Friday, April 29, 2011

Screening for renal cancer in recipients of kidney transplants

Screening for renal cancer in recipients of kidney transplants: "
Background. Renal cancer is the most common solid organ cancer in the kidney transplant population with an excess risk ~ 5-fold greater than the general population. It is uncertain whether routine screening for renal cancer is cost-effective. The aim of our study is to estimate the costs and health benefits of ultrasonographic (US) screening for renal cancer in the kidney transplant population.

Hypercalcaemia as a prodromal feature of indolent Pneumocystis jivorecii after renal transplantation

Hypercalcaemia as a prodromal feature of indolent Pneumocystis jivorecii after renal transplantation: "
Following renal transplantation, hypercalcaemia is frequently caused by persisting hyperparathyroidism. Unregulated extrarenal 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis, which is well recognized as a cause of hypercalcaemia in granulomatous diseases, may also occur after kidney transplantation. This mechanism is also likely to be responsible for hypercalcaemia reported during treatment of cytomegalovirus and associated with acute symptomatic pneumocystis jivorecii pneumonia (PCP). Hypercalcaemia as a prodromal feature of indolent PCP has not been described. We report a renal transplant recipient who developed hypercalcaemia 30 months post-transplant due to extrarenal production of 1,25(OH)2D. Two months later, PCP was diagnosed and hypercalcaemia resolved after initiation of treatment.
"

Elevated Fibroblast Growth Factor 23 is a Risk Factor for Kidney Transplant Loss and Mortality

Elevated Fibroblast Growth Factor 23 is a Risk Factor for Kidney Transplant Loss and Mortality: "
An increased circulating level of fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease (CKD), but its role in transplant allograft and patient survival is unknown.

Thursday, April 28, 2011

Epidemiology and risk factors for late infection in solid organ transplant recipients

Epidemiology and risk factors for late infection in solid organ transplant recipients: "
C. Cervera, M. Fernández-Ruiz, A. Valledor, L. Linares, A. Antón, M. Ángeles Marcos, G. Sanclemente, I. Hoyo, F. Cofán, M.J. Ricart, F. Pérez-Villa, M. Navasa, T. Pumarola, A. Moreno. Epidemiology and risk factors for late infection in solid organ transplant recipients. Transpl Infect Dis 2011. All rights reserved

Background
Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce.

Wednesday, April 27, 2011

Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis

Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis: "
H. Green, R. Rahamimov, U. Gafter, L. Leibovitci, M. Paul. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011. All rights reserved
Abstract: Urinary tract infection (UTI) is the most common bacterial infection in renal transplant recipients. To date there are no guidelines on antibiotic prophylaxis for UTI in this population.

Monday, April 25, 2011

Belatacept-Based Regimens Are Associated With Improved Cardiovascular and Metabolic Risk Factors Compared With Cyclosporine in Kidney Transplant Recipients (BENEFIT and BENEFIT-EXT Studies)

Belatacept-Based Regimens Are Associated With Improved Cardiovascular and Metabolic Risk Factors Compared With Cyclosporine in Kidney Transplant Recipients (BENEFIT and BENEFIT-EXT Studies): "Background. Cardiovascular disease, the most common cause of death with a functioning graft among kidney transplant recipients, can be exacerbated by immunosuppressive drugs, particularly the calcineurin inhibitors. Belatacept, a selective co-stimulation blocker, may provide a better cardiovascular/metabolic risk profile than current immunosuppressants.
Methods. Cardiovascular and metabolic endpoints from two Phase III studies (BENEFIT and BENEFIT-EXT) of belatacept-based regimens in kidney transplant recipients were assessed at month 12. Each study assessed belatacept in more intensive (MI) and less intensive (LI) regimens versus cyclosporine A (CsA). These secondary endpoints included changes in blood pressure, changes in serum lipids, and the incidence of new-onset diabetes after transplant (NODAT).
Results. A total of 1209 patients were randomized and transplanted across the two studies. Mean systolic blood pressure was 6 to 9 mm Hg lower and mean diastolic blood pressure was 3 to 4 mm Hg lower in the MI and LI groups versus CsA (P≤0.002) across both studies at month 12. Non-HDL cholesterol was lower in the belatacept groups versus CsA (P<0.01 MI or LI vs. CsA in each study). Serum triglycerides were lower in the belatacept groups versus CsA (P<0.02 MI or LI vs. CsA in each study). NODAT occurred less often in the belatacept groups versus CsA in a prespecified pooled analysis (P<0.05 MI or LI vs. CsA).
Conclusions. At month 12, belatacept regimens were associated with better cardiovascular and metabolic risk profiles, with lower blood pressure and serum lipids and less NODAT versus CsA. The overall profile of belatacept will continue to be assessed over the 3-year trials."

