Primary membranous nephropathy in the Italian region of Emilia Romagna: results of a multicenter study with extended follow-up.

BACKGROUND: Since primary membranous nephropathy is a heterogeneous disease with variable outcomes and multiple possible therapeutic approaches, all 13 Nephrology Units of the Italian region Emilia Romagna decided to analyze their experience in the management of this challenging glomerular disease. METHODS: We retrospectively studied 205 consecutive adult patients affected by biopsy-proven primary membranous nephropathy, recruited from January 2010 through December 2017. The primary outcome was patient and renal survival. The secondary outcome was the rate of complete remission and partial remission of proteinuria. Relapse incidence, treatment patterns and adverse events were also assessed. RESULTS: Median (IQR) follow-up was 36 (24-60) months. Overall patient and renal survival were 87.4% after 5 years. At the end of follow-up, 83 patients (40%) had complete remission and 72 patients (35%) had partial remission. Among responders, less than a quarter (23%) relapsed. Most patients (83%) underwent immunosuppressive therapy within 6 months of biopsy. A cyclic regimen of corticosteroid and cytotoxic agents was the most commonly used treatment schedule (63%), followed by rituximab (28%). Multivariable analysis showed that the cyclic regimen significantly correlates with complete remission (odds ratio 0.26; 95% CI 0.08-0.79) when compared to rituximab (p < 0.05). CONCLUSIONS: In our large study, both short- and long-term outcomes were positive and consistent with those published in the literature. Our data suggest that the use of immunosuppressive therapy within the first 6 months after biopsy appears to be a winning strategy, and that the cyclic regimen also warrants a prominent role in primary membranous nephropathy treatment, since definitive proof of rituximab superiority is lacking.

A Rare Case of Coronavirus Disease 2019 Survival in an Elderly Patient With Atheroembolic Renal Disease.

Atheroembolic renal disease (AERD) is a life-threatening illness. Coronavirus disease 2019 (COVID-19) has a high mortality rate in older patients with comorbidities. We report the case of severe-type COVID-19 in an 82-year-old female with AERD. She was treated with hydroxychloroquine-based therapy and overcame COVID-19. To our knowledge, this is the first report of a patient with AERD and COVID-19 pneumonia who overcame the infection and remains alive and well nine months following infection.

The PIRP project (Prevenzione Insufficienza Renale Progressiva): how to integrate hospital and community maintenance treatment for chronic kidney disease.

Chronic kidney disease (CKD) represents a global health burden with great economic impact on healthcare and therefore it requires appropriate interventions by Health Care Systems. The PIRP (Prevenzione Insufficienza Renale Progressiva) project is endorsed and funded by the Emilia-Romagna Regional Health Board and involves all the Nephrology Units of the Emilia-Romagna Region (Italy). The project has a predominantly clinical purpose and is expected to bring about a continuous quality improvement in the treatment of patients with CKD. Its aims are to intercept patients in an early phase of CKD, to delay their illness progression and to prevent cardiovascular complications. An integrated care pathway involving nephrologists, general practitioners (GPs) and other specialists has been created to identify patients to whom ambulatory care targeted on effective, efficient pharmaceutical and dietary treatment as well as on lifestyle modifications is subsequently provided. With the cooperation of GPs, in its 13 years of activity the project identified and followed up more than 25,000 CKD patients, who attended the Nephrology units with more than 100,000 visits. The effects of a closer and joint monitoring of CKD patients by GPs and nephrologists can be quantified by the reduction of the mean annual GFR decline (average annual CKD-EPI change: - 0.34 ml/min), and by the decrease in the overall incidence of patients who annually started dialysis in the Emilia-Romagna Region, that dropped from 218.6 (× million) in 2006 to 197.5 (× million) in 2016, corresponding to about 100 cases.

Secondary amyloidosis in autoinflammatory diseases and the role of inflammation in renal damage.

The release of proinflammatory cytokines during inflammation represents an attempt to respond to injury, but it may produce detrimental effects. The inflammasome is a large, multiprotein complex that drives proinflammatory cytokine production in response to infection and tissue injury; the best-characterized inflammasome is the nod-like receptor protein-3 (NLRP3). Once activated, inflammasome leads to the active form of caspase-1, the enzyme required for the maturation of interleukin-1beta. Additional mechanisms bringing to renal inflammatory, systemic diseases and fibrotic processes were recently reported, via the activation of the inflammasome that consists of NLRP3, apoptosis associated speck-like protein and caspase-1. Several manuscripts seem to identify NLRP3 inflammasome as a possible therapeutic target in the treatment of progressive chronic kidney disease. Serum amyloid A (SAA), as acute-phase protein with also proinflammatory properties, has been shown to induce the secretion of cathepsin B and inflammasome components from human macrophages. SAA is a well recognised potent activator of the NLRP3. Here we will address our description on the involvement of the kidney in autoinflammatory diseases driven mainly by secondary, or reactive, AA amyloidosis with a particular attention on novel therapeutic approach which has to be addressed in suppressing underlying inflammatory disease and reducing the SAA concentration.

Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1ß monoclonal antibody canakinumab.

Muckle-Wells syndrome (MWS) is a rare hereditary autoinflammatory disorder characterized by recurrent urticaria-like skin rashes, arthralgias, conjunctivitis, hypoacusia, and risk of reactive AA amyloidosis due to the progressive accumulation of amyloid fibrils in different organs. Its genetic defect lies in mutations in the NLRP3 gene, encoding the cryopyrin protein, and resulting in interleukin (IL)-1ß oversecretion. Renal involvement, in terms of proteinuria or renal insufficiency, can be observed in up to 25% of patients. Herein, we describe our experience with two Caucasian patients, father and son, aged 52 and 26 years, respectively, heterozygous for both V198M and R260W NLRP3 mutations who had AA amyloid deposits on renal biopsy. The fully human monoclonal antibody canakinumab, providing selective and prolonged IL-1ß blockade, was administered in both patients every 60 days over a period of 18 months. This treatment allowed to obtain amazing results: a rapid disappearance of any clinical symptoms, the stable normalization of serum amyloid-A and, furthermore, a marked improvement of glomerular filtration rate and proteinuria with no adverse events. Our data, though limited to only two patients, emphasize that therapeutic intervention with canakinumab, suppressing both inflammation and IL-1ß-mediated manifestations, can contribute to improve kidney function in MWS with overt renal amyloidosis.

Treatment of dyslipidemia in chronic kidney disease: Effectiveness and safety of statins.

Several cardiovascular (CV) risk factors may explain the high rate of CV death among patients with chronic kidney disease (CKD). Among them both traditional and uremia-related risk factors are implicated and, moreover, the presence of kidney disease represents "per se" a multiplier of CV risk. Plasma lipid and lipoprotein profiles are changed in quantitative, but above all in qualitative, structural, and functional ways, and lipoprotein metabolism is influenced by the progressive loss of renal function. Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly, by reducing the lipid profile, or via pleiotropic effects; it is supposed to be able to reduce both the progression of CKD and also proteinuria. These observations derive from a post-hoc analysis of large trials conducted in the general population, but not in CKD patients. However, the recently published SHARP trial, including over 9200 patients, either on dialysis or pre-dialysis, showed that simvastatin plus ezetimibe, compared with placebo, was associated with a significant low-density lipoprotein cholesterol reduction and a 17% reduction in major atherosclerotic events. However, no benefit was observed in overall survival nor in preserving renal function in patients treated. These recent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which, however, represents only a third of CV deaths in patients with CKD. Therefore, statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure, prevalent among CKD patients. The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial, in terms of no increase in cancer incidence, muscle pain, creatine kinase levels, severe rhabdomyolysis, hepatitis, gallstones and pancreatitis; thus confirming the handiness of statins in CKD patients. Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients.

Dyslipidemia in chronic kidney disease: are statins still indicated in reduction cardiovascular risk in patients on dialysis treatment?

BACKGROUND: Chronic kidney disease (CKD) is an increasingly health disease all around the world with a high burden of mortality and cardiovascular (CV) morbidity rate. Even when renal replacement therapy is reached, more than half patients die, mainly for CV causes due either to uremia-related cardiovascular risk factors (such as anemia, hyperhomocysteinemia, mineral bone disease-CKD with hyperparathyroidism, oxidative stress, hypoalbuminemia, chronic inflammation, prothrombotic factors) or to traditional ones (age, male gender, diabetes, obesity, hypertension, smoking, insulin levels, family history, dyslipidemia). Among the latter causes dyslipidemia represents one of the major, potentially correctable risk factor. METHODS AND RESULTS: Statins have demonstrated to effectively and safely reduce cholesterol levels in CKD patients. Here we will examine the effects of statins on CV risk factors in CKD patients and particularly in patients on dialysis treatment, in the light of the unfavorable results of the large trials 4D and AURORA, recently published, underlining the role of malnutrition/inflammation as confounding factor. Probably it will be that only with a real prevention, starting statins even in the early stages of CKD, as indicated by post hoc analysis of large trials, that we will reach results in reducing the mortality rate in CKD patients. In the meanwhile, all the other remediable CV risk factors have to be at the same time corrected.