Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. ...Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys.
NAFLD and Chronic Kidney Disease Marcuccilli, Morgan; Chonchol, Michel
International Journal of Molecular Sciences,
04/2016, Letnik:
17, Številka:
4
Journal Article, Book Review
Recenzirano
Odprti dostop
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.
Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A ...scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study.
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder that leads to kidney failure and has few treatment options. Metformin is well tolerated and safe in other patient ...populations. The primary objective of this clinical trial was to determine the safety and tolerability of metformin in patients with ADPKD and without diabetes mellitus.
Prospective randomized controlled double-blind clinical trial.
51 adults aged 30-60 years with ADPKD, without diabetes, and an estimated glomerular filtration rate (eGFR) 50-80 mL/min/1.73 m2.
Metformin (maximum dose 2,000 mg/d) or placebo for 12 months.
Coprimary end points were the percentage of participants in each group prescribed at the end of the 12-month period: (1) the full randomized dose or (2) at least 50% of the randomized dose. Secondary and exploratory outcomes were the effect of metformin compared with placebo on (1) the percentage change in total kidney volume (TKV) referenced to height (htTKV in mL/m) and (2) the change in eGFR over a 12-month period.
The participants’ mean age was 48 ± 8 (SD) years, and eGFR was 70 ± 14 mL/min/1.73 m2. The metformin group had no cases of lactic acidosis, and there was 1 episode of mild hypoglycemia in each group. Participants in the metformin group reported more adverse symptoms, mostly related to the gastrointestinal tract. Eleven of 22 metformin-treated participants (50%) completed the treatment phase on the full dose compared with 23 of 23 in the placebo group (100%). In the metformin group, 82% of participants tolerated at least 50% of the dose, compared with 100% in the placebo group. In exploratory analyses, changes in htTKV or eGFR were not significantly different between the groups.
Short study duration.
We found that 50% or more of the maximal metformin dose was safe and well tolerated over 12 months in patients with ADPKD. Safety of other preparations of metformin as well as its efficacy should be tested in future clinical trials.
Government and philanthropic grants (NIDDK and the Zell Foundation).
Registered at ClinicalTrials.gov with study number NCT02903511.
Vascular calcification is associated with significant cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Factors unique to patients with CKD, such as ...hyperphosphatemia, predispose these patients to early and progressive vascular calcification. Hyperphosphatemia appears to be involved in a number of mechanisms that trigger and advance the progression of vascular calcification, including (1) transition of vascular smooth muscle cells (VSMCs) from a contractile to an osteochondrogenic phenotype and mineralization of VSMC matrix through sodium-dependent phosphate cotransporters, (2) induction of VSMC apoptosis, (3) inhibition of monocyte/macrophage differentiation into osteoclast-like cells, (4) elevation of fibroblast growth factor 23 levels, and (5) decreases in klotho expression. Whether vascular calcification can be prevented or reversed with strategies aimed at maintaining phosphate homeostasis presently is unknown. This review discusses these mechanisms in depth, exploring the interplay among vascular calcification promoters, inhibitors, and substrate that affect phosphorus handling leading to vascular calcification in individuals with CKD.
CKD and Nonalcoholic Fatty Liver Disease Targher, Giovanni, MD; Chonchol, Michel B., MD; Byrne, Christopher D., MB BCh
American journal of kidney diseases,
10/2014, Letnik:
64, Številka:
4
Journal Article
Recenzirano
The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the ...presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.
Nicotinamide adenine dinucleotide (NAD
) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD
...precursors to augment NAD
bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD
precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD
metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.
Overweight and Obesity and Progression of ADPKD Nowak, Kristen L; Steele, Cortney; Gitomer, Berenice ...
Clinical journal of the American Society of Nephrology,
06/2021, Letnik:
16, Številka:
6
Journal Article
Recenzirano
Odprti dostop
On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the ...Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity.
A total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78±22 ml/min per 1.73 m
) who were at high risk of rapid progression were categorized by body mass index (BMI; calculated using nonkidney weight) as normal weight (18.5-24.9 kg/m
;
=670), overweight (25.0-29.9 kg/m
;
=429), or obese (≥30 kg/m
;
=213). Linear and multinomial logistic regression models were used to determine the association of baseline overweight and obesity with change in total kidney volume (TKV) over the 3-year study period.
