Kidney transplantation in multiple myeloma in 2023: A short review.

Patients with multiple myeloma (MM) frequently present with kidney involvement, of which a non-negligible proportion will progress to end-stage kidney disease. Kidney transplantation (KT) is the preferred kidney replacement therapy for selected patients; however, there are still many uncertainties regarding its application in MM patients. The risk of hematological relapse and subsequent graft loss or patient death often leads nephrologists to deem these patients unfit for KT. As such, data on KT in MM patients are heterogeneous and originate from individual case reports and small case series. Although MM is still an incurable disease, the addition of newer drugs and autologous hematopoietic stem cell transplant (HSCT) in the standard of care has been increasing patients' overall survival in recent decades. Risk stratification using cytogenetic studies and minimal residual disease detection are helpful in assessing the risk of relapse in patients who attain a complete response after HSCT. The greatest challenges remain the correct identification of patients who will most probably benefit from KT from a survival perspective and the determination of how long relapse-free survival should be before the transplant is performed.

Severe Acute Kidney Injury in Hospitalized Cancer Patients: Epidemiology and Predictive Model of Renal Replacement Therapy and In-Hospital Mortality.

BACKGROUND: Acute kidney injury (AKI) is a common complication among cancer patients, often leading to longer hospital stays, discontinuation of cancer treatment, and a poor prognosis. This study aims to provide insight into the incidence of severe AKI in this population and identify the risk factors associated with renal replacement therapy (RRT) and in-hospital mortality. METHODS: This retrospective cohort study included 3201 patients with cancer and severe AKI admitted to a Comprehensive Cancer Center between January 1995 and July 2023. Severe AKI was defined according to the KDIGO guidelines as grade ≥ 2 AKI with nephrological in-hospital follow-up. Data were analyzed in two timelines: Period A (1995-2010) and Period B (2011-2023). RESULTS: A total of 3201 patients (1% of all hospitalized cases) were included, with a mean age of 62.5 ± 17.2 years. Solid tumors represented 75% of all neoplasms, showing an increasing tendency, while hematological cancer decreased. Obstructive AKI declined, whereas the incidence of sepsis-associated, prerenal, and drug-induced AKI increased. Overall, 20% of patients required RRT, and 26.4% died during hospitalization. A predictive model for RRT (AUC 0.833 [95% CI 0.817-0.848]) identified sepsis and hematological cancer as risk factors and prerenal and obstructive AKI as protective factors. A similar model for overall in-hospital mortality (AUC 0.731 [95% CI 0.71-0.752]) revealed invasive mechanical ventilation (IMV), sepsis, and RRT as risk factors and obstructive AKI as a protective factor. The model for hemato-oncological patients' mortality (AUC 0.832 [95% CI 0.803-0.861]) included IMV, sepsis, hematopoietic stem cell transplantation, and drug-induced AKI. Mortality risk point score models were derived from these analyses. CONCLUSIONS: This study addresses the demographic and clinical features of cancer patients with severe AKI. The development of predictive models for RRT and in-hospital mortality, along with risk point scores, may play a role in the management of this population.

Acute kidney injury after allogeneic hematopoietic stem cell transplantation - Predictors and survival impact: A single center retrospective study.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting. PATIENTS AND METHODS: We performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019. RESULTS: AKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p=0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p=0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p<0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p=0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p=0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p=0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p=0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p=0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p=0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival. CONCLUSION: Patients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.

Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study / Lesión renal aguda después de trasplante de células madre hematopoyéticas alogénicas, factores predictivos e impacto en la supervivencia: un estudio retrospectivo en un solo centro

Introduction and objectives: Acute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting. Patients and methods: We performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019. Results: AKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p=0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p=0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p<0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p=0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p=0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p=0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p=0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p=0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p=0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival. Conclusion: Patients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit. (AU)

Introducción y objetivos: La lesión renal aguda (LRA) es una complicación frecuente del trasplante de células madre hematopoyéticas (TCMH) y parece estar asociado a un incremento en la morbilidad y la mortalidad. El objetivo de este estudio fue evaluar la incidencia, la etiología, los factores predictivos y el impacto en la supervivencia de la LRA temprana en el contexto posterior al TCMH alogénico. Pacientes y métodos: Se realizó un estudio retrospectivo en un único centro que incluyó 155 procedimientos de trasplante alogénico desde junio de 2017 hasta septiembre de 2019. Resultados: Se observó LRA en 50 pacientes (32%). En el análisis de múltiples variables, la edad (OR 31,55, IC del 95% [3,42; 290,80], p=0,002), la evidencia de enfermedad en el momento del trasplante (OR 2,54, IC del 95% [1,12; 5,75], p=0,025), reactivación de citomegalovirus (OR 5,77, IC del 95% [2,43; 13,72], p<0,001) y estancia hospitalaria>35 días (OR 2,66, IC del 95% [1,08; 6,52], p=0,033) fueron los factores predictivos independientes para LRA. La mayor edad (HR 1,02, IC del 95% [1,00; 1,04], p=0,029), la mayor duración de la estancia hospitalaria (HR 1,02, IC del 95% [1,01; 1,03], p=0,002), TCMH con acondicionamiento de intensidad reducida no relacionados emparejados (HR 1,91, IC del 95% [1,10; 3,33], p=0,022), aparición de enfermedad injerto contra huésped aguda de grado iii/iv (HR 2,41, IC del 95% [1,15; 5,03], p=0,019) y necesidad de ventilación mecánica (HR 3,49, IC del 95% [1,54; 7,92], p=0,003) predijeron una supervivencia inferior en el análisis de múltiples variables. La LRA temprana de cualquier etiología no se asoció con una peor supervivencia. Conclusión: Los pacientes sometidos a TCMH presentan un mayor riesgo de LRA, cuya etiología es con frecuencia multifactorial. Debido a la incidencia de LRA, la consulta a un nefrólogo especializado como parte del equipo multidisciplinario podría ser beneficiosa. (AU)

