Systemic autoinflammatory disease, IgA glomerulonephritis and renal cortical necrosis: coincidence or causation?

We present a patient with a rare systemic autoinflammatory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in extremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymphadenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and proteinuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclophosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid progression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenomenon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient's clinical manifestations.

Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Mevalonato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenomegalia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias mostrando nefropatía por IgA alternando actividad y cronicidad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatillos para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para generar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.

Antineutrophil cytoplasmic antibody-negative pauci-immune glomerulonephritis in a patient with Waldenstrom macroglobulinaemia.

Waldenstrom macroglobulinaemia (WM), the predominant subtype of lymphoplasmacytic lymphoma with bone marrow involvement and serum IgM paraprotein, is a haematological condition commonly associated with renal parenchymal involvement. However, antineutrophil cytoplasmic antibody (ANCA)-negative pauci-immune crescentic glomerulonephritis (PICGN) in kidney infiltrated by lymphoma is very rare, with only two cases described in chronic lymphocytic leukaemia in English literature so far. We herein report the first patient with WM developing ANCA-negative PICGN. He was a 76-year-old male who presented with elevated serum globulin level and bilateral groin lymph node enlargement, subsequently diagnosed to have WM after pathologic examination of the bone marrow and groin lymph node. One month later, he was found to have acute kidney injury and proteinuria. Renal biopsy confirmed the presence of parenchymal involvement by WM accompanied by PICGN; while ANCA testing was negative. He was treated with pulse methylprednisolone followed by oral prednisolone. In addition, six courses of intravenous rituximab and oral cyclophosphamide were given. There was significant improvement in both his renal and haematological conditions. The clinical course of this case suggested that ANCA-negative PICGN may represent a paraneoplastic syndrome and a rare manifestation of WM-associated renal lesion. Early kidney biopsy and prompt treatment may improve the outcome of patients.

The Pulsing Paradox: Successful Steroid Therapy in Infection-Related Glomerulonephritis.

The patterns of infection-related glomerulonephritis (IRGN) are rapidly changing in terms of age at presentation and sources of infection. The existing literature on the use of steroids in IRGN is inconsistent. A diabetic male in his sixties presented with features of anasarca, bilateral flank pain, and acute pulmonary edema. He had a non-healing ulcer over his right leg, with pus culture showing growth of methicillin-resistant Staphylococcus aureus (MRSA). Computed tomography (CT) of the kidneys, ureter, and bladder (KUB) showed features of bilateral pyelonephritis. The patient went on to develop acute renal failure and eventually required hemodialysis. A renal biopsy was performed, and features of IRGN with crescents were noted. Considering the presence of crescents in renal biopsy, a trial of steroids was given under antibiotic cover, which resulted in a near-complete resolution of renal failure.

Protein A immunoadsorption for anti-glomerular basement membrane nephritis.

Anti-glomerular basement membrane (GBM) nephritis is a rare autoimmune disorder characterized by acute and rapidly progressive glomerulonephritis. In this report, we present the case of a 52-year-old woman with anti-GBM nephritis who was treated with Staphylococcus Protein A immunoadsorption in combination with glucocorticoids and cyclophosphamide. After 8 cycles of immunoadsorption, the patient's anti-GBM antibodies decreased from 363 AU/mL to less than 20 AU/mL, accompanied by a dropped immunoglobin G level, although renal impairment persisted. We reviewed the therapeutic options for anti-GBM nephritis and compared plasma exchange, double filtration plasmapheresis, and immunoadsorption with regard to plasma consumption, allergic events, and plasma components loss. Protein A immunoadsorption appears to be a promising treatment modality for anti-GBM nephritis.

Application of the updated International IgA Nephropathy Prediction Tool in children one or two years post-biopsy.

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy.

Long-term outcomes of patients with IgA nephropathy in the German CKD cohort.

Background: The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established. Methods: From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.73 m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model. Results: The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1-0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m2. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15 ml/min/1.73 m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 [95% confidence interval (CI) 1.02-4.05], 3.8 (95% CI 1.92-7.5), 5.64 (95% CI 2.58-12.33) and 5.02 (95% CI 2.29-11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11-5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations. Conclusion: In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes.

A case of ANCA-negative pauci-immune crescentic glomerulonephritis with lung adenocarcinoma with mediastinal involvement successfully treated by corticosteroid and radiation therapy.

