Beneficial Effects of Ketoanalogues on the Evolution of Renal Function and Bone Mineral Disorders in Patients with Advanced Chronic Kidney Disease: A Pilot Study.

INTRODUCTION: The supplementation with Ketoanalogues in patients on very low-protein diets has shown a favorable effect on the evolution of renal function. The aim of the present study was to evaluate the progression of renal function in advanced chronic kidney disease patients on a low-protein diet (<0.8 g/kg/d) with or without additional Ketoanalogues. METHODS: The primary criterion is the evolution of the renal function at 6, 12, and 24 months for the two groups. The secondary criteria comprise the evolution of the body weight, mean blood pressure, 24-h proteinuria, salt and protein consumption, energy consumption, hemoglobin levels, serum albumin, prealbumin, C-reactive protein, liver function tests, serum electrolyte and phosphate levels, parathormone as well as calcium levels at the same time periods. RESULTS: There was a significant nephroprotective effect of the Ketoanalogues after 12 and 24 months with no differences in the protein consumption between the two groups. Mean blood pressure, hemoglobin levels, 24-hour proteinuria, serum electrolyte, liver function tests, salt and protein consumption, and serum albumin and prealbumin did not present any significant differences. Serum bicarbonate and calcium levels were higher while serum phosphate and parathormone levels were lower in the Ketoanalogue group at all follow-up time points. During the 24-month follow-up period, 4 patients from the Ketoanalogue group and 8 patients from the control group quit the study. CONCLUSION: A low-protein diet supplemented with Ketoanalogues exerts significant nephroprotective effects and better bone mineral metabolism parameters compared to a low-protein diet only.

The effect of intradialytic exercise on calcium, phosphorus and parathyroid hormone: a randomized controlled trial.

BACKGROUND: Patients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which results in high mortality rate in these patients. This study aimed to evaluate the effect of intradialytic exercise on regulation of these abnormalities in patients receiving chronic hemodialysis (HD). METHODS: In this randomized controlled trial conducted in an HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 min) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcomes were serum calcium, serum phosphorous and parathyroid hormone levels. Secondary outcomes were serum alkaline phosphatase and calcium-phosphorous product. RESULTS: The study included 44 participants randomized to intervention (n = 22) or control (n = 22). During the 6-month intervention period, significant between-group changes were observed in all primary and secondary outcomes between the intervention and control groups. Statistical analyses reveal a significant increase in serum calcium (P < 0.05) as well as a significant decrease in serum phosphorous, parathyroid hormone, alkaline phosphatase and calcium-phosphorous product (P < 0.05). CONCLUSION: Intradialytic exercise performed for at least 60 min during thrice weekly dialysis sessions improves bone mineral metabolism in adult patients receiving HD. Further studies should focus on observing and comparing the effect of different types of exercise on bone mineral disorders and all-cause mortality in HD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04916743, Registered on 08/06/2021. Registered trial name: The Effect of Intradialytic Exercise on Calcium, Phosphorous and Parathyroid Hormone: A Randomized Controlled Trial.

Parkinson's Disease Etiology: Insights and Associations with Phosphate Toxicity.

The present paper investigated the association of Parkinson's disease etiology with phosphate toxicity, a pathophysiological condition in which dysregulated phosphate metabolism causes excessive inorganic phosphate sequestration in body tissue that damages organ systems. Excessive phosphate is proposed to reduce Complex I function of the mitochondrial electron transport chain in Parkinson's disease and is linked to opening of the mitochondrial permeability transition pore, resulting in increased reactive oxygen species, inflammation, DNA damage, mitochondrial membrane depolarization, and ATP depletion causing cell death. Parkinson's disease is associated with α-synuclein and Lewy body dementia, a secondary tauopathy related to hyperphosphorylation of tau protein, and tauopathy is among several pathophysiological pathways shared between Parkinson's disease and diabetes. Excessive phosphate is also associated with ectopic calcification, bone mineral disorders, and low levels of serum vitamin D in patients with Parkinson's disease. Sarcopenia and cancer in Parkinson's disease patients are also associated with phosphate toxicity. Additionally, Parkinson's disease benefits are related to low dietary phosphate intake. More studies are needed to investigate the potential mediating role of phosphate toxicity in the etiology of Parkinson's disease.

