Effect of Thrombophilic Factors on Renal Graft Function: A Single-Center Experience.

BACKGROUND: Optimization of immunosuppressive therapy reduced the incidence of acute rejection, and therefore vascular complications, including graft thrombosis, which have emerged as the main cause of graft loss in the early post-transplant period. A thrombophilic condition may lead to renal graft loss. The aim of the study was to assess renal graft function in thrombophilic renal recipients receiving anticoagulation treatment. METHODS: This is a retrospective study including 29 renal recipients (ktx group) with a history of thrombosis and confirmed thrombophilic factor. Graft function was evaluated by median serum creatinine concentration at the third month after ktx (SCr1) and at the end of the observation (SCr2) with respect to hypercoagulability (factor V Leiden [FVL], mutation G20210A, antiphospholipid antibodies, deficiency of protein S [PS] or C [PC], factor VIII >200%). RESULTS: Recipients underwent retransplantation because of graft thrombosis (P < .001). They more often underwent urgent transplantation (P = .008), received induction therapy (P = .021), underwent an indication other than protocol biopsy (P = .001), or experienced acute rejection (P = .042). Differences in graft function (SCr2) were found at the end of observation (ktx group vs controls 1.9 mg/dL vs 1.3 mg/dL, respectively, P = .014). Multivariate analysis revealed inferior thrombophilic graft function in the model with SCr1 <2 mg/dL (odds ratio 0.07, 95% confidence interval 0.01-0.57, P = .014) and in the model with SCr2 <2 mg/dL (odds ratio 0.15; 95% confidence interval 0.04-0.54, P = .004). The incidence of antiphospholipid syndrome was 31%; FVIII, 31%; FVL, 24.1%; and PC/PS, 13.8%. After anticoagulation was introduced no thromboembolic events or bleeding complications occurred. CONCLUSION: Hypercoagulability is not a contraindication to ktx but may worsen graft function. Post-transplant care in thrombophilic recipients is demanding (retransplantation, immunization, protocol biopsy, anticoagulation), but is the only means by which to maintain a graft.

Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of Transplanted Kidney.

BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross-match-negative renal recipients with biopsy-proven ABMR composed the study group. Pulses of methylprednisolone (MP) and appropriate enhancement of net state of immunosuppression were applied in all individuals; 17/39 recipients were administered IVIG (IVIG group); the remaining 22/39 patients, identified to be nonadherent or unsatisfactorily immunosuppressed, were kept on the initial treatment (MP group). Serum creatinine concentration was obtained at each of 10 intended visits, and glomerular filtration rate (GFR) was estimated with the use of the standard Modification of Diet in Renal Disease (MDRD) formula. Generalized linear mixed model was used for statistical analysis. RESULTS: Renal function (modeled as linear slope of MDRD-based GFR change over time, separately for the pre- and post-intervention periods) improved significantly in IVIG-treated recipients. Pre-intervention slopes were -0.72 and -0.46 mL/min/mo for IVIG and MP groups, respectively (P = NS), whereas post-intervention the slopes changed to -0.03 and -0.47 mL/min/mo (IVIG and MP, respectively; P < .005). Within-group changes of slopes at the time of intervention were 0.69 and -0.01 mL/min/mo in IVIG (P < .01) and MP (P = NS) groups, respectively. The relative slope change (pre- to post-intervention) was 0.7 mL/min/mo in favor of the IVIG group (P < .033). None of the classic immunologic or nonimmunologic graft function predictors influenced GFR during 12 months of follow-up. CONCLUSIONS: IVIG improved graft function in renal recipients diagnosed with ABMR.

Dynamic Elastography in Diagnostics of Liver Fibrosis in Patients After Liver Transplantation Due to Cirrhosis in the Course of Hepatitis C.

