Clinical Outcomes of Patients With Primary Membranous Nephropathy and Subnephrotic Proteinuria

Objectives: To update the information about the prognosis of patients with primary membranous nephropathy (MN) and subnephrotic proteinuria and identify the relevant predictors.Methods: In total, 474 cases of biopsy-proven primary MN with at least 18 months of follow-up were reviewed to determine the outcomes of the subgroup of patients that presented with subnephrotic proteinuria. Clinical data included initial proteinuria and microhematuria, defined as the average proteinuria/microhematuria of the first 6 months during the course. Outcomes included partial remission (PR), complete remission (CR), nephrotic proteinuria progression, and kidney function progression, defined as ≥50% loss of kidney function or end-stage kidney disease.Results: In total, 205 patients with primary MN and subnephrotic proteinuria at biopsy were eligible. During a median follow-up of 43 months, 200 (97.56%), 167 (81.46%), and 53 (25.85%) patients attained PR, CR, and nephrotic proteinuria progression, respectively. Only one patient (0.49%) progressed to the kidney function progression. By multivariate Cox hazards regression analyses, the initial proteinuria was identified as the independent predictor for PR, CR, and nephrotic proteinuria progression with adjusted hazard ratios (aHRs) of 0.67 (95% confidence interval, 0.56–0.80), 0.50 (95% CI, 0.40–0.63), and 2.97 (95% CI, 2.23–3.97), respectively. A higher level of initial microhematuria was also associated with an increased risk of nephrotic proteinuria progression. The corresponding aHR was 1.11 (95% CI, 1.05–1.17).Conclusion: Among patients with primary MN and subnephrotic proteinuria, although the overall prognosis is excellent, dynamic detection and effective management of proteinuria remain important. In addition, initial microhematuria may be another predictor of nephrotic proteinuria progression.

IgA vasculitis nephritis clinical course and kidney biopsy – national study in children

The aim of the study was to investigate the relationship between the severity of typical clinical symptoms, severity of histopathological lesions in kidney biopsies in IgA vasculitis nephritis (IgAVN) and to propose indications for kidney biopsy in children. Material and methods This retrospective study enrolled 106 patients, included in the IgAVN registry of Polish children, diagnosed by kidney biopsy. Renal and extrarenal symptoms at onset of the disease were analyzed. Biopsy results were assessed using Oxford classifications (MEST-C). The patients were divided into 3 groups depending on the severity of proteinuria: A-nephrotic proteinuria with hematuria; B-non-nephrotic proteinuria with hematuria; C-isolated hematuria. Results The first symptoms of nephropathy were observed at the 0.7 (1–128.4) months from the onset of extrarenal symptoms. Kidney biopsy was performed on 39 (6–782) days after the onset of nephropathy symptoms. MEST-C score 4 or 5 was significantly more frequent in children from group A than in groups B and C. Significantly higher mean MEST-C score was found in patients with abdominal symptoms than without. In group A: S0 and T0 we found in significantly shorter time to kidney biopsy than in S1, T1–2 p < 0.05) and in group B the significantly shorter time in T0 compare to T1–2 p < 0.05). The ROC analysis shows that S1 changes appear in kidney biopsies in group A with cut off 21 days (AUC 0,702, p = 0.004, sensitivity 0.895 specificity 0.444) T1–2 changes after 35 days (AUC 0.685, p = 0.022, sensitivity 0.750, specificity 0.615), and in goupn B T1–2 cut off is 74 days (AUC 0,738, p = 0.002, sensitivity 0.667, specificity 0.833). Conclusions In childhood IgAVN, the severity of changes in the urine is clearly reflected in the result of a kidney biopsy. The biopsy should be performed in patients with nephrotic proteinuria no later than 3 weeks after the onset of this symptom in order to promptly apply appropriate treatment and prevent disease progression. Accompanying abdominal symptoms predispose to higher MESTC score.

Renal Thrombotic Microangiopathy in Concurrent COVID-19 Vaccination and Infection

We report on the development of nephrotic proteinuria and microhematuria, with histological features of renal thrombotic microangiopathy (TMA), following the first dose of BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) and COVID-19 diagnosis. A 35-year-old previously healthy man was admitted at our hospital due to the onset of foamy urine. Previously, 40 days earlier, he had received the first injection of the vaccine, and 33 days earlier, the RT-PCR for SARS-CoV-2 tested positive. Laboratory tests showed nephrotic proteinuria (7.9 gr/day), microhematuria, serum creatinine 0.91 mg/dL. Kidney biopsy revealed ultrastructural evidence of severe endothelial cell injury suggestive of a starting phase of TMA. After high-dose steroid treatment administration, complete remission of proteinuria was achieved in a few weeks. The association of COVID-19 with renal TMA has been previously described only in patients with acute renal injury. Besides, the correlation with COVID-19 vaccine has not been reported so far. The close temporal proximity (7 days) between the two events opens the question whether the histological findings should be ascribed to COVID-19 itself or to vaccine injection.

