Gut Microbiome in Chronic Kidney Disease.

With over 100 trillion microbial cells, the gut microbiome plays important roles in both the maintenance of health and the pathogenesis of disease. Gut microbiome dysbiosis, resulted from alteration of composition and function of the gut microbiome and disruption of gut barrier function, is commonly seen in patients with chronic kidney disease (CKD). The dysbiotic gut microbiome generates excessive amounts of uremic toxins, and the impaired intestinal barrier permits translocation of these toxins into the systemic circulation. Many of these uremic toxins have been implicated in the progression of CKD and increased cardiovascular risk. Various therapeutic interventions have been proposed that aim to restore gut microbiome symbiosis. If proven effective, these interventions will have a significant impact on the management of CKD patients. In this review, we discuss the consequences of gut microbiome dysbiosis in the context of CKD, discuss the consequences of gut dysbiosis, and highlight some of the recent interventions targeting the gut microbiome for therapeutic purposes.

Increased visceral adiposity is associated with coronary artery calcification in male patients with chronic kidney disease.

BACKGROUND/OBJECTIVE: Recent epidemiological data have shown that abdominal fat accumulation is associated with increased risk of cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to investigate the association between visceral adiposity and coronary artery calcification (CAC) in CKD patients. SUBJECTS/METHODS: Cross-sectional study with 65 nondialyzed CKD male patients (59 ± 9 years, CKD stages 3 and 4). Abdominal fat compartments were assessed by computed tomography (CT) at L4-L5 level. Visceral to subcutaneous (V/S) fat ratio was calculated. Visceral obesity was defined as a V/S fat ratio greater than the median value of the sample study (>0.55). CAC was detected by multi-slice CT. CAC scores were calculated with the Agatston method. RESULTS: CAC was present (calcium score >10 AU) in 66% of patients. In the group with visceral obesity, the CAC score was significantly higher. This group had lower adiponectin and higher leptin levels compared to patients without visceral obesity. In the whole sample, higher V/S fat ratio was associated with CAC score, independently of age, body mass index, diabetes, ionized calcium, smoking or renal function. CONCLUSION: Our results show an association between visceral obesity and CAC in CKD patients, suggesting a deleterious effect of visceral fat in these patients. Increased visceral adiposity might enhance cardiovascular risk in this particular population.

Visceral obesity assessed by computed tomography predicts cardiovascular events in chronic kidney disease patients.

BACKGROUND AND AIM: Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Although there is emerging evidence that excess visceral fat is associated with a cluster of cardiometabolic abnormalities in these patients, the impact of visceral obesity evaluated by a gold-standard method on future outcomes has not been studied. We aimed to investigate whether visceral obesity assessed by computed tomography was able to predict cardiovascular events in CKD patients. METHODS AND RESULTS: We studied 113 nondialyzed CKD patients [60% men; 31% diabetics; age 55.3 ± 11.3 years; body mass index (BMI) 27.2 ± 5.3 kg/m(2); estimated glomerular filtration rate (GFR) 33.7 ± 13.6 ml/min/1.73 m(2)]. Visceral and subcutaneous abdominal fat were assessed by computed tomography at L4-L5. Visceral to subcutaneous fat ratio >0.55 (highest tertile cut-off) was defined as visceral obesity. Cardiovascular events including acute myocardial infarction, angina, arrhythmia, uncontrolled blood pressure, stroke and cardiac failure were recorded during 24 months. Cardiovascular events were 3-fold higher in patients with visceral obesity than in those without visceral obesity. The Kaplan-Meier analysis indicated that patients with visceral obesity had shorter cardiovascular event-free time than those without visceral obesity (P = 0.021). In the univariate Cox analysis, visceral obesity was associated with higher risk of cardiovascular events (hazard ratio = 3.4; 95% confidence interval = 1.1-10.5; P = 0.03). The prognostic power of visceral obesity for cardiovascular events remained significant after adjustments for sex, age, diabetes, previous cardiovascular disease, smoking, sedentary lifestyle, BMI, GFR, hypertension, dyslipidemia and inflammation. CONCLUSION: Visceral obesity assessed by computed tomography was a predictor of cardiovascular events in CKD patients.

Cardiovascular disease in early kidney transplantation: comparison between living and deceased donor recipients.

BACKGROUND: Cardiovascular disease (CVD) mortality is extremely high among kidney transplant recipients (KTRs), particularly in the first months after transplantation. Few data are available comparing the cardiovascular profile between KTRs from living versus deceased donors. OBJECTIVES AND METHODS: The aim of the present study was to evaluate the prevalence of CVD in the first 2 months following transplantation, among 120 KTRs of living versus deceased donor organs. RESULTS: Left ventricular hypertrophy was observed in 65% of patients, coronary artery calcification in 30%, and cardiac arrhythmias in 46%. CVD was more prevalent among KTRs from deceased versus living donors: ventricular hypertrophy 87% versus 59% (P = .008); coronary artery calcification 42% versus 24% (P = .04); and cardiac arrhythmias 59% versus 39% (P = .06). Multiple logistic regression analysis adjusted for age and dialysis vintage, showed graft donor to not be associated with the prevalence of any CVD (ß coefficient 0.912, 95% confidence interval 0.276-3.012, P = .88). CONCLUSION: In conclusion, the present study demonstrated an elevated prevalence of CVD among KTRs. Patient characteristics, mainly longer length on dialysis seemed to contribute to a greater prevalence of cardiovascular complications among KTRs from deceased compared with living donors on univariate but not multivariate analysis.

