Risk of bleeding after percutaneous native kidney biopsy in patients receiving low-dose aspirin: a single-center retrospective study.

BACKGROUND: Although discontinuation of antiplatelet agents at least 5 days before kidney biopsy is commonly recommended, the evidence behind this practice is of low level. Indeed, few non-randomized studies previously showed an equivalent risk of bleeding in patients receiving aspirin therapy. METHODS: We conducted a single center retrospective study comparing the risk of complications after percutaneous native kidney biopsy in patients who received low-dose aspirin (ASA) within 5 days from biopsy and those who did not. The main outcome was the difference in the incidence of major complications (red blood cell transfusion, need for selective arterial embolization, surgery, nephrectomy). Secondary outcomes included difference in minor complications, comparison between patients who received ASA within 48 h or within 3-5 days, identification of independent factors predictive of major complications. RESULTS: We analyzed data on 750 patients, of whom 94 received ASA within 5 days from biopsy. There were no significant differences in the proportion of major complications in patients receiving or not receiving ASA (2.59% and 3.19%, respectively, percentage point difference 1%, 95% CI - 3 to 4%, p = 0.74). Groups were also comparable for minor complications; among patients receiving ASA, there were no differences in major bleeding between those who received ASA within 48 h or 3-5 days from biopsy. Significant baseline predictors of major bleeding in our cohort were platelet count lower than 120*103/microliter, higher diastolic blood pressure and higher blood urea. CONCLUSIONS: Treatment with low-dose ASA within 5 days from kidney biopsy did not increase the risk of complications after the procedure.

Skin reaction with Eosinophilia and Systemic Symptoms after lenalidomide in peritoneal Dialysis.

The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a fatal and immune-mediated idiosyncratic drug reaction, with symptoms of fever, skin eruptions (that involves more than half of the body surface), facial oedema and hematological disorders, all presenting within the latent period following drug intake. Effects can also be seen on multiple organs, most notably hepatitis in liver and acute interstitial nephritis in kidney, generally post-administration of allopurinol. The European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) classifies the DRESS Syndrome cases as "definite", "probable" or "possible", based on clinical and laboratory features. Different pathogenetic mechanisms have been involved in this disease, including immunological reactions and HHV-6 reactivation. In our experience, a 72-year-old male, affected by myeloma in peritoneal dialysis, developed a rare case of DRESS syndrome after lenalidomide administration (less than ten cases are known) with HHV-6 reactivation. According to literature, we withdrew the drug and gave methylprednisolone 0,8 mg/kg orally and IVIG 1 gr/kg for two days. Despite this therapy, DRESS syndrome relapsed during steroid taper with rash, thrombocytopenia, hepatitis and high troponin level. A single cycle of intravenous immunoglobulin 0,5 g/kg for four days was enough for syndrome remission. Only few cases are reported in literature, but because of the increasing use of lenalidomide and the autoimmune sequelae of DRESS syndrome, a broad workup and a multidisciplinar careful approach could help in diagnosis, treatment and follow-up.

Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images.

BACKGROUND AND OBJECTIVES: Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid-Schiff-stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores. RESULTS: We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r=0.41, P<0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1) inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts. CONCLUSIONS: The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_26_CJN01760222.mp3.

Artificial intelligence in glomerular diseases.

In this narrative review, we focus on the application of artificial intelligence in the clinical history of patients with glomerular disease, digital pathology in kidney biopsy, renal ultrasonography imaging, and prediction of chronic kidney disease (CKD). With the development of natural language processing, the clinical history of a patient can be used to identify a computable phenotype. In kidney pathology, digital imaging has adopted innovative deep learning algorithms (DLAs) that can improve the predictive capability of the examined lesions. However, at this time, these applications can only be used in research because there is no recognized validation to replace the conventional diagnostic applications. Kidney ultrasonography, used in the clinical examination of patients, provides information about the progression of kidney damage. Machine learning algorithms (MLAs) with promising results for the early detection of CKD have been proposed, but, still, they are not solid enough to be incorporated into the clinical practice. A few tools for glomerulonephritis, based on MLAs, are available in clinical practice. They can be downloaded on computers and cellular phones but can only be applied to uniracial cohorts of patients. To improve their performance, it is necessary to organize large consortia with multiracial cohorts. Finally, in many studies MLA development has been carried out using retrospective cohorts. The performance of the models might differ in retrospective cohorts compared to real-world data. Therefore, the models should be validated in prospective external large cohorts.

