Predictors and outcomes of acute kidney injury during autologous stem cell transplantation in AL amyloidosis.

BACKGROUND: Acute kidney injury (AKI) is a common complication after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with light chain (AL) amyloidosis. However, its incidence, predictors and outcomes are not well known. METHODS: This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT. AKI was defined as an increase in serum creatinine to ≥1.5 times the baseline occurring within the first 30 days of HDM/SCT. RESULTS: The median age was 58 years (range: 30-77). Kidney and cardiac involvement were present in 86.1% and 56.8%, respectively. The median estimated glomerular filtration rate (eGFR) was 83.5 mL/min/1.73 m2 (range: 9-213) and proteinuria was 2899 mg/day (range: 0-19 966). AKI occurred in 29.1% of patients. Dialysis was initiated in 15 patients (6.7%) and of these 12 (80%) were able to discontinue dialysis. Most of the episodes of AKI occurred within the first 2 weeks; with a median follow-up of 4.5 years (range: 0.1-16.5), AKI was associated with increased overall mortality [hazard rato (HR) = 4.53, 95% confidence interval (CI) 2-10.23]. The 10-year overall survival was 87.1% without AKI, versus 56.9% with AKI. AKI was also associated with an increased risk for end-stage kidney disease (ESKD) (HR = 4.6, 95% CI 1.44-14.38). The risk of developing ESKD at 10 years was 18.9% with AKI, versus 8.1% without AKI. Several risk factors were found and using multivariate logistic regression, a prediction model was developed that included three readily available variables: eGFR <60 mL/min/1.73 m2, interventricular septal thickness in diastole >12 mm and albumin <3 g/dL. This model was able to predict AKI development with an area under the curve of 0.8. CONCLUSIONS: AKI is common in the post-HDM/SCT period and it leads to increased risk for ESKD and death. Our prediction model is an easily deployable tool in clinical settings as part of the discussion with patients who are being prepared for HDM/SCT.

Correlation Between 24-Hour Urine Protein and Random Urine Protein-Creatinine Ratio in Amyloid Light-Chain Amyloidosis.

Rationale & Objective: Test the feasibility of replacing 24-hour urine collection with a single voided urinary protein-creatinine ratio (UPCR) in patients with amyloid light-chain (AL) amyloidosis. Study Design: Retrospective study examining the correlation between a 24-hour urine measurement and UPCR at various proteinuria levels using a linear regression analysis with Pearson's correlation coefficient (r). We assessed how using these 2 different measurements would alter the diagnosis, staging, and kidney response assessment in patients with AL amyloidosis. Setting & Participants: We included 265 patients with systemic AL amyloidosis who visited the Amyloidosis Center at Boston University between July 2018-January 2020 and had proteinuria measurement by both methods on the same day. Tests Compared: 24-hour urine collection for protein versus UPCR. Results: The correlation between 24-hour urine and UPCR was moderate in patients with proteinuria levels of 500-3,000 mg/day and >3,000 mg/day, with r values of 0.57 and 0.62, respectively. Replacing the 24-hour urine collection with UPCR changed kidney staging in 10% of the patients: 77% were reclassified to a worse kidney stage and 23% to a more favorable stage. The majority of changes (85%) in kidney staging occurred in the >3,000 mg/day cohort. There were 35 patients whose kidney response was assessed by concomitant 24-hour urine collection and UPCR with visits at least 6 months apart. Of these patients, 20% had discordance between the 24-hour urine collection and UPCR that changed their definition of organ response. Limitations: Given the rarity of AL amyloidosis, our sample size is small and from a single referral center. Conclusions: Although the 24-hour urine collection is cumbersome, we continue to recommend it in patients with AL amyloidosis because replacing the 24-hour urine collection with UPCR would change kidney staging and organ response in 10%-20% of patients. In addition, the correlation between the 2 modalities was moderate at best in patients with nephrotic-range proteinuria.

Outcomes of renal transplantation in patients with AL amyloidosis: an international collaboration through The International Kidney and Monoclonal Gammopathy Research Group.

Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020. With a median follow-up of 8.5 years, the median overall survival from renal transplantation was 8.6 years and was significantly longer in patients with complete and very good partial hematologic responses (CR + VGPR) compared to less than VGPR (9 versus 6.8 years; HR: 1.5, P = 0.04 [95% CI: 1-2.1]) at renal transplantation. Median graft survival was 7.8 years and was better in the CR + VGPR group (8.3 vs 5.7 years, HR: 1.4, P = 0.05 [95% CI: 1-2]). The frequency and time to amyloid recurrence in the graft was also lower (16% vs 37%, p = 0.01) and longer (median time not achieved vs 10 years, p = 0.001) in the CR + VGPR group. Comparing CR vs. VGPR there was no difference in overall or graft survival. Although 69 patients (29%) experienced hematologic relapse, treatment effectively prevented graft loss in the majority (87%). Renal transplantation in selected AL amyloidosis patients is associated with extended overall and renal graft survival. Patients with hematologic CR or VGPR have the most favorable outcomes, and these patients should be considered for renal transplantation.