Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

STUDY OBJECTIVES: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). METHODS: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. RESULTS: 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. CONCLUSIONS: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function.

Vascular Function in Chronic Kidney Disease and in Renovascular Disease

Cardiovascular mortality is 15 to 30 times higher in patients with chronic kidney disease than in the age-adjusted general population. Even minor renal dysfunction predicts cardiovascular events and death in the general population. In patients with atherosclerotic renovascular disease the annual cardiovascular event and death rate is even higher. The abnormalities in coronary and peripheral artery function in the different stages of chronic kidney disease and in renovascular disease are still poorly understood, nor have the cardiac effects of renal artery revascularization been well characterized, although considered to be beneficial. This study was conducted to characterize myocardial perfusion and peripheral endothelial function in patients with chronic kidney disease and in patients with atherosclerotic renovascular disease. Myocardial perfusion was measured with positron emission tomography (PET) and peripheral endothelial function with brachial artery flow-mediated dilatation. It has been suggested that the poor renal outcomes after the renal artery revascularization could be due to damage in the stenotic kidney parenchyma; especially the reduction in the microvascular density, changes mainly evident at the cortical level which controls almost 80% of the total renal blood flow. This study was also performed to measure the effect of renal artery stenosis revascularization on renal perfusion in patients with renovascular disease. In order to do that a PET-based method for quantification of renal perfusion was developed. The coronary flow reserve of patients with chronic kidney disease was similar to the coronary flow reserve of healthy controls. In renovascular disease the coronary flow reserve was, however, markedly reduced. Flow-mediated dilatation of brachial artery was decreased in patients with chronic kidney disease compared to healthy controls, and even more so in patients with renovascular disease. After renal artery stenosis revascularization, coronary vascular function and renal perfusion did not improve in patients with atherosclerotic renovascular disease, but in patients with bilateral renal artery stenosis, flow-mediated dilatation improved. Chronic kidney disease does not significantly affect coronary vascular function. On the contrary, coronary vascular function was severely deteriorated in patients with atherosclerotic renovascular disease, possibly because of diffuse coronary artery disease and/or diffuse microvascular disease. The peripheral endothelial function was disturbed in patients with chronic kidney disease and even more so in patient with atherosclerotic renovascular disease. Renal artery stenosis dilatation does not seem to offer any benefits over medical treatment in patients with renovascular disease, since revascularization does not improve coronary vascular function or renal perfusion.

Serum intact parathyroid hormone levels in cats with chronic kidney disease

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

Odonto-ungueal dysplasia: an apparently new autosomal dominant ectodermal dysplasia

We describe 27 subjects (11 women) from five generations of a family with an apparently hitherto undescribed ectodermal dysplasia. All of them presented dental and/or nail alterations only. A genetic analysis of the family suggests an autosomal dominant gene. Differential diagnosis considered eight conditions belonging to the same odonto-onychic (2-3) subgroup, as well as Fried's tooth and nail syndrome and hypodontia and nail dysgenesis (both in 1-2-3 subgroup).

Cultural adaptation and validation of the "Kidney Disease and Quality of Life - Short Form (KDQOL-SF™ 1.3)" in Brazil

The objective of the present study was to translate the Kidney Disease Quality of Life - Short Form (KDQOL-SF™1.3) questionnaire into Portuguese to adapt it culturally and validate it for the Brazilian population. The KDQOL-SF was translated into Portuguese and back-translated twice into English. Patient difficulties in understanding the questionnaire were evaluated by a panel of experts and solved. Measurement properties such as reliability and validity were determined by applying the questionnaire to 94 end-stage renal disease patients on chronic dialysis. The Nottingham Health Profile Questionnaire, the Karnofsky Performance Scale and the Kidney Disease Questionnaire were administered to test validity. Some activities included in the original instrument were considered to be incompatible with the activities usually performed by the Brazilian population and were replaced. The mean scores for the 19 components of the KDQOL-SF questionnaire in Portuguese ranged from 22 to 91. The components "Social support" and "Dialysis staff encouragement" had the highest scores (86.7 and 90.8, respectively). The test-retest reliability and the inter-observer reliability of the instrument were evaluated by the intraclass correlation coefficient. The coefficients for both reliability tests were statistically significant for all scales of the KDQOL-SF (P < 0.001), ranging from 0.492 to 0.936 for test-retest reliability and from 0.337 to 0.994 for inter-observer reliability. The Cronbach's alpha coefficient was higher than 0.80 for most of components. The Portuguese version of the KDQOL-SF questionnaire proved to be valid and reliable for the evaluation of quality of life of Brazilian patients with end-stage renal disease on chronic dialysis.

