Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis

Damodar A, Mustafa R, Bhatnagar J, Panesar M, Gundroo A, Zachariah M, Blessios G, Tornatore K, Weber‐Shrikant E, Venuto R. Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis.
Clin Transplant 2011: 25: 375–379. © 2010 John Wiley & Sons A/S. Abstract: Post‐transplant glomerulonephritis (PTGN) accounts for 4–10% of late graft loss. Six consecutive patients who developed PTGN 3–72 months post‐transplant presented to our center with deteriorating kidney function and proteinuria. Three had focal segmental glomerulosclerosis; one had membranoproliferative glomerulonephritis Type 1; one recurrent membranous nephropathy; and one recurrent immunoglobin A nephropathy. All six were treated with an aggressive immunosuppression regimen including rituximab, pulse steriods and/or maximization of mycophenolic acid and calcineurin inhibitor therapy. Four of the six patients received plasma exchange. The patients were followed for a minimum of nine months after treatment. Proteinuria decreased from 7.2 ± 4.4 to 1.4 ± 1.5 g (p = 0.04), while mean estimated glomerular filtration rate was 31.2 ± 13.1 and 42.5 ± 21.7 mL/min (p = 0.07) at nine months. No adverse events were noted. These observations suggest that immune modulating therapy may be of benefit in the treatment of PTGN.     

Plasma cell infiltrates and renal allograft outcomes in indigenous and non-indigenous people of the Northern Territory of Australia

Introduction: Plasma cell‐rich rejection is a distinct histological phenomenon associated with poor renal allograft outcomes. Aboriginal and Torres Straight Islander (ATSI) transplant recipients have poorer allograft survival and higher rates of acute rejection. We sought to determine whether a higher incidence of plasma cell‐rich infiltrates (PCIR) could account for poorer survival. Methods: Renal transplant biopsies performed in recipients from the Northern Territory of Australia between 1985 and 2007 were reviewed and correlated with outcome. Biopsies were designated PCIR positive when plasma cells constituted >10% of the interstitial infiltrate. Results: Four hundred and seventy‐seven biopsies from 177 recipients (108 ATSI) were performed. Median graft survival was shorter for recipients with PCIR: 4.0 years (interquartile range 2.18–6.41) versus 5.4 years (2.0–9.99) (P = 0.013). ATSI recipients had higher rates of plasma cell‐rich rejection (RR 1.76, 95% CI 1.43–2.17, P < 0.0001), which occurred earlier (251 vs 869 days, P = 0.03) compared with non‐indigenous recipients. On multivariate analysis, PCIR did not independently influence allograft survival. There was a correlation between PCIR and panel reactive antibody peak >20% (RR 1.29, 95% CI 1.03–1.56, P = 0.025), ≥5 human leukocyte antigen mismatches (RR 1.91, 1.41–2.58, p < 0.0001), increasing post‐transplant infection rate (>10 infections RR 5.11, 1.69–15.5, P = 0.004), and subsequent death from septicaemia (RR 1.6, 1.17–2.18, P = 0.003). Conclusion: PCIR is associated with infection and markers of chronic immunological stimulation but does not independently contribute to inferior renal allograft outcomes, even in ATSI recipients.     

The clinical and pathological characteristics of Chinese patients with pauci‐immune crescentic glomerulonephritis

