Renal Manifestations Research Articles

1029 FABRY DISEASE: A RARE CAUSE TO REMEMBER WHEN FACING ACUTE KIDNEY INJURY IN YOUNG

Abstract Introduction Anderson-Fabry disease (FD) is a rare X-linked hereditary disease caused by mutations in the alpha-galactosidase A (GLA) gene, a lysosomal hydrolase that catabolizes lipids. GLA deficency leads to a progressive accumulation of undegraded glycosphingolipids, mainly Globotriaosylceramide (GB3), within lysosomes of cells (epithelial and endothelial cells, neurons, cardiomyocytes and renal cells), leading to cellular dysfunction. The incidence of FD is 1:117.000 but in patients with end stage renal disease (ESRD), incidence is higher, ranging from 0.04% up to 1.16% in male dialysis patients. Classical form of the disease shows renal, cardiac and cerebrovascular involvements usually. Cardiac involvement includes hypertrophic cardiomyopathy, arrhythmias such as complete heart block, valve dysfunction and myocardial infarction. Renal manifestations include proteinuria, progressive loss of renal function with chronic kidney disease (CKD) that leads to ESRD. The diagnosis of FD can be very difficult and often is delayed due to subtle clinical manifestations, but an early diagnosis is crucial to start enzyme replacement therapy (ERT), based on recombinant human GLA, as soon as possible. Clinical Case we describe the case of a 36-years-old male admitted to the Emergency Room of our hospital due to asthenia, nausea, dysphagia, anuria and loss of weight. At physical examination, apical systolic murmur and a bilateral ankle edema. Blood pressure was 195/100 mmHg, heart rate 125 beats per minute, peripheral oxygen saturation 100%. Blood test showed Hemoglobin 8 g/dL, Blood Urea 422 mg/dL, Creatinine 20 mg/dL, Na+ 135 mEq/L, K+ 4 mEq/L, Phosphorus 9 mg/dL. Arterial blood gas analysis showed metabolic and lactic acidosis. The diagnosis of acute kidney injury (AKI) was made, and a dialytic treatment was scheduled. During dialytic session, the patient had a syncope. EKG showed a complete left bundle branch block (LBBB) with advanced atrio-ventricular block (2:1, complete). An echocardiogram highlighted a severe myocardial hypertrophy (septal wall 25 mm) involving also the right ventricle with “ground glass” aspect of the posterolateral, posterior and inferior septum, with minimal pericardial effusion. Heart MRI scan confirmed LV myocardial hypertrophy with circumferential aspect (interventricular septum 26.6 mm), mild decrease in left ventricular ejection fraction (47%) and myocardial hypointensity area in the FSE sequences. Renal ultrasound showed bilateral cortical hyperecogenity, small cortico-medullary border, initial reduction of kidney volume and diffuse perirenal edema. In consideration of the high probability of a storage disease, we performed genetic testing for FD and Gaucher disease, peri-umbilical fat biopsy for Amyloid Disease and a renal biopsy. The genetic test resulted positive for typical mutation of FD and renal biopsy documented ESRD secondary to glycosphingolipid storage disease ceramid type from FD. Conclusion Differential diagnosis of AKI in a young male should include FD, as suggested by the clinical case reported, and nephrologist should screen young patients for α-GLA enzyme deficiency (diagnostic for FD) possibly coupled with renal biopsy in uncertain cases.

Diverse renal manifestations of Alagille syndrome in Korean children

Purpose: To determine the prevalence, clinical manifestations, and outcomes of renal involvements in pediatric Alagille syndrome (ALGS).Methods: A total of 21 patients diagnosed with ALGS at age under 18 years who visited Samsung Medical Center from March 1999 to March 2022 were enrolled. ALGS was diagnosed either by clinical manifestations, targeted JAG1 sequencing, and/or liver biopsy. Medical records including sex, age, renal manifestations, urinalysis, serum creatinine, JAG1 sequencing, and ultrasonography were retrospectively reviewed.Results: The male to female ratio was 9:12. The mean age of patients at confirmative diagnosis of ALGS was 18.4 months. Sanger sequencing was performed for 17 patients. Sixteen of 21 patients (76.1%) showed JAG1 mutations. Renal involvement was found in 10 patients (47.6%). The most common type of anomaly was renal dysplasia (40%). One patient having renal dysplasia was pathologically confirmed with glomerular lipid deposition. Two patients (20%) manifested nephrocalcinosis/nephrolithiasis. Among eight renal-involved patients who survived, four (50%) progressed to chronic kidney disease stage 3. Two of these chronic kidney disease patients were diagnosed with hepatorenal syndrome. The other four patients had renal functions preserved, including two without any interventions and two who underwent urological interventions.Conclusions: The current study revealed a high prevalence of renal involvement in Korean pediatric ALGS with diverse phenotypes.

