Subnephrotic Range Proteinuria Research Articles

Prognostic Impact of Proteinuria at Manifestation in Adult Nephrotic Syndrome Patients: Insights from a Prospective Cohort Study.

Background and objective Nephrotic syndrome is a significant worldwide health concern impacting millions of people and is marked by heavy proteinuria, edema, and decreased serum levels of albumin. Albuminuria arises from abnormal glomerular permeability and impaired tubular reabsorption, contributing to declining kidney function and a heightened risk of cardiovascular complications. The objective of this study was to investigate the prognostic role of proteinuria on the persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) during follow-up and the dynamics of remission and relapse in various subtypes of nephrotic syndrome. Methods A total of 134 adult patients, diagnosed with various histopathological categories of nephrotic syndrome, were prospectively studied. Urine protein levels were assessed using the pyrogallol red-molybdate (PRM) method. The Kaplan-Meier analysis and log-rank test were utilized to assess the prognostic role of proteinuria at manifestation on persistent decline in estimated glomerular filtration rate(eGFR) (<30 ml/minute/1.73m2) and to evaluate remission and relapse based on proteinuria levels over an 18-month follow-up period. Results Patients with sub-nephrotic levels of proteinuria at manifestation did not progress to end-stage renal disease on follow-up. Patients with sub-nephrotic levels of albuminuria at manifestation were significantly associated with remission on follow-up. The Kaplan-Meier analysis indicated a significant probability of persistent eGFR decline (p < 0.001) in adult nephrotics with higher levels of albuminuria. Furthermore, patients with sub-nephrotic range proteinuria had earlier remission (p < 0.001) compared to those with relapse (p = 0.001) during the follow-up, as demonstrated by log-rank tests. Conclusion This study highlights that sub-nephrotic albuminuria at manifestation is linked to a reduced risk of renal progression and persistent eGFR decline compared to adult nephrotics with higher levels of albuminuria. Early detection and effective management of proteinuria, are crucial for preventing renal function decline and improving patient outcomes.

#2862 Genetics and electron microscopy: complementary tools for management of focal segmental glomerulosclerosis?

Abstract Background and Aims Focal segmental glomerular sclerosis (FSGS) defines a histologic lesion that represents a pattern of injury associated to different pathologic conditions affecting both children and adults. It is classified into primary forms, presumably immune-mediated, secondary forms, determined by a maladaptive response to different conditions, genetic and undetermined forms. According to Mayo Clinic classification, primary and secondary forms can de differentiated using electron microscopy (EM), with a podocytes foot process effacement (FPE) ≥80% identifying primary forms. Better understanding the role of Genetics in FSGS and response to treatment in different forms is of vital importance in this rare and multifaceted condition. We analyzed a discrete cohort of patients with FSGS examined both with EM and genetic testing (GT). Main aims of our study were: 1) assessment of GT in primary and secondary forms; 2) analysis of response to therapy according to histologic and genetic classification. Method This is a retrospective observational study on patients that received a histological diagnosis of FSGS, including EM, and underwent NGS genetic testing from January 2020 to June 2023. Primary and secondary forms of FSGS were distinguished by degree of pedicle fusion at EM, according to Mayo Clinic classification. Clinical, laboratory, genetic data and used therapies were recorded. Complete response (CR) to therapy was defined as a reduction of proteinuria to 0.3 g/day, with normalization of albuminemia. Partial response (PR) was defined as halving proteinuria into a sub-nephrotic range and increasing albuminemia up to 3.5 g/dL. Absent response was defined as a persisting nephrotic range proteinuria. Results In the study period, 33 patients receiving a histologic diagnosis of FSGS with EM examination underwent NGS testing. Of these, 25 had available genetic results and were included. Ten patients (40%) were females, 15 (60%) were males; mean age was 40.8 years (SD ±14.5); 20 (80%) were Caucasian, 4 (16%) Black, 1 (4%) Asian. Based on EM, 11 (44%) were classified as primary forms, 14 (56%) as secondary forms. Twelve (48%) patients presented with nephrotic syndrome. Of these, 10 had a primary form. Seven (28%) had nephrotic-range proteinuria without hypoalbuminemia, 6 (24%) had subnephrotic range proteinuria. Six (54.5%) of the primary forms and 8 (57.1%) of the secondary forms had a positive genetic testing (p = 0.78). Among secondary forms, through GT, one diagnosis of Fabry disease and one of Tuberous Sclerosis were made in patients without clear systemic symptoms. Fabry disease was confirmed by presence of zebra bodies at EM. All primary forms received immunosuppressive therapies, all being rituximab-based regimens; all secondary forms received support therapy. Nine (81.1%) primary forms and 9 (64.3%) secondary forms had at least a PR to treatment (4 CR in primary group and 1 CR in secondary group) (p = 0.33). Among primary forms, 5 of 6 patients (83%) with a positive GT had at least a PR with a strong immunosuppressive therapy. In secondary forms group 4 of 8 patients (50%) had at least PR with offered support therapy. Fabry and Tuberous Sclerosis were offered specific treatments with benefit. Conclusion Percentage of positive GT did not differ in primary and secondary forms of FSGS as defined by Mayo Clinic classification. Thus a positive GT should not be considered a unique feature of secondary forms. GT was critical for an unexpected diagnosis of systemic hereditary diseases, thus enabling adequate target therapies. We believe GT should be offered to all patients with FSGS. In primary FSGS, defined according to EM, more than 80% of patients had at least a PR following immunosuppressive therapy, even in patients with positive GT. In conclusion, as clinical presentation and light microscopy are not sufficient for an accurate diagnosis, combining EM and GT is of utmost importance in proper classification and management of FSGS.

