scholarly journals Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients

Author(s):  
Marco Basset ◽  
Paolo Milani ◽  
Virginia Valeria Ferretti ◽  
Mario Nuvolone ◽  
Andrea Foli ◽  
...  

Abstract Objectives Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. Methods From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson’s r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. Results A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. Conclusions UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients’ management.

Author(s):  
Melek Cihanbeylerden ◽  
Melike Bağnu Yüceege

Abstract Introduction Obstructive sleep apnoea (OSA) is a cause of hypoxia, and the correlation between hypoxia and microvascular complications is well known. Microalbuminuria (MAU) is a marker for endovascular dysfunction and an indicator of cardiovascular events and all-cause mortality in the general population. The aim of this study was to investigate the relationship between microvascular damage and the metabolic complications of OSA based on the presence of MAU. Material and method Urinary albumin/creatinine ratio (ACR) and microalbumin level were examined in patients with an apnoea-hypopnoea index (AHI) greater than 5/h (study group) and in patients with an AHI less than 5/h (control group). The exclusion criteria were other possible causes of MAU (hypertension, nephropathy, coronary artery disease, and severe thyroid dysfunction). Results Of 103 patients enrolled, 80 formed the group with OSA and 23 served as controls. According to the AHI values, the patients were divided into four groups as normal, mild, moderate and severe. There was no significant difference between the four groups in terms of the microalbumin level and urinary albumin/creatinine ratio. Conclusion In this study, no significant relationship was found between MAU and sleep apnoea.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e040214
Author(s):  
Shan Qin ◽  
Anping Wang ◽  
Shi Gu ◽  
Weiqing Wang ◽  
Zhengnan Gao ◽  
...  

ObjectiveThe relationship between obesity and albuminuria has not been clarified. This study aimed to investigate the correlation between obesity and the urinary albumin-creatinine ratio (UACR) in Southern and Northern China.DesignA descriptive, cross-sectional study.SettingEight regional centres in REACTION (China’s Risk Evaluation of cAncers in Chinese diabeTic Individuals, a lONgitudinal study), including Dalian, Lanzhou, Zhengzhou, Guangzhou, Guangxi, Luzhou, Shanghai and Wuhan.ParticipantsA total of 41 085 patients who were not diagnosed with chronic kidney disease (CKD) and had good compliance were selected according to the inclusion criteria. Patients who were diagnosed with CKD, who had other kidney diseases that could lead to increased urinary protein excretion, who were using angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers and whose important data were missing were excluded.ResultsParticipants with both, central and peripheral obesity, had a higher risk of elevated UACR, even after adjusting for multiple factors (OR: 1.14, 95% CI: 1.07 to 1.12, p<0.001), and the risk of high UACR in the South was more prominent than that in the North (OR South: 1.22, 95% CI: 1.11 to 1.34; OR North: 1.13, 95% CI: 1.04 to 1.22, p<0.001). The risk was also elevated in the male population, hypertensive individuals, glycosylated haemoglobin (HbA1c)≥6.5% and age ≥60 years in the South. Besides the above groups, diabetes was also a risk factor for the Northern population.ConclusionsIn China, people with both central and peripheral obesity are prone to a high UACR, and the southern population has a higher risk than northern population. Factors such as male sex, hypertension, HbA1c≥6.5% and an age ≥60 years are also risk factors for CKD.


Blood ◽  
2019 ◽  
Vol 133 (3) ◽  
pp. 215-223 ◽  
Author(s):  
Brian Lilleness ◽  
Frederick L. Ruberg ◽  
Roberta Mussinelli ◽  
Gheorghe Doros ◽  
Vaishali Sanchorawala

Abstract Immunoglobulin light chain amyloidosis (AL amyloidosis) is caused by misfolded light chains that form soluble toxic aggregates that deposit in tissues and organs, leading to organ dysfunction. The leading determinant of survival is cardiac involvement. Current staging systems use N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins T and I (TnT and TnI) for prognostication, but many centers do not offer NT-proBNP. We sought to derive a new staging system using brain natriuretic peptide (BNP) that would correlate with the Mayo 2004 staging system and be predictive for survival in AL amyloidosis. Two cohorts of patients were created: a derivation cohort of 249 consecutive patients who had BNP, NT-proBNP, and TnI drawn simultaneously to create the staging system and a complementary cohort of 592 patients with 10 years of follow-up to determine survival. In the derivation cohort, we found that a BNP threshold of more than 81 pg/mL best associated with Mayo 2004 stage and also best identified cardiac involvement. Three stages were developed based on a BNP higher than 81 pg/mL and a TnI higher than 0.1 ng/mL and compared with Mayo 2004 with high concordance (κ = 0.854). In the complementary cohort, 25% of patients had stage I, 44% had stage II, 15% had stage III, and 16% had stage IIIb disease with a median survival not reached in stage I, 9.4 years in stage II, 4.3 years in stage III, and 1 year in stage IIIb. This new Boston University biomarker scoring system will allow centers without access to NT-proBNP the ability to appropriately stage patients with AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00898235.


2021 ◽  
Author(s):  
Wanlu Su ◽  
Jie Wang ◽  
Songyan Yu ◽  
Kang Chen ◽  
Wenhua Yan ◽  
...  

