scholarly journals Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study

Blood ◽  
2020 ◽  
Vol 135 (21) ◽  
pp. 1833-1846 ◽  
Author(s):  
Virginie Royal ◽  
Nelson Leung ◽  
Stéphan Troyanov ◽  
Samih H. Nasr ◽  
Laure Écotière ◽  
...  

Abstract Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

2020 ◽  
Author(s):  
Joana Gameiro ◽  
Filipe Marques ◽  
José António Lopes

Abstract The incidence of acute kidney injury (AKI) has increased in the past decades. AKI complicates up to 15% of hospitalizations and can reach up to 50–60% in critically ill patients. Besides the short-term impact of AKI in patient outcomes, several studies report the association between AKI and adverse long-term outcomes, such as recurrent AKI episodes in 25–30% of cases, hospital re-admissions in up to 40% of patients, an increased risk of cardiovascular events, an increased risk of progression of chronic kidney disease (CKD) after AKI and a significantly increased long-term mortality. Despite the long-term impact of AKI, there are neither established guidelines on the follow-up care of AKI patients, nor treatment strategies to reduce the incidence of sequelae after AKI. Only a minority of patients have been referred to nephrology post-discharge care, despite the evidence of improved outcomes associated with nephrology referral by addressing cardiovascular risk and risk of progression to CKD. Indeed, AKI survivors should have specialized nephrology follow-up to assess kidney function after AKI, perform medication reconciliation, educate patients on nephrotoxic avoidance and implement strategies to prevent CKD progression. The authors provide a comprehensive review of the transition from AKI to CKD, analyse the current evidence on the long-term outcomes of AKI and describe predisposing risk factors, highlight the importance of follow-up care in these patients and describe the current therapeutic strategies which are being investigated on their impact in improving patient outcomes.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Zishan Lin ◽  
Xu Zhang ◽  
Xiaojuan Yu ◽  
Suxia Wang ◽  
Xinan Cen ◽  
...  

Abstract Background and Aims Light chain cast nephropathy is the most common paraprotein-associated kidney lesion in patients with multiple myeloma (MM). Rarely, light chain cast nephropathy could show crystalline appearance in patients with multiple myeloma, also known as crystalline light chain cast nephropathy. We here report the first retrospective study of crystalline light chain cast from a single centre. Method All native kidney biopsies were retrospectively studied in the Peking University First Hospital from 2000 to 2020. Newly diagnosed MM patients with were enrolled. Patients with light chain cast nephropathy at least one cast with crystalline appearance were identified as crystalline light chain cast nephropathy (Figure 1, n = 8), others were identified as ordinary light chain cast nephropathy (n = 18). Results The cohort of crystalline light chain cast nephropathy consisted of 6 men and 2 women with a median age of 59.5 (range, 41-73) years. All patients suffered from advanced multiple myeloma (1 with ISS staging II, 7 with ISS staging III) and acute kidney injury with a median eGFR of 5.59 (range, 2.27-26.04) mL/min/1.73m2. All patients except 1 required emergency dialysis at admission. Microhematuria was presented in 3 patients. Median proteinuria was 2.13 (rang, 0.83-3.59) g/24h and median serum albumin was 38.2 (30.7-46.7) g/L. No one presented with nephrotic syndrome. Monoclonal immunoglobulin, detected in all patients on serum protein immunofixation electrophoresis, was λ alone in 5 patients, κ alone in 1 patient, IgG λ in 1 patient, IgA λ in 1 patient. The 8 patients were followed up with a median time of 8 (range, 2-24) months. Three patients received VAD chemotherapy and 5 patients received bortezomib based regimens. At the time of last follow-up, 2 of 7 patients who needed emergency dialysis got rid of dialysis and the rest remained dialysis-dependent. Five patients died with a median time of 5 (range, 2-19) months, 2 patients achieved partial remission and 1 patient achieved complete remission. There was no significant difference in clinical features, treatments and main outcomes between crystalline light chain cast nephropathy patients and ordinary light chain cast nephropathy patients (Table 1). However, crystalline light chain cast nephropathy patients had higher early mortality than ordinary light chain cast nephropathy patients (50.0% vs 11.1%, p = 0.03). Conclusion Crystalline light chain cast nephropathy patients usually presented with acute kidney injury requiring emergency dialysis. Although various types of monoclonal immunoglobulin were detected, there was a dominance of the λ isotype. Compared to ordinary light chain cast nephropathy patients, crystalline light chain cast nephropathy patients had higher early mortality.


BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e024411 ◽  
Author(s):  
Melanie Meersch ◽  
Mira Küllmar ◽  
Carola Wempe ◽  
Detlef Kindgen-Milles ◽  
Stefan Kluge ◽  
...  

