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.

Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study.

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, ß2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

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.

Metformin associated lactic acidosis: a case series of 28 patients treated with sustained low-efficiency dialysis (SLED) and long-term follow-up.

BACKGROUND: Metformin associated lactic acidosis (MALA) is a well-known serious side effect of biguanides. However, the best treatment strategy remains a matter of debate. In the last 14 years, we observed a significant increase in hospitalizations for MALA to our Center. We report the outcomes of our clinical and therapeutic approach. METHODS: This is a single-center case series. Twenty-eight patients affected with MALA and acute kidney failure admitted between January 2000 and September 2014 were included. We analyzed comorbidities, laboratory tests and clinical parameters at admission, at 36 h and at discharge. All patients were treated with sustained low-efficiency dialysis (SLED) until normalization of serum lactate (≤ 3 mmol/L), bicarbonate (between 20 and 25 mmol/L) and potassium (between 4.0 and 5.1 mmol/L). RESULTS: The mortality rate was 21.4%, with all of the events occurring within 24 h from admission, and before or during the first hemodialysis treatment. Precipitating causes included; acute dehydration (86.4%), systemic inflammatory response syndrome (SIRS) (57.1%), sepsis (10.7%), nephrolithiasis (14.6%) and exposure to iodinated contrast (7.1%). No further episodes of lactic acidosis were described after discontinuing the drug over a mean follow-up of 27.2 months. Furthermore, while in 2010, we had a peak incidence of MALA of 76.8 cases per 100,000 patients on metformin, this rate fell after an education campaign conducted by specialists on the proper usage of metformin in patients at risk of MALA. Although the fall in incidence after the educational program was not necessarily causal, in 2014 the incidence was 32.9/100,000. CONCLUSIONS: We report an improved mortality rate in patients affected with MALA and acute kidney injury treated with SLED compared with other series published in literature. Rapid introduction of effective hemodialysis is critical in improving outcomes.

Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis.

BACKGROUND: Complement activation plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although it remains unclear which pathway is activated. Whether pauci-immune necrotizing crescentic glomerulonephritis (pauci-immune GN) with negative ANCA serology is part of the spectrum of AAV or a different disease entity is essentially unknown. METHODS: We used proteomic analysis to delineate the complement profile in a series of 13 kidney biopsies of patients with pauci-immune GN, with either proteinase 3 (PR3) (five patients) or myeloperoxidase (MPO) antibodies (four patients) or with consistently negative ANCA serology (four patients). Immunofluorescence staining of glomeruli was essentially negative in the PR3-ANCA and MPO-ANCA groups, while a mild staining for C3 was seen in the ANCA-negative cases. No electron-dense deposits were found in the PR3-ANCA and MPO-ANCA groups, but mesangial and few subepithelial deposits were clearly present in the ANCA-negative specimens. RESULTS: Mass spectrometry revealed low spectra numbers for C3 and immunoglobulins in both PR3-positive and MPO-positive patients with minimal or no C4 and C9. In contrast, larger spectra numbers for C3, moderate spectra numbers for C9, complement factor H-related protein-1 and low spectra numbers for C4, C5 and immunoglobulins were found in the ANCA-negative cases. CONCLUSION: While complement activation is noted in AAV, the complement activation appears to be more prominent in the ANCA-negative glomerulonephritis. The larger amount of C3 and moderate amount of C9 in the ANCA-negative glomerulonephritis implies activation of the alternate and terminal pathway of complement, suggesting that this entity may be caused or promoted by a genetic or acquired defect in the alternative pathway.

Familial antiglomerular basement membrane disease in zero human leukocyte antigen mismatch siblings
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Reported cases of familial Antiglomerular basement membrane (anti-GBM) disease are extremely rare. The single gene mutations that may play a role in the development of familial anti-GBM disease are currently unidentified. While human leukocyte antigen (HLA)-DR15 is known to be associated with an increased risk of anti-GBM disease, HLA types in patients with familial anti-GBM disease have never been reported. We present a case of a 65-year-old woman with rapidly-progressive glomerulonephritis and pulmonary involvement, consistent with Goodpasture's syndrome. Two of her 15 siblings also had a history of anti-GBM disease during adolescence and both received a kidney transplant. Our patient and her siblings were smokers and had also had exposure to kerosene, a low-viscosity hydrocarbon. HLA testing was performed and showed identical HLA typing (0 of 6 HLA mismatch) as one of her brothers with anti-GBM disease. Interestingly, they both had HLA-DR15. Despite severe acute kidney injury requiring hemodialysis, the patient responded well to the standard therapy with cyclophosphamide, plasmapheresis, and systemic corticosteroids. At her 3-month follow-up visit, the patient's kidney functions had recovered, and hemodialysis was discontinued. Concluding, we illustrate an extremely rare familial anti-GBM disease involving 3 siblings with potential links of HLA-DR15 and environmental triggers with the development of familial anti-GBM disease.
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Diagnosis of complement alternative pathway disorders.

Kidney diseases resulting from abnormal control of the complement alternative pathway include atypical hemolytic uremic syndrome, C3 glomerulonephritis, and dense-deposit disease, as well as atypical postinfectious glomerulonephritis. Although clinically diverse, they all result from loss of surface or fluid-phase complement control, caused by acquired or genetic defects in the complement alternative pathway. As such, the diagnostic approach is similar and includes a comprehensive biochemical, genetic, and pathologic analysis of the complement pathway. The biochemical test battery includes functional activity measurements of the entire complement pathway, functional and quantitative analysis of individual components and regulators, and quantification of activation products. In patients with a thrombotic microangiopathy, ADAMTS-13 activity should be determined to exclude a thrombotic thrombocytopenic purpura. The spectrum of genes currently known to be involved in the pathogenesis of alternative pathway disorders is rapidly expanding. Pathologic analysis of a kidney biopsy specimen is sophisticated with ad hoc immunofluorescence studies and laser microdissection with mass spectrometry. The identification of the underlying defect in the alternative pathway based on this comprehensive analysis will allow treatment to be directed to the site of dysregulation.

