Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients.

INTRODUCTION: Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. MATERIALS AND METHODS: Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. RESULTS: One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. CONCLUSION: The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Relevance of Flow Cytometric Auto-Crossmatch to the Post-transplant Course of Kidney Transplant Recipients.

INTRODUCTION: The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients. MATERIALS AND METHODS: The primary outcome variable was reduced renal function. Secondary endpoints were incidence of biopsy-confirmed chronic antibody-mediated rejection (CAMR) and recurrent glomerulonephritis (GN). RESULTS: There were no differences regarding initial serum creatinine levels between the study and control groups (P = .441). Patients who had positive auto-B FCXM had a significantly reduced renal function compared with the control group (P = .016). Four patients developed biopsy-confirmed CAMR in the study group and 1 patient in the control group (P = .047). Five patients had biopsy-confirmed recurrent GN in the GN study group, and only 1 patient had recurrent GN in the GN control group (P = .026). DISCUSSION: Kidney transplant recipients with positive auto-FCXM test had significantly reduced renal function and a higher incidence of recurrent GN and CAMR compared with the control group. The findings of this study suggest a potential role of auto-antibody causing positive auto-FCXM test result, meanwhile increasing the risk of CAMR, recurrent GN, and new-onset diabetes after tx.

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy.

BACKGROUND: The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. METHODS: Serum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (n = 23) with non-recurrent IgAN and control non-transplant IgAN patients (n = 44) and healthy relatives (n = 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated. RESULTS: All recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) (P = .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/µL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/µL [log10: 3.34 ± 0.27]) (P < .001 and P = .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53-0.85) for serum Gd-IgA1 (P = .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group (P = .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] (P = .224). CONCLUSIONS: This novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Renal transplantation in a patient with chronic granulomatous disease: case report.

Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population and is attributed to various factors, including infections, amyloidosis, and nephrotoxic anti-infective agents. In this report, we present our experience in transplantation for a patient with CGD complicated by isolated hepatic tuberculosis abscess. The course of the case demonstrates the absolute requirements for a multidisciplinary and compulsive approach before, during, and after transplantation. This case report also highlights the unexpectedly benign effects of immunosuppressive therapy in this patient population.

Kidney transplant recipients with functioning grafts for more than 15 years.

BACKGROUND: Renal transplantation is the best renal replacement therapy because it significantly improves patient survival. The developments in transplantation and increasing number of patients with end-stage renal disease (ESRD) have unmasked long-term complications secondary to immunosuppressive drugs and chronic renal failure. METHODS AND RESULTS: Eighty-six renal transplant recipients with grafts that have functioned more than 15 years were included in the study. This cross-sectional retrospective analysis of demographic, clinical, and laboratory findings was conducted in 3 Turkish transplantation centers. The mean age was 30.4 ± 10.2 years at the time of the transplantation. The mean time between the transplantation and the study was 19.1 ± 3.6 years. At the time of the study, mean creatinine level was 1.52 ± 0.60 mg/dL, 70.09% of the patients displayed glomerular filtration rates <60 mL/min/1.73 m(2). Urinary protein excretion was 0.57 ± 0.65 g/d. Hypertension and hyperlipidemia were the most common comorbid diseases. Twelve patients had diabetes and 9 cardiovascular disease. Seventeen patients had been diagnosed with skin and 5 with non-skin cancer. CONCLUSIONS: As the number of recipients with long-term functioning grafts increases, long-term complications become evident, particularly chronic renal failure. Survivors should be evaluated regularly and treated early for risk factors and complications to improve long-term graft and patient survival.

Outcome of kidney transplantation following end-stage renal disease due to reflux nephropathy.

BACKGROUND: Reflux nephropathy (RN) has an important place among the etiologies of end-stage renal disease (ESRD). In this retrospective study we sought to analyze posttransplantation complications among renal transplant recipients whose primary disease was RN. METHODS: Seven hundred forty-five patients who underwent transplantation in our institution between 1983 and 2006 were included in the study. The outcomes of patients with RN (Group 1) were compared with a control group (Group 2) that consisted of age-matched, nondiabetic patients whose primary disease was chronic glomerulonephritis or unknown etiologies. RESULTS: Group 1 consisted of 52 patients, including 20 males with a mean overall age of 25 years. Group 2 included 47 patients, including 21 males with a mean age of 27 years. There was no significant difference with regard to age, gender, donor type, donor age, modality of hemodialysis, or HLA match between the 2 groups. Group 1 graft survival rates in the first and fifth years were 95% and 90%, respectively, and in Group 2 they were 86% and 70%, respectively (P = .302 and P = .072, respectively). There was no significant difference with respect to follow-up duration, hospital stay, or incidence of biopsy-proven or clinically suspected acute rejection episodes between the groups. During the 6-year follow-up, the incidence of biopsy-proven chronic allograft nephropathy was the same in both groups. One patient in Group 1 and 2 in Group 2 died of cardiovascular issues; 1 Group 2 patient died of infection. The frequency of urinary tract infection in Group 1 was greater than that of Group 2 (40% vs, 23%; P = NS). CONCLUSION: Despite the higher incidence of urinary tract infections, there was no significant difference in posttransplantation complications or patient and graft survival rates between RN patients compared with the control group.

