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.

Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists.

BACKGROUND: Methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) is the most common disorder of cobalamin intracellular metabolism, an autosomal recessive disease, whose biochemical hallmarks are hyperhomocysteinemia, methylmalonic aciduria and low plasma methionine. Despite being a well-recognized disease for pediatricians, there is scarce awareness of its adult presentation. A thorough analysis and discussion of cobalamin C defect presentation in adult patients has never been extensively performed. This article reviews the published data and adds a new case of the latest onset of symptoms ever described for the disease. RESULTS: We present the emblematic case of a 45-year-old male, describing the diagnostic odyssey he ventured through to get to the appropriate treatment and molecular diagnosis. Furthermore, available clinical, biochemical and molecular data from 22 reports on cases and case series were collected, resulting in 45 adult-onset CblC cases, including our own. We describe the onset of the disease in adulthood, encompassing neurological, psychiatric, renal, ophthalmic and thromboembolic symptoms. In all cases treatment with intramuscular hydroxycobalamin was effective in reversing symptoms. From a molecular point of view adult patients are usually compound heterozygous carriers of a truncating and a non-truncating variant in the MMACHC gene. CONCLUSION: Adult onset CblC disease is a rare disorder whose diagnosis can be delayed due to poor awareness regarding its presenting insidious symptoms and biochemical hallmarks. To avoid misdiagnosis, we suggest that adult onset CblC deficiency is acknowledged as a separate entity from pediatric late onset cases, and that the disease is considered in the differential diagnosis in adult patients with atypical hemolytic uremic syndromes and/or slow unexplained decline in renal function and/or idiopathic neuropathies, spinal cord degenerations, ataxias and/or recurrent thrombosis and/or visual field defects, maculopathy and optic disc atrophy. Plasma homocysteine measurement should be the first line for differential diagnosis when the disease is suspected. To further aid diagnosis, it is important that genes belonging to the intracellular cobalamin pathway are included within gene panels routinely tested for atypical hemolytic uremic syndrome and chronic kidney disorders.

Nephrotoxicity in advanced thyroid cancer treated with tyrosine kinase inhibitors: An update.

Over the past decade, the prognosis of advanced thyroid cancer (TC) patients has dramatically improved thanks to the introduction of tyrosine kinase inhibitors (TKIs). Despite their effectiveness, these drugs are burdened with several side effects that can negatively affect quality of life and compromise therapy continuation. Among renal adverse events (RAEs), proteinuria is the most frequently reported in clinical trials and real-life experiences, especially during treatment with lenvatinib or cabozantinib. This peculiar toxicity is commonly associated with targeted therapies with anti-angiogenic activity, even if the mechanisms underlying its onset and progression are not entirely clear. RAEs should be early recognized and properly managed to avoid renal function worsening and life-threatening consequences. Aiming at providing a comprehensive summary that can help clinicians to identify and manage TKIs-related RAEs in TC patients, we reviewed the current evidence about this topic, from pathogenesis and potential risk factors to diagnosis and treatment.

Organizational determinants of hospital stay: establishing the basis of a widespread action on more efficient pathways in medical units.

Given the high hospital costs, the increasing clinical complexity and the overcrowding of emergency departments, it is crucial to improve the efficiency of medical admissions. We aimed at isolating organizational drivers potentially targetable through a widespread improvement action. We studied all medical admissions in a large tertiary referral hospital from January 1st to December 31st, 2018. Data were retrieved from the administrative database. Available information included age, sex, type (urgent or elective) and Unit of admission, number of internal transfers, main ICD-9 diagnosis, presence of cancer among diagnoses, surgical or medical code, type of discharge, month, day and hour of admission and discharge. National Ministry of Health database was used for comparisons. 8099 admissions were analyzed. Urgent admissions (80.5% of the total) were responsible for longer stays and were the object of the multivariate analysis. The variables most influencing length-of-stay (LOS) were internal transfers and assisted discharge: they contributed, respectively, to 62% and 40% prolongation of LOS. Also, the daily and weekly kinetics of admission accounted for a significant amount of variation in LOS. Long admissions (≥ 30 days) accounted for the 15.5% of total bed availability. Type of discharge and internal transfers were again among the major determinants. A few factors involved in LOS strictly depend on the organizational environment and are potentially modifiable. Re-engineering should be focused on making more efficient internal and external transitions and at ensuring continuity of the clinical process throughout the day and the week.

