Supplemented Very Low Protein Diet (sVLPD) in Patients with Advanced Chronic Renal Failure: Clinical and Economic Benefits.

The supplemented very low-protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and postponing the start of the dialysis treatment. However, sVLPD could expose the patient to the risk of malnutrition. This diet is also difficult to implement due to the required intake of large number of keto-analogue/amino acid tablets. In our Center, the Department of Nephrology and Dialysis of Azienda Sanitaria Territoriale n 1, Pesaro-Urbino, of Italy, respecting the guidelines of normal clinical practice, we prescribed sVLPD (0.3 g/prot/day) supplemented with only essential amino acids without the use of ketoanalogues in stage 5 patients and verified its efficacy, safety and clinical and economic effects. Over the 24 months period of observation the progression of chronic kidney disease (CKD) slowed down (mean eGFR 11.6 ± 3.3 vs. 9.3 ± 2.7 mL/min/1.73 m2, p < 0.001) and the start of the dialysis treatment (adjusted HR = 0.361, CI 0.200-0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant vs. non-compliant patients. This led to a substantial cost reduction for the National Health System. This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with essential amino acids could be extensively used to reduce the incidence of dialysis treatments, with a favorable economic impact on the NHS.

The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome.

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.

Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial.

BACKGROUND: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. METHODS: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. RESULTS: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. CONCLUSIONS: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. TRIAL REGISTRATION NUMBER: NCT01457001.

[SARS CoV-2 related disease features in a population of chronic hemodialysis patients].

Patients on chronic dialysis have an increased risk for SARS CoV-2 virus disease and its complications because of multiple comorbidities and alterations in the immune response caused by renal disease. In this retrospective observational study we describe the clinical features and the evolution of SARS CoV-2-related disease in 19 patients of our Pesaro and Fano facilities, where incidence and mortality of the epidemic were among the highest in Italy. A total of 176 patients were undergoing chronic treatment, 153 hemodialysis and 23 peritoneal dialysis. The incidence of infection was 10,8%, with 84% needing hospitalization and mortality amounting to 53%. The most frequent onset symptom was fever (84,2%) and the most used therapy was an association of low molecular weight heparin and hydroxychloroquine (57,9%). Comparing the deceased and survivor populations we noticed significant differences in age and presence of cardiopathy for what concerns anamnestic data and in fatigue and dyspnea in terms of clinical presentation. LDH and CPK resulted highest among deceased patients, while the use of enoxaparin was more frequent in survivors. By observing contagions over time, we also noticed that most of the cases, and the ones with worse clinical condition and outcome, all occurred in the early stage of the epidemic and in particular within the first 20 days from the implementation and codification of the measures to prevent its spread, the only modifiable factor that had an unmistakable effect on the evolution of events.

[SICI-GISE/SIN Consensus document: Contrast-induced acute kidney injury in interventional cardiology]. / Documento di consenso SICI-GISE/SIN: Danno renale acuto da mezzo di contrasto in cardiologia interventistica.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication that can affect outcome and prognosis of patients undergoing percutaneous diagnostic and interventional procedures. The Italian Society of Interventional Cardiology (SICI-GISE) has promoted a consensus project on the subject of CI-AKI in order to disseminate and implement nephroprotection strategies in interventional cardiology. The initiative was conducted in partnership with the Italian Society of Nephrology (SIN).

Clinical Management of Chronic Kidney Disease Patients in Italy: Results from the IRIDE Study.

BACKGROUND: Lack of adequate management of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. This study assessed the clinical management and outcome of stages 1-5 CKD patients. METHODS: Patients were prospectively followed for 3 years in 25 nephrology centers across Italy. Clinical characteristics were measured at baseline and every 6 months. Outcome measures included CKD staging, presence of comorbidities, treatment, mineral bone disorder (MBD) parameters, and patient outcomes. RESULTS: Of 884 enrolled patients (59.7% males, aged 66.2 ± 14.6 years), 587 (66.4%) completed the study. The majority of patients were referred by a general practitioner (44.7%) and had stage 3 or 4 CKD (40.9 and 23.8% respectively). Data reveal that 91.3% of patients had at least 1 concomitant disease, most frequently hypertension (80.1%) and dyslipidemia (42.5%); 94.6% of patients were receiving cardiovascular medication and 52.6% were receiving lipid-lowering medication. Approximately 40% of patients had proteinuria and intact parathyroid hormone levels outside the normal range. As expected, stages 4 and 5 CKD patients had a higher prevalence of proteinuria (68 and 74%), MBD (59 and 88%) and anemia (28 and 73%), as well as a higher risk of hospitalization (34.3 and 51.9%) and need for dialysis (69.5 and 70%). The overall probability of survival over 36 months was 90.6%. CONCLUSIONS: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount.

