Any reduction in maternal kidney mass makes a difference during pregnancy in gestational and fetal outcome.

Little is known about the effect tubulointerstitial nephropathies have in modulating maternal-fetal outcomes in pregnancy. Therefore, we analyzed the main outcomes of pregnancy in these women to gain a better understanding of the role of a reduction in maternal kidney mass. From the Torino Cagliari Observational Study (TOCOS) cohort, we selected 529 patients with a diagnosis of tubulointerstitial disease and focused on 421 patients with chronic kidney disease (CKD) stage 1, without hypertension but with proteinuria less than 0.5 g/day at referral. From a cohort of 2969 singleton deliveries from low-risk pregnancies followed in the same settings we selected a propensity score matched control cohort of 842 pregnancies match 2:1 for age, parity, body mass index, ethnicity, and origin. Time to delivery was significantly shorter in the study cohort 38.0 (Quartile 1-Quartile 3: 37.0-39.0) versus 39.0 (Q1-Q3 38.0-40.0) weeks, with respect to controls. Incidence of delivery of less than 37 gestational weeks significantly increased from controls (7.4%) to women with previous acute pyelonephritis (10.8%), other tubulointerstitial diseases (9.7%) and was the highest in patients with a single kidney (31.1%). Similarly, neonatal birthweight significantly and progressively decreased from controls (3260 g [Q1-Q3: 2980-3530]), previous acute pyelonephritis (3090 g [Q1-Q3: 2868-3405], other tubulointerstitial diseases (3110 g [Q1-Q3: 2840-3417]), and to solitary kidney (2910 g [Q1-Q3: 2480-3240]). Risk of developing preeclampsia was significantly higher in the CKD cohort (3.6% vs 1.7% in low-risk controls). Thus, even a small reduction in functional kidney mass, such as a pyelonephritic scar, is associated with a shorter duration of pregnancy and an increased risk of preterm delivery. The risk is proportional to the extent of parenchymal reduction and is highest in cases with a solitary kidney.

[An Integrated Multidisciplinary Approach to the Care of Renal Cancer Patients Undergoing Nephrectomy].

Kidney cancer is one of the most common cancers globally, ranking 9th and 14th among men and women, respectively. Advances in diagnostic techniques have enabled earlier and potentially less invasive interventions, however, this progress poses a challenge in managing low-malignancy tumors that were previously undiagnosed. To navigate treatment pathways, a deep understanding of the bidirectional relationship between Chronic Kidney Disease (CKD) and Renal Cell Carcinoma (RCC) is essential, influenced by risk factors such as hypertension and obesity. The debate between partial (PN) and radical nephrectomy (RN) continues to be fueled by a rich body of studies in the last two decades, aiming to determine the precise benefits of renal function preservation and overall survival. However, long-term monitoring remains inadequate. There is an urgent need for heightened clinical vigilance, urging meticulous periodic evaluations that include both eGFR and the urinary albumin-creatinine ratio, to identify potential deteriorations early. Furthermore, non-neoplastic renal parenchyma requires equal attention, often overshadowed by the assessment of tumor mass. A nuanced analysis is necessary to identify a range of nephropathies that guide more effective therapeutic strategies. A collaborative strategy that brings nephrologists, urologists, nuclear radiologists, oncologists, and pathologists together on a unified platform, focusing on a personalized medicine approach grounded on a profound analysis of individual risk factors, is pivotal in shaping the future of management and prevention strategies. This approach ensures a detailed therapeutic outlook and facilitates early interventions, marrying vigilance with interdisciplinary cooperation, thereby guarding against late diagnoses and offering patients a robust shield in their battle against kidney afflictions.

[Transplant Candidate with Cancer: Should We Proceed?]