Natural History of Proteinuria in Renal Transplant Recipients Developing De Novo Human Leukocyte Antigen Antibodies

Natural History of Proteinuria in Renal Transplant Recipients Developing De Novo Human Leukocyte Antigen Antibodies: "Background. The relationship between humoral rejection and human leukocyte antigen (HLA) antibodies is established. Proteinuria is the hallmark of glomerular injury. The relationship between HLA antibody and proteinuria was explored in renal transplant recipients developing de novo donor-specific antibodies (DSA) and nondonor-specific antibodies (NDSA).
Methods. Seventy-two patients with de novo HLA antibody (38 DSA and 34 NDSA) were identified from 475 prevalent renal transplant recipients (15.2%). Antibody surveillance occurred every 6 months, with specificity characterized by a combination of enzyme-linked immunosorbent assay, flow-bead cytometry, and Luminex bead analysis. Pooled analysis of every glomerular filtration rate (GFR) and urinary protein estimation in a 48-month window around the date of antibody detection was performed (4004 and 2084 measurements, respectively).
Results. GFR slope (−5.85 vs. −3.21 mL/min/1.73 m2 per year) and graft failure rate (29% vs. 9%, P=0.039) were worse in patients with DSA. Three-year graft survival after antibody detection was worse in patients with DSA (69.5% vs. 91.1%, P=0.035). Patients with DSA had significantly more proteinuria than those with NDSA and 205 control patients with no alloantibodies, from 6 months before antibody detection (0.91 vs. 0.39 g/L, P=0.015). Graft failure was more likely in patients with DSA with excess of 0.2 g/L at antibody detection (42% vs. 0%, P=0.008).
Conclusions. Proteinuria is associated with DSA detection and is likely to be an important factor that determines rapid GFR decline and earlier graft failure in patients developing de novo HLA antibodies."

Sirolimus and Proteinuria in Renal Transplant Patients: Evidence for a Dose-Dependent Effect on Slit Diaphragm-Associated Proteins

Sirolimus and Proteinuria in Renal Transplant Patients: Evidence for a Dose-Dependent Effect on Slit Diaphragm-Associated Proteins: "Background. The mechanisms underlying the development of proteinuria in renal-transplant recipients converted from calcineurin inhibitors to sirolimus are still unknown.
Methods. This is a single-center cohort study. One hundred ten kidney transplant recipients converted from calcineurin inhibitors to sirolimus in the period from September 2000 to December 2005 were included in the study. All patients underwent a graft biopsy before conversion (T0) and a second protocol biopsy 2 years thereafter (T2), according to our standard clinical protocol. On the basis of the changes observed in proteinuria between T0 and T2 (median 70%), the patients were divided into two groups: group I (<70%) and group II (>70%). The authors blinded the sirolimus blood trough levels. We investigated in vivo the effects of sirolimus on nephrin, podocin, CD2ap, and actin protein expression. Slit diaphragm (SD)-associated protein expressions were evaluated in T0 and T2 biopsies. The same analysis was performed in cultured human podocytes treated with different doses of sirolimus (5, 10, 20, and 50 ng/mL).
Results. The SD protein expression in group II T2 biopsies was significantly reduced compared with the T0 biopsies and with T2 group I biopsies. In addition, sirolimus blood trough levels directly and significantly correlated with the SD protein expression at T2 graft biopsies. Group II patients presented significantly higher sirolimus blood levels than group I. In vitro study confirmed that sirolimus effect on podocytes was dose dependent.
Conclusions. Our data suggest that sirolimus-induced proteinuria may be a dose-dependent effect of the drug on key podocyte structures."

