Non-nephrotic Proteinuria Research Articles

Nephrotic and Non-Nephrotic Focal Segmental Glomerulosclerosis: Clinical Characteristics, Etiology, and Columbia Classification

Introduction: Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney injury with diverse causes and pathogeneses, resulting in podocyte injury and depletion. It can be classified as primary, genetic, or secondary. Because FSGS classically has a worse prognosis in patients with nephrotic syndrome, most studies have focused on the treatment and evolution of these patients, resulting in a lack of data related to patients without nephrotic syndrome. The objective of this study was to establish the main etiologies, characteristics, and evolution of renal disease in FSGS patients with nephrotic and non-nephrotic proteinuria. Methods: This was a retrospective, single-center study that included 140 patients with a biopsy-confirmed diagnosis of FSGS in the 2009–2017 period. Patients were separated into those with and those without nephrotic syndrome at diagnosis, and these two groups were compared in terms of the clinical characteristics, histological profile, and outcome. Non-nephrotic patients with unfavorable progression were selected for ultrastructural analysis with electron microscopy. Results: During the study period, 32.9% of the patients with FSGS had non-nephrotic proteinuria at diagnosis. This group had a larger proportion of patients with hypertension and a not otherwise specified FSGS variant on histology. The proportion of patients with secondary forms of FSGS was comparable between the two groups, with HIV infection and systemic lupus erythematosus being predominant. Progression to renal replacement therapy occurred in 31.3% of the patients in the nephrotic group and in 26.8% of those in the non-nephrotic group, with no statistical difference between them. All of the non-nephrotic group patients who progressed to renal replacement therapy were analyzed by electron microscopy, the diagnosis of FSGS was confirmed, and there was the finding of high chronicity in these patients. Conclusions: Among patients with FSGS, those without nephrotic syndrome had a poor renal outcome at a frequency similar to that of those with nephrotic syndrome. Factors related to better renal survival were having had a complete response to treatment in the case of those with nephrotic syndrome and having achieved proteinuria values of less than 1.5 g/day in the case of those without nephrotic syndrome.

Tailored management strategies for IgA nephropathy based on clinical presentations.

The treatment landscape for IgA nephropathy (IgAN) is rapidly evolving with the introduction of novel therapies targeting diverse disease pathways. Some have already been approved in different countries, while others are under investigation in randomized controlled trials (RCTs) with encouraging results. However, almost all performed RCTs have included only patients with refractory non-nephrotic proteinuria and preserved renal function. Other clinical presentations (rapidly progressive forms, malignant hypertension, thrombotic microangiopathy, nephrotic syndrome) have received less attention and are systematically excluded from RCTs. On the other hand, certain aspects, such as the impact of hematuria or the management in special populations (e.g. pregnant patients or transplant recipients), remain underexplored. This review proposes therapeutic algorithms to guide treatment decisions in different clinical scenarios, while highlighting gaps in current research.

Reliability of GFR Estimated by Creatinine-Based Formulas in Moderate-to-Severe Proteinuria.

Creatinine-based Glomerular Filtration rate (GFR) formulas introduce a substantial bias in GFR estimations in patients with frank nephrotic syndrome. The bias and accuracy of creatinine-based GFR estimates (eGFR) in patients with non-nephrotic proteinuria need better characterization. We utilized data from the Ramipril in non-diabetic renal failure (REIN 1) and REIN 2 trials involving non-diabetic chronic kidney disease (CKD) patients with proteinuria to compare eGFRs derived from the CKD Epidemiology Consortium (CKD-EPI)formulas (with and without race), and the European Kidney Function Consortium (EKFC) equations with iohexol clearance (a gold-standard GFR measure, measured glomerular filtration rate [mGFR]). Bias was defined as the median difference between eGFR and mGFR, while accuracy was assessed using P30 and P15 metrics, which represent the percentage of eGFR values within ±30% and ±15% of mGFR, respectively. The median bias of the three formulas being compared did not differ, being minimal and in a strict range (0.04 to 0.05 ml/ml/min/1.73m2) in the REIN 1 study and (-0.04 to -0.03 ml/min/1.73 m2) in the REIN 2 study. These findings were confirmed in analyses stratified by age and mGFR. The global accuracy of the three formulas regarding P30% showed sufficient accuracy (P30 >75%) in REIN 1 and all strata in REIN 2, but the mGFR stratum <15 ml/min/1.73m2. The CKD-EPI (with and without race), and EKFC equations show no significant bias and sufficient accuracy in patients with proteinuria. These formulas can be safely applied to non-diabetic CKD patients with moderate to severe proteinuria.