Light Chain Restriction in Proximal Tubules-Implications for Light Chain Proximal Tubulopathy.

Monoclonal gammopathy (MG) causes various nephropathies, which may suffice for cytoreductive therapy even in the absence of diagnostic criteria for multiple myeloma or B-cell non-Hodgkin lymphoma. The aim of this study was to better understand the significance of light chain (LC) restriction or crystals (LC-R/C) in proximal tubules in the spectrum of LC-induced nephropathies. A consecutive cohort of 320 renal specimens with a history of B-cell dyscrasia was characterized. Special attention was paid to immunohistochemical LC restriction in proximal tubules, tubular crystals or constipation, and ultrastructural findings. Complementary cell culture experiments were performed to assess the role of LC concentrations in generating LC restriction. Light chain restriction or crystals in proximal tubules was found in a quarter of analyzed cases (81/316) and was associated with another LC-induced disease in 70.4% (57/81), especially LC cast-nephropathy (cast-NP) and interstitial myeloma infiltration. LC restriction without significant signs of acute tubular injury was observed in 11.1% (9/81). LC-R/C was not associated with inferior renal function compared to the remainder of cases, when cases with accompanying cast-NP were excluded. Besides crystals, cloudy lysosomes were significantly associated with LC-R/C on an ultrastructural level. In summary, LC-R/C is frequent and strongly associated with cast-NP, possibly indicating that a high load of clonal LC is responsible for this phenomenon, supported by the observation that LC restriction can artificially be generated in cell culture. This and the lack of significant tubular injury in a subgroup imply that in part LC-R/C is a tubular trafficking phenomenon rather than an independent disease process.

Acute Kidney Injury After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a Portuguese Population.

Background: Acute kidney injury (AKI) after cytoreductive surgery followed by the infusion of hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with a higher rate of major complications, resulting in prolonged hospitalization and increased mortality. Our objective was to evaluate the incidence of AKI and further progression to chronic kidney disease (CKD) in patients submitted to this procedure and recognize the associated risk factors. Methods: This retrospective study collected demographic, tumor-related, intraoperative, and postoperative data from 182 patients who underwent CRS/HIPEC from January 2016 to December 2019. Renal impairment was defined according to Kidney Disease Improving Global Outcomes criteria for AKI. We conducted univariate and multiple logistic regression analyses to assess the association between variables of interest and AKI. Results: Twenty-three patients (12.6%) developed AKI. In the AKI group, the risk for developing CKD was six times higher (odds ratio (OR) 6.48, confidence interval (CI) 1.601 - 26.255). Multivariate regression identified higher risk of developing AKI in patients who underwent HIPEC with cisplatin (OR 12.21, CI 1.26 - 109.70, P = 0.025), in each additional day spent in the intensive care unit (ICU) (OR 2.42, CI 1.07 - 5.45, P = 0.033), and an association for each unit increase in estimated glomerular filtration rate (eGFR) before HIPEC (OR 0.96, CI 0.94 - 0.98, P = 0.037) and AKI development. Conclusion: Patients who are at higher risk of AKI after CRS/HIPEC include those who performed cisplatin HIPEC regimen, had poorer preoperative renal function and had longer ICU stays. Early institution of preventive measures and frequent monitoring should be considered to minimize AKI risk and its associated morbidity, such as CKD progression.

IgA nephropathy in IgG kappa multiple myeloma.

Multiple myeloma (MM) frequently affects kidney function through multiple mechanisms. Nonetheless, some patients develop kidney injury due to other causes. A 54-year-old woman was diagnosed with IgG kappa MM developed IgA nephropathy without cast nephropathy. Further studies did not show criteria for MM progression or other causes. This case highlights the need for further investigation of kidney injury in MM patients (such as toxicity of previous drugs, infectious events, or immune-mediated disorders).

Thrombotic microangiopathy in oncology - a review.

