Metformin-Associated Lactic Acidosis Undergoing Renal Replacement Therapy in Intensive Care Units: A Five-Million Population-Based Study in the North-West of Italy.

BACKGROUND: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). METHODS: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. RESULTS: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. CONCLUSION: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=471917.

Increase of continuous treatments and regional citrate anticoagulation during renal replacement therapy in the ICUs of the North-West of Italy from 2007 to 2015.

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.

Dialysis choice in the context of an early referral policy: there is room for self care.

BACKGROUND: Predialysis care is vital for the patient and is crucial for dialysis choice: empowered, early referred patients tend to prefer out-of-hospital and self-care treatment; despite these claims, early referral remains too often a program more than a reality. Aim of the study was to evaluate the pattern and reasons for RRT choice in patients treated in a long-standing outpatient network, presently following 850 chronic patients (about 80% diabetics), working with an early referral policy and offering a wide set of dialysis options (home hemo and PD; self care and limited care hemodialysis; hospital hemodialysis). METHODS: Prospective historical study. All patients who started RRT in January 2001-December 2003 were considered. Correlations between demographical (sex, age, educational level) or clinical variables (pre-RRT follow-up, comorbidity, SGA and Karnofsky) and treatment choice have been tested by univariate (chi-square, Kruskal-Wallis) and multivariate models (logistic regression), both considering all choices and dichotomising choice into "hospital" versus "out of hospital dialysis". RESULTS: Hospital dialysis was chosen by 32.6% of patients; out of hospital in 67.4% (PD 26.5%, limited-care 18.4%, home hemodialysis 4.1%, self-care 18.4%). Hospital dialysis and PD were chosen by elderly patients (median age: 67.5 and 70 years respectively) with multiple comorbidities (75% and 92.3%); no difference for age, comorbidity, Karnofsky, SGA and educational level. 6/13 PD patients needed the help of a partner. Self-care/home hemodialysis patients were younger (median age 52), had higher educational level (p = 0.014) and lower prevalence of comorbidity (63.6% vs 94.7% in the other dialysis patients, p = 0.006). In the context of a long follow-up period (3.9 years) a statistically significant difference was found comparing hospital dialysis (3.3 years) vs out of hospital dialysis (4.9 years) (p = 0.035). In a logistic regression model, only pre-RRT follow-up was correlated with dialysis "hospital vs "out of hospital" choice (p = 0.014). CONCLUSION: Early nephrological follow-up may enhance self and home-based dialysis care.

Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients.

BACKGROUND: Guidelines for treating anemia in dialysis patients accept, as high-end range of serum ferritin useful to optimize erythropoietin therapy, values high as 500 to 900 microg/L, on the hypothesis that ferritin might be not representative of iron overload. METHODS: A superconducting quantum interference device (SQUID) was used to make direct noninvasive magnetic measurements of nonheme hepatic iron content in 40 dialysis patients treated with intravenous iron, and liver iron content was compared with biochemical markers of iron status. RESULTS: Only 12/40 (30%) patients showed normal hepatic iron content (SQUID <400 microg/g), while 32.5% had mild (400 to 1000 microg/g) and 37.5% severe (>1000 microg/g) iron overload, although 28/40 patients (70%) had serum ferritin below 500 microg/L. Among many parameters, hepatic iron content was only correlated with ferritin (r= 0.324, P= 0.04). The receiver operating characteristic (ROC) analysis showed the best specificity/sensitivity ratio to identify iron overload for ferritin >340 microg/L (W = 0.716). Multivariate logistic regression analysis demonstrated that an increase in serum ferritin of 100 microg/L and female gender were independent variables associated with moderate to severe hepatic iron overload: OR 1.71 (95% CI 1.10 to 2.67) and OR 10.68 (95% CI 1.81 to 63.15), respectively. CONCLUSION: Hepatic iron overload is frequent in dialysis patients with ferritin below currently proposed high-end ranges, and the diagnostic power of ferritin in indicating true iron stores is better than presumed. Safety concerns should prompt a reevaluation of acceptable iron parameters, focusing on potential gender-specific differences, to avoid potentially harmful iron overload in a majority of dialysis patients, mainly females.

Autonomic neuropathy and QT interval in hemodialysed patients.

