Association between non-malignant monoclonal gammopathy and adverse outcomes in chronic kidney disease: A cohort study

English version

Autoři: Anthony Fenton ^aff001; Rajkumar Chinnadurai ^aff003; Latha Gullapudi ^aff004; Petros Kampanis ^aff005; Indranil Dasgupta ^aff001; James Ritchie ^aff003; Stephen Harding ^aff005; Charles J. Ferro ^aff001; Philip A. Kalra ^aff003; Maarten W. Taal ^aff004; Paul Cockwell ^aff001
Působiště autorů: University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom ^aff001; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom ^aff002; Salford Royal NHS Foundation Trust, Salford, United Kingdom ^aff003; Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom ^aff004; Binding Site, Birmingham, United Kingdom ^aff005
Vyšlo v časopise: Association between non-malignant monoclonal gammopathy and adverse outcomes in chronic kidney disease: A cohort study. PLoS Med 17(2): e32767. doi:10.1371/journal.pmed.1003050
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1003050

Souhrn

Background

In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD).

Methods and findings

Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739). Participants were excluded if they had multiple myeloma or any other B cell lymphoproliferative disorder with end-organ damage. Median age was 71.0 years, 50.6% were male, median estimated glomerular filtration rate was 42.3 ml/min/1.73 m², and median urine albumin-to-creatinine ratio was 3.4 mg/mmol. All non-malignant MG was identified in the baseline serum of participants of RIISC. Further, light chain MG (LC-MG) was identified and studied in participants of RIISC, SKS, and RRID. Participants were followed up for kidney failure (defined as the initiation of dialysis or kidney transplantation) and death. Associations with the risk of kidney failure were estimated by competing-risks regression (handling death as a competing risk), and associations with death were estimated by Cox proportional hazards regression. In total, 102 (11.6%) of the 878 RIISC participants had an MG. During a median follow-up time of 74.0 months, there were 327 kidney failure events and 202 deaths. The presence of MG was not associated with risk of kidney failure (univariable subhazard ratio [SHR] 0.97 [95% CI 0.68 to 1.38], P = 0.85; multivariable SHR 1.16 [95% CI 0.80 to 1.69], P = 0.43), and although there was a higher risk of death in univariable analysis (hazard ratio [HR] 2.13 [95% CI 1.49 to 3.02], P < 0.001), this was not significant in multivariable analysis (HR 1.37 [95% CI 0.93 to 2.00], P = 0.11). Fifty-five (1.6%) of the 3,478 participants from all 3 studies had LC-MG. During a median follow-up time of 62.5 months, 564 of the 3,478 participants progressed to kidney failure, and 803 died. LC-MG was not associated with risk of kidney failure (univariable SHR 1.07 [95% CI 0.58 to 1.96], P = 0.82; multivariable SHR 1.42 [95% CI 0.78 to 2.57], P = 0.26). There was a higher risk of death in those with LC-MG in the univariable model (HR 2.51 [95% CI 1.59 to 3.96], P < 0.001), but not in the multivariable model (HR 1.49 [95% CI 0.93 to 2.39], P = 0.10). An important limitation of this work was that only LC-MG, rather than any MG, could be identified in participants from SKS and RRID.

Conclusions

The prevalence of MG was higher in this CKD cohort than that reported in the general population. However, the presence of an MG was not independently associated with a significantly higher risk of kidney failure or, unlike in the general population, risk of death.