[Bone protection in corticosteroid treated patients]. / Indagine sulla terapia di prevenzione del danno osseo nei pazienti trattati con corticosteroidi in Piemonte e valle d'Aosta.

The Piedmont Group of Clinical Nephrology compared the activity of 15 nephrology centers in Piedmont and Aosta Valley as regards bone protection in patients on corticosteroids therapy. Fracture prevalence shows great variability: in 4/15 centers (27%) no fractures were found, in 6/15 centers (40%) fractures were present in 1-4% of cases, in 1 center in 18% of patients. Clinical risk of fracture was based on sex, age and postmenopausal status in 11/14 of the centers (79%), history of fractures and bone disease in 4/14 centers (27%), smoking and alcohol consumption in 3 and 2 centers respectively, glucocorticoid dose and duration in 4, in children bone age and calcium phosphorus status. Dual energy X-ray absorptiometry was performed in 12 centers based on risk factors, in 8 (57%) DXA was performed during the follow-up, in 4 it was performed after 12 months and in 2 after 2-3 years. DXA is not prescribed in children. Only in one center, risk assessment is based on FRAX. Most of the patients are treated with vitamin D supplementation at a dose of steroids of 5 mg/d (80%). Calcium carbonate is used in 9 centers (60%), in two it is used only in the presence of low ionized calcium or bone mineral density. Bisphosphonates are used following AIFA prescription, in particular alendronate in all centers, risedronate in seven and denosumab in one. The analysis shows the great variability of the clinical and therapeutic approach regarding bone protection in patients on corticosteroids therapy, in Piedmont and Aosta Valley.

[Focal and segmental glomerulosclerosis in Piedmont and the Aosta Valley in Italy: case study and treatment]. / La glomerulosclerosi focale e segmentaria in Piemonte e Valle d'Aosta: casistica e trattamento.

In 2012, the Piedmontese Clinical Nephrology Group retrospectively analyzed a cohort of patients diagnosed with focal and segmental glomerulosclerosis (FSGS) in Piedmont and the Aosta Valley, with a special focus on frequency of disease, choice and duration of treatment at disease onset and during relapses. Seventeen centers participated. The total number of FSGS cases was 467: 148 were diagnosed between 1991 and 2000 and 319 between 2001 and 2010, corresponding to a 127% increase in the latter decade. First-line treatment in 9 centers was full-dose corticosteroid (CS) for 4 months with 8 centers using CS for 2-3 months. One center used additional iv CS pulse treatment. Dosage tapering lasted 3-9 months; in one center dose tapering lasted for less than 3 months. During first relapse, 10 centers used CS as drug of choice, 4 centers CS and cyclosporin (CyA), 3 centers CS and cyclophosphamide (CyF), with one center using chlorambucil instead of CyF. In 2 centers CyA or CyF were each considered appropriate and employed on an individual basis. Only one center considered mycophenolate (MMF) as a treatment option. If multiple relapses occurred, 14 centers chose CyA as drug of choice, 2 centers CyF (in association with low-dose CS) and 1 center did not report any multiple relapses. Eight centers proposed a variation in therapeutic approach: MMF (5), Rituximab (3), Tacrolimus (1), CyF (1), ACTH (1). If CS dependence occurred, the maximum dose allowed was considered to be 15 mg/day in 2 centers, 12.5 mg/die in 4 centers, 10 mg/die in 4 more centers, 7.5 mg/die in 1 center, and 5 mg/die in a further one. Three centers did not refer any experience with CS dependence. Only 4 centers had direct experience with MMF and maintained treatment for about 3 years. In relapsing cases with a good response to CyA, the drug was discontinued after 5 years in 2 centers, after 3 years in 2 centers, 2 years in 4 centers, 1 year and a half in 2 centers, and 1 year in 3 centers. CyA was used as a long-term treatment in 3 centers. In conclusion, Piedmontese nephrologists followed K-DOQI guidelines in typical cases of FSGS. When the disease presents with an atypical course nephrologists' decisions appeared to be influenced by their experience with atypical drugs, such as MMF and Rituximab. Studies with other drugs are needed to improve the prognosis of forms of FSGS resistant to current treatments, which have remained virtually unchanged since the 1970s.