Reliability of the spot urine protein/creatinine ratio for assessing proteinuria in patients with renal disease.

This study aimed to assess the reliability of the spot urine protein/creatinine (sP/Cr) ratio for evaluating proteinuria across different ranges and renal functions. In this retrospective study, we analyzed 24-hour urine protein excretion (24 h UP) and sP/Cr measurements in 216 patients with renal disease. Pearson correlation and Bland-Altman analyses were performed to evaluate the correlation and agreement between 24 h UP and the sP/Cr. The patients were categorized into the following three 24 h UP groups: 150 to 299 mg/24 hours, 300 to 3499 mg/24 hours, and >3500 mg/24 hours. Significant positive correlations were found between the sP/Cr and the first two 24 h UP groups (r = 0.9104 and r = 0.9721, respectively) but not between the third group (r = 0.3110). Bland-Altman analysis confirmed good agreement in the group with <3500 mg/day proteinuria. Estimated glomerular filtration rates ≥60 mL/minute and <60 mL/minute were significantly correlated with the sP/Cr (r = 0.8714 and r = 0.4516, respectively). The sP/Cr ratio is a reliable indicator for non-nephrotic proteinuria, irrespective of renal function, but is unreliable for nephrotic-range proteinuria.

Clinicopathological features and prognosis of IgA vasculitis nephritis with nephrotic-range proteinuria in children.

To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients.

Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy

AimsPodocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). MethodsWe collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. ResultsMean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). ConclusionsPodocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

Renal Lymphangiectasia: A Diagnostic and Therapeutic Challenge

Renal lymphangiectasia, a rare lymphatic disorder, manifests as cystic infiltration in the perirenal and para-pyelic space due to lymphatic drainage defects. Diagnosis hinges on imaging modalities like ultrasound, CT, and MRI. However, lack of awareness can lead to confusion with other renal cystic pathologies. Here, we present a case of renal lymphangiectasia in a child, detailing diagnostic and therapeutic strategies. The patient, a 2-year-old and 2-month-old girl from a consanguineous marriage, presented with persistent abdominal distension. Clinical examination revealed growth retardation and normal blood pressure but abdominal distension with dullness. Lab investigations indicated acute renal failure with non-nephrotic proteinuria. Radiologically, renal lymphangiectasia was confirmed by ultrasound showing microcysts and perirenal cystic lesions with ascites, corroborated by MRI and CT scans. Treatment involved nephroprotective therapy and diuretics for ascites. Surgical intervention was necessitated due to cyst size and compressive nature, involving iterative punctures, marsupialization, and percutaneous drainage. Postoperatively, recurrent ascites temporarily worsened renal function but returned to baseline afterward. renal lymphangiectasia necessitates careful management due to its potential to progress to chronic renal failure. The prognosis depends on factors like initial proteinuria severity, treatment response, and complication management. Personalized approaches are pivotal in its diagnosis and management.

Determinants of non-diabetic kidney diseases in type 2 diabetic patients: Twenty years of single center experience.