BACKGROUND: QT interval prolongation increases the risk of ventricular arrhythmias and sudden death in diabetic autonomic neuropathy and ischemic heart disease. In end-stage renal disease (ESRD), the effects of hemodialysis on QT interval are diverse and the influence of autonomic neuropathy has yet to be clearly defined. METHODS: Sixty-nine ERSD patients (age 64 +/- 14) were studied. Prior to the dialysis session, patients underwent four standard autonomic cardiovascular tests; before and after the dialysis session, a 12-lead ECG was recorded. Corrected QT intervals (QTc) were measured and QT dispersion (QTd) was calculated. Twelve subjects (age 59 +/- 6) with normal renal function served as control group. RESULTS: Compared to controls, ESRD patients showed a longer QTc (434 +/- 26 vs 414 +/- 28 ms; p = 0.016) and a similar QTd (35 +/- 13 vs 37 +/- 14 ms; p = 0.54).QTc was > 440 ms in 33.3% of the patients. No difference in the prevalence or score of autonomic neuropathy was observed between the subgroups with and without a prolonged QTc. After the hemodialysis session, QTc increased in 56% and decreased in 43% of the patients, and QTd increased in 45 % and decreased in 55% of the patients. QTc and QTd changes were not related to the presence of autonomic neuropathy. CONCLUSIONS: A large variability in QTc and QTd response was observed after hemodialysis. Autonomic neuropathy did not contribute to QTc and QTd length, nor to QTc and QTd change after dialysis.

Low-protein vegetarian diet with alpha-chetoanalogues prior to pre-emptive pancreas-kidney transplantation.

BACKGROUND: Pre-emptive pancreas-kidney transplantation is increasingly considered the best therapy for irreversible chronic kidney disease (CKD) in type 1 diabetics. However, the best approach in the wait for transplantation has not yet been defined. AIM: To evaluate our experience with a low-protein (0.6 g/kg/day) vegetarian diet supplemented with alpha-chetoanalogues in type 1 diabetic patients in the wait for pancreas-kidney transplantation. METHODS: Prospective study. Information on the progression of renal disease, compliance, metabolic control, reasons for choice and for drop-out were recorded prospectively; the data for the subset of patients who underwent the diet while awaiting a pancreas-kidney graft are analysed in this report. RESULTS: From November 1998 to April 2004, 9 type 1 diabetic patients, wait-listed or performing tests for wait-listing for pancreas-kidney transplantation, started the diet. All of them were followed by nephrologists and diabetologists, in the context of integrated care. There were 4 males and 5 females; median age 38 years (range 27.9-45.5); median diabetes duration 23.8 years (range 16.6-33.1), 8/9 with widespread organ damage; median creatinine at the start of the diet: 3.2 mg/dl (1.2-7.2); 4 patients followed the diet to transplantation, 2 are presently on the diet, 2 dropped out and started dialysis after a few months, 1 started dialysis (rescue treatment). The nutritional status remained stable, glycemia control improved in 4 patients in the short term and in 2 in the long term, no hyperkalemia, acidosis or other relevant side effect was recorded. Proteinuria decreased in 5 cases, in 3 from the nephrotic range. Albumin levels remained stable; the progression rate was a loss of 0.47 ml/min of creatinine clearance per month (ranging from an increase of 0.06 to a decrease of 2.4 ml/min) during the diet period (estimated by the Cockroft-Gault formula). CONCLUSIONS: Low-protein supplemented vegetarian diets may be a useful tool to slow CKD progression whilst awaiting pancreas-kidney transplantation.

Patient referral is influenced by dialysis centre structure in the Diamant Alpin Dialysis cohort study.

BACKGROUND: Late referral (LR) to the nephrologist of patients with progressing chronic kidney disease (CKD) has numerous deleterious effects and is observed in many countries. The contributing factors associated with LR are controversial and poorly defined. We hypothesized that these factors might be better identified by analysing patients starting dialysis in three distinct European countries within the same area. METHOD: The referral and progression of kidney failure patterns were analysed with demographic, clinical and biological data in 279 non-selected consecutive patients starting dialysis in eight centres of three adjacent regions in France, Italy and Switzerland. RESULTS: Early referral (>6 months before the start of dialysis) was seen in 200 patients (71.6%), intermediate referral (1-6 months) in 42 (15.1%) and LR (<1 month) in 37 (13.3%). However inter-centre variations were between 2 and 19% for LR and 6-50% for combined late and intermediate referral. There were no differences at the national levels, but LR was more frequent in the large city centres than in the private or regional structures, with 31 out of 169 (18.3%), two out of 55 (5.4%) and four out of 55 (7.3%), respectively, of their patients (P<0.01). By multivariate analysis, it appears that, besides the presence of an active cancer and the CKD progression rate, the centre structure and the referring physician (primary care physicians and nephrologists are less responsible for LR than other medical specialists) play a significant role in the practice of LR. CONCLUSIONS: Within a dialysis cohort spread over adjacent regions of three countries, LR has the same global distribution pattern, indicating that different health and social security systems do not play a major role in inducing or preventing this practice. The contributing factors for LR that were identified are the type of the referring physician and the structure of the dialysis unit. Both factors are potential targets for an educational and collaborative approach.