Pauci-immune crescentic glomerulonephritis (PICGN) is one of the pathologies causing rapidly progressive glomerulonephritis, often associated with anti-neutrophil cytoplasmic antibody (ANCA); however, in 10-30% of cases, ANCAs are negative. While a relatively large number of cases of ANCA-positive PICGN complicated with malignancy have been previously reported, the number of cases of ANCA-negative PICGN with malignancy is limited. The prognosis for such cases was poor, and many patients died within a relatively short period. Here, we report the case of ANCA-negative PICGN complicated with malignancy successfully treated by corticosteroid and radiation therapy. A 63-year-old Japanese man was admitted to our hospital due to spiking fevers in the previous 3 months. Based on the findings of imaging and pathological tests, he was diagnosed with locally advanced lung adenocarcinoma with mediastinal involvement. After admission, his renal function rapidly deteriorated, and urinalysis showed heavy proteinuria. In serological tests, serology for autoantibodies, including ANCAs, was negative. The kidney biopsy revealed PICGN with prominent endocapillary proliferation. We administered corticosteroid therapy for glomerulonephritis and subsequent radiation therapy for lung carcinoma, both of which were effective. He has been alive without progression of malignancy or kidney disease for 5 years after discharge. In patients with malignancy presenting with acute deterioration of kidney function, although infrequent, one of the conceivable pathological conditions to consider is ANCA-negative PICGN associated with malignancy. In such cases, even with negative antibodies such as ANCA, pathological examination is warranted, and a combination of anti-tumor therapy and immunosuppressive therapy is expected to be effective.

Clinical features and prognosis of patients with anti-GBM disease combined with mesangial IgA deposition.

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown. Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5µmol/L, IQR:270.0~702.0 vs. 515.8~1231.2µmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2µmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2µmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in the mesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease.

Pauci-immune necrotizing glomerulonephritis in a 24-year-old female with negative ANCA antibodies: A rare case report.

Key Clinical Message: Pauci-immune necrotizing glomerulonephritis (PING) is a small vessel renal vasculitis usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase or proteinase. A small proportion of PING patients do not have ANCA antibodies. Abstract: A condition known as Pauci-immune necrotizing glomerulonephritis, or PING for short, is a type of kidney inflammation that affects small blood vessels. This condition is typically linked with the existence of certain antibodies, specifically antineutrophil cytoplasmic antibodies or ANCA, which target myeloperoxidase or proteinase. However, it's worth noting that a minor percentage of individuals diagnosed with PING do not possess these ANCA antibodies. A 24-year-old woman with no previous medical history arrived at the ER due to various symptoms including joint pain, fever, difficulty swallowing, and shortness of breath. Despite multiple symptoms suggesting systemic lupus erythematosus (SLE), this diagnosis was ruled out based on the EULAR/ACR 2019 classification criteria and laboratory tests. Other potential diagnoses such as rheumatoid arthritis (RA) and eosinophilic garnulomatosis with polyaniitis (EGPA) were also excluded based on respective criteria. The patient was treated with a 3-day course of methylprednisolone, followed by prednisolone, which improved her creatinine levels. Subsequent tests for P-ANCA and C-ANCA were negative. A kidney biopsy confirmed necrotizing glomerulonephritis, consistent with pauci-immune vasculitis. A bronchoscopy revealed bleeding and hemorrhage in her lungs, but bacterial culture analysis was negative. The patient was given piperacillin, tazobactam, and vancomycin for septic coverage, as well as intravenous immunoglobulin (IVIg), which led to symptom improvement.

Pediatric Bilateral Hypoplastic Kidney Complicated With C1q Nephropathy: A Case Report.

Progressive kidney dysfunction is often observed in children with bilateral hypoplastic kidneys. While glomerulopathy can exacerbate hypoplastic kidney progression, only IgA nephropathy and post-streptococcal acute glomerulonephritis have been noted in such cases. Herein, we present a case of a four-year-old female patient with bilateral hypoplastic kidney, kidney dysfunction, and significant proteinuria (urinary protein/creatinine ratio > 1 g/gCr), prompting referral owing to persistent hematuria since two years of age. Enalapril was initiated; however, urinary findings exhibited no improvement despite stable symptoms and kidney function. Subsequently, a kidney biopsy was performed at six years of age, and C1q nephropathy was diagnosed. Given the presence of only mild mesangial proliferation, steroids were not administered; enalapril treatment was continued. By seven years of age, the patient's hematuria had resolved, and proteinuria levels had decreased. On the latest follow-up at 12 years of age, kidney function was preserved with only mild proteinuria. This case report highlights the favorable prognosis of asymptomatic C1q nephropathy characterized by mild mesangial proliferation, even in patients with hypoplastic kidneys, renal dysfunction, and significant proteinuria. It emphasizes the significance of timely pathological evaluation for guiding appropriate interventions in such patients.

[Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis].

AIM: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). MATERIALS AND METHODS: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). RESULTS: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. CONCLUSION: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network.

BACKGROUND: Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40-50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation. METHODS: In this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case-control group (n = 20). RESULTS: Eleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective. CONCLUSIONS: These data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.