Diabetic nephropathy is one of the most common complications associated with diabetes. However, non-diabetic kidney disease has been reported in patients with type 2 diabetes at varying incidence rates. The objective of our study is to investigate the occurrence, clinicopathological characteristics, and inflammatory markers linked to diabetic and non-diabetic nephropathy (NDN) in patients with type 2 diabetes mellitus (DM). Additionally, we aimed to explore the possibility of identifying non-diabetic pathology using different biopsy indications. A total of 159 patients with type 2 DM who underwent renal biopsy at a tertiary care nephrology clinic between January 2000 and January 2022 were enrolled in the study. We collected comprehensive data, including patient demographics, co-morbidities, diabetes duration, renal biopsy indications and results, serological markers, renal function, diabetic retinopathy (DRP), full blood count, blood biochemistry, urinalysis, and inflammatory markers. Patients were categorized based on their biopsy indications, and their biopsy results were classified into three groups: isolated NDN, isolated diabetic nephropathy (DN), and mixed nephropathy with concurrent NDN. We evaluated the relationship between biopsy indications and accompanying pathologies and statistically assessed the likelihood of each biopsy indication detecting non-diabetic renal pathology. Additionally, differences in other data, including demographic and laboratory results and medical histories, among the three groups were investigated. The most frequent indication of renal biopsy was atypical presentations of nephrotic syndrome or nephrotic range proteinuria (ANS/ANP) in 25.1% of patients. Other indications included unexplained renal failure (URF) in 22.6%, atypical presentations of non-nephrotic range proteinuria (ANNP) in 18.2%, acute kidney injury or rapidly progressive kidney dysfunction (AKI/RPKD) in 16.9%, microscopic hematuria in 15.7%, URF with ANNP in 11.3%, and severe nephrotic range proteinuria (SNP) in 9.4%. Renal biopsy revealed isolated NDN in 64.8%, DN in 25.1%, and mixed nephropathy in 10.1% of patients. Primary glomerular diseases were the main non-diabetic renal pathology, predominantly focal segmental glomerulosclerosis (FSGS) (36.4%) followed by MN (10.6%) and IgA nephropathy (7.5%). In comparison with the isolated DN and mixed nephropathy groups, patients in the isolated NDN group had significantly shorter diabetes duration, fewer DRP, as well as lower serum creatinine and neutrophil-to-lymphocyte ratio (NLR). Multivariate logistic regression analysis revealed that presence of hematuria (OR 4.40; 95% CI 1.34 - 14.46, p = 0.014), acute nephrotic range proteinuria (OR 11.93; 95% CI 1.56 - 90.77, p = 0.017), and AKI/APKD (OR 41.08; 95% CI 3.40 - 495.39, p = 0.003) were strong predictors of NDN. Lower NLR (OR 0.77; 95% CI 0.60 - 0.98, p = 0.035), shorter duration of diabetes (OR 0.90; 95% CI 0.84 - 0.97, p = 0.010), and absence of DRP (OR 0.35; 95% CI 0.12 - 0.98, p = 0.046) were also found to be independent indicators of NDN. Receiver operating characteristic curve (ROC) analysis revealed a cut-off value of ≤ 3.01 for NLR (sensitivity of 63.1%, specificity of 63.5%) with regards to predicting non-diabetic renal pathology (p = 0.006). Renal biopsy findings in patients with type 2 DM highlight that the prevalence of NDN may be higher than assumed, as presented mainly in the form of primary glomerular disease. The presence of AKI/RPKD, hematuria, and ANS/ANP serves as a reliable indicator of non-diabetic renal pathology. In more ambiguous situations, factors such as a shorter duration of diabetes, absence of DRP, and a lower NLR value may assist clinicians in biopsy decision.

A Case of Fibrillary Glomerulonephritis – When You Least Expect It

ABSTRACT Malignancies can be associated with a wide range of glomerular diseases, with each malignancy having a predilection for a particular glomerular disease. Fibrillary glomerulonephritis (FGN) is usually associated with paraproteinemia and commonly presents as nephrotic range proteinuria with or without the full-blown nephrotic syndrome. Here, we report the case of a young male with left flank pain, found to have left adrenal adenoma, incidentally detected to have microscopic hematuria and nonnephrotic proteinuria whose renal biopsy done during adrenalectomy showed FGN. Indeed, this case demonstrates an unexpected diagnosis with an unusual presentation in the background of an uncommon malignancy. Although difficult to establish causation, it can be considered a unique case of adrenal adenoma-associated FGN.

Genotype/phenotype relationship in mild congenital nephrotic syndrome

Introduction. Congenital nephrotic syndrome (CNS) is a severe disease complicated by hemodynamic instability, infections, thrombosis, growth disorder and progressive renal failure leading to end-stage kidney disease within a few years. The mutations of NPHS1 encoding nephrin is the most common cause of the CNS. The aim of this paper was to present a patient with NPHS1 homozygous Ser350Pro missense mutation that unexpectedly caused a mild clinical course of CNS. Case outline. We present a female patient who was diagnosed with severe nephrotic syndrome at 2.5 months of age. While waiting for the result of the genetic analysis, she was treated unsuccessfully with corticosteroids and angiotensin converting inhibitor (ACEI) four weeks, and then under Cyclosporine A (CsA) and ACEI she achieved partial remission within three months. Initially, the milder clinical course was explained by the positive effect of CsA, but as partial remission persisted even after the discontinuation of this drug, it remains unclear what influenced the improvement of the clinical course of the disease. At the time of writing this paper, the patient was 10.9 years old with normal serum creatinine, normal blood pressure and non-nephrotic proteinuria. Conclusion. NPHS1 homozygous Ser350Pro missense mutation may be presented by a mild clinical course of CNS. Further studies are needed to clarify a more predictive CNS genotype/phenotype relationship.