Implications of Complete Proteinuria Remission at any Time in Focal Segmental Glomerulosclerosis: Sparsentan DUET Trial

Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disease with high unmet clinical need. Interest in proteinuria as a surrogate end point for regulatory approval of novel treatments has increased. We assessed the relationship between achieving complete remission (CR) of proteinuria at least once during follow-up and long-term kidney outcomes. This post hoc analysis included all patients enrolled in the DUET trial of sparsentan in FSGS and the open-label extension (OLE). Evaluations occurred every 12 weeks, including blood pressure (BP), edema, proteinuria, and kidney function. CR was defined as a urine protein/creatinine ratio≤0.3g/g in a first morning urine sample. A total of 108 patients who received≥1 sparsentan dose were included in this study. During a median follow-up of 47.0 months, 46 patients (43%) experienced≥1 CR, 61% occurring within 12 months of starting sparsentan. There was an increased likelihood of CR with a higher sparsentan dose or baseline subnephrotic-range proteinuria. Achieving≥1 CR was associated with significantly slower rate of estimated glomerular filtration rate (eGFR) decline versus non-CR patients (P< 0.05). Use of immunosuppressive agents was more frequent in patients who achieved a CR. However, the antiproteinuric effect of sparsentan was additive to that achieved with concomitant immunosuppressive treatment. No unanticipated adverse events occurred. We conclude that sparsentan can be safely administered for extended periods and exerts a sustained antiproteinuric effect. Achievement of CR at any time during follow-up, even if it is not sustained, may be an indicator of a favorable response to treatment and a predictor of improved kidney function outcomes.

A study of clinicopathological features and selected laboratory parameters in a cohort of Sri Lankan patients with lupus nephritis

Introduction: Lupus nephritis (LN) is a complication of systemic lupus erythematosus that results in significant morbidity and mortality. Several studies have shown an association between certain pathological lesions and laboratory parameters in LN.Objective: The objectives were to describe the clinicopathological features and laboratory parameters in a cohort of Sri Lankan patients with biopsy-proven LN and determine the associations between the pathological features and laboratory parameters.Method: This was a retrospective, cross-sectional study of all renal biopsies of LN reported at the Department of Pathology, Faculty of Medicine, University of Colombo from January 2017 to December 2021.Results: Eighty cases were identified. The majority were females (95%, 76/80). The mean age at biopsy was 27 ± 10.71 years. Subnephrotic range proteinuria (43.8%, 35/80) was the commonest presentation. The most frequent histological type was class IV (66.3%, 53/80) followed by class II (15%, 12/80) and class III (10%, 8/80). Serum creatinine showed a significant association with both activity and chronicity indices. Glomerulosclerosis showed an association with serum creatinine levels while cellular/fibrocellular crescents were associated with both serum creatinine levels and red cells in urine.Conclusion: In this cohort of Sri Lankan patients with LN, the serum creatinine level showed an association with activity/chronicity indices and the presence of glomerulosclerosis and crescents in the renal biopsy. The presence of red cells in urine showed an association with crescents.

Clinicopathological spectrum of biopsy-proven renal diseases of patients at a single center in Sri Lanka: a cross sectional retrospective review

