Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Cohort Study of Outpatient Hemodialysis Management Strategies for COVID-19 in North-West London.

BACKGROUND: Dialysis patients are at risk of severe coronavirus disease 2019 (COVID-19). We managed COVID-19 hemodialysis outpatients in dedicated satellite dialysis units. This provided rare opportunity to study early disease progress in community-based patients. We aimed to (i) understand COVID-19 progression, (ii) identify markers of future clinical severity, and (iii) assess associations between dialysis management strategies and COVID-19 clinical outcomes. METHODS: We conducted a cohort study of all outpatients managed at a COVID-19 hemodialysis unit. We analyzed data recorded as part of providing COVID-19 clinical care. We analyzed associations between features at diagnosis and the first 3 consecutive hemodialysis sessions in patients who required future hospital admission, and those who had died at 28 days. RESULTS: Isolated outpatient hemodialysis was provided to 106 patients over 8 weeks. No patients received antiviral medication or hydroxychloroquine. Twenty-one patients (20%) were admitted at COVID-19 diagnosis; 29 of 85 patients (34%) were admitted after initial outpatient management; 16 patients (15%) died. By multivariate analysis, nonactive transplant list status, use of institutional transport, and increased white cell count associated with future hospitalization and increased age associated with death. Oxygen saturations progressively decreased over the first 3 dialysis sessions in the cohorts that progressed to future hospital admission or death. Mean ultrafiltration volume of the first 3 hemodialysis sessions was reduced in the same cohorts. CONCLUSIONS: Outpatient hemodialysis in patients with COVID-19 is safe for patients and staff. Features at the first 3 dialysis sessions can identify individuals at risk of future hospitalization and death from COVID-19.

Epidemiology of COVID-19 in an Urban Dialysis Center.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, many countries have instituted population-wide measures for social distancing. The requirement of patients on dialysis for regular treatment in settings typically not conducive to social distancing may increase their vulnerability to COVID-19. METHODS: Over a 6-week period, we recorded new COVID-19 infections and outcomes for all adult patients receiving dialysis in a large dialysis center. Rapidly introduced control measures included a two-stage routine screening process at dialysis entry (temperature and symptom check, with possible cases segregated within the unit and tested for SARS-CoV-2), isolated dialysis in a separate unit for patients with infection, and universal precautions that included masks for dialysis nursing staff. RESULTS: Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. We observed clustering in specific units and on specific shifts, with possible implications for aspects of service design, and high rates of nursing staff illness. A predictive epidemic model estimated a reproduction number of 2.2; cumulative cases deviated favorably from the model from the fourth week, suggesting that the implemented measures controlled transmission. CONCLUSIONS: The COVID-19 epidemic affected a large proportion of patients at this dialysis center, creating service pressures exacerbated by nursing staff illness. Details of the control strategy and characteristics of this epidemic may be useful for dialysis providers and other institutions providing patient care.

Successful management of post-transplant focal segmental glomerulosclerosis with therapeutic plasma exchange and rituximab.

BACKGROUND: Post-transplant focal segmental glomerulosclerosis (FSGS) is associated with renal allograft loss. Currently, optimal treatment remains controversial. METHODS: The aim of our study was to examine the efficacy and safety of therapeutic plasma exchange (TPE), and rituximab (RTX), in the management of post-transplant FSGS. The treatment protocol consisted of RTX and monthly cycles of 5 plasma exchanges for 6 months. We treated 10 transplant recipients with biopsy-proven post-transplant FSGS. Lastly, we compared the studied group to a historic control group of nine patients with post-transplant FSGS. RESULTS: 9 out of 10 patients achieved remission after the conclusion of treatment (4 complete and 5 partial), while 1 patient did not respond to treatment. During the follow-up period, there was one graft loss and one patient died while in remission from unrelated complications. There was a significant reduction in mean uPCR between diagnosis (517.4 ± 524.2 mg/mmol) and last follow-up (87 ± 121.6 mg/mmol) in the patients with sustained remission (p = 0.026). There was no significant decline in eGFR in the eight relapse-free responders at the end of follow-up. (54.4 ± 16.7 from 49.8 ± 20.4 ml/min) (p = 0.6) An increased response rate to the combined TPE and RTX treatment was demonstrated, when compared to a historic control group of nine patients with post-transplant FSGS, as only five out of nine patients achieved remission (two complete and three partial) in that group. CONCLUSIONS: In this study, treatment with TPE and RTX appears to be safe, well tolerated and effective in the management of patients with post-transplant FSGS.

Pre-emptive replacement of water treatment components improves responsiveness to erythropoiesis-stimulating agents in maintenance haemodialysis patients: a quality improvement report.

Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality. We examined the effect of water treatment component replacement on declining ESA responsiveness in the absence of chemical or microbiological standards failure. Pre-emptive renewal of the water treatment system supplying 802 standard-flux haemodialysis patients resulted in a significant rise in haemoglobin from (mean ± SD) 12.1 ± 1.2 to 12.3 ± 1.0 g/dl (p < 0.0001), accompanied by a significant decrease in prescribed dose of darbepoetin alfa from 47.9 ± 27.3 to 44.7 ± 27.6 µg/week (p < 0.0001). ESA responsiveness improved significantly from 0.060 ± 0.041 to 0.055 ± 0.040 µg/kg/g · dl(-1) (p < 0.0001) and the number of patients no longer requiring ESA therapy increased threefold. These benefits were derived in the absence of haemolysis or significant changes in water quality. Renewal of water system components should be conducted even in the absence of proven microbiological and chemical failure.

Invited manuscript poster on renal-related education American Society of Nephrology, Nov. 16-21, 2010. Improving access to kidney transplant information has increased preemptive living kidney donation.

Transplantation provides the best outcomes and quality of life for people with end-stage renal disease and therefore offers the optimum treatment of choice. Preemptive living donor (LD) transplantation is an increasingly preferable alternative to dialysis as transplantation outcomes indicate lower morbidity and mortality rates and greater graft and patient survival rates compared to those who are transplanted after dialysis has commenced. Despite nursing and medical teams giving information to patients regarding transplantation and living donation, the number of people coming forward for preemptive transplant work-up remained limited. Changing the format, environment, and quality of information given to patients and families seemed necessary in order to increase the number of preemptive transplants. Our data show that we have improved the access to the information seminars with attendance rising from 5 to 15 attendees per seminar (3 per year) in 2005 to average 65 attendees per seminar (6 per year) in 2010. By expanding the access to information for patients, their families and friends, living donation has increased with a growth in the proportion of preemptive LD transplants from 28% (23/81) in 2006 to 44% in 2010 (29/66; p = 0.05). We can conclude that expanding the pool accessing information has increased the number of preemptive (LD) transplants in our center.

Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient.

Metronidazole-induced central nervous system (CNS) toxicity causes a spectrum of neurological symptoms including ataxia, encephalopathy and peripheral neuropathy. It is associated with characteristic MRI changes of high signal intensity in the dentate nuclei. Given the increasing use of metronidazole, it is import to recognise this drug as a cause of ataxia, as it is entirely reversible on drug withdrawal.

ABO incompatible living renal transplantation with a steroid sparing protocol.

BACKGROUND: ABO incompatible (ABOi) live-donor renal transplantation is a successful and accepted form of treatment for patients with renal failure. Although there is significant controversy as to how antiblood group antibodies should be removed and their resynthesis prevented, subsequent immunosuppressive regimes have all involved steroids. We and other groups have successfully used steroid sparing regimes for conventional ABO compatible transplantation and this study describes the use of our steroid sparing protocol in ABOi transplantation. METHODS: We have transplanted 10 ABOi patients using 1 week of steroids (prednisolone 1 mg/kg for 4 days, 0.5 mg/kg for 3 days and then stopped), tacrolimus and mycophenolate mofetil. Steroids were reintroduced in the event of rejection. RESULTS: Patient- and allograft-survival 1 year posttransplantation is 100%. Three patients experienced antibody-mediated rejection within 2 weeks of transplantation, which was successfully reversed. There has been no late rejection. Allograft function was similar to our live-donor ABO compatible transplant patients receiving a similar steroid sparing regime (12-month mean creatinine 131+/-15 micromol/L vs. 138+/-48 micromol/L; mean CrCl 63.2+/-22 mL/min vs. 56.7+/-20 mL/min). CONCLUSIONS: This study shows that ABOi live-donor transplantation can be successfully accomplished using a steroid-sparing protocol.

Anaemia and congestive heart failure early post-renal transplantation.

BACKGROUND: Anaemia is common following renal transplantation and is associated with the development of congestive heart failure (CHF). However the prevalence of anaemia in the first year following transplantation and the association between anaemia occurring early and the development of CHF have been understudied. METHODS: In this study, 132 incident patients undergoing tacrolimus and mycophenolate mofetil-based renal transplantation were studied for the prevalence of, and risk factors for, anaemia and CHF in the early period post transplantation. RESULTS: Anaemia occurred in 94.5% and 53.1% of patients at 1 week and 12 months, respectively, and was associated with allograft dysfunction, hypoalbuminaemia, higher mycophenolic acid (MPA) levels, bacterial infection and hypoalbuminaemia. The association with hypoalbuminaemia may reflect the presence of chronic inflammation post-transplantation. Of patients displaying haemoglobin <11 g/dl, 41.1% and 29.4% were treated with erythropoiesis stimulating agents (ESAs) at 1 and 12 months respectively. CHF developed in 26 patients beyond 1 month post-transplantation, with echocardiographic left ventricular systolic function preserved in all but one. CHF was associated with anaemia and lower haemoglobin, allograft dysfunction, duration of dialysis and left ventricular hypertrophy on echocardiography prior to transplantation, suggesting the aetiology of CHF may involve the interplay of diastolic cardiac dysfunction, pre-load mismatch and after-load mismatch. CONCLUSIONS: Modification of risk factors may improve anaemia management post transplantation. Reducing the prevalence of anaemia may in turn reduce the incidence of CHF-these observations support the need for clinical trials to determine how anaemia management may impact CHF incidence.