Clinical characteristics and risk factors for kidney involvement in children with immunoglobulin A vasculitis.

Immumoglobulin A (IgA) vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP), is a self-limiting systemic vasculitis in children. Kidney involvement is associated with a long-term unfavorable outcome and can lead to significant morbidity. This study was conducted to describe the clinical and laboratory characteristics of childhood IgAV with kidney involvement and to identify risk factors associated with IgAV nephritis (IgAVN). This was an ambidirectional descriptive study of 77 children with IgAV. All demographic data, clinical features, and laboratory tests were collected from electronic medical records from January 2010 to December 2022. Risk factors for kidney involvement in IgAV were assessed using multivariate logistic regression. Kaplan-Meier survival analysis was used to calculate the time to commencement of kidney involvement. Twenty-five children (32.4% of the IgAV patients) developed IgAVN. The common findings in IgAV with kidney involvement were microscopic hematuria (100%), nephrotic range proteinuria (44%), and non-nephrotic range proteinuria (40%). Multivariate logistic regression showed that age greater than 10 years (adjusted hazard ratio, AHR 4.66; 95% confidence interval, CI, 1.91-11.41; p = 0.001), obesity (body mass index, BMI, z-score ≥ +2 standard deviations, SDs) (AHR 3.59; 95% CI 1.41-9.17; p = 0.007), and hypertension at onset (AHR 4.78; 95% CI 1.76-12.95; p = 0.002) were associated significantly with kidney involvement. During follow up, most IgAV patients developed nephritis within the first 9 months. Age greater than 10 years, obesity, and hypertension at presentation were predictive factors for IgAVN. Our study emphasized that IgAV patients with risk factors should be closely monitored for at least 1 year after the onset of the disease.

Kidney disease in antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use.

The epidemiology of primary FSGS including cluster analysis over a 20-year period

IntroductionFocal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre’s 20-year experience of primary FSGS.MethodsPatients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset.ResultsThe total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with ‘nephrotic-range proteinuria’; cluster 2 (n=43) with ‘non-nephrotic-range proteinuria’; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%.ConclusionPeople who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression.Trial registrationThis study protocol was reviewed and approved by the ‘Research and Innovation committee of the Northern Care Alliance NHS Group’, study approval number (Ref: ID 22HIP54).

IgA Nephropathy Associated with ANCA Vasculitis: Case Report and Literature Review

IgA nephropathy is the most common primary glomerulonephritis, it’s association with Antineutrophil cytoplasmic antibody (ANCA) vasculitis constitutes a rare way of presentation that is scarcely described in the literature and diagnosed in only 1-2% of the population. The typical clinical presentation is an episode of systemic arterial hypertension with macroscopic hematuria, non-nephrotic proteinuria, acute kidney injury and in the worst-cases if the disturb persists end-stage chronic kidney disease. The definitive diagnosis is made through a biopsy, which shows the main characteristics of this nephropathy, which consists in crescent-shaped glomeruli formation, fibrinoid necrosis, mesangial deposits of IgA, as well as positive ANCA antibodies. Treatment consists in systemic corticosteroids and immunosuppressants to prevent progression to end-stage renal disease. We present a case of a 55-year-old female patient with a history of upper respiratory tract infection 2 weeks prior to the development of macroscopic hematuria, foamy urine, non-nephrotic proteinuria, and persistent acute kidney injury in whom IgA nephropathy was determined, which had a successfully response to treatment with high doses of corticosteroids and systemic immunosuppressants.