Recurrent Glomerulonephritis Under Rapid Discontinuation of Steroids

Recurrent Glomerulonephritis Under Rapid Discontinuation of Steroids: "Background. Recurrent glomerulonephritis (GN) remains an important cause of kidney allograft loss and whether rapid discontinuation of steroids (RDS) is associated with a higher risk of recurrence is not known.
Methods. We studied recurrence rate, and graft and patient survival in four groups of recipients: 216 recipients with GN transplanted under RDS (group 1), 978 concurrent non-GN recipients transplanted under RDS (group 2), 260 historic comparator group transplanted for GN between 1994 and 1999 with steroid maintenance (group 3), and 950 recipients who were also transplanted between 1994 and 1999 for non-GN and also maintained on steroids (group 4). Regression analysis adjusting for donor and recipient factors, steroid and sirolimus use, and also GN type was used to address factors associated with recurrent disease.
Results. The 1-, 5-, and 7-year recurrence rate in the GN group under RDS was 6.7%, 13.7%, and 19.2% and in historic GN recipients maintained on steroids it was 2.4%, 3.8%, and 5.3%, respectively (P<0.0001). RDS was associated with a higher adjusted risk of recurrent disease for all GN types (hazard ratio 4.86; 95% confidence interval 2.34-10.07; P<0.0001). Graft and patient survival were similar in the two GN groups and both were highest among all groups. Notably, death-censored graft survival was not different among the groups.
Conclusion. Steroid avoidance may be associated with a higher rate of recurrent GN but no apparent increase in risk of graft loss. This group of recipients needs to be studied more carefully, in larger numbers, and for a longer time period.
(C) 2011 Lippincott Williams & Wilkins, Inc."

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Multicenter Experience

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Multicenter Experience: "Background. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease (ESRD). The optimal timing of kidney transplantation (KTX) for ESRD as a result of AAV and the risk of AAV relapse after KTX are not well defined. We report our experience with AAV patients who underwent KTX at our institutions between 1996 and 2010. Median follow-up was 64 months.
Methods. Retrospective multicenter cohort study.
Results. Eighty-five patients (45 men/40 women; mean age 49 years) received a KTX for ESRD secondary to microscopic polyangiitis (n=43) or Wegener's granulomatosis (n=42). Twenty-four patients underwent preemptive KTX and 69 received a living-donor KTX. All patients were in remission at the time of KTX. Fifty-eight patients received induction therapy. In 64 patients, maintenance immunosuppression was with prednisone, mycophenolate mofetil, and tacrolimus. At the time of KTX, 29 patients were ANCA-positive. The vasculitis relapse rate was 0.02 per patient-years and was not influenced by disease category, ANCA subtype, or remission duration before KTX. There were 23 rejection episodes in 13 patients with seven graft losses. Median serum creatinine at 1 year was 1.3 mg/dL in 75 patients with more than 1 year follow-up and 1.4 mg/dL at last follow-up. The graft and patient survival rates were 100% at 1 year, 97.9% and 93.4% at 5 years, and 79.0% and 67.4% at 10 years, respectively.
Conclusions. KTX is a safe and an effective option for treating ESRD secondary to AAV. Relapses are rare with current immunosuppression.
(C) 2011 Lippincott Williams & Wilkins, Inc."

Prospective monitoring of BK virus reactivation in renal transplant recipients in North India

Prospective monitoring of BK virus reactivation in renal transplant recipients in North India: "

R. Thakur, S. Arora, R. Nada, M. Minz, K. Joshi. Prospective monitoring of BK virus reactivation in renal transplant recipients in North India. Transpl Infect Dis 2011. : xx: 000–000. All rights reserved

Abstract: Background. BK nephropathy (BKN) is an important complication of renal transplantation with a reported incidence between 1% and 10% in different parts of the world. Early diagnosis is important to plan early therapeutic strategies. The epidemiology and evolution of BKN is relatively unknown in India and hence, the present study has been designed to prospectively monitor the activation of BK virus (BKV) in renal transplant recipients in India.