BACKGROUND: Assessment of the dynamics and degree of liver fibrosis in patients after liver transplantation is a basic element in the process of determining transplant survival prognosis. It allows planning and early initiation of prophylaxis or treatment, which translates into increased chances of preventing cirrhosis and of long-term optimal function of the graft. The aim of this study was to compare the results of biopsy and dynamic elastography in diagnostics of transplanted liver fibrosis, as well as determination of the stiffness cut-off point for assessment of significant fibrosis. PATIENTS AND METHODS: The study included 36 patients who had undergone liver transplantation due to cirrhosis in the course of hepatitis C virus (HVC) infection. Fibrosis was assessed in bioptates according to the METAVIR score (F0-F4). Elastography was performed using FibroScan; receiver operating characteristic curve analysis was used to identify the cut-off point for significant fibrosis (≥F2). RESULTS: The median stiffness in kPa for the whole group F0-F4 was 6.3 (range 3.4-29.9); for ≥F2 it was 6.9 (3.4-29.9), whereas for F0-F1 it was 4.4 (3.5-8.0). It was demonstrated that the value of 4.7 kPa in elastography is a statistically significant cut-off point for differentiation between the groups F0-F1 and F2-F4 (sensitivity: 93%, specificity: 57%, positive predictive value: 90%, negative predictive value: 66%), area under the receiver operating characteristic curve: 0.746 (95% confidence interval: 0.53-0.95, P < .05). CONCLUSIONS: Elastography is a promising tool for noninvasive assessment of significant liver fibrosis in patients after transplantation due to cirrhosis in the course of hepatitis C; it allows reduction in the number of biopsies performed.

Antiphospholipid antibodies in renal allograft recipients.

BACKGROUND: Antiphospholipid antibodies (APLAs) are associated with an increased risk of thrombosis. The role of APLAs as a marker of thrombosis in renal recipients has not been established. We sought to determine the prevalence of APLAs in renal recipients and investigate their association with thrombosis. MATERIAL: The study included 37 renal recipients: 17 women and 20 men of ages 22-69 years. The 2 subgroups were one of patients without (n = 27; T-) and a second, with a history of severe thrombosis (n = 10; T+) subgroups, We determined lupus anticoagulant (coagulation methods) and anticardiolipin antibodies (ACL), anti-Beta2GlicoproteinI antibodies (anti-B2GPI), antiprothrombin antibodies (anti-PT) in immunoglobulin (Ig)G and IgM isotype using enzyme-linked immunosorbent assay. The determinations were made twice at a 6-months interval. The mean duration of follow-up was 12 months. RESULTS: The most commonly detected antibodies were anti-ß2GPI IgM (16.22%) and aCL IgG (13.8%). No differences were identified when the prevalence APLA was compared between T- and T+. A significant correlation was found between anti-ß2GPI IgM and aCL IgM (P = .0328); anti-ß2GPI IgM and aCL IgG (P = .0198) and aCL IgM and aCL IgG (P = .0252). No differences in serum creatinine were observed between the T- and T+ cohorts. During the follow-up, 2 female patients in the T+ produced APLAs and were treated with low-molecular-weight heparin. During follow-up one patient developed thrombosis (TMA), which led to graft loss. The other patient with normal renal graft function did not experience a recurrence of thrombosis. CONCLUSIONS: The prevalence of APLAs in renal transplant recipients was higher than in the general population. The study did not demonstrate any predictive value of APLAs as markers of thrombosis in renal recipients. Routine determination of APLAs is not necessary in all transplant recipients.

The significance of antiphospholipid antibodies in liver recipients.

