Preservation of kidney function in kidney transplant recipients by alkali therapy (Preserve-Transplant Study): rationale and study protocol

Kaposi Sarcoma (KS) is driven by human herpes virus 8 causing vascular proliferation which is induced by loss of immune function most often due to HIV or immunosuppressants. KS occurs with increased incidence in kidney transplant recipients, but rarely is disseminated. We report a 64-year-old male who developed severely disseminated KS 5 months after ABO-incompatible kidney-transplantation. No guidelines for chemotherapy exist in this case and reduced kidney function and impaired immune system complicates the use of systemic chemotherapy in kidney transplant recipients. A combination of paclitaxel and gemcitabine followed by two days of hemodialysis treatment was chosen since paclitaxel can be given in full dose independently of kidney function and gemcitabine is metabolised to 2′,2′-difluorodeoxyuridine which is found to be highly dialysable. The present treatment was well tolerated by the patient with one episode of leukopenia and elevated alanine transaminase during treatment which resolved. There were no serious adverse events and the patient obtained a complete remission verified by Positron Emission Tomography CT after ending chemotherapy and at one-year follow up.

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The association of two single-nucleotide polymorphisms of the FOXP3 gene (rs3761548 and rs3761547) with renal allograft function and survival in kidney transplant recipients

Immunopathologia Persa ◽

10.34172/ipp.2021.21 ◽

2020 ◽

Vol 7 (2) ◽

pp. e21-e21

Author(s):

Vahideh Ebrahimzadeh Attari ◽

Seyed Sadroddin Rasi Hashemi ◽

Solmaz Oloufi ◽

Leili Aghebati Maleki ◽

Dariush Shanehbandi ◽

...

Keyword(s):

Serum Creatinine ◽

Serum Creatinine Level ◽

Kidney Transplant ◽

Creatinine Level ◽

Kidney Function ◽

Renal Allograft ◽

Regulatory Protein ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Allograft Function

Introduction: The FOXP3 protein is an immune regulatory protein that specifically maintains the function and differentiation of regulatory T cells (Tregs) and prevents autoimmunity. Variations in FOXP3 gene may alter its function and also the immune response. Objectives: The present study was conducted to investigate the association of the FOXP3 gene polymorphisms -3499 A/G and -3279 A/C with renal allograft function and survival in kidney transplant recipients. Patients and Methods: In this cross-sectional study, 150 eligible kidney transplant recipients were evaluated. Kidney function was evaluated at three- and five-year post-transplant using serum creatinine level and glomerular filtration rate as indicators. Genotyping of the study participants was performed using the PCR– restriction fragment length polymorphism method. Results: The frequencies of AA, AG, and GG genotypes of the -3499 A/G polymorphism were 62.42%, 29.53%, and 8.05%, respectively. For the -3279 A/C polymorphism, the frequencies of the AA, AC, and CC genotypes were 21.33%, 32%, and 46.67%, respectively. The mean ± SD of serum creatinine level, three and five years after transplantation were 1.70 ± 1.58 and 1.87 ± 1.94, respectively. Serum creatinine level and kidney function did not show any significant association with these polymorphisms. Conclusion: In the present study, only 10% of participants experienced episodes of severe kidney dysfunction and we did not find any significant association between kidney function and the subjects’ genotypes. Further epidemiologic studies with greater sample sizes may be needed to clarify this association.

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P0004REDUCED EXPRESSION OF PROXIMAL ACID-BASE TRANSPORT PROTEINS IN KIDNEY TRANSPLANT PATIENTS WITH METABOLIC ACIDOSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0004 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Anna Wiegand ◽

Arezoo Daryadel ◽

Pedro Henrique Imenez da Silva ◽

Ariana Gaspert ◽

Rudolf Peter Wuthrich ◽

...

Keyword(s):

Kidney Transplantation ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Proximal Tubule ◽

Kidney Transplant ◽

Transport Proteins ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Acid Base ◽

Alkali Therapy

Abstract Background and Aims Metabolic acidosis (MA) is a frequent complication of chronic kidney disease and an independent risk factor for kidney disease progression and mortality. MA is highly prevalent after kidney transplantation (12%-58%)(1). However, there are scarcely any data available on the underlying pathomechanisms and in particular molecular mechanisms involved in metabolic acidosis after kidney transplantation. Thus, we wanted to investigate the expression of key acid base transport proteins in kidney biopsies of kidney transplant recipients with and without metabolic acidosis. Method We evaluated 22 kidney transplant biopsies including 9 biopsies from kidney transplant recipients (KTR) with MA, nine biopsies from KTRs without MA (control) and four biopsies from KTRs with MA that were consequently subjected to alkali therapy (Alkali therapy). Immunofluorescence staining was used to identify key renal acid-base transport proteins. Additionally, six control kidneys were analyzed. Immunofluorescence staining was used to identify key renal acid-base transport proteins along the nephron. In addition, RNA extraction and full RNA sequencing analysis of all biopsies –where available- was performed. Results In the proximal tubule, we observed reduced immunostaining for the sodium bicarbonate cotransporter NBCe1 (SLC4A4) in the MA group compared to the control and alkali group, whereas the alkali group demonstrated the strongest staining of all three groups. In the distal nephron, expression of the chloride/bicarbonate exchanger Pendrin (SLC26A4) and the B1 subunit of the V-ATPase (ATP6V1B1) were markedly stronger in the alkali and control group compared to the MA group. Expression of other acid base proteins such as Renal ammonia transporter RhCG (SLC42A3), Carbonic Anhydrase II, Glutamate dehydrogenase, anion exchanger AE1 (SLC4A1) and the B2 subunit of the V-ATPase (ATP6V1B2) showed no difference among all groups. Interestingly, the B2 subunit was absent in the proximal tubule in transplant biopsies of all groups. In kidney biopsies of transplant recipients with metabolic acidosis RNA abundance of NBCe1, CAII and Pendrin was lower while RhCG and B1 RNA counts were not different when compared to recipients without metabolic acidosis. Conclusion Our data demonstrate altered protein and mRNA expression of several key acid base transporters in kidney biopsies of transplant recipients with metabolic acidosis. Treatment with alkali may have the potential to reverse or prevent these changes in renal allografts after transplantation.

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Mediterranean Style Diet and Kidney Function Loss in Kidney Transplant Recipients

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.06710619 ◽

2020 ◽

Vol 15 (2) ◽

pp. 238-246 ◽

Cited By ~ 5

Author(s):

António W. Gomes-Neto ◽

Maryse C.J. Osté ◽

Camilo G. Sotomayor ◽

Else van den Berg ◽

Johanna Marianna Geleijnse ◽

...

Keyword(s):

Kidney Transplant ◽

Mediterranean Diet ◽

Kidney Function ◽

Graft Failure ◽

Graft Loss ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mediterranean Diet Score ◽

The Mediterranean ◽

Diet Score

Background and objectivesDespite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients.Design, setting, participants, & measurementsWe included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points.ResultsDuring median follow-up of 5.4 (interquartile range, 4.9–6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently.ConclusionsAdherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients.

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