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There is a paucity of data on the prognosis for patients returning to peritoneal dialysis (PD) after a failed transplant. PD has an advantage over hemodialysis in preserving residual renal function, which is associated with better outcomes. We have reviewed the electronic charts of patients on PD in a tertiary academic hospital for the last 8 years. We have compared technique survival, peritonitis-free survival, and residual diuresis in two groups: patients with graft failure which returned to PD (PD-KTx, N = 18) and patients starting PD for other causes (PD-not KTx, N = 163). The median follow-up was similar between groups [42(16,71) in PD-not KTx vs. 48(22,90) months in PD-KTx, p = 0.293]. Kaplan–Meier survival comparing PD-KTx and PD-not KTx showed no difference in technique survival (p = 0.196), and peritonitis-free survival (log-rank 0.238), which were confirmed in a fully adjusted Cox regression. Diuresis at baseline and at the end of the first year was similar between groups (p = 0.799 and p = 0.354, respectively). Six out of 18 patients from the PD-KTx group had the immunosuppression maintained and none of those had peritonitis. The reduction of diuresis across the first year of PD was significant for all patients, except for those on continued immunosuppressive therapy. PD is a worthy dialysis alternative after a failed kidney transplant, providing similar outcomes when compared to patients who started PD for other reasons.

Peritoneal equilibration test (PET) is the gold standard for evaluating peritoneal transport, and measurement of the drain volume after 4-h dwell time with glucose 4.25% is a simple means of evaluating failure of ultrafiltration. The study objective was to verify if the measurement of the volume drained after 4 h dwell of icodextrin at 7.5% (ICO), has a better correlation with the parameters of PET. Patients in a peritoneal dialysis program (N = 35) underwent three procedures: PET; determination of the drain volume after a 4-h dwell with glucose 4.25%; and determination of the drain volume after a 4-h dwell with ICO. Among patients who were classified as high transporters, the ultrafiltration volume was greater after ICO use. The ICO ultrafiltration volume correlated negatively with the ratio between the 4- and 0-h dialysate glucose concentrations (D4/D0 ratio, r = -0.579; P = 0.002), correlating positively with the dialysate-to-plasma ratio for creatinine (D/PCr ratio, r = 0.474; P = 0.002). For ICO, the area under the receiver operating characteristic curve was 0.867 and 0.792 for the D/PCr and D4/D0 ratios (P

Objective to explore the status of concentration of klotho and fibroblast growth factor 23 (FGF23) in cerebrospinal fluid (CSF) of patients with narcolepsy. Patients/methods 59 patients with narcolepsy and 17 control individuals were enrolled. We used radioimmunoassay, human klotho enzyme-linked immunosorbent assay (ELISA), human intact FGF23 ELISA and spectrophotometry to measure hypocretin-1, klotho, FGF-23 and phosphorus, respectively. T-Student Test was used to compare klotho and phosphate concentrations, Mann–Whitney U Test were used to compare FGF-23 levels between groups. ANOVA Test was used to compare klotho and phosphate CSF concentrations among narcolepsy patients with CSF hypocretin-1 110 pg/ml (HCRT+) versus control subjects. Results Klotho and phosphorus CSF levels were lower in narcoleptic patients than in control (908.18 ± 405.51 versus 1265.78 ± 523.26 pg/ml; p = 0.004 and 1.34 ± 0.25 versus 1.58 ± 0.23 mg/dl; p = 0.001, respectively). We found higher FGF-23 levels in narcoleptic patients (5.51 versus 4.00 pg/mL; p = 0.001). Klotho and phosphorus CSF levels were lower in both HCRT- and HCRT+ than controls. Moreover, there were higher FGF-23 levels in both HCRT-/HCRT+ groups versus controls. However, we did not find differences comparing HCRT- and HCRT+ groups, analyzing CSF klotho, FGF-23 or phosphorus levels. Conclusions Patients with narcolepsy have decreased CSF concentration of klotho and increased CSF levels of FGF-23. These findings may play a role in understanding the pathogenesis of narcolepsy.

BackgroundRenal replacement therapy (RRT) is usually indicated for patients with chronic kidney disease (CKD) with glomerular filtration rate below 10 ml/ml/min/1.73m2. However, the need for RRT and timing of dialysis initiation are debatable for patients aged 70 years or older. We here describe the study design and methodology of the Aging Nephropathy Study (AGNES) protocol that aims at evaluating to what extent geriatric-related conditions such as frailty, cognitive dysfunction, and presence of comorbidities have an impact on survival and RRT initiation in this group of patients. In this manuscript we provide detailed information about the AGNES study design and methodology.MethodsAGNES is a prospective observational cohort that aim to investigate clinical, biochemical and demographic factors associated with RRT initiation and mortality of patients with CKD stage 4 or 5 who are aged 70 years and older. We plan to include 200 patients over 5 years. Clinically stable outpatients on conservative management for at least 6 months will be recruited from the Nephrogeriatric Clinic at theHospital das Clinicas da Universidade de Sao Paulo, Brazil. Eligible patients are submitted to a full clinical examination, geriatric assessment, and blood test at baseline. Following the baseline visit the patients are being monitored during an observational follow up period of at least 12 months during which patients will be contacted in the clinic at their regular follow up or by phone until either RRT initiation or death occurs. This cohort includes evaluation of cognition by the education-adjusted 10-point Cognitive Screener (10-CS), frailty by Fried index score, a complete nutritional assessment (by body composition assessment, global subjective assessment and dietary intake), comorbidities by Charlson comorbidity index and biochemical markers including FGF-23 and Klotho.DiscussionThe AGNES cohort, a real-world study of current clinical practice in elderly patients with advanced CKD prior to dialysis initiation, will shed light into progression of CKD and its complications, indications of RRT and factors determining survival. This investigation will elucidate to what extent geriatric conditions, nutritional status and clinical factors are associated with survival, quality of life and RRT initiation in elderly CKD patients not yet on dialysis.Trial registrationRegistered onClinicalTrials.govon 18 October 2019 (NCT04132492).

Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries. Resumo Pacientes em hemodiálise são expostos ao cálcio, por meio do dialisato, pelo menos três vezes por semana. As alterações no cálcio sérico variam de acordo com a transferência de massa de cálcio durante a diálise, que é dependente do gradiente entre a concentração de cálcio no plasma e no dialisato (d [Ca]) e o estado de renovação do esqueleto que altera a capacidade do osso de incorporar cálcio. Embora subestimado, o d [Ca] pode potencialmente causar balanço positivo de cálcio que leva a danos em órgãos sistêmicos, incluindo associações com mortalidade, disfunção miocárdica, tolerabilidade hemodinâmica, calcificação vascular e arritmias. A fisiopatologia desses efeitos adversos inclui alterações do cálcio sérico, supressão do hormônio da paratireóide e calcificação vascular por meio de efeitos diretos e indiretos. Alguns órgãos são mais suscetíveis a alterações na homeostase do cálcio. Nesta revisão, discutimos os dados existentes e os mecanismos potenciais que ligam o d [Ca] ao equilíbrio do cálcio com a consequente disfunção no esqueleto, miocárdio e artérias.

Studies investigating bone histology in children with chronic kidney disease (CKD) are scarce.Forty-two patients, mean age 11.3 ± 4.3 years with stage 5 CKD on dialysis, underwent double tetracycline labeling bone biopsy and the relationship between clinical features, biochemical markers, and bone densitometry (DXA) was investigated.Low bone turnover was present in 59% of patients, abnormal mineralization in 29%, and low bone volume in 7%. Higher bone formation rate was found in non-Caucasian patients, whereas abnormal mineralization occurred in older and shorter children. We found no impact of gender and etiology of renal disease in our population. Parathormone (PTH) and alkaline phosphatase (AP) showed positive associations with bone turnover. ROC curve analysis showed a fair performance of biomarkers to predict TMV status. PTH 2 times ULN independently associated with low bone turnover (RR 5.62, 95% CI 1.01-31.24; p = 0.049), in a model adjusted for race, calcitriol dosage, and calcium. It was also associated with abnormal mineralization (RR 1.35, 95% CI 1.04-1.75; p = 0.025), in a model adjusted for BMD scores, AP, age, and calcitriol. PTH and AP significantly predicted turnover and mineralization defect, although with low specificity and sensitivity, reaching a maximum value of 64% and 67%, respectively.While PTH and AP were associated with turnover and mineralization, we recognize the limitation of their performance to clearly distinguish high from low/normal bone turnover and normal from abnormal mineralization. Our results reinforce the need to expand knowledge about renal osteodystrophy in pediatric population through prospective bone biopsy studies. Graphical abstract.

Hypokalemia is a well-described electrolyte disturbance in patients on peritoneal dialysis (PD). Hyperkalemia, however, is still overlooked, although it also represents a risk factor for mortality. Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ACE/ARB), diuretics, and proton pump inhibitor (PPI) can interfere with potassium levels in these patients. This is a retrospective study that evaluated monthly serum potassium in a 5-year period. Serum potassium disturbances were evaluated as time-average and number of hypo- and hyperkalemia episodes per patient. Prescribed medication such as ACE/ARB, diuretics, and omeprazole were recorded. We evaluated 2025 potassium measurements obtained from 146 patients on PD. Serum potassium ranged from 2.5 to 8.3 mEq/L with an average of 4.72 ± 0.74 mEq/L. Hypokalemia was found in 59 measurements (2.9%) obtained from 35 patients (23.9%) whereas hyperkalemia was demonstrated in 269 (13.3%) measurements obtained from 74 patients (50.7%). Hypokalemia was associated with low albumin (p = 0.022), and omeprazole use (p = 0.024). Black race was a protector factor (p = 0.031). Omeprazole-associated hypokalemia was seen only in non-anuric patients and remained an independent risk factor even after adjustments. Patients who had hyperkalemia were more likely to be anuric (p = 0.001) and in use of furosemide (p = 0.0001). Hyperkalemia and hypokalemia are very frequent in patients on PD and should be closely monitored. Interventional studies should address the impact of discontinuing omeprazole in the levels of potassium.

BackgroundHypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism.MethodsWe assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels..ResultsOne thousand six hundred ten patients (64 ± 15 years, 46.8% men, 25.3% diabetic) were included. At beggnining of follow up eGFR was between 45 and 60, 30–45 and 15-30 ml/min/1.73m2in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria (19.6% with LFT vs. 15.4% without LFT,p = 0.032). Median follow-up time was of 21 months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was − 0.05(− 0.26, 0.23) ml/min/1.73m2, reaching 1.7(1.3, 2.4) ml/min/1.73m2by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT.ConclusionsWe confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies.

Background: Patients with chronic kidney disease (CKD) are less likely to be submitted to coronary artery bypass grafting (CABG) then clinical medical treatment based on the potential high risk of mortality. However, whether patients on maintenance dialysis who underwent an elective CABG experience high hospital- and long-term mortality is still debatable. Methods: This is a prospective observational study that evaluated patients who underwent elective CABG. Three groups were compared: reference (n = 167, estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2), CKD3–4 (n = 84, eGFR 15–59 mL/min/1.73 m2), and maintenance hemodialysis (n = 31). Demographic, clinical, biochemical, fluid balance data, and Sequential Organ Failure Assessment (SOFA) scores were assessed daily for the same observer from day 1 (surgery) to hospital discharge. Results: The main outcomes were in-hospital and 1-year mortality. Patients aged 63 ± 10, 63 ± 8, and 65 ± 6 years old, in reference, CKD3–4, and dialysis groups, respectively (p = 0.605). Patients from the reference group had a lower prevalence of diabetes (p = 0.010) and hypertension (p = 0.021). SOFA scores were higher in CKD3–4 and dialysis groups (p = 0.001), though this difference disappeared without the renal component (p = 0.326). In-hospital mortality (n = 17) was similar across groups (p = 0.955). There was no difference in 1-year mortality among groups even after adjustments for age, diabetes, intraoperative blood loss, and time on ventilation. Conclusions: CABG short-term mortality seems not to be greater among selected patients on maintenance dialysis. A multidisciplinary team has been helping cardiologists and cardiac surgeons in the decision-making process regarding the best approach in coronary artery disease, and CABG should be considered a worthy therapeutic option.

