The low-protein diet for chronic kidney disease: 8 years of clinical experience in a nephrology ward.

BACKGROUND: Guidelines indicate that a low-protein diet (LPD) delays dialysis in severe chronic kidney disease (CKD). We assessed the value of these guidelines by performing a retrospective analysis in our renal clinical practice. METHODS: The analysis was performed from 1 January 2010 to 31 March 2018 in 299 CKD Stage 4 patients followed for 70 months in collaboration with a skilled nutritionist. The patients included 43 patients on a controlled protein diet (CPD) of 0.8 g/kg/day [estimated glomerular filtration rate (eGFR) 20-30 mL/min/1.73 m2 body surface (b.s.)], 171 patients on an LPD of 0.6 g/kg/day and 85 patients on an unrestricted protein diet (UPD) who were not followed by our nutritionist (LPD and UPD, eGFR <20 mL/min/1.73 m2 b.s.). RESULTS: eGFR was higher in CPD patients than in UPD and LPD patients (21.9 ± 7.4 mL/min/1.73 m2 versus 17.6 ± 8.00 mL/min/1.73 m2 and 17.1 ± 7.5 mL/min/1.73 m2; P = 0.008). The real daily protein intake was higher in UPD patients than in LPD and CDP patients (0.80 ± 0.1 g/kg/day versus 0.6 ± 0.2 and 0.63 ± 0.2 g/kg/day; P = 0.01). Body mass index (BMI) was stable in the LPD and CPD groups but decreased from 28.5 ± 4.52 to 25.4 ± 3.94 kg/m2 in the UPD group (P < 0.001). The renal survival of UPD, LPD and CPD patients was 47.1, 84.3 and 90.7%, respectively, at 30 months (P < 0.001), 42.4, 72.0 and 79.1%, respectively, at 50 months (P < 0.001) and 42.4, 64.1 and 74.4%, respectively, at 70 months (P < 0.001). The LPD patients started dialysis nearly 24 months later than the UPD patients. Diet was an independent predictor of dialysis [-67% of RR reduction (hazard ratio = 0.33; confidence interval 0.22-0.48)] together with a reduction in BMI. CONCLUSIONS: An LPD recommended by nephrologists in conjunction with skilled dietitians delays dialysis and preserves nutritional status in severe CKD.

Sodium removal and plasma tonicity balance are not different in hemodialysis and hemodiafiltration using high-flux membranes.

BACKGROUND: The clinical benefits of on-line hemodiafiltration (HDF) versus high-flux membranes hemodialysis (hf-HD) are still debated. In fact, although a superiority of one treatment over the other, especially in terms of mortality, did not emerge from the analysis of clinical trials, improved intradialytic vascular stability and cardiovascular mortality have been observed in patients undergoing HDF rather than hf-HD; the lower removal of sodium (Na+) during HDF seems to play a major role. The plasma concentration of Na+ is the major determinant of plasma tonicity, which, by determining the flow of water between the intracellular and the extracellular compartment, contributes to the vascular refilling process and the maintenance of blood pressure during the hemodialysis treatment. Plasma tonicity also depends on plasma glucose concentration, especially in patients with diabetes mellitus with hyperglycaemia at the start of hemodialysis treatment. MATERIALS AND METHODS: We evaluated the removal of Na+ and plasma tonicity balance during a 2-week period by performing 2-3 consecutive sessions of hf-HD followed by 2-3 consecutive sessions of HDF, or vice versa, in 47 patients (40% diabetics) on chronic hemodialysis. Identical parameters were used in all dialytic sessions. RESULTS: Na+ removal per session was - 224 ± 144 mmol and - 219 ± 152 mmol, respectively, in hf-HD and in HDF (p = 0.79). The plasma tonicity balance per session was - 575 ± 310 mOsm and - 563 ± 328 mOsm, respectively, in hf-HD and in HDF (p = 0.75). CONCLUSIONS: The removal of Na+ and plasma tonicity balance did not differ between hf-HD and HDF. This observation suggests that factors other than those assessed in our study might explain the improved cardiovascular stability reported in HDF.

Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

[Assisted peritoneal dialysis]. / La Dialisi Peritoneale Assistita con l'impiego degli OSS come caregiver.

Peritoneal dialysis (PD) has a prevalence in Italy that does not exceed 10% of patients in substitution treatment. Among the barriers, which hinder access to DP, the lack of patient autonomy or family support has great importance. In 2012 in Lombardy, the lack of support has prevented 155 new patients to use DP and has forced 17 to stop it. According to the Italian Census of 2012, made by the Peritoneal Dialysis Study Group, Assisted DP involved the 24.5% of patients in 2010. In these cases, the caregiver was a family member in 80.8% of cases, a carer in 12.4%, a homecare nurse in 2.5% and the retirement home staff in 3.9%. In Italy, several regional Governments have sought to encourage home dialysis with economic contributions to the patient or the family. However, so far, none of these interventions has managed to increase the use of DP. In January 2004, we started a program of Assisted PD, using health worker as caregiver, in agreement with ASL Milano and ICP Milano Hospital. In the first 6 months of activity we treated 4 patients, 3 of them had been treated with hemodialysis. We had no critical cases and patients have welcomed this solution. In addition, the costs related to the Assisted PD are lower in comparison with the costs of the hospital hemodialysis. Considering the reliability of the first results, ASL has decided to raise the economic contribution for this activity, allowing us to increase the number of patients to include in Assisted PD.

Early sympathetic activation in the initial clinical stages of chronic renal failure.

Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age: 60.7±1.8 years, mean±SEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate: 40.7 mL/min per 1.73 m2, MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (high-performance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0±2.1 versus 45.7±2.0 bursts per 100 heartbeats; P<0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first: 41.0±2.7; second: 51.9±1.7; third: 59.8±3.0; fourth: 61.9±3.3 bursts per 100 heartbeats), the statistical significance (P<0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (r=-0.59; P<0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression.

Behaviour of regional adrenergic outflow in mild-to-moderate renal failure.

OBJECTIVES: Chronic renal failure is characterized by a marked sympathetic activation. No information exists, however, as to whether the adrenergic overdrive is confined to selected vascular districts or is rather generalized to the whole cardiovascular system. METHODS: In 15 patients aged 60.5 +/- 2.0 years (mean +/- SEM) with stable chronic renal failure belonging to stage 2-3 of the Kidney Foundation classification and in 12 age-matched healthy controls, we measured arterial blood pressure (Finapres), heart rate (ECG), venous plasma norepinephrine (high-performance liquid chromatography) and postganglionic sympathetic nerve traffic in skeletal muscle and skin areas (microneurography). Muscle and skin nerve traffic measurements were made in a randomized sequence over two periods of 30 min each, spaced by a 20-30-min interval. Measurements also included evaluation of skin sympathetic responses to emotional stimuli. RESULTS: Muscle sympathetic nerve traffic was markedly and significantly greater in renal failure patients compared with controls (58.2 +/- 3.6 vs. 36.8 +/- 5.7 bursts/100 heart beats, P < 0.01), with this also being the case for plasma norepinephrine (380.6 +/- 63 vs. 210.8 +/- 29 pg/ml, P < 0.05). By contrast, skin sympathetic nerve traffic was superimposable in the two groups (11.5 +/- 0.8 vs. 12.7 +/- 1.7 bursts/minute, P = not significant), this being the case also for the responses to emotional arousal. CONCLUSION: These data provide the first evidence that the sympathetic activation characterizing renal failure is not generalized to the entire cardiovascular system. This may depend on the fact that the two sympathetic districts are governed by mechanisms that are differently affected by the chronic uraemic state.

Improvement of endothelial function in uraemic patients on peritoneal dialysis: a possible role for 5-MTHF administration.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. METHODS: We examined the effect of oral treatment with 15 mg/daily of 5-methyltetrahydrofolate (5-MTHF) for 12 weeks, on homocysteinaemia and endothelial function in 19 patients undergoing peritoneal dialysis and compared them, for the same period of time, to a control group of patients on peritoneal dialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by the inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after sublingual administration of glyceryl trinitrate. Finally, oxidative stress was assessed by evaluating the conjugated dienes plasma levels. RESULTS: Plasma homocysteine concentrations fell by 30% after oral treatment with 5-MTHF. Endothelial function improved significantly after oral 5-MTHF treatment (13.8 +/- 1.2% vs 11.4 +/- 1.4%; P < 0.02) while in the control group we observed a worsening of basal values from 12.1 +/- 2.66% to 8.7 +/- 2.90% (P < 0.02). The conjugated dienes plasma levels did not change either. CONCLUSIONS: Our study demonstrated that 5-MTHF administration improves endothelial dysfunction in patients undergoing peritoneal dialysis. This effect appears to be independent of the reduction in homocysteine plasma levels.

Plasma homocysteine levels and cardiovascular mortality in patients with end-stage renal disease.

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis in patients with normal renal function. Plasma homocysteine (Hcy) is increased in patients with chronic renal failure (CRF) and could be linked to their high cardiovascular (CV) morbidity and mortality. We prospectively studied 77 patients (47 males and 30 females aged 62.85 +/- 1.53 yrs) who had been on maintenance hemodialysis (HD) (4 hr/x3/week) for 65.5 +/- 7.23 months. Patients were followed-up for 44 months. At baseline, blood samples were taken for hemoglobin (Hb), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, serum calcium, serum phosphates, parathyroid hormone (PTH), Hcy, vitamin B12, serum and erythrocyte folate and methylentetrahydrofolate-reductase (t-MTH-FR) genotype determination. Plasma Hcy levels of patients were divided into four quartiles. The univariate analysis demonstrated a significant relationship between Hcy and diastolic blood pressure (BP) (r=0.45; p=0.003), and both plasma (r=-0.30; p=0.03) and erythrocyte (r=-0.48; p=0.01) folate levels and CV score (r=0.39; p=0.007). Kaplan-Meier analysis showed that the mortality rate due to CV events was statistically significantly higher in the 4th Hcy quartile (68%; 12 patients) vs. the 3rd quartile (12%; two patients), the 2nd quartile (28%; four patients) and the 1st quartile (14%; two patients) (log-rank test p=0.02). Cox's regression analysis for CV survival showed that Hcy was a positive CV mortality predictor (beta=0.02; hazard ratio=1.031; 95% confidence interval (95% CI): 1.013-1.050; p=0.001), while LDL cholesterol and albumin related negatively to CV mortality (LDL cholesterol: beta=-0.02; hazard ratio=0.095; 95% CI: 0.0957-0.0997; p=0.035; albumin: beta=-2.35; hazard ratio=0.097; 95% CI: 0.011-0.847; p=0.026). Our results show that Hcy is a strong independent mortality predictor in HD patients with a 3% increase in mortality for each 1 micromol/L increase in plasma Hcy concentration. This agrees with previous findings confirming the role of Hcy in predicting CV risk factors in uremic patients.