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Background: Systemic steroids are recommended for patients with IgA nephropathy (IgAN) and proteinuria. However, there are concerns about their safety due to an excess of serious adverse events (SAEs) in previous randomised trials. This study evaluates the incidence of SAEs in IgAN patients receiving different treatment regimens in clinical practice., Methods: Multicentre, retrospective, observational cohort study of 1209 patients (M/F: 864/345, mean age: 41.73 ± 14.92 years) with biopsy-proven IgAN treated with renin angiotensin system (RAS) inhibitors (RASI) (n = 285), intravenous + oral steroids (n = 633), oral steroids (n = 99), steroids + immunosuppressants (n = 192)., Results: A total of 119 (9.8%) adverse events were reported, of which 67 (5.5%) were considered treatment-emergent, and 36 (2.9%) were SAEs (n = 23, 63.8% were infections). One patient died due to sepsis. A significant association was observed between AEs and immunosuppression [8 (2.8%) in RASI, 60 (9.4%) in steroids + immunosuppressants, 14 in oral steroids (14.1%) and 37 pts (19.2%) in steroids + immunosuppressants (p < 0.01)], age and estimated glomerular filtration rate (eGFR), but not with proteinuria and sex. On multivariate analysis, only older age was associated with the occurrence of SAEs., Conclusions: According to our findings, the incidence of SAEs during therapy with steroids alone or associated with immunosuppressors is lower in everyday clinical practice than in randomised clinical trials., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: A considerable minority of patients on waiting lists for kidney transplantation either have no diagnosis (and fall into the subset of undiagnosed cases) because kidney biopsy was not performed or histological findings were non-specific, or do not fall into any well-defined clinical category. Some of these patients might be affected by a previously unrecognised monogenic disease., Methods: Through a multidisciplinary cooperative effort, we built an analytical pipeline to identify patients with chronic kidney disease (CKD) with a clinical suspicion of a monogenic condition or without a well-defined diagnosis. Following the stringent phenotypical and clinical characterization required by the flowchart, candidates meeting these criteria were further investigated by clinical exome sequencing followed by in silico analysis of 225 kidney-disease-related genes., Results: By using an ad hoc web-based platform, we enrolled 160 patients from 13 different Nephrology and Genetics Units located across the Piedmont region over 15 months. A preliminary "remote" evaluation based on well-defined inclusion criteria allowed us to define eligibility for NGS analysis. Among the 138 recruited patients, 52 (37.7%) were children and 86 (62.3%) were adults. Up to 48% of them had a positive family history for kidney disease. Overall, applying this workflow led to the identification of genetic variants potentially explaining the phenotype in 78 (56.5%) cases., Conclusions: These results underline the importance of clinical exome sequencing as a versatile and highly useful, non-invasive tool for genetic diagnosis of kidney diseases. Identifying patients who can benefit from targeted therapies, and improving the management of organ transplantation are further expected applications., (© 2020. The Author(s).)

Background: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI)., Methods: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU., Results: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints., Conclusions: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI., Competing Interests: Special thanks to Jacqueline Rodriguez, who revised the manuscript for English language, and to Claudia Giuliani, for graphic support. We express gratitude to Immunopathology Group of Italian Society of Nephrology and to ACSI Onlus “Amici contro la Sarcoidosi Italia”, the Italian national society of Sarcoidosis patients.Francesco Rastelli and Ivano Baragetti were responsible for the work. Other authors contributed to the data collection and reviewed and revised the manuscript as supervisors.Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20 + B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients. Five patients with IgG-RD were investigated: three had tubulointerstitial nephritis (TIN), while two had retroperitoneal fibrosis (RPF). In the patients with TIN, renal biospy was repeated after 1 year. In the patients with TIN, estimated glomerular filtration rate (eGFR) at 12 months increased from 9 to 24 ml/min per 1.73 m 2 ; IgG/IgG4 decreased from 3,236/665 to 706/51 mg/dl; C3/C4 increased from 49/6 to 99/27 mg/dl; CD20 + B-cells decreased from 8.7% to 0.5%; Regulatory T-cells decreased from 7.2% to 2.5%. These functional and immunologic changes persisted at 24 months and in two patients at 36 months. A repeat renal biopsy in the patients with TIN showed a dramatic decrease in interstitial plasma cell infiltrate with normalization of IgG4/IgG positive plasma cells. The patients with RPF showed a huge regression of retroperitoneal tissue. In this sample of patients with aggressive IgG4-RD and renal involvement, treatment aimed at depleting B cells and decreasing antibody and cytokine production was associated with a substantial, persistent increase in eGFR, and a definite improvement in immunologic, radiologic and histological parameters., Competing Interests: CONFLICTS OF INTEREST All the authors declare no conflicts of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format.

Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE-angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy., Competing Interests: The authors declare no conflicts of interest.

Background: Acute renal infarction is a rare condition whose diagnosis is often delayed. Major risk factors include atrial fibrillation, valvular or ischemic heart disease, renal artery thrombosis/dissection and coagulopathy., Methods: We reviewed the medical records of 18 patients admitted to our Nephrology Department between 1999 and 2015 for acute renal infarction diagnosed by computed tomography. Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy was performed in some patients during follow-up to assess parenchymal lesions and estimate differential kidney function., Results: Mean age was 59.8 years. Major associated risk factors included hypertension (44 %), obesity (33 %), atrial fibrillation (28 %), peripheral vascular disease (17 %), smoking (17 %), prior thromboembolic event (11 %), diabetes (11 %), estroprogestinic therapy (11 %). Seventy-two percent of patients presented with flank pain. Mean serum creatinine was 1.2 ± 0.6 mg/dl. Acute kidney injury occurred as the initial manifestation in two patients. Patients were managed conservatively, with low molecular weight heparin (83 %) or aspirin (11 %). At the end of follow-up serum creatinine was 1.1 ± 0.3 mg/dl; one patient remained on chronic hemodialysis. 58 % of patients who underwent renal scintigraphy after a median of 8 months had a reduced contribution of the previously affected kidney to total renal function., Conclusion: Risk factors associated with the development of chronic kidney disease following renal infarction are unknown. In our subjects, renal function remained stable in all but one patient who developed end stage renal disease. Further studies should focus on etiology and evolution of kidney function in patients with acute renal infarction.

Background: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease., Methods: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared., Results: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m 2 and an eGFR of <90 ml/min/1.73 m 2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m 2 ) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy., Conclusion: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

In this paper we concentrate on the role of infections in IgA nephropathy both from a pathogenetic and clinic point of view. The current hypotheses as regards the role of infections in the pathogenesis of IgA nephropathy are: (a) role of particular pathogens, (b) chronic exposure to mucosal infections, (c) abnormal handling of commensal microbes (gut microbiota). We also focus on particular infections reported in association with classic IgA nephropathy (HIV, malaria, Chlamydia, Lyme disease), as well as on IgA dominant-infection-associated glomerulonephritis. This is a unique form of glomerulonephritis, where IgA deposition is dominant. It is mostly recognized in old, diabetic patients and in association with staphylococcal infection.

Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits., Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy., Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR., Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline., (© 2015 S. Karger AG, Basel.)

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.

Frequency of autoimmune diseases secondary to biologic drugs used in rheumatic disorders (bio-DMARDS) is increasing. Reports of renal diseases is also increasing. The literature reports small series and many case reports of association between the use of a biologic drug and glomerular, vascular or interstitial nephropathies elapsing several months to more than 3 years from the beginning of treatment. Some of the reported glomerular diseases are already known to be possibly associated to the rheumatic disease. Prevention consists in careful clinical, immunologic and renal evaluation before giving bioDMARDS and in careful monitoring. These nephropathies and autoimmune diseases may go into remission just by drug discontinuation, which is mandatory in case of renal, nervous and pulmonary involvement. Corticosteroids or immunsuppressive drugs may be necessary.

