Search Results (17)

Background/Objectives: Automation improves efficiency in laboratory workflow but may fail to detect clinically relevant abnormalities in patients with nephropathy. This study aimed to identify dipstick parameters associated with nephropathy-related sediment findings and to propose practical criteria to guide manual microscopy review based on these associations. Methods: Urine samples from in- and outpatients, primarily from the nephrology unit, were collected at a university hospital from July 2022 to September 2023. Samples were analyzed within two hours using LabUMat 2 and UriSed 3 analyzers. Manual microscopy was performed on all specimens by two experienced technicians. Sediments were classified as suggestive or not of nephropathy based on hematuria with dysmorphism, hyaline and pathological casts, lipiduria, or renal tubular epithelial cells. Results: Of 503 samples, 146 (29%) showed sediment findings indicative of nephropathy, which were significantly associated with dipstick positivity for protein and blood. Among nephropathy samples, 71.2% had protein ≥1+ or blood ≥2+. Using this combination as a criterion for manual sediment review yielded a sensitivity of 71.2%, a specificity of 73.9%, and a 3.84-fold increased relative risk of detecting nephropathy-related elements (p < 0.001). The criteria performed best among nephrology outpatients, with sensitivity of 79.5%, specificity of 63.9%, and relative risk of 3.91 (p < 0.001). Conclusions: Dipstick protein ≥1+ or blood ≥2+ helps identify patients who may benefit from manual sediment review, supporting diagnostic accuracy in nephropathy. Each institution should define its criteria based on patient profile, analytical methods, and workflow. Full article

Renal failure is one of the most important manifestations of multiple myeloma. It is caused by renal lesions such as cast nephropathy, immunoglobulin deposition disease, AL amyloidosis or other glomerular and/or tubular diseases, mostly due to the toxic effect of free light chains in serum. Renal failure can represent a clinical emergency and is associated with poor outcome in newly diagnosed and relapsed/refractory multiple myeloma patients. Although progression-free survival and overall survival have improved with the introduction of novel agents, renal failure remains a challenge for the treatment of patients with multiple myeloma. Monoclonal antibodies are a component of therapy for newly diagnosed and relapsed/refractory patients and, based on clinical trials and real-world experience, are also safe and effective for subjects with renal failure, even if they are on dialysis. Most of the data are on anti-CD38 and anti-SLAM7 antibodies, but new antibody–drug conjugates such as belantamab mafodotin and bispecific antibodies also appear to be effective in myeloma kidney disease. In the future, we will have to face some challenges, such as defining new criteria for renal response to treatment, defining specific trials for these difficult-to-treat patients and integrating different therapeutic options. Full article

Kidney involvement with resulting kidney failure leads to increased mortality in patients with multiple myeloma (MM). Cast nephropathy (CN), in particular, if left untreated, quickly leads to kidney failure requiring dialysis and has a very poor prognosis for the affected patient. The gold standard for diagnosing kidney involvement is a kidney biopsy. However, due to bleeding risk, this cannot be done in every patient. We recently reported that a quotient of urine light chain (LCurine) to glomerular filtration rate (eGFR) is a non-invasive diagnostic tool for patients with kidney involvement in MM. But this quotient has not yet been tested in everyday clinical practice. In this study, our LCurine/eGFR ratio was tested on 67 patients in two centers. Enrollment took place between January 2019 and September 2023. A total of 18 of the 67 patients had CN. With the threshold defined in our initial paper, we were able to show a sensitivity of 100% with a specificity of 85.7% for CN in patients with MM. As a result, the LCurine/eGFR quotient recognizes 100% of all CN and can therefore detect this group, which has a very poor prognosis, without the need for a kidney biopsy. Full article