BackgroundThe clinical presentation of renal diseases can vary widely. The lack of a comprehensive national registry for Sri Lanka makes it difficult to provide a detailed record of the various clinical presentations and histopathology of renal disorders in the nation. Therefore, this study aims to provide a record of the spectrum of renal diseases in Sri Lanka.MethodsRenal biopsies performed at the nephrology unit in Colombo South Teaching Hospital (CSTH), Sri Lanka from March 2018 to October 2019 was retrospectively studied. Indications for renal biopsy were nephrotic range proteinuria, sub nephrotic range proteinuria, acute kidney injury without obvious etiology, chronic renal disease without obvious etiology and haematuria.ResultsA total of 140 native kidney biopsies were analyzed in which majority were females (55.7%). The mean age of the population was 46 ± 15.3 years. The most common indications for renal biopsy were nephrotic range proteinuria (54.3%), followed by sub-nephrotic range proteinuria (14.3%), nephrotic range proteinuria with haematuria (14.3%), sub-nephrotic range proteinuria with haematuria (9.3%), AKI without known cause (4.3%), and CKD without known cause (3.6%). The leading histopathological diagnoses were FSGS (22.1%), lupus nephritis (20%), PSGN (17.1%), DN (12.1%), HTN (9.3%), MCD (6.4%), IgA nephropathy (5.7%), IN (4.3%), vasculitis (2.1%), and MGN (0.7%).ConclusionsThe most common indication for renal biopsy was nephrotic range proteinuria in our population. FSGS was the most prevalent histopathological diagnosis and the least frequent diagnosis reported was MGN. The spectrum of renal diseases could differ according to the study location and it changes over time. Therefore, a renal biopsy registry is needed for documenting the changing disease pattern in Sri Lanka.

The diagnostic value of native kidney biopsy in low grade, subnephrotic, and nephrotic range proteinuria: A retrospective cohort study.

In nephrotic range proteinuria of adult-onset, kidney biopsy is the diagnostic gold standard in determining the underlying cause of disease. However, in low grade or subnephrotic proteinuria the diagnostic value of kidney biopsy as first-line diagnostics is less well established. We conducted a retrospective analysis of all native kidney biopsies at our institution (n = 639) between 01/2012 and 05/2021 for comparison of histological diagnoses and clinical outcomes stratified by amount of proteinuria at the time of kidney biopsy: A: <300mg/g creatinine (low grade), B: 300-3500mg/g creatinine (subnephrotic), C >3500mg/g creatinine (nephrotic). Nephrotic range proteinuria was associated with the highest frequency (49.3%) of primary glomerulopathies followed by subnephrotic (34.4%) and low grade proteinuria (37.7%). However, within the subnephrotic group, the amount of proteinuria at kidney biopsy was linearly associated with renal and overall survival (HR 1.05 per Δ100mg protein/g creatinine (95% CI: 1.02-1.09, p = 0.001)) independent of present histological diagnoses and erythrocyturia. Frequency of primary glomerulopathies supports to perform kidney biopsy in patients with subnephrotic proteinuria. These patients have a substantial risk of ESKD and death upon follow-up. Therefore, diagnostic accuracy including histopathology is essential to guide personalized treatment and avert detrimental courses.

Henoch-Schonlein Purpura in a Newly Diagnosed HIV Patient.

HIV infection is associated with multisystemic manifestations due both to secondary infections caused by a decrease in the CD4+ T-cell count and to the pathogenicity of the HIV virus itself. A common renal manifestation is HIV-associated nephropathy, which is frequently seen in the African population with the APOL1 gene mutation; however, other forms of glomerulopathy such as IgA nephropathy, commonly noted in other ethnicities, are also seen. Vasculitis has rarely been associated with HIV infection and mainly involves small blood vessels, although any size of blood vessel may be involved. The association of Henoch-Schonlein purpura (HSP) with HIV is rare and not well understood. We describe a 53-year-old African American woman with a newly diagnosed HIV infection who presented with a purpuric rash over the bilateral lower extremities with haematuria. Initial work-up revealed renal dysfunction with elevated ESR. Urinalysis was positive for glomerular haematuria and sub-nephrotic range proteinuria. Serum complement level, c-antineutrophil cytoplasmic antibody (ANCA), p-ANCA and anti-nuclear antibody (ANA) were negative. Renal biopsy revealed mesangial IgA deposits with crescent glomerulopathy and fibrinoid necrosis, while skin biopsy revealed leucocytoclastic vasculitis. A diagnosis of HSP was made based on American College of Rheumatology (ACR) criteria. The patient’s renal function and purpura improved with a 5-day course of steroid pulse therapy. This case of HSP in a newly diagnosed HIV patient is unusual for the presence of crescentic glomerulopathy.LEARNING POINTSHenoch-Schonlein purpura (HSP) associated with HIV infection is uncommon but documented; however, all four features of HSP are rarely seen together.Crescent glomerulopathy is rarely seen in HIV-associated HSP.HSP associated with HIV is treated with antiretroviral drugs, while the role of steroid and immunosuppressive therapy remains controversial.