Soluble Tyro-3 and Axl may reflect the current activity and renal involvement in patients with microscopic polyangiitis and granulomatosis with polyangiitis.

This study investigated whether soluble Tyro-3 (sTyro-3), sAxl, and sMer could reflect the current activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). This study retrospectively reviewed the medical records of 76 patients with MPA and GPA, and measure the serum concentrations of sTyro-3, sAxl, and sMer using the stored serum at AAV diagnosis. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices included Birmingham vasculitis activity index (BVAS), five-factor score, the short-form 36-item health survey, and vasculitis damage index. High AAV activity was defined as the highest tertile of BVAS. The median age of the 47 MPA and 29 GPA patients was 66.0 years and 43.4% were men. The serum concentrations of sTyro-3 and sAxl were significantly correlated with BVAS and the total score of renal manifestation. The serum concentrations of sTyro-3 and sAxl were independently correlated with BVAS (β=0.343 and β=0.310, respectively). In addition, the serum concentrations of sTyro-3 and sAxl were independently associated with the renal involvement of MPA and GPA (OR 1.003 and OR 1.055, respectively). This study demonstrated the potential of the serum concentrations of sTyro-3 and sAxl to reflect the current activity and renal involvement in patients with MPA and GPA.

Successful treatment of infectious endocarditis-associated glomerulonephritis during active hepatitis C infection: a case report

BackgroundHepatitis C virus (HCV) may play a pathogenic role in several forms of immune complex glomerulonephritis (GN). We present a patient whose initial clinical presentation instilled suspicion of HCV-related renal involvement. Yet, histopathologic data oriented towards a different diagnosis.Case presentationA 68-year old man presented with kidney dysfunction, cryoglobulins, low C4 level, high HCV—RNA and cutaneous vasculitis. The first hypothesis was a hepatitis C-related cryoglobulinemic glomerulonephritis. Renal biopsy revealed endocapillary and mesangial cells hypercellularity with complement C3 and IgM deposits. The echocardiography showed an infectious endocarditis (IE) on aortic valve. Appropriate antibiotic therapy and a prosthetic valve replacement were performed, obtaining recovery of renal function.ConclusionHCV infection may be linked to multiple renal manifestations, often immune-complex GN such as cryoglobulinemic membrano-proliferative GN. Renal disease due to IE is usually associated to focal, segmental or diffuse proliferative GN, with prominent endocapillary proliferation. The most common infectious agents are Staphylococcus aureus and Streptococcus species.This case report may be relevant because the renal dysfunction was highly suggestive of a cryoglobulinemic GN on a clinical ground, but the histologic pattern after performing the renal biopsy oriented towards a different cause of the underlying disease, that required a specific antibiotic treatment. The renal biopsy is always required to confirm a clinical suspicious in patients affected by multiple comorbidities.

Renal manifestations at initial diagnosis of childhood acute leukemias: a retrospective analysis from a single center

article: Renal manifestations at initial diagnosis of childhood acute leukemias: a retrospective analysis from a single center - Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2022 October;181(10):717-23 - Minerva Medica - Journals

Long COVID.

The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), was primarily focused on the involvement of the respiratory system, as themost common clinical manifestation of the disease. Currently, also long COVID poses a significant problemfor medicine and public health worldwide. It is characterized by persistent symptoms from various organs orsystems, often present for several weeks and months after acute phase of SARS-CoV-2 infection. Currently,the most frequently used description for long COVID referred to symptoms that last more than three monthsafter the onset. Numerous data confirm long-term effects of COVID-19, including pulmonary, cardiovascular,neurological, renal, hematologic, gastrointestinal, endocrine and psychosocial manifestations. It is necessary tomonitor patients after acute phase of COVID-19 to detect and treat possible multi-organ long-term consequencesof SARS-CoV-2 infection.

The Assessment of Renal Functional Reserve in β-Thalassemia Major Patients by an Innovative Ultrasound and Doppler Technique: A Pilot Study.

