Assessment of current clinical practice throughout the UK for the diagnosis and management of monoclonal gammopathy of renal significance

Abstract Since the inception of the term monoclonal gammopathy of renal significance (MGRS) in 2012 by the International Kidney and Monoclonal Gammopathy Research Group, there have been no consensus guidelines specifically pertaining to the UK regarding to patient management. We aimed to identify both regional and cross‐discipline variation in current clinical practice, to provide insight and rationale for a potential standardised pathway in the future. A national survey of 88 consultants from the disciplines of haematology and nephrology was conducted between June 2020 and July 2021. Agreement was evident for aspects of the diagnostic pathway, including presenting features likely to raise suspicion of MGRS and the most pertinent confounding factors to consider before renal biopsy. However, significant variability was identified in both the cohort of diagnostic tests used, as well as urinary work‐up for patients with suspected MGRS. Treatment and monitoring frequency was also an aspect of management identified as variable. Despite differences in clinical practice across the UK, MGRS diagnosis was widely regarded to be the joint responsibility of both disciplines. The results provide an indication of inter‐regional and interdisciplinary differences in practice, highlighting the need for improved awareness and standardised protocol for management of MGRS that applies to the UK population.


Survey population
In total, 113 individuals commenced the survey, and 88 recorded a response suitable for analysis. Data were collected across the UK and participants grouped into larger geographic regions for subsequent analysis (Table 1).
Following the establishment of MGRS as a distinct clinical entity, awareness of the condition has increased. Participants from each specialty were asked how frequently they saw MGRS patients (new and follow-up) in their clinic. Of the two disciplines, nephrologists reported that they were more likely to see MGRS patients each month (>4

Presenting features
Distinguishing MGRS from other monoclonal gammopathies and renal diseases can be challenging due to non-specificity of presenting symptoms. Clinicians were asked to identify which features they considered to be most indicative of a potential MGRS diagnosis ( Figure 1). Free text responses were coded to enable quantitative analysis. A composite category-renal impairment and paraprotein-was created for responses, which clearly indicated that the coincidence of both these features were important (42/83 -52.6%).
Haematologists and nephrologists identified declining renal func-

Diagnostic tests
To gauge clinical practice, respondents were asked to provide an indication of which tests they would request to make a diagnosis of MGRS.
Twenty-five tests were identified by the participants (Figure 2A). a One individual completed all other survey questions but did not provide their region. They are included in comparative analysis between nephrology and haematology but are omitted from regional analysis.    We also wanted to determine if there were regional differences in tests requested ( Figure 2B). Serum free light chain testing and SPE were the most frequently ordered tests in all regions of the UK. Ten of 25 tests were ordered at least once by a clinician from each region. Participants were asked which tests they would request, in order to understand their current practice ( Table 2).
Protein/creatinine ratio and protein/creatinine ratio and albumin/creatinine ratio were the most frequently used urine tests across the two disciplines. Protein/creatinine ratio was favoured by nephrologists (43.5%), whereas a combination of both protein/creatinine ratio and albumin/creatinine ratio was preferred by haematologists (39.5%).
The most popular tests in the East region were protein/creatinine ratio and albumin/creatinine ratio (57.1%), whereas protein/creatinine ratio was used most frequently in the other regions. The South had the greatest proportion of clinicians requesting all three tests.

Monoclonal protein involvement
Identification of the causative monoclonal immunoglobulin is impor- Twenty-four different combinations of tests were identified from respondents. Of these, six were unique to nephrology and seven unique to haematology, indicating differences between the two specialties (Table S3). The testing combinations were ranked according to frequency of use and the five cohorts of tests that were most frequently requested are displayed in Table 3.
The five most frequently used cohorts of tests were assigned a number that corresponded to their popularity amongst the surveyed clinicians. Regional differences were then assessed according to the frequency of use of these different tests (

Renal biopsy
Participants were asked which factors were most pertinent when considering a renal biopsy ( This was followed by age and severe renal impairment (age 56.8% and 39.5%, severe renal impairment 48.6% and 39.5%, haematologist and nephrologists, respectively). In each instance, a greater proportion of haematologists considered these features to be confounding. Additional factors identified by participants included small/single kidney (6.25%), frailty (5%) and whether the result of the biopsy was likely to change treatment (3.8%).
Clinicians were asked which speciality they believe has the responsibility for diagnosing MGRS. A proportion of participants 12/88 (13.6%) felt that this duty lies with nephrology and 2/88 (2.3%) with haematology, but there was strong consensus overall that the responsibility for the diagnosis of these patients should be jointly shared by both specialities 74/88 (84.1%).

Response and monitoring
We asked which parameters were considered most critical in deter- Clinicians were asked which treatment modalities they use.

DISCUSSION
The results of this survey provide insight into current clinical practice concerning MGRS across the disciplines of both haematology and nephrology as well as regional differences in MGRS management.
These results represent, to our knowledge, the first national survey on current clinical practice for MGRS.
Of the two disciplines, nephrologists were more likely to see MGRS patients, which is perhaps due to the renal abnormalities provoked by the disease. Interestingly, there were no differences in the reported frequency of referrals from haematology to nephrology and vice versa.
MGRS diagnosis can prove challenging, so participants were asked to indicate the presenting features that they most associate with these conditions, to provide an indication of symptom awareness and reflect their experience. In the absence of national guidelines, we surmised that there might be regional differences in the features deemed most predictive of a diagnosis.
Consensus was evident amongst clinicians that declining renal func- provides information regarding possible diabetic nephropathy. These results are further confounded by regional variation in the availability and funding of specific tests, again highlighting the need for standardisation.
Declining renal function should be accounted for whilst interpreting mildly abnormal FLC ratios [3, 17 -19]. The variability of FLC ratio depends on the assay used [20,21]. Since Freelite is the most widely used FLC assay in the UK, we asked respondents whether they used a renal reference range when interpreting results. There was no difference identified in the overall utilisation of a renal reference range according to speciality. However, there were regional differences, with the greatest proportion of clinicians utilising a renal reference range in the South (81.8%).
Renal biopsy is recommended by the IKMG for a definitive diagnosis of MGRS [2,3]. Whilst the procedure carries inherent-associated risks, rates of haemorrhagic complications have been found to be similar in patients with and without MGRS [22,23]. To assess perception about renal biopsy, participants were asked about confounding factors. The responses were concordant. Risk of bleeding was identified as the most pertinent factor, followed by age and severe renal impairment. Notably, a higher proportion of haematologists raised concerns (Table 6), which may be due to a lack of practical experience, since renal biopsy is a procedure performed exclusively by nephrologists. This disparity in perception should be addressed by raising awareness of the condition so that it does not preclude the referral of a patient for renal biopsy, where appropriate.
There was significant variability noted in the frequency of followup appointments scheduled by the two specialities. This highlights a potential concern of inadequate monitoring, identification of adverse events of treatment delivered and early relapse.
There is strong consensus and appetite from clinicians of both disciplines to share responsibility for patients with MGRS. A joint approach provides expertise on clone directed chemotherapy as well as appropriate management of renal issues. This raises an issue regarding potential establishment of joint clinics and regional multidisciplinary team discussions for the cross-speciality management of these patients and improved outcomes.
In conclusion, this large survey generates important real-world information, albeit with limitations stemming from variability in regional responses to the survey and differing availability of tests for each centre. Whilst aspects of regional and interdisciplinary variation in the management of MGRS patients were expected, this research represents, to our knowledge, the first substantiated evidence of this assumption. The data presented here underscore the need to establish dual discipline services for effective patient management.