Fibrillary Glomerulonephritis Research Articles

An Updated Comprehensive Review on Diseases Associated with Nephrotic Syndromes.

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated approaches. This review focuses on all aspects of entities that are associated with nephrotic syndromes with updated information on recent advances in each field. This includes podocytopathies (focal segmental glomerulosclerosis and minimal-change disease), membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, fibrillary glomerulonephritis, amyloidosis, and monoclonal gammopathy of renal significance in the context of the nephrotic syndrome, but also renal involvement in systemic diseases, diabetic nephropathy, and drugs that are associated with nephrotic syndromes.

Case of Crescentic Fibrillary Glomerulonephritis with Linear IgG Mimicking Anti-glomerular Basement Membrane Nephritis with Good Response to Treatment

Case of Crescentic Fibrillary Glomerulonephritis with Linear IgG Mimicking Anti-glomerular Basement Membrane Nephritis with Good Response to Treatment

Rare Case of Fibrillary Glomerulonephritis with Concomitant Acute Interstitial Nephritis Related to Cemiplimab Use

Rare Case of Fibrillary Glomerulonephritis with Concomitant Acute Interstitial Nephritis Related to Cemiplimab Use

Congophilic fibrils in the glomeruli with polyclonal immunoglobulin gamma staining - another cause for diagnostic overlap: A case report

BACKGROUND Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities. Renal amyloid heavy and light chain (AHL) is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin (Ig) heavy chain and a single light chain, further supported by mass spectrometry (MS) and serum studies for monoclonal protein. But polyclonal light chain staining can pose a challenge. CASE SUMMARY Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma (IgG) staining pattern by immunofluorescence. The patient is a 62-year-old Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria. Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence, ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm. Congo red was positive while DNAJB9 was negative. MS suggested a diagnosis of amyloid AHL type with IgG and lambda, but kappa light chains were also present supporting the immunofluorescence staining results. Serum immunofixation studies demonstrated IgG lambda monoclonal spike. The patient was started on chemotherapy. The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after. CONCLUSION Tissue diagnosis of AHL amyloid can be tricky. Thorough confirmation using other available diagnostic techniques is recommended in such cases.

#2984 SLE associated fibrillary glomerulonephritis vs SLE nephritis with fibrils: can a straightforward distinction always be made?

Abstract Background and Aims Fibrillary glomerulonephritis (FGN) is an uncommon but serious kidney disease with unclear aetiology, variable prognosis, and a not well-established treatment. FGN has been associated with autoimmune diseases including SLE. Other aetiologies comprise diabetes, malignancies, HCV and chronic infections. Our goal is to discuss the pathologic and clinical differential diagnosis conundrums that a patient with a suspected SLE presented. Method We present the case of a 53-year-old woman evaluated for proteinuria (1 g/24 h), and glomerular haematuria. Renal function was normal. She referred mild arthralgias for the past two years. Her medical history was unremarkable for diabetes and hypertension. ANA and anti-dsDNA were positive. The rest of the immunological work-up was normal as well as protein immunofixation/free light chains. HCV, HBV, and HIV serology was negative. A thorough evaluation for malignancy was negative. A renal biopsy was performed. Results The renal biopsy showed enlarged glomeruli with mesangial matrix expansion (Congo-red negative), mild mesangial hypercellularity and focal endocapillary hypercellularity without hyaline deposits, fibrinoid necrosis or crescents, without significant chronic lesions (Fig. 1). A probable diagnosis based on light microscope could be that of a lupus nephritis class III with low activity and low chronicity indices. Immunofluorescence demonstrated weak or moderate immunofixation of IgG (2+), IgA(1+), C3(2+), C1q(1+), κ(1+) and λ(1+) in the mesangium and segmentally in the capillary walls with a smudgy appearance. IgM, C4, fibrinogen and albumin were negative. The lack of a full-house pattern and, more significantly, the low C1q intensity raised some questions about the validity of a lupus nephritis diagnosis. Ultrastructural evaluation revealed abundant fibrils that occupied the mesangium and permeated the glomerular basement membranes (GBMs). Fibrils were non branching and randomly oriented with a mean diameter of ∼15 nm (range: 11,87 nm -18,84 nm) (Fig. 2). No electron dense deposits, fingerprint deposits or tubuloreticular inclusions were detected. Immunohistochemical staining for DNA-J heat-shock protein family member B9 (DNAJB9) was then performed showing strong positivity in the mesangial matrix and GBMs. Interestingly, C4d was also strongly positive with the same pattern as DNAJB9. The diagnosis of fibrillary glomerulonephritis was suggested, mostly based on ultrastructural evaluation and immunohistochemical findings. Conclusion It is well known that the characteristic features of lupus nephritis (intense C1q staining, full-house staining, extraglomerular deposits, tubuloreticular inclusions, and combined subendothelial and subepithelial deposits) are, in some cases, neither universally present nor specific for lupus nephritis. Of special interest is the identification of fibrils in the renal biopsy of an SLE patient. The crucial importance of distinguishing between SLE associated FGN and SLE nephritis with fibrils is based on the generally poor renal prognosis of FGN as well as the unsatisfactory performance of immunosuppression. The differential diagnosis can be very challenging especially when DNAJB9 is not available.