BACKGROUND: The presence of antiphospholipid antibodies (APLAs) may be associated with increased thrombotic risk. Liver graft thrombosis may necessitate retransplantation. AIM: To determine the prevalence of APLAs among liver recipients and to investigate the relationship between APLAs and liver graft thrombosis. MATERIALS AND METHODS: We included 33 Caucasian patients aged 22 to 75 years who displayed stable liver graft function (21 women and 12 men). The patients were divided into 2 subgroups: high thrombotic risk subgroup T(-) and at low risk T(+) subgroups. The T(-) included 25 patients, T(+) included 8 recipients with a history of severe thrombosis. We investigated: lupus anticoagulant, anticardiolipin antibodies (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), antiprothrombin antibodies (immunoglobulin (Ig)G and IgM isotype), protein C and S activities, factor VIII, antithrombin, ADAMTS-13 and anti-ADAMTS-13. The 2 determinations were performed at an interval of 6 months. The mean follow-up was 19.5 ± 4.6 months. RESULTS: The most commonly detected antibodies were anti-ß2GPI IgM (25%) and aCL IgG (15.63%). Comparing the prevalence of APLAs between T(-) and T(+), we observed a significant difference only for aCL IgM (P = .0183), which was not confirmed on a second determination after 6 months. We noted correlations between aCL IgM and number of thrombotic episodes (P = .0040) and between aCL IgM and anti-ß2GPI IgM (P = .0074; rho 0.45). Despite receiving low-molecular-weight heparin or aspirin recurrence of thrombosis occurred in 4 T(+) patients: 3 hepatic artery thrombosis and 1 splenic artery thrombosis. Only 1 patient had APLAs; the other 2, protein C or S deficiency and the fourth, a normal test. CONCLUSIONS: The prevalence of APLAs in liver recipients is greater than that in the general population. The usefulness of APLAs as a marker of thrombosis was not demonstrated suggesting multifactorial etiologies of liver graft thrombosis.

Strains of Klebsiella pneumoniae producing extended spectrum beta-lactamases, isolated from organ recipients.

OBJECTIVE: The aims of this work were to define the effectiveness of identification of the extended-spectrum beta-lactamases (ESBL) phenotype, and to define the genotype of Klebsiella pneumoniae ß-lactamase. MATERIALS AND METHODS: We identified ESBL phenotypes in 110 strains of K pneumoniae isolated from samples from patients of transplantation wards, using the double-disk synergy test (DDST). For the chosen strains, polymerase chain reaction (PCR) was applied to detect genes determining SHV, CTX-M, and TEM. RESULTS: We showed synergism of clavulanic acid and investigated antibiotics including ceftazidime (89.1%), cefotaxime (80%), and aztreonam (82.7%) against ESBL-positive strains PCR revealed that TEM and CTX-M were present in 88.89% of strains. CONCLUSIONS: The ESBL mechanism of resistance is frequent among K pneumoniae strains isolated from transplant recipients. Strains with simultaneous synthesis of more than one beta-lactamase predominated.

The dominant sequence types of vancomycin-resistant Enterococcus faecium among transplantation ward patients.

OBJECTIVES: Vancomycin-resistant enterococci (VRE) frequently cause therapeutic problems and provide information about the epidemiological condition of the ward. MATERIALS AND METHODS: VRE isolated from patients on transplantation wards in 2007-2008 were compared using 2 molecular methods: RFLP-PFGE (restriction fragment length polymorphism-pulse field gel electrophoresis) and MLST (multilocus sequence typing). RESULTS: The analysis covered 29 Enterococcus faecium strains resistant to glycopeptides, each from a different patient. All organisms were typed using 2 molecular methods. MLST results were compared with an international base. The 30 examined strains belonged to 8 different worldwide known sequence types. All could be recognized as representatives of a single clonal complex CC17. CONCLUSION: Both methods of typing appeared to be useful to asses the epidemiological condition of the investigated wards.

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 patient's 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.

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.

Optimal mycophenolic acid and mycophenolic acid glucuronide levels at the early period after kidney transplantation are the key contributors to improving long-term outcomes.