When the earth trembles in the Americas: the experience of Haiti and Chile 2010.

The response of the nephrological community to the Haiti and Chile earthquakes which occurred in the first months of 2010 is described. In Haiti, renal support was organized by the Renal Disaster Relief Task Force (RDRTF) of the International Society of Nephrology (ISN) in close collaboration with Médecins Sans Frontières (MSF), and covered both patients with acute kidney injury (AKI) and patients with chronic kidney disease (CKD). The majority of AKI patients (19/27) suffered from crush syndrome and recovered their kidney function. The remaining 8 patients with AKI showed acute-to-chronic renal failure with very low recovery rates. The intervention of the RDRTF-ISN involved 25 volunteers of 9 nationalities, lasted exactly 2 months, and was characterized by major organizational difficulties and problems to create awareness among other rescue teams regarding the availability of dialysis possibilities. Part of the Haitian patients with AKI reached the Dominican Republic (DR) and received their therapy there. The nephrological community in the DR was able to cope with this extra patient load. In both Haiti and the DR, dialysis treatment was able to be prevented in at least 40 patients by screening and adequate fluid administration. Since laboratory facilities were destroyed in Port-au-Prince and were thus lacking during the first weeks of the intervention, the use from the very beginning on of a point-of-care device (i-STAT®) was very efficient for the detection of aberrant kidney function and electrolyte parameters. In Chile, nephrological problems were essentially related to difficulties delivering dialysis treatment to CKD patients, due to the damage to several units. This necessitated the reallocation of patients and the adaptation of their schedules. The problems could be handled by the local nephrologists. These observations illustrate that local and international preparedness might be life-saving if renal problems occur in earthquake circumstances.

Comparison of nutritional status in hemodialysis patients with and without failed renal allografts.

BACKGROUND: The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aimed to compare the nutritional status and its relation with inflammation in patients on HD with and without previous kidney transplantation. METHODS: Forty-three patients with failed renal allografts (27 males; mean age 36±9 yr) and 40 never transplanted HD patients (24 males; mean age 39±9 yr) were included in the study. Body weight, triceps (TSF), biceps (BSF), subscapular (SSSF), and suprailiac skinfold thicknesses (SISF); mid-arm, mid-arm muscle, hip and waist circumferences; as well as body mass indices (BMIs) were determined as anthropometric parameters. Moreover, biochemical markers of nutritional status, including serum cholesterol and albumin as well as high-sensitive C-reactive protein (hs-CRP), as a marker of inflammation, were measured. Associations among these variables were analyzed. RESULTS: There were no significant differences considering age, gender or duration of renal replacement therapy between the two groups. The TSF (p<0.0001), BSF (p=0.005), SSSF (p=0.001), SISF (p<0.0001) skinfold thicknesses; mid-arm (p=0.003) and mid-arm muscle circumferences (p=0.037) and BMIs (p=0.001) of the patients with failed renal allografts were significantly lower than those of the never transplanted HD patients. Waist circumference was significantly lower as well (p=0.028). Patients with failed transplants were characterized by lower serum albumin (p<0.0001) and higher hs-CRP levels (p=0.001) as compared with never transplanted HD patients. CONCLUSIONS: This study confirms the concept that retained failed allografts may induce chronic inflammation in chronic HD patients which may result in a worse nutritional status.

Endothelial dysfunction in peritoneal dialysis patients with and without failed renal transplants.

BACKGROUND: Endothelial dysfunction (ED) is a common, early abnormality that predisposes patients to develop atherosclerosis and cardiovascular events; inflammation is associated with atherosclerosis and malnutrition. Patients with failed transplants are usually complicated by inflammation; however, ED in this group of patients has not been well defined. In this cross-sectional study, we sought to investigate ED among naïve peritoneal dialysis (nPD) patients who were never transplanted as well as patients with failed renal transplants who were re-starting peritoneal dialysis (fTxPD). METHODS: Twenty-five nPD patients (15 female/10 males; mean age, 44 +/- 11 years), and 12 fTxPD patients (4 males; mean age, 37 +/- 10 years) were included in the study. Coronary flow reserve (CFR) measurements were used to evaluate ED. Serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin, and intact parathyroid hormone (iPTH) were measured. Also, highly sensitive C-reactive protein (hs-CRP) levels and weekly Kt/V were determined as possible confounding factors. Results were compared between the 2 groups. RESULTS: There were no significant differences regarding age, gender, mean systolic and diastolic blood pressures, or smoking status. Mean duration on PD, peritoneal transport characteristics, PD modality and doses, frequency of peritonitis episodes, as well as serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin and iPTH levels were similar between the 2 groups. Weekly Kt/V of both groups were similar as well. However, hs-CRP levels were significantly higher (34 +/- 52 vs 6.7 +/- 7.5 mg/L; P = .017) and CFR significantly lower among patients with fTxPD compared with nPD patients (1.52 +/- 0.20 vs 1.91 +/- 0.53; P = .022). CONCLUSION: ED was more prominent among patients with failed transplants than nPD cases, suggesting that the failed allograft may be responsible for this abnormality.