#1297 Approaches to renal response assessment in rare monoclonal immunoglobulin related glomerulopathies

Abstract Background and Aims AL-amyloidosis (AL) and monoclonal immunoglobulin (MIg) deposition disease are common types of MIg-related glomerulopathies (MIgG) and are well-studied including approaches to treatment and hematological and renal responses (RR) assessment. Other rare MIgG comprise very diverse patterns of glomerular injury e.g. proliferative glomerulonephritis with MIg deposition (PGNMID), C3-glomerulopathy, fibrillary glomerulonephritis etc. Although RR defined as decrease in 24 h proteinuria by 30% without kidney function decline was validated only for renal AL it is widely used for MIg deposition disease and rare MIgG without validation. Nevertheless, the best approach to RR assessment in rare MIgG is still unclear. To shed some light on this problem we performed this study. Method We retrospectively analyzed 31 patients with rare MIgG who were treated with clone-specific treatment and had available follow-up (FUP) ≥6 months (mo). The following morphological patterns were diagnosed: PGNMID (n = 9), C3-glomerulopathy (n = 9), thrombotic microangiopathy (n = 5), cryoglobulinemic glomerulonephritis (n = 3), fibrillary glomerulonephritis (n = 3), immunotactoid glomerulonephritis (n = 1) and membranous nephropathy (n = 1). Patients’ baseline parameters are shown on Fig. 1 as well as treatment modalities. Hematological response defined according to currently accepted criteria is demonstrated on Fig. 1. We evaluated two approaches to the RR assessment: 1) at least partial renal response (PR) defined as 24 h proteinuria decreased by 50% from the baseline and <3.5 g, and 2) according to Palladini's criteria for AL (AL-RR) i.e. 24 h proteinuria decreased by 30% from the baseline or <0.5 g. Both RR were considered as achieved only in the absence of estimated glomerular filtration rate (eGFR) decline >25%. Time points for RR assessment were 6, 12 and 24 mo from the clone-specific treatment initiation. Renal outcome was estimated as initiation of renal replacement therapy or eGFR <15 ml/min/1.73 m2 at the end of follow-up. Death-censored renal survival was analyzed by the Kaplan-Meier method. Cox regression analysis was applied to determine which RR was independently associated with long-term kidney outcome. P-value was assumed at <0.05. Median FUP was 19 (7; 50) mo. FUP ≥12 and ≥24 mo were available in 26 and 17 patients, respectively. Results Total number of patients who achieved AL-RR at any RR assessment time point was 22 (71%). At 6, 12 and 24 mo the achievement of AL-RR was registered in 17, 16 and 10 patients, respectively. PR cumulatively was achieved in 19 (61%) patients: at time points of 6, 12, and 24 mo it was registered in 14, 14 and 9 cases, respectively. The 5-year cumulative renal survival in those who had AL-RR was better than in not responders (Fig. 2A). Patients who ever achieved PR had better cumulative renal survival compared with patients with no renal remission (Fig. 2B). In univariate Cox regression analysis the achievement of AL-RR (Exp(β) 0.158 (95% CI 0.03; 0.819)) was associated with renal outcome as well as the achievement of PR (Exp(β) 0.074 (95% CI 0.09; 0.626)). In multivariate Cox regression model adjusted for eGFR at the time of kidney biopsy AL-RR vs no response was estimated as an independent predictor of renal long-term prognosis (Exp(β) 0.082 (95% CI 0.009; 0.725)) as well as eGFR (Exp(β) 0.89 (95% CI 0.821; 0.985)). The only independent predictor of renal outcome in the model including eGFR at the time of kidney biopsy (Exp(β) 0.85 (95% CI 0.72; 0.99), p = 0.05) was PR (Exp(β) 0.011 (95% CI 0; 0.547), p = 0.021). Conclusion The classical concept of complete and partial renal remission seems to be more appropriate for rare MIgG and requires further validation studies.