Methicillin-Resistant Staphylococcus aureus Peritonitis due to Hematogenous Dissemination from Central Venous Catheter in a Maintenance Dialysis Patient.

Staphylococcus aureus is a Gram-positive bacterium commonly associated with severe infections in hospitalized patients. S. aureus produces many virulence factors leading to local and distant pathological processes. Invasiveness of S. aureus generally induces metastatic infections such as bacteremia, infective endocarditis, osteomyelitis, arthritis, and endophthalmitis. Peritoneal localization from extra-abdominal infection can be a potential consequence of S. aureus infection. Two cases of metastatic peritonitis have been described in patients on peritoneal dialysis with concomitant peripheral vascular catheter-related bloodstream infection. We reported a case of peritoneal metastatic infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in a patient on maintenance hemodialysis. A 37-year-old man was admitted with fever and chill due to jugular central vascular catheter (CVC)-related bloodstream infection caused by MRSA. CVC was placed after switching the patient from peritoneal dialysis to hemodialysis for scarce adherence to fluid restriction. Detection of MRSA on the peritoneal effluent combined with a total white blood cell count of 554 cells/mm3 prompted the diagnosis of satellite MRSA peritonitis. Antibiotic treatment with daptomycin and simultaneous CVC and peritoneal catheter removal resolved the infectious process. No further metastatic localizations were detected elsewhere. In conclusion, S. aureus can induce metastatic infections far from the site of primary infection. As reported in this case, peritonitis can be secondary to the hematogenous dissemination of S. aureus especially in hospitalized patients having a central line.

Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study.

BACKGROUND: Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. METHODS: We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. RESULTS: Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. CONCLUSIONS: After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.

Clinical Presentation, Renal Histopathological Findings, and Outcome in Patients with Monoclonal Gammopathy and Kidney Disease.

Monoclonal gammopathies are associated with acute and chronic kidney injury. Nephrotoxicity of the secreted monoclonal (M)-protein is related to its biological properties and blood concentration. Little is known about epidemiology, clinical manifestations, and outcome of monoclonal gammopathies in patients with kidney disease. We retrospectively collected data about demographics, clinical manifestations, and renal histological lesions of all patients (n = 1334) who underwent kidney biopsy between January 2000 and March 2017. Monoclonal gammopathy was detected in 174 (13%) patients with a mean age of 66.4 ± 13.1 years. The spectrum of monoclonal gammopathies comprised monoclonal gammopathy of undetermined significate (MGUS) (52.8%), multiple myeloma (MM) (25.2%), primary amyloidosis (AL) (9.1%), smoldering MM (SMM) (4%), non-Hodgkin lymphoma (NHL) (6.8%), and Hodgkin lymphoma (HL) (1.7%). Monoclonal gammopathy of renal significance (MGRS) accounted for 6.5% in patients with MGUS and 14.2% in patients with SMM. Evaluation of kidney biopsy revealed that M-protein was directly involved in causing kidney injury in MM (93.1%). MM was the only gammopathy significantly associated with an increased risk of kidney injury (odds ratio [OR] = 47.5, CI 95%, 13.7-164.9; P ≤ 0.001). While there were no significant differences in the progression toward end-stage renal disease or dialysis (P = 0.776), monoclonal gammopathies were associated with a different risk of death (P = 0.047) at the end of the follow-up. In conclusion, monoclonal gammopathy was a frequent finding (13%) in patients who underwent kidney biopsy. M-protein was secreted by both premalignant (56.8%) and malignant (43.2%) lymphoproliferative clones. Kidney biopsy had a key role in identifying MGRS in patients with MGUS (6.5%) and SMM (14.2%). Among monoclonal gammopathies, only MM was significantly associated with biopsy-proven kidney injury. The rate of end-stage renal disease or dialysis was similar among monoclonal gammopathies, whereas NHL, MM, and SMM showed a higher rate of deaths.

Monoclonal B lymphocytosis in a kidney transplant recipient.

