Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease

BACKGROUND: Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown. METHODS: Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m(2), 2.5 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid–base parameters (urinary ammonium excretion). RESULTS: Patients in the lowest tertile of baseline serum bicarbonate (23.1 ± 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21–7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 ± 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06–1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (−0.12 mL/min/1.73 m(2)/year, 95% CI −0.20 to −0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth. CONCLUSIONS: In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD

Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopressin activity reduces proteinuria, renal hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis in animal models. The potential detrimental influence of vasopressin is probably mediated by its effects on mesangial cell proliferation, renin secretion, renal hemodynamics, and blood pressure. In this review, we discuss the increasing body of evidence pointing towards the contribution of vasopressin to chronic kidney disease progression in general and to autosomal dominant polycystic kidney disease in particular. These data allude to the possibility that interventions directed at lowering vasopressin activity, for example by the administration of vasopressin receptor antagonists or by drinking more water, may be beneficial in chronic kidney disease. Copyright (C) 2011 S. Karger AG, Base

Associations of Genetic Factors, Educational Attainment, and Their Interaction With Kidney Function Outcomes

Both genetic predisposition and low educational attainment (EA) are associated with higher risk of chronic kidney disease. We examined the interaction of EA and genetic risk in kidney function outcomes. We included 3,597 participants from the Prevention of Renal and Vascular End-Stage Disease Cohort Study, a longitudinal study in a community-based sample from Groningen, the Netherlands (median follow-up, 11 years; 1997-2012). Kidney function was approximated by obtaining estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C. Individual longitudinal linear eGFR trajectories were derived from linear mixed models. Genotype data on 63 single-nucleotide polymorphisms, with known associations with eGFR, were used to calculate an allele-weighted genetic score (WGS). EA was categorized into high, medium, and low. In ordinary least squares analysis, higher WGS and lower EA showed additive effects on reduced baseline eGFR; the interaction term was nonsignificant. In analysis of eGFR decline, the significant interaction term suggested amplification of genetic risk by low EA. Adjustment for known renal risk factors did not affect our results. This study presents the first evidence of gene-environment interaction between EA and a WGS for eGFR decline and provides population-level insights into the mechanisms underlying socioeconomic disparities in chronic kidney disease

Kidney Function, Albuminuria and Life Expectancy

Background: Lower estimated glomerular filtration rate is associated with reduced life expectancy. Whether this association is modified by the presence or absence of albuminuria, another cardinal finding of chronic kidney disease, is unknown. Objective: Our objective was to estimate the life expectancy of middle-aged men and women with varying levels of eGFR and concomitant albuminuria. Design: A retrospective cohort study. Setting: A large population-based cohort identified from the provincial laboratory registry in Alberta, Canada. Participants: Adults aged ≥30 years who had outpatient measures of serum creatinine and albuminuria between May 1, 2002 and March 31, 2008. Measurements: Predictor : Baseline levels of kidney function identified from serum creatinine and albuminuria measurements. Outcomes : all cause mortality during the follow-up. Methods: Patients were categorized based on their estimated glomerular filtration rate (eGFR) (≥60, 45–59, 30–44, and 15–29 mL/min/1 · 73 m 2 ) as well as albuminuria (normal, mild, and heavy) measured by albumin-to-creatinine ratio or urine dipstick. The abridged life table method was applied to calculate the life expectancies of men and women from age 40 to 80 years across combined eGFR and albuminuria categories. We also categorized participants by severity of kidney disease (low risk, moderately increased risk. high risk, and very high risk) using the combination of eGFR and albuminuria levels. Results: Among men aged 50 years and with eGFR ≥60 mL/min/1.73 m 2 , estimated life expectancy was 24.8 (95% CI: 24.6–25.0), 17.5 (95% CI: 17.1–17.9), and 13.5 (95% CI: 12.6–14.3) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for men with mild and heavy albuminuria was 7.3 (95% CI: 6.9–7.8) and 11.3 (95% CI: 10.5–12.2) years shorter than men with normal proteinuria, respectively. A reduction in life expectancy was associated with an increasing severity of kidney disease; 24.8 years for low risk (95% CI: 24.6–25.0), 19.1 years for moderately increased risk (95% CI: 18.7–19.5), 14.2 years for high risk (95% CI: 13.5–15.0), and 9.6 years for very high risk (95% CI: 8.4–10.8). Among women of similar age and kidney function, estimated life expectancy was 28.9 (95% CI: 28.7–29.1), 19.8 (95% CI: 19.2–20.3), and 14.8 (95% CI: 13.5–16.0) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for women with mild and heavy albuminuria was 9.1 (95% CI: 8.5–9.7) and 14.2 (95% CI: 12.9–15.4) years shorter than the women with normal proteinuria, respectively. For women also a graded reduction in life expectancy was observed across the increasing severity of kidney disease; 28.9 years for low risk (95% CI: 28.7–29.1), 22.5 years for moderately increased risk (95% CI: 22.0–22.9), 16.5 years for high risk (95% CI: 15.4–17.5), and 9.2 years for very high risk (95% CI: 7.8–10.7). Limitations: Possible misclassification of long-term kidney function categories cannot be eliminated. Possibility of confounding due to concomitant comorbidities cannot be ruled out. Conclusion: The presence and degree of albuminuria was associated with lower estimated life expectancy for both gender and was especially notable in those with eGFR ≥30 mL/min/1.73 m 2 . Life expectancy associated with a given level of eGFR differs substantially based on the presence and severity of albuminuria

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality:results from the PREVEND study and meta-analysis

BACKGROUND: Chronic diseases are associated with an inflammatory response. We determined the association of two inflammatory markers, GlycA and high-sensitivity C-reactive protein (hsCRP), with overall and cause-specific mortality in a cohort of men and women.METHODS: Cox regression analyses were used to examine associations of GlycA and hsCRP with all-cause, cancer and cardiovascular mortality in 5526 subjects (PREVEND cohort; average follow-up 12.6 years).RESULTS: GlycA was associated with all-cause mortality (n = 838), independent of clinical risk factors and hsCRP (hazard ratio 1.43 [95% confidence interval (CI): 1.09-1.87] for top versus bottom quartiles). For hsCRP, the association with all-cause mortality was nonsignificant after adjustment for GlycA. GlycA and hsCRP were associated with cancer mortality in men (n = 248), but not in women (n = 132). Neither GlycA nor hsCRP was independently associated with cardiovascular mortality (n = 201). In a meta-analysis of seven population-based studies, including 8153 deaths, the pooled multivariable-adjusted relative risk of GlycA for all-cause mortality was 1.74 (95% CI: 1.40-2.17) for top versus bottom quartiles. The association of GlycA with all-cause mortality was somewhat stronger than that of hsCRP. GlycA and hsCRP were not independently associated with cardiovascular mortality. The associations of GlycA and hsCRP with cancer mortality were present in men, but not in women.CONCLUSIONS: GlycA is significantly associated with all-cause mortality. GlycA and hsCRP were each not independently associated with cardiovascular mortality. The association of GlycA and hsCRP with cancer mortality appears to be driven by men.</p