Introduction Restless legs syndrome (RLS) is a highly prevalent sleep movement disorder usually accompanied by periodic limb movements of sleep (PLMS). The incidence of RLS and PLMS in patients with end-stage renal disease (ESRD) on dialysis is much higher. Clinically, RLS and PLMS can co-occur. We hypothesized that patients with ESRD on dialysis would have a distinct presentation of RLS, with a higher prevalence of PLMS. Methods We examined clinical, demographic, biochemical, and polysomnographic characteristics of RLS in patients on dialysis matched to control subjects with normal renal function based on age, sex, body mass index, and frequency of apneas and hypopneas per hour of sleep, defined by the apnea and hypopnea index (AHI), in a proportion of 3:1. Patients with ESRD were on hemodialysis three times per week. Polysomnography was performed overnight in the sleep laboratory. Findings Patients on dialysis compared to control subjects had a lower amount of N3 sleep (77.6 ± 39.9 minutes vs. 94.8 ± 33.7 minutes, p = 0.037) and REM sleep (55.6 ± 27.5 minutes vs. 74.1 ± 28.4 minutes, p = 0.006), regardless of the presence of RLS. Among the patients on dialysis, those with RLS had higher PLMS. In the control group, patients with RLS had a lower ferritin level, which was not observed in the dialysis group. There was a significant interaction between PLMS and ESRD (p = 0.001), with a higher prevalence of PLMS in patients with ESRD on dialysis in a model adjusted for AHI, sex, arousals, and age. Factors that were associated with PLMS were RLS (p = 0.003), ESRD (p = 0.0001), and AHI (p = 0.041), with an adjusted R2 of 0.321. Conclusion RLS in patients with ESRD on dialysis is independently associated with PLMS, regardless of the severity of sleep apnea, arousals, and age.

Background: Current guidelines recommend assessment of 25-vitamin D status in patients with chronic kidney disease (CKD). Although significant differences among assays have been described, the impact of CKD on this variability has never been tested. Methods: We tested the variability between two 25-vitamin D assays in patients with CKD (eGFR < 60 mL/min/1.73m2) who had consecutive 25-vitamin D measurements in 2015 (Assay 1 - Diasorin LIASON 25 TOTAL - D assay®) and 2016 (Assay 2 - Beckman Coulter Unicel Xl 800®). The cohort consisted of 791 adult patients (122 with normal renal function and 669 with CKD - 33, 30, and 37% in stages 3, 4, and 5 on dialysis, respectively). Results: Levels of 25-vitamin D were lower and the prevalence of hypovitaminosis D using assay 1 was higher than using assay 2 in patients with CKD, regardless of similar levels of calcium, phosphate, and parathyroid hormone. As kidney function decreased, the percentage of disagreement between the assays increased. Conclusion: There is a noteworthy variability between assays in patients with CKD such that the diagnosis of hypovitaminosis D is modified. The mechanism behind this result is still unclear and might be due to a possible interference in the analytical process. However, the clinical significance is unquestionable, as the supplementation of vitamin D can be erroneously prescribed to these patients.

Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%, high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.

Although diuretics are often prescribed to control fluid overload, they can change Chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters. Previous studies have shown an association between diuretic prescription and changes in both calciuria and parathormone levels. However, the causal relationship could not be confirmed. In addition, the effects of diuretics on bone mineral density and turnover markers are yet to be established. To evaluate the effects of diuretics on CKD-MBD, we have performed a prospective randomized trial comparing hydrochlorothiazide with furosemide in a stage 3CKD population followed for 1 year. Furosemide increased bone remodeling and parathormone levels, whereas hydrochlorothiazide attenuated parathyroid hormone rise and decreased bone turnover markers., Highlights • Diuretics may change parathormone (PTH), although a randomized trial was missing. • Patients with CKD were randomized to either Furosemide or Hydrochlorothiazide. • Furosemide increased PTH levels, CTx and P1NP. • Hydrochlorothiazide attenuated PTH rise and decreased CTx and P1NP.

Background Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). Methods In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. Results Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. Conclusions Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.

Mineral and bone metabolism disorders are relatively common among patients with end-stage renal disease on maintenance hemodialysis. Corneal and conjunctival calcification is the main extravascular site for calcification. Recently, this form of calcification has been linked to vascular calcification. Secondary hyperparathyroidism can lead to high levels of calcium and phosphorus and increase the risk of calcification. Here, we report a case of a 38-year-old female with severe hyperparathyroidism who underwent eye examination before and after parathyroidectomy. Anterior segment optical coherence tomography showed an improvement in the number and size of ocular calcifications 6 months after surgery. This case calls attention to the importance of eye examination in patients on dialysis and brings the possibility of recovery of calcification in a short-term follow-up.

