The Therapeutic Strategies for Uremic Toxins Control in Chronic Kidney Disease

Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal–renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.

P0797VERY LOW PROTEIN DIET (VLPD) WITH KETOANALOGUE SUPPLEMENTS AS CONSERVATIVE MANAGEMENT OF UREMIA IN ELDERLY PATIENTS: A SINGLE-CENTER EXPERIENCE

Background and Aims EDTA published data gathered between 2012 and 2016 showed greatly reduced survival in elderly prevalent dialysis patients as compared to similar aged individuals in the general population: a 70 year-old dialysis patient had a life expectancy of 5 years (instead of 16), an 80 year-old patient could expect to survive 3 years (instead of 9). This was due to the multiple comorbidities often present in elderly patients with advanced Chronic Kidney Disease (CKD). This burden of disease is further increased by dialysis itself, in particular by hemodynamic instability during treatment and by vascular access problems which often determine the need for central venous catheter insertion and for hospitalization. In 2007 the DODE study (a randomized, controlled, multicentric study in which our center took part) validated a conservative treatment of uremia based upon a Very Low Protein Diet supplemented with ketoanalogues (sVLPD): survival in patients on conservative management was similar to that of patients on chronic dialysis; also, no negative effect on nutritional status was observed. Our aim was to analyse clinical and epidemiologic data and outcomes of patients treated at our center with a sVLPD. Method We analized 222 selected from a group of approximately 300 patients with stage 5 CKD managed conservatively with a sVLPD (0.3 g/kg/day proteins). The inclusion criterion was active follow-up for at least six months; patients unable to maintain fluid and electrolyte balance with medical therapy were excluded. Except for one patient, all subjects were aged 75 years and older. Clinical and epidemiologic data were recorded at the beginning, during and at the end of follow-up. Results Mean age at the beginning of observation was 80 ± 7 years (51-96); 48% of patients were male (107), 52% were female (115). Median initial Renal Residual Function (RRF, ml/min) was 6,3 ± 2,1 ml/min, at the end of follow-up it was 5,3 ± 2,9 ml/min. The most common significant comorbidities were hypertension (84,5%), heart (61,4%) and vascular disease (48,6%); these and other significant comorbidities are illustrated in Fig. 1. Conservative management allowed to delay the initiation of dialysis by an average of one year; 24% of patients continued on the sVLPD for two year and some patients reached a duration of treatment of 7 years. Median duration of sVLPD is shown in Fig. 2. At the end of follow-up 40% of patients had begun chronic hemodialysis and 9% peritoneal dialysis, 8% were still on conservative management, 27% were deceased (Fig. 3). Conclusion The supplemented Very Low Protein Diet is an effective treatment which can delay the beginning of chronic dialysis in elderly stage 5 CKD patients with multiple comorbidities. It is a safe treatment and does not increase morbility and mortality. Current epidemiologic data (incident patients in dialysis: 170 pmp/year, 50% aged over 70 years old) support the use of this conservative strategy which can represent a valid alternative to dialysis in selected patients.

Very Low Protein Diet for Patients with Chronic Kidney Disease: Recent Insights

Use of nutritional therapy (NT) in chronic kidney disease (CKD) patients is still debated among nephrologists, but it represents a fundamental point in the conservative treatment of CKD. It has been used for years and it has new goals today, such as (1) the reduction of edema, diuretics, and blood pressure values with a low sodium-content diet; (2) the dose reduction of phosphate levels and phosphate binders; (3) the administration of bicarbonate with vegetables in order to correct metabolic acidosis and delay CKD progression; (4) the reduction of the number and the doses of drugs and chemical substances; and (5) the lowering of urea levels, the cure of intestinal microbioma, and the reduction of cyanates levels (such as indoxyl-sulphate and p-cresol sulphate), which are the most recent known advantages achievable with NT. In conclusion, NT and especially very low protein diet (VLPD) have several beneficial effects in CKD patients and slows the progression of CKD.

The Effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-Analysis

The effects of ketoanalogues (KA) on chronic kidney disease (CKD) deterioration have not yet been fully confirmed. To strengthen the evidence of the role of KA in CKD, PubMed and Embase were searched for studies published through February 2019. Effect sizes from ten randomized control trials (RCTs) and two non-RCTs comprising a total of 951 patients were pooled and analyzed. A restricted protein diet supplemented with ketoanalogues (RPKA) was found to significantly delay the progression of CKD (p = 0.008), particularly in patients with an estimated glomerular filtration rate (eGFR) > 18 mL/min/1.73 m2 (p < 0.0001). No significant change in eGFR was found when comparing a very-low-protein diet and a low-protein diet (p = 0.10). In addition, compared with the placebo, RPKA did not cause malnutrition (albumin: p = 0.56; cholesterol: p = 0.50). Moreover, RPKA significantly decreased phosphorous levels (p = 0.001), increased calcium levels (p = 0.04), and decreased parathyroid hormone (PTH) levels (p = 0.05) in patients with eGFR < 18 mL/min/1.73 m2. In conclusion, RPKA could slow down the progression of CKD in patients with eGFR > 18 mL/min/1.73 m2 without causing malnutrition and reverse CKD-MBD in patients with eGFR < 18 mL/min/1.73 m2.