Clinical Differences in Lupus Nephritis in Thai Patients with Systemic Lupus Erythematosus with Positive vs. Negative Anti-dsDNA Antibody

Objective: Anti-double strand deoxyribonucleic antibody (anti-dsDNA) is thought to trigger tissue inflammation-particularly in the kidney-in systemic lupus erythematosus (SLE). The association between anti-dsDNA and lupus nephritis (LN) has not been reported among Thais. The authors aimed to define the association between the clinical characteristics of positive vs. negative antidsDNA antibody in patients having SLE with LN. Materials and Methods: A historical cohort was conducted of SLE patients followed-up at Srinagarind Hospital, Khon Kaen University, Thailand, between January 2009 to December 2013. The authors excluded patients not tested for anti-dsDNA. Results: Of 132 SLE patients, the female was 123 cases. The respective mean age at onset and mean age during the study was 28.0&plusmn;11 and 35.2&plusmn;11.2 years. The mean duration of disease was 5.7&plusmn;4.7 years. Ninety-six cases were tested for anti-dsDNA, of whom 73 (76%) were positive. There was a significant association between the presence of anti-dsDNA antibody and subnephrotic range proteinuria (p=0.048) and negative association with LN class IV A/C at onset (p=0.04). Conclusion: Anti-dsDNA was positive in around three-quarters of Thai SLE patients and the presence of the antibody was associated with renal involvement, particularly subnephrotic range proteinuria. Keywords: Systemic lupus erythematosus; Autoimmune diseases; Anti-dsDNA antibody; Lupus nephritis; Proteinuria

Poststreptococcal Glomerulonephritis without Hypertension in a Patient with Concealed Skin Lesions

Poststreptococcal Glomerulonephritis (PSGN) is an acute inflammation of renal glomerular parenchyma and is sequelae of pharyngitis or skin infection caused by nephritogenic strains of group A beta-Haemolytic Streptococcus. PSGN is conventionally diagnosed based upon clinical findings and demonstration of recent streptococcal infection by a positive skin/throat culture or serologic tests. Hereby, authors present a case of PSGN in an 18-year-old normotensive male is reported who presented with anasarca. On evaluation, the patient had subnephrotic range proteinuria without haematuria and normal serum creatinine. Concealed healing skin lesions in the gluteal region, suggestive of impetigo were noted and hence, arrived at the diagnosis of PSGN. He was treated with intravenous antibiotics, following which symptoms improved. Young patients with acute presentation of oedema or proteinuria with possible renal cause warrants thorough head to foot examination for unseen skin lesions in otherwise overlooked areas. PSGN responds promptly with early antibiotic therapy.

HANTAVIRUS CARDIOMYOPATHY IN A PATIENT WITH NEWLY DIAGNOSED SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hantavirus infection, traditionally associated with Hantavirus Pulmonary Syndrome in critically ill adults, has been described in less severe illness with resultant cardiopulmonary consequences, particularly in strains endemic to Texas. Characterized by pulmonary infiltrates and azotemia, cardiomyopathy is a feared complication of acute disease. Systemic Lupus Erythematosus (SLE), a pathology of diffuse inflammation, may serve as a predisposition to the development of viral sequelae. CASE PRESENTATION: A 37-year-old healthy female with occupational lumber exposure presented with one week of persistent, positional and pleuritic pain and dyspnea following self-limited upper respiratory symptoms.She was afebrile and hypertensive (140/100) with tachycardia (102) and ambulatory pulse oximetry 88%. Auscultation was limited due to pain with inspiration but exam yielded no murmurs or rubs. Electrocardiogram revealed no PR or ST segment changes and CT angiogram demonstrated bilateral ground glass opacities and reactive lymphadenopathy without pulmonary embolism.Laboratory analysis returned significant for creatinine 1.28, albumin 2.7, troponin <.03, negative HIV and respiratory virus panel and normal complements. Urine studies had subnephrotic range proteinuria without casts. Serologic studies reported ANA >1:2560, elevated RNP, Rheumatoid Factor, Smith and SS-A antibodies and positive IgM testing for hantavirus. Echocardiogram verified an ejection fraction of 25-30% without pericardial effusion. Coronary and pulmonary artery catheterization were negative for ischemic heart disease or pulmonary hypertension. DISCUSSION: She was treated with colchicine, prednisone and furosemide with improvement. Given the presence of specific antibodies, negative cardiac catheterization, characteristic echocardiographic findings and clear viral trigger, the patient was clinically diagnosed with hantavirus cardiomyopathy in the setting of newly diagnosed SLE serving as a predisposition to a worsening inflammatory cascade. Due to high pretest probability and invasive nature of the procedure, endomyocardial biopsy was deferred. Ejection fraction recovered after three months following therapy with carvedilol and lisinopril. Hantavirus has been described as a precipitant of functional, often reversible, cardiomyopathy without myocardial structure disruption. Given the rapid return of cardiac function following guideline directed medical optimization, we posit a significant viral contribution. CONCLUSIONS: This case contributes to the body of literature identifying hantavirus as a cause of functional cardiomyopathy. In the setting of co-morbid SLE, it lends to the importance of considering infectious etiologies in tandem with underlying inflammatory physiology. We believe the incidence of hantavirus to be underreported and must be considered in a patient with pulmonary infiltrates, renal involvement and cardiomyopathy. Reference #1: Knust B, Rollin PE. Twenty-year summary of surveillance for human hantavirus infections, United States. Emerg Infect Dis. 2013;19(12):1934–1937 Reference #2: Fabiano P. Saggioro, Marcos A. Rossi, Maria Irma S. Duarte, Carmen Cinira S. Martin, Venâncio A. F. Alves, Marcos L. Moreli, Luis Tadeu M. Figueiredo, Jorge E. Moreira, Alessandra A. Borges, Luciano Neder, Hantavirus Infection Induces a Typical Myocarditis That May Be Responsible for Myocardial Depression and Shock in Hantavirus Pulmonary Syndrome, The Journal of Infectious Diseases, Volume 195, Issue 10, 15 May 2007, Pages 1541–1549, https://doi.org/10.1086/513874 Reference #3: Machado, A. M., De Figueiredo, G. G., Sabino dos Santos Jr, G., & Figueiredo, L. T. M. (2009). Laboratory diagnosis of human hantavirus infection: novel insights and future potential. Future Virology, 4(4), 383-389. DISCLOSURES: No relevant relationships by Molly Horstman, source=Web Response No relevant relationships by Christopher Nemeh, source=Web Response No relevant relationships by Thiennga Vo, source=Web Response