Introduction: Body composition is critical for the evaluation of patients with Chronic Kidney Disease (CKD) and can be obtained from either multifrequency bioelectrical impedance analysis (BIA) or dual-energy absorptiometry (DXA). Although the discrepancy between the results obtained from both methods has already been described, reasons are unknown, and might be related to secondary hyperparathyroidism, which is associated with bone loss. Methods: We have evaluated 49 patients (25 males and 24 females): 20 with CKD not on dialysis and 29 on maintenance hemodialysis [18 with severe hyperparathyroidism (HD-SHPT) and 11 submitted to parathyroidectomy (HD-PTX)]. All patients underwent DXA and BIA. Results: The median age and body mass index (BMI) were 49 years and 25.6 kg/m2, respectively. Patients exhibited low bone mineral content (BMC) measured by DXA, particularly those from the HD-SHPT group. The largest BMC measurement disagreement between DXA and BIA was found in the HD-SHPT group (p=0.004). Factors independently associated with this discrepancy in BMC measurement were serum phosphate (p=0.003) and patient group (p=0.027), even after adjustments for age, BMI, and gender (adjusted r2=0.186). PTX attenuated this difference. Discussion: BIA should be interpreted with caution in patients with SHPT due to a loss of accuracy, which can compromise the interpretation of body composition. Resumo Introdução: A composição corporal é fundamental para a avaliação de pacientes com Doença Renal Crônica (DRC), e pode ser obtida por análise de impedância bioelétrica por multifrequência (BIA) ou absorciometria de dupla energia (DXA). Embora a discrepância entre os resultados obtidos pelos dois métodos já tenha sido descrita, os motivos são desconhecidos e podem estar relacionados ao hiperparatireoidismo secundário, devido à perda óssea. Métodos: Avaliamos 49 pacientes (25 homens e 24 mulheres): 20 com DRC não em diálise e 29 em hemodiálise de manutenção [18 com hiperparatireoidismo grave (HD-SHPT) e 11 submetidos à paratireoidectomia (HD-PTX)]. Todos os pacientes foram submetidos à DXA e BIA. Resultados: A mediana da idade e do índice de massa corporal (IMC) foram de 49 anos e 25,6 kg/m2, respectivamente. Os pacientes exibiram baixo conteúdo mineral ósseo (CMO) medido pelo DXA, particularmente aqueles do grupo HD-SHPT. A maior discordância da medida do CMO entre DXA e BIA foi encontrada no grupo HD-SHPT (p = 0,004). Os fatores independentemente associados a essa discrepância na medida do CMO foram fosfato sérico (p = 0,003) e grupo de pacientes (p = 0,027), mesmo após ajustes para idade, IMC e sexo (r2 ajustado = 0,186). PTX atenuou essa diferença. Discussão: A BIA deve ser interpretada com cautela em pacientes com HPTS devido a uma perda de precisão, o que pode comprometer a interpretação da composição corporal.

Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]2D3). PTH promotes calcium release from the bone and enhances tubular calcium resorption through direct action on these sites. Hallmarks of secondary hyperparathyroidism associated with chronic kidney disease (CKD) include increase in serum fibroblast growth factor 23 (FGF-23), reduction in renal 1,25[OH]2D3 production with a decline in its serum levels, decrease in intestinal calcium absorption, and, at later stages, hyperphosphatemia and high levels of PTH. In this paper, we aim to critically discuss severe CKD-related hyperparathyroidism, in which PTH, through calcium-dependent and -independent mechanisms, leads to harmful effects and manifestations of the uremic syndrome, such as bone loss, skin and soft tissue calcification, cardiomyopathy, immunodeficiency, impairment of erythropoiesis, increase of energy expenditure, and muscle weakness.

Background Fluid overload is a risk factor for morbidity, mortality, and prolonged ventilation time after surgery. Patients on maintenance hemodialysis might be at higher risk. We hypothesized that fluid accumulation would be directly associated with extended ventilation time in patients on hemodialysis, as compared to patients with chronic kidney disease not on dialysis (CKD3–4) and patients with normal renal function (reference group). Methods This is a prospective observational study that included patients submitted to isolated and elective coronary artery bypass surgery, divided in 3 groups according to time on mechanical ventilation: 48 h. The same observer followed patients daily from the surgery to the hospital discharge. Cumulative fluid balance was defined as the sum of daily fluid balance over the first 5 days following surgery. Results Patients requiring more than 48 h of ventilation (5.3%) had a lower estimated glomerular filtration rate, were more likely to be on maintenance dialysis, had longer anesthesia time, needed higher dobutamine and noradrenaline infusion following surgery, and had longer hospitalization stay. Multivariate analysis revealed that the fluid accumulation, scores of sequential organ failure assessment in the day following surgery, and the renal function (normal, chronic kidney disease not on dialysis and maintenance hemodialysis) were independently associated with time in mechanical ventilation. Among patients on hemodialysis, the time from the surgery to the first hemodialysis session also accounted for the time on mechanical ventilation. Conclusions Fluid accumulation is an important risk factor for lengthening mechanical ventilation, particularly in patients on hemodialysis. Future studies are warranted to address the ideal timing for initiating dialysis in this scenario in an attempt to reduce fluid accumulation and avoid prolonged ventilation time and hospital stay.

High glucose concentration can activate TLR4 and NF-κB, triggering the production of proinflammatory mediators. We investigated whether the NF-κB pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Adult male Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups – progressors and non-progressors – could be formed based on the degree of glomerulosclerosis. Only progressors exhibited renal TLR4, NF-κB and IL-6 activation. This scenario was already present in rats with short-term DM (2 months), at a time when no overt glomerulosclerosis can be detected. Chronic treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented activation of renal TLR4, NF-κB or IL-6, without interfering with blood glucose. PDTC prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-κB p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-κB pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD.

Although we have seen tremendous advances in the comprehension of CKD-MBD pathophysiology during the last few years, this was not accompanied by a significant change in mortality rate and quality of life. This review will address the traditional and updated pathophysiology of CKD-MBD along with the therapeutic limitations that affect CKD-MBD and proposed alternative treatment targets. An innovative concept brings the osteocyte to the center of CKD-MBD pathophysiology, in contrast to the traditional view of the skeleton as a target organ for disturbances in calcium, phosphate, parathyroid hormone, and vitamin D. Osteocytes, through the synthesis of FGF-23, sclerostin, among others, are able to interact with other organs, making bone an endocrine organ. Thus, osteocyte dysregulation might be an early event during the course of CKD. This review will revisit general concepts on the pathophysiology of CKD-MBD and discuss new perspectives for its treatment.

Background Although a successful kidney transplant (KTx) improves most of the mineral and bone disorders (MBD) produced by chronic kidney disease (CKD), hyperparathyroidism may persist (pHPT). Current guidelines recommend parathyroidectomy if serum parathormone is persistently elevated 1 year after KTx, because pHPT has been recently associated with poor graft outcomes. However, whether patients with pHPT and adequate renal function are at risk for long-term graft failure is unknown. Methods Longitudinal follow-up of 911 adults submitted to KTx between January 2005 and December 2014, with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min 1 year after surgery. Clinical and laboratory data were collected from electronic database. Graft failure was defined as return to dialysis. Results Overall, 62% of the patients were classified as having pHPT 1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up, death-censored graft survival was lower in the pHPT group (P = .009), even after adjustment for age at KTx, donor age, donor type, acute rejection, parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR] 1.99; 1.004–3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff to predict pHPT at 1 year (specificity = 92.1%). Conclusion Having pHPT after a successful KTx increases the long-term risk of death-censored graft failure. This result highlights the need for better recognition and management of CKD-MBD before and during the first year after KTx, and opens a discussion on the more appropriate timing to perform parathyroidectomy.

