Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria

Ekser, Burçin; Mangus, Richard S.; Kubal, Chandrashekhar A.; Fridell, Jonathan A.; Powelson, John A.; Nagaraju, Santosh; Mihaylov, Plamen; Phillips, Carrie L.; Saxena, Romil; Goggins, William C.

doi:10.1159/000447785

Cited by 5 publications

(4 citation statements)

References 20 publications

(28 reference statements)

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“…Oxalate nephropathy affecting allograft kidneys has been reported in patients with enteric hyperoxaluria due to gastric bypass ( 28 , 29 , 30 ) and pancreatic insufficiency ( 31 ), similar to our findings. The apparent temporal increase in ingestion-associated oxalate nephropathy was not observed in our small cohort of kidney transplant patients.…”

Section: Discussionsupporting

confidence: 92%

Increased Rates of Supplement-Associated Oxalate Nephropathy During COVID-19 Pandemic

Fong

Wusirika²,

Rueda³

et al. 2022

Kidney International Reports

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Section: Discussionsupporting

confidence: 92%

Increased Rates of Supplement-Associated Oxalate Nephropathy During COVID-19 Pandemic

Fong

Wusirika²,

Rueda³

et al. 2022

Kidney International Reports

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“…Furthermore, recent epidemiologic studies link kidney stone recurrence to the development of chronic kidney disease (CKD) [5]. Additional complications in some patients with secondary hyperoxaluria may include oxalate nephropathy, nephrocalcinosis and progression to end-stage renal disease and damage to the transplanted kidney if present [6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme

Langman

Grujić²,

Pease³

et al. 2016

Am J Nephrol

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Background: Hyperoxaluria may result from increased endogenous production or overabsorption of dietary oxalate in the gastrointestinal tract leading to nephrolithiasis and, in some, to oxalate nephropathy and chronic kidney disease. ALLN-177 is an oral formulation of a recombinant, oxalate specific, microbial enzyme oxalate decarboxylase intended to treat secondary hyperoxaluria by degrading dietary oxalate in the gastrointestinal tract, thereby reducing its absorption and subsequent excretion in the urine. Methods: This double-blind, placebo controlled, randomized, cross-over, phase 1 study of ALLN-177 evaluated the tolerability of ALLN-177 and its effect on urinary oxalate excretion in 30 healthy volunteers with hyperoxaluria induced by ingestion of a high oxalate, low calcium (HOLC) diet. The primary end point was the difference in the mean 24-hour urinary oxalate excretion during the ALLN-177 treatment period compared with the placebo treatment period. Results: The daily urinary oxalate excretion increased in the study population from 27.2 ± 9.5 mg/day during screening to 80.8 ± 24.1 mg/day (mean ± SD) on the HOLC diet before introducing ALLN-177 or placebo therapy for 7 days. Compared to placebo, ALLN-177 treatment reduced urinary oxalate by 11.6 ± 2.7 mg/day, p = 0.0002 (least squares mean ± SD). Conclusions: In healthy volunteers, with diet-induced hyperoxaluria treatment with ALLN-177, when compared to placebo, significantly reduced urinary oxalate excretion by degrading dietary oxalate in the gastrointestinal tract and thereby reducing its absorption. ALLN-177 may represent a new approach for managing secondary hyperoxaluria and its complications.

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“…Evidence for interventions like low oxalate diet, calcium supplementation, probiotics, therapies specific to the underlying condition (e.g., pancreatic enzyme supplementation in those with pancreatic insufficiency), and intestinal transplant is mostly from case reports. 13,[34][35][36][37] A unique study was that by Roodnat et al involving 10 patients with known or presumed EH awaiting KT. 21 They implemented an intensive protocol comprised of a low oxalate diet, cholestyramine, sodium bicarbonate, and calcium supplementation 6 mo before KT.…”

Section: Discussionmentioning

confidence: 99%

Prospective Assessment of the Prevalence of Enter Hyperoxalosis in Kidney Transplant Candidates

Mejia

Tariq

Alotaibi³

et al. 2023

Transplantation Direct

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Background. Enteric hyperoxalosis (EH) is an emerging cause of kidney transplantation (KT) dysfunction. We sought to determine the prevalence of EH and factors that affect plasma oxalate (POx) among at-risk KT candidates. Methods. We prospectively measured POx among KT candidates evaluated at our center from 2017 to 2020 with risk factors for EH namely bariatric surgery, inflammatory bowel disease, or cystic fibrosis. EH was defined by a POx ≥10 μmol/L. Period-prevalence of EH was calculated. We compared mean POx across 5 factors: underlying condition, chronic kidney disease (CKD) stage, dialysis modality, phosphate binder type, and body mass index. Results. Of 40 KT candidates screened, 23 had EH for a 4-y period prevalence of 58%. Mean POx was 21.6 ± 23.5 μmol/L ranging from 0 to 109.6 μmol/L. 40% of screened had POx >20 μmol/L. Sleeve gastrectomy was the most common underlying condition associated with EH. Mean POx did not differ by underlying condition (P = 0.27), CKD stage (P = 0.17), dialysis modality (P = 0.68), phosphate binder (P = 0.58), and body mass index (P = 0.56). Conclusions. Bariatric surgery and inflammatory bowel disease were associated with a high prevalence of EH among KT candidates. Contrary to prior studies, sleeve gastrectomy was also associated with hyperoxalosis in advanced CKD. POx concentrations observed in EH reached levels associated with tissue and potentially allograft deposition. Concentrations can be as high as that seen in primary hyperoxaluria. More studies are needed to assess if POx is indeed a modifiable factor affecting allograft function in patients with EH.

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Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria

Cited by 5 publications

References 20 publications

Increased Rates of Supplement-Associated Oxalate Nephropathy During COVID-19 Pandemic

Increased Rates of Supplement-Associated Oxalate Nephropathy During COVID-19 Pandemic

A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme

Prospective Assessment of the Prevalence of Enter Hyperoxalosis in Kidney Transplant Candidates

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