Insights into the Role of Renal Biopsy in Patients with T2DM: A Literature Review of Global Renal Biopsy Results.

IntroductionRenal biopsy performed in patients with type 2 diabetes mellitus (T2DM) for atypical or suspected diabetic kidney disease (DKD) reveals one of three possibilities: diabetic nephropathy (DN, pathological diagnosis of DKD), nondiabetic kidney disease (NDKD) and DN plus NDKD (mixed form). NDKD (including the mixed form) is increasingly being recognized worldwide. With the emerging concept of DKD and the complexity of routine application of renal biopsy, the identification of “clinical indicators” to differentiate DKD from NDKD has been an area of active research.MethodsThe PubMed database was searched for relevant articles mainly according to the keyword search method. We reviewed prevalence of the three types of DKD and different pathological lesions of NDKD. We also reviewed the clinical indicators used to identify DKD and NDKD.ResultsThe literature search identified 40 studies (5304 data) worldwide between 1977 and 2019 that looked at global renal biopsy and pathological NDKD lesions. The overall prevalence rate of DN, NDKD and DN plus NDKD is reported to be 41.3, 40.6 and 18.1%, respectively. In Asia, Africa (specifically Morocco and Tunisia) and Europe, the most common isolated NDKD pathological type is membranous nephropathy, representing 24.1, 15.1 and 22.6% of cases, respectively. In contrast, focal segmental glomerulosclerosis is reported to be the primary pathological type in North America (specifically the USA) and Oceania (specifically New Zealand), representing 22% and 63.9% of cases, respectively. Tubulointerstitial disease accounts for a high rate in the mixed group (21.7%), with acute interstitial nephritis being the most prevalent (9.3%), followed by acute tubular necrosis (9.0%). Regarding clinical indicators to differentiate DKD from NDKD, a total of 14 indicators were identified included in 42 studies. Among these, the most commonly studied indicators included diabetic retinopathy, duration of diabetes, proteinuria and hematuria. Regrettably, indicators with high sensitivity and specificity have not yet been identified.ConclusionTo date, renal biopsy is still the gold standard to diagnose diabetes complicated with renal disease, especially when T2DM patients present atypical DKD symptoms (e.g. absence of diabetic retinopathy, shorter duration of diabetes, microscopic hematuria, sub-nephrotic range proteinuria, lower glycated hemoglobin, lower fasting blood glucose). We conclude that renal biopsy as early as possible is of great significance to enable personalized treatment to T2DM patients.

