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Background: A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking., Methods: We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events., Results: At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen., Conclusions: This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial., Clinical Trial Registry Name and Registration Number: Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: Primary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease may have different long-term outcomes. After 10 years of follow-up, 35%-50% of the untreated patients with persistent nephrotic syndrome may die or progress to end stage renal disease. The 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend that initial therapy should consist of alternating steroids and an alkylating agent for 6 months. Recent observational studies showed that the anti-CD20 antibody rituximab may be effective in inducing remission. We designed a pilot multicentre randomised trial to inform the design of a larger trial testing the efficacy and safety of treatment with steroids and cyclophosphamide versus rituximab in patients with primary MN and heavy proteinuria (>3.5 g/24 hours)., Methods and Analysis: This pilot, open-label, two-parallel-arm, randomised clinical trial will enrol 70 patients with primary MN and heavy proteinuria. Patients will be randomised in a 1:1 ratio to either the intervention arm (rituximab) or the active comparator arm (corticosteroid/alkylating-agent therapy). The study will provide estimates of the probability of complete remission of proteinuria and risk of serious side effects at 12 months to inform the design of a larger trial. We will also assess the recruitment potential of each participating centre to address study feasibility., Ethics and Dissemination: The trial received ethics approval from the local ethics boards. We will publish pilot data to inform the design of a larger clinical trial., Trial Registration Numbers: NCT03018535; 2011-006115-59., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Autosomal Dominant Polycystic Kidney Disease(ADPKD) is the most frequent renal genetic condition and involves 7 to 10% of subjects undergoing renal replacement therapy. It is estimated that between 24,000 and 34,000 subjects in Italy are affected by this condition. For an illness that has long been neglected due to a lack of treatment options, an attractive treatment possibility is now available: tolvaptan has shown clinical efficacy regarding disease progression in two clinical trials (ADPKD patients with mild renal failure and ADPKD patients with advanced renal failure). The possible liver toxicity expressed in about 4% of the subjects exposed to the drug and an important aquaretic effect suggest prudence and attention in the use of this new molecule. Based on these critical points, some clinicians with direct experience in the use of the drug have briefly collected in the pages to follow the main clinical recommendations for the treatment of ADPKD patints. The recommendations concern the general approach to the patient affected by ADPKD but with particular attention to the aspects related to the new treatment. The delicate task of introducing the opportunities and limitations of the offered therapy to the patient will be deepened. Finally, the document wants to suggest how best to organize a clinic dedicated to this condition., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Autosomal Polycystic Kidney Disease ( ADPKD) is the most common inherited renal disease. ADPKD is caused by mutations in PKD1 and PKD2, encoding polycystin 1 and 2, respectively. ADPKD is a systemic disease, with renal and extrarenal involvement. Renal disease is characterized by formation and growth of cysts, with progressive destruction of renal parenchyma and development of End Stage Renal Disease (ESRD) in about 50% of affected individuals at the age of 60 years. Extrarenal disease usually involves the liver, heart and vasculature. Cardiovascular manifestations occur in a high percentage of patients with ADPKD, including hypertension, left ventricular hypertrophy, cardiac valvular abnormalities, and intracranial aneurysms. An early treatment of hypertension may decreased the risk of cardiovascular complications, the leading cause of morbidity and mortality. The antihypertensive agents of choice should be ACE inhibitors and angiotensin II receptor antagonists. In this review, we will focuses on the cardiovascular problems of patients with ADPKD., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Factors predicting rapid progression of kidney disease in ADPKD can be divided into genetic (non-modifiable) and clinical (modifiable) risk factors. Patients harbouring PKD1 mutations, in particular if truncating, have a more severe form of ADPKD. Clinical risk factors include decrease in glomerular filtration rate and renal blood flow at a young age; high total kidney volume; hypertension and urological complications <35 years; albuminuria/proteinuria. The renal disease is also more severe in males and in subjects with family history of ESRD <55 years. In recent years, two models for predicting progression in ADPKD have been published: the Mayo model, based on height-adjusted TKV, age and eGFR, and the Brest model, based on PKD gene mutation type, gender, and early onset of hypertension and urological complications. With the emergence of new disease-modifying therapies, prediction tools are essential. However, the high variability in ADPKD makes the predicting models difficult to apply on an individual patient basis. Thus, the above-mentioned predicting models should be viewed as complimentary to clinical evaluation and follow-up. In the future, an individual risk score linking genetic, imaging and clinical data might prove the most accurate way of predicting long-term outcome.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist.

Already known to ancient Egyptians, gout is one of the first diseases which have been described as a clinical entity. To date, gout is the most common form of inflammatory arthritis. Gout is defined by the deposition of monosodium urate crystals within tissues, causing episodes of acute arthritis and the development of tophi, nephrolithiasis, and urate nephropathy. Hyperuricemia, i.e. levels of serum uric acid above 6.8 mg / dL(404mol/L), is a condition necessary, yet not sufficient for gout to develop. The increasing incidence of risk factors such as hypertension, obesity, and renal failure together with an ever-growing life expectancy has led in recent decades to a significant increase in gout prevalence, which has more than doubled when compared to the 1960s. This article addresses the issue of gout by highlighting the role played by the kidneys in uric acid homeostasis; the clinical effect of crystal deposition in tissues, including the kidney; the more recent guidelines on diagnosis and management strategies, with special regard to the use of old and new drugs in renal patients.

Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.