SUMMARY In the present study, we investigated pauci‐immune crescentic glomerulonephritis (PICGN) in Chinese patients. During 13 years (1985–98), 6400 patients underwent non‐transplanting renal biopsy in the Nanjing Jinling Hospital. Twenty‐four patients were diagnosed as having PICGN. They were 16 women and eight men with a median age of 33 (range 10–76 years). Microscopic polyarteritis (33.3%) and polyarteritis nodosa (8.3%) were the secondary diseases. The incidence of PICGN was 0.37% in renal biopsies and 22.9% in crescentic glomerulonephritis. Clinically, most patients (75.0%) showed rapidly progressive nephritis with enlarged kidneys. Onset gross haematuria was noted in 58.3% of the patients, hypertension 45.8%, nephrotic syndrome 41.7%, and oliguria 25.0%. However, systemic symptoms were rare except anaemia. Pathologically, we observed necrosis of glomerular capillaries (62.5%), infiltration of monocytes and neutrophil cells in glomeruli (66.7%), and vasculitis in interstitium (53.3%), in addition to glomerulosclerosis more than 50% (45.8%), severe tubular atrophy (83.3%) and interstitial fibrosis (75.0%). Antineutrophil cytoplasmic antibodies were positive in 52.2%. All patients except two received intensively immunosuppressive therapy. Sixteen patients were subjected to long‐term follow up (median 29.8, range 8–92 months), 12 of them had life‐sustaining renal function, four had normal range of serum creatinine (< 124 μmol/L), only four patients were dialysis dependent.     

A pilot study of ultrasound evaluation of gastric emptying in patients with end‐stage renal failure: a comparison with healthy controls

This prospective study was designed to evaluate gastric volume and content in patients with renal failure and healthy controls after an overnight fast, immediately after a light meal and at 6 h after the meal. Thirty subjects in each group were recruited. At each scanning session, gastric antral cross‐sectional area was measured in the supine recumbent and right lateral decubitus positions, and a qualitative assessment of gastric contents was made using the Perlas three‐point grading system. Six hours after the meal, the mean (SD) antral cross‐sectional area in the supine position was 471 (195) mm² in patients with renal failure and 319 (106) mm² in healthy controls (p = 0.028), whereas in the right lateral position it was 756 (320) and 521 (180) mm², respectively (p = 0.21). In terms of the qualitative assessments of gastric contents, all subjects had an empty stomach after an overnight fast. Five patients with renal failure and no controls had Perlas grade 2 images, indicating significant gastric contents, 6 h after a meal (p = 0.026). This study supports the use of bedside gastric ultrasound as a point‐of‐care test for patients with known risk factors for delayed gastric emptying.     

DAA‐based antiviral treatment of patients with chronic hepatitis C in the pre‐ and postkidney transplantation setting

DAA‐based regimens for chronic hepatitis C infection encourage treatment of “difficult‐to‐treat” cohorts. This study investigated efficacy and safety of DAA‐based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty‐five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir‐based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV‐RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty‐four (96%) patients achieved SVR 12/24 (ITT‐analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely – both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re‐infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient – SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real‐life cohorts.     

Ethnic and Gender Related Differences in the Risk of End‐Stage Renal Disease After Living Kidney Donation

There is limited data pertaining to the risk of End Stage Renal Disease (ESRD) after living kidney donation. The Organ Procurement and Transplantation Network and the Center for Medicare and Medicaid Services databases were used to identify living kidney donors (LKDs) who subsequently developed ESRD and to calculate LKD ESRD rates. We found 126 cases of ESRD among 56 458 LKDs (0.22%) who donated during October 1, 1987–March 31, 2003. The overall LKD ESRD rate was 0.134 per 1000 years at risk, with an average duration of follow‐up of 9.8 years. ESRD rates for LKDs overall and for Black, White, male and female donors compared favorably to the ESRD incidence in the general population. The LKD ESRD rate was nearly five times higher for Blacks than for Whites and two times higher for males than females. However, these ethnic and gender‐related differences were similar to those previously reported for ESRD in the general population. Our findings do not show an increase in the risk of ESRD for LKDs and support the current practice of living kidney donation. Further research is needed to determine if improved donor screening or follow‐up will reduce the risk of postdonation ESRD.     