P0306ACUTE KIDNEY INJURY AFTER CHECKPOINT INHIBITOR TREATMENT: FACING THE FUTURE

Abstract Background and Aims Checkpoint inhibitors (CPI) are used to treat solid organ metastatic malignancies. They act on by triggering a vigorous immune response against tumoral cells, preventing their proliferation. CPIs reinvigorate antitumor immune responses by interrupting co-inhibitory signaling pathways and promote immune-mediated elimination of tumor cells.This is not a selective response, deriving in immune related adverse events (irAEs). The kidney can potentially be damaged with an incidence of 13-29%. The most frequent type of toxicity is acute interstitial nephritis (AIN). Method We evaluated all the patients with solid organ metastatic malignancies treated with immunotherapy that developed acute renal injury (AKI) and underwent to kidney biopsy from March 2018 to November 2019 at Vall d’Hebron University Hospital. Results 11 patients with solid organ metastatic malignancies treated with immunotherapy developed AKI and underwent to kidney biopsy during the study period. The most frequent malignancy was lung cancer - in 6 patients-, followed by 3 patients with melanoma. 8 patients (72%) had already received previous oncological therapy, and for the remaining 3 patients (27%), CPI was the first line therapy. 8 patients (72%) were treated with anti-PD1 (programmed cell death protein 1), 4 patients (36 %) received anti PDL-1 (programmed death-ligand 1) 1 of these patients in combination with an anti CTLA-4 (cytotoxic T-lymphocyte antigen 4) and another patient received both anti PD1 and anti PDL-1. The time between the start of CPI and the onset of the AKI ranged between 2-11 months. The most frequent urine findings were subnephrotic range proteinuria with a mean protein/creatinine (mg/g creatinine) 503.6 ± 190.5 and leukocyturia in 9 of 11 patients. Mean creatinine (mg/dl) at diagnosis was 3.4 ± 1.3. 10 out of the 11 patients were diagnosed of AIN after performing a kidney biopsy. The remaining patient presented chronic changes (IFTA and glomerulosclerosis) in the biopsy, performed after receiving steroids for a month. 3 patients who presented AIN received pulses of methylprednisolone 250-500mg as induction treatment and 7 patients received prednisone 1mg/kg/day. Mean prednisone accumulated dose (mg) during the first month of treatment was 1387.5 ± 540. 9 patients experienced complete recovery of kidney function and two patients progressed to CKD. Conclusion We reported 11 patients who presented AKI associated to CPI treatment and underwent to kidney biopsy in the last 20 months at our center. 10 out of 11 presented biopsy confirmed CPI related AIN. In our experience, CPI related AIN is the most frequent renal lesion associated to the novel immunotherapy treatments. This entity seems to have good renal prognosis as long as steroid treatment is early started.

P0463KIDNEY INVOLVEMENT IN PARAPROTEINEMIC DISEASES - ANALYSIS OF THE SINGLE CENTER REGISTER OF KIDNEY BIOPSIES

Abstract Background and Aims Kidneys are often damaged in paraproteinemic conditions. Paraproteins are monoclonal immunoglobulins or immunoglobulin fractions that are produced by a clonal population of B- or plasma cell lineage and can cause a variety of histological patterns of kidney injury, such as light chain (AL) amyloidosis or light chain cast nephropathy (LCCN). Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders in which a monoclonal immunoglobulin secreted by B- or plasma cell clone causes renal damage. By definition, these disorders do not meet diagnostic criteria for overt, symptomatic multiple myeloma or a lymphoproliferative disorder, but in contrast to monoclonal gammopathy of undetermined significance (MGUS) there is evidence of end-organ damage that can warrant therapy. Method All patients with paraproteinemic kidney disease were identified by retrospective review of the Hospital Register of kidney biopsies done at Department of Nephrology and Dialysis, in Dubrava University Hospital, Zagreb, from 2009 until 2018. Every kidney biopsy was analyzed by light, immunofluorescent and electron microscopy. Laboratory findings, including serum protein electrophoresis, serum free light chain level and immunofixation of serum proteins, were done for every patient. Clinical and histologic features of patients and features of underlying hematological conditions were analyzed. Results We identified 47 patients (3,28% of all biopsies that were done in that period) with kidney disease with clear hematological background. The mean patients' age at the time of the biopsy was 63 years and 27 of them were females. Two patients had signs of direct infiltration of kidneys with malignant lymphomic cells (non-Hodgkin lymphoma) and were excluded from the analysis. Clinical presentation of the patients at the time of biopsy were: proteinuria in 85% of patients, full nephrotic syndrome in 55%, azotemia in 66% of patients (80% had acute kidney injury of unclear etiology) and hematuria in 12,7%. Most common histologic patterns of kidney injury were AL amyloidosis (45%) and LCCN (30%) but additionally 7 different histological patterns were found: light chain depostion disease, light chain proxymal tubulopathy, fibrillary and imunotactoid glomerulopathy, proliferative glomerulonephritis with monoclonal immunoglobulin deposition, crioglobulinemic glomerulopathy type I and tubulointerstitial damage caused by immunoglobulin deposition. Figure 1 shows main features of patients with AL amyloidosis and cast LCCN. Conclusion Kidney disease can be initial presentation of an underlying paraproteinemia and, as our data showed, can clinicaly present with acute kidney injury, nephrotic or subnephrotic range proteinuria or full nephrotic syndrome. Variety of histologic patterns of kidney injury were described and AL amyloidosis and LCCN were the most common histological findings. Detailed hematologic workup should follow kidney biopsy in order to determine the exact nature and extension of the disease and therefore the most appropriate therapy.

Acute interstitial nephritis associated with immune checkpoint inhibitors: a single-centre experience.