Patients and methods. In this study, 32 renal allograft recipients were prospectively monitored with protocol biopsies of allografts, BKV DNA load in plasma, and viral particles in urine by electron microscopy (EM) on day 1, and at 1, 3, and 6 months. Additionally, the baseline BKV DNA load in plasma was quantitated in 21 corresponding donors.

Results. On follow-up in 32 recipients, 9.7%, 23.8%, 19.2%, and 13.3% of patients showed viral profiles by EM at day 1, 1 month, 3 months, and 6 months, respectively. BKV DNA positivity in plasma was 25.8%, 42.9%, 15.4%, and 20% at day 1, 1 month, 3 months, and 6 months, respectively, with mean BKV copy number/mL plasma of 1796, 1029, 2611, and 3318, respectively. A total of 15.7% (17/108) urine samples of 32 renal recipients were positive by urine EM. Out of 100 protocol biopsies, none developed histologically demonstrable cytopathic effects of BKN, although 8% biopsies were SV-40 large T antigen (SV-40 T Ag) positive. By quantitative real-time polymerase chain reaction assay, 27/108 (25%) of recipients' plasma samples were positive for BKV. Peak viremia and viruria occurred at 1–3 months post transplantation. The baseline viremia in donors was predictive of viremia positivity in the post-transplantation period at 1 month. Twenty-four episodes of graft dysfunction were attributed mainly to rejection.

Conclusion. The study shows a total of 15.7% and 25% urine and plasma samples were positive for BKV at any time during a 6-month follow-up. The highest incidence of BK viruria and viremia occurred at 1 month. In protocol biopsies, focal positivity of SV-40 T Ag was seen in 8% biopsies.
"

Poor Outcomes Associated With Neutropenia After Kidney Transplantation: Analysis of United States Renal Data System

Poor Outcomes Associated With Neutropenia After Kidney Transplantation: Analysis of United States Renal Data System: "Background. Posttransplant neutropenia (PTN) is relatively common after kidney transplantation, and may result in a reduction of immunosuppression, which may precipitate acute rejection. Granulocyte colony-stimulating factors (GCSF) have been used to treat PTN, although outcomes associated with use of this medication in this population are unknown.
Methods. In a retrospective cohort of 41,705 adult Medicare primary patients transplanted from January 2001 to June 2006, we assessed Medicare claims for neutropenia, leukopenia, and GCSF use, respectively. Outcomes included allograft loss and death.
Results. There were 6043 (14.5%) patients with claims for PTN. Factors associated with PTN included female gender, Caucasian ethnicity, ischemic heart disease, donor cytomegalovirus positive, deceased donor, expanded donor criteria, delayed graft function, elevated panel reactive antibody, higher human leukocyte antigen mismatch, and later year of transplant. Thymoglobulin induction, tacrolimus, and mycophenolate mofetil were also associated. PTN was less frequent among patients with congestive heart failure, recipient cytomegalovirus positive, and interleukin-2 induction. PTN was associated with increased risk of allograft loss (adjusted hazard ratio, 1.59; 95% confidence interval, 1.43-1.76; P<0.001) and death (adjusted hazard ratio, 1.74; 95% confidence interval, 1.59-1.90; P<0.001). Of the 6043 patients with PTN, 740 (12.2%) received GCSF. Patients who received GCSF had a lower risk of death on unadjusted analysis, but this only trended towards significance after adjustment.
Conclusions. Neutropenia after renal transplantation is common and is associated with an increased risk of allograft loss and death. GCSF was used in 12% of cases and did not increase risk of allograft loss. Strategies to avoid PTN and greater use of GCSF may be indicated to prevent graft loss and death.
(C) 2011 Lippincott Williams & Wilkins, Inc."