INTRODUCTION: Suboptimal mycophenolic acid (MPA) and its metabolite MPA glucuronide (MPAG) levels are associated with significant increased incidences of graft loss. This study assessed the influence of MPA and MPAG C(0) levels on glomerular filtration rate (GFR) values and histopathologic changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: This prospective study of 42 low-risk patients receiving mycophenolate mofetil, prednisone, and a low or normal cyclosporine dose included histological assessment, according to the Banff'97 classification, of protocol biopsies before and at 3, 12, and 36 months after transplantation, as well as GFR at 1, 3, 12, 36, and 60 months and MPA enzyme-linked immunosorbent assay, MPAG (HPLC/UV) C(0) levels at 7 days as well as at 1, 3, 12, and 36 months. RESULTS: We observed nonlinear, significant correlations between MPA, MPAG C(0) levels and subclinical rejection episodes (SCR) according to chronic interstitial changes (ci), chronic tubulitis (ct), arteriolar hyalinization (ah) and chronic allograph nephropathy (CAN) indices in protocol biopsies. MPA C(0) levels below 1.0 to 1.5 microg/mL at day 7 were associated with an increased risk of SCR (P < .03), ci > or = 2 (P < .05), CAN > or = 2 (P < .04), and ah > or = 2 (P < .07). MPAG C(0) levels above 100 to 150 microg/mL at day 7 were associated with a decreased risk of ct > or = 2 (P < .01), ci > or = 2 (P < .04), or CAN > or = 2 (P < .04). We also observed a significant linear positive correlation between MPA C(0) level and a significant negative correlation between MPAG C(0) level at 1 month with GFR. CONCLUSION: Optimal MPA and MPAG exposure in the early posttransplant period may improve renal graft outcomes.

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.

Bisphosphonates are effective prophylactic of early bone loss after renal transplantation.

INTRODUCTION: Rapid bone loss and fractures occur early after solid organ transplantation. We examined the preliminary results of a prospective study evaluating the efficacy of prophylactic use of bisphosphonates in renal allograft recipients. METHODS: Bone mineral density (BMD) was measured at the lumbar spine and the hip by dual energy X-ray absorptiometry at 1, 6, 12 months. Alendronian or risedronian were initiated for patients with osteopenia or osteoporosis at 1 month who had no contraindications to bisphosphonates. The treatment lasted at least 6 months. Sixty-six patients were included in the study; 39 were treated with bisphosphonates (A), and 27 were drug-free (B). Presently, 24 group A and 13 group B patients have completed the 12-month observation period. RESULTS: In group A 53.8% (21) subjects had osteoporosis and 46.2% (18), osteopenia. Mean T-score L(2)-L(4) in group A at 1, 6, and 12 months were: (-)2.22 +/- 1.06; (-)2.07 +/- 1.25; (-)1.89 +/- 1.07, respectively. The T-score increase between 6 and 12 months was significant (P = 0.0014). The relative rise in BMD L(2)-L(4) between 1 and 12 months was 2.26%. In group B mean T-score L(2)-L(4) at 1, 6, and 12 months were: (-)0.26 +/- 1.34; (-)0.80 +/- 1.19; (-)1.2 +/- 1.59, respectively. The T-score decrease between 1 and 12 months in group B was significant (P = .0082). The 12-month relative decrease in femoral neck and trochanter BMD in group B was (-)2.1% and (-)2.75%, respectively. CONCLUSION: Bisphosphonates are effective for prophylaxis of rapid bone loss early after renal transplantation.

Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-beta levels and histological changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21). METHODS: In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation. RESULTS: We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3 months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL, respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.

Tubular and glomerular proteinuria in diagnosing chronic allograft nephropathy with relevance to the degree of urinary albumin excretion.