The benefits of tonsillectomy in IgA nephropathy (IgAN) are still debated. Tonsillectomy may remove pathogen sources and reduce the mucosal associated lymphoid tissue (MALT), limiting degalactosylated IgA1 (deGal-IgA1) production, which is considered to be the initiating pathogenetic event leading to IgA glomerular deposition. In the European network VALIGA, 62/1147 IgAN patients underwent tonsillectomy (TxIgAN). In a cross-sectional study 15 of these patients were tested and compared to 45 non-tonsillectomized IgAN (no-TxIgAN) and healthy controls (HC) regarding levels of deGal-IgA1, and markers of innate immunity and oxidative stress, including toll-like receptors (TLR)2, 3, 4 and 9 mRNAs, proteasome (PS) and immunoproteasome (iPS) mRNAs in peripheral blood mononuclear cells (PBMC), and advanced oxidation protein products (AOPP). Levels of deGal-IgA1 were lower in TxIgAN than in no-TxIgAN (p = 0.015), but higher than in HC (p = 0.003). TLR mRNAs were more expressed in TxIgAN than in HC (TLR4, p = 0.021; TLR9, p = 0.027), and higher in TxIgAN than in no-TxIgAN (p ≤ 0.001 for TLR2, 4, 9). A switch from PS to iPS was detected in PBMC of TxIgAN in comparison to HC and it was higher than in no-TxIgAN [large multifunctional peptidase (LMP)2/β1, p = 0.039; LPM7/β5, p < 0.0001]. The levels of AOPP were significantly higher in TxIgAN than HC (p < 0.001) and no-TxIgAN (p = 0.033). In conclusion, the activation of innate immunity via TLRs and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy, even though the levels of aberrantly galactosylated IgA1 were lower in patients with IgAN who had tonsillectomy. The residual hyperactivation of innate immunity in tonsillectomized patients may result from extra-tonsillar MALT.

Introduction: Demographic analysis shows the ageing of the global population and the consequent increase in the age of hospitalized subjects and of patients starting dialysis. Hence, interest in the feasibility, safety, and usefulness of renal biopsy in elderly patients is growing. We examined the data of 131 patients over the age of 75 who underwent renal biopsy. We analyzed the safety of the procedure, treatment, and outcomes., Results: Histological diagnoses included: membranous glomerulonephritis (GN) 20.6%, crescentic GN 12.9%, IgAGN 10.6%, focal segmental glomerulosclerosis 9.1%, acute GN 4.5%, amyloidosis 9.1%, and acute tubular necrosis 3.8%. Mean glomerular obsolescence was 28.9 Â ± 27.9%. Mean age of the patients was 78.7 Â ± 5.73 years. At the time of biopsy, serum creatinine (SCr) was 4.47 Â ± 2.56 mg/dL and proteinuria was 4.82 Â ± 6.78 g/day. Targeted treatment was given to 51.9% of patients, 52.9% of whom had a good clinical response. Eight patients had clinically non-relevant side effects (11.7%). A positive response (defined as a more than 50% reduction of SCr, or by partial or complete remission of proteinuria) was observed in 36 patients (52.9%). 76 patients were monitored for 57 Â ± 9.89 months: 18 patients were on dialysis (follow-up 2.56 Â ± 3.61 months), 15 died (follow-up 58.5 Â ± 13.43 months), and 52 remained under nephrologic observation for 36 Â ± 31 months (SCr was 2.56 Â ± 0.75 mg/dL and proteinuria was 4.82 Â ± 6.78 g/day)., Conclusion: In our experience, renal biopsy is safe even in very elderly patients; it allowed targeted treatment in 51.9% of patients, 52.9% of whom had a good clinical response, possibly contributing to prolonged patient survival and improved quality of life.