Abstract BackgroundThe metabolic score for insulin resistance (METS-IR) is a novel noninsulin-based metabolic index used as a substitution marker of insulin resistance. However, whether METS-IR is associated with the urinary albumin–creatinine ratio (UACR) is not well known. Therefore, we explored the associations between METS-IR and UACR and compared the discriminative ability of METS-IR and its components for elevated UACR. MethodsThis study included 37,290 subjects. METS-IR was calculated as follows: (Ln [2 × fasting blood glucose (FBG) + fasting triglyceride level (TG 0 )] × body mass index (BMI))/[Ln (high-density lipoprotein cholesterol (HDL-C))]. Participants were divided into four groups on the basis of METS-IR: <25%, 25%–49%, 50%–74%, and ≥75%. Logistic regression analyses were conducted to determine the associations between METS-IR vs. its components (FBG, TG 0 , BMI, and HDL-C) with UACR. ResultsParticipants with the highest quartile METS-IR presented a more significant trend towards elevated UACR than towards its components (odds ratio [OR]: 1.260, 95% CI: 1.152–1.378, P < 0.001 in all subjects; OR: 1.321, 95% CI: 1.104–1.579, P = 0.002 in men; OR: 1.201, 95% CI: 1.083–1.330, P < 0.001 in women). There were significant associations between METS-IR and UACR in younger participants (<65 years for women and 55–64 years for men). Increased METS-IR was significantly associated with UACR in men with FBG ≥ 5.6 mmol/L or postprandial blood glucose ≥ 7.8 mmol/L and systolic blood pressure ≥ 120 mmHg or diastolic blood pressure ≥ 80 mmHg. The relationships were significant in women with diabetes and hypertension.ConclusionsIncreased METS-IR was significantly associated with elevated UACR, and its discriminative power for elevated UACR was superior to that of its components. This findings support the clinical significance of METS-IR for evaluating renal function damage.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Mizuki Ogura ◽  
Tadao Ishida ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Junichiro Nashimoto ◽  
...  

BACKGROUND: High dose chemotherapy followed by autologous peripheral blood stem cell transplantation is an effective treatment for multiple myeloma. However, many patients with newly diagnosed multiple myeloma are transplant-ineligible because of their age and complications, result in a poorer prognosis than transplant-eligible patients. Furthermore, many of them cannot complete normal chemotherapy because of low tolerability. Here, we investigated the efficacy and safety of modified bortezomib with lenalidomide and dexamethasone (mVRD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. STUDY DESIGN: A retrospective observational analysis was performed on patients who received mVRd-lite for the first line chemotherapy between Jan. 2016 and Mar. 2020 in our hospital. Patients who received high dose dexamethasone to reduce tumor burden, and patients who received bortezomib with dexamethasone or lenalidomide with dexamethasone as a reduction regimen of mVRd-lite were also included. We evaluated ORR, OS, PFS and adverse effect. mVRD-lite at first was administered over a 28-day cycle. Bortezomib 1.3 mg/m2 weekly was administered subcutaneously on days 1, 8, 15 and 22. Lenalidomide 15 mg was given orally 18 days, omitted on days 1, 8, 15, which are the days of bortezomib administration. Dexamethasone 20 mg was given orally on days 1, 2, 8, 9, 15, 16, 22, which are the day of and day after bortezomib. We also reviewed patients background, especially complication of light-chain amyloidosis and considered the impact of cardiac amyloidosis on patient prognosis. This study was conducted with the permission of the Ethics Review Board in our hospital. RESULTS: The subjects analyzed totaled 40 transplant-ineligible patients. 11(27.5%) patients were AL amyloidosis associated with multiple myeloma and 8(20%) patients had cardiac amyloidosis. Median age at diagnosis was 73 (range 48-86) and Male:Female=1:1. Most of them were judged inadequate to transplantation due to their age, general condition, or complication. One patient was ruled unfit to transplantation, because of his refusion. The Revised International Staging System (R-ISS) were I in 5 (12.5%), II in 25 (62.5%) and III in 8 (20%). 5(25%) patients switched to maintenance therapy. 17(42.5%) patients discontinued treatment, because of adverse effect (cardiac failure 4 ; two of them combined with cardiac amyloidosis, rash 4, peripheral neuropathy 3, infection 3, etc). 2(5%) patients died during treatment by mVRd-lite, because of Grade 4 adverse effect, such as pneumonia. 11(27.5%) patients died during observation period and causes of death were primary disease and TRM. 1(2.5%) patient was died of heart failure associated with cardiac amyloidosis. The overall response rate(ORR) during treatment period of mVRd-lite was obtained in 34(85%), including sCR in 5 (12.5%), VGPR in 13 (32.5%) and PR in 14(30%). 2(5%) patients achieved MRD negative. SD were observed in 3(7.5%) patients. 3(7.5%) patients were not evaluated efficacy because of treatment interruption by adverse effect. Overall survival rate at two year is 64.3%, median OS was not reached, at a median follow-up of 20 months. CONCLUSIONS: Transplant-ineligible multiple myeloma patients are associated with poor prognosis. Modified RVD-lite is one of the appropriate therapeutic options, in the transplant-ineligible multiple myeloma patients. Twenty-five percent of patients with cardiac amyloidosis had treatment discontinued due to cardiac complications. Further study is needed for treatment of patients with multiple myeloma complicated with cardiac amyloidosis. Disclosures Ishida: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau. Nashimoto:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Suzuki:Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Bristol-Myers Squibb, Celgene and Amgen: Research Funding.


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