Promising response of proliferative glomerulonephritis with monoclonal IgG deposits to low-dose daratumumab: a case report.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare disease without standardized treatment modalities. Daratumumab is a human IgG monoclonal anti-CD38 antibody that has been demonstrated to be highly effective and safe in the treatment of PGNMID. This article reports a 66-year-old female who suffered from edema in both lower limbs and face for 6 years with mild proteinuria and hypoproteinemia. Renal biopsy displayed eight glomeruli, among which two presented with glomerulosclerosis, and the remaining six exhibited moderate diffuse hyperplasia of glomerular mesangial cells and stroma with endothelial cell proliferation. Immunofluorescence microscopy revealed lumpy and diffuse deposits of C3, C1q, IgG, and κ light chain in the glomerular mesangium, with strongly positive staining for IgG3 and varying degrees of weak to negative staining for IgG1, IgG2, IgG4, and λ light chain. Additionally, ultrastructural analysis unveiled that the glomerular basement membrane was segmentally thickened, accompanied by diffuse pedicle fusion, segmental tethered insertion, subendothelial deposits, and electron-dense material in tethered areas. The patient received a total dose of 800 mg of daratumumab (400 mg daily for two consecutive days), as well as daily prednisone (25 mg) and valsartan (80 mg), for treatment and achieved complete remission after three-month follow-up. This case represents an early attempt to treat PGNMID with low-dose daratumumab but requires long-term follow-up.

First Successful Treatment of a Patient with a Primary Immune Complex-Membranoproliferative Glomerulonephritis with Iptacopan: A Case Report.

Introduction: Nowadays, there is insufficient evidence for the recommendation of management patients with a primary membranoproliferative glomerulonephritis (MPGN). A better understanding of the pathogenesis has led to the reclassification of primary MPGN and distinction into the two main entities of either primary immune complex-MPGN or C3 glomerulopathy. Both entities share overlapping pathophysiological features with complement alternative pathway (AP) dysregulation. Iptacopan is an oral inhibitor of the complement factor B that effectively blocks the complement AP. Case Presentation: We report the first successful treatment of a 47-year-old man suffering from a primary immune complex-MPGN with iptacopan. So far established immunosuppressive therapies with prednisone and mycophenolate mofetil failed to control the current flare of the disease, mainly presenting with impaired kidney function and proteinuria within the nephrotic range. However, 3 months after starting the treatment with iptacopan urine protein-creatinine ratio decreased impressively to a level of 100-150 mg/mmol. Thereafter, low-level proteinuria and kidney function remained stable during follow-up. Do date, the treatment with iptacopan is continued as a monotherapy and is well tolerated. Conclusion: To the best of our knowledge, this is the first case report which suggests that iptacopan may be an interesting treatment option for primary immune complex-MPGN.

Paraneoplastic Syndrome After Kidney Transplantation: Frequency, Risk Factors, Differences to Paraneoplastic Occurrence of Glomerulonephritis in the Native Kidney, and Implications on Long-Term Kidney Graft Function.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients' survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients.

Outcome of Glomerular Disease Manifesting After Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2.

Introduction Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can upregulate the immune system and may contribute to glomerular disease (GD). Here, we describe a spectrum of GD that manifested following vaccination against SARS-CoV-2 (COVID-19 vaccinations). Material and methods This was a descriptive study of 10 cases enrolled between January 2021 and January 2023. Patients with biopsy-proven GD that manifested following COVID-19 vaccinations were included. Results We found 10 cases of biopsy-proven GD following the COVID-19 vaccination. This included five cases of minimal change disease (MCD), three cases of focal segmental glomerulosclerosis (FSGS), one case of C3 glomerulonephritis (C3GN), and one case of IgA nephropathy (IgAN). The pre-existing disease was found in the last two patients (IgAN and C3GN) who got unmasked following vaccination. We did not observe any relation between vaccine type (Covisheld; six cases vs. Covaxin; four cases) and GD. In most cases (8/10 cases, 80.0%), GD developed after a repeat dose (second or booster dose). The onset time following vaccination was typically less than a week, and even less following a repeat dose. Conclusion Post-vaccination GD can be either de novo or a flare-up of a pre-existing one. The onset time following vaccination was typically less than a week for both Covishield and Covaxin.

Clinical Spectrum of Acute Post-streptococcal Glomerulonephritis in Children: A Kashmir Experience.

