6-tips diet: a simplified dietary approach in patients with chronic renal disease. A clinical randomized trial.

BACKGROUND: The beneficial effects of dietary restriction of proteins in chronic kidney disease are widely recognized; however, poor compliance to prescribed low-protein diets (LPD) may limit their effectiveness. To help patients to adhere to the dietary prescriptions, interventions as education programmes and dietary counselling are critical, but it is also important to develop simple and attractive approaches to the LPD, especially when dietitians are not available. Therefore, we elaborated a simplified and easy to manage dietary approach consisting of 6 tips (6-tip diet, 6-TD) which could replace the standard, non-individualized LPD in Nephrology Units where dietary counselling is not available; hence, our working hypothesis was to evaluate the effects of such diet vs a standard moderately protein-restricted diet on metabolic parameters and patients' adherence. METHODS: In this randomized trial, 57 CKD patients stage 3b-5 were randomly assigned (1:1) to receive the 6-TD (Group 6-TD) or a LPD containing 0.8 g/kg/day of proteins (Group LPD) for 6 months. The primary endpoint was to evaluate the effects of the two different diets on the main "metabolic" parameters and on patients' adherence (registration number NCT01865526). RESULTS: Both dietary regimens were associated with a progressive reduction in protein intake and urinary urea excretion compared to baseline, although the decrease was more pronounced in Group 6-TD. Effects on serum levels of urea nitrogen and urinary phosphate excretion were greater in Group 6-TD. Plasma levels of phosphate, bicarbonate and PTH, and urinary NaCl excretion remained stable in both groups throughout the study. 44 % of LPD patients were adherent to the dietary prescription vs 70 % of Group 6-TD. CONCLUSIONS: A simplified diet, consisting of 6 clear points easily managed by CKD patients, produced beneficial effects either on the metabolic profile of renal disease and on patients' adherence to the dietary plan, when compared to a standard LPD.

[Characteristics of patients with chronic kidney disease referred to a nephrology outpatient clinic: results of Nefrodata study]. / Le caratteristiche dei pazienti con insufficienza renale cronica afferenti agli ambulatori di nefrologia: risultati dallo studio Nefrodata®.

Chronic kidney disease is acknowledged as one of the most relevant disease for public health. Knowledge of epidemiology of CKD may allow public health interventions both for prevention and treatment in order to limit burden and management costs. Nefrodata is a multicentric, prospective, and observational study conducted in Italy, including patients with CKD followed in a specialist setting. The study uses a web-based data setting; it includes 1263 subjects with an estimate glomerular filtration rate (eGFR) less than 60 ml/min *1,73 sqm, followed in outpatient clinics in Italy. Patients' characteristics analysis evidences that old subjects (mean age of 70.3 13.4 years, 55% of them older than 70 years), with cardiovascular morbidity (50,6%) and diabetics (37%) have a high prevalence. With the reduction of residual renal function, prevalence of hyperphospatemia, metabolic acidosis, use of erythropoiesis-stimulating agents, Vitamin D, and diuretics increases. Also allopurinol and gastric-protective drugs are widely used. Fifty-four and eight % of patients with CKD stage 4 and 65.9% of patients with CKD stage 5 received indication on nutritional therapy.

Urine creatinine excretion and clinical outcomes in CKD.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine creatinine excretion is a reliable approximation of muscle mass. Whether changes in urine creatinine predict clinical outcomes in persons with CKD is unknown. This work studied the relationship between urine creatinine and patient and renal survival in people with CKD not requiring renal replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This longitudinal cohort study included incident stages 3-5 CKD patients referred to the renal clinic at the University Federico II in Naples between January of 1995 and December of 2005. Clinical data and urine creatinine were updated at each visit. Main outcomes were all-cause mortality and kidney failure requiring dialysis. RESULTS: This study enrolled 525 individuals and followed them for a median of 6 years (range of 4 months to 15 years). Urine creatinine excretion declined by 16 mg/d per year (95% confidence interval, 14 to 19) in participants with CKD stages 3a, 3b, and 4, and it remained stable in participants with stage 5 CKD. Per each 20 mg/d decline in urine creatinine, mortality increased by 3% (adjusted hazard ratio, 1.03; 95% confidence interval, 1.01 to 1.05), and the risk of initiating dialysis increased by 2% (adjusted hazard ratio, 1.02; 95% confidence interval, 1.01 to 1.03). These associations were independent of body mass index and GFR. CONCLUSIONS: In persons with CKD stages 3 and 4, urine creatinine declines at a rate of 16 mg/d per year. Lower urine creatinine excretion predicts greater risk of kidney failure and patient mortality.