Thrombotic microangiopathy is a syndrome triggered by a wide spectrum of situations, some of which are specific to the Oncology setting. It is characterized by a Coombs-negative microangiopathic haemolytic anemia, thrombocytopenia and organ injury, with characteristic pathological features, resulting from platelet microvascular occlusion. TMA is rare and its cancer-related subset even more so. TMA triggered by drugs is the most common within this group, including classic chemotherapy and the latest targeted therapies. The neoplastic disease itself and hematopoietic stem-cell transplantation could also be potential triggers. Evidence-based medical guidance in the management of cancer-related TMA is scarce and the previous knowledge about primary TMA is valuable to understand the disease mechanisms and the potential treatments. Given the wide spectrum of potential causes for TMA in cancer patients, the aim of this review is to gather the vast information available. For each entity, pathophysiology, clinical features, therapeutic approaches and prognosis will be covered.

A Rare Case of Renal AA Amyloidosis Secondary to Sjogren's Syndrome.

AA amyloidosis is a rare complication of chronic inflammatory disorders and has been associated with rheumatoid arthritis and ankylosing spondylitis. We present a case of AA amyloidosis secondary to Sjogren's syndrome (SS). A 79-year-old woman presented with rapidly progressive renal failure and complaints of asthenia, anorexia and generalized oedema. She had severe renal failure (creatinine 6.0 mg/dl), with microscopic haematuria, nephrotic proteinuria and low serum albumin levels, and an increased erythrocyte sedimentation rate. Serum protein electrophoresis revealed a peak in the gamma globulin zone. The patient was started on haemodialysis and corticosteroids. Clinical results showed the patient met the diagnostic criteria for primary SS, and neoplastic haematological disease was excluded. Renal biopsy revealed a diagnosis of AA amyloidosis. Renal AA amyloidosis is a rare condition in patients with primary SS. However, in patients with proteinuria and/or renal failure, it should be included in the differential diagnosis and a renal biopsy should be performed. LEARNING POINTS: Sjogren's syndrome should be regarded as a predisposing condition for the development of renal AA amyloidosis.Sjogren's syndrome and renal AA amyloidosis have been diagnosed simultaneously in some patients.A renal biopsy should be performed in patients with Sjogren's syndrome and proteinuria and/or renal failure.

PLA2R-positive (primary) membranous nephropathy in a child with IPEX syndrome.

BACKGROUND: Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare primary immunodeficiency syndrome characterized by the development of multiple autoimmune disorders in affected individuals. Different forms of renal injury have been reported in IPEX syndrome, and membranous nephropathy (MN) is among the most common glomerulopathies found. However, the exact pathogenesis of MN in this setting has not been elucidated, and it is not clear whether it is part of the clinical spectrum of the disease or secondary to medications, infections or other concomitant insults. DIAGNOSIS/TREATMENT: We describe a child diagnosed with IPEX syndrome shortly after birth who presented with nephrotic syndrome at the age of 11 weeks. Renal biopsy revealed a MN with enhanced immunohistochemical staining for phospholipase A2 receptor (PLA2R). CONCLUSION: This is the first report of a PLA2R-positive MN in a patient with IPEX syndrome. We suggest that, in this context, MN results from an autoimmune process against podocytic antigens, namely PLA2R.

When kidneys are no longer a friend: An ‘out of the box’ management for an unexpected evolution of an uncommon disease / Cuando los riñones dejan de ser un amigo: Una gestión ‘fuera de la caja’ de una evolución imprevista de una enfermedad poco común

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Haematological malignancies and acute kidney injury requiring nephrology consultation: challenging the worst of the worst.

BACKGROUND: Acute kidney injury (AKI) often complicates the course of haematological malignancies (HMs) and confers a worse prognosis. The majority of these patients are managed by the attending physician, yet, a small group, mostly coincident with the worst presentation and outcomes, requires nephrology consultation, challenging the clinician with ethical issues regarding the decision to initiate or forgo renal support therapy. The purpose of this work is to identify the prognostic determinants for in-hospital mortality in this population. METHODS: A retrospective, observational chart review was undertaken at a single tertiary referral oncological centre. We reviewed the medical records of in-hospital patients with AKI and HM between 1 January 1995 and 31 December 2014 who met the criteria for RIFLE (Risk, Injury, and Failure; and Loss; and End-stage kidney disease) classification of I or higher and were followed by a nephrologist. RESULTS: Three hundred and forty-five patients were included in the study. Predictors of in-hospital death in patients with HM and AKI were septic shock [odds ratio (OR) 4.290 (95% CI 2.058-8.943)], invasive mechanical ventilation (IMV) [OR 4.305 (95% CI 2.075-8.928)] and allogeneic stem cell transplantation (SCT) [OR 2.232 (95% CI 1.260-3.953)]. The combination of each risk factor was used to estimate the probability of dying. Patients with all three risk factors had a risk of death of 86%. CONCLUSIONS: Septic shock, IMV and allogeneic SCT were identified as independent predictors of death in patients with HM and AKI, with only a small chance of survival if all three were present. Depending on the combination of risk factors, the indication for aggressive life support therapies, such as RST, might be questionable.