Raising awareness of chronic kidney disease in a Brazilian urban population

The incidence and prevalence of chronic kidney disease have been increasing in recent years in developing countries. The aim of this study was to report the results of a general chronic kidney disease awareness program applied to an urban population in a large Brazilian city. From January 2002 to January 2005 a total of 8883 individuals in the city of Curitiba (PR, Brazil) were screened for hypertension, body mass index, hematuria, and proteinuria. A family history and previous medical diagnosis of hypertension and diabetes mellitus (DM) were also recorded. Of the 8883 individuals assessed, 56% were women, subject median age was 47 years (range: 17-93 years) and more than 90% were Caucasian. Thirty percent had signs of hematuria, 6% had proteinuria, and 3% had hematuria and proteinuria. The median of mean arterial pressure values was 93 mmHg (range: 71-135 mmHg) and 16% of the population screened had a history of hypertension. A significant positive family history of both hypertension or DM was present in 42% (P < 0.0001; chi-square = 83.18) and 7% (P < 0.0001; chi-square = 161.31) of the hypertensive group, respectively. Finally, the prevalence of hypertension and DM was significantly higher in older individuals with proteinuria. In the present study, a higher prevalence of hematuria and proteinuria was found in older individuals with hypertension and diabetes compared to the general population. These data confirm the need for public awareness of renal disease in high-risk individuals.

Adherence to drug therapy in kidney disease

Non-adherence to drug therapy has not been extensively studied in patients with chronic kidney disease (CKD). The objective of the present study was to identify determinants of non-adherence to drug therapy in patients with CKD, not on dialysis. A prospective cohort study involving 149 patients was conducted over a period of 12 months. Adherence to drug therapy was evaluated by the self-report method at baseline and at 12 months. Patients who knew the type of drug(s) and the respective number of prescribed pills in use at the visit preceding the interview were considered to be adherent. Patients with cognitive decline were assessed by interviewing their caregivers. Mean patient age was 51 ± 16.7 years. Male patients predominated (60.4%). Univariate analysis performed at baseline showed that non-adherence was associated with older age, more pills taken per day, worse renal function, presence of coronary artery disease, and reliance on caregivers for the administration of their medications. In multivariate analysis, the factors that were significantly associated with non-adherence were daily use of more than 5 pills and drug administration by a caregiver. Longitudinal evaluation showed an increase in non-adherence over time. Medication non-adherence was lower (17.4%) at the baseline period of the study than after 1 year of the study (26.8%). Compared to the baseline period, the percentage of adherent patients who became non-adherent (22%) was lower than the percentage of non-adherent patients who became adherent (50%). In CKD patients not on dialysis, non-adherence was significantly associated with the number of pills taken per day and drug administration by third parties. Adherence is more frequent than non-adherence over time.

Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease

Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ2=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease.

Chronic kidney disease in disadvantaged populations

The increased burden of chronic kidney disease (CKD) in disadvantaged populations is due to both global factors and population-specific issues. Low socioeconomic status and poor access to care contribute to health care disparities and exacerbate the negative effects of genetic or biological predisposition. Provision of appropriate renal care to these populations requires a two-pronged approach: expanding the reach of dialysis through development of low-cost alternatives that can be practiced in remote locations, and implementation and evaluation of cost-effective prevention strategies. Kidney transplantation should be promoted by expansion of deceased donor transplant programs and use of inexpensive, generic immunosuppressive drugs. The message of World Kidney Day 2015 is that a concerted attack against the diseases that lead to end-stage renal disease, by increasing community outreach, better education, improved economic opportunity, and access to preventive medicine for those at highest risk, could end the unacceptable relationship between CKD and disadvantage in these communities.

Prognostic effect of high-flux hemodialysis in patients with chronic kidney disease

We investigated the prognostic effects of high-flux hemodialysis (HFHD) and low-flux hemodialysis (LFHD) in patients with chronic kidney disease (CKD). Both an electronic and a manual search were performed based on our rigorous inclusion and exclusion criteria to retrieve high-quality, relevant clinical studies from various scientific literature databases. Comprehensive meta-analysis 2.0 (CMA 2.0) was used for the quantitative analysis. We initially retrieved 227 studies from the database search. Following a multi-step screening process, eight high-quality studies were selected for our meta-analysis. These eight studies included 4967 patients with CKD (2416 patients in the HFHD group, 2551 patients in the LFHD group). The results of our meta-analysis showed that the all-cause death rate in the HFHD group was significantly lower than that in the LFHD group (OR=0.704, 95%CI=0.533-0.929, P=0.013). Additionally, the cardiovascular death rate in the HFHD group was significantly lower than that in the LFHD group (OR=0.731, 95%CI=0.616-0.866, P<0.001). The results of this meta-analysis clearly showed that HFHD decreases all-cause death and cardiovascular death rates in patients with CKD and that HFHD can therefore be implemented as one of the first therapy choices for CKD.

