), aimed at reduction of gastrointestinal (GI) complications. METHODS Seventy-four patients (mean age 42.3 years) switched from MMF to MPS were included in the study and followed-up for 3 months (Visit 0, Visit 2 after 1 month and Visit 3 after 3 months). The mean time from transplantation to switch was 3.7 years. During Visit 2 and 3 the following were recorded: impact of treatment change on the severity of GI symptoms (4 point scale: 1-worsening, 2-no change, 3-improvement, 4-resolution), EC-MPS tolerance, adverse events (AEs), patient compliance and physician satisfaction with treatment (4 point scale: 1-bad, 2-fair, 3-good, 4-very good). RESULTS Sixty-three patients completed the study (85.1%). EC-MPS dose ranged from 720 to 1440 mg. GI symptom severity score averaged at 3.41. Symptoms most commonly compelling a conversion were: abdominal pain, diarrhea, abdominal colic, nausea, anorexia and vomiting. Out of 175 complaints, 144 (82%) either improved or resolved, 5 (2.86%) aggravated, and 25 (14.86%) persisted. Patient compliance and mean physician satisfaction score averaged at 3.70 and 3.02 at Visit 3, respectively. 9 AEs (2 severe) were reported. Causal relationship with the medication was suspected in 5 cases (1 case of SAE). The most common AEs were: anemia, infection (including sepsis), GI symptoms (abdominal pain, diarrhea). CONCLUSIONS The following was concluded in our study: (1) sodium mycophenolate is well tolerated; (2) after switching from MMF to EC-MPS, gastrointestinal symptoms alleviated; (3) EC-MPS is a safe medication, with a low adverse events rate.

Lymphocyte counts in kidney allograft recipients are associated with IMPDH2 3757T>C gene polymorphism.

Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme for de novo synthesis of guanine nucleotides, is required for lymphocyte proliferation. Inhibition of IMPDH by mycophenolic acid (MPA) constitutes part of an immunosuppressive therapy in kidney allograft recipients. The 3757T>C polymorphic variant (rs11706052) of the IMPDH2 gene, which encodes 1 of 2 IMPDH isoenzymes, has been associated with increased IMPDH activity and reduced ability of MPA to exert antiproliferative effects on lymphocytes. The association of IMPDH2 3757T>C SNP with posttransplant courses of kidney allograft recipients remains unclear. Therefore, the aim of the present study was to evaluate associations between this single nucleotide polymorphism and common posttransplant complications among Polish kidney allotransplant recipients. We observed that the frequency of IMPDH2 3757C allele in this group (n=177) did not differ significantly from a control cohort representing the background population of Poland (n=550). There were no significant differences between patients carrying the IMPDH2 3757CT and TT genotypes with respect to acute rejection risk, neutropenia, or incidences of serious infections or gastrointestinal side effects. However, we noted that the 3757C allele was associated with higher lymphocyte counts and a reduced incidence of lymphopenia among kidney allograft recipients. Our findings may be of practical significance to tailor immunosuppressive regimens in kidney transplant recipients.

Molecular epidemiology of vancomycin-resistant Enterococcus faecium infecting recipients of solid organs in the transplant surgery ward in 2005 and 2006.

BACKGROUND The aim of the investigations was to compare the vancomycin-resistant Enterococcus faecium (VREfm) strains obtained from our patients. MATERIALS AND METHODS Strains were compared using restriction fragment length polymorphism-pulsed field gel electrophoresis (RFLP-PFGE) of bacterial DNA. RESULTS VREfm infected 26 liver recipients, 22 kidney recipients, and 9 other surgery or nephrology patients. Only five strains possessed the vanB determinant. The PFGE analysis revealed two large and several small groups of related strains. CONCLUSIONS The PFGE analysis enabled the investigation of VRE epidemiology among patients after transplantation. Strains with similar patterns most probably originated from one source and clearly suggested an outbreak.