Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.

Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

INTRODUCTION: The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target. AIM: We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients. MATERIALS AND METHODS: We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects. RESULTS: Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin (p = 0.018 and p = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; p = 0.03 and p = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD (p = 0.026) or with LPD and inulin (p = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-α) (p = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) (p = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1ß (p = 0.529) and IL-6 (p = 0.828) in the two groups. CONCLUSIONS: LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.

Reduction in Heart Rate Variability in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV). OBJECTIVE: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC). MATERIALS AND METHODS: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment. RESULTS: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001). CONCLUSIONS: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors.

Peritoneal dialysis in older adults: Evaluation of clinical, nutritional, metabolic outcomes, and quality of life.

The number of older adults requiring dialysis is increasing worldwide, whereas the use of peritoneal dialysis (PD) in this population is lower with respect to younger patients, despite the theoretical advantages of PD respect to hemodialysis. This is most likely due to the concern that older patients may not be able to correctly and safely manage PD.We aimed to prospectively compare clinical, nutritional and metabolic outcomes and measures of quality of life between younger (<65 years old) and older (≥65 years old) patients on PD.PD patients were enrolled and divided into 2 groups according to age (Group A < 65 years, Group B ≥ 65 years). Clinical and instrumental parameters, and quality of life were evaluated at baseline (start of PD) (T0) and at 24 months (T1). Technique survival, mortality, total number of hospitalizations, and the index of peritonitis (episodes of peritonitis/month) were also evaluated.Fifty-one patients starting PD were enrolled. Group A included 22 patients (48.7 ±â€Š8.3 years), and Group B consisted of 29 patients (74.1 ±â€Š6.4 years). At baseline, the 2 groups showed no differences in cognitive status, whereas Group A showed higher total cholesterol (P = .03), LDL (P = .03), and triglycerides (P = .03) levels and lower body mass index (P = .02) and carotid intima media thickness (P < .0001) with respect to Group B. At T1 Group B showed, compared to baseline, a significant reduction in albumin (P < .0001) and phosphorus (P = .045) levels, while no significant differences on body composition, technique survival, total number of hospitalizations, index of peritonitis, and quality of life indices were observed.Our data do not show clinically relevant barriers to use PD in older adult patients, supporting its use in this population. Nutritional and metabolic parameters should be carefully monitored in older PD patients.

Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P < 0.001, P = 0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P < 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P < 0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P < 0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons-Smith classification) in patients on conservative therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D.In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs.

Cardiac, Inflammatory and Metabolic Parameters: Hemodialysis versus Peritoneal Dialysis.

INTRODUCTION: Mortality in dialysis patients is higher than in the general population, and cardiovascular disease represents the leading cause of death. Hypertension and volume overload are important risk factors for the development of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal dialysis (PD) patients. Other factors are mainly represented by hyperparathyroidism, vascular calcification, arterial stiffness and inflammation. The aim of this study was to compare blood pressure (BP) and metabolic parameters with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch calcification (AAC) and LV mass index (LVMI)] between PD and HD patients. MATERIALS AND METHODS: 45 patients (23 HD and 22 PD patients) were enrolled. BP measurements, echocardiography and chest X-ray were performed in each patient to determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated. RESULTS: LVMI was higher in PD than HD patients (139 y 19 vs. 104 y 22; p = 0.04). In PD patients, a significant correlation between iPTH, C-reactive protein and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03, respectively). The CTR was increased in PD patients as compared to HD patients, while no significant differences in cardiac calcifications were determined. CONCLUSIONS: Our data indicate that HD patients present more effective BP control than PD patients. Adequate fluid and metabolic control are necessary to assess the adequacy of BP, which is strongly correlated with the increase in LVMI and with the increased CTR in dialysis patients. PD is a home therapy and allows a better quality of life, but PD patients may present a further increased cardiovascular risk if not adequately monitored.

Tenofovir-Related Nephropathies in HIV-Infected Patients.

BACKGROUND: The number of human immunodeficiency virus (HIV)-infected patients has increased significantly, although the number of deaths due to HIV and acquired immunodeficiency syndrome (AIDS) has dramatically reduced. Highly active antiretroviral therapy (HAART) has increased not only survival but also the risk of deaths caused by other diseases or by long-term side effects of these drugs. AIM: The aim of this study is to evaluate the nephrotoxicity of one of the most common anti-retroviral drugs, tenofovir disoproxil fumarate (TDF). MATERIALS AND METHODS: We examined 27 patients with HIV infection (10 women). Patients assumed TDF for a mean period of 8.03 months. Indexes of renal function and serum electrolytes were measured, and glomerular filtration rate was estimated (eGFR). Proteinuria, glycosuria, bicarbonaturia, and phosphaturia were assessed, and renal ultrasound examination was carried out. RESULTS: Acute kidney injury with glycosuria, bicarbonaturia, and phosphaturia was seen in 22 patients. Substantial recovery of renal function occurred in 19 patients. CONCLUSION: This study highlights that TDF nephrotoxicity is a widely frequent but reversible form of renal damage with preferentially proximal tubular dysfunction. We suggest that all patients at the time of HIV diagnosis should carry out a screening for kidney disease with eGFR assessment, proteinuria, and urine analysis.

[New therapeutic prospects for renal transplant: extracorporeal photochemotherapy]. / Nuove prospettive terapeutiche per il trapianto di rene: la fotochemioterapia extracorporea.

Since 1960, different classes of immunosuppressive drugs have been used in the post-transplant follow-up. Each is assessed for its effectiveness in preventing rejection but also on the basis of the many side effects induced by prolonged treatment. To reduce these side effects, continuous development of knowledge and medical technology to create cutting-edge therapies in the field is necessary. One of these is extracorporeal photochemotherapy (ECP), an immunomodulatory therapy approved by the United States Food and Drug Administration in 1988 for the treatment of advanced forms of cutaneous T-cell lymphoma. EC P is a useful therapeutic tool for the development of immunomodulation supported by CD8+ clone-specific cytotoxic lymphocytes. The T cells targeted by EC P are modified by photoactivation and seem to develop marked immunogenicity with no suppression of the immune response. Recent studies suggest the possible utility of EC P in the treatment of glomerulonephritis and in countering rejection after transplantation of organs including the kidney.

[Quality of life assessment in patients on hemodialysis and peritoneal dialysis]. / Qualità di vita e aspetti psicologici dell'anziano uremico in trattamento dialitico: confronto tra emodialisi e dialisi peritoneale.

Assessment of the quality of life (QoL) of patients with end-stage renal disease undergoing replacement therapy is very important. The aim of our study was to assess the QoL of patients on hemodialysis (HD) and peritoneal dialysis (PD). To determine the state of health of the patients as well as psychological aspects we used two international questionnaires: the Health-Related Short Form (SF-36) and the Psychological General Well-being Index (PGWBI). The study included 48 patients (26 men, 22 women) with chronic kidney disease (KDOQI: 5). All patients were on dialysis treatment. Their mean age was 63 years (range 59-73) and the mean duration of dialysis was 18 months (range 12-34). Twenty-four patients (13 men, 11 women) were on DP and 24 (13 men, 11 women) on HD. The results demonstrate that the PD and HD groups diverged on almost all scales. The scales that measure both the mental and physical dimensions of QoL showed PD to be associated with a higher level of psychophysical well-being than HD. The SF-36 revealed that both the physical and mental dimensions were directly influenced by the type of treatment. On the depression scale of PGWBI we found that patients on HD were more prone to depression than patients on PD. In conclusion, PD appears to have clear advantages in terms of QoL, especially in elderly patients, thanks to the possibility to perform the treatment independently at the patient's home.