The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study

INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR).AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function.MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun” were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used.RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a “mixed” rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR + IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease.CONCLUSION: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.

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The determinants, biomarkers, and consequences of microvascular injury in kidney transplant recipients

AJP Renal Physiology ◽

10.1152/ajprenal.00163.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. F9-F19 ◽

Cited By ~ 1

Author(s):

Alice Doreille ◽

Mélanie Dieudé ◽

Heloise Cardinal

Keyword(s):

Kidney Disease ◽

Kidney Transplant ◽

Interstitial Fibrosis ◽

Ischemia Reperfusion ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hla Antibodies ◽

Microvascular Injury ◽

Antibody Mediated Rejection ◽

Peritubular Capillaries

Independent of the initial cause of kidney disease, microvascular injury to the peritubular capillary network appears to play a central role in the development of interstitial fibrosis in both native and transplanted kidney disease. This association is explained by mechanisms such as the upregulation of profibrotic genes and epigenetic changes induced by hypoxia, capillary leakage, endothelial and pericyte transition to interstitial fibroblasts, as well as modifications in the secretome of endothelial cells. Alloimmune injury due to antibody-mediated rejection and ischemia-reperfusion injury are the two main etiologies of microvascular damage in kidney transplant recipients. The presence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies, histological findings, such as diffuse C4d staining in peritubular capillaries, and the extent and severity of peritubular capillaritis, are commonly used clinically to provide both diagnostic and prognostic information. Complement-dependent assays, circulating non-HLA antibodies, or evaluation of the microvasculature with novel imaging techniques are the subject of ongoing studies.

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MO995DO THE TIMELINE AND SPECTRUM OF INFECTIONS CHANGE AFTER ANTI-REJECTION THERAPY IN KIDNEY TRANSPLANT RECIPIENTS?

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab111.0019 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Arvind Krishnakumar ◽

Selvin Sundar Raj Mani ◽

Rizwan Alam ◽

Manish Lalwani ◽

Athul Thomas ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Median Time ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Care Hospital ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection

Abstract Background and Aims The infections in kidney transplant recipients has been well defined. The timeline of infections and type of infection among patients who received anti-rejection therapy for acute rejection when compared to the patients who did not develop an acute rejection. Method Renal transplant recipients with post-transplant median follow up of four years from July 2009-June 2018 were included in a retrospective cohort study at a tertiary care hospital. Demographic characteristics, biopsy proven rejections, infections and graft and patient outcome were collected from transplant records and the hospital clinical workstation. Early and late acute rejections were defined as less than and more than 3 months respectively. The rates of various infections, type and time to develop an infection in the acute rejection group were compared with the patients who did not develop any rejection. Results A total of 794 patients underwent kidney transplant during the study with mean age of 35.5±12 years and 78% being male. Two hundred and eight four patients (35.8 %) had one or more biopsy proven rejections during the median follow up of 48 months (IQR 28,77). 213 patients (75%) developed early acute rejection (less than 3 months) while the remainder developed late acute rejection. The median time to develop the first acute rejection was 12 days (IQR 6,93.3). Majority of the patients (176, 62%) developed biopsy proven acute cellular rejection, 77 patients (27.1%) acute antibody mediated rejection and rest (10.9%) either mixed or borderline rejection who were treated. The proportion of BKV infection and infective diarrhea were more in rejection group when compared to no rejection group which was statistically significant (refer Table 1). At follow up, the patients who developed rejection had more graft loss (p value 0.010) but no increase in mortality. The predictors of infection among the patients who received anti-rejection therapy were identified. The median time to develop any infection in both groups were also compared. The spectrum of infections and outcome following early and late rejections were compared. Subgroup analysis was done to look at the eGFR, proteinuria trend, graft outcomes in patients with no rejection, rejection without any infection at follow up and rejection with any infection at follow up. The effect of type of anti-rejection therapy on spectrum of infections was also studied. Conclusion This is one of the few studies which looked at the effect of anti-rejection therapy in kidney transplant recipients. Anti-rejection treatment received post kidney transplant resulted in increased rates of BKV infection and infective diarrhea. Patients with acute rejection had more graft loss during follow up with no significant effect on mortality.

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MO202RITUXIMAB TREATMENT IN NEPHROLOGY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0080 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Mouna Malki abidi ◽

Samia Barbouch ◽

Hajji Mariem ◽

Tasnim Mesbahi ◽

Amel Harzallah ◽

...

Keyword(s):

B Cells ◽

Kidney Transplant ◽

Large Cell ◽

Kidney Transplant Patient ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection ◽

Maintenance Immunosuppression ◽

Interesting Alternative

Abstract Background and Aims The B cells have a central role in the pathogenesis of several renal pathologies. Rituximab, a monoclonal antibody directed against the CD20 receptor expressed on the surface of B cells is an interesting alternative to conventional treatments of kidney pathologies. Method We conducted a descriptive retrospective study of the use of rituximab in nephrology patients. Results We collected 25 patients including 12 women and 13 men. The mean age was 33,5 [16-55] years. The rituximab was indicated for an extramembranous glomerulopathy in 6 patients, a focal segmental glomerulosclerosis in 4 patients, a minimal change disease in 4 patients, a lupus nephritis in 5 patients, and a granulomatosis with polyangiitis in 2 patients. Four kidney transplant patient received rituximab for the treatment of antibody mediated rejection in 3 cases and large cell lymphoma in 1 case. The average time between the diagnosis of the renal disease and starting treatment with rituximab was of 76 +/- 46,5 months. And it was of 16 [ 0,7 ; 59,8] months after transplantation in kidney transplant recipients. Side effects have been observed in 11 cases (44%). A favorable response has been obtained in 10 cases (40 %), within an average of 2,27 months, with at least one relapse in 4 cases. The follow-up time was 36,33 +/- 31,67 months. Conclusion Rituximab has been shown to be helpful in several cases of kidney disease. It may reduce the need for maintenance immunosuppression and help in some cases that are refractory to other therapies.

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Response to treatment in kidney transplant recipients with acute antibody-mediated rejection: A follow-up biopsy study

Clinical Nephrology ◽

10.5414/cn109819 ◽

2020 ◽

Vol 93 (2) ◽

pp. 85-90

Author(s):

Funda TaslÄ± Alkan ◽

Erhan Tatar ◽

Murat Karatas ◽

Cenk Simsek ◽

Ismail Can Tercan ◽

...

Keyword(s):

Kidney Transplant ◽

Response To Treatment ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection

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Long-term follow-up of polyneuropathy in diabetic kidney transplant recipients

Diabetes ◽

10.2337/diabetes.37.9.1247 ◽

1988 ◽

Vol 37 (9) ◽

pp. 1247-1252 ◽

Cited By ~ 4

Author(s):

J. A. Van der Vliet ◽

X. Navarro ◽

W. R. Kennedy ◽

F. C. Goetz ◽

J. J. Barbosa ◽

...

Keyword(s):

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Diabetic Kidney ◽

Long Term Follow Up

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Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽

10.3390/antiox10071102 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1102

Author(s):

Angelica Rodriguez-Niño ◽

Diego O. Pastene ◽

Adrian Post ◽

M. Yusof Said ◽

Antonio W. Gomes-Neto ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Cox Regression ◽

Carbonyl Stress ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

High Concentrations ◽

Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

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