Beta-thalassemia syndromes are the most common inherited monogenic disorders worldwide. The most common pathophysiologic and clinical renal disease manifestations of in β-TM patients is the tubular dysfunctions related to iron overload, chronic anemia, and the need for chronic iron chelation therapy. The aim of this pilot study is to apply an innovative ultrasound and Doppler technique to assess the Renal Functional Reserve (RFR) in β-TM patients, and to evaluate its reliability in iron overload tubulopathy. Ultrasound assessment of intra-parenchymal renal resistive index variation (IRRIV) has recently been proposed as a safe and reproducible technique to identify RFR presence. We define the preserved RFR when the Delta Renal Resistive Index (RRI) is >0.05 (baseline RRI-minimum RRI value during stress) in the Renal Stress Test (RST). Nineteen β-TM patients were enrolled for this study. In our series, we found a strong negative correlation between mean ferritin values and Delta RRI (R = -0.51, p = 0.03). This pilot study suggested the RST as reliable tool for assessing the RFR by ultrasound. Specifically, RST could help in clinical practice suggesting the patient's management and iron chelation therapy.

Renal manifestations in connective tissue diseases

Connective tissue diseases (CTD) comprise agroup of inflammatory systemic diseases that can affect various organs. Kidney involvement is frequently associated with significant irreversible damage and often before patients become symptomatic. Screening tests of blood and urine as well as clinical vigilance are therefore essential for all CTDs with possible renal involvement. Akidney biopsy is the gold standard for the diagnosis, prognosis and treatment decisions. Acommon and severe organ involvement in systemic lupus erythematosus (SLE) is glomerulonephritis (GN), also collectively referred to as lupus nephritis (LN). If left untreated LN often leads to end-stage renal failure. The treatment depends on the clinical parameters and histopathology of the renal involvement. Mycophenolate mofetil and cyclophosphamide are potent but nonspecific immunosuppressants which have been available for many years. Recently, new substances specific for LN have also been approved for the first time. Kidney involvement in Sjogren's syndrome has been far less studied. In studies the frequency of renal involvement is still unclear and ranges from 5% to 33%. Tubulointerstitial nephritis (IN) is the typical form of renal involvement which clearly differs from GN in its clinical presentation. Recommendations for treatment are based exclusively on retrospective studies. Arenal crisis in systemic scleroderma (SSc) is a rare but feared complication with ahigh mortality. An antiphospholipid syndrome (APS) nephropathy (APSN) can occur during CTD. These entities are vasculopathies and often thrombotic microangiopathies, which clearly differ from GN and IN in terms of pathophysiology, clinical features and treatment. This article provides an overview of the diversity of the most important renal manifestations of CTDs.

D313Y Variant in Fabry Disease: A Systematic Review and Meta-analysis.

There is accumulating evidence in the literature indicating a strong correlation between Fabry disease (FD) phenotypes and specific sequence variations in the Galactosidase Alpha (GLA) gene. Among them, the potential pathogenicity and clinical relevance of D313Y variation in patients with FD remain debated. We performed a systematic review and meta-analysis of studies reporting D313Y as single occurring variant in the GLA gene and sought to evaluate (1) the prevalence of D313Y variation in different populations with or without clinical manifestations of FD, (2) the clinical FD phenotype in D313Y-positive patients, and (3) the proportion of D313Y-positive patients presenting abnormal laboratory findings (alpha-galactosidase-A deficiency or globotriaosylceramide accumulation). Forty cohorts comprising 211 individuals with D313Y variation among 42,723 participants with available GLA gene-sequencing data were included. Patients highly suspected for FD had a higher prevalence of D313Y variation (4.9%, 95% CI 1.6%-9.9%; I2 = 95.5%) compared with the general population (0%, 95% CI 0%-0.1%; I2 = 1.9%; p = 0.004). The prevalence of D313Y variation was 0.6% (95% CI 0.3%-1%; I2 = 74.1%), 0.4% (95% CI 0.2%-0.7%; I2 = 0%), and 0.3% (95% CI 0.2%-0.4%; I2 = 0%) in patients presenting with neurologic, cardiac, or renal manifestations, respectively. D313Y was associated with a milder, late-onset FD phenotype, as indicated by the mean patient age of 51 years (95% CI 44-59; I2 = 94%) and the evidence of alpha-galactosidase A deficiency and globotriaosylceramide accumulation in 26.7% (95% CI 15.3%-40%; I2 = 34%) and 16.2% (95% CI 8%-26.4%; I2 = 35%) of cases, respectively. D313Y-positive patients displayed predominantly neurologic FD manifestations (58.1%, 95% CI 37.7%-77.1%; I2 = 78%), with central and peripheral nervous system (CNS/PNS) involvement noted in 28.2% (95% CI 15.4%-43.2%; I2 = 51%) and 28.5% (95% CI 17.8%-40.5%; I2 = 61%) of cases, respectively. D313Y variation seems to correlate with an atypical, mild late-onset phenotype with predominantly neurologic FD manifestations. Monitoring for CNS/PNS involvement is thus paramount to identify D313Y-positive patients with latent or early-FD pathology, which may qualify for enzyme-replacement therapy or chaperone treatment.

