e17011 Background: The relapse rate for patients with clinical stage I seminoma is approximately 20% and surveillance is strongly preferred. Risk- adapted management with adjuvant carboplatin chemotherapy is another option for those at high risk of relapse but no consensus on high risk factors has yet been determined. Tumour size > 4 cm, lymphovascular and rete testis invasion have been inconsistently associated with the risk of relapse. In our centre all patients with stage I seminoma are managed with surveillance wich gives us the opportunity to investigate risk factors for relapse. The aim of this study was to investigate the association of tumour size, lymphovascular invasion and rete testis invasion with the risk of relapse in patients with stage I seminoma. Methods: We identified patients with clinical stage I seminoma diagnosed between 2010 and 2020 who had tumour size, lymphovascular invasion and rete testis invasion reported in their medical record. Relapse rate was rhe primary outcome and the variables for relapse were tumour size > 4, lymphovascular invasion and rete testis invasion. To evaluate this variables The Cox proportional hazard model was built. Results: In total, 97 patients were evaluated. Median age of the population was 36 years (range 22- 56 years). 29 patients (29.8 %) relapsed and the median relapse time was 16 months (range 3 -57 months). Median follow- up time for patients without relapse was 9.3 years. Lymphovascular invasion and tumour size > 4 were statistically significant and independent risk factors for relapse. Lymphovascular invasion was associated with approximately 2,38 times higher risk of relapse. Tumour size > 4 cm was associated with 2,6 times higher risk of relapse and was the strongest predictor of relapse. Rete testis invasion slightly increased the risk of relapse but this was not statistically significant. Results are shown in Table 1. Conclusions: Tumour size and lymhpovascular invasion were independent factors associated with increased risk of relapse while rete testis invasion was not. The strongest risk factor for relapse was tumour size > 4 cm which is consistent with previous studies. Since the risk of relapse for stage I seminoma is acceptably low and disease specific- survival high surveillance is the preferred option. For patients not suitable for surveillance risk-adapted management with well defined risk factors can be useful in clinical practice. Results. Variable coef HR (exp(coef)) SE(coef) z p-value Lower 95% CI Upper 95% CI Lymphovascular invasion 0,8665 2,3785 0,3848 2,25 0,0245 1,1187 5,0645 Tumour size > 4 cm 0,9498 2,5852 0,3807 2,49 0,0128 1,2227 5,4627 Rete testis invasion 0,2002 1,2217 0,4087 0,49 0,6234 0,5516 2,7061 HR = hazard ratio; CI = confidence interval.

This report describes data collected by the Croatian Registry of Renal Biopsies (CRRB) for the period of 5 years. The aim of this study is to report the relative frequency of nephropathies according to gender, age, clinical presentation, and renal function at the time of renal biopsy based on the histologic diagnosis. Ten centers (90%) provided the data for 1732 native kidney biopsies during the period 2019-2023. We assessed the anthropometric data, data on kidney function(eGFR), 24-hour proteinuria, hematuria, serum albumin level, arterial hypertension, histological diagnosis, and complications after renal biopsy. Examined group consisted of 58% males, median age 55 y (18–93 y) and 42% women, median age 56 y (18–87 y). Biopsy rate of 86, 6 p.m.p./year was relatively constant through the 5-year period except for pandemic years 2020 and 2021 when it was reduced by half. Males had a more impaired renal function at the time of renal biopsy (eGFR 53.1 vs 60 ml/min/1.73 m2P < 0.001), nephrotic syndrome (24-hour proteinuria 4.9 vs 3.8 g/dU P < 0.001), and hypertension (139/83 vs 133/81 mmHg P < 0.001). The most prevalent clinical presentations were urinary abnormalities e.g. asymptomatic proteinuria and hematuria (32.9%) and nephrotic syndrome (28.3%) Among all biopsy cases, primary glomerular diseases were the most prevalent histology group (45.2%); IgA nephropathy (IgAN) being most frequent (39.5.1%), followed by focal segmental glomerulosclerosis (FSGS) (27.6%) and membranous nephropathy (MN) (19.1%). Secondary glomerular diseases were diagnosed in 33.1% of cases. Within secondary glomerular diseases, pauci-immune glomerulonephritis (PIGN) was most often found (28.8%), followed by lupus nephritis 19.3% and diabetic nephropathy 16.3%. During the observed period IgAN was the most prevalent disease 16.5% except for the year 2020. when PIGN was most prevalent reflecting the indications for biopsy during COVID pandemic. Incidence of IgAN decreased from 2.5 to 2.2/per 100 000 population during the 5 year period while FSGS increased 1.4–2.1/per 100 000 population. Among secondary causes we observe increase in incidence of diabetic nephropathy by 25% and decrease of vascular causes by 22%. The most common disease in patients presented with nephrotic proteinuria was minimal change disease (MCD) (78%) and membranous nephropathy 75% in those presented with urinary abnormalities thin membrane disease (55%) and lupus nephritis (53%) and in nephritic syndrome acute tubulointerstitial nephritis (25%) and acute tubular injury (23%). Patients with DN had the highest blood pressure levels (147/82 mmHg) at the time of kidney biopsy. Patients older than 65 years had higher sCr (263 vs 183 μmol/l) and proteinuria (4.79 vs 4.29 g/dU). Most prevalent diagnosis in older group was PIGN. There were no significant differences in any parameters between continental and Mediterranean part of Croatia. The frequency of severe complications ( symptomatic hematoma, blood transfusion or gross hematuria) was 6%. CRRB provides representative data of the epidemiology of biopsy proven renal disease in Croatia. Availability of these data will be a valuable source to nephrologists to stimulate further research and comparison with other national registries.

