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


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: 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

Štítky
Interní lékařství

Článek vyšel v časopise

PLOS Medicine


2020 Číslo 2

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×