First case report of using Ofatumumab in kidney transplantation AB0 incompatible. / PRIMO CASE REPORT DI UTILIZZO DELL' OFATUMUMAB NEL TRAPIANTO RENALE AB0 INCOMPATIBILE.

Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment. Ofatumumab is a fully humanized monoclonal anti-CD20 antibody. As a fully humanized antibody, Ofatumumab may avoid immunogenic reactions. The patient tolerated the administration of the drug showing no signs of adverse side effects and with good clinical efficacy. Our case report suggest that Ofatumumab is a valid alternative B cell depleting agent.

[Census of the renal and dialysis units by Italian Society of Nephrology: nephrologist's workload for renal patient assistance in Italy (2014-2015)]. / Censimento a cura della Società Italiana di Nefrologia delle strutture nefrologiche e della loro attività in Italia nel 2014-2015: il lavoro del nefrologo.

BACKGROUND: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted acensusof the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to theyear 2014. METHODS: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit. RESULTS: Renal and dialysis activity was performed by over 2718 physicians (45 pmp). The management of the acute renal failure was one of the most frequent activities in the public renal units (12,206 patients in ICU and 140.00 dialysis sessions). There were performed about 9000 AV fistulas and 1700 central vascular catheters insertions. In the census, there are a lot of data regarding organization, workforce and workload of the renal unit in Italy. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

[Census of the renal and dialysis units by Italian Society of Nephrology: structure and organization for renal patient assistance in Italy (2014-2015)]. / Censimento a cura della Società Italiana di Nefrologia delle strutture nefrologiche e delle loro attività in Italia nel 2014-2015: l'organizzazione.

BACKGROUND: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to the year 2014. METHODS: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit. RESULTS: 615 renal units were identified. From these 615 units, 332 were public renal centres (of which 318 centres answered to the census) and 283 were private dialysis centres (of which 113 centres answered to the census). The results show 6 public renal units pmp. Renal biopsies were 4624 (81 pmp). The nephrology beds are about 41 pmp. There are 7.304 nurses working in HD wards, 1.692 in the nephrology wards and only 613 for outpatients clinics. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

Achievement of NKF/K-DOQI recommended target values for bone and mineral metabolism in incident hemodialysis patients: results of the FARO-2 cohort.

BACKGROUND: Mineral Bone Disorders (MBD) is prevalent in hemodialysis (HD) patients and associated with increased cardiovascular mortality. The FARO-2 study evaluated the achievement of the NKF/K-DOQI guidelines on recommended target values for serum calcium (Ca), phosphorous (P) and intact parathyroid hormone (PTH) levels on survival in incident HD patients. METHODS: Data were collected by questionnaire from 568 incident HD patients followed prospectively over a 3-year period from 26 Italian dialysis units. The cumulative probability of time-to-death for CKD-MBD treatment characteristics was determined by the Kaplan-Meier curves. RESULTS: Serum PTH levels (median values at 6 months vs. 36 months; 225 vs. 254 pg/ml), Ca (8.8 vs. 8.9 g/dl) and P (5.1 vs. 4.8 mg/dl) were not significantly different at 6 months versus follow-up. The majority of incident HD patients (60-70%) who were followed up for 36 months did not achieve the NKF/K-DOQI recommended target values. Survival rates were higher in patients on target for three parameters versus patients off target (survival at 24 months: at target 95.7% (95% CI: 84.0-98.9) versus not on target 71.1% (95% CI: 66.3-75.4, p < 0.01)). The 30.1% of patients on target for three MBD parameters at least once during the follow-up period had better survival rates compared to those not reaching these targets (survival at 24 months: at least once 88.0% (95% CI: 81.9-92.1); 67.7% (95% CI: 61.9-72.8, p < 0.01)). CONCLUSION: Our findings indicate that incident HD patients who achieved target levels (for three MBD parameters) for at least one visit have a lower risk of mortality.

Conversion from epoetin and darbepoetin to C.E.R.A. in non-dialysis CKD patients: a multicenter Italian prospective study in nephrology practice.