Anti-HLA antibody profile of Turkish patients with end-stage renal disease.

Exposure to human leukocyte antigens (HLA) via blood transfusions, pregnancies, and previous transplantations can result in anti-HLA antibody production. The presence of anti-HLA antibodies in recipient sera before transplantation is an important risk factor. To demonstrate the anti-HLA antibody status of Turkish end-stage renal disease (ESRD) patients, 674 patients (mean age, 40.35 +/- 13.15 years; female/male, 328/346) were enrolled into the study. Anti-HLA antibody screening and identification tests were performed using an enzyme-linked immunosorbent assay (ELISA) method. The panel-reactive antibody (PRA)-negative group consisted of 564 (83.6%) and the PRA-positive group consisted of 110 (17.3%) patients. Of the 110 (17.3%) PRA-positive patients, 43 (6.4%) were class I (+) and class II (-); 19 (2.8%) were class I (-) and class II (+); 48 (7.1%) were both class I and II (+). The most frequent antibodies were directed against the A2 crossreactive group (CREG) and the A10 CREG with less frequent reactions against the B7 CREG, indicating antibodies to both frequent (members of A2 CREG) and relatively rare (members of A10 CREG and B7 CREG antigens). These data also suggested that some antibodies occur at greater than expected frequency because of shared epitopes. Our findings confirmed the significant correlation between female gender, pregnancy, failed graft history, long dialysis duration, and blood transfusions with PRA positivity (P < .05).

Association between chronic hepatitis C infection and coronary flow reserve in dialysis patients with failed renal allografts.

BACKGROUND: Hepatitis C infection occurs frequently among patients with end-stage renal disease and increases the risk of atherosclerotic cardiovascular diseases. Endothelial dysfunction (ED) is an early event in the pathogenesis of atherosclerosis. It has been reported among patients treated with hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation. The aim of the present study was to evaluate effects of chronic hepatitis C infection on ED in patients with failed renal transplants. METHODS: Twenty-six nondiabetic, anti-hepatitis C virus (HCV)-positive (15 females, mean age: 38 +/- 8 years) and 26 anti-HCV-negative patients (15 females, mean age: 36 +/- 5 years), all of whom had returned to PD or HD after renal transplant failure were studied to assess coronary flow reserve (CFR) by transthoracic Doppler echocardiography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured as markers of chronic inflammation. CFR recordings and intima-media thickness measurements were performed using the Vivid 7 echocardiography device. RESULTS: Demographic and clinical characteristics of patients were similar between the two groups. Serum hs-CRP levels were significantly higher among HCV-positive patients versus HCV-negative counterparts. HCV-positive patients showed lower CFR measurement than HCV-negative ones. Also, a negative correlation was observed between serum hs-CRP levels and CFR values. CONCLUSION: CFR values are worse among anti-HCV-positive patients with failed renal transplants compared with anti-HCV-negative subjects. Graft dysfunction per se may aggravate a proinflammatory states thereby inducing ED. Furthermore, the presence of HCV is a greater trigger of ED among patients with renal failed grafts.

The role of the International Society of Nephrology/Renal Disaster Relief Task Force in the rescue of renal disaster victims.

Disasters are a major cause of distress and material as well as corporal damage. Next to direct trauma, the crush syndrome inducing multiorgan problems as a consequence of muscle compression and the release of muscular contents into the bloodstream is the most important cause of death; this is to a large extent related to the induction of severe acute kidney injury, for which dialysis is a life-saving therapy. The practical means (both hardware and personnel) to do so are, however, often lacking in disaster conditions. The Renal Disaster Relief Task Force (RDRTF) offered support for renal problems in the aftermath of several disasters, e.g. the Marmara earthquake (1999) in Turkey, the Bam earthquake (2003) in Iran, and the Kashmir earthquake (2005) in Pakistan. A preconceived intervention plan is followed with adaptations according to local conditions. Material and personnel are dispatched to the disaster areas. These interventions have been life-saving for a substantial number of victims. The current article describes the structure and approach of the RDRTF.

Earthquakes and crush syndrome casualties: lessons learned from the Kashmir disaster.