Drug-induced acute interstitial nephritis (AIN) is a significant cause of acute kidney injury. According to the literature, AIN is most commonly induced by antibiotics or anti-inflammatory drugs. Secondary minimal change disease (MCD) can also have iatrogenic trigger, although very rare. In this case report, we present a 67-year-old female patient with biopsy-proven combined AIN and MCD induced by rosuvastatin. This patient, with previously normal renal function and no significant comorbidities or chronic therapy, presented to the emergency department with acute onset of eyelid and extremities edema lasting for 10 days, along with decreased urination. She had no skin changes such as rash or pruritus but had a persistent cough and pain in the calves and heels. The workup revealed acute kidney injury (Urea: 26.3 mmol/L; Creatinine: 465 µmol/L; eGFR: 8 ml/min/1.73 m²) accompanied by hyperkalemia (5.5 mmol/L), hypocalcemia (2.05 mmol/L), hyperphosphatemia (2.23 mmol/L), hypoalbuminemia (27 g/L), and an elevated sedimentation rate (68 mm/3.6 s). The blood count, coagulogram, hepatogram, and ferrogram were unremarkable, and inflammatory parameters were stable. On examination, the patient was hypertensive (175/105 mmHg), oliguric and had anasarca. Urinalysis showed proteinuria (3+) and erythrocyturia (3+). The patient was admitted to the department for further treatment, and non-selective proteinuria of nephrotic range was confirmed in 24-hour urine collection (protein: 10,200 mg/dU; albumin: 5,500 mg/dU). Additional history revealed that she had been taking rosuvastatin, prescribed for mixed hyperlipidemia, for the past two months. Conservative supportive therapy was initiated to manage proteinuria, control blood pressure, and reduce peripheral edema. An ACE inhibitor was introduced at the maximum dose, and diuresis was stimulated with parenteral human albumin combined with diuretics. An ultrasound examination revealed bilateral kidneys of normal size (100 mm) with normal parenchyma. On the fifth day after admission a kidney biopsy was performed and sent for analysis by immunofluorescence, light, and electron microscopy. The findings from light and immunofluorescence microscopy were consistent with acute tubulointerstitial nephritis with eosinophilia and minimal change disease with extensive loss of podocyte foot processes on 85% of the examined surface. The histopathological and clinical findings were indicative of combined acute kidney injury caused by presumably rosuvastatin. Upon admission rosuvastatin was discontinued and renal function recovery was already underway, with a decrease in creatinine levels. Oral prednisone therapy (1 mg/kg of body weight daily for 14 days) was initiated, followed by tapering over four weeks. The patient was discharged with additional therapy consisting of perindopril, indapamide, amlodipine, and moxonidine. At the four-week follow-up after initiating corticosteroid therapy, the patient achieved complete recovery of renal function (Urea: 6.9 mmol/L; Creatinine: 86 µmol/L; eGFR: 61 ml/min/1.73 m²), correction of electrolyte imbalances (K: 4.0 mmol/L; Na: 140 mmol/L; Ca: 2.14 mmol/L; P: 1.7 mmol/L), and regular diuresis with proteinuria <60 mg/dU and albuminuria <10 mg/dU. Prednisone therapy was successfully tapered, with the recommendation to avoid statins. To our knowledge and based on a review of the literature, this is so far the only case of combined AIN and secondary MCD induced by rosuvastatin use. In our patient, who had no other potential cause of acute kidney failure, eight weeks of rosuvastatin therapy led to acute renal injury with nephrotic syndrome. Kidney biopsy findings showed interstitial infiltrates predominantly composed of eosinophils and extensive podocyte foot processes effacement. Withdrawal of the culprit drug, combined with prednisone treatment (1 mg/kg/day), resulted in complete recovery of renal function.