Background/Aims: Peritoneal dialysis (PD) has gained interest over the last decade as a viable option for early start dialysis. It is still unknown if shorter break-in periods and less time for proper patient evaluation and training could influence technique survival in comparison to planned-start PD. Methods: A prospective and observational study that compared technique survival in a cohort of patients who started either early or planned PD. Early start PD was defined as break-in period from 3 to 14 days with no previous nephrologist follow-up or patient training. Results: A total of 154 patients were included (40 as early start PD), followed by a median time of 381 days. Comparing early vs. planned-start PD, groups were similar concerning age 56 (40; 70) vs. 48 (32; 63) years, p=0.071, body mass index (BMI) 23.3 ± 4.2 vs. 23.8 ± 4.0 kg/m2, p=0.567 and male gender (60 vs. 48%, p=0.201), respectively. Comparing early vs. planned-start groups, there were no differences regarding PD dropout for peritonitis (7.5 vs. 11.4%, p=0.764), catheter dysfunction (12.5 vs. 17.5%, p=0.619) and patient burnout (0 vs. 4.4%, p=0.328), respectively. Less patients in early start group quit PD for peritoneal membrane failure in comparison to planned-start group (2.5 vs. 16.7%, p=0.026). In multivariate cox-regression analysis, the only factors independently associated with technique failure were BMI> 25 kg/m² (p=0.033) and Diabetes Mellitus (p=0.013), whereas no differences regarding early vs. planned-PD start were observed (p=0.184). Conclusion: Despite the adverse scenario for initiating dialysis, early start PD had similar outcomes in comparison to planned-start PD in long-term follow-up.

Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated β-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.

Results from bone biopsy and high-resolution peripheral quantitative computed tomography (HR-pQCT) were compared in 31 CKD patients. There was an agreement mainly for cortical compartment that may represent a perspective on the fracture risk assessment. HR-pQCT also provided some clues on the turnover status, which warrants further studies. Chronic kidney disease (CKD) patients are at high risk of bone disease. Although bone biopsy is considered the best method to evaluate bone disease, it is expensive and not always available. Here we have compared, for the first time, data obtained from bone biopsy and HR-pQCT in a sample of CKD patients on dialysis. HR-pQCT and dual-energy X-ray absorptiometry (DXA) were performed in 31 CKD patients (30 on dialysis). Biopsies were analyzed by quantitative histomorphometry, and classified according to TMV. We have found an inverse correlation between radius cortical density measured by HR-pQCT, with serum, as well as histomorphometric bone remodeling markers. Trabecular density and BV/TV measured through HR-pQCT in the distal radius correlated with trabecular and mineralized trabecular bone volume. Trabecular number, separation, and thickness obtained from HR-pQCT and from bone biopsy correlated with each other. Patients with cortical porosity on bone histomorphometry presented lower cortical density at the distal radius. Cortical density at radius was higher while bone alkaline phosphatase was lower in patients with low turnover. Combined, these parameters could identify the turnover status better than individually. There was an agreement between HR-pQCT and bone biopsy parameters, particularly in cortical compartment, which may point to a new perspective on the fracture risk assessment for CKD patients. Besides classical bone resorption markers, HR-pQCT provided some clues on the turnover status by measurements of cortical density at radius, although the significance of this finding warrants further studies.

Chronic kidney disease (CKD) is characterized by loss of renal function and a consequent increase of serum uremic toxins, which contribute to inflammation status. Deficiency of 25-vitamin D, often found in patients with CKD, has been included as an inflammatory factor since it might modulate the immune system. The aim of this study was to investigate the role of 25-vitamin D on inflammatory pathways in healthy and uremic environment. Toll-like receptor 4 (TLR4), oxidative stress (ROS), vitamin D receptor (VDR), 1-α hydroxylase (CYP27), 24 hydroxylase, cathelicidin, and MCP-1 were evaluated in monocytes exposed to a uremic serum pool compared with healthy pool. The human monocytes lineage (U937) was incubated with or without 25-vitamin D (50 ng/ml for 24 hours). TRL4, VDR, CYP27, CYP24, and ROS were evaluated by flow cytometry. We used ELISA to measure IL-6, TNF-α, IL-10, cathelicidin, and MCP-1 in the cell culture supernatant. We observed a higher expression of TRL-4, IL-6, TNF-α, IL-10, cathelicidin and MCP-1 in monocytes incubated with uremic serum when compared with serum from healthy individuals. Supplementation of 25-vitamin D was able to reduce the expression of TRL4, cathelicidin, and MCP-1 in the uremic environment. There was no difference in the expression of VDR, CYP27 and CYP24 intracellular enzymes. This in vitro study showed that the uremic pool activates inflammatory response in monocytes, which was reversed by 25-vitamin D supplementation; this finding suggests that 25-vitamin D has an anti-inflammatory role in the uremic environment.