Vascular access survival and morbidity on daily dialysis: a comparative analysis of home and limited care haemodialysis.

BACKGROUND: Concerns about vascular access failure may have limited the widespread use of daily haemodialysis (DHD). We assessed the incidence and type of vascular access complications during DHD and other schedules, both at home and on limited care haemodialysis. METHODS: All patients were treated in a limited care and home haemodialysis unit with a stable caregiver team (November 1998-November 2002). Vascular access failure, surgical treatment, angioplasty and declotting were studied alone or in combination by univariate and multivariate models. We analysed the effects of age, sex, comorbidity, previous vascular events, schedule, setting of treatment (home, limited care), dialysis follow-up, vascular access (native vs prosthetic, first vs subsequent) and setting of vascular access creation. 'Intention to treat' and 'per protocol' analyses were performed. RESULTS: In 2160 patient-months (home dialysis: DHD 400 months, non-DHD 655 months; limited care: DHD 208 months; non-DHD 897 months), 57 adverse events occurred (27 failures), in which 30 were at home (nine DHD) and 27 were in limited care (five DHD). The probability of remaining free from adverse events at 6 and 12 months was 89% and 80% on DHD and 79% and 76% on other schedules ('intention to treat'). Univariate analyses revealed a significant difference for the setting of the vascular access creation (lower risk of vascular access complications in our centre) and sex (male sex was protective). Logistic regression and Cox analyses confirmed the role for the setting of the vascular access creation. CONCLUSIONS: Although DHD did not appear as a risk factor for vascular access morbidity or failure at home or in a limited care centre setting, the setting of vascular access creation may influence its success.

Patients on renal replacement therapy for 20 or more years: a clinical profile.

BACKGROUND: Long-term survivors are living evidence of the goals and limits of renal replacement therapy (RRT). METHODS: A cross-sectional study was performed on all cases (188 patients) with RRT follow-up >/=20 years in Piemonte, northern Italy (4 350 000 inhabitants, 22 dialysis centres). Study included revision of clinical charts and assessment of functional (Karnofsky scale, Ks) and nutritional status (subjective global assessment, SGA). According to treatment history, patients were sorted into three groups: group 1, 56 patients always on dialysis; group 2, 40 patients on dialysis with previous graft; group 3, 92 grafted patients. RESULTS: Age differed between group 1 and groups 2 and 3 (59.5+/-11.5 vs 51.5+/-7.9 and 51.0+/-9.0 years; P=0.001). Prevalence of comorbidity was higher in groups 1 and 2 (94.6% and 95%) compared with group 3 (81.5%), reflecting selection during follow-up. Twenty-two cases (11.7%) had no comorbidity; these patients were younger (44.3+/-8.5 years) and 17 out of 22 had a functioning graft. The most common comorbidities were vasculopathy (73.4%), bone disease (72.9%) and cardiopathy (33.5%). Severe visual impairment was a common problem (18%), with a higher prevalence in patients with cardiovascular comorbidity (32%). Severe depression was found in 13.3% of cases. Despite comorbidity, functional scores (Ks) were good (higher in group 3 (88.1+/-15) than in groups 1 and 2 (67.9+/-21.9 and 75.5+/-18, respectively); P=0.000) and 64% of patients were well nourished. The combination of cardiovascular comorbidity, bone disease and visual impairment may reflect the premature ageing of RRT patients. CONCLUSION: Despite the high prevalence of comorbidity, long-term follow-up may promote good clinical conditions at least in some patients, highlighting the therapeutic potentials of dialysis in an era of reconsideration of open acceptance of RRT.