#198 Different patterns of renal thrombotic microangiopathy

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function. The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA. Method We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients. Results Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD). Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis). Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1). When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1). Conclusion Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy. The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important. Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.

#1346 Inpatient and outpatient service review of a Greek reference centre for glomerular diseases

Abstract Background and Aims The glomerulonephritis (GN) is a rare and complicated disease with high demand of hospital resources while the chronic kidney disease and end-stage renal disease present increased prevalence in these patients. Method We retrospectively assessed the inpatient and outpatient service of a Greek reference centre for glomerular diseases during the pre-Covid-19 period 2018-2020. Results 267 patients (38% female, median age 65 ± 23 years) included. All patients underwent a kidney biopsy by the nephrologist without complications. ANCA associated GN (18%), Focal Segmental Glomerulosclerosis/Minimal Change Disease (17.5%), IgA nephropathy (17%), Membranous Nephropathy (12.6%), Lupus Nephritis (5%), Membranoproliferative GN (3%), Fibrillary GN (3%), Monoclonal Gammopathy of Renal Significance (3.3%) and IgG4-related disease (2%.) are encompassed. We reported median 75 new patients per year. Regarding the inpatient service, we observed an increasing trend to the hospitalizations during this period (274, 452, 461 hospitalizations in 2018, 2019, 2020 respectively). The AAGN was the most common disease of hospitalizations through this period (53% in 2018, 33% in 2019, 39% in 2020), whereas the second most common was the FSGS/MCD (28% in 2018, 13% in 2019, 23.8% in 2020). The outpatient's service review also revealed an increasing number of visits per person per year (279, 456 and 464 total visits in 2018, 2019 and 2020 respectively). The disease with the highest number of visits per person was reported the AAV (median 3.25 visits per patient per year). All the patients were managed in adherence to the latest guidelines for GN in collaboration with a multidisciplinary team, consisting of nephrologist, rheumatologist, cardiologist, and pathologist. Finally, we reported complete response at 76% of the patients and in terms of renal improvement, 46% presented eGFR≥60 ml/min/1.73 m2, 45% eGFR<60 ml/min/1.73 m2 and only 9% progressed to ESRD after the first year of treatment. Conclusion Patients with GN present an increased need for hospitalization and regular outpatient visits. Addressing these diseases necessitates the expertise of a multidisciplinary team to provide comprehensive care that maximizes the potential for sustained positive long-term outcomes.

353 Diagnostic Conundrum: Drug-Induced Interstitial Nephritis, Atypical Anti-GBM or Fibrillary Glomerulonephritis?

353 Diagnostic Conundrum: Drug-Induced Interstitial Nephritis, Atypical Anti-GBM or Fibrillary Glomerulonephritis?

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.

A Study of Nodular Glomerulopathy – A Single-center Experience and Review

ABSTRACT Background: Mesangial expansion is a histopathological manifestation characterized by abnormal proliferation of mesangial cells and accumulation of matrix proteins within the central region of the glomerulus. While diabetes is a well-known cause of mesangial expansion, several rare diseases can also present with this pathology. This study aimed to estimate the prevalence of lesions exhibiting mesangial expansion in a tertiary care center in Tirunelveli, India, and elucidate the spectrum of disorders contributing to mesangial expansion lesions in renal biopsies. Methodology: A retrospective analysis of renal biopsies conducted at Tirunelveli Medical College and Hospital from 2016 to 2022 was performed. Kidney tissue samples were subjected to light microscopy and immunofluorescence studies using appropriate stains. Patients with isolated mesangial expansion were identified. Demographic details, clinical indications for biopsy, and pathological findings were recorded and analyzed. Results: Out of 616 kidney biopsies, mesangial expansion was present in 39 patients (6.33%). Notably, nodular mesangial expansion was observed in 33 patients (5.3%), with diabetes being the most prevalent associated condition (74.19%). Amyloidosis, heavy chain deposition disease, fibrillary glomerulonephritis, collagen fibrotic glomerulopathy, and idiopathic nodular glomerulosclerosis were identified as other contributors to mesangial expansion. Glomerular filtration rate and interstitial fibrosis and tubular atrophy were worse in the diabetic population. Conclusions: This study sheds light on the varied etiologies contributing to mesangial expansion beyond diabetes, emphasizing the importance of specialized staining methods for precise diagnosis.