Luminex-Based Desensitization Protocols: The University of Wisconsin Initial Experience

Luminex-Based Desensitization Protocols: The University of Wisconsin Initial Experience: "Background. We have demonstrated that immunodominant donor-specific antibody (DSA) more than 100 mean fluorescence intensity (MFI) at the time of transplant is associated with a significantly higher risk of rejection. We now present short-term outcomes of DSA-based desensitization (DSZ) strategies in patients with a negative complement-dependent cytotoxicity crossmatch.
Methods. Between January 1, 2009, and January 1, 2010, live-donor kidney transplant recipients were divided into three protocols based on their immunodominant DSA MFI pretransplant (D1: 100-500, D2: 501-1000, and D3: 1001-3000). Deceased donor kidney transplant recipients were stratified into two protocols (D4: 501-1000 and D5: 1001-3000). The intensity of the conditioning treatment increased with DSA levels and included thymoglobulin induction, plasmapheresis, and intravenous immunoglobulin in the highest risk groups. We compared outcomes between desensitized patients (DSZ) and those undergoing no DSZ (or D0) during the same interval.
Results. Forty-eight of 249 (23%) kidney transplants underwent DSZ (n=20, 4, 3, 4, and 17 in D1-D5 protocols, respectively). There was more retransplantation (50% vs. 18%, P<0.001) and live donor transplantation (56% vs. 30%, P<0.001) in the DSZ group. In this group, mean peak panel reactive antibody and MFI at transplant were 51%+/-7% and 960+/-136, respectively. The incidence of antibody-mediated rejection (25% vs. 12.5%, P=0.008) and acute cellular rejection (23% vs. 14%, P=0.02) was greater in the DSZ group. However, mixed rejection (8%), graft loss (0 vs. 6), patient death (0 vs. 3), cytomegalovirus infection (15% vs. 12%), and 1-year serum creatinine (1.4+/-0.5 and 1.4+/-0.4 mg/dL) were similar between DSZ and no-DSZ groups.
Conclusion. Long-term follow-up is needed to determine the role of Luminex-based strategies in current preconditioning regimens.
(C) 2011 Lippincott Williams & Wilkins, Inc."

Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up: "Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term."

Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation

Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation: "In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL, N = 318) or tacrolimus with MMF (Tac/MMF, N = 316). Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault) and was comparable at 66.4 mL/min (SE 1.4) with Tac/SRL and at 65.2mL/min (SE 1.3) with Tac/MMF (completers). Biopsy-confirmed acute rejection was 15.1% (Tac/SRL) and 12.3% (Tac/MMF). In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P<.05) while CMV, leukopenia, and diarrhea incidences were higher with Tac/MMF (P<.05). The incidence of any antidiabetic treatment for >30 consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens."

FGF-23 Levels before and after Renal Transplantation

FGF-23 Levels before and after Renal Transplantation: "Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25(OH)2VitD levels were measured at the same time periods. Renal threshold phosphate concentration (TmPO4/GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 ± 146 versus 37 ± 9 pg/mL, P<.01) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25(OH)2VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (P<.005). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation."

Wednesday, April 20, 2011

Membranoproliferative Glomerulonephritis Type I in Renal Transplantation Patients: A Single-Center Study of a Cohort of 68 Renal Transplants Followed Up for 11 Years