The diagnosis of chronic allograft nephropathy (CAN) is based on pathological examination according to Banff 97 schema. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria for noninvasive recognition of CAN. One hundred and thirty renal allograft recipients (at least 90 days after transplantation) who had undergone diagnostic allograft biopsy were included in the study. Beta2-microglobulin, alpha1-microglobulin, albumin, immunoglobulin G, total protein, and creatinine concentrations were obtained from the second morning urine specimen. Raw data and values calculated per 1 g of creatinine excreted in urine along with time after transplantation, serum creatinine, and its change over a period of 2 months prior to biopsy were taken for analysis. Urine proteins were measured using a nephelometric method. Statistical calculations were performed using MANOVA and stepwise discriminant analysis (SDA). Statistical diagnosis and staging of CAN matched the pathological method in 68% of a preliminary SDA. Therefore patients were divided into normoalbuminuric, microalbuminuric, and macroalbuminuric groups. There was no significant differences between protein excretion, except alpha1-microglobulinuria (CAN 0 vs 2, P = .018; CAN 1 vs 2, P = .041), beta2-microglobulinuria (CAN 0 vs 2, P = .026; CAN 1 vs 2, P = .0033), and total proteinuria (CAN 0 vs 2, P = .042) in the normoalbuminuric group. Nevertheless, diagnoses obtained using SDA were 89%, 91%, and 92% identical to the results of pathological examinations, for normoalbuminuric, microalbuminuric, and macroalbuminuric groups, respectively. In conclusion, tubular and glomerular proteinuria measurements may be useful for a noninvasive CAN diagnosis and staging only with regard to degree of urinary albumin excretion.

The role of the protocol biopsies in renal allograft recipients.

Subclinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy. In a prospective study 32 low-risk patients were randomized to either a reduced CsA dose (5 mg/kg/d) and daclizumab (group A, n = 16) for 7 months posttransplant with subsequent CsA tapering/withdrawal, or to a normal CsA dose (10 mg/kg/day) without daclizumab (group B, n = 16). Both groups received MMF and prednisone. Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx. The number of rejection episodes was the primary endpoint. The secondary endpoints were: renal function, histological parameters related to CsA, and serum levels of TGF-beta and PDGF-BB. A low incidence of clinically suspected rejection episodes was observed (19% in group A and 12.4% in group B; P = NS). Although protocol biopsies showed 12 subclinical rejection episodes (six in group A, six in group B), serum creatinine levels were not different between the examined groups at 3 months. However, at 12 months, there was a statistically improved mean creatinine level in group A patients (1.2 mg/dL +/- 0.5 in group A vs 1.54 mg/dL in group B; P <.05). Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies (with no differences between groups, or between 3 and 12 months in both groups). Serum TGF-beta and PDGF-BB did not differ between the groups. Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocols. Immunosuppressive regimens with low CsA doses followed by the drug's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.

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.

Pneumonia in kidney allograft recipients.

Infectious complications, including pneumonia, remain one of the leading causes of morbidity and mortality in kidney allograft recipients. The aim of the study was to evaluate the relationship between pneumonia occurrence and treatment duration and recipient age, cause of native kidney insufficiency, dialysis duration, time between transplantation and onset, HLA matching, PRA immunosuppressive protocol, acute rejection incidence and treatment, kidney function at the pneumonia onset, as well as presence of comorbid conditions. One hundred and twenty pneumonia cases occurred in kidney allograft recipients transplanted between 1991 and 2000 with 12 to 120 months follow-up. Twenty five percentage of pneumonia episodes were diagnosed during the first posttransplant month, 25% between 2 and 6 months, and 25% at 0.5 to 3 years. Treatment duration measured from pneumonia onset to the study endpoint of recovery, which was defined as antibiotic withdrawal, show 50% of patient we cured after 15 days and 75% after 24 days of treatment. The risk of prolonged pneumonia treatment was associated with: second versus first kidney transplantation with RR = 2.3 (P <.02) and medians of treated time 28 versus 15 days; as well as serum creatinine level above 2 mg/dL (RR = 1.4; P <.098). Exposure to enhanced-potency immunosuppressive protocols including induction therapy with mono- or polyclonal antibodies increased the RR = 1.65 (P <.02), and lengthened the time to 18 versus 14 days. Maintenance immunosuppression with agents other than cyclosporine also enhanced the risk. (RR = 2.18; P <.068).