Renal manifestations in vasculitides of small and medium-sized vessels

Small-vessel vasculitides, in particular, are frequently manifested in the kidneys. A distinction is made between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and immune complex vasculitides. Even within the AAVs there are differences with respect to renal involvement, which manifest as necrotizing glomerulonephritis (GN) but renal involvement is much rarer in eosinophilic granulomatosis with polyangiitis than in microscopic polyangiitis and granulomatosis with polyangiitis. Disease progression, organ manifestation and prognosis vary according to the ANCA status. In immune complex vasculitides (cryoglobulinemic vasculitis, IgA vasculitis, hypocomplementemic urticarial vasculitis and antiglomerular basement membrane, GBM, disease), endothelial-adjacent activation of neutrophilic granulocytes leads to local vessel wall damage with subsequent ischemic tissue damage, similar to AAV. The sparse evidence of immune complexes is different in pauci-immune AAV. Polyarteritis nodosa is adisease with variable clinical presentations with necrotizing vasculitis of small and medium-sized arteries. Intrarenal aneurysms and hemorrhages but not GN lead to renal damage. Diagnostically, the detection of specific autoantibodies (e.g. anti-GBM), cryoglobulins or increased complement turnover can be decisive. Renal biopsy with qualified immunohistopathology is particularly important in cases of initial manifestation and unclear constellation of findings. The treatment of renal vasculitis is adapted to the severity, stage of disease, extrarenal organ manifestation and pathogenesis. It ranges from glucocorticoid monotherapy to moderate immunosuppression, up to targeted biologic therapy, chemotherapy and plasmapheresis.

PSAT210 A Case of Asymptomatic Severe Hypocalcemia: Consideration of Genetic Causes

Abstract Calcium sensing receptor (CaSR) activating mutations are a rare etiology of calcium dyscrasias in the general population. Of these, hypocalciuric hypocalcemia and autosomal dominant hypocalcemia (ADH) type 1 are the most common subtypes, with a prevalence of 74.1 and 3.9 per 100,000, respectively. Although rare, these mutations should be considered in patients with a family history of hypocalcemia, particularly if asymptomatic, as the treatment goals and replacement strategies differ from typical primary hypoparathyroidism, with which they are often mistaken. We present a case of a 41-year-old male with a history of treated vitamin D deficiency and anxiety who presented to endocrinology clinic for severe asymptomatic hypocalcemia (serum calcium 6.0-7.0). Family history pertinent for a mother, sister, and brother also with hypocalcemia, and brother with single childhood hypocalcemic seizure at age 4. Patient reported being on and off calcium, calcitriol, and ergocalciferol for years and has never had any symptoms regardless of his regimen or serum calcium. Specifically, he had no personal history of paresthesia, muscle cramping, or kidney stones. No family history of osteoporosis, fracture, kidney stone, or renal disease. Laboratory evaluation over the last 30 years most pertinent for serum calcium 6.0-9.5 on varying supplement/medication regimens, low-normal PTH, initially elevated and now normal serum phosphorous, low-normal serum magnesium, and 24h urinary calcium quite variable but as high as >300mg/d (when serum calcium within normal limits). Genetic testing revealed a heterozygous DNA sequence change detected on exon 7 of the CaSR gene, which has been previously found to be a pathogenic cause of ADH. Activating mutations of the CaSR (typically ADH type 1) clinically present as hypocalcemia, low or low-normal PTH, hyperphosphatemia, hypomagnesemia, and increased urinary calcium. When starting the evaluation for these mutations, it is important to note that there are two types of ADH. Type 1 mutations occur as an activating mutation at the CaSR causing hypersensitivity to calcium, while type 2 activating mutations occur at a different locale (G alpha 11 subunit). Despite mutations at different sites, each type leads to a similar gain-of-function mutation and a very similar clinical presentation. The clinical significance of differentiating these diagnoses from primary hypoparathyroidism (PHP) lies in the goals of treatment and in the adverse effects of over-supplementation of calcium in ADH. In PHP, patients generally have symptomatic hypocalcemia, and calcium can and should be supplemented to prevent adverse events of chronic hypocalcemia. Contrastingly, in CaSR mutation conditions, mild and even significant hypocalcemia is well tolerated. If patients’ serum calcium is normalized, they often experience significant hypercalciuria and renal manifestations therein, such has nephrocalcinosis and nephrolithiasis. Therefore, treatment of patients with CaSR activating mutations should be aimed at relieving hypocalcemia symptoms, if any are present. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Paraproteinämien und Nierenbeteiligung

