Outcomes of kidney transplant recipients with ESKD due to plasma cell dyscrasia: A case series.

Transplant centers have historically been reluctant to proceed with kidney transplantation in individuals with plasma cell dyscrasias (PCDs) due to concern for high rates of PCD recurrence and PCD-related mortality. As novel therapies for PCDs have improved hematologic outcomes, strategies to optimize kidney transplantation in individuals with PCD-mediated kidney disease are needed. In this single-center case series we discuss our protocol for the transplantation of individuals with ESKD attributed to PCD as well as the hematologic and allograft outcomes of 12 kidney transplant recipients with ESKD attributed to PCD. Median follow-up time after kidney transplantation was 44 months (IQR 36, 84). All patients had a functioning allograft 1 year after kidney transplantation. 9/12 patients were alive and had a functioning allograft 5 years after kidney transplantation. Five patients experienced relapse of PCD (of whom three responded well to subsequent therapies) and four patients developed secondary malignancies, including three patients with urologic malignancies. This case series demonstrates that patients with kidney disease attributed to PCD have favorable outcomes with kidney transplantation. Transplant evaluation in patients with PCDs should involve a multidisciplinary team of transplant nephrologists and oncologists to select appropriate candidates. Providers should consider screening for urologic malignancies pre- and post-transplantation.

Predicting long-term kidney allograft outcomes: pitfalls and progress.

Early identification of kidney transplant recipients at risk of progressive allograft dysfunction may allow clinicians to provide closer monitoring and more aggressive risk factor modification. In this issue, Raynaud et al. presented a latent class model that clustered kidney transplant recipients into 8 risk categories of post-transplant kidney function loss. This commentary discusses some of the advantages, but also challenges, of the use of latent class analyses, including the clinical applicability of models that are often derived from such approaches.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

Safe and effective use of eculizumab in the treatment of severe Shiga toxin Escherichia coli-associated hemolytic uremic syndrome.

PURPOSE: A severe case of Shiga toxin Escherichia coli (STEC)-associated hemolytic uremic syndrome (HUS) successfully treated with eculizumab is reported. SUMMARY: An 18-year-old man was admitted to the intensive care unit with HUS due to laboratory-confirmed STEC O121. He was initially treated with plasmapheresis and required hemodialysis for anuric acute kidney injury. Plasmapheresis was stopped due to complications. He continued to show evidence of ongoing hemolysis and kidney injury. Due to the lack of clinical improvement in renal function and hematologic status as well as the severity of the patient's symptoms, the decision was made to initiate eculizumab. The patient was given i.v. eculizumab 900 mg infused over 35 minutes weekly for four weeks, followed by 1200 mg infused over 35 minutes one week later as the fifth dose and then every two weeks thereafter. The patient also received i.v. ciprofloxacin 400 mg infused over 60 minutes once every 24 hours for meningococcal prophylaxis and bacterial eradication. After initiation of eculizumab, the patient's platelet count rapidly improved. After three doses of eculizumab, the patient's renal function improved, and further hemodialysis was no longer required. The patient continued to receive twice-monthly eculizumab infusions to complete a two-month treatment course (seven doses), at which point his renal function returned to baseline. The initial two infusions were administered as an inpatient, and the remainder was infused in the outpatient setting. CONCLUSION: An 18-year-old man who developed severe HUS due to STEC O121 and was unresponsive to traditional supportive therapies was successfully treated with eculizumab.