Background and Objectives: The clinical presentation and survival factors in patients with myeloma-related kidney impairment (MRKI) at diagnosis remain a topic of ongoing research, given the complex interplay between nephrology and hematology. To date, no studies have specifically reported outcomes for these patients in Eastern Europe. Materials and Methods: We conducted a retrospective, unicentric study of consecutive newly diagnosed patients with MRKI in our tertiary nephrology service in Romania between 2015 and 2020; follow-up extended until 1 September 2022, covering a study period of 90 months. Results: We identified 89 consecutive patients with MRKI (median age 66 years, 38% male, median eGFR 5 mL/min). The majority of patients had arterial hypertension (71%) and systemic atherosclerosis (58%), and the most frequent clinical features at presentation were asthenia (75%) and bone pain (51%). Light-chain-restricted myeloma was the most common type (55%), with kappa free light chain being more frequent (53%). Among the patients, 81% presented with acute kidney injury (AKI), and 38% required hemodialysis at diagnosis. During the study period, 65% of the patients died, and hypoalbuminemia and the need for hemodialysis at diagnosis were significantly associated with mortality in multivariate analysis. Conclusions: Patients with MRKI who present to the nephrologist more frequently exhibit light chain restriction and most often present with AKI, with one-third requiring hemodialysis at diagnosis. Moreover, hypoalbuminemia and the initiation of hemodialysis at diagnosis were significantly associated with increased mortality. Full article

Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies associated with WM and IgM MGUS than that seen in patients with multiple myeloma, where cast nephropathy predominates. In WM, uncommonly direct infiltration of the renal system by lymphoma or cast nephropathy with a high light-chain level can occur. AL amyloidosis can present with nephrotic syndrome as a feature with IgM MGUS or WM. Cryoglobulinaemia and light-chain deposition disease are other important potential causes of renal impairment with IgM MGUS and WM. There are other rarer monoclonal gammopathy of renal significance (MGRS) conditions characterised by typically isolated kidney disease that are causally related to a B-cell or plasma-cell clonal disorder usually in a precancerous MGUS state, although in some renal pathologies, the association is less clear. Central to the majority of these diagnoses is the need for an accurate renal histological diagnosis, and management requires close joint working of renal and haematology teams. Full article

Transcription factor PAX8, expressed during embryonic kidney development, has been previously detected in various kidney tumors. In order to investigate expression of PAX8 transcription factor in acute kidney injury (AKI) and chronic kidney diseases (CKD), immunohistochemical analysis was performed. Presence, location and extent of PAX8 expression were analyzed among 31 human kidney samples of AKI (25 autopsy cases, 5 kidney biopsies with unknown etiology and 1 AKI with confirmed myoglobin cast nephropathy), as well as in animals with induced postischemic AKI. Additionally, expression pattern was analyzed in 20 kidney biopsy samples of CKD. Our study demonstrates that various kidney diseases with chronic disease course that results in the formation of tubular atrophy and interstitial fibrosis, lead to PAX8 expression in the nuclei of proximal tubules. Furthermore, patients with PAX8 detected within the damaged proximal tubuli would be carefully monitored, since deterioration in kidney function was observed during follow-up. We also showed that myoglobin provoked acute kidney injury followed with large extent of renal damage, was associated with strong nuclear expression of PAX8 in proximal tubular cells. These results were supported and followed by data obtained in experimental model of induced postischemic acute kidney injury. Considering these findings, we can assume that PAX8 protein might be involved in regeneration process and recovery after acute kidney injury. Thus, accordingly, all investigation concerning PAX8 immunolabeling should be performed on biopsy samples of the living individuals. Full article

Background: The simultaneous occurrence of impaired kidney function and paraproteinemia is common in our constantly aging society. Both can be independent entities; however, renal insufficiency can also be caused by the paraprotein. We assessed all kidney biopsies in patients with monoclonal gammopathy in our clinic over the past 20 years and evaluated the histological results. Methods: Biopsies were systematically performed in nearly all patients with paraproteinemia and impaired kidney function (n = 178). The histological findings were systematically evaluated and correlated with the initial clinical diagnosis. Results: We found cast nephropathy (CN) in n = 66 (37.1%) biopsies, AL amyloidosis in n = 31 (17.4%) biopsies, monoclonal immunoglobulin deposition disease (MIDD) in n = 7 (3.9%) biopsies and other renal diseases (ORDs) in n = 74 (41.6%) biopsies. In the latter group, paraprotein-associated changes were found in 37 of 74 (50%) patients, whereas paraprotein-independent changes were found in the other half. Whereas, in the group of patients with MGUS, the findings were heterogenous, most of the patients with known multiple myeloma (MM) or B-NHL showed malignancy-associated changes in the kidney. The biopsy changed the diagnoses in a significant proportion of the patients: The group of patients with MM grew from 71 to 112 patients, whereas, in the MGUS group, only 31 of 44 patients remained. Conclusion: Kidney biopsies in patients with paraproteinemia and renal impairment show a wide range of findings that can lead to a change in diagnosis. Full article

Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in nephrons enhanced by prolonged exposure to sHyb, particularly in the presence of promoting factors, as highlighted by a literature reviewed and by personal experience. The aim of our update is to retrace CN in its pathophysiology, risk factors, diagnosis and treatment, underlining the role of sHyb, promoting factors, and CN-AKI diagnostic criteria in the different clinical settings associated with this often-concealed disease. Our purpose is to focus on clinical manifestation of CN, exploring the possible transition to CKD. Cholemic nephropathy is an overlooked clinical entity that enters differential diagnosis with other causes of AKI. Early diagnosis and treatment are essential because renal injury could be fully reversible as rapidly as bilirubin levels are reduced. In conclusion, our proposal is to introduce an alert for considering CN in diagnostic and prognostic scores that include bilirubin and/or creatinine with acute renal involvement, with the aim of early diagnosis and treatment of sHyb to reduce the burden on renal outcome. Full article

Monoclonal gammopathies (MG) encompass a variety of disorders related to clonal expansion and/or malignant transformation of B lymphocytes. Deposition of free immunoglobulin (Ig) components (light or heavy chains, LC/HC) within the kidney during MG may result over time in multiple types and degrees of injury, including acute kidney injury (AKI). AKI is generally a consequence of tubular obstruction by luminal aggregates of LC, a pattern known as “cast nephropathy”. Monoclonal Ig LC can also be found as intracellular crystals in glomerular podocytes or proximal tubular cells. Proliferative glomerulonephritis with monoclonal Ig deposits is another, less frequent form of kidney injury with a sizable impact on renal function. Hypercalcemia (in turn related to bone reabsorption triggered by proliferating plasmacytoid B cells) may lead to AKI via functional mechanisms. Pharmacologic treatment of MG may also result in additional renal injury due to local toxicity or the tumor lysis syndrome. The present review focuses on AKI complicating MG, evaluating predictors, risk factors, mechanisms of damage, prognosis, and options for treatment. Full article

Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19–26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed. Full article

Background: Anticoagulant-related nephropathy (ARN) is a form of acute kidney injury that mainly occurs in patients with previously unrecognized glomerular disease in addition to excessive anticoagulation. Since a renal biopsy is not performed in most cases, the diagnosis is often presumptive. Methods: Here, we present the characteristics of a national Slovenian patient cohort with histologically verified ARN, from the first case in 2014 to December 2020, and a review of the current literature (Pubmed database). Results: In Slovenia, ARN has been detected in 13 patients, seven of whom were treated with coumarins, and others with direct oral anticoagulants. In seven patients, ARN appeared after excessive anticoagulation. As many as 11 patients had underlying IgA nephropathy. Similar to the global data presented here, the pathohistological impairment associated with pre-existing glomerulopathy was mild and disproportionate to the degree of functional renal impairment. The majority of our patients with ARN experienced severe deterioration of renal function associated with histological signs of accompanying acute tubular injury, interstitial edema, and occlusive red blood cell casts. These patients were treated with corticosteroids, which (in addition to supportive treatment and discontinuation of the anticoagulant drug) led to a further improvement in renal function. Conclusions: Anticoagulant therapy combined with a pre-existing glomerular injury may lead to ARN. In addition to discontinuation of the anticoagulant and supportive care, corticosteroids, which are currently listed in only a few cases in the world literature, may have a positive influence on the course of treatment. However, the benefits of steroid treatment must be weighed against the risk of complications, especially life-threatening infections. Full article

