The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

[Polytrauma and Acute Kidney Injury: A Multidisciplinary Approach].

The development of acute kidney injury (AKI) in polytrauma patients is a common and serious complication, with an incidence ranging from 6% to 50%. Polytrauma is a complex pathological condition that involves the collaboration of various specialists. On one hand, hemodynamic stabilization through fluid therapy and aminic support, with specific attack protocols, managed by anesthetists. On the other hand, if necessary, the initiation of renal replacement therapy such as Continuous Renal Replacement Therapy (CRRT), managed by nephrologists. CRRT is chosen both for managing fluid balance and ensuring the removal of toxic substances, as well as for proper control of electrolytes and acid-base balance.

Use of CFTR Modulators for Cystic Fibrosis in a Patient with Liver Transplant and ESRD on Hemodialysis.

Cystic fibrosis is an autosomal recessive disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most recent therapeutic approach to cystic fibrosis aims to correct structural and functional abnormalities of CFTR protein. CFTR modulators including ivacaftor-tezacaftor-elexacaftor are used in patients with F508del mutation, with clinical improvement. To date, there are no experiences of CFTR modulator therapy in cystic fibrosis patients with organ transplantation and severe renal impairment. We report the case of a patient diagnosed with cystic fibrosis with F508del mutation, who underwent liver transplantation at the age of 19 and started hemodialysis at the age of 24 due to end-stage renal disease secondary to membranous glomerulonephritis. She was treated with Kaftrio (ivacaftor-tezacaftor-elexacaftor) with clinical benefits on appetite, improvement of body mass index, and reduction of pulmonary exacerbations. A reduction of dosage to 75% of the standard dose was required due to alterations of the liver function. Conclusions. Use of CFTR modulators in patient with cystic fibrosis, liver transplant and end-stage renal disease could be considered safe but a clinical and laboratoristic monitoring of hepatic function is needed.

[Acute kidney injury in severely burned patient: prevention and treatment].

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF). The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena.

[Minimal change disease during lithium therapy: case report].

Lithium is a largely used and effective therapy in the treatment of bipolar disorder. Its toxic effects on kidneys are mostly diabetes insipidus, hyperchloremic metabolic acidosis and tubulointerstitial nephritis. Also, a correlation between lithium and minimal change disease has sometimes been described. We report here the case of a patient with severe bipolar disorder on lithium therapy who, without any pre-existing nephropathy, developed nephrotic syndrome and AKI with histopathologic findings pointing to minimal change disease. The patient was treated with symptomatic therapy; the discontinuation of lithium therapy resulted in the remission of AKI and of the nephrotic syndrome, thus suggesting a close relationship between lithium and minimal change disease.

[Minimal Change Relapse During Pregnancy].

The appearance of nephrotic syndrome during pregnancy is considered an exceptional event, whose incidence is around 0.012-0.025% of all pregnancies, and it is even more rare when the cause is represented by minimal lesions glomerulonephritis. In this article we will describe the case of a patient with a histological diagnosis of glomerulonephritis with minimal lesions, tending to frequent relapses. She was in complete remission since 2013 after treatment with cyclosporine. suspended in May 2017. After few weeks she become pregnant, and the pregnancy was regular until the 23rd week. when a recurrence of nephrotic syndrome appears. She was treated with steroids bolus followed by oral steroid, and afterwards gave birth to a live fetus with spontaneous delivery at 37 weeks The few data in the literature confirm that recurrence of glomerulonephritis due to minimal lesions in pregnancy should be treated rapidly with steroids, that can induce rapid remission and protect both the pregnant than the fetus from even serious damage.

[Atypical hemolytic uremic syndrome related to Oxalyplatin Cancer Chemotherapy responsive to Eculizumab]. / Sindrome emolitico uremica atipica secondaria a chemioterapia con Oxaliplatino responsiva a Eculizumab.

We describe the case of a patient with adenocarcinoma of the colon treated with FOLFOX-4 (5-Fluorouracil, Folinic acid, Oxalyplatin), with subsequent appearance of atypical hemolytic uremic syndrome (aHUS). From 1999 to 2009, 13 cases of atypical HUS receiving chemotherapy with oxaliplatin have been described, as well as some sporadic cases. None of these cases has been treated with eculizumab. This is the first report of a patient with aHUS secondary to Oxalyplatin treated with Eculizumab. This treatment induced a complete remission of the syndrome and, later on, it has been discontinued with clinical and laboratory permanent remission. We identified some genetic mutations in this patient that might have a pathogenic role in the determining aHUS when associated with exposure to Oxalyplatin. Oxalyplatin withdrawal and its replacement to Irinotecan allowed the patient to receive first line chemotherapy continuation (FOLFIRI) with the same life expectancy and the same symptoms free period.

The ultrastructural basis of renal pathology in monoclonal gammopathies.

The kidney is frequently involved in the course of monoclonal gammopathies (MG). Renal involvement presents different clinical-morphological patterns, which can occur either at the onset or in a late phase of the hematological disease, as well as after chemotherapy. The reasons for the organ tropism of monoclonal immunoglobulins (Igs) are still unknown. Currently, it is well known that some primary structure alterations in monoclonal Igs and/or in their segments correlate to nephrotoxicity. On the other hand, it is impossible to predict the pathogenicity and the clinical manifestations induced by a specific monoclonal Ig based on its specific conformational modifications. Pathogenicity and organ tropism are probably complex phenomena, which involve specific protein factors, patient factors, target organ characteristics and monoclonal plasmacellular mass entities. However, aminoacidic sequence analysis of nephrotoxic Igs and some recent in vitro studies have allowed two different monoclonal light chain (LC) types to be distinguished. Glomerulopathic LCs (G-LCs) in the mesangium recognize their target structure and induce two distinct mesangiopathies, monoclonal Ig deposition disease (MIDD) and AL-amyloidosis (AL). Tubulopathic LCs (T-LCs) act on the proximal or on the distal tubule and cause, respectively, Fanconi syndrome (FS) and cast nephropathy. Pathogenic monoclonal Igs have the propensity to deposit in different renal parenchymal structures in extracellular sites, because of the transformation of soluble precursors in insoluble products. Evidence suggests that somatic mutations can destabilize the normal LCs globular soluble structure and this could be the major driving force for precipitation. Based on these features, MG can be classified as conformational and depositional diseases. Electronmicroscopy (EM) analysis of renal biopsies in MG patients with glomerular diseases distinguishes two morphological aspects. MIDD and a recently identified entity named proliferative glomerulonephritis (GN) with monoclonal IgG deposits are both characterized by non-organized granular electrondense deposits. AL, immunotactoid (IT) glomerulopathy and monoclonal cryoglobulinemia are, instead, characterized by organized deposits such as fibrils or microtubules. Tubular diseases in MG patients produce two different histological patterns. In FS, monoclonal Igs form crystals in the renal interstitium able to induce a local intense flogosis, while in cast nephropathy monoclonal Igs precipitate with Tamm-Horsfall protein (THP) in the proximal tubular lumen and induce tubular obstruction. The different morphological aspects are unrelated to specific clinical manifestations, while renal biopsy can diagnose different entities that can respond to different therapeutical schedules. This reveals the importance of the renal biopsy in the clinical management of the renal pathology in plasma cells dyscrasias, mainly when supported by the most advanced techniques of immunoelectronmicroscopy and polymerase chain reaction (PCR)-mediated analysis. Further elucidation of the molecular events involved in the pathogenesis of the different forms of renal damage is needed to design new and more effective therapeutical strategies. In particular, urinary proteomics seem to be promising in this setting.