Osteoporosis in Patients with CKD: A Diagnostic Dilemma.

Osteoporosis in patients with chronic kidney disease (CKD) is a complex problem, with diagnostic criteria and treatment plans often debated. The debate creates a practice dilemma for clinicians faced with an aging population and an increasing incidence of fragility fractures. This article discusses the dilemma as seen from the perspective of the nephrology clinician on differentiating osteoporosis from other bone mineral disorders in patients with progressive CKD in order to provide the most efficacious and safe care.

Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta-analysis.

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post-transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate-treated kidney transplant recipients through meta-analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow-up duration was more than 6 months. We performed random-effects meta-analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm(2) , 95% CI 0.012-0.099 and 0.053 g/cm(2) , 95% CI 0.032-0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.

Associations between acute kidney injury and bone fractures: a retrospective cohort study.

Background: Acute kidney injury (AKI) is common. An AKI episode may disrupt the normal mineral bone balance maintained by normal kidney function, thereby modifying the risk of developing bone fractures. However, it remains unclear whether an AKI episode is associated with the risk of bone fractures. Methods: Using retrospective cohort study from an Australian Local Health District, we examined the association between an AKI episode and bone fractures using patient data between 2008 and 2017. Time-varying Cox proportional hazards and propensity-matched analysis were used to examine the association. Sensitivity analyses were undertaken to capture the impact of confirmed AKI status and AKI severity. Results: Of 123 426 included patients, 14 549 (12%) had an AKI episode and 12 505 (10%) had a bone fracture. In the unadjusted analysis, AKI was associated with bone fractures [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.88-2.11]. This association persisted in the adjusted analysis (HR 1.50, 95% CI 1.41-1.59) and propensity-matched dataset (HR 1.71, 95% CI 1.59-1.83). The sensitivity analysis yielded similar results, with the AKI patients having a higher risk of fractures compared with no AKI patients in the adjusted analysis (HR 1.34, 95% CI 1.25-1.43) and in the propensity-matched dataset (HR 1.44, 95% CI 1.33-1.55). Similar results were seen in the subsidiary sensitivity analysis excluding patients without baseline creatinine. We did not find an increased risk of bone fractures with increasing AKI severity (P = .7). Interaction tests demonstrated a significant association between sex and age category with AKI status and fractures, but not CKD stage or osteoporosis. Conclusions: AKI is associated with a greater risk of bone fractures. This could have implications for managing and screening for bone disease in patients post-AKI episode. This association should be examined in other cohorts and populations for verification.

Bilateral or Unilateral Aldosterone Hypersecretion and Responsiveness to Therapy Are Associated with Differences in Calcium/Phosphate Homeostasis in Patients with Primary Aldosteronism.

Introduction Primary aldosteronism is characterized by the autonomous excretion of aldosterone, which may induce bone mineral disorders. Methods A total of 96 patients with primary aldosteronism were analyzed to identify differences in the regulation of serum calcium/phosphate balance between patients with unilateral and bilateral aldosterone hypersecretion and to determine whether or not adrenalectomy or mineralocorticoid receptor blockers affected such differences. Results Serum phosphate concentrations were significantly lower in patients with unilateral aldosterone hypersecretion than in patients with bilateral aldosterone hypersecretion (2.96±0.45 vs. 3.36±0.55 mg/dL, p<0.05), and recovered after adrenalectomy (2.96±0.45 vs. 3.49±0.32 mg/dL, p<0.01). In patients with bilateral aldosterone hypersecretion, the baseline serum phosphate levels were significantly lower in responders to mineralocorticoid receptor blocker treatment, defined as post-treatment plasma renin activity ≥1 ng/mL/h, than in non-responders. In responders, these levels tended to recover after treatment. A weak negative correlation between the plasma aldosterone concentration (PAC) and serum phosphate was observed, but there were no associations between the PAC and serum calcium concentration or between the aldosterone renin ratio and serum calcium and phosphate concentrations. Conclusion The effects on calcium/phosphate homeostasis may differ according to the primary aldosteronism subtype.

Endocrinological disorders in acute kidney injury: an often overlooked field of clinical research.