Recurrent Light Chain Proximal Tubulopathy in a Kidney Allograft.

We describe a rare case of light chain proximal tubulopathy developing in a kidney transplant 12 months following transplantation. The patient was known to have a monoclonal gammopathy of undetermined significance (MGUS) for more than 15 years. A kidney biopsy done to determine the cause of decline in kidney transplant function showed light chain proximal tubulopathy characterized by numerous eosinophilic and fuchsinophilic granules in proximal tubular epithelial cells, which stained for κ light chains on pronase-based immunofluorescence studies. Electron microscopy confirmed the diagnosis and showed numerous amorphous and geometrically shaped inclusions in proximal tubular epithelial cells. Evaluation of free light chains revealed markedly elevated κ light chains and bone marrow biopsy showed 5% to 10% κ light chain-restricted plasma cells. Retrospective evaluation of the native kidney biopsy performed 15 years earlier also showed numerous fuchsinophilic granules in proximal tubules that stained brightly for κ light chains on pronase-based immunofluorescence studies. The patient was treated with a regimen of bortezomib and dexamethasone with good partial hematologic response and improvement of kidney function. To summarize, we describe a case of recurrent light chain proximal tubulopathy in the transplant, which is an unusual but important cause of decreased kidney function in the setting of a monoclonal gammopathy.

Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease.

BACKGROUND: To determine the effect of statins on renal hemodynamics in normal volunteers and those with autosomal dominant polycystic kidney disease either with mild or moderate renal dysfunction. METHODS: Thirty-two study subjects were enrolled in this study: 11 normal volunteers, 11 study subjects with autosomal dominant polycystic kidney disease (ADPKD) and mild kidney disease and 10 study subjects with ADPKD and moderate kidney disease. Subjects in each group received simvastatin 40 mg once daily for a period of 4 weeks. Renal blood flow was measured based on para-amino-hippurate (PAH) clearance and with the use of a magnetic resonance (MR) scanner at the beginning and following 4 weeks of therapy with statins. RESULTS: At the end of the study, except for the lipid profile, which was significantly lower in all groups, other laboratory results showed no change. Four weeks of therapy with simvastatin resulted in no change in serum creatinine, 24-h urinary protein, sodium, iothalamate clearance, PAH clearance or renal blood flow as measured by MRI or based on PAH clearance. CONCLUSIONS: Four weeks of therapy with simvastatin did not change renal blood flow in the study subjects with ADPKD with mild-to-moderate renal dysfunction or in healthy volunteers. CLINICAL TRIAL REGISTRATION NUMBER: NCT02511418.

Bortezomib-induced acute interstitial nephritis.

Acute interstitial nephritis (AIN) is one of the important causes of acute kidney injury (AKI) resulting from inflammatory tubulointerstitial injury induced by medications, infections and systemic diseases. Bortezomib has been increasingly used especially in renal related indications such as multiple myeloma and monoclonal gammopathy of renal significance. Severe allergic reactions from bortezomib treatment including AIN have not been described in the literature. We report a 47-year-old white man who developed biopsy-proven allergic AIN after treatment with bortezomib for his C3 glomerulonephritis. The patient's kidney function improved after treatment with glucocorticoid therapy and discontinuation of bortezomib, but worsened with recurrent AKI episode after re-initiation of bortezomib. His renal function improved after glucocorticoid therapy and discontinuation of bortezomib. To our knowledge, this is the first report of a biopsy-proven AIN from bortezomib.

[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.

[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.

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.

Treatment of primary membranous nephropathy: where are we now?

In the last 10 years, basic science and clinical research have made important contributions to the understanding and management of primary membranous nephropathy (MN). The identification of antibodies directed against the M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A protein have added a new perspective on diagnosis, monitoring the immunological activity, predicting prognosis and guiding therapy in patients with primary MN. Mounting evidence suggests that quantification and follow-up of antiPLA2R Abs levels can help in assessing prognosis and evaluate the response to treatment. The kidney disease improving global outcomes guidelines published in 2012 have not been updated. New data on the use of rituximab suggest it should be considered as a potential initial therapy in the treatment of patients with primary MN.

FSGS: from pathogenesis to the histological lesion.

Focal and segmental glomerulosclerosis (FSGS) is a generic term that in the current terminology can be appropriate for identifying two conditions. First, a morphological pattern of injury characterized by the occlusion of a single or group of glomerular capillary loops by sclerotic material, indicating a precise histological lesion but with a wide range of etiological interpretations. Second, a pauci-immune renal disease called idiopathic or primary FSGS, which is a podocytopathy triggered by an endogenous cytotoxin that recognizes the podocyte as its sole target. Based on the current and past literature, we do not possess practical tools to easily provide a precise classification of an FSGS lesion, although some clues may be of help in everyday clinical practice. Reactive forms, genetic forms, adaptive forms, forms associated with a deregulation of the proliferation and forms secondary to local glomerular inflammation are the etiological classes known to be associated with the development of an FSGS lesion. However, diagnosing each single case based on clinical, serological and histological criteria is still far from easy and mostly depends on the experience of the renal team, which should involve skilled nephrologists and pathologists.