Ultrastructural Examination of Glomerular Fibrillary Deposits in Diabetic Nephropathy

Glomerular fibrillary deposits have occasionally been reported in diabetic nephropathy, but no large-scale, ultrastructural evaluation of these deposits has been reported so far. Here, we report our study of glomerular non-Congophilic, DnaJ homolog subfamily B member 9 negative fibrillary deposits in diabetic nephropathy as characterized by transmission electron microscopy. Clinical data from 55 patients with biopsy-confirmed diabetic nephropathy and 18 healthy living donors were reviewed, and their biopsies were evaluated by light microscopy, immunofluorescence, and electron microscopy. Small fibrillary structures with a diameter of 10 ± 1 nm were present in all cases with diabetic nephropathy, regardless of the histologic class. In addition, glomerular fibrillary structures with a diameter of 23 ± 5 nm or 30 ± 7 nm were present in 35 cases. Interestingly, especially the small- and medium-sized fibrils, usually without apparent organization, were comparable with fibrils in fibrillary glomerulopathy. We conclude that glomerular fibrillary deposits occur far more commonly in renal biopsies of patients with diabetic nephropathy than generally considered. This is an important finding because their similarity to fibrils in fibrillary glomerulonephritis may complicate the histologic diagnostic process, especially in cases of overlapping clinical manifestations. Therefore, when encountering fibrillary deposits on electron microscopy, it is important to consider diabetic nephropathy as an alternative diagnosis.

The Prevalence and Clinicopathological Spectrum of Nondiabetic Renal Disease in Patients with Diabetes in a Tertiary Care Center.

Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM), leading to end-stage renal disease. A wide spectrum of nondiabetic renal diseases (NDRDs) is reported in type 2 DM. We retrospectively reviewed the medical records of patients with type 2 DM who underwent a kidney biopsy from September 2019 to November 2021 at our center. Patients were grouped as having isolated DN, isolated NDRD, or mixed NDRD with underlying DN. According to the 379 renal biopsies performed during the study period, 57 patients had DM. The prevalence of DN, isolated NDRD, and combined pathologies was 36.8%, 35.1%, and 28.1%, respectively. The most common NDRD was infection-related glomerulonephritis (IRGN) (50.0%), followed by membranous nephropathy (3.0%), focal segmental glomerulosclerosis (10%), pyelonephritis (10%), minimal change disease (1.8%), fibrillary glomerulonephritis (1.8%), and ANCA-associated vasculitis (1.8%). The most common pathological finding of NDRD in the mixed group was IRGN (56.3%), followed by acute tubular injury (31.3%). The duration of DM was significantly shorter (4.8 ± 2.3 years vs. 9.7 ± 3.3 years, P = 0.035) in NDRD patients compared with patients with DN. NDRD was observed in 15% and mixed lesions in 25% of patients, with concomitant diabetic retinopathy (P = 0.029). We conclude that with increasing evidence of NDRD even in patients with DN, careful application of renal biopsies in diabetic patients would assist in the early diagnosis and institution of specific therapy for NDRD to ensure better patient and renal survival.