Monoclonal B lymphocytosis (MBL) is a lymphoproliferative condition characterised by expansion of a B-cell clone in peripheral blood, with an often indolent clinical course. The presence of a B clonal population alone is several hundred times more common in the general population than chronic lymphocytic leukaemia and other non-Hodgkin's lymphoma subtypes, it usually does not represent a malignant condition and it requires follow-up only, without specific treatment. There are few studies describing MBL in solid organ transplant recipients, thus, the concern is raised when enrolling MBL affected subjects in waiting lists. We report the experience of a patient affected by MBL who underwent kidney transplantation, with particular attention to preoperative screening and immunosuppressants impact on post-transplant lymphoproliferative disease risk, to aid clinicians in the evaluation process of transplant candidates affected by similar conditions.

Evaluation of the Classification Accuracy of the Kidney Biopsy Direct Immunofluorescence through Convolutional Neural Networks.

BACKGROUND AND OBJECTIVES: Immunohistopathology is an essential technique in the diagnostic workflow of a kidney biopsy. Deep learning is an effective tool in the elaboration of medical imaging. We wanted to evaluate the role of a convolutional neural network as a support tool for kidney immunofluorescence reporting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: High-magnification (×400) immunofluorescence images of kidney biopsies performed from the year 2001 to 2018 were collected. The report, adopted at the Division of Nephrology of the AOU Policlinico di Modena, describes the specimen in terms of "appearance," "distribution," "location," and "intensity" of the glomerular deposits identified with fluorescent antibodies against IgG, IgA, IgM, C1q and C3 complement fractions, fibrinogen, and κ- and λ-light chains. The report was used as ground truth for the training of the convolutional neural networks. RESULTS: In total, 12,259 immunofluorescence images of 2542 subjects undergoing kidney biopsy were collected. The test set analysis showed accuracy values between 0.79 ("irregular capillary wall" feature) and 0.94 ("fine granular" feature). The agreement test of the results obtained by the convolutional neural networks with respect to the ground truth showed similar values to three pathologists of our center. Convolutional neural networks were 117 times faster than human evaluators in analyzing 180 test images. A web platform, where it is possible to upload digitized images of immunofluorescence specimens, is available to evaluate the potential of our approach. CONCLUSIONS: The data showed that the accuracy of convolutional neural networks is comparable with that of pathologists experienced in the field.

TRPP2 dysfunction decreases ATP-evoked calcium, induces cell aggregation and stimulates proliferation in T lymphocytes.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is mainly characterised by the development and enlargement of renal cysts that lead to end-stage renal disease (ESRD) in adult patients. Other clinical manifestations of this pathology include hypertension, haematuria, abdominal pain, cardiovascular system alterations and intracranial aneurysms. ADPKD is linked to mutations in either PKD1 or PKD2 that codifies polycystin-1 (PC1) and polycystin-2 (PC2 or TRPP2), respectively. PC1 and TRPP2 are membrane proteins that function as receptor-channel elements able to regulate calcium homeostasis. The function of polycystins has been mainly studied in kidney cells; but the role of these proteins in T lymphocytes is not well defined. METHODS: T lymphocytes were produced from ADPKD1 and ADPKD2 patients as well as from non-ADPKD subjects undergoing renal replacement therapy (RRT) and healthy controls. Protein expression and phosphorylation levels were analysed by western blotting, cell proliferation was calculated by direct counting using trypan blue assay and intracellular calcium concentration was measured by Fura-2 method. RESULTS: PKD2 mutations lead to the significant reduction of TRPP2 expression in T lymphocytes derived from ADPKD patients. Furthermore, a smaller TRPP2 truncated protein in T lymphocytes of patients carrying the mutation R872X in PKD2 was also observed, suggesting that TRPP2 mutated proteins may be stably expressed. The silencing or mutation of PKD2 causes a strong reduction of ATP-evoked calcium in Jurkat cells and ADPKD2 T lymphocytes, respectively. Moreover, T lymphocytes derived from both ADPKD1 and ADPKD2 patients show increased cell proliferation, basal chemotaxis and cell aggregation compared with T lymphocytes from non-ADPKD subjects. Similarly to observations made in kidney cells, mutations in PKD1 and PKD2 dysregulate ERK, mTOR, NFkB and MIF pathways in T lymphocytes. CONCLUSIONS: Because the alteration of ERK, mTOR, NFkB and MIF signalling found in T lymphocytes of ADPKD patients may contribute to the development of interstitial inflammation promoting cyst growth and kidney failure (ESRD), the targeting of inflammasome proteins could be an intriguing option to delay the progression of ADPKD.