Averting the legacy of kidney disease - focus on childhood

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Use of intravascular ultrasonography for the characterization of coronary artery disease in patients with chronic kidney disease

INTRODUCTION: Chronic kidney disease patients present a very high cardiovascular mortality. Nevertheless, a comparative description of lesion characteristics, using intravascular ultrasound in dialysis patients, has not yet been reported. The objective of the present study was to analyze the plaque morphology through intravascular ultrasound in comparison to their counterparts with normal renal function. METHODS: Patients were screened for coronary artery disease, and the coronary angiography was performed when indicated. Plaque morphology was evaluated by ultrasound, and findings were compared to a group of patients with coronary artery disease, who presented normal renal function, it carefully matched for all Framingham risk factors and lesion location at the coronary artery tree. RESULTS: One hundred and thirty-nine patients from a single center of hemodialysis were screened for the study. Patients with coronary lesions confirmed at the angiography presented lower hemoglobin (10.8 ± 1.5 versus 12.0 ± 19; p < 0.046) levels and higher levels of low-density lipoprotein (110.6 ± 25.8 versus 75.5 ± 43.1; p < 0.004), when compared to the ones without coronary artery disease. The ultrasound revealed greater proximal reference diameter (4.1 ± 0.6 versus 3.7 ± 0.5; p < 0.007), smaller crossed sectional area (4.2±1.6 versus 5.2 ± 1.8; p < 0.02), and the calcification was located in a deeper arterial layer (69 versus 9%; p < 0.004) in patients with chronic kidney disease when compared to the Control Group. CONCLUSION: Lesions of the patients with chronic kidney disease presented a larger proximal diameter and intense calcification in the deeper layer of the vessel, which suggest a greater positive remodeling effect in response to a more aggressive atherosclerotic process in the medial section of the artery.

Impact of training at ventilatory threshold on cardiopulmonary and functional capacity in overweight patients with chronic kidney disease

INTRODUCTION: Chronic kidney disease (CKD) and obesity are both associated with reduced physical capacity. The potential benefit of aerobic training on physical capacity has been recognized. The exercise intensity can be established using different methods mostly subjective or indirect. Ventilatory threshold (VT) is a direct and objective method that allows prescribing exercise intensity according to individual capacity. OBJECTIVES: To evaluate the impact of aerobic training at VT intensity on cardiopulmonary and functional capacities in CKD patients with excess of body weight. METHODS: Ten CKD patients (eight men, 49.7 ± 10.1 years; BMI 30.4 ± 3.5 kg/m², creatinine clearance 39.4 ± 9.8 mL/min/1.73 m²) underwent training on a treadmill three times per week during 12 weeks. Cardiopulmonary capacity (ergoespirometry), functional capacity and clinical parameters were evaluated. RESULTS: At the end of 12 weeks, VO2PEAK increased by 20%, and the speed at VO2PEAK increased by 16%. The training resulted in improvement in functional capacity tests, such as six-minute walk test (9.2%), two-minute step test (20.3%), arm curl test (16.3%), sit and stand test (35.7%), and time up and go test (15.3%). In addition, a decrease in systolic and diastolic blood pressures was observed despite no change in body weight, sodium intake and antihypertensive medication. CONCLUSION: Aerobic exercise performed at VT intensity improved cardipulmonary and functional capacities of overweight CKD patients. Additional benefit on blood pressure was observed. These results suggest that VT can be effectively applied for prescribing exercise intensity in this particular group of patients.

Vitamin D and Kidney disease: what we know and what we do not know

Vitamin D deficiency is common in the chronic kidney disease (CKD) population. CKD has been recognized as a significant public health problem and CKD patients are at increased risk of total and cardiovascular morbidity and mortality. There are increasing epidemiological data suggesting that vitamin D deficiency may play a role in overall morbidity and mortality associated with CKD. The vitamin D hormonal system is classically implicated in the regulation of calcium homeostasis and bone metabolism but there is ample evidence to support the claim that extra renal conversion of 25(OH)D to 1.25(OH)2 has significant biological roles beyond those traditionally ascribed to vitamin D. Based on the current state of evidence this review intends to give an update on novel biological and clinical insights with relevance to the steroid hormone vitamin D specifically in patients with kidney disease.