Renal manifestations in patients with monoclonal paraproteinemia are frequent. Cast nephropathy is a disease that only occurs in manifest multiple myeloma with a high tumor burden. In contrast, monoclonal gammopathy of renal significance (MGRS) is defined as renal involvement due to a nephrotoxic clone that from a hematological standpoint would per se not require treatment. The diagnosis of MGRS can only be made by renal biopsy. Here monotypic immunoglobulin (Ig) deposits can be found in either organized (amyloidosis, fibrillary glomerulonephritis, GN, immunotactoid GN, cryoglobulinemic GN) or nonorganized forms (monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits). There are two forms of MGRS that can occur without the deposition of Ig, namely C3 glomerulopathy and thrombotic microangiopathy. For cast nephropathy there is always a fundamental indication for chemotherapy. The data on mechanical elimination of light chains by plasmapheresis or high cut-off dialysis are inconsistent. In patients with MGRS the indications for treatment must be made based on the renal prognosis in a cooperation between nephrologists and hematologists. Only a clone-directed treatment can lead to an improvement of renal function.

Multiple Myeloma and Acute Kidney Injury: Mechanisms Involved

The renal manifestations of multiple myeloma are devastating coupled with a disease as aggressive as the aforementioned. Its pathophysiological understanding has been clarified over time and has revealed the different mechanisms by which difficult-to-manage kidney damage occurs. However, the different therapies that have been developed have made this disease have an increasingly better prognosis. It is still a therapeutic challenge to treat myeloma together with a disease as complex as kidney disease.

Screening for Fabry’s disease in a high-risk subpopulation of FMF

BackgroundFamilial Mediterranean fever (FMF) is an autosomal recessive disease associated with mutations in the Mediterranean fever gene (MEFV) that manifests with recurrent episodes of febrile serositis. Fabry’s disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A gene and presents with a wide range of gastrointestinal, skin, vascular, renal and neurological manifestations. FMF and FD share similar manifestations, which may lead to misdiagnosis of one as the other; mostly FD is misdiagnosed as FMF. Moreover, various overlapping manifestations may stem from comorbidities, commonly coupled to FMF (such as Behcet's disease, inflammatory bowel disease, glomerulonephritis, fibromyalgia, and multiple sclerosis), as well as from colchicine adverse effects, which may add to the diagnostic confusion. Thus, we postulated that screening FMF for FD will lead to the identification of patients falsely diagnosed with FMF or who, in addition to FMF, suffer from FD that was previously missed.MethodsTo identify missed FD among the FMF population, we performed chemical and genetic analyses for FD in blood samples obtained from a cohort of FMF patients followed in the specialized FMF center of our institution. To increase the likelihood of detecting patients with FD, we enriched the surveyed FMF population with patients exhibiting manifestations shared by patients with FD or who deviate from the typical FMF presentation.Results and conclusionsOf 172 surveyed FMF patients in a cohort derived from a clinic dedicated to FMF, none had FD. Thus, the postulation of increased odds for detecting FD in patients with FMF was not confirmed. Further exploration for FD in FMF population, is nevertheless recommended.