[Renal biopsy practice in Piedmont and Valle d'Aosta]. / Indagine sulle modalità di esecuzione delle biopsia renale in Piemonte e Valle d'Aosta.

In 2010 a questionnaire was administered to the renal units of Piedmont and Valle d'Aosta to analyze their procedures for renal biopsy (RB). Seventy-eight percent of units performed RBs, 57% for more than 20 years, but only 43% performed at least 20 BRs per year. 20/21 units performed RB in an inpatient setting and 1/21 in day hospital with the patient remaining under observation the night after. Thirty-two percent did not consider a single kidney as a contraindication to RB, 59% considered it a relative contraindication and 9% considered it an absolute contraindication. In 90.5% of units there was a specific protocol for patient preparation for RB and 86% used a specific informed consent form. Ninety-five percent of units performed ultrasound-guided RB, 60% of them using needle guides attached to the probe. In 81% of units the left side was preferred; 71% put a pillow under the patient's abdomen. All units used disposable, automated or semi-automated needles. Needle size was 16G in 29%, 18G in 58%, and both 16G and 18G in 14% of units; 1 to 3 samples were drawn. One third of units had a microscope available for immediate evaluation of specimen adequacy. After RB, 86% of units kept patients in the prone position for 2-6 hours and all prescribed a period of bed rest (at least 24 hours in 90.5%). 90.5% of units followed a specific postbiopsy observation protocol consisting of blood pressure, heart rate and red blood cell measurements at different times, and urine monitoring and ultrasound control within 12-24 hours (only half of them also employing color Doppler). One third of all units discharged patients after 1 day and two thirds after 2-3 days; all prescribed abstention from effort and from antiplatelet drugs for 7-15 days. In 9 units both RB and tissue processing and examination were done in the same hospital, while 12 units sent the samples elsewhere. 76% obtained results in 2-4 days, 19% in 6-7 days, and 5% in 10-15 days. Less than 20% of the interviewed operators were fully familiar with the clauses of hospital insurance securing their activity. Use of RB is widespread in Piedmont and Valle d'Aosta but its practice shows variation between centers.

[Restrospective analysis of the renal biopsy activity in Piedmont]. / Indagine retrospettiva sull'esecuzione delle biopsie renali in Piemonte.