Comparison of Patients with Hospital-recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: a Nationwide Study in Denmark

Background: Registry-based studies of nephrotic syndrome (NS) may only include a subset of patients with biochemical features of NS. To address this, we compared patients with laboratory-recorded nephrotic proteinuria and hypoalbuminemia to patients with hospital-recorded NS. Methods: We identified adult patients with first-time hospital-recorded NS (inpatients, outpatients or emergency room visitors) in the Danish National Patient Registry and compared them to adults with first-time recorded nephrotic proteinuria and hypoalbuminemia in Danish laboratory databases during 2004-2018, defining date of admission or laboratory findings as index date. We characterised these cohorts by demographics, comorbidity, medication use, and laboratory and histopathological findings. Results: We identified 1,139 patients with hospital-recorded NS and 5,268 patients with nephrotic proteinuria and hypoalbuminemia of which 760 patients were identified with both. Within one year of the first recorded nephrotic proteinuria and hypoalbuminemia, 18% had recorded hospital diagnoses indicating the presence of NS, while 87% had diagnoses reflecting any kind of nephropathy. Among patients identified with nephrotic proteinuria and hypoalbuminemia, most recent eGFR was substantially lower (median of 35 vs. 61 ml/min/1.73 m2), fewer underwent kidney biopsies around index date (34% vs. 61%), and prevalence of thromboembolic disease (25% vs 17%) and diabetes (39% vs. 18%) was higher when compared to patients with hospital-recorded NS. Conclusions: Patients with nephrotic proteinuria and hypoalbuminemia are five-fold more common than patients with hospital-recorded NS, and they reveal a lower eGFR and more comorbidity. Selective and incomplete recording of NS may be an important issue when designing and interpreting studies of risks and prognosis of NS.

Crosstalk between proteinuria, plasma oxalic acid and inflammation in glomerulonephritis patients: an exploratory study

In the present exploratory cross-sectional cohort study, we evaluated whether plasma and urine oxalate concentrations in patients with primary glomerulonephritis depend not only on the glomerular filtration rate but also on the proteinuria level and influence the inflammatory response. Methods. We enrolled 100 participants, including 76 patients with glomerulonephritis having chronic kidney disease stage (CKD) 1–3b (69.7% of them with nephrotic syndrome) and 24 healthy volunteers. We excluded patients with diabetes, cardiovascular disease and those with glomerulonephritis with an estimated GFR (eGFR) < 30 mL/min/1.73 m2. In addition to routine hematological and biochemical tests, plasma oxalate concentration, urinary oxalate excretion, and serum interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) levels were assessed in all study participants. Results. We observed that plasma oxalic acid concentration was significantly higher in patients with glomerulonephritis (19.0 [5.9–45.2] µmol/L) than in healthy volunteers (5.5 [3.8–7.3] µmol/L, p < 0.0001). Moreover, nephrotic proteinuria was significantly associated with plasma oxalic acid elevation independent of the patients’ age, sex, glomerular filtration rate, and body mass index (odds ratio = 1.42, 95% confidence interval = 1.13–1.77, p = 0.002). In turn, the increased plasma oxalic acid concentration was associated with high levels of serum IL-6 and MCP-1, which may be cardiovascular risk factors in patients with primary glomerulonephritis. Conclusions. Nephrotic proteinuria was significantly associated with the elevation of plasma oxalic acid concentration and hyperoxaluria in glomerulonephritis patients with CKD stages 1–3b. Plasma oxalate at least partly promotes inflammation, which may be a cardiovascular risk factor in patients with glomerulonephritis in the early stages of CKD. Future studies should recruit at least 156 participants to confirm our preliminary results, validate nephrotic proteinuria as a risk factor for oxalate metabolism violation or determine the role of impaired oxalate homeostasis in clinical outcomes in patients with glomerulonephritis.

Identification of Lupus Podocytopathy with Coexistent Glomerular Diseases – A Case Report