Abstract Background and Aims Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol. Method In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease. Conclusion Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.

BACKGROUND:Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS:Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS:MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.

e13080 Background: The combination of CDK4/6i and endocrine therapy (ET) is the standard of care in the first-line treatment of hormone receptor positive (HR+), HER2- aBC. In registrational studies, the progression-free survival (PFS) of all three CDK4/6i ranged from 23.8 to 28.12 months and overall survival (OS) from 53.9 to 66.8. In Croatia, both ribociclib and palbociclib were approved for clinical use in August 2018 and abemaciclib in November 2019. Methods: This retrospective study included patients with endocrine-sensitive HR+, HER2- aBC treated with aromatase inhibitor (AI) and CDK4/6i in the first-line setting between August 2018 and October 2023 at University Hospital Centre Zagreb. Ethics committee approval was obtained before the study was commenced. Patient demographics, clinical presentation, tumor characteristics and treatment data were collected. Real-world PFS (rwPFS) and OS analyses were done with the final data cut-off date of December 31, 2023, using type 1 right censoring. Data were analyzed using the Kaplan-Meier method. Results: Of the 274 patients treated with a combination of CDK4/6i and ET in the first-line setting, 172 with endocrine-sensitive tumors (98 de novo metastatic and 74 with treatment-free interval longer than 12 months) were eligible for the study, of which 41.86% (72/172) received ribociclib, 44.19% (76/172) palbociclib, and 13.95% (24/172) abemaciclib. Overall rwPFS was 48 months (95% CI:35-53). In the abemaciclib group, median rwPFS and OS were not reached in the follow-up period. The rwPFS was 48 (95% CI:27-53) for ribociclib and 47 (95% CI:30-49) for palbociclib. The overall OS was 62 months (95% CI:47-62). Median OS in the ribociclib group was 62 months (95% CI:40-62) and in the palbociclib group 52 (95% CI:42-54) months. Conclusions: The PFS and OS results for palbociclib and ribociclib in this retrospective real-world study correlate with results from randomized clinical trials, confirming some inferiority of palbociclib compared to ribociclib in the context of OS. Due to the later availability of the drug, larger sample size and longer follow-up will be needed to make definitive conclusions on the efficacy of abemaciclib.

Abstract Background and Aims Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome in adult population. Our aim was to assess long term renal outcome of primary membranous nephropathy patients. Method In this retrospective study adult patients with biopsy proven membranous nephropathy from 2000 till 2015 with follow up of at least 5 years from UHC Zagreb were included. Extensive clinical workup was done to exclude patients with secondary MN. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results Between 2000 and 2015, 48 patients were diagnosed to have idiopathic/primary membranous nephropathy, out of which 33 (68%) MN patients had follow up of at least 5 years and where further analyzed. They were predominantly male 20 (60.6%) of average age of 52 years (min – max 19 - 76). High risk MN patient 25 (75%) were treated with immunosuppressive therapy, dominantly with cyclophosphamide and corticosteroids. During the median follow up of 10 (7 – 14) years, 19 (57%) accomplished complete remission and 11 (33%) partial remission. One (3%) patient did not achieve remission and 2 (6.1%) were in relapse of nephrotic syndrome at last follow up. Proteinuria significantly decreased (6.2 (3.3 – 10.9) vs. 0.2 (0.14 – 0,90); p < 0.001) and there was no significant change in creatinine level (87 (42.8 – 101.5) vs. 93 (68.5 – 140.5; p = 0.332)). In follow up there were 5 (15%) carcinomas detected; one of each origin (colon, pancreas, lung, prostate, lymph nodes) approximately 7,8 years after the diagnose of MN. Limitation of this study could be selection bias but there was no difference in renal function at presentation of all MN patients and those who had at least 5 years follow up. Conclusion Renal long-term outcome of patients with idiopathic MN in our cohort was excellent. Nevertheless, there is high prevalence of cancer and therefore regular screening for cancer disease should take place in this population of patients. Also, drugs with cancerogenic potential should be avoided, as well as bear in mind cumulative dose of drugs applied.