A Review of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited renal disorder; it is defined by progressive renal cyst formation and subsequent renal enlargement that leads to end-stage renal disease. Until recently, only symptomatic treatments for ADPKD existed. However, therapies that address the underlying pathophysiology of ADPKD are now available and accurate identification of the rate of disease progression is essential. SUMMARY: Published data on the different imaging modalities for measuring kidney and cyst volumes in ADPKD are reviewed. The advantages and drawbacks of the different techniques for calculating kidney volume from renal imaging are also examined, including the use of manual planimetry, stereology, and the ellipsoid equation, as well as the prospect of semi- and fully automatic techniques. The translation of these approaches into clinical practice and their role in informing treatment decisions is discussed. Key Messages: These new therapies require the accurate monitoring of disease progression, which along with diagnosis and prognosis, relies on the effective use of renal imaging techniques. There is growing support for the use of total kidney volume as a measure of cyst burden and as a prognostic predictor of renal function in ADPKD, showing promise as a marker of disease progression.

[Practical approach to patient therapy affected by Autosomal Dominant Autosomic Polycystic Kidney Disease].

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.

Defective glycolysis and the use of 2-deoxy-D-glucose in polycystic kidney disease: from animal models to humans.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies. Several of these potential treatments have proved effective in slowing down disease progression in pre-clinical animal studies, while only one has subsequently been proven to effectively slow down disease progression in patients, and it has recently been approved for therapy in Europe, Canada and Japan. Among the affected cellular functions and pathways, recent investigations have described metabolic derangement in ADPKD as a major trait offering additional opportunities for targeted therapies. In particular, increased aerobic glycolysis (the Warburg effect) has been described as a prominent feature of ADPKD kidneys and its inhibition using the glucose analogue 2-deoxy-D-glucose (2DG) proved effective in slowing down disease progression in preclinical models of the disease. At the same time, previous clinical experiences have been reported with 2DG, showing that this compound is well tolerated in humans with minimal and reversible side effects. In this work, we review the literature and speculate that 2DG could be a good candidate for a clinical trial in humans affected by ADPKD.

Comparison of Total Kidney Volume Quantification Methods in Autosomal Dominant Polycystic Disease for a Comprehensive Disease Assessment.

BACKGROUND: In recent times, the scientific community has been showing increasing interest in the treatments aimed at slowing the progression of the autosomal dominant polycystic kidney disease (ADPKD). Therefore, in this paper, we test and evaluate the performance of several available methods for total kidney volume (TKV) computation in ADPKD patients - from echography to MRI - in order to optimize patient classification. METHODS: Two methods based on geometric assumptions (mid-slice [MS], ellipsoid [EL]) and a third one on true contour detection were tested on 40 ADPKD patients at different disease stage using MRI. The EL method was also tested using ultrasound images in a subset of 14 patients. Their performance was compared against TKVs derived from reference manual segmentation of MR images. Patient clinical classification was also performed based on computed volumes. RESULTS: Kidney volumes derived from echography significantly underestimated reference volumes. Geometric-based methods applied to MR images had similar acceptable results. The highly automated method showed better performance. Volume assessment was accurate and reproducible. Importantly, classification resulted in 79, 13, 10, and 2.5% of misclassification using kidney volumes obtained from echo and MRI applying the EL, the MS and the highly automated method respectively. CONCLUSION: Considering the fact that the image-based technique is the only approach providing a 3D patient-specific kidney model and allowing further analysis including cyst volume computation and monitoring disease progression, we suggest that geometric assumption (e.g., EL method) should be avoided. The contour-detection approach should be used for a reproducible and precise morphologic classification of the renal volume of ADPKD patients.

[Clinical diagnosis of Autosomal Dominant Polycystic Kidney Disease]. / Diagnosi clinica del Rene Policistico Autosomico Dominante.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder related to kidney. ADPKD is usually easy to diagnose in people who have a family history of ADPKDs developing typical symptoms, including flank, abdominal pain or macroscopic hematuria. In this setting, diagnosis in adults at risk for ADPKD is commonly performed by ultrasonography, which reveals two enlarged kidneys with multiple bilateral cysts. ADPKD may be more difficult to diagnose in the absence of family history or in subjects with atypical presentation, including asymmetric or focal renal imaging findings, discordant disease within family, early onset of ADPKD and development of ESRD before 30 yr of age. The presence of a total of three or more renal cysts for at-risk subjects aged 15-39 years and two cysts or more in each kidney for at-risk subjects aged 40-59 years are sufficient for the diagnosis of ADPKD. The absence of any renal cyst is sufficient for disease exclusion only for at-risk subjects aged 40 years or older. If the family history is negative, the diagnosis of ADPKD can be made in a patient with enlarged kidneys, numerous cysts, presence of liver cysts and absence of findings suggesting a different cystic disease. If the imaging diagnosis is not clear or showing atypical manifestations in subjects, molecular genetic testing should be performed.