Restless legs syndrome (RLS) is a highly prevalent sleep disease among patients on hemodialysis. The physiopathology is still unclear, and may be multifactorial. Because of the association between iron metabolism and chronic kidney disease-mineral and bone disorders (CKD-MBD), we hypothesized that both factors would be associated with RLS.We have evaluated hemodialysis patients, in a face-to-face interview for the diagnosis and severity of RLS, as measured by the International Restless Legs Syndrome Study Group. Clinical, demographic, and biochemical characteristics were measured.Out of 101 adult patients included, RLS was found in 29 (28.7%). Adjusted multinomial regression analysis revealed that age older than 35 years, transferrin saturation less than 47%, serum ferritin level less than 700 ng/mL, hemoglobin level less than 9.8 g/dL, serum phosphate level higher than 5.2 mg/dL, FGF-23 higher than 2,000 RU/mL, and C-reactive protein less than 1.24 mg/dL were independently associated with RLS. RLS was classified as mild, moderate, severe, and very severe in 3.4%, 41.7%, 44.8%, and 10.1% of patients, respectively. Scores of severity correlated significantly with erythropoietin dose/kg/w (p = 0.046), phosphate (p = 0.003), and inversely with serum albumin (p = 0.003) and calcium (p = 0.008). Phosphate and 25(OH)-vitamin D correlated with transferrin saturation. Patients with severe/very severe symptoms were mostly women, presented with lower serum iron, ionic calcium, and serum albumin levels and higher levels of serum phosphate, and higher percentage of 25(OH)-vitamin D deficiency and levels of FGF-23 higher than 2,000 RU/mL than did those with mild/moderate symptoms.CKD-MBD factors besides iron metabolism are associated with RLS in patients on hemodialysis, providing new insights into the understanding of RLS in this population.

Background: Conventional hemodialysis (HD) is associated with dialysis-induced hypotension (DIH) and ineffective phosphate removal. As the main source of extracellular fluid removed during HD are the legs, we sought to reduce DIH and increase phosphate removal by using cycling and pneumatic compression, which would potentially provide higher venous return, preserving central blood flow and also offering more phosphate to the dialyzer. Methods: We evaluated 21 patients in a randomized crossover fashion in which each patient underwent 3 different HD: control; cycling exercise during the first 60 min; and pneumatic compression during the first 60 min. Data obtained included bioelectrical impedance, hourly blood pressure measurement, biochemical parameters, and direct quantification of phosphate through the dialysate. DIH was defined as a drop in mean arterial pressure (MAP) ≥20 mm Hg. Results: There was no difference in the ultrafiltration rate (p = 0.628), delta weight (p = 0.415), delta of total, intra and extracellular body water among the control, cycling, and pneumatic compression (p = 0.209, p = 0.348, and p = 0.467 respectively). Delta MAP was less changed by pneumatic compression when compared to control, cycling, and pneumatic compression respectively (-4.7 [-17.2, 8.2], -4.7 [-20.5, -0.2], and -2.3 [-8.1, 9.0] mm Hg; p = 0.021). DIH occurred in 43, 38, and 24% of patients in control, cycling, and pneumatic compression respectively (p = 0.014). Phosphate removal did not increase in any intervention (p = 0.486). Higher phosphate removal was dependent on ultrafiltration, pre dialysis serum phosphate, and higher parathyroid hormone. Conclusion: Pneumatic compression during the first hour of dialysis was associated with less DIH, albeit there was no effect on fluid parameters. Neither exercise nor pneumatic compression increased phosphate removal.

Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2)=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.

The outlines of the current manuscript are: 1. Re-establish the link between hypertension and SDB including prevalence, mechanism, and reversal of process (i.e. improvement in hypertension with improvement in SDB), why it is important-cardiovascular mortality with numbers. 2. Re-establish the link between hypertension and CKD including same points as above. Then ask if both CKD and SDB are combined, what happens to hypertension and cardiovascular mortality. 3. Lastly, talk about links between CKD and SDB on how each process feeds on the other and is a growing, common problem.

Introduction: Mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD) constitute a syndrome defined by changes in calcium, phosphorus (P), vitamin D and parathormone, fibroblast growth factor 23 (FGF-23) and its specific cofactor, Klotho. CKD-MBD, as well as smoking, are associated with an increased risk of cardiovascular disease. However, it is not known whether or not smoking impacts the cardiovascular risk in CKD- MBD. Objective: To analyze the relationship between smoking and CKD-MBD markers. Methods: We evaluated 92 patients divided into: 1) Control Group: non-smokers without CKD; 2) CKD group in stages III and IV under conservative treatment (20 non-smokers and 17 smokers); 3) CKD group on dialysis (21 non-smokers and 19 smokers). Clinical, demographic, and biochemical markers were compared between the groups. Results: FGF-23 and Klotho levels were not different between smokers and non-smokers. Patients in the CKD group on conservative treatment had higher serum P than non-smokers (p = 0.026) even after adjusted for renal function (p = 0.079), gender (p = 0.145) and age (p = 0.986). Conclusion: Smoking confers a higher cardiovascular risk to CKD patients under conservative treatment as it is associated with higher levels of P. Further studies are needed to confirm and better elucidate this finding.

Although chronic kidney disease is associated with other bone disorders, osteoporosis can be found in this context, and it is defined based on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry. As CKD progresses, the percentage of normal BMD decreases, whereas that of osteopenia/osteoporosis increases, mostly due to hip involvement, particularly in patients with reduced renal function. Osteoporosis is a highly prevalent disease in patients with chronic kidney disease (CKD). We investigated the features of bone mineral density (BMD) in patients with assorted kidney diseases and hypothesized that low BMD, as measured by dual-energy X-ray absorptiometry (DXA), would be more prevalent as kidney function decreased and would correlate with biomarkers of mineral and bone disease. DXA obtained from January 1, 2008, to December 31, 2017, clinical, demographic, and biochemical data at the time of image acquisition were recorded. Data from 1172 patients were included in this study (81.3% women, 79.9% white, and 8.1% diabetic). Osteopenia and osteoporosis in at least one site (total hip or spine) were found in 32.7% and 20.0% of patients, respectively. As CKD progressed, the percentage of patients with normal BMD decreased, whereas the percentage of osteopenia and osteoporosis increased, which was mostly due to the total hip involvement, particularly in patients with estimated glomerular filtration rate (eGFR) 90 ml/min as reference, the odds ratios for osteoporosis/osteopenia at the hip were 1.51 (95% CI 1.01–2.24) and 1.91 (95% CI 1.13–3.20) for patients with eGFR 30–60 and 15–30 ml/min/1.73 m2, respectively. No CKD stage was significantly associated with the risk of osteoporosis/osteopenia at the spine. Our results highlighted that low BMD in patients with CKD is associated with age and hyperparathyroidism, and affects predominantly the hip.