Abstract Background and Aims Light chain deposition in the kidney is an important histologic feature having a significant role in the pathogenesis of glomerular and autoimmune diseases, including lupus nephritis (LN). However, there is no study examining differences in light chain deposition profile between proliferative and non-proliferative LN. Method We have conducted a retrospective cohort study to evaluate the characteristics and prognostic significance of light chain deposition profile in the kidney of subjects with proliferative and non-proliferative LN. We have collected data on demographics, clinical and laboratory parameters and histopathology (light, immunofluorescent and electron microscopy). Lambda domination (LD) was defined as lambda intensity—kappa intensity ≥ +1. SLE was diagnosed using the American College of Rheumatology criteria and renal outcomes per KDIGO guidelines. Proliferative LN was defined as those containing classes III and IV, while all other classes comprised non-proliferative LN. Results A total of 56 patients with biopsy-proven LN were followed up for at least one year after kidney biopsy (79% women, mean age at biopsy 38 ± 13 years). A total of 71% of patients had proliferative LN. Mean number of glomeruli per biopsy sample was 26 ± 12. Mean immunofluorescent intensity was 1.6 ± 1.0 for lambda and 1.8 ± 1.0 for kappa light chain. A total of 42 (75%) patients had light chain deposition in the glomerulus with 4 (7%) having restricted lambda chain deposition and none had restricted kappa chain deposition. Patients with proliferative LN had more frequent light chain deposition in glomeruli than those with non-proliferative lupus (88% vs. 57%, p = 0.049) , with no difference in LD (24% vs. 14%, p = 0.71). There was no difference between frequency of restricted lambda chain deposition between proliferative and non-proliferative LN (5% vs. 17%, p = 0.60). A total of 12 (21%) patients had LD in the glomerulus. When examining renal outcomes at one year post-biopsy, 55% of patients achieved complete response (CR), 30% achieved partial response (PR) and 15% had no response. There were no differences in achievement of remission (CR or PR) between patients with proliferative and non-proliferative LN (87% vs. 90%, p = 0.93). We also found no difference in frequency of light chain deposition and achievement of remission in proliferative or non-proliferative LN (both p>0.05). Conclusion Light chain deposition is prevalent in LN and is more frequent in patients with proliferative LN. Further studies examining their pathophysiologic properties and potential prognostic value are much warranted.

BACKGROUND:The unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed toward methylated cell-free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development. METHODS:In the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis. RESULTS:Statistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue. CONCLUSIONS:The DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA.

Heavy chain deposition disease (HCDD) is a rare entity associated with monoclonal gammopathy of renal significance. It is characterized by deposition of monoclonal heavy chain, usually gamma type, along the glomerular and tubular basement membranes and vessel walls. If left untreated, the disease progresses to ESRD within 2 years with almost inevitable recurrence in renal allograft. Apart from kidney biopsy, the workup includes monoclonal immunoglobulin testing and clonal identification, which subsequently guide the treatment; however, these tests can be negative in 20

We investigated the polarisation of CD68+ macrophages and perforin and granulysin distributions in kidney lymphocyte subsets of children with IgA vasculitis nephritis (IgAVN). Pro-inflammatory macrophage (M)1 (CD68/iNOS) or regulatory M2 (CD68/arginase-1) polarisation; spatial arrangement of macrophages and lymphocytes; and perforin and granulysin distribution in CD3+ and CD56+ cells were visulaised using double-labelled immunofluorescence. In contrast to the tubules, iNOS+ cells were more abundant than the arginase-1+ cells in the glomeruli. CD68+ macrophage numbers fluctuated in the glomeruli and were mostly labelled with iNOS. CD68+/arginase-1+ cells are abundant in the tubules. CD56+ cells, enclosed by CD68+ cells, were more abundant in the glomeruli than in the tubuli, and co-expressed NKp44. The glomerular and interstitial/intratubular CD56+ cells express perforin and granulysin, respectively. The CD3+ cells did not express perforin, while a minority expressed granulysin. Innate immunity, represented by M1 macrophages and CD56+ cells rich in perforin and granulysin, plays a pivotal role in the acute phase of IgAVN.

