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.

Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.

OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73±115.9, at day 14: 302.2±126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.

[Renal Infarction: multicentric cases in Piedmont].

We describe factors associated to renal infarction, clinical, instrumental and laboratoristic features, and therapeutic strategies too. This is an observational, review and polycentric study of cases in Nephrologic Units in Piedmont during 2013-2015, with diagnosis of renal infarction by Computed Tomography Angiography (CTA). We collected 48 cases (25 M, age 57±16i; 23 F age 70±18, p = 0.007), subdivided in 3 groups based on etiology: group 1: cardio-embolic (n=19) ; group 2: coagulation abnormalities (n= 9); group 3: other causes or idiopathic (n=20). Median time from symptoms to diagnosis, known only in 38 cases, was 2 days (range 2 hours- 8 days). Symptoms of clinical presentation were: fever (67%), arterial hypertension (58%), abdominal o lumbar pain (54%), nausea/vomiting (58%), neurological symptoms (12%), gross hematuria (10%). LDH were increased (>530 UI/ml) in 96% of cases (45 cases out of 47), PCR (>0.5 mg/dl) in 94% of cases (45 out of 48), and eGFR <60 ml/min in 56% of cases (27 out of 48). Comparison of the various characteristics of the three groups shows: significantly older age (p=0.0001) in group 1 (76±12 years) vs group 2 (54±17 years) and group 3 (56±17 years); significantly more frequent cigarette smoking (p = 0.01) in group 2 (67%; 5 cases out of 9) and group 3 (60%; 12 cases out of 20) than group 1 (17%). No case has been subjected to endovascular thrombolysis. In 40 out of 48 cases, anticoagulant therapy was performed after diagnosis: in 12 (32%) cases no treatment, in 12 cases (30%) heparin, in 8 cases (20%) low molecular weight heparin, in 4 cases (10%) oral anticoagulants, in 3 cases fondaparinux (7%), in 1 case (2%) dermatan sulfate. CONCLUSIONS: Although some characteristics may guide the diagnosis, latency between onset and diagnosis is still moderately high and is likely to affect timely therapy.

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.

[Severe hyperkalemia in patients referred to an emergency departement: the role of antialdosterone drugs and of renin-angiotensin system blockers]. / Iperpotassiemia severa in pazienti afferenti ad un pronto soccorso: ruolo degli antagonisti dell'aldosterone e dei modulatori del sistema renina-angiotensina.

We analyzed the clinical features and the factors associated with the presence of hyperkalemia (serum potassium >5.3 mmol/L) in a cohort of patients presenting to an Emergency Department. A total of 168 cases were observed (89 males and 79 females), mean age 77.512 years. Fifty-six patients were diabetics (33.3%), 51 patients had chronic kidney disease (30%) and 36 patients with cardiac failure (21.4%). Sixty-nine patients (41%) were treated with RAS-blockers (ACE-I n = 50; ARBs, n = 19). 65 subjects were taking loop diuretics (39%), 17 (10%) thiazides. Thirty-one (18%) were assuming antialdosterone drugs; 16 (52%) out of these had a positive history of heart failure and 14 (41%) had a positive history of chronic kidney disease. In 85 cases (51%) patients were receiving an ACE/ARB or an antialdosterone drug. In 125 patients (74%) eGFR at presentation was <60 ml/min/1.73 m2. Serum potassium values were significantly higher in patients treated with both ACE/ARB and antialdosterone drugs. In 20 cases (12%) serum potassium was 6.5 mmol/L; these patients assumed antialdosterone drugs more frequently, alone and mostly in association with ACE-I/ARBs (65% vs 7%; p<0.0001). The simultaneous assumption of ACE-I/ARBs and antialdosterone drugs emerges as the major cause of severe hyperkalemia in our cases, thus confirming the warnings about this association in the presence of advanced age and reduced glomerular filtration rate.

[Acute pielonephritis and renal abscesses in Piedmont and Aosta Valley]. / Indagine sulla pielonefrite acuta e sugli ascessi renali in Piemonte e Valle d'Aosta.

The Piedmont Group of Clinical Nephrology compared the activity of 18 nephrology centers in Piedmont and Aosta Valley as regards acute pielonephritis (APN). Data from more than 500 cases per year of APN were examined. The microbial spectrum of APN consists mainly of Escherichia coli and Klebsiella pneumoniae. Diagnosis was based on both clinical and radiological criteria in most of the centers (computed tomography-CT o Magnetic Resonance Imaging-MRI). In four centers diagnosis was made with the radiological criteria and in one center only with the clinical features. CT and MRI were performed in about 47% and 44% of cases respectively. Urine culture was positive in 22 up to 100% of cases. The most commonly used antibiotics were fluoroquinolones (ciprofloxacin or levofloxacin) and ceftriaxone (50% of centers) or amoxicillin/clavulanic acid (25% of centers). In 75% of the centers, patients received a combination of two antibiotics (aminoglycoside in 22% of them ). In 72% of the centers, almost 50% of the patients were re-examined, while 38.8% of centers re-examined all the patients. Renal ultrasound was inappropriate to identify abscesses. The mean of patients in whom renal abscesses were detected by CT or MRI was 18.2%. The analysis shows a high variability in the way of diagnosing and treating APN in Piedmont and Aosta Valley regions. This suggests that even if APN is a frequent pathological condition, practical recommendations are required.