Membranoproliferative Glomerulonephritis Type I in Renal Transplantation Patients: A Single-Center Study of a Cohort of 68 Renal Transplants Followed Up for 11 Years: "Background. To evaluate the long-term outcome of renal transplant patients with membranoproliferative glomerulonephritis (MPGN) type I and the impact of recurrence.
Methods. The outcomes of 68 renal transplants performed between 1976 and 2009 in 63 patients with MPGN were compared with those of 136 controls matched for time of transplantation, sex, age, and source of donors.
Results. The mean posttransplant follow-up was 131.3+/-83.8 months for patients with MPGN and 139.21+/-88.7 months for controls. At 15 years, patient survival rates were 76.2% in patients with MPGN and 78.8% in controls (P=ns), whereas pure graft survival rates were 68% in MPGN and 67.9% in controls (P=ns). MPGN recurred in 16 patients (23.5%) 44+/-30.3 months after transplant (range, 3.5-105 months). Of recurrent grafts, nine were lost for recurrence within 116.5+/-51.36 months, three patients died with functioning kidney, the other 4 grafts are functioning 156.7+/-47.5 months after transplantation. Graft survival at 15 years was 73.5% in nonrecurrent and 40.4% in recurrent patients (P=0.02). Patients with recurrence were younger at diagnosis of MPGN (17.64+/-5.02 years vs. 22.9+/-9.6 years; P=0.037) and had low C3 more frequently than nonrecurrent patients (75% vs. 28.8%; P=0.01). Proteinuria was higher in recurrent patients who lost the graft in comparison with those with functioning graft (7.14+/-4.05 vs. 2.86+/-1.95; P=0.02).
Conclusions. The long-term patient and graft survival were similar in patients with MPGN and in controls. Recurrence occurred in one-fourth of patients and caused graft loss in 56%. Younger age at diagnosis of MPGN and low C3 during transplantation seems to be predictive of recurrence.
(C) 2011 Lippincott Williams & Wilkins, Inc."

Fibrillary Glomerulonephritis: A Report of 66 Cases from a Single Institution

Fibrillary Glomerulonephritis: A Report of 66 Cases from a Single Institution: "Background and objectives


Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease. Most previously reported cases were idiopathic. To better define the clinical-pathologic spectrum and prognosis, we report the largest single-center series with the longest follow-up.

Design, setting, participants, & measurements
The characteristics of 66 FGN patients who were seen at Mayo Clinic, Rochester, between 1993 and 2010 are provided.

Results
The mean age at diagnosis was 53 years. Ninety-five percent of patients were white, and the female:male ratio was 1.2:1. Underlying malignancy (most commonly carcinoma), dysproteinemia, or autoimmune disease (most commonly Crohn's disease, SLE, Graves' disease, and idiopathic thrombocytopenic purpura), were present in 23, 17, and 15% of patients, respectively. Presentation included proteinuria (100%), nephrotic syndrome (38%), renal insufficiency (66%), hematuria (52%), and hypertension (71%). The most common histologic pattern was mesangial proliferative/sclerosing GN followed by membranoproliferative GN. During an average of 52.3 months of follow-up for 61 patients with available data, 13% had complete or partial remission, 43% had persistent renal dysfunction, and 44% progressed to ESRD. The disease recurred in 36% of 14 patients who received a kidney transplant. Independent predictors of ESRD by multivariate analysis were older age, higher creatinine and proteinuria at biopsy, and higher percentage of global glomerulosclerosis.

Conclusions
Underlying malignancy, dysproteinemia, or autoimmune diseases are not uncommon in patients with FGN. Prognosis is poor, although remission may occur in a minority of patients without immunosuppressive therapy. Age, degree of renal impairment at diagnosis, and degree of glomerular scarring are predictors of renal survival.
"

A Systematic Review and Meta-Analysis of Rituximab in Antibody-mediated Renal Allograft Rejection

A Systematic Review and Meta-Analysis of Rituximab in Antibody-mediated Renal Allograft Rejection: "
Background: The standard treatment of antibody-mediated rejection (AMR) consists of antilymphocyte antibody, intravenous immunoglobulin, and plasmapheresis. This treatment is associated with a high rate of resistance and refractory AMR. Recent interest has focused on use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody.

Objective: We conducted a systematic review and meta-analysis of studies of RTX in AMR of the renal allograft.

Methods: Combining two comprehensive search themes (AMR and RTX), we searched electronic databases from 1969 through 2010, supplemented by a manual review of abstracts from nephrology and transplant meetings, and reference lists of review articles. All studies evaluating explicit response of patients with AMR to RTX were included. The outcome was pooled odds ratio (OR) of response to RTX.

Results: A total of 114 studies were identified, 94 of which were excluded on initial screening. Analysis of the 10 studies (249 patients) showed an OR of 3.16 (95% CI: 1.75–5.70) for response to RTX. Reported adverse effects included BK virus nephropathy, cytomegalovirus (CMV) viremia, pneumonia, herpes zoster, and septic shock.