[Genetics and genetic counseling]. / Genetica e counseling genetico.

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.

Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy.

BACKGROUND: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. METHODS: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. RESULTS: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. CONCLUSION: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Reliability of Total Renal Volume Computation in Polycystic Kidney Disease From Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: Total renal volume (TRV) is an important quantitative indicator of the progression of autosomal dominant polycystic kidney disease (ADPKD). The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease proposes a method for TRV computation based on manual tracing and geometric modeling. Alternative approaches for TRV computation are represented by the application of advanced image processing techniques. In this study, we aimed to compare TRV estimates derived from these two different approaches. MATERIALS AND METHODS: The nearly automated technique for the analysis of magnetic resonance (MR) images was tested on 30 ADPKD patients. TRV was computed from both axial (KVax) and coronal (KVcor) acquisitions and compared to measurements based on geometric modeling (KVap) by linear regression and Bland-Altman analysis. In addition, to assess reproducibility, intraobserver and interobserver variabilities were computed. RESULTS: Linear regression analysis between KVax and KVcor resulted in an excellent correlation (KVax = 1KVcor - 0.78; r(2) = 0.997). Bland-Altman analysis showed a negligible bias and narrow limits of agreement (bias: -11.7 mL; SD: 54.3 mL). Similar results were obtained by comparison of volumes obtained applying the nearly automated method and the one based on geometric modeling (y = 0.98x + 75.9; r(2) = 0.99; bias: -53.7 mL; SD: 108.1 mL). Importantly, geometric modeling does not provide reliable TRV estimates in huge kidney affected by regional deformation. Intraobserver and interobserver variability resulted in very small percentage error <2%. CONCLUSIONS: The results of this study provide the feasibility of using a nearly automated approach for accurate and fast evaluation of TRV also in markedly enlarged ADPKD kidneys including exophytic cysts.

Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy?

The benefits of tonsillectomy in IgA nephropathy (IgAN) are still debated. Tonsillectomy may remove pathogen sources and reduce the mucosal associated lymphoid tissue (MALT), limiting degalactosylated IgA1 (deGal-IgA1) production, which is considered to be the initiating pathogenetic event leading to IgA glomerular deposition. In the European network VALIGA, 62/1147 IgAN patients underwent tonsillectomy (TxIgAN). In a cross-sectional study 15 of these patients were tested and compared to 45 non-tonsillectomized IgAN (no-TxIgAN) and healthy controls (HC) regarding levels of deGal-IgA1, and markers of innate immunity and oxidative stress, including toll-like receptors (TLR)2, 3, 4 and 9 mRNAs, proteasome (PS) and immunoproteasome (iPS) mRNAs in peripheral blood mononuclear cells (PBMC), and advanced oxidation protein products (AOPP). Levels of deGal-IgA1 were lower in TxIgAN than in no-TxIgAN (p = 0.015), but higher than in HC (p = 0.003). TLR mRNAs were more expressed in TxIgAN than in HC (TLR4, p = 0.021; TLR9, p = 0.027), and higher in TxIgAN than in no-TxIgAN (p ≤ 0.001 for TLR2, 4, 9). A switch from PS to iPS was detected in PBMC of TxIgAN in comparison to HC and it was higher than in no-TxIgAN [large multifunctional peptidase (LMP)2/ß1, p = 0.039; LPM7/ß5, p < 0.0001]. The levels of AOPP were significantly higher in TxIgAN than HC (p < 0.001) and no-TxIgAN (p = 0.033). In conclusion, the activation of innate immunity via TLRs and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy, even though the levels of aberrantly galactosylated IgA1 were lower in patients with IgAN who had tonsillectomy. The residual hyperactivation of innate immunity in tonsillectomized patients may result from extra-tonsillar MALT.