BackgroundCheckpoint inhibitors (CPIs) are used to treat solid organ metastatic malignancies. They act by triggering a vigorous immune response against tumoural cells, preventing their proliferation and metastasis. However, this is not a selective response and can cause immune-related adverse events (irAEs). The kidney can potentially be damaged, with an incidence of irAEs of 1–4%. The most frequent type of toxicity described is acute interstitial nephritis (AIN).MethodsWe conducted a study of patients with solid organ metastatic malignancies treated with immunotherapy who developed acute renal injury and underwent kidney biopsy in the last 14 months at the Vall d’Hebron University Hospital.ResultsIn all, 826 solid organ malignancies were treated with immunotherapy in our centre, 125 of them (15.1%) developed acute kidney injury (AKI), 23 (18.4% of AKI) visited the nephrology department and 8 underwent kidney biopsy. The most frequent malignancy was lung cancer, in five patients (62%), followed by two patients (25%) with melanoma and one patient (12%) with pancreatic cancer. Four patients (50%) had already received previous oncological therapy, and for the remaining four patients (50%), CPI was the first-line therapy. Five patients (62%) were treated with anti-programmed cell death protein 1, three patients (37%) received anti-programmed death ligand 1 and two (25%) patients were treated in combination with anti-cytotoxic T-lymphocyte antigen 4. The time between the start of CPI and the onset of the AKI ranged from 2 to 11 months. The most frequent urine findings were subnephrotic-range proteinuria, with a mean protein:creatinine ratio of 544 mg/g (standard deviation 147) and eosinophiluria. All patients were biopsied after being diagnosed with AIN. Three patients (37%) received treatment with pulses of methylprednisolone 250–500 mg/day and five patients (62%) received prednisone 1 mg/kg/day. Seven patients (87%) experienced recovery of kidney function and one patient (12%) progressed to chronic kidney disease. ConclusionsWe report on eight patients with CPI-related AIN diagnosed in the last 14 months at our centre. The novel immunotherapy treatment of metastatic solid organ malignancies carries a higher risk of irAEs. The kidney is one of the most commonly affected organs, frequently presenting as an AIN and exhibiting a favourable response to steroid treatment.

Autosomal Dominant Tubulointerstitial Kidney Disease—Uromodulin Misclassified as Focal Segmental Glomerulosclerosis or Hereditary Glomerular Disease

IntroductionFocal segmental glomerulosclerosis (FSGS) is a histopathologically defined kidney lesion. FSGS can be observed with various underlying causes, including highly penetrant monogenic renal disease. We recently identified pathogenic variants of UMOD, a gene encoding the tubular protein uromodulin, in 8 families with suspected glomerular disease.MethodsTo validate pathogenic variants of UMOD, we reviewed the clinical and pathology reports of members of 8 families identified to have variants of UMOD. Clinical, laboratory, and pathologic data were collected, and genetic confirmation for UMOD was performed by Sanger sequencing.ResultsBiopsy-proven cases of FSGS were verified in 21% (7 of 34) of patients with UMOD variants. The UMOD variants seen in 7 families were mutations previously reported in autosomal dominant tubulointerstitial kidney disease-uromodulin (ADTKD-UMOD). For one family with 3 generations affected, we identified p.R79G in a noncanonical transcript variant of UMOD co-segregating with disease. Consistent with ADTKD, most patients in our study presented with autosomal dominant inheritance, subnephrotic range proteinuria, minimal hematuria, and renal impairment. Kidney biopsies showed histologic features of glomerular injury consistent with secondary FSGS, including focal sclerosis and partial podocyte foot process effacement.ConclusionOur study demonstrates that with the use of standard clinical testing and kidney biopsy, clinicians were unable to make the diagnosis of ADTKD-UMOD; patients were often labeled with a clinical diagnosis of FSGS. We show that genetic testing can establish the diagnosis of ADTKD-UMOD with secondary FSGS. Genetic testing in individuals with FSGS histology should not be limited to genes that directly impair podocyte function.

Clinical Profile, Histopathological Features and Outcome of IgA Nephropathy in a Tertiary Care Hospital in India.

IgA nephropathy (IgAN) is reported to be more common in Asians and is considered to be a very progressive disease with worse outcome. The present study encompasses a cohort of biopsy-proven IgAN in a tertiary care hospital to characterize the initial clinical presentation, Oxford classification profile and one year follow up of patients with clinical and biochemical investigations. All renal biopsies with a diagnosis of primary IgAN were included. In all biopsies with ≥8 viable glomeruli, the MEST-C scores were analyzed, according to the Oxford criteria. Demographic and clinical data included age, gender, presence of hypertension, presence of hematuria and edema. Baseline investigations include urine protein semiquantitative, spot urine protein creatinine ratio, 24-h urinary protein, serum creatinine, and serum albumin. All the details of the use of antiproteinuric drugs and immunosuppressive drugs were recorded. Total 48 renal biopsies (21.62%) were diagnosed as primary IgAN. Thirty-seven (77.08%) had renal dysfunction on initial presentation out of which 31 (64.5%) patients had subnephrotic range proteinuria (SNRP). MEST-C lesions distribution were interpreted in 39 patients. 42.85% of patients with nephrotic range proteinuria (NRP) and 55.55% of patients with SNRP had renal deterioration during follow up period while 28.57% patients with NRP and 41.66% patients with SNRP had reached end-stage renal disease (ESRD). Our study population of IgAN has a unique clinical profile with hypertension, microscopic hematuria and subnephrotic proteinuria as the predominant clinical presentation. In spite of low MEST-C score in our study cohort, the disease has an aggressive course with 47.91% of patients with renal function deterioration and about one third follow up patients approaching ESRD during the study period.

