Is Metabolic Acidosis a Friend or Foe for Cardiovascular Disease in Kidney Transplant Recipients?

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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Secular Trends in Cardiovascular Disease Among Kidney Transplant Recipients.

Transplantation Journal ◽

10.1097/00007890-201407151-01742 ◽

2014 ◽

Vol 98 ◽

pp. 520

Author(s):

N. Lam ◽

K. Naylor ◽

S. Shariff ◽

E. McArthur ◽

G. Knoll ◽

...

Keyword(s):

Cardiovascular Disease ◽

Kidney Transplant ◽

Secular Trends ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Clinical Features of Kidney Transplant Recipients Admitted to the Intensive Care Unit

Progress in Transplantation ◽

10.1177/1526924817746685 ◽

2017 ◽

Vol 28 (1) ◽

pp. 56-62 ◽

Cited By ~ 5

Author(s):

Flávio Geraldo Rezende Freitas ◽

Fábio Lombardi ◽

Eduardo Souza Pacheco ◽

Tainá Veras de Sandes-Freitas ◽

Laila Almeida Viana ◽

...

Keyword(s):

Cardiovascular Disease ◽

Intensive Care Unit ◽

Hospital Mortality ◽

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Saps 3 ◽

Icu Admission ◽

Transplant Patients ◽

Kidney Transplant Patients

Introduction: There is a paucity of data regarding the complications in kidney transplant patients who may require intensive care unit (ICU) management, despite being the most common solid organ transplant worldwide. Objective: To identify the main reasons for ICU admission and to determine the factors associated with hospital mortality in kidney transplant recipients. Design: This single-center retrospective cohort study was conducted between September 2013 and June 2014, including all consecutive kidney transplant patients requiring ICU admission. We collected data on patient demographics, transplant characteristics, clinical data, and prognostic scores. The independent determinants of hospital mortality were identified by multiple logistic regression analysis. We also assessed the performance of Simplified Acute Physiology Score 3 (SAPS 3) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Results: We analyzed data from 413 patients, the majority of whom were admitted late after renal transplantation (1169 days; 63-3003 days). The main reason for admission was sepsis (33.2%), followed by cardiovascular disease (16%). Age (odds ratio [OR] 1.05, confidence interval [CI], 1.01-1.09), SAPS 3 score (OR 1.04, CI, 1.01-1.08), the need for mechanical ventilation (OR 26.47, CI, 10.30-68.08), and vasopressor use (OR 3.34, CI, 1.37-8.13) were independently associated with hospital mortality. The performance of SAPS 3 and APACHE II scores was poor in this population and overestimated the mortality rates. Conclusion: Sepsis was the main reason for ICU admission in kidney transplant recipients, followed by cardiovascular disease. Age and disease severity were associated with hospital mortality.

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