Major earthquakes may provoke a substantial number of crush casualties complicated by acute kidney injury (AKI). After the 1988 Armenian earthquake, the International Society of Nephrology (ISN) established the Renal Disaster Relief Task Force (RDRTF) to organize renal care in large disasters; this approach proved to be useful in several recent disasters. This paper depicts the organizational aspects of the rescue intervention during the Kashmir earthquake, in 2005. Specific problems were fierce geographic circumstances, lack of pre-registered local keymen, transportation problems, and inexperience of local teams to cope with problems related to mass disasters. Once treatment was installed, global outcomes were favorable. It is concluded that well-organized international help in renal disasters can be effective in saving many lives, but still necessitates conceptual adaptations owing to specific local circumstances.

Rhabdomyolysis.

Rhabdomyolysis is the disintegration of striated muscles resulting in the release of muscular cell contents into the extracellular fluid. Crush syndrome is systemic manifestations caused by rhabdomyolysis; the most important component of crush syndrome is acute kidney injury. Non-physical and physical causes play a role in the aetiology of rhabdomyolysis. Clinical spectrum varies from asymptomatic elevation in creatine kinase to acute tubular necrosis and multiorgan failure. Myoglobinuria, increased serum creatine kinase level and hyperkalaemia are the most important laboratory parameters. Vigorous hydration with isotonic saline followed by alkaline solutions and mannitol are useful in the treatment of rhabdomyolysis.

Isolated hepatic tuberculous abscess in a renal transplant recipient.

Tuberculous liver abscess is rare worldwide. We report a 26-year-old renal transplant recipient who presented with fever, fatigue, and weight loss. Ultrasound (US) of the abdomen showed a cystic mass of 7x6 cm in the subcapsular region of right liver lobe. US-guided percutaneous drainage was performed and 100 mL of yellow-colored pus was aspirated. The patient was empirically started on ampicillin sulbactam treatment. Despite this treatment, the symptoms persisted. Subsequent control abdominal US showed the persistence of a cystic mass of 7x6 cm with thin septation in the subcapsular region near the right liver lobe, which were subsequently diagnosed as a focal hepatic tuberculous abscess by positive culture in Löwenstein-Jensen medium. He was concomitantly started on systemic antituberculous therapy. A tuberculous liver abscess must be considered in the differential diagnosis. Percutaneous drainage along with systemic antituberculous chemotherapy must be considered as an alternative to surgery for the management. A greater awareness of this clinical entity is required for successful treatment.

Utilization of elderly donors in living related kidney transplantation.

Kidney transplantation has become the treatment of choice for end-stage renal disease. However, its application is limited due to inadequate organ supply, mainly because many dialysis patients do not have suitable living donors. The increasing discrepancy between organ supply and demand has forced many transplant centers to consider using organs procured from marginal donors. The aim of this study was to investigate whether utilization of kidneys from living related elderly donors is safe for the recipients in the long term. We analyzed the clinical results of 296 consecutive recipients of living related renal transplants, among whom 44 recipients received kidneys from donors over 60 years of age. By the end of 12 months, the mean serum creatinine level of the recipients who were transplanted from the older donors was higher (1.55 +/- 0.45 mg/dL) than that from other donors (1.21 +/- 0.3 mg/dL), but the difference was not significant (P = .08). In the long term (60 months), the graft function was similar (1.88 +/- 0.55 vs 1.52 +/- 0.38) for both groups. The similarity in outcomes of ideal versus older donors as shown less in the present series has encouraged us to utilize elderly living donors. We concluded that transplantations performed from the elderly donors yielded similar results to those of conventional donors. The long waiting list for transplantation, the treatment of choice for end-stage renal disease, should encourage us to be more flexible about donor selection.

Health-related quality of life after kidney transplantation in comparison intermittent hemodialysis, peritoneal dialysis, and normal controls.

The purpose of this study was to compare the quality of life (QOL) in renal transplantation patients. QOL is one of the important indicators of the effects of medical treatment. In this cross-sectional study, QOL was analyzed in 302 renal transplant recipients compared with 64 hemodialysis (HD) patients, 207 (PD) peritoneal dialysis patients, and 278 normal controls (NC) matched as closely as possible to the grafted patients regarding age, gender, education, and occupation. All groups were asked to estimate their subjective QOL by responding to sociodemographic data, Turkish adapted instruments of the Nottingham Health profile (NHP), and the Short-form 36 (SF-36). Transplant recipients were significantly younger than the HD and PD patients (P < .0001). There was no statistically significant differences between normal controls and transplant patients ages. Among the three renal replacement methods, QOL in transplants was clearly better than that in HD or PD patients (P < .0001). The QOL measured by the NHP and SF-36 scale showed that the normal population was statistically significantly better than the transplant recipients (P < .0001). Transplant renal replacement therapy provides a better QOL compared with other replacement methods.