A novel GLA mutation in a Fabry family with glucose-6-phosphate dehydrogenase deficiency.

Fabry disease is an X-linked lysosomal disease caused by mutations of the alpha-galactosidase A (GLA) gene at chromosome subband Xq22.1. To date, more than 600 genetic mutations have been identified to determine the nature and frequency of the molecular lesions causing the classical and milder variant phenotypes and for precise carrier detection. We report here a Fabry family (mother, son and daughter) where the alpha-galactosidase A defect was associated with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Mutation analysis revealed for the GLA gene the presence of a new mutation, i.e., a small deletion (c.452delA) on exon 3 and for the G6PD gene the presence of 2 mutations, p.V68M (G6PD Asahi, G6PD A+) and p.N126D (G6PD A+) on exon 3 and exon 4, respectively.

Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients.

BACKGROUND: Lower responsiveness to erythropoiesis-stimulating agents (ESA-R) predicts cardiovascular (CV) events. Whether ESA-R also affects the risk of end-stage renal disease (ESRD) is unknown. METHODS: We evaluated ESA-R in 194 consecutive chronic kidney disease (CKD) patients, regularly seen in outpatient nephrology clinics, who started erythropoiesis-stimulating agent (ESA) therapy between 2002-06. Exclusion criteria were causes of anaemia other than CKD or recent transfusion. ESA-R was calculated as (Hb1-Hb0)/time/ESA dose (g/dL/month/10 µg/week of ESA). Patients were classified, from lower to higher tertile of ESA-R, as poor, intermediate and good responders. Time to ESRD was the primary outcome. RESULTS: Age was 64±16 years, 48% were male, 34% had diabetes and 32% had CV disease, glomerular filtration rate (GFR) 24±13 mL/min/1.73 m2 and proteinuria 0.6 g/dL (interquartile range 0.2-1.9). First ESA dose was 23.7±10.8 µg/week; haemoglobin (Hb) increased from 9.9±0.8 g/dL to 11.0±1.2 g/dL at first control, obtained after 1.4±0.4 months. These changes corresponded to an ESA-R of 0.37±0.38 g/dL/month/10 µg/week of ESA and tertiles limits were 0.17 and 0.47. Poor responders were younger and had lower GFR and higher proteinuria than intermediate and good responders. During the first 6 months of ESA therapy, poor responders showed lower Hb levels and sustained longer periods of Hb level<11 g/dL. During follow-up (median 3.0 years), 99 patients reached ESRD. At multivariable Cox's analysis, poor responsiveness was associated with higher risk of ESRD (hazard ratio 2.49, 95% confidence interval 1.28-4.84). CONCLUSION: ESA-R predicts renal prognosis in CKD patients followed in nephrology practice, where ESRD is the predominant outcome and ESA is commonly used at low dose.

Nephrotic syndrome and autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the development and growth of cysts in the kidneys and other organs. In ADPKD patients, nephrotic range proteinuria is unusual and needs to be investigated further to exclude coexisting glomerular disease. Among the anecdotal case reports of ADPKD associated with nephrotic syndrome, focal segmental glomerulosclerosis occurs most frequently. METHODS: We report the case of a 26-year-old male with ADPKD and concomitant nephrotic syndrome, in which an ultrasound (US)-guided renal biopsy showed a mesangioproliferative glomerulonephritis. We treated the patient with prednisone 1 mg/kg/day, because of the failure of treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker association. RESULTS: After 6 months of steroid treatment, we observed a stability of his GFR and a reduction of proteinuria. CONCLUSION: This case report and other cases of the literature underline the importance of a renal biopsy in patients with ADPKD and nephrotic syndrome in order to make an accurate diagnosis and an appropriate treatment/prevention of renal function deterioration.