A Case of Fibrillary Glomerulonephritis Presenting as Rapidly Progression Glomerulonephritis in a Patient with Untreated Hepatitis C

A Case of Fibrillary Glomerulonephritis Presenting as Rapidly Progression Glomerulonephritis in a Patient with Untreated Hepatitis C

Diagnosis of Fibrillary Glomerulonephritis with Positive Immunoglobulin A-κ Deposits Presenting as Membranous Nephropathy Using Immunoelectron Microscopy: A Case Report and Literature Review

ABSTRACT Fibrillary glomerulonephritis (FGN) is a rare disease characterized by randomly arranged fibrils with a diameter of 10–30 nm on immunoelectron microscopy. Clinically, renal insufficiency, hypertension, hematuria, and proteinuria are the typical symptoms of FGN. Currently, there are limited treatment options for FGN, and transplant recurrence is common. We reported the case of a middle-aged Chinese woman diagnosed with FGN with positive immunoglobulin A-κ deposits presenting as membranous nephropathy.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Proteomic Analysis of Complement Proteins in Glomerular Diseases

Complement plays an important role in the pathogenesis of glomerulonephritis (GN). Even though the underlying etiology of GN might be different, complement activation with subsequent glomerular deposition of complement proteins result in glomerular injury and progression of the lesions. Routine immunofluorescence microscopy (IF) includes staining for only complement factors C3c and C1q. Therefore, with regard to evaluation of the complement pathways, routine kidney biopsy provides only limited information. In this study, using laser microdissection of glomeruli followed by mass spectrometry, complement proteins and pathways involved in GN were analyzed. We found that C3 followed by C9 are the most abundant complement proteins in GN, indicating activation of classical or lectin or alternative, and terminal pathways, either exclusively or in a combination of pathways. Furthermore, depending on the type of GN, C4A and/or C4B were also present. Therefore, membranous nephropathy (MN), fibrillary GN, and infection-related GN showed C4A dominant pathways, whereas lupus nephritis (LN), proliferative GN with monoclonal Ig deposits, monoclonal Ig deposition disease (MIDD), and immunotactoid glomerulopathy showed C4B dominant pathways. Significant deposition of complement regulatory proteins, factor H-related protein-1 (FHR-1) and factor H-related protein-5 (FHR-5), were also detected in most GN. This study shows accumulation of specific complement proteins in GN. The complement pathways, complement proteins, and the amount of complement protein deposition are variable in different types of GN. Selective targeting of complement pathways may be a novel option in the treatment of GN.

IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium.

Fibrillary glomerulonephritis (FGN), a rare disease is pathologically characterized by glomerular fibril accumulation ranging from 12 to 24nm in diameter with negative Congo red staining. Recently, the identification of DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sensitive and specific marker for FGN has revolutionized diagnosis of this disease. However, few recent studies have reported DNAJB9-negative glomerulonephritis with fibrillar deposits. As such, it remains unclear whether DNAJB9-negative cases can be considered equivalent to FGN. Here, we report the case of a 70-year-old woman who developed renal impairment and nephrotic-range proteinuria. Renal biopsy and pathological examination revealed focal glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed IgA-dominant deposition of polytypic IgG in the glomerulus. Electron microscopy revealed hump-like subepithelial electron dense deposits with fibrils of 15-25nm in diameter. These findings were consistent with FGN; thus, Congo red and direct fast scarlet (DFS) staining, and immunohistochemistry for DNAJB9 were performed. In addition to negative Congo red/DFS/DNAJB9 staining, laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) resulted negative for DNAJB9, which is a highly sensitive and specific marker for FGN. The patient's renal function further declined, prompting administration of rituximab weekly for 2weeks, similar to the treatment for FGN. This is a unique case of IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium, unlike previous DNAJB9-negative cases. Thus, DNAJB9-negative cases diagnosed based on accurate electron microscopic evaluation must be gathered, and LMD and LC-MS/MS must be used to analyze the organized fibrillar deposits to reveal the disease entity.

Recurrence of rare disease after kidney transplant

The incidence of chronic kidney diseases (CKDs) by rare etiologies is growing along with other CKDs. This mini-review discusses the epidemiology, pathogenesis, clinical presentation, and diagnosis of rare kidney disease recurrence after kidney transplantation (KTx) including primary hyperoxaluria (PH), adenine phosphoribosyl transferase (APRT), C3 glomerulopathy (C3 GP), and fibrillary glomerulonephritis (FGN). It was shown that PH, like acute rejection, causes delayed graft function, confusing the physicians. Moreover, C3 GP is more prevalent than FGN among kidney transplant patients. Therefore, it is necessary to monitor rare diseases (RDs) before KTx in patients with any history of bilateral nephrocalcinosis or nephrolithiasis.

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.