Objective Light chain deposition has been shown to be an important histologic hallmark with differences in isotype, characteristics and ratio of kappa and lambda light chains having a significant role in pathobiology, pathogenesis and prognosis of several glomerular diseases. However, there is, to the best of our knowledge, no study dedicated to evaluating light chain deposits in patients with lupus nephritis (LN). Methods We have conducted a retrospective cohort study to evaluate the characteristics and prognostic significance of light chain deposition profile in the kidney of subjects with LN. We have collected data on demographics, clinical and laboratory parameters and histopathology (light, immunofluorescent and electron microscopy). Lambda domination (LD) was defined as lambda intensity – kappa intensity ≥ +1. SLE was diagnosed using the ACR criteria and renal outcomes per KDIGO. Results A total of 56 patients with LN were followed up for at least one year after kidney biopsy (79% women, mean age at biopsy 38±13 years). Mean number of glomeruli per biopsy sample was 26±12. A total of 42 (75%) patients had light chain deposition in the glomerulus with 4 (7%) having restricted lambda chain deposition and none had restricted kappa chain deposition. Mean immunofluorescent intensity was 1.6±1.0 for lambda and 1.8±1.0 for kappa light chain. A total of 12 (21%) patients had LD in the glomerulus. When examining renal outcomes at one year post-biopsy, 55% of patients achieved complete response (CR), 30% achieved partial response (PR) and 15% had no response. There were no differences in achievement of remission (CR or PR) between patients with vs. without light chain deposition (88% vs. 71%, p=0.60) as well as between those with vs. without LD (90% vs. 83%, p>0.99). Conclusion Light chain deposition is prevalent in LN, but LD is much lower than in IgA nephropathy. While their deposition did not affect renal outcomes in our patients, light chains are an important factor to consider in LN patients, especially where restriction is present and further work-up, primarily for hematologic disease, is needed. Further investigation of the potential effect of pathobiologic characteristics of light chains in LN is warranted.

Abstract Background and Aims Microvascular lesions (MVL) can be found in the kidneys of lupus nephritis (LN) patients and might be associated with worse outcomes. There are very few studies which evaluated MVLs in these patients and we aimed to provide a comprehensive evaluation of all MVLs, their frequency, characteristics and association with renal outcomes one year after kidney biopsy. Method We have conducted a retrospective cohort study to evaluate the characteristics and prognostic significance of MVLs in the kidney of subjects with LN. We have collected data on demographics, clinical and laboratory parameters and histopathology (light, immunofluorescent and electron microsopy). MVLs were characterized according to previous classifications. SLE was diagnosed using the American College of Rheumatology criteria. Results A total of 56 patients with biopsy-proven LN were followed up for at least one year after kidney biopsy (79% women, mean age at biopsy 38±13 years). Forty patients (71%) had MVLs in the kidney. The most common MVLs were arteriolar endotheliocyte swelling (54%), arteriolar hyalinosis (25%) and endothelialitis (8%) and the frequency distribution of all microvascular lesions is shown in Figure. Median number of lesions in the MVL group was 1 (interquartile range 1 to 2) and subjects had up to 6 MVLs. There was no difference in the median number of MVLs across LN classes (p>0.05). Proteinuria was highest in class V (5.5 g/day, p = 0.06 vs. all other classes). Subjects with MVLs had lower baseline proteinuria compared with those with no lesions (3.6 vs. 5.4 g/day, p = 0.037), but there was no difference in serum creatinine (92 vs. 119 umol/L, p = 0.25). There were no differences in the occurrence or number of MVLs across LN classes (p = 0.63). The number of MVLs was not correlated with proteinuria (p>0.05). There was no difference in the frequency of proliferative lupus between MVL and no MVL groups (79% vs. 60%, p = 0.15). A total of 48% of subjects achieved complete response (CR), 27% achieved partial response (PR) and 25% had no response (NR). MVLs were not associated with response (defined as CR or PR) in a multivariate regression model (OR 3.5 [0.5, 24.6]). Conclusion MVLs are common in LN. They were associated with lower baseline proteinuria, but not with proliferative LN or renal outcomes. The association with proteinuria warrants further research.

Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.

Abstract BACKGROUND. Bortezomib is a well-known frontline therapy for newly-diagnosed multiple myeloma (MM). There have been several case reports about skin vasculitis as a rare side effect of this medicine and one case report about intestinal vasculitis. We are now demonstrating 1st case of a vasculitis affecting skin, intestine and kidney in a single patient. CASE PRESENTATION. Our patient is a 77-year-old woman with MM treated with bortezomib, melphalan and prednisone. She developed leukocytoclastic vasculitis of legs, bloody diarrhea and nephrotic proteinuria. Since the hematological response had been achieved, her condition was understood as a side effect of bortezomib and was completely resolved by discontinuation of the drug and administration of corticosteroids. CONCLUSIONS. These three simultaneous signs suggest a common pathophysiology of the vasculitis manifesting on skin, intestine and kidney also known as Henoch-Schönlein purpura (HSP) and to the best our knowledge is 1st report of this combination of side effects of bortezomib therapy. Clinicians should be aware of this rare, yet possible side effect when treating patients with bortezomib so they could timely recognise it and treat it.

IntroductionGenetic kidney diseases are underdiagnosed; namely, from 7% to 40% of patients suffering from chronic kidney disease (CKD) can carry a pathogenic variant, depending on population characteristics. Hereditary tubulointerstitial kidney diseases, including autosomal dominant tubulointerstitial kidney diseases (ADTKD), are even more challenging to diagnose. ADTKD is a rare form of genetic kidney disease resulting from pathogenic variants in the MUC1, UMOD, HNF1B, REN, SEC61A1, and DNAJB11 genes. There is no typical clinical or histopathological sign of ADTKD, it is characterized by progressive CKD, an autosomal dominant inheritance pattern, and tubular atrophy with interstitial fibrosis on kidney biopsy. There is no significant proteinuria, and the urinary sediment is bland. The patients usually do not have severe arterial hypertension. There can be a history of early gout, especially when compared to the UMOD gene variants. Children can have enuresis due to a loss of renal concentration. On ultrasound, the kidneys can appear normal or small in size. Renal cysts are not pathognomonic for any of the named diseases. End-stage renal disease (ESRD) develops at the average age of 45, but this can be very variable. Family history that suggests autosomal dominant inheritance and CKD fulfilling the aforementioned characteristics of tubulointerstitial kidney disease should raise suspicion of ADTKD. In the setting of a negative family history for CKD, clinical suspicion should be raised based on clinical characteristics, including early onset of hyperuricemia or gout and compatible histology on the kidney biopsy. Contrary to the aforementioned characteristics of ADTKD, in the case of HNF1B-related disease, there is a more complex clinical presentation with extrarenal manifestations of the disease (diabetes mellitus, hypomagnesemia, neurologic and psychiatric disturbances, etc.). The diagnosis of ADTKD is based on a positive family history and a detection of the pathogenic variant in one of the genes in an affected individual.AimThe aim of our study is to present two case reports of ADTKD with different characteristics (slowly progressive CKD vs. complex clinical presentation with an extrarenal manifestation of the disease) with a literature review.MethodsA 34-year-old patient with CKD and a positive family history of CKD in whom kidney biopsy showed nonspecific chronic changes, with only genetic analysis confirming the diagnosis of MUC1-related ADTKD. Our second case is of a 17-year-old patient with an unremarkable family history who was initially referred to genetic counseling due to cognitive and motor impairment with long-lasting epilepsy. Extensive workup revealed increased serum creatinine levels with no proteinuria and bland urinary sediment, along with hypomagnesemia. His genetic analysis revealed 17q12 deletion syndrome, causing the loss of one copy of the HNF1B gene, the AATF, and the LHX1 gene.ConclusionAutosomal dominant tubulointerstitial kidney diseases are challenging to diagnose due to a lack of typical clinical or histopathological signs as well as an uncharacteristic and versatile clinical presentation. Increased clinical awareness is crucial for the detection of these diseases.