47 Systemic lupus erythematosus in Tunisian children: a case series

BackgroundChildhood–onset systemic lupus erythematosus (c-SLE) is the prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition, characterized by simultaneous or sequential organ involvement. Compared with the adult onset form, c-SLE is thought to have a worse prognosis.ObjectivesTo review the epidemiological, and bio-clinical, characteristics of a c-SLE case series.MethodsThe files of patients diagnosed as c-SLE in the pediatrics department of Monastir, Tunisia from January 2004 to March 2022 were reviewed. Mean and standard-deviations were used to express normally-distributed variables, as verified by the Kolmogorov-Smirnov statistical test.ResultsFourteen patients were collected. Female to male ratio was 6:1. Mean ages at lupus onset and diagnosis were 9.9 ± 1.4 years, [5–13.8 years] and 10.75 ± 2.3 years [6–14 years], respectively. Only two children had a family history of autoimmune disease.The initial admission was motivated primarily by skin and musculoskeletal manifestations, in 64.3% and 51.7% of cases, respectively. General signs (fever, asthenia) were observed in 35.7% of cases, hematological and gastrointestinal manifestations in 28.6% of cases each. In 3 cases, upper gastric endoscopy was performed prior to admission, in view of abdominal pain and vomiting.The physical examination noted various anomalies. Malar rash (50%) and discoid lupus (28.6%) were the most frequent cutaneous manifestations, while skin biopsy was performed in three cases, all favorable for lupus. The musculoskeletal manifestations comprised arthralgia (71.4%), arthritis and myositis (14.3% each). Hematological manifestations included thrombocytopenia and leukopenia in 4 cases each, as well as 3 cases of auto-immune hemolytic anaemia and splenomegaly. Renal manifestations were dominated by proteinuria in 7 cases, followed by hematuria in 6 cases, and 2 cases of hypertension (associated with renal failure in one case). The renal biopsy was performed in one case showed a stage-2 lupus nephritis. Pleural effusion was observed in 3 cases, 3 cases of pneumonia, 2 cases of pericarditis, one case of myo-pericarditis and one case of central nervous system (CNS) lupus.Relevant results of the laboratory workup are illustrated in the following table:47 Table 1Laboratory testPerformed (%)Abnormal results (%)Erythrocyte sedimentation rate14 (100%)13 (92%)Antinuclear anti-bodies14 (100%)13 (92%)AntiDNA antibodies7 (50%)5 (71%)AntiSm antibodies8 (57%)5 (62%)Antiphospholipid antibodies8 (57%)5 (62%)Complement11 (78%)9 (81%)The formal diagnosis of SLE was established according to the ACR-1997 criteria in 7 cases (50%), the SLICC-2012 in 4 cases (28.6%) and EULAR/ACR-2019 in 3 cases (21.4%). The c-SLE diagnosis was associated with coeliac disease and Hashimoto thyroiditis in one case each.The therapeutic management was based on corticosteroids in 11 cases, followed by hydroxychloroquine in 3 cases, while cyclophosphamides and immunoglobulin were used for one case each.The outcomes were heterogeneous. Among 11 patients with sufficient follow-up, 6 cases of remission and 2 cases of relapse were noted. Major adverse events were not infrequent: one case each of cardiac tamponade, macrophage activation syndrome and severe CNS lupus were observed, all fatal.ConclusionChildhood–onset systemic lupus is a challenging disease, both to diagnose and to treat. The development of new criteria of higher specificity and sensitivity has greatly helped identify the incomplete types of lupus and allow for early stage diagnosis, and therefore prevent the serious complications of the disease.