Bone biopsy defines classical diseases that constitute the renal osteodystrophy. There is a recent concern regarding other histological findings that are not appreciated by using the turnover, mineralization, and volume (TMV) classification. Iron (Fe) overload has been considered a new challenge and the real significance of the presence of this metal in bones is not completely elucidated. Therefore, the main goal of the current study was to not only to identify bone Fe, but also correlate its presence with demographic, and biochemical characteristics. This is a cross-sectional analysis of bone biopsies performed in 604 patients on dialysis from 2010 to 2014 in a tertiary academic Hospital. Histomorphometric findings revealed the presence of Fe in 29.1%. Fe was associated with higher levels of serum ferritin and serum calcium. No TMV status was related to Fe bone overload. Our study has highlighted that the presence of Fe in one-third of bone samples has unknown clinical significance. The lack of other contemporary bone biopsy study reporting Fe prevents us from comparison. The findings presented here should be specifically addressed in a future research and will require attention prior to implementation of any clinical guideline. If any proposed treatment, however, would change the bone Fe-related morbidity is undetermined.

Background: Diuretics are widely used in patients with chronic kidney disease (CKD). While thiazide-like diuretics limit urinary calcium excretion, loop diuretics (LD) promote calcium wasting, which might facilitate the development of secondary hyperparathyroidism (HPT2). We sought to investigate, in CKD patients not on dialysis, the influence of either hydrochlorothiazide (Hydro) or furosemide (Furo) on circulating parathyroid hormone (PTH) and whether such actions are determined by the effects of these compounds on calcium excretion. Methods: Electronic charts of all nephrology outpatients (CKD stages 2-5) who were given Hydro or Furo were included. We assessed estimated glomerular filtration rate (eGFR), biochemical parameters and 24-hour calcium excretion. Hyperparathyroidism was defined as PTH >65 pg/ml. Results: Out of 275 patients, 108 (29%) were taking Hydro and 167 (61%) Furo. Patients on Hydro were younger, mostly female and had higher eGFR. The median 24-hour urinary calcium excretion in the overall cohort was 41 (22, 76), being lower in Furo than in Hydro patients (37 (16, 68) vs. 47 (26, 88) mg/24 h, respectively, p = 0.016). Logistic regression showed that, after adjustment for eGFR, calcium excretion rate was found not to increase the risk ratio for HPT2, whereas Furo was a strong predictor of HPT2. Conclusion: Furo increased the risk of HPT2 among CKD patients compared to Hydro. This effect was independent of eGFR or calcium excretion. The use of LD in CKD, currently preferred in advanced stages, should be reappraised.

Parathyroidectomy (PTx) seems to improve cardiovascular outcomes and reduce blood pressure levels. However, the effect of PTx on hemodynamic changes during hemodialysis (HD) is still overlooked. This was a prospective cohort design. Patients with end-stage renal disease on maintenance HD were included. Diabetes and nonsinusal rhythm were exclusion criteria. History of PTx was recorded. Finometer monitor was used to access parameters immediately pre- and post-HD sessions. Cardiac index (CI) variation (ΔCI) and peripheral arterial resistance variation (ΔPAR) were the variables of interest. Biochemical and echocardiographic data were also obtained. PTx patients (n = 11) were matched to non-PTx patients (n = 20). ΔPAR was lower in PTx group in comparison with non-PTx group (P = 0.039), which was independent of parathyroid hormone (PTH) levels. Multiple regression analysis showed that PTx, ΔCI, and dialysate calcium remained independently associated with PAR variation and even adjusted for ultrafiltration rate (adjusted r2 = 0.64). In conclusion, parathyroidectomized patients have impaired capacity of vasoconstriction in response to ultrafiltration, an effect independent of serum PTH levels. Further studies are needed to elucidate mechanisms explaining the interaction between PTx and systemic vascular tonus.

Sleep apnea (SA), a condition associated with increased cardiovascular risk, has been traditionally associated with obesity and aging. However, in patients with fluid-retaining states, such as congestive heart failure and end-stage renal disease, both prevalence and severity of SA are increased. Recently, fluid shift has been recognized to play an important role in the pathophysiology of SA, since the fluid retained in the legs during the day shifts rostrally while recumbent, leading to edema of upper airways. Such simple physics, observed even in healthy individuals, has great impact in patients with fluid overload. Correction of the excess fluid volume has risen as a potential target therapy to improve SA, by attenuation of nocturnal fluid shift. Such strategy has gained special attention, since the standard treatment for SA, the positive airway pressure, has low compliance rates among its users and has failed to reduce cardiovascular outcomes. This review focuses on the pathophysiology of edema and fluid shift, and summarizes the most relevant findings of studies that investigated the impact of treating volume overload on SA. We aim to expand horizons in the treatment of SA by calling attention to a potentially reversible condition, which is commonly underestimated in clinical practice.

Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%. Parathyroid hormone was suppressed (15 pg/mL), associated with a low-normal 25-hydroxyvitamin D (26 ng/mL) concentration but high 1,25-dihydroxyvitamin D concentration (92 pg/mL). Serum intact FGF-23 (fibroblast growth factor 23) was undetectable. Genetic analysis revealed tumoral calcinosis due to a compound heterozygous mutation in FGF23, c.201G>C (p.Gln67His) and c.466C>T (p.Gln156*). Due to lack of other treatment options and because the patient was facing severe vascular complications, we initiated a daily hemodialysis program even in the setting of normal kidney function. This unusual therapeutic option successful controlled hyperphosphatemia and reduced metastatic tumoral lesions. This is a report of a new mutation in FGF23 in which dialysis was an effective treatment option for tumoral calcinosis with normal kidney function.