Introduction/Objective Lupus podocytopathy (LP), featured by nephrotic syndrome, is a unique subtype of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis (FSGS) on renal biopsy with diffuse podocyte foot process effacement and no capillary-loop immune deposits. LP usually presents on a background of ISN/RPS class I or class II lupus nephritis, and very rarely may present without immune deposits. Diagnosis of LP, when confounded by other glomerular diseases associated with nephrotic syndrome, can be very challenging and requires thorough clinical and pathology correlations. Methods Here we report a case of LP in a patient with nephrotic syndrome and multiple comorbidities affecting kidneys. A 24-year-old female with type-I diabetes, psoriasis, and intermittent arthritis/rash of unknown etiology, presented with abrupt onset of nephrotic proteinuria attributed to recent low dose prednisone therapy, and renal insufficiency. A renal biopsy showed nodular glomerulosclerosis and FSGS. No immune deposits were identified by immunofluorescence or electron microscopy. Ultrastructurally there was also diffuse glomerular basement membrane thickening and over 90% podocyte foot process effacement. With no established systemic lupus erythematosus (SLE), the case was initially diagnosed as diabetic nephropathy with coexistent FSGS as the etiologies for nephrotic proteinuria, and the patient was put on ACEI and diuretics. However, massive proteinuria persisted, and the patient also developed pancytopenia. Serology concurrent with the biopsy came out later showing positive autoantibodies against dsDNA, Smith, and Histone. With continued worsening of creatinine, a renal biopsy was repeated revealing essentially similar findings to the first biopsy. Results Integrating the serology results and clinical presentation, SLE was favored. The pathology findings were re- evaluated and considered to be most consistent with LP and coexistent diabetic nephropathy, with FSGS either a component of LP or an independent lesion secondary to diabetes or hypertension. The patient was started with high dose prednisone at 60 mg/day. One month later, her proteinuria, serum creatinine, pancytopenia, skin rash, and arthritis were all significantly improved. Conclusion LP can be easily masked by coexistent glomerular diseases. Sufficient awareness of the entity is necessary for the appropriate diagnosis and treatment.

Non-Hodgkin lymphoma–associated AA amyloidosis

Amyloidosis is a rare complication of non-Hodgkin lymphoma, almost exclusively of AL-type, AA-type amyloidosis secondary to non-Hodgkin lymphoma is extremely rare. We report a case of a 55-year-old woman diagnosed with follicular lymphoma that developed nephrotic proteinuria; further investigation confirmed the diagnosis of AA-type amyloidosis, and other long-term inflammatory disorders were excluded. Despite initiation of combined chemotherapy, there was no hematological response and kidney function and clinical condition continued to deteriorate. This case describes an unexpected association, AA-type amyloidosis secondary to non-Hodgkin lymphoma, a condition with poor renal prognosis where treating the underlying disease is paramount.

P0121KIDNEY BIOPSY FINDINGS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Background and Aims The aim of the study is to evaluate kidney biopsy findings other than renal diabetic changes in patients with type 2 diabetes mellitus. Method Diabetic patients with kidney biopsy between January 2003 and January 2020 were enrolled to the study. Kidney biopsy was performed to patients with suspicion of kidney disease other than diabetic nephropathy. The suspicious cases were patients without diabetic retinopathy, diabetes mellitus history less than 5 years, creatinine increase faster than expected course and hematuria. Demographic features, biopsy finding were all noted. Results Totally, 135 patients’ data were evaluated in which 54.1% was male. Demographic characteristics of the patients and laboratory data are given in Table 1. Mean age was 55.4±11 years and mean diabetes duration was 6.9±6.3 years. Mean duration of diabetes was 5.3±5.5 years in patients with nondiabetic nephropathy whereas it was 10.2±6.4 and 11.2±7.6 years in patients with diabetic and/or nondiabetic pathologies respectively (p&lt;0.05). Serum creatinine and proteinuria level were lower, and hemoglobin levels were higher in patients with nondiabetic nephropathy (p &lt;0.05).C3 was low in 3.7% of patients. ANA and ANCA positivity were seen in 8.1% and 3.7% of the patients, respectively. Patients without diabetic retinopathy was 81.7% of the total cohort. Biopsy indications were renal insufficiency (8.9%), nephrotic syndrome (24.4%), non-nephrotic proteinuria (16.4%), renal insufficiency with nephrotic range proteinuria (25.9%), renal insufficiency with non-nephrotic proteinuria (24.4%). Mean glomeruli number was 19.3±11.1. Ten patients had macroscopic hematuria in which all resolved with conservative care. Early diabetic changes, diffuse and/or nodular glomerulosclerosis were present in 3.1% and 96.9% of diabetic patients, respectively. Biopsies with diabetic changes with other nondiabetic pathologies were 3% of the biopsies. Isolated nondiabetic nephropathy was found in 23.7% of patients. Pathologic findings other then diabetic changes were as follows in patients without diabetic nephropathy: focal segmental glomerulosclerosis (FSGS) 49.5%, membranous glomerulonephritis 14,1%, Ig A nephropathy 12,1%, membranoproliferative glomerulonephritis 5 %, crescentic glomerulonephritis 4,1%, acute tubular necrosis 4,1%, amyloidosis 3%, tubulointerstitial damage 2%, others 6,1%. Conclusion Biopsy in diabetic patients is beneficial to show both diabetic nephropathy and other kidney pathologies. Kidney biopsy may be performed if there is suspicion of other glomerular pathologies. Focal segmental sclerosis was the most common pathology in our patients without diabetic nephropathy