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 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.

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.

Key Points: Kidney involvement in patients with multiple myeloma has many different findings in kidney histology. Persistent dialysis requirement is a major cause of mortality. The rapid initiation of modern myeloma therapy is essential to prevent the need for dialysis and reduce mortality. Background: Acute or CKD affects 20%–40% of patients with multiple myeloma (MM). While the negative prognostic effect of kidney involvement is established, the specific effect of different histological patterns remains poorly understood. We aimed to characterize the clinical outcomes associated with distinct kidney histologies in patients with MM. Methods: We retrospectively analyzed 193 patients with MM who underwent kidney biopsy, comparing outcomes with 62 patients with MM without kidney disease. Patients were categorized by histological findings: cast nephropathy (CN, n =120), lightchain (AL) amyloidosis ( n =19), monoclonal Ig deposition disease (MIDD, n =8), and other renal disease ( n =46). We evaluated kidney function, dialysis requirements, treatment responses, and survival across histological subtypes and treatment modalities (conventional therapy versus modern agents including proteasome inhibitors, CD38 antibodies, and autologous stem cell transplantation). Results: The CN and MIDD groups had the lowest median eGFR at biopsy (13.0 and 25.5 ml/min per 1.73 m ² , respectively). Nephrotic-range proteinuria (>3.5 g/24 hours per Kidney Disease Improving Global Outcomes) was observed in the AL amyloidosis group (median 3910 mg/24 hours). KRT was initiated in 42.5% of patients. The proportion achieving KRT independence was 42.4% in the CN group and 50% in the other renal disease group, whereas none in the AL amyloidosis or MIDD groups recovered sufficient native kidney function. Modern combination therapy significantly improved renal outcomes, with 100% of patients receiving triple therapy showing renal response. KRT dependency was the strongest predictor of mortality: Patients remaining on KRT had significantly shorter survival compared with those never requiring KRT (12.7 versus 56.2 months, P < 0.001). The extent of improvement in kidney function did not influence survival; only dialysis status was prognostically relevant. Conclusions: Kidney histology determines distinct clinical trajectories in patients with MM, with CN showing potential for dialysis reversibility. Modern combination therapies significantly improve renal outcomes. The requirement for ongoing KRT was the primary predictor of overall survival.