Urinary Urea Excretion and Long-term Outcome After Renal Transplantation

Deetman, Petronella E.; Said, M. Yusof; Kromhout, Daan; Dullaart, Robin P. F.; Kootstra‐Ros, Jenny E.; Sanders, Jan-Stephan; Seelen, Marc A.; Gans, Rijk O. B.; Navis, Gerjan; Joosten, Michel M.; Bakker, Stephan J. L.

doi:10.1097/tp.0000000000000464

Cited by 23 publications

(25 citation statements)

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“…We conclude that the beneficial effect of USE on reducing the risk of premature graft failure is mainly dependent upon sulfur intake through dietary protein. Our current findings corroborate an earlier study of us where we found that low protein intake, as reflected by low 24 h urinary urea excretion, is associated with increased risk for premature graft failure in RTR [35,36]. The current guideline of the "Kidney Disease: Improving Global Outcomes" workgroup does not provide specific recommendations regarding protein intake for RTR [38], neither does the guideline of the "National Kidney Foundation Kidney Disease Outcomes Quality Initiative" (NKF KDOQI) [39,40].…”

Section: Discussionsupporting

confidence: 93%

“…Dietary sources of sulfate are sulfur-containing amino acids via animal or plant protein or sulfate-rich foods(components), such as beer and preservatives. We found that USE has a very high correlation with urinary urea excretion, which reflects total protein intake in stable RTR [24,35,36]. Additionally, USE is also strongly correlated to estimated total protein intake which can be calculated with the urea nitrogen excretion-derived Maroni formula (Fig.…”

Section: Discussionmentioning

confidence: 66%

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Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

et al. 2020

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Hydrogen sulfide (H 2 S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-fourhour urinary sulfate excretion (USE) may reflect H 2 S bioavailability. We aimed to investigate the association of USE with graft failure in a large prospective cohort of renal transplant recipients (RTR). We included 704 stable RTR, recruited at least 1 year after transplantation. We applied logrank testing and Cox regression analyses to study association of USE, measured from baseline 24 h urine samples, with graft failure. Median age was 55 [45-63] years (57% male, eGFR was 45 AE 19 ml/min/1.73 m 2). Median USE was 17.1 [13.1-21.1] mmol/24 h. Over median follow-up of 5.3 [4.5-6.0] years, 84 RTR experienced graft failure. RTR in the lowest sex-specific tertile of USE experienced a higher rate of graft failure during follow-up than RTR in the middle and highest sex-specific tertiles (18%, 13%, and 5%, respectively, log-rank P < 0.001). In Cox regression analyses, USE was inversely associated with graft failure [HR per 10 mmol/24 h: 0.37 (0.24-0.55), P < 0.001]. The association remained independent of adjustment for potential confounders, including age, sex, eGFR, proteinuria, time between transplantation and baseline, BMI, smoking, and high sensitivity C-reactive protein [HR per 10 mmol/24 h: 0.51 (0.31-0.82), P = 0.01]. In conclusion, this study demonstrates a significant inverse association of USE with graft failure in RTR, suggesting high H 2 S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 66%

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

et al. 2020

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“…Our study is unique because of the large study population and the ability to study potential mechanisms of the association between protein intake and mortality and graft failure. Recently, we have found in a cohort of 940 RTR that protein intake is inversely associated with mortality and graft failure, similar to this study . We were, however, not able to explain the underlying mechanisms of the association.…”