Background The transition from pre-dialysis chronic kidney disease (CKD) to renal replacement therapy (RRT) is a stressful event. Anxiety, depression and stress are frequent conditions in this population, and might play a role on the choice of dialysis modality. Methods This is a prospective study that included stages 4-5 CKD patients during a dialysis multi-disciplinary education program. Demographic, clinical, and laboratory data were evaluated. Hospital Anxiety and Depression Scale and a Perceived Stress Scale assessed levels of anxiety, depression and stress, respectively. Results A total of 67 from 190 recruited patients were included (59 ± 15 years, 54% males). Comparing patients who chose peritoneal dialysis (PD) and hemodialysis (HD), there were no differences on anxiety (p = 0.55), and depression scores (p = 0.467), and stress (p = 0.854). Anxious (p = 0.007) and depressive (p = 0.030) patients presented lower levels of phosphate than those not affected. There was a significant correlation (p

Background/Aims: Hyperphosphatemia is associated with high mortality rate in patients on dialysis. Conventional hemodialysis (HD) is a limit technique in removing phosphate (P). There is a widespread belief that P is removed mainly in the first hour of HD. The aim of this study was to certify the percentage of 1-hour removal of P as compared to the entire procedure. Methods: data from the first dialysis of the week of 21 patients (13 men, age 44±15 years), for 3 consecutive dialysis sessions were evaluated. Fresh dialysate samples were collected at 1 hour and at the end of the session from a partial spent dialysate collection method. Results: Pre dialysis serum P was 4.7±1.7 mg/dl. Reduction rate of serum P was 47.4 ± 14.3 and 45.1 ± 10.8% in 1- and 4-hour of HD, respectively (p=0.322). P removal was 194 (145, 242) mg in 1-hour (pConclusion: despite the P serum concentration normalizing in the first hour of hemodialysis, the removal in the same period reaches only 25% of the entire session.

Introduction Obstructive sleep apnea (OSA) is common in edematous states, notably in hemodialysis patients. In this population, overnight fluid shift can play an important role on the pathogenesis of OSA. The effect of compression stockings (CS) and continuous positive airway pressure (CPAP) on fluid shift is barely known. We compared the effects of CS and CPAP on fluid dynamics in a sample of patients with OSA in hemodialysis, through a randomized crossover study. Methods Each participant performed polysomnography (PSG) at baseline, during CPAP titration, and after 1 week of wearing CS. Neck circumference (NC) and segmental bioelectrical impedance were done before and after PSG. Results Fourteen patients were studied (53 ± 9 years; 57% men; body mass index 29.7 ± 6.8 kg/m2). Apnea–hypopnea index (AHI) decreased from 20.8 (14.2; 39.6) at baseline to 7.9 (2.8; 25.4) during CPAP titration and to 16.7 (3.5; 28.9) events/h after wearing CS (CPAP vs. baseline, p = 0.004; CS vs. baseline, p = 0.017; and CPAP vs. CS, p = 0.017). Nocturnal intracellular trunk water was higher after wearing CS in comparison to baseline and CPAP (p = 0.03). CS reduced the fluid accumulated in lower limbs during the day, although not significantly. Overnight fluid shift at baseline, CPAP, and CS was −183 ± 72, −343 ± 220, and −290 ± 213 ml, respectively (p = 0.006). Overnight NC increased at baseline (0.7 ± 0.4 cm), decreased after CPAP (−1.0 ± 0.4 cm), and while wearing CS (−0.4 ± 0.8 cm) (CPAP vs. baseline, p

As the world's population ages, the incidence of chronic kidney disease (CKD) is growing. There is ongoing debate regarding whether high levels of parathyroid hormone (PTH) would be more common in elderly than young patients, and which factors are driven the risk of secondary hyperparathyroidism (SHPT), independent of renal function.Elderly patients (age ≥ 65 years, N = 518) were compared to a 1:1 sex- and estimated glomerular filtration rate (eGFR)-matched sample of young patients (age 65 years), in a cross-sectional analysis. Demographic, biochemical and drug prescription data were collected from electronic charts. The main outcome measure was the prevalence of SHPT, defined as PTH 65 pg/mL.Elderly patients presented higher serum calcium and PTH levels and lower serum phosphate, and were taking more diuretics than young patients. SHPT was more frequent among elderly patients (49.4 vs. 38.6%, p = 0.005), and it was associated with lower eGFR, low levels of 25(OH) vitamin D and with furosemide therapy, while thiazide use was a protector factor. Elderly patients with 25(OH) vitamin D 40 ng/mL were protected against SHPT. The Ca/PTH ratio was lower in elderly than in young patients [0.15 (0.10, 0.20) vs. 0.16 (0.11, 0.23), respectively, p = 0.003].CKD elderly patients have higher risk of SHPT than young, which cannot be explained solely by renal function. Besides low levels of vitamin D, furosemide therapy and a distinct relationship between calcium and PTH are possible factors contributing to SHPT. Whether this is a result of renal resistance to PTH or an altered set point to calcium deserves further investigation.

Fluid displacement from the legs during recumbency while in bed might narrow the upper airway (UA) in association with nuchal fluid accumulation that may contribute to the pathogenesis of obstructive sleep apnea (OSA). The aim of this study was to test the hypothesis that rostral fluid displacement from the legs causes a greater decrease in UA cross-sectional area (UA-XSA) and a greater increase in UA mucosal water content (UA-MWC) and internal jugular venous volume (IJVVol) in subjects with OSA than in those without OSA.Subjects underwent baseline assessment of leg fluid volume (LFV) measured by bio-electrical impedance, as well as UA-XSA and UA-MWC by magnetic resonance imaging. They were then randomly assigned to a 20-min period either with or without application of lower body positive pressure (LBPP) of 40 mm Hg, followed by a 15-min washout period, after which they crossed over to the other arm of the study. Measurements of LFV, UA-MWC, and UA-XSA were repeated after each arm of the study.In 12 subjects without sleep apnea, UA-XSA increased and UA-MWC decreased significantly, whereas in 12 subjects with OSA, UA-XSA decreased and UA-MWC increased significantly in response to LBPP. The changes in UA-XSA and UA-MWC in response to LBPP differed significantly between the 2 groups (p = 0.006 and p0.001, respectively), despite similar changes in LFV and IJVVol.Our results suggest that rostral fluid shift may contribute to the pathogenesis of OSA at least partly through narrowing of the UA due to transudation of fluid into the UA mucosa.