Clinical Characteristics and Histopathology in Adults With Focal Segmental Glomerulosclerosis

Rationale & ObjectiveFew data are available regarding histological features at the time of focal segmental glomerulosclerosis (FSGS) diagnosis among diverse real-world populations. This study describes clinical and histological characteristics, and correlates of histological disease severity, in adults with FSGS who underwent a clinical kidney biopsy. Study DesignReal-world cohort study with data derived from health records. Setting& Participants: Adults with FSGS by kidney biopsies from Arkana Laboratories during 1 January 2016 to 31 May 2020. ExposuresRace, CKD stage, nephrotic proteinuria, age, sex, and hypertension. OutcomesSevere histological disease, defined as global glomerulosclerosis in >50% of glomeruli and >25% interstitial fibrosis and tubular atrophy (IFTA). Analytical ApproachDemographic, clinical, and histological characteristics were compared between race groups. Correlates of severe disease were analyzed by multiple logistic regression. ResultsAmong 2,011 patients with FSGS, 40.6% were White and 23.6% Black. White patients were older (52.8 versus 45.5 years, P < 0.001) with higher estimated glomerular filtration rate (eGFR) than Black patients (53.5 versus 43.1 ml/min/1.73 m2, P < 0.001). A higher proportion of Black patients had global glomerulosclerosis ≥50% (32.1% versus 14.6%, P < 0.001) or IFTA >50% (34.6% versus 14.7%, P < 0.001). Severe histological disease was more likely in Black patients (odds ratio 2.46; 95% confidence interval 1.59, 3.79; P < 0.001). A higher proportion of patients with nephrotic than non-nephrotic proteinuria exhibited diffuse foot process effacement. LimitationsUnequal representation across United States (US) regions, missing demographic and clinical data, and lack of data on primary versus secondary FSGS, treatments, or outcomes. ConclusionsBlack patients were more frequently diagnosed at younger age with lower eGFR and more severe histological disease compared with White patients. Timelier identification of FSGS could increase the opportunity for therapeutic intervention, especially for high-risk patients, to mitigate disease progression and complications.

Histopathology Findings and Outcomes of Non-Nephrotic Range Proteinuria in Adults and Children

Histopathology Findings and Outcomes of Non-Nephrotic Range Proteinuria in Adults and Children

An Atypical Course of Visceral Leishmaniasis After Kidney Transplantation: A Case Report From Iran

Organ transplantation can lead to human visceral leishmaniasis (VL) transmission in humans. This report aims to describe the possible complications related to an atypical course of VL after kidney transplantation. A 61-year-old man who suffered end-stage renal failure received a deceased donor kidney transplant after 2 years of hemodialysis. Tacrolimus, mycophenolate mofetil, and prednisolone were used for immunosuppressive therapy, and renal function remained stable for 2.5 years. He was referred to our hospital because of fever and malaise. Physical and radiological examinations showed mild splenomegaly and cervical and inguinal lymphadenopathy. Laboratory data showed bicytopenia, elevated C-reactive protein, serum creatinine, and non-nephrotic proteinuria. Bone marrow biopsy aspiration showed no abnormality. Polymerase chain reaction confirmed the diagnosis of Leishmania infantum. Anti-leishmanial therapy was initiated with liposomal amphotericin B for 2 weeks, and the patient became clinically stable. So far, there has been no evidence of clinical or biological relapse, and kidney function is stable. Considering that VL has become increasingly widespread in immunocompromised patients in endemic regions, especially in patients with transplants, it is crucial to screen and rule out VL as a cause of infection in these patients. The probability of this problem should be considered in every patient with a transplant in endemic and nonendemic areas. Furthermore, our study showed that through timely diagnosis using noninvasive methods and standard treatments, mortality caused by this disease can be properly prevented.

Caracterización y tratamiento de los pacientes adultos con glomeruloesclerosis focal y segmentaria.

Introduction: Glomerulopathies constitute the third cause of chronic kidney disease. Within these, focal segmental glomerulosclerosis (FSGS) is one of the most prevalent in Latin America. Each patient has a varied clinical presentation and etiology, as well as different treatments and evolution. The study aimed to characterize patients with histological diagnosis of FSGS based on their clinical presentation, evolution, and treatment in three public nephrology reference hospitals in Quito-Ecuador. Methods: The present observational, longitudinal, retrospective study was conducted from January 2012 to December 2020 at the Hospitals Carlos Andrade Marín, Eugenio Espejo, and Hospital de las Fuerzas Armadas N1. The variables were demographic, clinical, laboratory, and treatment. Descriptive statistics, proportions, and confidence intervals for a proportion are used. A follow-up of 6, 12, and 24 months was carried out. Results: 98 FSGS records were analyzed, constituting 15.2% of all kidney pathologies. This pathology was more frequent in men (60.2%) and Hispanics (98%), with a median age of 40. 95.9% and 67.3% of the patients had no history of diabetes or hypertension, respectively. The main symptom at diagnosis was non-nephrotic proteinuria (65.3%), and 7.1% of patients required dialysis at the onset of the disease. At six months, only 24% of patients achieved remission. The most common first-line treatments were corticosteroids, followed by mycophenolate, while the most frequently used second-line drug was cyclosporine.