85 Systemic lupus erythematosus in Tunisian children: a case series

BackgroundChildhood–onset systemic lupus erythematosus (c-SLE) is the prototype of a multisystem, inflammatory, heterogeneous autoimmune condition, characterized by simultaneous or sequential organ involvement. Compared with the adult-onset form, c-SLE have a worse prognosis.ObjectivesTo review the epidemiological, and bio-clinical, characteristics of a c-SLE case series.MethodsThe files of patients diagnosed as c-SLE in the pediatrics department of Monastir, Tunisia from January 2004 to March 2022 were reviewed. Mean and standard-deviation were used to express normally-distributed variables, as verified by the Kolmogorov-Smirnov statistical test.ResultsFourteen patients were collected. Female to male ratio was 6:1. Mean ages at lupus onset and diagnosis were 9.9 ± 1.4 years, [5–13.8 years] and 10.75 ± 2.3 years [6–14 years], respectively. Only two children had a family history of autoimmune disease.The initial admission was motivated primarily by skin and musculoskeletal manifestations, in 64.3% and 51.7% of cases, respectively. General signs (fever, asthenia) were observed in 35.7% of cases, hematological and gastrointestinal manifestations in 28.6% of cases each. In 3 cases, upper gastric endoscopy was performed prior to admission, in view of abdominal pain and vomiting.The physical examination noted various abnormalities. Malar rash (50%) and discoid lupus (28.6%) were the most frequent cutaneous manifestations, while skin biopsy was performed in three cases, all in keeping with lupus. The musculoskeletal manifestations were arthralgia (71.4%), arthritis and myositis (14.3%). Hematological manifestations included thrombocytopenia and leukopenia in 4 cases, as well as 3 cases of auto-immune hemolytic anaemia and splenomegaly. Renal manifestations were proteinuria in 7, haematuria in 6, and hypertension in 2 (with renal failure in one of the patients). The renal biopsy that was performed in one subject showed a class 2 lupus nephritis. Pleural effusion was observed in 3, pneumonia in 3, pericarditis in 2, myo-pericarditis in 1 and central nervous system (CNS) lupus in 1.Relevant results of the laboratory workup are illustrated in the following table:85 Table 1Laboratory testPerformed (%)Abnormal results (%)Erythrocyte sedimentation rate14 (100%)13 (92%)Antinuclear anti-bodies14 (100%)13 (92%)AntiDNA antibodies7 (50%)5 (71%)AntiSm antibodies8 (57%)5 (62%)Antiphospholipid antibodies8 (57%)5 (62%)Complement11 (78%)9 (81%)The formal diagnosis of SLE was established according to the ACR-1997 criteria in 7 cases (50%), the SLICC-2012 in 4 cases (28.6%) and EULAR/ACR-2019 in 3 cases (21.4%). The c-SLE diagnosis was associated with coeliac disease and Hashimoto thyroiditis in two of the subjects respectively.The therapeutic management was based on corticosteroids in 11 cases, hydroxychloroquine in 3, while cyclophosphamides and immunoglobulin were used for two subjects respectively.The outcomes were heterogeneous. Among 11 patients with sufficient follow-up, 6 cases of remission and 2 cases of relapse were noted. Major adverse events were not infrequent: one case each of cardiac tamponade, macrophage activation syndrome and severe CNS lupus were observed, all fatal.ConclusionChildhood–onset systemic lupus is a challenging disease, both to diagnose and to treat. The development of new criteria of higher specificity and sensitivity has greatly helped identify the incomplete types of lupus and allow for early-stage diagnosis, therefore preventing the serious complications of the disease.

S760 Epidemiology of Glomerulonephritis as an Extraintestinal Manifestation of Inflammatory Bowel Disease: A Large Population-Based Study

Introduction: Inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and Ulcerative colitis (UC), are known to cause many extraintestinal manifestations. There is limited data describing the association between IBD and renal manifestations. This study provides epidemiologic data to further understand the association between IBD and glomerulonephritis (GN). Methods: The aim of this study was to investigate if IBD is associated with GN. Data was collected from a commercial database (Explorys Inc, Cleveland, OH), an aggregate of EHR data from 27 integrated healthcare systems in the US between 1/2017-1/2022. We identified patients with CD and UC based on Systemized Nomenclature of Medicine – Clinical Terms. We compared the prevalence of GN at least 30 days post-CD or post-UC diagnosis to a control cohort without CD or UC. We excluded patients with a diagnostic predisposition for development of GN (Table). Results: Of the 34,063,760 patients, we identified 149,630 cases of CD and 127,300 cases of UC. There were 310 and 260 cases of glomerulonephritis at least 30 days after diagnosis of CD and UC, respectively. Overall prevalence of glomerulonephritis for CD and UC was 207/100000 persons and 203/100000 persons, whereas for the cohort without CD and UC was 72/100000 persons and 72/100000 persons. Prevalence ratios (PR) of developing glomerulonephritis after at least 30 days of a CD and UC diagnosis were 2.88 (95% CI, 2.57-3.22, p< 0.001) and 2.83 (95% CI, 2.51-3.20, p< 0.001), respectively. Figure shows prevalence and PR in CD and UC sub-categorized by demographics. Membranous GN was the most prevalent (CD 90, UC 90), followed by proliferative (CD 50, UC 50), mesangiocapillary (CD 30, UC20), diffuse (CD 10, UC 0) and focal membranoproliferative (CD 10, UC 10). Conclusion: In this large population-based study, glomerulonephritis was significantly more prevalent in patients with both CD and UC compared to those without IBD. Further studies are needed to understand the pathophysiological mechanism underlying renal involvement.Figure 1.: Prevalence and prevalence ratios of glomerulonephritis after at least 30 days post-CD and post-UC diagnosis. Table 1. - Diagnoses excluded prior to analysis Excluded diagnoses Systemic lupus erythematosus Goodpasture's syndrome Hereditary nephritis Post-infectious GN Granulomatosis with polyangiitis Allergic grandulomatosis angiitis Alport syndrome Human immunodeficiency virus Hepatitic B virus Hepatitis C virus Nephrotic syndrome with membranoproliferative glomerulonephritis Primary pauci-immune necrotizing and crescentic glomerulonephritis Berger's immunoglobulin A or immunoglobulin G nephropathy

