Ultraprocessing makes food products more convenient, appealing, and profitable. Recent studies show that high ultraprocessed food (UPF) intake is associated with cardiometabolic diseases.
The aim of ...this study is to investigate the association between UPF consumption and risks of kidney function decline in the general population.
In a prospective, general population–based Lifelines cohort from Northern Netherlands, 78,346 participants free of chronic kidney disease (CKD) at baseline responded to a 110-item FFQ. We used a multivariable regression analysis to study the associations of the proportion (in grams/day) of UPFs in the total diet with a composite kidney outcome incident CKD or a ≥30% estimated glomerular filtration rate (eGFR) decline relative to baseline and annual change in eGFR.
On average, 37.7% of total food intake came from UPFs. After 3.6 ± 0.9 years of follow-up, 2470 participants (3.2%) reached the composite kidney outcome. Participants in the highest quartile of UPF consumption were associated with a higher risk of the composite kidney outcome (OR, 1.27; 95% CI, 1.09–1.47; P = 0.003) compared with those in the lowest quartile, regardless of their macro- or micronutrient intake or diet quality. Participants in the highest quartile had a more rapid eGFR decline (β, –0.17; 95% CI, –0.23 to –0.11; P < 0.001) compared with those in the lowest quartile. Associations were generally consistent across different subgroups.
Higher UPF consumption was associated with a higher risk of a composite kidney outcome (incident CKD or ≥30% eGFR decline) and a more rapid eGFR decline in the general population, independent of confounders and other dietary indices.
There is increasingly evidence that the interactions between vitamin D, fibroblast growth factor 23 (FGF-23), and klotho form an endocrine axis for calcium and phosphate metabolism, and derangement ...of this axis contributes to the progression of renal disease. Several recent studies also demonstrate negative regulation of the renin gene by vitamin D. In chronic kidney disease (CKD), low levels of calcitriol, due to the loss of 1-alpha hydroxylase, increase renal renin production. Activation of the renin-angiotensin-aldosterone system (RAAS), in turn, reduces renal expression of klotho, a crucial factor for proper FGF-23 signaling. The resulting high FGF-23 levels suppress 1-alpha hydroxylase, further lowering calcitriol. This feedback loop results in vitamin D deficiency, RAAS activation, high FGF-23 levels, and renal klotho deficiency, all of which associate with progression of renal damage. Here we examine current evidence for an interaction between the RAAS and the vitamin D-FGF-23-klotho axis as well as its possible implications for progression of CKD.
Multimorbidity is considered a major challenge for current health care. Lifestyle interventions, as a broad and generic approach, may have the potential to improve the management of care among ...patients with multimorbidity. The objective of this study was to evaluate the association of multimorbidity defined within the cardiometabolic disease domains with dietary patterns, representing habitual dietary intake.
We studied 129 369 participants from the Lifelines Cohort study (42% male, 45±13 years (range 18-93)) in which diet was assessed using a 110-item food frequency questionnaire. A composite morbidity score was applied in multivariable ordered logistic regression to test the association with dietary patterns derived by principal components analysis, based on sex-specific dietary pattern scores.
Four dietary patterns were retained, accounting for 26.6% of the variation in overall diet. After control for potential confounders, men and women in the highest quintile of "meat, alcohol and potato pattern" and "snack pattern" had a higher likelihood of having higher morbidity scores than those in the lowest quintile (e.g. men: OR = 1.83(95% CI:1.71-1.97), OR = 1.18(95% CI 1.11-1.27 respectively). The opposite was observed with respect to the "bread and sweets pattern" and "vegetable, fish and fruit pattern" (e.g. women: OR = 0.88(95% CI: 0.81-0.96), OR = 0.86(95% CI 0.81-0.92 respectively). The association partially attenuated after adjusting for BMI, but the associations remained significant among men.
Robust associations between dietary patterns and multimorbidity within the cardiometabolic domain, in particular a "meat, alcohol and potato pattern", suggest an important opportunity of dietary interventions in multimobidity prevention. Generic prevention strategies based on population derived dietary patterns may have the potential to enhance lifestyle management among people with multimorbidity.
Most transplant centers in the Netherlands use estimated glomerular filtration rate (eGFR) for evaluation of potential living kidney donors. Whereas eGFR often underestimates GFR, especially in ...healthy donors, measured GFR (mGFR) allows more precise kidney function assessment, and therefore holds potential to increase the living donor pool. We hypothesized that mGFR-based donor screening leads to acceptance of donors with lower pre-donation eGFR than eGFR-based screening. In this longitudinal cohort study, we compared eGFR (CKD-EPI) before donation in one center using mGFR-based screening (mGFR-cohort, n = 250) with two centers using eGFR-based screening (eGFR-cohort1, n = 466 and eGFR-cohort2, n = 160). We also compared differences in eGFR at five years after donation. Donor age was similar among the cohorts (mean±standard deviation (SD) mGFR-cohort 53±10 years, eGFR-cohort1 52±13 years, P = 0.16 vs. mGFR-cohort, and eGFR-cohort2 53±9 years, P = 0.61 vs. mGFR-cohort). Estimated GFR underestimated mGFR by 10±12 mL/min/1.73m.sup.2 (mean±SD), with more underestimation in younger donors. In the overall cohorts, mean±SD pre-donation eGFR was lower in the mGFR-cohort (91±13 mL/min/1.73m.sup.2) than in eGFR-cohort1 (93±15 mL/min/1.73m.sup.2, P<0.05) and eGFR-cohort2 (94±12 mL/min/1.73m.sup.2, P<0.05). However, these differences disappeared when focusing on more recent years, which can be explained by acceptance of more older donors with lower pre-donation eGFR over time in both eGFR-cohorts. Five years post-donation, mean±SD eGFR was similar among the centers (mGFR-cohort 62±12 mL/min/1.73m.sup.2, eGFR-cohort1 61±14 mL/min/1.73m.sup.2, eGFR-cohort2 62±11 mL/min/1.73m.sup.2, P = 0.76 and 0.95 vs. mGFR-cohort respectively). In the mGFR-cohort, 38 (22%) donors were excluded from donation due to insufficient mGFR with mean±SD mGFR of 71±9 mL/min/1.73m.sup.2. Despite the known underestimation of mGFR by eGFR, we did not show that the routine use of mGFR in donor screening leads to inclusion of donors with a lower pre-donation eGFR. Therefore eGFR-based screening will be sufficient for the majority of the donors. Future studies should investigate whether there is a group (e.g. young donors with insufficient eGFR) that might benefit from confirmatory mGFR testing.