[Health Technology Assessment to evaluate the economic advantage of offering of low-protein diet to pre-dialysis patients in Campania (Italy)]. / Un modello HTA a sostegno dell'offerta della dieta ipoproteica ai nefropatici della Campania.

A low-protein diet is well known to slow the progression of chronic renal failure, delay initiation of dialysis, while achieving significant economic benefits. In the context of a Health Technology Assessment (HTA), a budget impact analysis model was implemented to evaluate the economic advantage of offering of low-protein diet to nephropathic patients in Campania (Italy). The implemented model takes into account only the direct costs to the national healthcare system. In particular, costs related to supplying low-protein foods are compared to dialysis costs avoided, in a scenario that evaluates different indices of Numbers Needed to Treat and compliance to treatment. Results indicate that when compliance to treatment is at least 50% and NNT is £ 50, supplying a low-protein diet to all kidney disease patients in the pre-dialysis phase, namely with an estimated Glomerular filtration rate > 45, in Campania (which in the year 2009 were equal to 25,000 subjects), is economically advantageous. In this perspective, the authors argue that distribution of low-protein foods by local pharmacies could be an appropriate choice as it would allow the products to be offered at a discounted price and create a favorable setting for increasing adherence to treatment.

Simultaneous multicystic kidney and Anderson-Fabry disease: 2 separate entities or same side of the coin.

We present the case of a 54-year-old man with multicystic kidney and concomitant Anderson-Fabry disease. He was referred to our hospital with multiple renal and hepatic cysts, without apparent family history of autosomal dominant polycystic kidney disease. His clinical history suggested Anderson-Fabry disease, so an extensive work-up for Anderson-Fabry disease was subsequently undertaken. The alpha-galactosidase activity in his serum was low, and a final diagnosis of Anderson-Fabry disease with concomitant multicystic kidney was confirmed by genetic analysis.

Prognosis of CKD patients receiving outpatient nephrology care in Italy.

BACKGROUND AND OBJECTIVES: Prognosis in nondialysis chronic kidney disease (CKD) patients under regular nephrology care is rarely investigated. Design, setting, participants, & measurements We prospectively followed from 2003 to death or June 2010 a cohort of 1248 patients with CKD stages 3 to 5 and previous nephrology care ≥1 year in 25 Italian outpatient nephrology clinics. Cumulative incidence of ESRD or death before ESRD were estimated using the competing-risk approach. RESULTS: Estimated rates (per 100 patient-years) of ESRD and death 8.3 (95% confidence interval [CI], 7.4 to 9.2) and 5.9 (95% CI 5.2 to 6.6), respectively. Risk of ESRD and death increased progressively from stages 3 to 5. ESRD was more frequent than death in stage 4 and 5 CKD, whereas the opposite was true in stage 3 CKD. Younger age, lower body mass index, proteinuria, and high phosphate predicted ESRD, whereas older age, diabetes, previous cardiovascular disease, ESRD, proteinuria, high uric acid, and anemia predicted death (P < 0.05 for all). Among modifiable risk factors, proteinuria accounted for the greatest contribution to the model fit for either outcome. CONCLUSIONS: In patients receiving continuity of care in Italian nephrology clinics, ESRD was a more frequent outcome than death in stage 4 and 5 CKD, but the opposite was true in stage 3. Outcomes were predicted by modifiable risk factors specific to CKD. Proteinuria used in conjunction with estimated GFR refined risk stratification. These findings provide information, specific to CKD patients under regular outpatient nephrology care, for risk stratification that complement recent observations in the general population.

Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease.