Klíčová slova:

Cohort studies – Coronary heart disease – diabetes mellitus – Glomerular filtration rate – Chronic kidney disease – Kidneys – Renal arteries – Urine

Zdroje

1. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362–9. doi: 10.1056/NEJMoa054494 16571879

2. Fermand JP, Bridoux F, Dispenzieri A, Jaccard A, Kyle RA, Leung N, et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood. 2018;132(14):1478–85. doi: 10.1182/blood-2018-04-839480 30012636

3. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48. doi: 10.1016/S1470-2045(14)70442-5 25439696

4. Leung N, Bridoux F, Hutchison CA, Nasr SH, Cockwell P, Fermand JP, et al. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood. 2012;120(22):4292–5. doi: 10.1182/blood-2012-07-445304 23047823

5. Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378(3):241–9. doi: 10.1056/NEJMoa1709974 29342381

6. Kristinsson SY, Bjorkholm M, Andersson TM, Eloranta S, Dickman PW, Goldin LR, et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study. Haematologica. 2009;94(12):1714–20. doi: 10.3324/haematol.2009.010066 19608666

7. Haynes R, Hutchison CA, Emberson J, Dasgupta T, Wheeler DC, Townend JN, et al. Serum free light chains and the risk of ESRD and death in CKD. Clin J Am Soc Nephrol. 2011;6(12):2829–37. doi: 10.2215/CJN.03350411 22034503

8. Ritchie J, Assi LK, Burmeister A, Hoefield R, Cockwell P, Kalra PA. Association of serum ig free light chains with mortality and ESRD among patients with nondialysis-dependent CKD. Clin J Am Soc Nephrol. 2015;10(5):740–9. doi: 10.2215/CJN.09660914 25825483

9. Stringer S, Sharma P, Dutton M, Jesky M, Ng K, Kaur O, et al. The natural history of, and risk factors for, progressive chronic kidney disease (CKD): the Renal Impairment in Secondary care (RIISC) study; rationale and protocol. BMC Nephrol. 2013;14 : 95. doi: 10.1186/1471-2369-14-95 23617441

10. Hoefield RA, Kalra PA, Baker P, Lane B, New JP, O’Donoghue DJ, et al. Factors associated with kidney disease progression and mortality in a referred CKD population. Am J Kidney Dis. 2010;56(6):1072–81. doi: 10.1053/j.ajkd.2010.06.010 20692750

11. McIntyre NJ, Fluck RJ, McIntyre CW, Taal MW. Skin autofluorescence and the association with renal and cardiovascular risk factors in chronic kidney disease stage 3. Clin J Am Soc Nephrol. 2011;6(10):2356–63. doi: 10.2215/CJN.02420311 21885790

12. Hutchison CA, Harding S, Hewins P, Mead GP, Townsend J, Bradwell AR, et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008;3(6):1684–90. doi: 10.2215/CJN.02290508 18945993

13. Hutchison CA, Plant T, Drayson M, Cockwell P, Kountouri M, Basnayake K, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol. 2008;9 : 11. doi: 10.1186/1471-2369-9-11 18808676

14. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–509. doi: 10.1080/01621459.1999.10474144

15. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet. 2010;375(9727):1721–8. doi: 10.1016/S0140-6736(10)60482-5 20472173

Článek An evaluation of Chile’s Law of Food Labeling and Advertising on sugar-sweetened beverage purchases from 2015 to 2017: A before-and-after study

Článek A multicomponent secondary school health promotion intervention and adolescent health: An extension of the SEHER cluster randomised controlled trial in Bihar, India

Článek Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study

Článek Impact of the announcement and implementation of the UK Soft Drinks Industry Levy on sugar content, price, product size and number of available soft drinks in the UK, 2015-19: A controlled interrupted time series analysis

Článek Estimating progress towards meeting women’s contraceptive needs in 185 countries: A Bayesian hierarchical modelling study

Článek Emerging priorities for HIV service delivery

Článek Digitally enabled aged care and neurological rehabilitation to enhance outcomes with Activity and MObility UsiNg Technology (AMOUNT) in Australia: A randomised controlled trial

Článek Association of coincident self-reported mental health problems and alcohol intake with all-cause and cardiovascular disease mortality: A Norwegian pooled population analysis

Článek The effect of assessing genetic risk of prostate cancer on the use of PSA tests in primary care: A cluster randomized controlled trial

Článek Virological suppression and clinical management in response to viremia in South African HIV treatment program: A multicenter cohort study

Článek Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

Článek Improving air quality needs to be a policy priority for governments globally