Fibroblast growth factor 23 in chronic kidney disease: bridging the gap between bone mineral metabolism and left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major cardiovascular complication in chronic kidney disease (CKD) patients. For a successful management of LVH, the comprehensive understanding of the classical and the new emerging factors associated with LVH is of paramount importance. The aim of the present study was to evaluate the clinical correlates of bone mineral metabolism with the occurrence of LVH in nondialyzed CKD patients. METHODS: This cross-sectional study included 96 patients with stages 2-4 CKD. Demographic characteristics, clinical profiles, laboratory tests and transthoracic echocardiogram were performed. RESULTS: LVH was observed in 36% of the patients. Patients with LVH were older, had a higher prevalence of hypertension, and higher levels of intact parathormone, fibroblast growth factor 23 and C-reactive protein. Serum phosphorus, alkaline phosphatase and vitamin D were not associated with the presence of LVH. In the multiple logistic regression analyses only FGF23 remained as a variable independently associated with LVH. CONCLUSION: We confirmed the high prevalence of LVH in nondialyzed CKD patients and showed that FGF23, an early marker of phosphorus load, was an important factor associated with LVH in these patients. Monitoring of FGF23 could be important for the management of LVH in this population.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients.

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Evaluation of the role of severe hyperparathyroidism on coronary artery calcification in dialysis patients.

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of dying from a cardiovascular event, mainly due to coronary calcification. Among the various uremic and dialysis-specific risk factors for coronary calcification are mineral metabolism disorders. The role that secondary hyperparathyroidism (SHPT) consequent to the altered calcium and phosphate metabolism plays in the pathogenesis of coronary calcification remains unclear. The aim of this study was to evaluate the prevalence of coronary artery calcification in dialysis patients with severe SHPT submitted to multislice coronary tomography (MSCT) and to identify risk factors for coronary calcification. METHODS: This study involved 23 adult dialysis patients (age >18 years) with severe SHPT who were candidates for parathyroidectomy (PTX). All were submitted to MSCT and bone densitometry during the month preceding PTX. Fasting blood samples were collected immediately before surgery. Markers of mineral metabolism, including ionized calcium, phosphorus, alkaline phosphatase, intact-parathyroid hormone (iPTH), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand, were analyzed. Dyslipidemia was assessed by determination of LDL, HDL and VLDL-cholesterol and triglyceride levels. Agatston units (AU) were used to calculate calcium scores. RESULTS: No coronary calcification was found in 30% of the patients. Moderate (calcium score > 100 AU) and severe (calcium score >400 AU) calcification was observed in 12 and 36% of the patients, respectively. In the univariate analysis, calcium volume correlated positively with VLDL-cholesterol (r = 0.44; p = 0.03) and, albeit less than significantly, with age (r = 0.35; p = 0.09), triglycerides (r = 0.39; p = 0.05) and Framingham risk index (r = 0.37; p = 0.07). We also found that OPG correlated negatively with bone mineral density at the L2-L4 lumbar vertebrae (r = -0.54; p = 0.007) and femoral neck (r = -0.43; p = 0.04). CONCLUSIONS: Although high levels of PTH should be considered a risk factor for cardiovascular death, the real role of severe SHPT on coronary calcification is to be clarified.

Resting energy expenditure and its determinants in hemodialysis patients.

OBJECTIVE: Chronic kidney disease is associated with several metabolic disturbances that can affect energy metabolism. As resting energy expenditure (REE) is scarcely investigated in patients on hemodialysis (HD) therapy, we aimed to evaluate the REE and its determinants in HD patients. DESIGN: Cross-sectional study. SETTING: Dialysis Unit of the Nephrology Division, Federal University of São Paulo, Brazil. SUBJECTS: The study included 55 patients (28 male, 41.4+/-12.6 years old) undergoing HD therapy thrice weekly for at least 2 months, and 55 healthy individuals pair matched for age and gender. Subjects underwent fasting blood tests, as well as nutritional assessment, and the REE was assessed by indirect calorimetry. RESULTS: REE of HD patients was similar to that of pair-matched controls (1379+/-272 and 1440+/-259 kcal/day, respectively), even when adjusted for fat-free mass (P=0.24). REE of HD patients correlated positively with fat-free mass (r=0.74; P<0.001) and body mass index (r=0.37; P<0.01), and negatively with dialysis adequacy (r=-0.46; P<0.001). No significant univariate correlation was found between REE and age, dialysis vintage, serum creatinine, urea, albumin, bicarbonate, parathyroid hormone (PTH) or high-sensitivity C-reactive protein (CRP). In the multiple linear regression analysis, using REE as dependent variable, the final model showed that besides the well-recognized determinants of REE such as fat-free mass and age, PTH and CRP were the independent determinants of REE in HD patients (R (2)=0.64). CONCLUSIONS: In this study, the REE of HD patients was similar to that of healthy individuals, even with the positive effect of secondary hyperparathyroidism and inflammation on REE of these patients.