BACKGROUND: Ambulatory blood pressure (BP) measurement allows a better risk stratification in essential hypertension compared with office blood pressure measurement, but its prognostic role in nondialysis chronic kidney disease has been poorly investigated. METHODS: The prognostic role of daytime and nighttime systolic BP (SBP) and diastolic BP (DBP) in comparison with office measurements was evaluated in 436 consecutive patients with chronic kidney disease. Primary end points were time to renal death (end-stage renal disease or death) and time to fatal and nonfatal cardiovascular events. Quintiles of BP were used to classify patients. RESULTS: The mean (SD) age of the patients was 65.1 (13.6) years, and the glomerular filtration rate was 42.9 (19.7) mL/min/1.73 m(2); 41.7% of the participants were women, 36.5% had diabetes, and 30.5% had cardiovascular disease. Office-measured SBP/DBP values were 146 (19)/82 (12) mm Hg; daytime SBP/DBP was 131 (17)/75 (11) mm Hg, and nighttime SBP/DBP was 122 (20)/66 (10) mm Hg. During follow-up (median, 4.2 years), 155 and 103 patients reached the renal and cardiovascular end points, respectively. Compared with a daytime SBP of 126 to 135 mm Hg, patients with an SBP of 136 to 146 mm Hg and those with an SBP higher than 146 mm Hg had an increased adjusted risk of the cardiovascular end point (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.13-4.41 and 3.07; 1.54-6.09) and renal death (1.72; 1.02-2.89 and 1.85; 1.11-3.08). Nighttime SBPs of 125 to 137 mm Hg and higher than 137 mm Hg also increased the risk of the cardiovascular end point (HR, 2.52; 95% CI, 1.11-5.71 and 4.00; 1.77-9.02) and renal end point (1.87; 1.03-3.43 and 2.54; 1.41-4.57) with respect to the reference SBP value of 106-114 mm Hg. Office measurement of BP did not predict the risk of the renal or cardiovascular end point. Patients who were nondippers and those who were reverse dippers had a greater risk of both end points. CONCLUSION: In chronic kidney disease, ambulatory BP measurement and, in particular, nighttime BP measurement, allows more accurate prediction of renal and cardiovascular risk; office measurement of BP does not predict any outcome.

Fabry disease: perspectives of urinary proteomics.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the lysosomal enzyme a-galactosidase A (a-GalA). The resulting deficiency in a-GalA activity leads to intra-lysosomal accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organ systems. As a consequence, a multisystem disorder develops, culminating in strokes and progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though monitoring treatment is hampered by a lack of surrogate markers of response. Furthermore, even if signs and symptoms of the disease become manifest in childhood, its diagnosis is often delayed. Biomarkers that predict disease progression and respond relatively quickly to effective therapy may be useful to follow individual patients or groups of patients. Here we report the use of 2 different mass spectrometry-based proteomic techniques to identify disease-associated compositional changes that can be used as early biomarkers of the pathology, as well as for monitoring the effectiveness of ERT. To this purpose, we compared the renal Fabry urinary proteome with normal (control) urine using, respectively, 2-dimensional gel electrophoresis and label-free quantification. Our preliminary results show that the urinary protein pattern of affected patients can be easily distinguished from that of healthy subjects both qualitatively and quantitatively, thus encouraging further studies in the search for FD-specific biomarkers using this proteomic approach.

Prevalence and prognosis of mild anemia in non-dialysis chronic kidney disease: a prospective cohort study in outpatient renal clinics.

BACKGROUND/AIMS: we evaluated prevalence and prognosis of mild anemia, defined as Hb (g/dl) 11-13.5 in males and 11-12 in females, in a prospective cohort of stage 3-5 chronic kidney disease (CKD) patients. METHODS: we enrolled 668 consecutive patients in 25 renal clinics during 2003. Patients with frank anemia (Hb <11 or erythropoiesis-stimulating agents) at enrolment were excluded. Mild anemia was evaluated at two visits planned with an interval of 18 ± 6 months to identify four categories: no anemia at both visits, mild anemia at visit 1 resolving at visit 2 (RES), mild anemia persisting at both visits (PER), and progression from no anemia or mild anemia at visit 1 to mild or frank anemia at visit 2 (PRO). RESULTS: mild anemia was present in 41.3% at visit 1 and 34.1% at visit 2. We identified PER in 22% patients, RES in 10%, and PRO in 26%. In the subsequent 40 months, 125 patients developed end-stage renal disease (ESRD) and 94 died. At competing risk model, PER predicted ESRD (hazard ratio, HR, 1.82, 95% confidence interval, CI, 1.01-3.29) while PRO predicted both ESRD (HR 1.81, 95% CI 1.02-3.23) and death (HR 1.87, 95% CI 1.04-3.37). CONCLUSION: in non-dialysis chronic kidney disease, mild anemia is prevalent and it is a marker of risk excess when persistent or progressive over time.

Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry.

BACKGROUND AND OBJECTIVES: These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement therapy were included. RESULTS: Most men (86 of 121, 71%) had more rapid loss of kidney function than the normal adult population (loss of eGFR > -1 ml/min per 1.73 m(2) per year), whereas fewer women (133 of 341, 39%) had rapid loss of kidney function. Patients with rapid progression had significantly higher mean averaged urinary protein to urinary creatinine ratios (UP/Cr) than patients with slower progression (1.5 versus 0.2 for men; 1.4 versus 0.5 for women; P < 0.0001). Patients were grouped into quartiles based on averaged UP/Cr; renal function in men declined more rapidly with higher UP/Cr, with the steepest declines observed in men with UP/Cr > 1.5 (mean eGFR slope, -5.6 ml/min per 1.73 m(2) per year; n = 30). eGFR slope declined more slowly in women, with the steepest declines observed in women with UP/Cr > 1.2 (mean eGFR slope, -1.3 ml/min per 1.73 m(2) per year; n = 85). Regression models of eGFR slope indicated that UP/Cr is the most important indicator of renal disease progression in adult Fabry patients. In women, lower baseline eGFR and age were also associated with renal disease progression. Women who had clinical events had more rapid loss of kidney function. CONCLUSIONS: Urinary protein excretion is strongly associated with renal disease progression in men and women with Fabry disease.

End-stage renal disease in patients with Fabry disease: natural history data from the Fabry Registry.

BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase activity, is associated with progressive loss of kidney function. This study was undertaken to characterize Fabry disease among patients who reached end-stage renal disease. METHODS: Data from 2,712 patients in the Fabry Registry were analysed to identify clinical characteristics of patients who received renal replacement therapy (RRT) during the natural history period (i.e. prior to any enzyme replacement therapy). RESULTS: A total of 213 patients [186 of 1,359 males (14%) and 27 of 1,353 females (2%)] received RRT at a median age of 38 years in both males and females. Males who received RRT were diagnosed at a median age of 35 years, compared to 23 years for non-RRT males. Sixty-one males and 10 females were not diagnosed with Fabry disease until after they had received RRT. Compared to other Fabry Registry patients, a higher percentage of RRT patients also experienced either a serious cardiovascular event or a stroke. Ninety-two of 186 males who had RRT (50%) experienced a cardiac event or stroke, compared to 230 of 1,173 non-RRT males (20%). Ten of 27 RRT females (37%) had experienced a cardiac event or stroke, compared to 226 of 1,326 non-RRT females (17%). Patients who had RRT experienced cardiovascular events and strokes at earlier ages than did patients who had not received RRT, and most received RRT before having a cardiac event or stroke. CONCLUSIONS: While all Fabry patients are at risk of cardiovascular events and strokes, patients with Fabry nephropathy who develop kidney failure appear to have concurrent involvement of other major organ systems. It is important that Fabry patients are diagnosed early and that their renal function is monitored carefully.

Assessment of nutritional practice in Italian chronic kidney disease clinics: a questionnaire-based survey.