Individuals who suffer from end-stage renal disease are at a higher risk of developing certain types of tumors. This risk increases as kidney function deteriorates further. Dialysis patients often witness a surge in the incidence of such malignancies. Interestingly, after the initial period following a kidney transplant, there is a dip in the number of deaths related to neoplasms. However, a long-term view reveals a progressive increase in the risk of developing tumors. The evaluation process for transplant candidacy is thorough, taking into account several factors, including the individual's history of neoplasms and the implications of immunosuppressive therapy. Immunosuppressive therapy is a double-edged tool in managing post-transplant complications, as it can foster environments conducive to neoplasm growth. It is essential to reevaluate, with the aid of an oncological opinion, the waiting time between cancer recovery and the listing for kidney transplantation, based on clinical data and follow-up. Independent of the type of tumor, the requirement to treat and achieve remission delays the listing process, consequently extending the time spent with end-stage renal disease and undergoing dialysis. These factors correlate with increased mortality, heightened risk of cardiovascular disease, and graft loss.

[Classification and Management of MGRS Related Diseases].

Monoclonal Gammopathies of Renal Significance (MGRS) are a complex group of disorders characterized by the production of aberrant monoclonal proteins that interact with kidney structures, causing tissue damage. Unlike neoplastic forms, kidney damage in MGRS does not correlate with clone mass or circulating monoclonal protein levels, conferring unique pre-neoplastic or non-neoplastic properties to the responsible clones. This manuscript explores the heterogeneity of monoclonal proteins involved, varying from full immunoglobulins to free light chains (FLC), and how they result in a spectrum of kidney lesions with differing prognoses. We also elaborate on diagnostic challenges, emphasizing the indispensable role of kidney biopsy, including advanced techniques like laser microdissection and mass spectrometry (LMD/MS) for deposit characterization, particularly in ambiguous or complex cases. Clinical management and treatment considerations, including the necessity for clone identification, are also discussed.

Radiopacity of Sodium Zirconium Cyclosilicate in Computed Tomography: a case of a patient with Hyperkalemia and kidney disease.

Sodium Zirconium Cyclosilicate (SZC) is commonly used for treating hyperkalemia because it sequesters gastrointestinal potassium ions, thereby reducing serum potassium levels. However, a less-discussed aspect of SZC is its radiopacity on x-ray-based imaging techniques. The European Medicines Agency (EMA) has only vaguely addressed this issue. Radiopaque substances like SZC can interfere with diagnostic imaging, creating challenges for clinicians and radiologists. We present the case of a 34-year-old Italian male to illustrate these concerns.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

The impact of the secondary infections in ICU patients affected by COVID-19 during three different phases of the SARS-CoV-2 pandemic.

Microbial secondary infections can contribute to an increase in the risk of mortality in COVID-19 patients, particularly in case of severe diseases. In this study, we collected and evaluated the clinical, laboratory and microbiological data of COVID-19 critical ill patients requiring intensive care (ICU) to evaluate the significance and the prognostic value of these parameters. One hundred seventy-eight ICU patients with severe COVID-19, hospitalized at the S. Francesco Hospital of Nuoro (Italy) in the period from March 2020 to May 2021, were enrolled in this study. Clinical data and microbiological results were collected. Blood chemistry parameters, relative to three different time points, were analyzed through multivariate and univariate statistical approaches. Seventy-four percent of the ICU COVID-19 patients had a negative outcome, while 26% had a favorable prognosis. A correlation between the laboratory parameters and days of hospitalization of the patients was observed with significant differences between the two groups. Moreover, Staphylococcus aureus, Enterococcus faecalis, Candida spp, Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently isolated microorganisms from all clinical specimens. Secondary infections play an important role in the clinical outcome. The analysis of the blood chemistry tests was found useful in monitoring the progression of COVID-19.

Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario.

Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are effective therapeutic agents for the palliative treatment of metastatic non-small-cell lung cancer (NSCLC); the aim of our study was to investigate the acute and chronic renal toxicities in this setting. We collected data on 292 patients who received cisplatin (35%), carboplatin-based regimens (25%), or ICI monotherapy (40%). The primary and secondary outcomes were compared to the acute kidney injury (AKI) rate and the mean estimated GFR (eGFR) decay between groups, respectively, over a mean follow-up duration of 15 weeks. We observed 26 AKI events (8.9%), mostly stage I AKI (80.7%); 15% were stage II AKI, 3.8% were stage III, and none required renal replacement therapy or ICU admission. The AKI rates were 10.9%, 6.8%, and 8.9% for the cisplatin, carboplatin, and ICI groups, respectively, and no significant differences were observed between the groups (p = 0.3). A global mean eGFR decay of 2.2 mL/min was observed, while for the cisplatin, carboplatin, and ICI groups, the eGFR decay values were 2.3 mL/min, 1.1 mL/min, and 3.5 mL/min, respectively. No significant differences were observed between the groups. Cisplatin/carboplatin-based CT and ICIs resulted in a similar incidence of AKI and eGFR decay, suggesting the safety of their cautious use, even in CKD patients.

History of Preeclampsia in Patients Undergoing a Kidney Biopsy: A Biphasic, Multiple-Hit Pathogenic Hypothesis.

Introduction: It is not fully elucidated whether preeclampsia (PE) is a marker or a cause of chronic kidney disease (CKD). To test the hypothesis of a biphasic relationship between PE and CKD, we assessed PE prevalence in women who underwent a kidney biopsy. Methods: This retrospective, observational study recruited patients who underwent a kidney biopsy after delivery in 2014 to 2019 in 3 Italian Centers (Cagliari, Bari, Messina); low-risk pregnancies observed in Cagliari served as controls. A history of PE was assessed on the clinical charts and by phone interview. Results: In the biopsy cohort (379 pregnancies, 205 patients; 38 PE in 32 patients), kidney biopsy shows clustering in the first 5 years after PE (11 of 32). Pre-existing CKD was detected in 8 of 11 of these cases. Focal-segmental glomerulosclerosis (FSGS) and complex lesions were found in 12 of 32 biopsies. The odds ratio (OR) of having had a PE episode, compared with 561 low-risk pregnancies, was 10.071 (95% CI: 4.859-20.875; P < 0.001); multiparity maintained a protective effect (OR: 0.208). The delivery-to-biopsy time was significantly shorter in women with PE, both considering the first or the last PE versus the first or last delivery in patients with or without PE episodes. The characteristics of PE did not differ as compared with low-risk controls. Conclusion: Within the limitation of the retrospective design, our study, quantifying the association between needing a kidney biopsy and history of PE, suggests a biphasic pattern, with a peak in the first 5 years after delivery (probably due to pre-existing diseases) and a later increase, suggesting that PE may have later played as one hit in a multiple-hit pathogenesis.

How Genetics Can Improve Clinical Practice in Chronic Kidney Disease: From Bench to Bedside.

Chronic kidney disease (CKD) is considered a major global health problem with high socio-economic costs: the risk of CKD in individuals with an affected first degree relative has been found to be three times higher than in the general population. Genetic factors are known to be involved in CKD pathogenesis, both due to the possible presence of monogenic pathologies as causes of CKD, and to the role of numerous gene variants in determining susceptibility to the development of CKD. The genetic study of CKD patients can represent a useful tool in the hands of the clinician; not only in the diagnostic and prognostic field, but potentially also in guiding therapeutic choices and in designing clinical trials. In this review we discuss the various aspects of the role of genetic analysis on clinical management of patients with CKD with a focus on clinical applications. Several topics are discussed in an effort to provide useful information for daily clinical practice: definition of susceptibility to the development of CKD, identification of unrecognized monogenic diseases, reclassification of the etiological diagnosis, role of pharmacogenetics.

COVID-19 Vaccine Hesitancy in Patients on Dialysis in Italy and France.

