Jhaveri, Kenar D.

Onconephrology is an upcoming and expanding subspecialty that deals with the intersections between hematology/oncology and nephrology. With the paradigm shift in the understanding of cancer immunobiology and mechanisms of oncotherapeutic drug toxicities, it is important for a nephrologist to have a sound understanding of this field. Over the last 5 years, there have been immense developments in our understanding of kidney-related adverse events from various targeted, immuno- and cellular-based therapies. Pathogenic mechanisms of electrolyte imbalance, hypertension (oncohypertension), and AKI from multiple forms of cancer therapies have been explored. Significant research has also been conducted in the field of transplant onconephrology. In this review, we have tried to assimilate the most recent updates in the last 2 years in this ever-growing and fascinating field.

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Abstract Background: Thrombotic microangiopathy (TMA) is a hematologic syndrome associated with endothelial injury, microvascular thrombosis, and hemolytic anemia resulting in end organ damage. TMA is rarely associated with multiple myeloma (MM) and is usually reported in the setting of allogeneic hematopoietic stem cell transplants (AHSCT), with associated graft versus host disease and calcineurin inhibitor use. We present 11 cases of TMA in MM patients not associated with AHSCT. Methods: Cases were collected from multiple centers in patients with confirmed diagnosis of MM. TMA was diagnosed by the presence of thrombocytopenia and evidence of microangiopathic hemolytic anemia. Results: Eleven patients with MM were identified to have developed TMA during the course of their disease. Two patients presented with TMA at the time of MM diagnosis. A third had been off treatment for over a year prior to presenting with a TMA which correlated with a significant increase in her free light chains. The other cases occurred during active treatment. All remaining patients received proteasome inhibitors, with three patients on bortezomib-based regimens and five patients on carfilzomib. One patient on a bortezomib-based regimen had been stable prior to developing a TMA in the setting of sepsis. In the remaining patients, the TMA developed rapidly after initiating the proteasome inhibitor. In all cases, the TMA improved after drug withdrawal. One patient was later rechallenged with bortezomib and again developed TMA. Discussion: A review of the literature reveals only nine cases of TMA with MM. Of these, 4 patients had TMA as the initial presentation of MM, and 5 patients were on treatment, most often bortezomib-based regimens. Our series patients match those in the literature closely and demonstrate that TMAs can occur in MM outside of the context of AHSCT. In roughly one third of patients, TMAs were the initial presentation of MM and improved with treatment of the MM. In others, the use of proteasome inhibitors appears to be associated with development of TMA. In these cases, the temporal correlation, resolution of TMA after medication withdrawal, and the instance of recurrence of TMA with rechallenge of bortezomib, support a causal relationship between the medication and the TMA. Thus, a high clinical suspicion for TMA must exist for patients on proteasome inhibitors who develop worsening anemia and thrombocytopenia. Medication should be withdrawn if TMA is diagnosed. Disclosures Vij: Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy; Takeda: Consultancy, Research Funding; Novartis: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Merck: Consultancy.