Conclusion: This study suggests that RTX is a reasonable therapeutic option in the treatment of AMR. Further randomized studies are necessary to establish its efficacy and safety.
"

Effect of Obesity on the Outcome of Kidney Transplantation: A 20-Year Follow-Up

Effect of Obesity on the Outcome of Kidney Transplantation: A 20-Year Follow-Up: "Background. Cardiovascular disease is both a major threat to the life expectancy of kidney transplant recipients and an important determinant of late allograft loss. Obesity is an important risk factor for cardiovascular disease.
Methods. We investigated the relation between both pretransplant and 1-year posttransplant body mass index (BMI) with patient and renal graft survival in a cohort of 1810 adult patients. Sixty-one percent of all patients were men; median age (interquartile range [IQR]) was 46 years (35–56 years); median (IQR) pretransplant BMI was 23.0 kg/m2 (20.8–25.6 kg/m2); 1 year after transplantation, the median (IQR) BMI had increased 1.6 kg/m2 (0.3–3.2 kg/m2) and median (IQR) follow-up time was 8.3 years (5.3–12.0 years). We categorized BMI as follows: less than or equal to 20, more than 20 to less than or equal to 25 (normal), more than 25 to less than or equal to 30, and more than 30 (obesity) kg/m2.
Results. Using a Cox proportional hazards model, after adjustment for cardiovascular risk factors, the relative risks (95% confidence intervals) of death and death-censored graft failure during all follow-up for pretransplant obesity compared with normal BMI were 1.22 (0.86–1.74) and 1.34 (1.02–1.77), respectively; for obesity 1 year after transplantation compared with normal BMI, it was 1.39 (1.05–1.86) and 1.39 (1.10–1.74), respectively; and for change in BMI (per 5 kg/m2 increment) during the first year after transplantation, it was 1.23 (1.01–1.50) and 1.18 (1.01–1.38), respectively.
Conclusions. One year posttransplant BMI and BMI increment are more strongly related to death and graft failure than pretransplant BMI among kidney transplant recipients. Patients with BMI more than 30 kg/m2 compared with a normal BMI have approximately 20% to 40% higher risk for death and graft failure."

Albuminuria, Proteinuria, and Novel Urine Biomarkers as Predictors of Long-term Allograft Outcomes in Kidney Transplant Recipients

Albuminuria, Proteinuria, and Novel Urine Biomarkers as Predictors of Long-term Allograft Outcomes in Kidney Transplant Recipients: "Background: Proteinuria is an established marker of decreased kidney function after kidney transplant. It recently has been suggested that albuminuria might be a more reliable marker. Although albuminuria often is regarded as a marker of glomerular damage, because chronic renal allograft damage is believed to be predominantly an interstitial process, albuminuria in this case might reflect tubular damage. Accordingly, we investigated the value of albuminuria, proteinuria, and tubular damage markers (KIM-1 [kidney injury molecule 1], NAG [N-acetyl-β-d-glucosaminidase], NGAL [neutrophil gelatinase-associated lipocalin], and H-FABP [heart fatty acid binding protein]) in predicting graft outcome in kidney transplant recipients.Study Design: Prospective observational cohort study.Setting & Participants: 606 patients visiting our outpatient kidney transplant clinic in 2001-2003 were included and used in the analysis for death-censored graft failure. Median follow-up was 4.7 (25th-75th percentile, 3.8-5.2) years. 577 patients had follow-up longer than 1 year and were included in the analysis for estimated glomerular filtration rate (eGFR) decrease. Median follow-up was 3.2 (25th-75th percentile, 2.7-3.7) years.Predictors: Urine protein, albumin, and tubular damage markers in 24-hour urine samples.Outcomes: Death-censored graft failure and decrease in eGFR.Results: There were 42 patients with graft failure; mean eGFR change was −0.46 ± 3.7 (standard deviation) mL/min/1.73 m2/y. The area under the receiver operating characteristic curve for death-censored graft failure showed that albuminuria (0.78; 95% CI, 0.59-0.76) was significantly higher than proteinuria (0.67; 95% CI, 0.59-0.76; P = 0.001), NGAL (0.63; 95% CI, 0.52-0.74; P = 0.02), and H-FABP (0.62; 95% CI, 0.53-0.73; P = 0.005) and not significantly different from KIM-1 (0.74; 95% CI, 0.66-0.82) and NAG (0.75; 95% CI, 0.67-0.83). Results were similar for the eGFR decrease outcome.Limitations: Single-center observational study.Conclusions: Measuring albuminuria may provide superior predictions for long-term renal outcomes after kidney transplant than total proteinuria. Additional assessment of urinary excretion of tubular damage markers may have limited value."

