Michel Chonchol

Background and objectives: Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. Design, setting, participants & measurements: We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A (n=540; mean eGFR =91±17 ml/min per 1.73 m²) and B (n=462; mean eGFR =48±12 ml/min per 1.73 m²). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Results: Median (interquartile range) intact fibroblast growth factor 23 was 44 (33–56) pg/ml in HALT-PKD Study A and 69 (50–93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, −3.62; 95% confidence interval, −4.12 to −3.12 versus quartile 1, −2.51; 95% confidence interval, −2.71 to −2.30 ml/min per 1.73 m²; P for trend 2; P for trend P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m² did not improve risk prediction. Conclusions: Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline.

TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults. We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m2 or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis. Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = −1.18, 95% CI −2.03, −0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02– 1.20, p = 0.006). In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.

Article: Sodium and fluid management in the conservative management of chronic kidney disease - Panminerva Medica 2017 June;59(2):116-23 - Minerva Medica - Journals

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases.

Longitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49–0.89), cardiac events (HR, 0.71; 95% CI, 0.53–0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34–0.62) in time-dependent analyses. No significant associations of 1,25(OH)₂D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13–2.18), cardiac events (HR, 1.49; 95% CI, 1.06–2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07–2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.