Melatonin, a pineal hormone, is well known to regulate the sleep–wake cycle. Besides, the hormone has been shown to display pleiotropic effects arising from its powerful anti-oxidant and anti-inflammatory activities. Recent studies have reported that melatonin exerts protective effects in animal models of kidney disease. However, the potential effects of melatonin on aristolochic acid (AA)-induced nephropathy (AAN) have not yet been investigated. Here, we found that the administration of melatonin ameliorated AA-induced renal dysfunction, as evidenced by decreased plasma levels of blood urea nitrogen and creatinine and histopathological abnormalities such as tubular dilatation and cast formation. The upregulation of tubular injury markers after AA injection was reversed by melatonin. Melatonin also suppressed AA-induced oxidative stress, as evidenced by the downregulation of 4-hydroxynonenal and reduced level of malondialdehyde, and modulated expression of pro-oxidant and antioxidant enzymes. In addition, p53-dependent apoptosis of tubular epithelial cells, infiltration of macrophages and CD4⁺ T cells into damaged kidneys, and renal expression of cytokines and chemokines were inhibited by melatonin. Moreover, melatonin attenuated AA-induced tubulointerstitial fibrosis through suppression of the tumor growth factor-β/Smad signaling pathway. These results suggest that melatonin might be a potential therapeutic agent for AAN. Full article

Pyrrole-imidazole (PI) polyamides are novel gene silencers that strongly bind the promoter region of target genes in a sequence-specific manner to inhibit gene transcription. We created a PI polyamide targeting human TGF-β1 (hTGF-β1). To develop this PI polyamide targeting hTGF-β1 (Polyamide) as a practical medicine for treating progressive renal diseases, we examined the effects of Polyamide in two common marmoset models of nephropathy. We performed lead optimization of PI polyamides that targeted hTGF-β1 by inhibiting in a dose-dependent manner the expression of TGF-β1 mRNA stimulated by PMA in marmoset fibroblasts. Marmosets were housed and fed with a 0.05% NaCl and magnesium diet and treated with cyclosporine A (CsA; 37.5 mg/kg/day, eight weeks) to establish chronic nephropathy. We treated the marmosets with nephropathy with Polyamide (1 mg/kg/week, four weeks). We also established a unilateral urethral obstruction (UUO) model to examine the effects of Polyamide (1 mg/kg/week, four times) in marmosets. Histologically, the renal medulla from CsA-treated marmosets showed cast formation and interstitial fibrosis in the renal medulla. Immunohistochemistry showed strong staining of Polyamide in the renal medulla from CsA-treated marmosets. Polyamide treatment (1 mg/kg/week, four times) reduced hTGF-β1 staining and urinary protein excretion in CsA-treated marmosets. In UUO kidneys from marmosets, Polyamide reduced the glomerular injury score and tubulointerstitial injury score. Polyamide significantly suppressed hTGF-β1 and snail mRNA expression in UUO kidneys from the marmosets. Polyamide effectively improved CsA- and UUO-associated nephropathy, indicating its potential application in the prevention of renal fibrosis in progressive renal diseases. Full article

Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in a wider context, such as in the case reported in this paper, which for the first time describes an association between syphilis infection and IgA-dominant glomerulonephritis. A 16-year-old woman, referred to a general hospital due to a seizure, was found to be unknowingly pregnant. Based on hypertension and nephrotic proteinuria, she was initially diagnosed with PE. Immunological tests, as well as hepatitis and HIV tests showed negative results. However, secondary syphilis was diagnosed. In discordance with the PE diagnosis, urinalysis showed glomerular microhematuria with cellular casts. Proteinuria and hypertension did not remit after delivery, which was made via caesarean section, due to uncontrolled hypertension, at an estimated gestational age of 29 weeks. A male baby, weighing 1.1 kg (6.5 centile) was born. The baby was hospitalized in the neonatal intensive care unit, where he developed subependymal hemorrhage and thrombocytopenia, and neonatal syphilis was diagnosed. The mother underwent a kidney biopsy one week after delivery, leading to the diagnosis of IgA-dominant postinfectious glomerulonephritis. Mother and child were treated with support and antibiotic therapy, and were discharged in good clinical conditions four weeks later. Four months after delivery, the mother was normotensive without therapy, with normal kidney function and without hematuria or proteinuria. In conclusion, this case suggests that IgA-dominant postinfectious glomerulonephritis should be added to the spectrum of syphilis-associated glomerulonephritides, and underlines the need for a careful differential diagnosis with CKD in all cases of presumed PE. While diagnosis relies on kidney biopsy, urinary sediment, a simple and inexpensive test, can be the first step in distinguishing PE from other nephropathies. Full article

Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention. Full article