Excess dietary sodium and inadequate potassium intake by hypertensive patients in Italy: results of the MINISAL-SIIA study program.

INTRODUCTION: The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population. METHODS: A total of 1232 hypertensive patients were recruited consecutively by 47 centers recognized by the Italian Society of Hypertension. The enrolled participants were on stable antihypertensive treatment. Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium excretion were measured and used as proxy for the average daily sodium and potassium intake. RESULTS: The average sodium intake was 172  mmol (or 10.1  g of salt/day) among men and 138 (or 8.1) among women, with no difference among geographical areas. Over 90% of men and 81% of women had a consumption higher than the recommended standard dietary intake of 5  g/day. The average potassium intake was 63 and 56  mmol, respectively in men and women, again without geographical differences, nearly 92% of men and 95% of women having an intake lower than the recommended intake (100  mmol/day or 3.9  g/day). There was a significant trend to a gradual decrease in sodium intake with age in both sexes (P <0.001). There was also a direct association between BMI and sodium intake in both sexes, this association being independent of age (P < 0.001). CONCLUSION: In this national sample of the Italian hypertensive population, dietary sodium intake was largely higher and potassium intake much lower than the recommended intakes, and this was true for all geographical areas. Overweight and obese hypertensive patients had particularly high sodium intakes.

[Immigrants and dialysis: a survey in Piedmont]. / Immigrazione e uremia: indagine nei centri dialisi del Piemonte.

The number of immigrants has been rapidly increasing in Italy in the last decade, with potentially profound effects on the national health care system. Yet, few data are available on the clinical and demographic features of these subjects, or on their need for nephrological care and dialysis treatment. A survey was conducted in 19 dialysis facilities of Piedmont (a northwestern Italian region) about immigrants on chronic dialysis treatment. Data on native country, administrative position, clinical and dialysis aspects were anonymously collected. Overall, 93 immigrant dialysis patients coming from 24 foreign countries were registered. Most of them were young (mean age 46∓14 years) and on extracorporeal treatment (87%); late referral (38%) or starting dialysis in emergency (17%) were common modalities of presentation. Glomerular (33%) or unknown (31%) nephropathies were the most representative causes of end stage renal disease. No difference in incidence of HCV, HBV and HIV compared with native Italian patients was observed. Notably, more than 50% of the immigrant patients had low-level knowledge of Italian. As regards administrative position, 69% were regular foreign citizens, 19% were temporary foreign workers, and 9% had a residence permit. Our survey confirms the existence of a young immigrant population on dialysis in Piedmont, whose social and relational problems are more challenging than clinical aspects and call for new organizational models to manage this growing population on dialysis.

Is it possible to diagnose primary anti-phospholipid syndrome (PAPS) on the basis of renal thrombotic microangiopathy (PAPS nephropathy) in the absence of other thrombotic process?

The kidneys are a major target of PAPS. The histologic lesions of PAPS nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most characteristic. It is still not clear in the literature whether the nephropathy can be the unique manifestation of PAPS in the absence of other thrombotic processes; that is: do the renal microthrombotic lesions allow to make the diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this purpose we present three clinical cases. The first patient had severe hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive. The histologic picture was characterized by basement membrane reduplication and arteriolar mucoid degeneration, which are features of early phase of TMA. The second patient had severe hypertension. The detection of anti-cardiolipin antibodies was performed several times and resulted positive three times, four months after the diagnosis as well. The renal histologic features were consistent with late lesions of TMA. The third patient had severe hypertension, rapidly progressive renal failure, tricuspidal valve insufficiency and two positive anti-phospholipid antibodies determinations three weeks apart (in two occasions anti-cardiolipin and in one occasion LAC as well were found). The renal lesions were characteristic for TMA. In conclusion we think that patients with TMA and antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.

The verapamil versus amlodipine in nondiabetic nephropathies treated with trandolapril (VVANNTT) study.

BACKGROUND: We tested whether the combination of verapamil (V) or amlodipine (A) with trandolapril (T) affected proteinuria differently from T alone in patients with nondiabetic nephropathies. METHODS: After T, 2 mg, in open conditions for 1 month, 69 patients were randomly assigned to be administered T, 2 mg, combined with V, 180 mg, plus a placebo or T, 2 mg, plus A, 5 mg, once a day in a double-blind fashion. Patients were followed up for 8 months. RESULTS: Proteinuria diminished significantly after T treatment from mean protein excretion of 3,078 +/- 244 (SEM) to 2,537 +/- 204 mg/24 h (P = 0.018). In the randomized phase, there was a slight reduction in proteinuria in both groups without significant differences within and between treatments (T + V, protein from 2,335 +/- 233 to 2,124 +/- 247 mg/24 h; T + A, protein from 2,715 +/- 325 to 2,671 +/- 469 mg/24 h). The selectivity index (SI; calculated as the ratio of immunoglobulin G to albumin clearance) was slightly and not significantly reduced in patients treated with T plus V from a median of 0.20 (interquartile range, 0.13) to 0.16 (interquartile range, 0.15; P = not significant), whereas it significantly increased from 0.20 (interquartile range, 0.14) to 0.30 (interquartile range, 0.14; P = 0.0001) in patients treated with T plus A. Modifications in SI and serum creatinine levels at the end of the study from randomization were significantly directly correlated (r = 0.45; P = 0.001). The number of patients reporting adverse effects was significantly higher in the T plus A than T plus V group (63.8% versus 33.3%; P = 0.016). CONCLUSION: In patients with nondiabetic proteinuric nephropathies treated with T, the combination of V or A does not significantly increase its antiproteinuric effect.