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin-angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m(2), the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.

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.

Vaptans, vasopressin V2 receptor antagonists, are new drugs indicated in the treatment of Inappropriate ADH Secretion Syndrome (SIADH). We report a case of SIADH in a patient affected by AIDS. During a hospitalization for an ongoing CMV meningitis she developed a severe hyponatremia (114 mEq/L), which was initially treated with restriction of free water. When the diagnosis of SIADH was done (plasma Osmolarity 240 mOsm/kg, urinary sodium >30 mEq/24 h, normal volemia, lack of hypocorticosurrenalism and hypothyroidism), tolvaptan was given at the dose of 15 mg/day. Important fluctuations of plasma Na were observed thereafter (119-143 mEq/L). The progressive reduction of the drug (to 2 mg/die) allowed a stable correction of natremia. Unconsciousness determined the impossibility of the patient to freely access to water, thus explaining the fluctuations of natremia and the difficult management of the drug. Only a posology reduction to doses lower than those available for sale allowed a stable correction of natremia.

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.

Acute pyelonephritis (APN) is a frequent pathological condition. Its etiology is prevalently due to E. coli and risk factors include sexual activity, genetic predisposition, old age and urinary instrumentation. No correlation between APN and vesicoureteral reflux has been established in adults. The diagnosis of APN is usually clinical, but computed tomography (CT) and magnetic resonance imaging (MRI) allow a more precise definition and can document evidence of abscesses. Severe cases should be treated with a fluoroquinolone or an extended-spectrum cephalosporin. Treatment should last 10-14 days. The long-term evolution of APN is prevalently favorable in adults, even though formation of cortical scars and development of macroalbuminuria and renal failure have been described. The formation of renal abscesses is underestimated and must be evaluated by CT or MRI. Abscesses need to be drained only when they are large, and medical treatment is successful in the majority of cases.

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 <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.

Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

The characteristics of patients hospitalized in nephrology wards in Italy have changed in recent years due to the aging Italian population and the increased immigration. We analyzed the demographic and clinical characteristics of patients hospitalized in our nephrology ward (17 beds) from 15 November 2008 to 15 November 2009. In this period there were 507 hospitalizations including 448 patients. The mean age was 64.4+/-18 years (range 16-96 years). Foreigners accounted for 10% of the total; their mean age was significantly lower than that of Italian patients (38.2+/-13.4 vs 67.4+/-15.9 years, p<0.01). 36.3% of patients were on dialysis, 10% were transplant recipients: the reasons for admission in these cases were internal medicine related; 18.15% were hospitalized because of emergency unit crowding without indications for admission to a nephrology ward. Hospitalization lasted a mean of 13+/-13 days. The most frequent diagnosis at discharge was acute renal failure (ARF) (28.9%) (prerenal 42.1%, obstructive 12.2%, drug induced 6.8%, other causes of ARF 38.7%). Patients with ARF were older than patients with other kidney conditions (67.05+/-16.98 vs 56.03+/-18.65 years, p<0.01). ARF resolved or improved in 86 patients (63.7%). Other diagnoses were cardiovascular disease 25.1%, glomerular disease 18.7%, acute pyelonephritis 10.6%, other 16.7%. Foreign patients presented infectionrelated diseases more often than Italian patients (39.2% vs 20.4%, p=0.02). 392 patients were discharged to their homes, 40 (7.9%) found a place in a long-term care facility or home for the elderly, 25 (4.9%) in other hospital units, and 50 patients died (9.8%). In conclusion, patients hospitalized in nephrology wards in 2009 were mostly elderly with a high frequency of cardiovascular disease and diabetes. The most frequent diagnosis was prerenal ARF. These data suggest the necessity of improving the prevention of this type of kidney disease. Moreover, the length of hospitalization, which is increasing because of difficult clinical and social situations, could be shortened if more nursing homes, convalescent homes and homes for the elderly were available in Italy.