Clinical and immunological factors associated with lupus nephritis in an Argentine patient population: A cross-sectional study

IntroductionIn recent decades, the prevalence of systemic lupus erythematosus (SLE) has increased thanks to early detection and the impact of new therapies on the survival of those affected. Up to 90% will have histopathological signs of kidney disease in the first 3 years of the disease, but lupus nephritis of clinical relevance will appear in 50% of cases, affecting kidney function and mortality. Despite aggressive therapeutic strategies, the prognosis of patients with LN remains unfavourable, mainly due to the high risk of progression to end-stage renal disease (10%–20%) and mortality from all causes. ObjectiveTo describe the clinical and immunological risk factors of a group of patients with lupus, comparing clinical and serological characteristics in relation to renal involvement to establish possible associations. Materials and methodsCross-sectional study in which 87 patients with SLE were included. Clinical and immunological variables were analyzed. Bivariate and multivariate analyses were performed using the presence of nephritis as an outcome. ResultsThe prevalence of lupus nephritis was 59%. The significantly associated variables were arterial hypertension (OR 3.1, 95% CI 1.02–9.40), age of onset of lupus less than 25 years (OR 2.7, 95% CI 1.08–6.73), the presence of reticular livedo (OR 4.1, 95% CI 1.09–15.7), positive anti-DNA (OR 2.9, 95% CI 1.18–7.24) and low levels of complement (OR 4.0, 95% CI 1.64–10.2). ConclusionsUrinary sediment abnormalities were the most common renal manifestation and lupus debut before the age of 25 seems to increase the risk of developing nephritis. Future research is required for a better explanation of the associations found.

Early Autosomal-Dominant Polycystic Kidney Disease is Related to Liver and Cyst Volumes, Hepatic Parenchyma Volume, and Patient-Reported Effects

Aim: Polycystic liver infections are the most prevalent extra renal manifestation of autosomal-dominant polycystic kidney disease (PKD). People are living longer and there are more chances of spread on infections and these infections may cause different diseases but these can be improved by providing the proper knowledge among the lay men and control over these diseases can be made like better kidney survival, less death from heart disease, new treatments for kidney transplants, and more people with polycystic liver failure. There is a lack of research that completely characterizes PKD in big cohorts. Many other researchers has also been made to observe the size of the liver and the number of cysts which are linked to the size of the hepatic parenchyma, but this study is the specific to the polycystic kidney disease and its effect over the liver with the volume of cyst. This is the only studyin the region. . Methods: cross-sectional studies has been conducted to investigate the relationship between the initial volumes of the liver which was determined by MRI, and the patient’s demographics, the outcomes of these results also depends upon the quality of life of the patients. This research was conducted from January 2021 to June 2021 at Mayo Hospital, Lahore Pakistan. The information is gathered from the randomized, placebo-controlled trial that is currently being conducted at five tertiary-care medical facilities. In this the comparison was made between the groups of angiotensin I–converting enzyme inhibitor and an angiotensin II–receptor blocker. These findings were based on the normal situation o fthe blood [ressure. Because normal blood pressure related with the proper renal functioning. These tests were performed for 558 patients with ADPK (age, 16–50 y). Practical implication: We can easily implement these findings to PKD in hospitals and find the best treatment method according to this. Results: The significant level of hepatomegaly was seen in number of individuals diagnosed with ADPKD. Hepatomegaly was also existed in cysts as well as parenchyma. Cysts were found more often in women, and both the liver and cyst sizes were observed to be larger in women with the increase in age. Patients whose illness had progressed significantly demonstrated a significant reduction in the situation of liver parenchyma. In this study some minor irregularities were noticed in the results of laboratory testing on the liver, and splenomegaly and hypersplenism remained related to the severity of PLD. Inferior quality of life was connected with having a larger amount of damage in the liver tissue. Conclusion: Even in the earliest stages of ADPKD, hepatomegaly is rather prevalent, and it cannot be diagnosed properly just by the presence of cysts. Even for those who didn't have cysts, parenchymal volumes have been discovered to be substantially bigger than liver volumes in people without ADPKD or these predicted by basic tests performed in the specific laboratories. The harshness of PLD remained linked to changed biochemical also hematologic characteristics, in addition to a worse quality of life in patients. Keywords: Hepatomegaly, Polycystic liver infections, extra-renal manifestation, autosomal-dominant polycystic kidney diseases.

OA04 Paediatric APS - children are not just small adults

OA04 Paediatric APS - children are not just small adults