Clinical and histological comparison of IgA nephritis and renal IgA vasculitis.

BACKGROUND: IgA nephritis (IgAN) and renal IgA vasculitis (IgAV) show renal IgA deposits, but whether these two diseases are distinct entities or a spectrum of the same condition is under debate. In this study, we add perspective by contrasting the clinical course and histological presentation using the Oxford classification and the National Institutes of Health lupus nephritis activity index (LN-AI) and chronicity index (LN-CI) in IgAN and IgAV. METHODS: In this single-center, retrospective study, kidney biopsies of 163 adult patients with IgAN and 60 adult patients with IgAV were compared according to the Oxford MEST-C Score, LN-AI, and LN-CI. At the time of biopsy, clinical presentation was compared in terms of age, arterial hypertension, diabetes mellitus, extrarenal manifestations, as well as estimated glomerular filtration rate, proteinuria, and urine sediment. IgAV patients and all IgAN patients with crescents received immunosuppressive treatment. After biopsy, kidney function was followed until patients reached end-stage renal disease (ESRD) or they died. RESULTS: The clinical course and kidney histology differ in IgAN and IgAV. IgAV patients showed more microhematuria and nephritic sediment, while IgAN patients had a greater history of arterial hypertension, more proteinuria, and a higher risk for ESRD. These clinical differences were associated with histological differences, as kidney biopsies of IgAN patients were characterized by glomerulosclerosis and tubular atrophy, while kidney biopsies of IgAV patients were characterized by endocapillary hypercellularity and crescents. Overall, tubular atrophy and a LN-CI ≥ 4 were associated with a higher risk for ESRD in IgAN and IgAV. CONCLUSION: Our study supports the notion that IgAN and IgAV follow distinct courses, suggesting that they require different treatment strategies. Moreover, we make a point that the Oxford classification and LN-CI can be useful in categorizing and predicting long-term prognosis not only in IgAN, but also in IgAV.

The Urine Light Chain/eGFR Quotient as a Tool to Rule out Cast Nephropathy in Myeloma-Associated Kidney Failure.

Kidney involvement with resulting kidney failure leads to increased mortality in patients with multiple myeloma (MM). Cast nephropathy (CN), in particular, if left untreated, quickly leads to kidney failure requiring dialysis and has a very poor prognosis for the affected patient. The gold standard for diagnosing kidney involvement is a kidney biopsy. However, due to bleeding risk, this cannot be done in every patient. We recently reported that a quotient of urine light chain (LCurine) to glomerular filtration rate (eGFR) is a non-invasive diagnostic tool for patients with kidney involvement in MM. But this quotient has not yet been tested in everyday clinical practice. In this study, our LCurine/eGFR ratio was tested on 67 patients in two centers. Enrollment took place between January 2019 and September 2023. A total of 18 of the 67 patients had CN. With the threshold defined in our initial paper, we were able to show a sensitivity of 100% with a specificity of 85.7% for CN in patients with MM. As a result, the LCurine/eGFR quotient recognizes 100% of all CN and can therefore detect this group, which has a very poor prognosis, without the need for a kidney biopsy.

Single Center Experience Using Monoclonal COVID-19 Antibodies in the Management of Immunocompromised Patients with COVID-19.

The medical care of immunocompromised patients with COVID-19 infection causes major hurdles in the management of these patients in clinical practice. However, poor responses to vaccinations in patients with oncological or autoimmune diseases require rapid action and effective care in this fragile patient population. Monoclonal antibodies (mAb) offer an effective therapeutic option with a favorable toxicity profile. We have retrospectively reviewed the first 100 patients treated with mAb in our clinic and assessed the individual vaccine response, side effects of mAb, hospitalization rate and mortality. None of the outpatients treated with mAb had to be hospitalized. In particular, the third SARS-CoV-2 vaccination had a significant effect on the seroconversion (37.5% vs. 77.8% positive patients) in the entire group of patients studied. No side effects of 3°/4° were observed following mAb administration; the mortality in the entire cohort was 7%. Our data and experience show good effectiveness and a favorable tolerability profile of mAb, supporting the feasibility of this therapy in everyday clinical practice. Of note, in immunocompromised patients, both the vaccination status and success need to be recorded in a systematic manner and taken into account in terms of therapeutic intervention using mAb in case of a SARS-CoV-2 infection.

Histological Findings in Kidney Biopsies of Patients with Monoclonal Gammopathy-Always a Surprise.

Background: The simultaneous occurrence of impaired kidney function and paraproteinemia is common in our constantly aging society. Both can be independent entities; however, renal insufficiency can also be caused by the paraprotein. We assessed all kidney biopsies in patients with monoclonal gammopathy in our clinic over the past 20 years and evaluated the histological results. Methods: Biopsies were systematically performed in nearly all patients with paraproteinemia and impaired kidney function (n = 178). The histological findings were systematically evaluated and correlated with the initial clinical diagnosis. Results: We found cast nephropathy (CN) in n = 66 (37.1%) biopsies, AL amyloidosis in n = 31 (17.4%) biopsies, monoclonal immunoglobulin deposition disease (MIDD) in n = 7 (3.9%) biopsies and other renal diseases (ORDs) in n = 74 (41.6%) biopsies. In the latter group, paraprotein-associated changes were found in 37 of 74 (50%) patients, whereas paraprotein-independent changes were found in the other half. Whereas, in the group of patients with MGUS, the findings were heterogenous, most of the patients with known multiple myeloma (MM) or B-NHL showed malignancy-associated changes in the kidney. The biopsy changed the diagnoses in a significant proportion of the patients: The group of patients with MM grew from 71 to 112 patients, whereas, in the MGUS group, only 31 of 44 patients remained. Conclusion: Kidney biopsies in patients with paraproteinemia and renal impairment show a wide range of findings that can lead to a change in diagnosis.

The urine light chain/glomerular filtration rate (GFR) quotient shows a high sensitivity and specificity to detect cast nephropathy in monoclonal light chain disease.

BACKGROUND: Cast nephropathy (CN) is associated with a unfavourable outcome in monoclonal light chain (mLC) disease, but also more possible LC-related renal diseases as well as non-LC-related disease can occur. Thus, it is crucial to understand the underlying renal disease. On the other hand, LC can interfere with coagulation preventing kidney biopsy as the gold standard. We sought to develop a non-invasive algorithm to diagnose CN with a good sensitivity and specificity. METHOD: We analysed data from patients with mLC disease who underwent kidney biopsy. The patients were classified in 4 groups according the renal histology: CN, AL amyloidosis, light chain deposition disease, and other renal disease. Afterwards, different algorithms were calculated for their sensitivity and specificity. RESULTS: CN showed a significant higher concentration of serum-free LC and urine LC (LCu), but there was a wide and overlapping range with the other groups. The best accuracy was achieved for a LCu/GFR ratio >2 in patients with lambda LC and either a LCu/GFR > 1 and proteinuria <8 g/24 h or a LCu/GFR > 5 in patients with proteinuria >8 g/24 h in patients with kappa LC. In lambda LC, the sensitivity and specificity for CN was 94% and 90%, respectively; in kappa LC 87% and 81%, respectively. DISCUSSION: In patients with coagulation disturbances due to LC, a non-invasive algorithm can separate patients with CN from other renal disease in mLC disease.