MATERIALS AND METHODS

Study population and design

All the patients in our center with a kidney-biopsy-proven AL amyloidosis between 1990 and 2024 were included in this study. Patients diagnosed with AA amyloidosis or other types of amyloidosis were excluded. All patients in this study had kidney involvement confirmed with a kidney biopsy with amyloid deposits on the kidney tissue. All study patients had an underlying monoclonal protein demonstrated by serum and/or urinary immunofixation. Patients were classified according to receipt of anti-plasma cell therapy and stratified by time to kidney and hematological response.

This study was conducted in accordance with the Declaration of Helsinki. Given the retrospective nature of the study, a waiver of informed consent from individual patients was granted.

Clinical and laboratory data

Following a standardized protocol, data from included patients were extracted from medical records at disease onset and at the end of follow-up. Patients were followed according to routine clinical practice, with clinical and laboratory assessments performed approximately every 3–6 months. Recorded clinical variables included age, sex, kidney presentation, and extra-kidney manifestations. Laboratory parameters comprised SCr, eGFR (ml/min/1.73 m²), and 24-h urinary protein excretion. Treatments received during follow-up, especially chemotherapy, were also recorded. Time to hematologic response, time to kidney response, need for kidney replacement therapy (KRT), and time to death were also determined.

Diagnosis of AL amyloidosis and definitions

The diagnosis of amyloidosis was established by the demonstration in light microscopy of Congo red deposits with apple-green birefringence on tissue biopsy samples. In all the cases, immunohistochemistry for AA amyloidosis was negative and immunofluorescence microscopy showed Ig light chain restriction. Electron microscopic features of randomly disposed, rigid, nonbranching, and variably long fibrils were also considered diagnostic.

Hematologic response was defined as a 50% reduction in measurable monoclonal protein levels (partial response), or complete eradication by immunofixation (complete response). Given the long study period, hematologic responses were retrospectively categorized based on the available laboratory data in medical records, using serum FLC–based criteria when these measurements were available. Partial kidney response was defined as a ≥50% reduction in initial proteinuria in the absence of a worsening of SCr or eGFR ≥25% from baseline. Complete kidney response was defined as proteinuria <0.5 g/24 h in the absence of worsening SCr or eGFR ≥25% from baseline [4, 12]. According to the time from treatment initiation to kidney response, patients were categorized as having very early kidney response (0–6 months), early kidney response (6–12 months), and late kidney response (>12 months). Also, the patients were stratified according to time to hematologic response in very early (0–6), early (6–12), and late (>12 months) hematological response groups. End stage kidney disease (ESKD) was defined as the presence of an eGFR under 15 ml/min/1.73 m2, the need for KRT or a pre-emptive kidney transplantation. Kidney baseline was defined as the time of AL amyloidosis diagnosis. The eGFR was calculated using the CKD-EPI formula. Acute kidney injury (AKI) at baseline was defined according to KDIGO guidelines criteria [13].

Outcomes

The primary outcome was the time from treatment initiation to kidney response. Secondary outcomes included the proportion of patients achieving hematologic and kidney response, time to hematologic response, kidney and overall survival, and treatment duration.

Statistical analysis

This was a retrospective, observational cohort study. Categorical data were expressed as absolute numbers and percentages. Continuous data were expressed as mean and standard deviation (SD) and, in the case of non-normal distribution, as median and interquartile range (IQR). The Kolmogorov-Smirnov test was used to test for normality. Comparisons were made using the t test for normally distributed continuous variables and the Mann-Whitney U test for non-normally distributed continuous variables. The chi-square or Fisher’s exact test were employed to compare the qualitative variables. The statistical significance level was set at P < .05. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative incidence of dialysis among patients who received and those who did not receive treatment. For the analysis of continuous quantitative variables that follow a normal distribution in three groups, the ANOVA test was used, while for variables that did not follow a normal distribution, the Kruskal-Wallis test was applied. In cases where statistically significant differences were detected, a post hoc analysis using Dunn’s test and Bonferroni correction was performed to identify which groups were different. Cox proportional hazards regression models were used to analyze the main determinants of kidney survival. Covariables in multivariable models were selected on the basis of prior knowledge. Statistical analyses were conducted using IBM SPSS Version 22.0. A _P _< .05 was considered to be significant.