Social support and treatment adherence in patients with end‐stage renal disease: A systematic review

Successful dialysis in end‐stage renal disease (ESRD) largely depends on the patients’ ability to adhere to several clinical requirements and life‐style changes. Social support has been consistently linked to better health outcomes in a number of chronic diseases. The current study presents a systematic review of the literature on the relationship between social support and treatment adherence in ESRD. The search was performed on Web of Science, PsycInfo, ScienceDirect, and Scopus from January 19 to May 15, 2019. Two hundred and twenty‐four records were identified. After quality assessment, 17 studies were included for qualitative synthesis. This review comprised a total of 2362 patients. Most patients were on hemodialysis (97.5%) for an average of 58.2 months. Results suggested an overall pattern of mixed findings regarding the association between social support and treatment adherence. Adherence to fluid restrictions was the type of adherence with more significant associations with social support (63%). Mixed results were found for adherence to dialysis sessions (50%) and to medication (50%). Associations between adherence to diet restrictions and social support were found in 44% of the included studies. No significant associations were found between social support and adherence to follow‐up consults. All of the included studies combining several types of adherence into an overall score found significant associations with social support. Findings suggested that it might be particularly beneficial to focus future research and clinical efforts toward social support from family, significant others, and health professionals, to improve patient's with ESRD treatment adherence.     

Challenges in containing the burden of hepatitis B infection in dialysis and transplant patients in India

Aim: Whether or not completing the hepatitis B vaccination in patients who have undergone kidney transplantation in the middle of incomplete vaccination schedule leads to development of protective antibody titres is not known. This study was designed to determine whether the strategy of completing hepatitis B virus (HBV) vaccination after transplantation is efficacious. Methods: Sixty‐four end‐stage renal disease (ESRD) patients were screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti‐HBs), hepatitis B e‐antigen (HBeAg) and HBV DNA. HBsAg negative patients received four doses of 40 µg recombinant HBV vaccine. Schedule was continued in after transplantation period if it was incomplete before transplant. Anti‐Hbs titres were evaluated at 1, 3, 6, 9 and 12 months. Results: Past HBV infection was noted in 12 patients: 10 by serology plus viraemia and two by viraemia alone. Of the 46 patients without current or past HBV infection who had received at least two doses of the vaccine before transplant, 17 each had received two and three doses and 12 had completed the schedule. Seventeen (37%) exhibited protective titres. Patients who had completed vaccination were more likely to have protective titres than those incompletely vaccinated (P = 0.02). Five patients responded to post‐transplant vaccination. Conclusion: Partially vaccinated patients do not mount an adequate antibody response despite continued vaccination in the post‐transplant period, whereas complete vaccination provides protection in 60%. The present study data highlights the need of administration of a full schedule of HBV vaccination before kidney transplantation. Nucleic acid‐based tests can identify occult HBV infection.     

Functional characterization of late outgrowth endothelial progenitor cells in patients with end‐stage renal failure

Renal transplantation is potentially curative in renal failure, but long‐term efficacy is limited by untreatable chronic rejection. Endothelial damage contributes to chronic rejection and is potentially repairable by circulating endothelial progenitor cells (EPC). The frequency and function of EPC are variably influenced by end‐stage renal failure (ESRF). Here, we isolated and functionally characterized the late outgrowth EPC (LO‐EPC) from ESRF patients to investigate their potential for endothelial repair. Patients with ESRF generated more LO‐EPC colonies than healthy controls and had higher plasma levels of IL‐1rα, IL‐16, IL‐6, MIF, VEGF, Prolactin, and PLGF. Patients' LO‐EPC displayed normal endothelial cell morphology, increased secretion of PLGF, MCP‐1, and IL‐1β, and normal network formation in vitro and in vivo. They demonstrated decreased adhesion to extracellular matrix. Integrin gene profiles and protein expression were comparable in patients and healthy volunteers. In some patients, mesenchymal stem cells (MSC) were co‐isolated and could be differentiated into adipocytes and osteocytes in vitro. This is the first study to characterize LO‐EPC from patients with ESRF. Their behavior in vitro reflects the presence of elevated trophic factors; their ability to proliferate in vitro and angiogenic function makes them candidates for prevention of chronic rejection. Their impaired adhesion and the presence of MSC are areas for potential therapeutic intervention.