Outcomes of minimal change disease without nephrotic range proteinuria.

Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy.

#3269 EPIDEMIOLOGY OF PRIMARY FSGS INCLUDING CLUSTER ANALYSIS OVER A 20-YEAR PERIOD

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome (NS) in adults. This epidemiological study describes a renal centre's 20 year ‘real world' experience of patients with primary FSGS including cluster analysis. Method This retrospective analysis was conducted on patients diagnosed with primary FSGS at a tertiary renal centre with a catchment population of 1.55 million, over 2 decades. Data collection included baseline demographics, laboratory results, immunosuppression (IS) and outcomes: Complete &amp; partial remission, relapse, progression to renal replacement therapy (RRT) and mortality. A two-step cluster analysis was used to reveal groupings to aid prognostication and treatment decisions. Pre-specified cluster variables were: Serum albumin (sAlb), urine protein: creatinine ratio (uPCR) &amp; estimated glomerular filtration rate (eGFR). Results 87 patients were identified with primary FSGS after exclusion of secondary causes. Mean age was 49.3 years, 60.9% male, 86.2% white with median eGFR 46 ml/min, uPCR 573 mg/mmol, sAlb 33g/l (Table 1). Rates of partial and complete remission were 23% &amp; 49.4% respectively. Progression to RRT occurred in 27.4%, death in 27.4%. Comparing those receiving IS vs not: sAlb was lower 23 g/L vs 40 g/L (p&amp;lt;0.001), uPCR was higher 795 mg/mmol vs 318 mg/mmol (p &amp;lt;0.001). The IS group was more likely to achieve complete remission (62% vs 40%, p = 0.041), but relapsed more 48.6% vs 22% (p&amp;lt;0.027). There were no statistically significant differences between mortality or RRT. The 2-step cluster analysis separated the cohort into 3 clusters, see Fig. 1: Cluster 1 (n = 26) with ‘nephrotic range proteinuria’ mean sAlb 30 g/L, uPCR 778 mg/mmol and eGFR 72 ml/min; Cluster 2 (n = 43) with ‘non-nephrotic range proteinuria’, mean sAlb 39 g/L, uPCR 284 mg/mmol and eGFR 46 ml/min; Cluster 3 (n = 18) ‘NS’ sAlb 20 g/L, uPCR 1117 mg/mmol and eGFR 25 ml/min. IS use was comparable in the NS (cluster 3) and nephrotic range proteinuria (cluster 1) cohorts, but lower in cluster 2 (non-nephrotic range proteinuria) 77.8% &amp; 69.2% vs 11.6% p &amp;lt;0.001. Rates of complete remission were greatest in clusters 1 &amp; 3 vs cluster 2: 57.7% &amp;66.7% vs 37.2% though this did not achieve statistical significance (p 0.067). Conclusion Although there have been several recent US &amp; Asian reviews of primary FSGS, this study provides a review of the epidemiology of FSGS over a 20-year period in a predominantly white cohort in the UK. In general, the patients who received IS had lower sAlb and achieved remission more frequently. Although the aetiology of primary FSGS is unknown, it is hypothesised that it is due to an undiscovered circulating permeability factor. After the exclusion of secondary causes, KDIGO suggests only making the diagnosis in the presence of NS. Despite this the average sAlb in most epidemiological studies of primary FSGS have been above 30g/l. This is likely because of the inclusion of undiagnosed genetic or adaptive FSGS, but it may also be true that NS phenotype alone is too insensitive to diagnose primary ‘antibody driven’ FSGS. Our cluster analysis highlighted 3 potential FSGS phenotypes: A nephrotic cluster that clearly require IS; a cohort with preserved sAlb and non-nephrotic range proteinuria who will benefit from supportive care; lastly a cluster with heavy proteinuria but a sAlb &amp;gt; 30g/l. This group may still have antibody driven disease and thus benefit from immunosuppression and potentially genetic testing. The study received grant support from CSL Vifor