BACKGROUND: The prevention of malnutrition in patients with progressive chronic kidney disease (CKD) presents a challenge to nephrologists. We evaluated nutritional practice and routines, at a national level, related to the nutritional management of nondialyzed CKD patients. METHODS: A questionnaire-based survey (32 open and 9 multiple-choice questions) was used to assess the evaluation of nutritional status in nondialyzed CKD outpatients at baseline and during follow-up. Data were obtained for 230 Italian public nephrology centers (63% of the total number of Italian public nephrology centers). RESULTS: There was a dedicated dietitian at only 19% of the centers. At baseline, body weight, body mass index, and serum albumin were determined in almost all centers, nutrient intakes and bioimpedance analysis in half the centers, and subjective global assessment and skinfold thickness in a small proportion of centers. During follow-up, the rate of assessments decreased by 8% for weight, 14% for nutrient intake, and 29% for subjective global assessment and skinfold thickness. Overall, the K/DOQI minimum criteria for nutritional assessment were fulfilled in only two thirds and half of the clinics at baseline and during follow-up, respectively. Multivariate analysis showed that the number of nutritional variables evaluated was significantly related to the size of the CKD clinic and the presence of a dietitian at baseline, but only with the presence of dietitian during follow-up. Daily urinary output was collected at 90% of the centers, but urea and sodium excretions were determined in only 59% and 57% of cases, respectively. The rate of assessment for urinary solutes during follow-up was higher at centers where a very low protein diet was prescribed. CONCLUSIONS: The indications about nutritional assessment for CKD patients are poorly translated into practice patterns, especially with respect to the evaluation of nutrient intakes and additional but simple variables such as skinfold-thickness measurement and bioimpedance analysis. The presence of a dedicated dietitian appears to improve the quality of nutritional assessment in CKD.

Effect of a low- versus moderate-protein diet on progression of CKD: follow-up of a randomized controlled trial.

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/m(2) 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 m(2), proteinuria had protein excretion of 1.67 g/d, body mass index was 27.1 kg/m(2), 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.

Setting dialysis start at 6.0 ml/min/1.73 m2 eGFR--a study on safety, quality of life and economic impact.

BACKGROUND: End-stage renal disease care requires enormous economic resources. A timely dialysis start could reduce the costs of the renal replacement therapy (RRT). Our aim was to measure the time to dialysis in CKD patients, with an estimated glomerular filtration rate (eGFR)

Epoetin therapy and hemoglobin level variability in nondialysis patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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). RESULTS: 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]). CONCLUSIONS: 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.

Italian randomized trial of hemoglobin maintenance to prevent or delay left ventricular hypertrophy in chronic kidney disease.

BACKGROUND: This study is part of a 3-country study testing whether normal levels of hemoglobin (Hgb) delay the progression of left ventricular (LV) growth in chronic kidney disease (CKD) patients not on dialysis. METHODS: This was an open-label, randomized, multicenter, controlled trial conducted in 27 tertiary-care hospitals in Italy. Treated subjects (n=46) received epoetin-alpha (EPO-alpha) to maintain Hgb levels in the range 12-14 g/dL. Control subjects (n=49) were not treated unless their Hgb decreased to 9.0 g/dL. Primary outcome was LV mass index (MI) change after 24 months. Subcutaneous EPO-alpha was withdrawn in Europe and the study prematurely terminated; therefore, a 12-month analysis was carried out. RESULTS: Mean age was 57 years (38% were women, 18% with diabetes, 76% taking ACEI or ARB and 22% statins). EPO-alpha median final dose was 2,000 IU/week. Hgb significantly increased (12.4 -/+ 1.1 g/L) for the treatment group and decreased for controls (11.3 -/+ 1.3 g/L; p<0.001). The intention-to-treat analysis was conducted in 78 patients. Mean baseline LVMI for treated patients and controls was 109.5 -/+ 23 g/m2 and 108.7 -/+ 29 g/m2, respectively. LVMI did not change among controls, whereas it decreased slightly, though not significantly, among treated patients. CONCLUSIONS: The current Italian trial was negative, maybe due to its limitations: lack of power, 1-year follow-up and normal LVMI in some patients at start; however, it was consistent with other published studies. Thus, it is unlikely that targeting hemoglobin in the normal range for CKD patients is of benefit.

Renal transplantation and sleep: a new life is not enough.

Renal transplantation is associated with better survival and improved quality of life compared to maintenance dialysis. Although many sleep disorders improve or even disappear after a successful transplantation, sleep quality remains low, and the prevalence of sleep complaints, although lower than in dialysis patients, is much higher than in the general population. Few studies have dealt with sleep problems of renal transplant patients: despite reporting obvious differences in the prevalence of the single sleep disorders, all underline the importance of psychological problems in conditioning sleep. In the diagnosis of sleep disorders, the nephrologist must learn to distinguish medical risk factors (pain, pruritus, tremors, drugs) and psychological aspects (depression, anxiety, fear), since they are potentially modifiable with the appropriate treatment.