BACKGROUND: In non-dialysis patients (ND-CKD), C.E.R.A. has been extensively investigated in ESA-naïve subjects but no data are available on its efficacy after switch from other ESA. METHODS: In this prospective, multicenter, open-label study lasting 24 weeks, ND-CKD patients (n = 157) receiving ESA were converted to C.E.R.A. at doses lower than recommended. Primary outcome was the prevalence of Hb target (11-12.5 g/dl). RESULTS: Age was 73 ± 13 years and GFR was 26.2 ± 9.4 ml/min/1.73 m(2); male gender, diabetes and prior cardiovascular disease were 49, 33 and 19%, respectively. Doses of darbepoetin (25 ± 16 µg/week, n = 124) and epoetin (5,702 ± 3,190 IU/week, n = 33) were switched to low dose C.E.R.A. (87 ± 17 µg/month). During the study, prevalence of Hb target increased from 60% to 68% at week-24, while that of Hb < 11 g/dl declined from 32% to 16% (p < 0.001). Hb increased from 11.3 ± 0.8 at baseline to 11.7 ± 0.9 g/dl at week-24 (p = 0.01) without changes in C.E.R.A. dose. Significant predictors of Hb increase were low BMI, low Hb and longer dosing intervals before switch. These factors also predicted the risk of Hb overshooting (Hb > 12.5 g/dl) occurring in 57 patients. CONCLUSIONS: In ND-CKD, conversion from other ESAs to C.E.R.A. is associated with a better anemia control induced by a greater Hb increase in patients previously treated with ESAs at extended dosing interval. This parameter should be considered when switching to long-acting ESA for its potential impact on the risk of overshooting.

What can we learn from a statistically inconclusive trial? Consensus conference on the EVOLVE study results.

The link between serum parathyroid hormone (iPTH) and cardiovascular (CVS) mortality has not been fully elucidated. The EVOLVE Study was designed to test whether a drug such as cinacalcet, aimed at lowering iPTH, could reduce the astonishingly high cardiovascular risk in patients on maintenance dialysis (CKD-5D). Accordingly, the primary outcome of the study was the combined endpoint of time to death or hospitalization due to CVS factors or from any cause. Time to bone fracture and parathyroidectomy were regarded as secondary endpoints. At study completion, the Intention-To-Treat analysis documented a non- significant 7% (Hazard Ratio: 0.93; 95% Confidence interval: 0.85-1.02; P = 0.11) reduction of the primary composite endpoint. However, the intention to treat analysis does not take into account adherence to drug regimens or control for factors that may potentially jeopardize the conduction of the study. In particular, in spite of a careful pre-planned study sample calculation, the final power of the EVOLVE study was 54% instead of the assumed 90%, greatly reducing the reliability of study results. Furthermore, the pre-planned multivariable adjustment of the primary endpoint suggests a nominally significant reduction of the risk of the primary composite endpoint when age is entered into the statistical model. The sensitivity analysis further corroborates this result. The Lag Time Censoring Analysis (LTCA) evidenced a nominally significant 15% risk reduction of the composite endpoint among patients allocated to cinacalcet if the patients follow-up was terminated 6 months after the study drug discontinuation, as pre-planned in the protocol. It is interesting that the LTCA suggests that the effect of cinacalcet weakened over time and became insignificant after about 1 year from drug discontinuation. Although authors could not detect any effect of cinacalcet on bone fracture associated with cinacalcet use, the secondary analyses of the EVOLVE trial suggest a nominally significant 60-70% risk reduction of parathyroidectomy and a reassuring safety profile of prolonged exposure to cinacalcet. In summary, the EVOLVE study adds to the list of inconclusive randomized clinical trials in Nephrology. However, the preplanned exploratory and sensitivity analyses suggest that when imbalances of patients characteristics at study entry (i.e. age) or study drug discontinuation are considered, a 'nominally' significant risk reduction in CVS and parathyroidectomy associated with cinacalcet treatment is noted.

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study.

BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study. MATERIALS AND METHODS: In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective. RESULTS: Four cohorts were identified: patients treated with oral (PO) calcitriol (n=182), intravenous (IV) calcitriol (n=34), IV paricalcitol (n=62), and IV paricalcitol+cinacalcet therapy (n=20); the cinacalcet monotherapy group was not analysed due to low number of patients (n=9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300 pg/ml; p<0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol+cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort's PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p=0.020, p=0.012, and p=0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol+cinacalcet cohort (p<0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns. CONCLUSIONS: The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol+calcimemtics (p<0.001), without a significant difference in terms of baseline severity and PTH control.

[Acetate-free biofiltration]. / Acetate-free biofiltration.

Acetate-free biofiltration is a dialysis method with high biocompatibility. The lack of acetate results in decreased stimulation of the production of inflammatory mediators. Other favorable features have been added over the years, such as the possibility to modulate the concentration of potassium in the dialysate, thereby reducing the risk of arrhythmias; the possibility to constantly monitor the blood volume during treatment to reduce the risk of intradialytic hypotension; and a reduced need for heparin thanks to a membrane with a specially treated surface. In this review we discuss the specifics of acetate-free biofiltration.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

BACKGROUND: Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN: A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS: 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION: AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES: Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS: More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS: A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS: This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.