Acute kidney injury (AKI) is a common comorbidity, affecting approximately one in five hospitalized adults. The kidney is the site for the production, metabolism or excretion of most hormones, including the production of erythropoietin (EPO), the active form of vitamin D, renin, thrombopoietin, and the excretion of insulin, catecholamines, gastrin and many other hormones. Therefore, it is reasonable to say that AKI can have a considerable impact on the endocrine system. Although the effects of AKI on various parameters, including cardiovascular parameters, serum electrolytes and acid-base disorders, neuro-humoral mechanisms and neurological outcomes have been extensively studied, the endocrinological consequences of AKI are understudied. Thyroid dysfunction, mainly euthyroid sick syndrome, hypo/hyperglycemia, bone mineral disorders, changes in EPO and atrial natriuretic peptide (ANP) levels are commonly found in AKI. EPO, thyroxine and ANP administration have been evaluated as potential tools to prevent or treat AKI with varying success, while the effects of AKI on some key hormones, including cortisol and insulin, have never been studied. Aim of this narrative review is to illustrate what is known and what is not known about the endocrinological outcomes of AKI. Few clinical trials are ongoing: however, there is a clear need for large-scale randomized controlled trials investigating the endocrinological consequences of AKI.

Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease.

The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in advanced chronic kidney disease (CKD). In addition to nitrogen waste products, many pathological biochemical processes also play a role in vascular calcification in chronic kidney damage. Magnesium, a cation vital for the body, may substantially reduce cardiovascular diseases' risk and progression. This narrative review aimed to address the relationship between hypomagnesemia and vascular calcification, which promotes further cardiovascular complications in diabetes, aging, and CKD. Articles with predefined keywords were searched for in the PubMed and Google Scholar databases with specific inclusion and exclusion criteria. We hypothesized that a decrease in serum magnesium levels contributes to increased vascular calcification and thereby increases cardiovascular mortality. In summary, based on existing evidence in the literature, it appears that simple and inexpensive oral magnesium supplementation may reduce the cardiovascular mortality of patients who are already severely affected by such diseases; in this context, the concept of 'normal' vs. 'ideal' serum magnesium levels should be carefully re-examined.

Role of cytochrome P450 2C8 genetic polymorphism and epoxygenase uncoupling in periodontal remodelling affecting orthodontic treatment.

In genome-wide association studies, the CYP2C8 gene locus has been reported to be associated with bisphosphonate-related osteonecrosis of the jaw, a severe devastating side effect of antiresorptive bone treatment. The aim of this study was to elucidate the putative pathomechanism explaining the association between the genetic polymorphism with the alleles CYP2C8*2 and *3 causing low CYP2C8 activity, and disturbed periodontal remodelling in periodontal fibroblasts cultured from patients undergoing orthodontic treatment. CYP2C8 activity, enzyme expression and substrate metabolism were detected in human periodontal fibroblast cultures. Zoledronic acid caused enhanced reactive oxygen species (ROS) production in periodontal fibroblasts, which was enhanced by arachidonic acid as inflammatory signal. Enhanced bisphosphonate-induced uncoupling of the CYP2C8 enzyme was detected in the variant allele (CYP2C8*3) with the result of increased H2 O2 production and lowered substrate oxidation. Conversely, substrate (amodiaquine) addition led to decreased H2 O2 production in isolated CYP2C8 enzymes, but in CYP2C8*3 enzyme, increased H2 O2 was still detected, especially in presence of arachidonic acid. CYP2C8 variants leading to decreased enzyme activity in substrate oxidation may enhance ROS production by reaction uncoupling, and thus, contribute to difficulties in orthodontic treatment and the risk of side effects of antiresorptive drugs.

Complications of Kidney Disease.

Understanding the physiology of the kidney and the pathophysiology of common complications of chronic kidney disease (CKD) is essential. The rise of CKD across the United States demands that nurses be prepared to care for these patients. Cardiovascular complications, anemia, and bone formation issues are the most common complications. Approximately 30 million people (15% of adults) are reported to have CKD. By 2020 there will be a 14.4% increase in the prevalence of CKD, and by 2030, the increase will be up by 16.7%. Nurses are integral to providing care that can slow or halt the progression of CKD.