Membranoproliferative Glomerulonephritis- A Disease or a Pattern of Injury?

Introduction:Membranoproliferative Glomerulonephritis (MPGN) is a pattern of glomerular injury resulting from wide range of diseases sharing a common pathogenesis and thus, presented with large spectrum of clinical presentation starting from slowly progressive subnephrotic range proteinuria to nephritic syndrome and Rapidly Progressive Glomerulonephritis (RPGN). Aim: The aim of the study was to do reanalysis of the aetiological classification of MPGN and its prognostic outcomes. Materials and Methods: A retrospective, cohort study was conducted including the patients of all age groups with MPGN pattern of injury, from February, 2018 to August, 2018 at a Tertiary Healthcare Centre of West Bengal, India. All specimens were examined by two nephropathologists at the institute using both light microscope and immunofluorescence microscope. Haematoxylin and Eosin (H&amp;E), Periodic Acid-Schiff (PAS), silver methanamine, Masson’s Trichrome (MT) stained smears were prepared for light microscopy. Specimens for immunofluorescence microscopy were stained using Fluorescein Isothiocyanate (FITC) conjugated polyclonal rabbit anti-sera against human IgG, IgM, IgA, C3, C1q, kappa, lambda. Correlations were evaluated using Spearman’s rank correlation. A p&lt;0.05 was considered as statistically significant. GRAPHPAD PRISM 5 was used for statistical analysis. Results: From a total of 47 cases, 41 cases in immunoglobulin associated group, 4 cases in C3 nephropathy group and 2 cases in pauci-immune group were found. Autoimmune diseases had the strongest association followed by infections and dysproteinemia. Severity and chronicity parameters were more prevalent in the immunoglobulin positive group. The pauci-immune group showed maximum vascular involvement, indicating it to arise from a vascular pathology. Conclusion: Membranoproliferative Glomerulonephritis is not a single disease entity instead this pattern of injury could be seen in a variety of diseased condition.

Minimal change disease and Kimura's disease responding to tacrolimus therapy

Kimura's disease (KD) usually presents with a subcutaneous swelling and associated lymphadenopathy in the periauricular area. KD has a tendency to involve the kidneys. Proteinuria is reported in 12%-16% of cases, and around 60%-70% of them develop nephrotic range proteinuria. We are reporting a case of KD which developed around 12 years later in a patient of biopsy-proven steroid responsive minimal change disease. Recurrent swellings of KD and subnephrotic range proteinuria responded to low-dose tacrolimus therapy (0.05 mg/kg).

Celiac disease with subnephrotic range proteinuria: an enigma unresolved

Celiac disease, an autoimmune mediated enteropathy is associated with a variety of autoimmune diseases involving various organ systems to various extents, among which the renal involvement, although rare, needs a special reference. According to the literature, celiac disease is mostly associated with IgA nephropathy. Lupus nephritis and focal segmental glomerulosclerosis type of renal involvement has also been described to occur in association with celiac disease but many case reports have described patients of celiac disease presented with nephrotic or subnephrotic range proteinuria which have remained unexplained till date. Here we present such a case of with subnephrotic range proteinuria with normal kidney biopsy whose association has been explored.

The long-term outcomes and histological transformation in class II lupus nephritis.

Objectives:To examined the short and long-term outcome of class II lupus nephritis (LN).Methods:This retrospective study included patients with class II LN at their first renal biopsy between January 1996 and December 2016 in King Khaled University Hospital, Riyadh, Saudi Arabia. The rate of complete remission, worsening renal function, and histological transformation in the second biopsy were examined.Results:The study included 32 female patients with class II LN. The most frequent presentation (62.5% of patients) was hematuria with subnephrotic range proteinuria. The clinical presentation included acute kidney injury in 22% of patients, and 9.4% had nephrotic range proteinuria. Management with steroid monotherapy in 25 patients resulted in complete remission for 92% of these patients at 6 months. After a median follow up of 8 years, 2 patients had a doubling of their serum creatinine. During the follow up 17 patients (53%) needed a second biopsy, which revealed transformation to other classes (65%).Conclusions:Daily steroid monotherapy may be an appropriate first-line treatment for class II LN that presents with subnephrotic range proteinuria and normal kidney function. Patients with acute kidney injury and/or nephrotic range proteinuria may warrant more aggressive immunosuppressive regimens.