Alessandro Amore

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.

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 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.

The refinement of our knowledge of the functioning of the immune system, both innate and adaptive, in the last decade has fundamentally modified the interpretation of the pathogenesis of systemic lupus erythematosus (SLE). In this autoimmune disease the main pathogenetic mechanism leads to the production of autoantibodies specific to self antigens (tolerated or not) favored by a genetic condition and triggered by endogenous factors, such as estrogens or exposure to sunlight, and exogenous factors, such as viruses. T cells were thought to play a predominant role. The identification of a population of B cells located in marginal areas of the germinal centers and equipped with receptors belonging to the family of Toll-like receptors (TLR) (either extracellular, such as TLR4, or intracellular, such as TLR3, which recognize DNA and RNA) and High Mobility Box Protein 1 (HMBP1), capable in a T-independent manner of self-reactive activities with IgG autoantibody production and release, has greatly advanced the understanding of the pathogenesis of SLE. The T and B lymphocyte populations interact in complex ways, with interference of tolerance-inducing regulatory T cells and inflammation-inducing Th17 cells, finely regulating the cross-talk in the lymphocyte system. This review will discuss the latest knowledge on the pathogenesis of SLE.

Over the last 20 years a large body of evidence has demonstrated that in chronic renal failure there is progressive chronic inflammation, which increases after the start of dialysis. In this phase a fundamental role is played by bioincompatibility reactions induced by contact with the different dialysis materials: membranes, plastic lines, dialysis fluids as well as contaminants present in water. Clinically evident symptoms induced by bioincompatibility reactions are usually taken into serious account by nephrologists, while more subtle chronic effects, noxious in the long term, are often underconsidered. Since the 1990s many efforts have been addressed to membrane improvement and water treatment, while there is still a lot to be done for better dialysates. Acetate dialysis is routinely used in only about 5% of patients worldwide but over 80% of patients are exposed to the lower acetate concentrations present in standard bicarbonate dialysate. These concentrations are not negligible and are able to induce chronic reactions mainly converging on the endothelium, stimulating and maintaining the atherogenesis process with important long-term implications for cardiovascular morbidity. This review presents and discusses the available data on the cellular and molecular effects induced by acetate, even at low concentrations.

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.

Experimental and clinical evidence supports the involvement of inflammation and innate immunity in chronic renal disease. Immune dysfunction in end-stage renal