Selective stenting and the course of atherosclerotic renovascular nephropathy.

BACKGROUND: The effectiveness of percutaneous revascularisation (PTRA) in the treatment of atherosclerothic renovascular nephropathy (ARN), a leading cause of progressive renal failure, is still a matter of debate. METHODS: we reviewed 52 patients submitted to selective stenting from 1991 to 2000 because of ARN, followed for a mean of 22.3 months before and 24.6 after the procedure, looking for complications, re-stenosis rates, blood pressure, renal function and survival. RESULTS: Arterial patency was achieved in 97.1% of procedures (71.6% by stent deployment); complications occurred in 42% of patients, and re-stenoses in 17.3% of vessels, most often in those without a stent (31.6% vs 8.3%). No effect was detectable on hypertension and renal failure in the whole group, but in the subgroup without technical failure or early dialysis start PTRA reduced the creatinine clearance (BCRC) decline from 0.9 to 0.19 mL/min/month. At univariate analysis, BCRC outcome was better in bilateral or single kidney stenoses, proteinuria < 1 g/day, serum creatinine < 4 mg/dL and resistance index < 0.8. Survival was 68.9% at five years, with a mortality rate of 4.5/100 person-years. CONCLUSIONS: Renal outcome of successful PTRA differs from case to case, but efficacy is substantial. Primary stenting in ostial stenosis and selection of patients based on prognostic factors seem likely to improve the effectiveness.

Acute pyelonephritis: analysis of 52 cases.

Acute pyelonephritis (APN) is a frequent disease, but diagnostic approach, evolution into abscesses, and indication to hospitalization are still open problems. We have made a retrospective analysis of APN cases observed in our hospital. We identified 58 patients (pt) and selected 52 of these who presented fever and loin pain at the onset (31 were hospitalized in Nephrology and 21 in other units). Urine culture was positive in 11/48 cases (22.9%), blood cultures in 3/26 cases (11.5%) (Escherichia coli). Renal sonography was normal in 20/48 cases (41.6%) and suggestive for APN in 23/48 cases (47.9%). CT with contrast medium was normal in 9/28 cases (32.1%) and positive in 19/28 cases (67.8%), with evidence of unique or multiple hypodense areas; abscesses were found in 8 patients (28.5%). No statistically significant differences were found between patients with positive or negative CT as regards fever, leukocytosis, ESR, CRP, CRP at 20 days, urinary leukocytes, urine culture, duration of symptoms before hospitalization. Moreover no differences were found between patients with and without abscesses. CT was performed more frequently among patients hospitalized in Nephrology than among patients hospitalized in other services (24/31-77.4%-vs. 4/21-19%-, p = 0.05). NMR was abnormal in 6/9 cases. A radiographic documentation of APN was obtained in 61.53% of patients with clinical diagnosis of APN. Of these, only 18.7% had positive urine culture. In conclusion, our data suggest that demonstration of urine infection is not necessary for APN diagnosis, when clinical and/or radiologic diagnosis of APN has been made. Evolution into abscesses is frequent and not easily susceptible on clinical ground; for this reason we think it is advisable to perform CT or NMR systematically. Differences in clinical behavior between different units suggest the need for diagnostic guidelines.

Salt intake and kidney disease.

We have reviewed the role of salt intake in kidney diseases, particularly in relation to renal hemodynamics, renal excretion of proteins, renal morphological changes and progression of chronic renal failure. High salt intake may have detrimental effects on glomerular hemodynamics, inducing hyperfiltration and increasing the filtration fraction and glomerular pressure. This may be particularly important in elderly, obese, diabetic or black patients, who have a high prevalence of salt-sensitivity. Changes in salt intake may influence urinary excretion of proteins in patients with essential hypertension, or diabetic and non diabetic nephropathies. Moreover, high sodium intake may blunt the antiproteinuric effect of various drugs, including angiotensin-converting-enzyme inhibitors and calcium antagonists. Experimental studies show a direct tissue effect of salt on the kidney, independent of its ability to increase blood pressure, inducing hypertrophy, fibrosis and a decrease in glomerular basement membrane anionic sites. However, no firm conclusion can be drawn about the relationship between salt consumption and progression of chronic renal failure, because most information comes from conflicting, small, retrospective, observational studies. In conclusion, it would appear that restriction of sodium intake is an important preventive and therapeutic measure in patients with chronic renal diseases of various origin, or at risk of renal damage, such as hypertensive or diabetic patients.