In fully adjusted models, higher BMI was associated with greater annual percent change in TKV (difference of 1.20 95% confidence interval (95% CI), 0.85 to 1.55 per five-unit higher BMI). Overweight and obesity were associated with higher odds of annual percent change in TKV of ≥7% versus <5% (overweight: odds ratio, 2.04 95% CI, 1.45 to 2.87; obese: odds ratio, 4.31 95% CI, 2.83 to 6.57 versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of -0.95 95% CI, -2.32 to 0.40 ml/min per 1.73 m
per year per five-unit higher BMI). The three-way interaction (treatment×time×BMI group) was not statistically significant in linear mixed models with an outcome of TKV (log-transformed estimated coefficient comparing the treatment effect for overweight versus normal weight: 0.56% 95% CI, -0.70% to 1.84% per year;
=0.38; obese versus normal weight: 0.07% 95% CI, -1.47% to 1.63% per year;
=0.93) or eGFR (estimated coefficient comparing overweight versus normal weight: -0.07 95% CI, -0.95 to 0.82 ml/min per 1.73 m
per year;
=0.88; obese versus normal weight: 0.22 95% CI, -0.93 to 1.36 ml/min per 1.73 m
per year;
=0.71).
Overweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization.
Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4, NCT00428948.
Patients with chronic kidney disease (CKD) have a reduced lifespan, and a substantial proportion of these individuals die from cardiovascular disease. Although a large percentage of patients with CKD ...have traditional cardiac risk factors such as diabetes, hypertension and abnormalities in cholesterol, interventions to address these factors--which have significantly decreased cardiovascular mortality in the general population--have not shown such benefit in the CKD population. In addition, the severity and extent of cardiovascular complications in patients with CKD is disproportionate to the number and severity of traditional risk factors. This realization has focused attention on nontraditional cardiac risk factors that are particularly relevant to patients with CKD, including decreased hemoglobin levels, microalbuminuria, increased inflammation and oxidative stress, and abnormalities in bone and mineral metabolism. However, large prospective trials in patients with advanced CKD or in those requiring chronic dialysis have not shown that normalization of these nontraditional risk factors improves survival. Moreover, the mechanisms by which these nontraditional risk factors contribute to cardiovascular disease are unknown. Therefore, although current treatment of patients with CKD includes management of traditional and nontraditional risk factors, the value of modifying some nontraditional risk factors remains unclear.
The associations between dietary sodium intake (DSI), dietary potassium intake (DPI), and kidney stone disease (KSD) are not clear. We examined The National Health and Nutrition Examination Survey ...2011–2018 to determine the independent associations between daily DSI, DPI, DSI/DPI, and KSD prevalence. In total, 19,405 participants were included for analysis, of which 1,895 had KSD. Higher DSI was not associated with increased odds of KSD in regression analysis when DSI was modeled as a continuous variable (OR = 0.99, 95% CI: 0.99–1.00, p = 0.2), or when comparing highest quartile of DSI to lowest quartile (OR = 0.84, 95% CI: 0.68–1.04, p = 0.1). Unlike DSI, higher DPI was strongly associated with reduced odds of KSD in regression analysis when DPI was modeled as a continuous variable (OR = 0.99, 95% CI: 0.99–0.99, p = 0.02), or when comparing highest quartile of DPI to lowest quartile (OR = 0.75, 95% CI: 0.60–0.94, p = 0.01). Lastly, higher DSI/DPI was also strongly associated with increased odds of KSD in regression analysis when DSI/DPI was modeled as a continuous variable (OR = 1.1, 95% CI: 1.01–1.20, p = 0.03), or when comparing highest quartile of DPI to lowest quartile (OR = 1.30, 95% CI: 1.10–1.70, p = 0.008). All the observed relationships were independent of total calorie intake. In conclusion, both lower DPI and higher DSI/DPI are associated with an increased risk of KSD. Future prospective studies are needed to clarify these causal relationships.
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