IntroductionAcute kidney injury (AKI) is a well-recognised complication of critical illness which is of crucial importance for morbidity, mortality and health resource utilisation. Renal replacement therapy (RRT) inevitably entails an escalation of treatment complexity and increases costs for those patients with severe AKI. However, it is still not clear whether regional citrate anticoagulation or systemic heparin anticoagulation for continuous RRT (CRRT) is most appropriate. We hypothesise that, in contrast to systemic heparin anticoagulation, regional citrate anticoagulation for CRRT prolongs filter life span and improves overall survival in a 90-day follow-up period (coprimary endpoints).Methods and analysisWe will conduct a prospective, randomised, multicentre, clinical trial including up to 1450 critically ill patients with AKI requiring CRRT. We suggest to investigate the effect of regional citrate anticoagulation for CRRT as compared with systemic heparin anticoagulation. The two coprimary outcomes are filter life span and overall survival in a 90-day follow-up period. Secondary outcomes are length of stay in the intensive care unit; length of hospitalisation; duration of CRRT; recovery of renal function at days 28, 60, 90 and 1 year; requirement for RRT after days 28, 60, 90 and 1 year; 28 days, 60 days, 90 days and 1-year all-cause mortality; major adverse kidney events at days 28, 60, 90 and 1 year; bleeding complications; transfusion requirements; infection rate and costs of RRT. Additionally, in an add-on study involving several of the participating centres, blood samples from recruited patients will be collected at different time points to analyse whether the anticoagulation strategy has an impact on immune response as evidenced by leucocyte recruitment and function.Ethics and disseminationThe RICH trial has been approved by the Federal Institute for Drugs and Medical Devices, the leading Ethics Committee of the University of Münster and the corresponding Ethics Committee at each participating site.Trial registration numberNCT02669589.


2020 ◽  
Vol 7 ◽  
pp. 205435812092262
Author(s):  
Angela Chou ◽  
Christopher Long ◽  
Leon Vonthethoff ◽  
Shir-Jing Ho ◽  
Franziska Pettit ◽  
...  

Rationale: Crystalglobulinemia is a rare complication of monoclonal gammopathy wherein crystallized immunoglobulins deposit in various organs causing occlusive vasculopathy, endothelial damage, and thrombosis. It should be differentiated from light chain cast nephropathy without crystalline nephropathy through timely diagnosis with a kidney biopsy. Presenting concerns of the patient: We report a case of a 74-year-old female with polyarthralgia, chest pain, petechial rash, and acute kidney injury. Diagnoses: Kidney biopsy revealed eosinophilic casts in the tubular lumen and similar occlusive crystalline deposits within the glomerular vasculature and interlobular arteries. Bone marrow biopsy and serum electrophoresis confirmed immunoglobulin G (IgG) κ multiple myeloma. Interventions: Dialysis was initiated for severe oligoanuric acute kidney injury. The patient was treated with 5 sessions of plasmapheresis and 11 cycles of clone reduction chemotherapy with CyBorD (cyclophosphamide, bortezomib, and dexamethasone). Outcomes: This patient achieved excellent kidney recovery and is no longer dialysis dependent. Teaching points: Crystalglobulinemia should be suspected in patients with rapidly progressive acute kidney injury and monoclonal gammopathy. Timely investigation with kidney biopsy to differentiate this condition from light chain cast nephropathy and initiation of appropriate treatment can lead to remission of disease and excellent recovery of kidney function.


2012 ◽  
Vol 52 (188) ◽  
Author(s):  
R Hada ◽  
B Poudyal ◽  
A Sharma ◽  
R Khatri

Cast nephropathy is one of the major causes of renal failure in patients with multiple myeloma resulting from precipitation of free light chains inside the tubules. Timely diagnosis and treatment confers a better prognosis though around 10% of patients with cast nephropathy remain dialysis dependent in spite of treatment.We report the clinical course and outcome of a patient presenting with acute kidney injury and oliguria, preceded by acute gastroenteritis and intake of Chinese medications and dialysis dependent state for eight weeks. Kidney biopsy revealed cast nephropathy with lambda light chain restriction and severe tubular injury. Serum protein electrophoresis was normal with no “M spike” but serum free light chain ratio was altered with very high lambda and normal kappa light chain levels. Bone marrow biopsy showed >85% atypical plasma cells. Haemodialysis was continued and chemotherapy with bortezomib, doxorubicin and dexamethasone was started. Kidney function gradually improved with discontinuation of dialysis after 1 month and complete remission of acute kidney injury and myeloma in 4 months of chemotherapy.   Keywords: acute kidney injury; bortezomib; cast nephropathy; multiple myeloma.


2019 ◽  
Vol 72 (8) ◽  
pp. 550-553 ◽  
Author(s):  
Martin J Magers ◽  
Hristos Z Kaimakliotis ◽  
Marcelo P Barboza ◽  
Elhaam Bandali ◽  
Nabil Adra ◽  
...  

