High levels of fibroblast growth factor 23 are associated with mortality, CKD progression, and calcification in CKD patients. The aim of this pilot study is to assess whether a very-low-protein diet ...(0.3 g/kg per day) with a consequent low intake of phosphorus would reduce fibroblast growth factor 23 compared with a low-protein diet (0.6 g/kg per day) in CKD patients not yet on dialysis.
A prospective, randomized, controlled crossover study was performed in which 32 patients were randomized into two groups. Group A (16 patients) received a very-low-protein diet (0.3 g/kg body wt per day) supplemented with ketoanalogues during the first week and a low-protein diet during the second week, and group B (16 patients) received a low-protein diet during the first week and a very-low-protein diet during the second week. Fibroblast growth factor 23, seric, and urinary phosphate levels were measured at baseline and the end of each study period.
After only 1 week of the very-low-protein diet, reductions in fibroblast growth factor 23 levels (33.5%), serum phosphate (12%), and urinary phosphate (34%) with the very-low-protein diet compared with the low-protein diet were observed. Serum and urinary phosphate levels and protein intake were significant determinants of fibroblast growth factor 23 (95% confidence interval=1.04-1.19, 1.12-1.37, and 1.51-2.23, respectively).
A very-low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor 23 levels in CKD patients not yet on dialysis.
Background Whether low-protein-diet (LPD) as opposed to moderate-protein-diet (MPD) regimens improve the long-term survival of patients with chronic kidney disease (CKD) or induce protein-caloric ...malnutrition is unknown. Study Design Intention-to-treat analysis of follow-up data from a randomized controlled trial. Setting & Participants 423 patients with CKD (stages 4-5) were randomly assigned between January 1999 and January 2003 and followed up until December 2006 or death. The first phase of follow up was from January 1999 to June 2004; additional follow-up was from July 2004 to December 2006. Intervention LPD versus MPD (protein intake, 0.55 vs 0.80 g/kg/d). Outcomes Protein-caloric malnutrition (defined as the occurrence of 1 of the following: loss of body weight > 5% in 1 month or 7.5% in 3 months or body mass index < 20 kg/m2 with serum albumin level < 3.2 g/dL and normal C-reactive protein level <0.5 mg/dL), dialysis, death, or the composite outcome of dialysis and death. Results Baseline mean age was 61 years, estimated glomerular filtration rate was 16 mL/min/1.73 m2 , proteinuria had protein excretion of 1.67 g/d, body mass index was 27.1 kg/m2 , protein intake was 0.95 g/kg/d, and there were 57% men. Duration of follow-up was 32 months (median, 30 months; 25th-75th percentiles, 21-39). Average protein intakes were 0.73 ± 0.04 g/kg/d for the LPD and 0.9 ± 0.06 g/kg/d for the MPD. 3 patients (0.7%) met criteria for protein-caloric malnutrition. 48 patients died (11%), 83 initiated dialysis therapy (20%), and 113 (27%) reached the composite outcome. In unadjusted Cox survival analyses, effects of the LPD on these outcomes were 1.01 (95% CI, 0.57-1.79), 0.96 (95% CI, 0.62-1.48), and 0.98 (95% CI, 0.68-1.42), respectively. Limitations Low event rates for dialysis therapy initiation and death. Conclusions Most patients, who were regularly followed up in CKD clinics, were acceptably adherent to the prescribed dietary protein intake restrictions; the LPD and MPD did not lead to protein wasting; and the LPD did not decrease the risk of death or dialysis therapy initiation compared with the MPD.
p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite ...p-cresyl-sulphate causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies to reduce plasma p-cresol levels are highly demanded but not available yet. Because it has been reported that the phosphate binder sevelamer sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. Patients receiving sevelamer had plasma p-cresol and serum high sensitivity C-reactive protein concentrations significantly lower than those receiving lanthanum or no drug. Conversely, no difference was observed among the different groups either in residual glomerular filtration rate, total weekly dialysis dose, total clearance, urine volume, protein catabolic rate, serum albumin or serum phosphate levels. Multiple linear regression analysis showed that none of these variables predicted plasma p-cresol concentrations that, instead, negatively correlated with the use of sevelamer. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect cardiovascular risk because of its anti-inflammatory effect.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in ...reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis.
The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated.
At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval.
The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate.
COVID-19 is one of the most important problems for public health, according to the number of deaths associated to this pathology reported so far. However, from the epidemiological point of view, the ...dimension of the problem is still unknown, since the number of actual cases of SARS-CoV-2 infected people is underestimated, due to limited testing. This paper aims at estimating the actual Infection Fatality Ratio (number of deaths with respect to the number of infected people) and the actual current prevalence (number of infected people with respect to the entire population), both in a specific population and all over the world. With this aim, this paper proposes a method to estimate Infection Fatality Ratio of a still ongoing infection, based on a daily estimation, and on the relationship between this estimation and the number of tests performed per death. The method has been applied using data about COVID-19 from Italy. Results show a fatality ratio of about 0.9%, which is lower than previous findings. The number of actual infected people in Italy is also estimated, and results show that (i) infection started at the end of January 2020; (ii) a maximum number of about 100,000 new cases in one day was reached at the beginning of March 2020; (iii) the estimated cumulative number of infections at the beginning of October 2020 is about 4.2 million cases in Italy (more than 120 million worldwide, if a generalization is conjectured as reasonable). Therefore, the prevalence at the beginning of October 2020 is estimated at about 6.9% in Italy (1.6% worldwide, if a generalization is conjectured).