Background In the pediatric population, acute post-streptococcal glomerulonephritis (PSGN) is a common glomerular etiology of hematuria and acute hypertension leading to hospitalization. We conducted this study to know the clinical profile and occurrence of acute PSGN in patients presenting with features of acute nephritic syndrome. Methods This prospective observational study was conducted on children aged between two and 18 years, presenting with clinical features of acute glomerular nephritis (AGN). After due ethical considerations, all eligible patients were enrolled and underwent detailed clinical assessment, laboratory, and imaging evaluation, followed by protocolized treatment. Relevant data were collected and analyzed to reach valid results. Results Out of 60 patients with AGN, PSGN was found in 83.3% of the patients (50/60). The age group under five years was the most commonly involved, with a male/female ratio of 1.6:1. Around half of the studied patients were from the lower middle class, and 40 (80%) were from rural backgrounds. Facial puffiness was the most common clinical presentation, seen in 45 (90%) patients. Hypocomplementemia and proteinuria were seen in all PSGN patients. Pyoderma was the most common preceding infection, seen in 38 (76%) patients, followed by pharyngitis. Acute kidney injury (AKI) was the most common complication, seen in 12 (24%) patients. Complete resolution of the signs and symptoms was seen in 37 (74%) patients at the time of discharge, which increased to 47 (94%) patients at six months post discharge. Conclusion PSGN stands to be the most common cause of pediatric AGN. The population under five years of age, with a past history of pyoderma, is more predisposed to PSGN. The potential for the occurrence of AKI and other life-threatening complications is high, for which early diagnosis and institution of proper treatment would be very beneficial.

The Coexistence of Microscopic Polyangiitis and Rheumatoid Arthritis: A Case Report.

Microscopic polyangiitis (MPA) is a rare autoimmune disease characterized by the inflammation and necrosis of small vessels, primarily affecting kidneys and lungs. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) due to the presence of ANCA. MPA can manifest as diffuse alveolar hemorrhage (DAH) and rapidly progressive glomerulonephritis. In contrast, rheumatoid arthritis (RA) is an inflammatory disease that mainly targets the synovial joints. The coexistence of these two conditions presents significant diagnostic challenges, highlighting the need for further research and understanding. We report a case of a 58-year-old male with a past medical history of RA, chronic bronchitis, tobacco use, and recent Legionella pneumonia who presented with acute dyspnea. The patient was intubated for acute hypoxemic respiratory failure. Laboratory workup revealed anemia, hyponatremia, and acute kidney injury. Urinalysis showed hematuria and proteinuria. A CT scan of the chest exhibited bilateral extensive patchy infiltrates. He was transfused with one packed red blood cell (PRBC) unit. Hemoglobin decreased below 6 g/dL after transfusion. A bronchoscopy revealed erythema throughout the tracheobronchial tree, and blood on bronchial alveolar lavage suggested DAH. High-dose steroids were started. Subsequent laboratory results were positive for rheumatoid factor (RF), perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), and antinuclear antibody (ANA). The kidney biopsy demonstrated focal crescentic necrotizing glomerulonephritis pauci-immune type, confirming MPA. RA pathogenesis involves immune dysregulation and activation of various cells, leading to the release of cytokines. Antibodies such as RF and anti-cyclic citrullinated peptide (anti-CCP) can be detected up to 10 years before the clinical manifestation of RA. Recent studies have revealed a predominance of MPA in AAV while coexisting with RA. The underlying mechanism of its occurrence remains unclear. Our patient had recurrent respiratory symptoms and renal dysfunction before hospitalization. MPA-RA overlap syndrome is potentially treatable and clinicians should maintain a high index of suspicion when encountering patients with preexisting RA. Timely initiation of immunosuppressive therapy at early stages is essential to prevent renal and pulmonary complications. ANCA serology should be assessed in these cases.

Lupus-like manifestations after allogenic hematopoietic stem cell transplantation: a rare case of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.

Full-house nephropathy in antinuclear antibody-negative systemic lupus erythematosus: A case report.

Key Clinical Message: Antinuclear antibody-negative full-house lupus nephritis though previously reported, is fairly uncommon. Some patients go on to develop antibodies later in the disease course. The presence of RO-52 antibody in this case suggests an underlying immunological cause. Swift management based on strong clinical suspicion can be life-saving to the patient. Abstract: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and is more likely to progress to end-stage renal disease (ESRD). With the recent EULAR/ACR criteria mandating antinuclear antibody (ANA) positivity as an entry criterion, clinicians are faced with a diagnostic dilemma in diagnosing cases of seronegative SLE. We present the case of a 25-year-old female who presented with photosensitive malar rash, hair loss, oral ulcers, menorrhagia, and kidney dysfunction, suggestive of SLE. Her ANA tests were negative, raising doubts about the diagnosis. Biopsy was delayed owing to anemia and thrombocytopenia, and clinical judgment led to the patient being diagnosed with LN, with prompt treatment resulting in significant improvement. Renal biopsy subsequently confirmed the case as diffuse class IV LN with full-house nephropathy. This case highlights the limitations of relying solely on ANA positivity in diagnosing LN and underscores the need for a comprehensive diagnostic approach for SLE that incorporates clinical features, immunological markers, and patient demographics. ANA-negative SLE patients demand heightened clinical suspicion, especially when other diagnostic parameters align with the disease. Swift intervention with immunosuppressive therapy, as seen in this case, can be life-saving.