Heavy metals are common in our environment, and all individuals are exposed to them to some extent. These toxic metals have several harmful effects on the body, including the kidney, which is a very ...sensitive organ. Indeed, heavy metal exposure has been linked to an increased risk of chronic kidney disease (CKD) and its progression, which may be explained by the well-established nephrotoxic effects of these metals. In this hypothesis and narrative literature review, we will shed light on the potential role that another highly common problem in patients with CKD, iron deficiency, may play in the damaging effects of heavy metal exposure in this patient group. Iron deficiency has previously been linked with an increased uptake of heavy metals in the intestine due to the upregulation of iron receptors that also take up other metals. Furthermore, recent research suggests a role of iron deficiency in the retention of heavy metals in the kidney. Therefore, we hypothesize that iron deficiency plays a crucial role in the damaging effects of heavy metal exposure in patients with CKD and that iron supplementation might be a strategy to combat these detrimental processes.
Abstract
Background
Phosphate (Pi) toxicity is a strong determinant of vascular calcification development in chronic kidney disease (CKD). Magnesium (Mg2+) may improve cardiovascular risk via ...vascular calcification. The mechanism by which Mg2+ counteracts vascular calcification remains incompletely described. Here we investigated the effects of Mg2+ on Pi and secondary crystalline calciprotein particles (CPP2)-induced calcification and crystal maturation.
Methods
Vascular smooth muscle cells (VSMCs) were treated with high Pi or CPP2 and supplemented with Mg2+ to study cellular calcification. The effect of Mg2+ on CPP maturation, morphology and composition was studied by medium absorbance, electron microscopy and energy dispersive spectroscopy. To translate our findings to CKD patients, the effects of Mg2+ on calcification propensity (T50) were measured in sera from CKD patients and healthy controls.
Results
Mg2+ supplementation prevented Pi-induced calcification in VSMCs. Mg2+ dose-dependently delayed the maturation of primary CPP1 to CPP2 in vitro. Mg2+ did not prevent calcification and associated gene and protein expression when added to already formed CPP2. Confirmatory experiments in human serum demonstrated that the addition of 0.2 mmol/L Mg2+ increased T50 from healthy controls by 51 ± 15 min (P < 0.05) and CKD patients by 44 ± 13 min (P < 0.05). Each further 0.2 mmol/L addition of Mg2+ led to further increases in both groups.
Conclusions
Our results demonstrate that crystalline CPP2 mediates Pi-induced calcification in VSMCs. In vitro, Mg2+ delays crystalline CPP2 formation and thereby prevents Pi-induced calcification.
Non-alcoholic fatty liver disease (NAFLD) is likely to be associated with elevated plasma branched-chain amino acids (BCAAs) and may precede the development of type 2 diabetes (T2D). We hypothesized ...that BCAAs may be involved in the pathogenesis of T2D attributable to NAFLD and determined the extent to which plasma BCAAs influence T2D development in NAFLD. We evaluated cross-sectional associations of NAFLD with fasting plasma BCAAs (nuclear magnetic resonance spectroscopy), and prospectively determined the extent to which the influence of NAFLD on incident T2D is attributable to BCAA elevations. In the current study, 5791 Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort participants without T2D at baseline were included. Elevated fatty liver index (FLI) ≥60, an algorithm based on triglycerides, gamma-glutamyltransferase, body mass index (BMI) and waist circumference, was used as proxy of NAFLD. Elevated FLI ≥ 60 was present in 1671 (28.9%) participants. Cross-sectionally, BCAAs were positively associated with FLI ≥ 60 (β = 0.208,
< 0.001). During a median follow-up of 7.3 years, 276 participants developed T2D, of which 194 (70.2%) had an FLI ≥ 60 (log-rank test,
< 0.001). Cox regression analyses revealed that both FLI ≥60 (hazard ratio (HR) 3.46, 95% CI 2.45⁻4.87,
< 0.001) and higher BCAA levels (HR 1.19, 95% CI 1.03⁻1.37,
= 0.01) were positively associated with incident T2D. Mediation analysis showed that the association of FLI with incident T2D was in part attributable to elevated BCAAs (proportion mediated 19.6%). In conclusion, both elevated FLI and elevated plasma BCAA levels are associated with risk of incident T2D. The association of NAFLD with T2D development seems partly mediated by elevated BCAAs.
In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of ...gene-disrupting variants may represent a risk factor for allograft rejection.
We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses.
In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the
locus represented by rs893403 (hazard ratio with the risk genotype vs. nonrisk genotypes, 1.84; 95% confidence interval CI, 1.35 to 2.50; P = 9.8×10
). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2004 donor-recipient pairs (hazard ratio, 1.55; 95% CI, 1.25 to 1.93; P = 6.5×10
). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10
). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses.
We found that the
locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (Funded by the Columbia University Transplant Center and others.).
PDF