Aims. Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels. Methods. Both ...inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data. Results. A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre-adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients. Conclusions. In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Intrapatient variability of hemoglobin (Hb) is a newly proposed determinant of adverse outcome in chronic kidney disease (CKD). We evaluated whether intensity of epoetin therapy affects Hb ...variability and renal survival in nondialysis CKD.
We calculated the individual therapeutic index (TI) for epoetin (EPO; difference between rates of visits that required EPO dosage change and those with effective EPO change) from 1198 visits during the first year of EPO in 137 patients. Renal death was registered in the subsequent 18.1 mo. Analysis was made by TI tertile (lower, middle, and higher; i.e., from more to less intensive therapy).
Main features and visit number were similar in tertiles. Lower Hb response to first EPO dosage was an independent predictor of higher TI (P = 0.002). The area under the curve for Hb (11.56 +/- 0.87, 11.46 +/- 1.20, and 10.95 +/- 1.48 g/dl per yr; P = 0.040) decreased from lower to higher tertile. Hb variability increased in parallel, as shown by the reduction of time with Hb at target (time in target, from 9.2 +/- 2.0 to 3.0 +/- 2.2 mo; P < 0.0001) and the wider values of within-patient Hb standard deviation (from 0.70 to 0.96; P = 0.005) and Hb fluctuations across target (P < 0.0001). In Cox analyses (hazard ratio 95% confidence interval), risk for renal death was increased in the middle and higher tertiles (2.79 1.36 to 5.73 and 2.94 1.40 to 6.20) and reduced by longer time in target (0.90 0.83 to 0.98).
Lack of adjustment of EPO worsens Hb variability in CKD. Hb variability may be associated with renal survival, but further studies are needed to explore the association versus causal relationship.
Instability of hemoglobin levels during epoetin therapy is a new problem in hemodialysis. We evaluated extent and correlates of time in target, that is, the time spent with hemoglobin > or = 11 g/dl ...during the first year of epoetin and its association with renal survival.
Data were collected in 917 visits for 12.0 mo in 119 patients with chronic kidney disease; thereafter, patients started renal survival analysis for 10.1 mo. At baseline, hemoglobin was 10.0 +/- 0.8 g/dl and GFR was 22.1 +/- 14.2 ml/min per 1.73 m2.
Hemoglobin target, reached in 1.5 mo, was steadily maintained in only 24% of patients. Time in target was not merely due to differences in time to target; after first achievement of target, in fact, a reduction of hemoglobin < 11 g/dl occurred in 51% of patients. At multivariate analysis, male gender, basal GFR and hemoglobin levels, first epoetin dose, and iron supplementation were directly associated with length of time in target. A lower risk for renal death (dialysis n = 53; death n = 8) was detected in the higher tertile of time in target (11.3 mo) versus lower tertile (3.2 mo). This difference persisted at Cox analysis after adjustment for age, gender, GFR, BP, and proteinuria.
In chronic kidney disease, time in target during the first year of epoetin therapy is frequently short depending not only on time to target but also on post-target hemoglobin reductions, correlates with male gender, timing, and intensity of initial therapy and is coupled with better renal survival.
We tested for the presence of coronary calcifications in patients with chronic renal disease not on dialysis and studied its progression in 181 consecutive non-dialyzed patients who were followed for ...a median of 745 days. Coronary calcifications (calcium score) were tallied in Agatston units by computed tomography, and the patients were stratified into two groups by their baseline calcium score (100U or less and over 100U). Survival was measured by baseline calcium score and its progression. Cardiac death and myocardial infarction occurred in 29 patients and were significantly more frequent in those patients with calcium scores over 100U (hazard ratio of 4.11). With a calcium score of 100U or less, the hazard ratio for cardiac events was 0.41 and 3.26 in patients with absent and accelerated progression, respectively. Thus, in non-dialyzed patients, the extent of coronary calcifications was associated to cardiac events, and progression was an independent predictive factor of cardiac events mainly in less calcified patients. Hence, assessment of coronary calcifications and progression might be useful for earlier management of risk factors and guiding decisions for prevention of cardiac events in this patient population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigated the effects of visit-to-visit systolic blood pressure variability (SBPV) on both mortality and dialysis inception in a cohort of chronic kidney disease (CKD) patients not requiring ...dialysis therapy. Furthermore, we also explored the carry-over effect of visit-to-visit SBPV on mortality after dialysis initiation.
We conducted a longitudinal retrospective, observational, multi-centre study in three tertiary care nephrology outpatient clinics. All the ambulatory CKD patients admitted to the outpatient clinics from 1 January 2004 to 31 December 2005 were screened for study eligibility. We selected all consecutive patients older than 18 years of age with a mean estimated glomerular filtration rate of <60 mL/min/m(2), free from cardiovascular disease. SBPV was defined as the ratio of the SD to the mean SBP of five values recorded during a run-in phase of 4-5 months. Data on dialysis inception and mortality were recorded through 31 December 2010.
Overall, we selected a cohort of 374 elderly (median age: 79 years) subjects. A total of 232 (62%) and 103 (29%) patients were male and had diabetes, respectively. A significant association between SBPV and the risk of death but not of CKD progression to dialysis was noted at univariate and after multivariable adjustments (hazard ratio for all-cause mortality per 1% increase in SBPV: 1.05; 95% confidence interval: 1.02-1.09; P = 0.001). Notably, no lethal event was recorded after dialysis initiation.
Current findings suggest that SBPV may be of use for risk stratification in CKD patients.
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