INTRODUCTION: Patients on dialysis (HDPs) are a category at high risk from COVID-19 and thus a high-priority group for vaccination. COVID-19 vaccine hesitancy has been a concern since the availability of the first vaccine. The objective of this study was to determine hesitancy rates and factors associated with hesitancy toward COVID-19 vaccination in HDP. METHODS: HDP were surveyed with an ad hoc questionnaire in 4 large dialysis facilities in Europe: Le Mans and Paris, in France, and Cagliari and Pavia, in Italy. The questionnaire explored different domains associated with vaccine hesitancy, such as perception of disease severity, sources of information about the vaccine and the disease, and confidence in the health care system. RESULTS: A total of 417 patients (average age 69 years, 60% men) agreed to answer the questionnaire. Hesitancy was associated with younger age (P = 0.003), lower perception of disease severity (P < 0.001) and vaccine efficacy (P < 0.001), and lower trust in vaccination (P < 0.001) and in the health care system and scientists (P < 0.001) in the univariate analysis. In the multivariate models, concerns about side effects (P = 0.004) and vaccine efficacy (P < 0.001) and living in France (P = 0.04) remained associated with higher vaccine hesitancy, whereas having received an influenza vaccine (P = 0.032) and trusting scientists (P = 0.032) were associated with a more positive attitude toward vaccination. CONCLUSIONS: HDPs have a good understanding of the risks associated with COVID-19. Vaccine hesitancy was not associated with educational level, age, or gender but rather with lack of confidence in vaccine efficacy and concerns about safety. HDPs were quite skeptical about the health care system but generally trusted scientists.

Unexpected Outcomes of Renal Function after Radical Nephrectomy: Histology Relevance along with Clinical Aspects.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common events after radical nephrectomy (RN). In this study we aimed to predict AKI and CKD after RN relying on specific histological aspects. We collected data from a cohort of 144 patients who underwent radical nephrectomy. A histopathological review of the healthy part of the removed kidney was performed using an established chronicity score (CS). Logistic regression analyses were performed to predict AKI after RN, while linear regression analysis was adopted for estimated glomerular filtration rate (eGFR) variation at 1 year. The outcomes of the study were to determine variables correlated with AKI onset, and with eGFR decay at 1 year. The proportion of AKI was 64%. Logistic analyses showed that baseline eGFR independently predicted AKI (odds ratio 1.04, 95%CI 1.02:1.06). Moreover, AKI (Beta -16, 95%CI -21:-11), baseline eGFR (Beta -0.42, 95%CI -0.52:-0.33), and the presence of arterial narrowing (Beta 10, 95%CI 4:15) were independently associated with eGFR decline. Our findings showed that AKI onset and eGFR decline were more likely to occur with higher baseline eGFR and lower CS, highlighting that RN in normal renal function patients represents a more traumatic event than its CKD counterpart.

Chronic Kidney Disease of Undetermined Etiology around the World.

BACKGROUND: Epidemics of chronic kidney disease of uncertain etiology (CKDu) are occurring on the Pacific coast of Central America, in Sri Lankan and Indian agricultural communities, and in other hotspots around the world. CKDu primarily affects male agricultural workers, and traditional risk factors such as diabetes and hypertension are not involved in the pathogenesis. Although a causal factor has not yet been identified, culprits include repeated volume depletion-induced kidney injury, as well as exposure to agrichemicals, heavy metals and nephrotoxins contained in drugs, beverages, and traditional medications. Multiple risk factors may interact in a synergistic fashion thus resulting in chronic kidney damage. The absence of undefined protective factors may amplify the risk. SUMMARY: This review focuses on the current understanding of CKDu by analyzing epidemiology, potential risk factors, and clinical and pathological features as well as geographical peculiarities of each disease. We also focus our attention on the etiology of these conditions in which multiple factors may synergistically contribute to the development and progression of the disease. The last part of the manuscript is dedicated to the research agenda and practical recommendations. Key Messages: Since renal replacement therapy is not extensively available in areas where CKDu is widespread, prevention by avoiding all known potential risk factors is crucial. Innovative healthcare solutions and social policies in endemic areas along with collaborative clinical research projects are needed to better identify factors involved in disease promotion and progression.

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial.

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.

Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.