Nutritional status of hemodialysis patients with secondary hyperparathyroidism

The repercussions of secondary hyperparathyroidism on the nutritional status of chronic renal failure patients have not been well established. Therefore, the aim of this study was to compare the nutritional indices of hemodialysis patients with and without secondary hyperparathyroidism. Sixteen hemodialysis patients with serum parathyroid hormone (PTH) levels higher than 420 pg/ml (hyperparathyroidism group) were matched for gender, age and length of dialysis treatment to 16 patients with serum PTH between 64 and 290 pg/ml (control group). The following parameters were assessed: anthropometric indices (body mass index, skinfold thickness, midarm muscle circumference and body fat), 4-day food diaries, protein catabolic rate, biochemical indices (blood urea nitrogen, serum creatinine, albumin, ionized calcium, inorganic phosphorus, serum alkaline phosphatase, PTH, pH and HCO3) and dialysis efficiency. We did not observe differences in the anthropometric indices between the two groups. Only calcium intake was significantly different between groups (307.9 mg/day for the hyperparathyroidism group vs 475.8 mg/day for the control group). Protein catabolic rate tended to be higher in the hyperparathyroidism group compared to the control group (1.3 vs 0.9 g kg-1 day-1; P = 0.08). Except for blood urea nitrogen (86.4 vs 75.7 mg/dl), alkaline phosphatase (175 vs 65 U/l) and PTH (898 vs 155 pg/ml), no other differences were found between groups in the biochemical indices studied. PTH was directly correlated with protein catabolic rate (r = 0.61; P<0.05) and length of dialysis (r = 0.53; P<0.05) only in the hyperparathyroidism group. Considering the indices used, we could not demonstrate the deleterious effect of high PTH levels on the nutritional status of hemodialysis patients. Indirect evidence, however, suggests an action of PTH on protein metabolism

Correçäo da anemia da insuficiência renal crônica pela eritropoetina humana recombinante liofilizada por via subcutânea / Anemia correction of chronic kidney failures by recombinant human erythropoietin freeze drying by subcutaneous injections

A eritropoetina recombinante humana (rHuEPO) tem-se mostrado a medicaçäo de escolha na correçäo da anemiado paciente renal crônico. OBJETIVO. Analisar a eficácia de uma nova preparaçäo de rHuEPO na correçäo da anemia de pacientes renais crônicos mantidos em hemodiálise, exclusivamente administrada por via subcutânea, estudando seus efeitos colaterais e pesquisando fatores preditivos de resposta para a medicaçäo. MÉTODOS. Doze pacientes em programa regular de hemodiálise foram tratados com rHuEPO liofilizada por via subcutânea, durante 18 meses, com dose inicial de 20U/Kg/diálise, efetuando-se monitorizaçäo clínica e laboratorial adequada. RESULTADOS. Onze pacientes terminaram o protocolo, alcançando hematócrito (Htc) alvo de 30 por cento e mantendo-o durante todo o tempo de estudo. A dose média utilizada para a correçäo da anemia foi de 65U/Kg diálise e a de manutençäo de Htc alvo de 51U/Kg diálise. Já na 12ª semana do estudo, comprovou-se aumento significativo do Htc (18,4 ñ 3,5 por cento vs. 25,4 ñ 3,8 por cento, p < 0,5), acompanhado por hemoglobina e eritrócitos. Leucócitos e plaquetas aumentaram significativamente a partir da 24ª semana e mantiveram-se assim até o final do estudo. Na análise dos exames bioquímicos dos pacientes, apenas o potássio se elevou na 4ª e 12ª semanas, voltando ao basal na 24ª semana de estudo. A avoluçäo dos parâmetros séricos do metabolismo do ferro mostrou diminuiçöes intermitentes e estatisticamente significantes da saturaçäo de transferrina na 1ª, 12ª e 24ª semanas, voltando aos valores basais ao final do estudo; a ferritina sérica näo se alterou (582,7 ñ 700,9ng/mL vs. 700,0 ñ 651,6ng/mL). Peso e pressäo arterial näo se alteraram, porém dois pacientes, antes normotensos, tornaram-se hipertensos e dois outros, com hipertensäo controlada, necessitaram reajuste de droga para novo controle da pressäo (35 por cento). Um paciente apresentou convulsäo tipo grande mal, evoluindo sem seqüelas. CONCLUSAO. A rHuEPO utilizada neste protocolo comprovou ser uma droga eficaz, segura e com efeitos colaterais passíveis de controle