The Piedmont Group of Clinical Nephrology has compared the activity of 18 nephrology centers in the region Piedmont/Valle d'Aosta with regard to renal biopsy (RB). Data on the RBs performed in every nephrology unit, taking into account their entire experience (in some cases spanning more than 30 years), were analyzed. 3396 RBs were performed between 1996 and 2011. Thirty to forty percent were done in patients aged >-65 years (1568 in patients >-65 years, 29 in patients >-85 years). 598 BRs were performed in children over the last 20 years. The following contraindications to RB were considered: chronic renal failure by 8 centers (44.4%), serum creatinine (SCr >3 mg/dL) by 3 centers, longitudinal renal size <8 cm by 3 centers, and renal cortex thickness <1 cm by 2 centers. 1798 RBs were performed in patients with SCr >2 mg/dL and 275 in patients on dialysis. The percentage of RBs performed in patients with SCr >2 mg/dL ranged from 27% to 55% between centers. As regards RB in the course of acute renal failure in an ANCA-positive context, 4 centers allowed administration of corticosteroids and 8 centers administration of immunosuppressive treatment as well, even in the absence of histological data. In drug-related nephropathies, RB was considered indicated to confirm the farhypothesis of immunoallergic interstitial nephropathy either if the responsible drug was not among the traditional ones known to induce tubulo-interstitial renal disease or if the pharmacological hypothesis seemed no longer sufficient to justify the renal presentation. All centers but one were against performing RB in case of atheroembolic disease. Three centers performed RB in the intensive care unit. As regards RB in patients undergoing treatment with anticoagulants, aspirin was discontinued 5-14 days before the procedure (mean 8 days) and given again 7-15 days afterwards (mean 11.4 days). Ten centers replaced the anticoagulants with low-dose heparin, which was discontinued the day before the procedure; 11 centers asked advice from cardiologists. RB was repeated in 113 cases after a delay of 1 month to 8 years from the first RB. Our analysis shows uniformity in the approach to RB in this Italian region, with some differences compared with the literature: particular attention was paid to severely critical patients, elderly patients, and patients treated with anticoagulant drugs.

[Application of guidelines in clinical practice: a multicenter analysis of the treatment of membranous glomerulonephritis in Piedmont, Italy]. / Applicazione delle linee-guida nella realta' clinica: indagine multicentrica sul trattamento della glomerulonefrite membranosa in Piemonte.

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

Renal involvement in systemic amyloidosis--an Italian retrospective study on epidemiological and clinical data at diagnosis.

BACKGROUND: Few data are available on epidemiology and clinical picture of renal involvement in different forms of systemic amyloidosis. METHODS: Patients with biopsy-proven systemic amyloidosis diagnosed in Italy between January 1995 and December 2000 were selected from 49 Nephrology and Internal Medicine Units provided they showed signs characteristic of renal involvement. Clinical and laboratory information were collected by using a specific data form for diagnosis integrated by a questionnaire on diagnostic tools. Collected data were matched both with the Italian Registry of Renal Biopsies (IRRB) and the Registry of the Italian Society of Amyloidosis (SIA) in order to approximate the incidence of the disease. RESULTS: Of all patients, 373 were finally selected throughout Italy with an estimated mean incidence of renal amyloidosis of 2.1 per million population (p.m.p.) per year. Of those, 237 were affected from AL (primary) amyloidosis, 104 from AA (secondary) amyloidosis and 6 from AF (heredofamilial) forms. In 26 cases the type of amyloidosis remained undetermined. Among patients with AL, 36 presented an associated multiple myeloma (MM). Rheumatoid arthritis (RA) was the commonest underlying disease in AA. Median age ranged between 63 and 65 years in all groups. Males were prevalent in AL and females in AA. The main clinical features of renal involvement were represented by nephrotic syndrome and renal failure observed in 59 and 54% of cases, respectively. The presence of a lambda light chain, either in serum or urine was significantly associated to a more elevated urinary protein loss and to a reduced renal function. Patients with AA showed a worse renal function at presentation than patients with AL, possibly due to a late diagnosis and/or referral to nephrology units. Diagnosis was obtained by renal biopsy in 315 cases, by abdominal fat tissue (AFT) aspiration/biopsy in 156 patients and by other organ biopsies in 47 patients. Characterization of deposits was extremely variable among referring centres. CONCLUSIONS: Our results point to an increased incidence of renal amyloidosis observed in Italy over the period 1996-2000 with AL as the prevalent type. Characterization of amyloid deposits still remains the major diagnostic challenge of the disease. The institution of networks dedicated to rare diseases is strongly recommended in order to effectively afford this challenge.