The magnitude and time course of changes in mycophenolic acid 12-hour predose levels during antibiotic therapy in mycophenolate mofetil-based renal transplantation.

There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.

Clinical outcomes of renal transplantation using liquid chromatographic monitoring of tacrolimus.

It is suggested that specific methods of Tacrolimus monitoring rather than immunoassays which over-estimate Tacrolimus levels, should be used in transplant recipients. There is limited data, however, comparing clinical outcomes of renal transplantation using each of these techniques. In this study, 40 renal transplant recipients with Tacrolimus monitoring by Microparticle Enzyme Immunoassay (MEIA; target trough level 10-15 ng/ml) were compared with 40 patients monitored by High Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS; target trough level 8-13 ng/ml). All received anti CD25 antibody induction and Mycophenolate Mofetil in a steroid sparing protocol. No demographic differences were seen between MEIA and HPLC-MS groups. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying Tacrolimus levels within target range at three and six months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in 4 patients in the MEIA group and 1 patient in the HPLC-MS group (P = 0.17). Biopsy proven acute Tacrolimus nephrotoxicity occurred in 6 patients in the MEIA group, and 7 in the HPLC-MS group (P = NS). No difference was seen in serum creatinine or estimated creatinine clearance at 3 or 6 months. No difference between groups was seen in systolic or diastolic blood pressure, or total cholesterol at 3 or 6 months. 2 patients in the MEIA group developed CMV disease and 1 developed posttransplantation diabetes mellitus. CMV and posttransplantation diabetes were not seen in the HPLC-MS group. 2 patients in each group developed reversible tremor. This study suggests that renal transplantation with HPLC-MS monitoring of Tacrolimus is safe and effective.

Five years of steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil.

Steroid sparing with tacrolimus and mycophenolate mofetil (MMF) is associated with good short-term renal transplant outcomes. However, late allograft dysfunction and failure remain concerns. In this study, 101 consecutive patients underwent renal transplantation with tacrolimus, MMF, and 7 days of corticosteroids only. After a median follow-up of 51 months (range 36-62), overall patient survival is 97%, and overall survival with graft function is 91%. The acute rejection rate at 12 months was 19%. Late rejection was uncommon, with only three further episodes beyond 12 months. Graft function was stable during the study, with a mean creatinine of 140 micromol/L and mean estimated creatinine clearance of 57 ml/min at the end of follow-up. Six patients developed posttransplant diabetes mellitus (three cases beyond 12 months). This steroid avoidance regimen is associated with excellent medium-term patient and graft outcomes, and a low incidence of side effects.

Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation.

Evidence suggests that steroid sparing in renal transplantation is associated with good outcomes, although there are limited data regarding steroid sparing in Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we describe the use of these agents in 101 consecutive patients undergoing renal transplantation using only a 7-day course of prednisolone. Median follow-up was 33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%, respectively. The acute rejection rate at both 6 and 12 months was 19%, with two episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was administered to 25 patients at high immunological risk: a trend toward a lower rejection rate was seen in these patients compared with those at lower risk but not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed vascular involvement. Allograft function was preserved at 12 months with a mean creatinine of 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus was 3.5%. This steroid-sparing regime is associated with excellent patient and graft outcomes, and a low incidence of side effects.

Outcome of renal transplantation in South Asian recipients is similar to that in non-Asians.

BACKGROUND: The United Kingdom has a large South Asian population, in which there is a high rate of renal disease and which forms a significant percentage of the renal transplant waiting list. Information about short- and long-term transplant outcomes in this ethnic group is limited, although it has been suggested that graft survival is poorer in this population compared with non-Asians. METHODS: The authors examined the outcome and determinants of medium-term (5-year) survival in 245 renal transplants, 53 of which were performed in South Asian patients between 1995 and 2002. RESULTS: Three-year survival with a functioning graft was 89% for the non-Asians and 85% for the South Asians. At 5 years, this deviated to 83% and 70%, respectively, for the two groups, but this did not reach statistical significance. Acute rejection rates were similar in the two groups. South Asian ethnicity was not a significant predictor of medium-term graft loss in the authors' study. CONCLUSIONS: In this cohort of patients, South Asian ethnic background did not confer a survival disadvantage after renal transplantation.