Cost-Effectiveness of Initiating Dialysis Early: A Randomized Controlled Trial

Cost-Effectiveness of Initiating Dialysis Early: A Randomized Controlled Trial: "Background: Planned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs.Study Design: Patients with progressive chronic kidney disease and a Cockcroft-Gault estimated glomerular filtration rate of 10-15 mL/min/1.73 m2 were randomly assigned to start dialysis therapy at a glomerular filtration rate of either 10-14 (early start) or 5-7 mL/min/1.73 m2 (late start).Setting & Population: Of the original 828 patients in the IDEAL (Initiation of Dialysis Early or Late) Trial in renal units in Australia and New Zealand, 642 agreed to participate in this cost-effectiveness study.Study Perspective & Timeframe: A societal perspective was taken for costs. Patients were enrolled between July 1, 2000, and November 14, 2008, and followed up until November 14, 2009.Intervention: Planned earlier start of maintenance dialysis therapy.Outcomes: Difference in quality of life and costs.Results: Median follow-up of patients (307 early start, 335 late start) was 4.15 years, with a 6-month difference in median duration of dialysis therapy. Mean direct dialysis costs were significantly higher in the early-start group ($10,777; 95% CI, $313 to $22,801). Total costs, including costs for resources used to manage adverse events, were higher in the early-start group ($18,715; 95% CI, −$3,162 to $43,021), although not statistically different. Adjusted for differences in baseline quality of life, the difference in quality-adjusted survival between groups over the time horizon of the trial was not statistically different (0.02 full health equivalent years; 95% CI, −0.09 to 0.14).Limitations: Missing quality-of-life questionnaires and skewed cost data, although similar in each group, decrease the precision of results.Conclusion: Planned early initiation of dialysis therapy in patients with progressive chronic kidney disease has higher dialysis costs and is not associated with improved quality of life."

Mycophenolate Mofetil Initiation in Renal Transplant Patients at Different Times Posttransplantation: The TranCept Switch Study

Mycophenolate Mofetil Initiation in Renal Transplant Patients at Different Times Posttransplantation: The TranCept Switch Study: "Background. Despite evidence of favorable long-term effects of mycophenolate mofetil (MMF) in renal transplantation, its introduction at different times posttransplant has not been studied in large cohorts.
Methods. Single-organ renal allograft recipients (n=2217) who had MMF introduced 6 months to more than 20 years posttransplantation for various reasons were included in TranCept Switch, a multicenter, noninterventional, observational 4-year study. Changes in renal function before and after the introduction of MMF were analyzed.
Results. MMF was introduced because of renal function decline in 43% of patients and poor tolerability with previous treatment in 23% of patients. The change in slope of the calculated glomerular filtration rate (modification of diet in renal diseases formula) regression line before and after MMF initiation was +2.01 mL/min per year (P<0.001) on average. The greatest benefit was noted in patients who received MMF because of renal function decline and in whom calcineurin inhibitor treatment was subsequently reduced or withdrawn (+3.09 mL/min per year). Time from transplantation to MMF introduction influenced the glomerular filtration rate at MMF initiation (slow progressive deterioration) but not the direction of the slope change, which was positive even for late introduction.
Conclusion. MMF introduction may be associated with improvement or stabilization of renal function even several years after transplantation.
(C) 2011 Lippincott Williams & Wilkins, Inc."