Section: Discussionsupporting

confidence: 69%

Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients

Said

Deetman

Vries

et al. 2015

Clinical Transplantation

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The effect of a low protein intake on survival in renal transplant recipients (RTR) is unknown. A low protein intake may increase risks of malnutrition, low muscle mass, and death. We aimed to study associations of protein intake with mortality and graft failure and to identify potential intermediate factors. Protein intake was estimated from 24‐h urinary urea excretion (24‐h UUE). Graft failure was defined as return to dialysis or retransplantation. We used Cox regression analyses to analyze associations with outcome and potential intermediate factors in the causal path. In 604 RTR, mean ± SD 24‐h UUE was 380 ± 114 mmol/24‐h. During median follow‐up for 7.0 yr (interquartile range: 6.2–7.5 yr), 133 RTR died and 53 developed graft failure. In univariate analyses, 24‐h UUE was associated with lower risk of mortality (HR [95% CI] = 0.80 [0.69–0.94]) and graft failure (HR [95% CI] = 0.72 [0.56–0.92]). These associations were independent of potential confounders. In causal path analyses, the association of 24‐h UUE with mortality disappeared after adjustment for muscle mass. Low protein intake is associated with increased risk of mortality and graft failure in RTR. Causal path analyses reveal that the association with mortality is explained by low muscle mass. These findings suggest that protein intake restriction should not be advised to RTR.

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“…Furthermore, despite significant hypertrophy and hyperfiltration in the remaining kidney after nephrectomy, kidney function remains normal over a prolonged period (>20 y) ( 67 , 68 ). A recent trial found that after kidney transplant there was a negative correlation between protein intake and mortality and graft failure in normal-weight individuals with an eGFR >45 mL ⋅ min −1 ⋅ 1.73 m − 2 ( 69 ), suggesting a protective effect of protein intake on kidney health. Moreover, despite numerous studies that found that an HP diet increases GFR ( 30 , 33 , 49 , 53 , 70 , 71 ), to date there is no evidence linking HP intake to kidney disease in healthy individuals or those at risk of kidney disease due to pre-existing conditions such as obesity, hypertension, or dyslipidemia ( 62 ).…”

Section: Discussionmentioning

confidence: 99%

'Changes in Kidney Function Do Not Differ between Healthy Adults Consuming Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis

Devries

Sithamparapillai²,

Brimble³

et al. 2018

The Journal of Nutrition

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BackgroundHigher-protein (HP) diets are advocated for several reasons, including mitigation of sarcopenia, but their effects on kidney function are unclear.ObjectiveThis meta-analysis was conducted to determine the effect of HP intakes on kidney function in healthy adults.MethodsWe conducted a systematic review and meta-analysis of trials comparing HP (≥1.5 g/kg body weight or ≥20% energy intake or ≥100 g protein/d) with normal- or lower-protein (NLP; ≥5% less energy intake from protein/d compared with HP group) intakes on kidney function. Medline and EMBASE databases were searched. Randomized controlled trials comparing the effects of HP with NLP (>4 d duration) intakes on glomerular filtration rate (GFR) in adults without kidney disease were included.ResultsA total of 2144 abstracts were reviewed, with 40 articles selected for full-text review; 28 of these were analyzed and included data from 1358 participants. Data were analyzed using random-effects meta-analysis (RevMan 5; The Cochrane Collaboration), meta-regression (STATA; StataCorp), and dose-response analysis (Prism; GraphPad). Analyses were conducted using postintervention (post) GFR and the change in GFR from preintervention to post. The post-only comparison showed a trivial effect for GFR to be higher after HP intakes [standardized mean difference (SMD): 0.19; 95% CI: 0.07, 0.31; P = 0.002]. The change in GFR did not differ between interventions (SMD: 0.11; 95% CI: −0.05, 0.27; P = 0.16). There was a linear relation between protein intake and GFR in the post-only comparison (r = 0.332, P = 0.03), but not between protein intake and the change in GFR (r = 0.184, P = 0.33). The main limitation of the current analysis is the unclear risk of selection bias of the included trials.ConclusionsPostintervention GFR comparisons indicate that HP diets result in higher GFRs; however, when changes in GFR were compared, dietary protein had no effect. Our analysis indicates that HP intakes do not adversely influence kidney function on GFR in healthy adults.

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Urinary Urea Excretion and Long-term Outcome After Renal Transplantation

Abstract: Urinary urea excretion, a marker for protein intake, was inversely related to graft failure in RTR with BMI less than 25 kg/m and in RTR with an eGFR of 45 mL per min per 1.73 m or higher. In addition, urinary urea excretion was inversely related to mortality.

Cited by 23 publications

References 31 publications

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients

'Changes in Kidney Function Do Not Differ between Healthy Adults Consuming Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis

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