AimsTo describe a large tertiary care academic centre’s experience with patients who achieve a complete pathological response (ie, ypT0N0) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with emphasis on morphological features present in the RC and clinical outcome.Methods41 patients with ypT0N0 disease following transurethral resection of bladder tumour (TURBT), NAC and RC with available clinical follow-up information were analysed. Slides from all RCs were reviewed to confirm pathological stage and assess for morphological parameters (eg, foreign body giant cell reaction, dystrophic calcification, scar and fat necrosis).ResultsWith median follow-up of 32.8 months, the recurrence-free survival at 1 and 5 years was 97.4% and 93.5%, while the overall survival at 3 and 5 years was 94.2% and 88.6%, respectively. No patients died of urothelial carcinoma. Stage assigned at TURBT was 1 pTa (2%), 1 pT1 (2%), 38 pT2 (93%) and 1 pT3a (2%). 17 TURBTs demonstrated variant histology, with the majority of these being squamous (65%). The most common morphological features present at RC were scar (100%), foreign body giant cell reaction (80%), chronic inflammation within lamina propria (68%) and dystrophic calcifications (39%). Other morphological features were less common or absent.ConclusionypT0N0 disease at RC portends an excellent prognosis, regardless of stage or variant histology in the TURBT; scar, foreign body giant cell reaction, chronic inflammation and dystrophic calcifications are often present.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yannis Lombardi ◽  
Franck Boccara ◽  
Kadiatou Baldet ◽  
Stéphane Ederhy ◽  
Pascal Nhan ◽  
...  

Abstract Background and Aims Acute kidney injury (AKI) occurring after diuretic treatment initiation for acute heart failure (AHF) is a common phenomenon, with an incidence estimated between 20 and 50% of AHF hospitalizations. Previous studies found that persistent AKI is associated with poor prognosis. Treatment-induced hemoconcentration is associated with improved prognosis, but several definitions previously used are not suited for clinical practice. Transient AKI, with or without hemoconcentration, is of unsettled prognosis. We aim to determine the independent prognostic value of transient AKI, persistent AKI and hemoconcentration in the context of AHF hospitalization, using practical definitions. Method Data were obtained from the Greater Paris University Hospitals (GPUH) Clinical Data Warehouse. Patients hospitalized for AHF in various GPUH units were included. AHF hospitalization was defined as hospitalization with at least one AHF ICD-10 code and at least one recorded furosemide administration. Bumetanide is rarely used in GPUH hospitals hence it was not considered. AKI in a period of 14 days following first furosemide administration was defined based on KDIGO guidelines. Hemoconcentration was defined as an increase in serum proteins ≥ 5 g/l during the same period. Multivariate logistic regression was performed to determine which characteristics were predictive of AKI. Cox regression of 100 days all-cause mortality using multiple confounders was performed to determine the prognostic value of transient AKI (< 14 days), persistent AKI (≥ 14 days) and hemoconcentration. Patients with AKI upon hospital entry were excluded from regression analyses. AKI and hemoconcentration were treated as time-dependent covariates to adjust for immortality bias. Results Five hundred seventy nine patients were included. Among them, 529 had no AKI upon hospital entry and 513 had at least one recorded serum proteins and creatinine value following furosemide initiation. Median follow-up was 114 days. AKI in a period of 14 days following furosemide initiation occurred in 234 patients (40.4%). At baseline, patients in the AKI group more frequently suffered from chronic kidney disease or presented with clinical and echocardiographic signs of right heart failure. Independent predictors of AKI were arterial hypertension upon furosemide initiation (adjusted OR 1.86 [1.08 – 3.22]), elevated serum creatinine upon furosemide initiation (adjusted OR 1.07 [1.01 – 1.14] per 10 µmol/l increase) and initial intravenous administration of furosemide (adjusted OR 2.42 [1.39 – 4.29]). Death during follow-up occurred in 35% of patients in the AKI group compared to 21% in the non-AKI group (p < 0.001). In multivariate analysis, persistent AKI was independently associated with increased mortality in a period of 100 days following furosemide initiation (adjusted HR 2.31 [1.07 – 4.99]). Transient AKI was not significantly associated with mortality (adjusted HR 0.64 [0.34 – 1.19]). Hemoconcentration was independently associated with decreased mortality (adjusted HR 0.46 [0.27 – 0.79]). Conclusion After furosemide initiation during hospitalization for AHF, persistent AKI (≥ 14 days) was independently associated with increased 100 days mortality. Hemoconcentration, using a definition suited for clinical practice (≥ 5 g/l increase in serum proteins), was independently associated with decreased 100 days mortality. No significant association was found between mortality and transient AKI (< 14 days). Those findings show that laboratory tests at a limited cost – serum proteins and creatinine – are helpful to evaluate treatment response and mortality risk during AHF. Prospective randomized controlled trials are needed to establish diuretic strategies based on both AKI and hemoconcentration.


2018 ◽  
Vol 43 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Eva Rodríguez ◽  
Carlos Arias-Cabrales ◽  
Sheila Bermejo ◽  
Adriana Sierra ◽  
Carla Burballa ◽  
...  

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