Monitoring and management of chronic kidney disease in ambulatory care – analysis of clinical and claims data from a population-based study

The glomerular filtration rate (eGFR) was estimated using the CKD-EPI Eq [11]. The urinary albumin-creatinine ratio (ACR) was calculated for all participants with available urinary albumin and creatinine measurements in SHIP-START-2 (n = 1321). Participants were classified according to the KDIGO albuminuria categorisation [2]. Diabetes was coded when participants reported diabetes in the questionnaire, or had HbA1c ≥ 6.5%, or serum glucose ≥ 11.1 mmol/L in any of the SHIP-START surveys. Hypertension was defined as blood pressure > 140/90 mmHg, or taking antihypertensive medication. Further details concerning measurements and testing methods are provided in supplement 1.

ICD-10 codes and billing codes (GOPs) were available for SHIP-START participants’ statutory health insurance during the observation period (supplement 1). Coding of CKD with ICD codes N18 and N19 (suspected or confirmed) and billing codes for laboratory tests of creatinine (32,066, 32,067), haemoglobin (32,038, 32,120), albumin (urine or serum) (32,435), calcium (32,082), parathyroid hormone (32,411), Vitamin D (32,413), phosphate (32,086) and urinary dip stick testing (32,030), urine microscopy (32,031) and microalbuminuria (32,135) were analysed. Sonographic examinations were represented by GOPs 33,042 and 33,043, nephrological co-treatment by the billing codes for nephrological care (13,591, 13,592, 13,600, 13,602, 13,610).

Assessment of quality of care is based on the recommendations of the NICE and KDIGO guidelines for the management of chronic kidney disease, including the KDIGO guideline on CKD-Mineral and Bone Disorder (CKD-MBD), as well as the German guideline on kidney disease in diabetes and the recommendations for referral of the German Society of Nephrology [2, 6, 7, 12‐14].

Descriptive statistics of the study data and comparison of participants with and without available claims data were performed using R version 4.2.0 with the package kidney.epi. Correlation between eGFR and age was assessed using Spearman’s rank correlation [15, 16]. Statistical analysis for categorical variables when comparing baseline characteristics of participants with and without linked claims data consisted of Pearson's Chi-squared tests with Yates' continuity correction and effect size Cramér’s V. For continuous variables, we reported p-values derived from Mann–Whitney-U tests and the absolute value of Cliff’s delta for effect sizes.

To date, no German data were available for CKD coding and monitoring. Coding is a surrogate parameter for physicians having diagnosed the patient with CKD and incorporating this knowledge into patient management. International studies show that only 15–38% of patients with CKD are coded [19‐22]. The proportion of coded CKD in our analysis was within this range (20%) and increased with diminishing kidney function. This reflects the limited clinical significance of decreased kidney function in older adults and is congruent with the findings in literature. The importance of coding for quality assessment is that when using claims data this has a large impact on the denominator for quality assessment, since only coded patients will be included. Our data suggest that claims data do not capture many patients in stage G3a.

The awareness of kidney damage was 28% in the German DEGS study (DEGS1, 2008–2011) [17]. In our analysis, only 9% with reduced GFR reported having CKD and less than half of those with stage G4 (3/8). This is in line with data from the National Health and Nutrition Examination Survey of U.S. Center of Disease Control Surveillance program for the years 2008–2012, suggesting overall CKD awareness of 10–13% in stages 3–4 with awareness increasing with stage from 3–5% in stage G3a to 38–51% in stage G4 and being negatively correlated with age[23]. The lower diagnosis awareness found in our study can be partly explained by the significantly higher age and higher rate of comorbidities of the SHIP-START population [9, 10, 24].

Our data do not allow drawing conclusions about whether the diagnosis was not made, not communicated or not remembered by the patient. From the nephrologist perspective, it is desirable for patients to be aware of their CKD [24, 25]. From a primary care perspective, other health issues are often more prominent and information about CKD does not always appear to be crucial for older people and might lead to unnecessary worries [26, 27]. On the other hand, being aware of decreased kidney function may be useful for dose-adjustment of kidney-excreted drugs and avoiding nephrotoxic substances [28]. Patients who are aware of their CKD can inform other physicians and pharmacists about their condition. However, to date, there is no evidence for a benefit of specific patient education in reducing CKD progression [29, 30]. Awareness of CKD cannot be measured with claims data.

Serum creatinine measurements and urinary dip stick testing, which are prerequisites for staging of CKD, were performed predominantly in participants with impaired kidney function, but also very frequently in patients without renal impairment (Table 2). The frequency of measurements increased with increasing CKD stage and partially exceeded the monitoring recommendations of the KDIGO and NICE guidelines [2, 6]. These recommendations are based on expert consensus, because there are no empirical studies on monitoring intervals. The high frequency of measurements in many patients may be caused by the fact that anaemia and creatinine measurement are often ordered as part of routine laboratory testing and because creatinine used to be part of the 2-yearly preventive check-up examination (from the age of 35) and many physicians still tend to include it [31]. Additionally, it indicates a lack of coordination and communication in ambulatory care. Albuminuria was measured by urinary dip stick testing in the majority of participants. This might be due to the fact that dip stick testing is part of the preventive check-up examination. Quantitative measurement of albuminuria by ACR, as recommended by guidelines, is necessary at least once for the classification of CKD according to KDIGO [2]. The claims data indicate that quantitative albuminuria is rarely assessed. It must be kept in mind that data were collected prior to the release of the KDIGO guideline in 2012 and measurement of ACR was not formally required during the study period. Future assessment of quality of care for CKD should include at least one measurement of ACR.

The KDIGO guideline on mineral and bone disorder in chronic kidney disease (CKD-MBD) recommends with limited evidence to monitor for CKD-MBD every 6–12 months from stage G3 onwards [2, 12]. However, phosphate, calcium and parathyroid hormone assessments were significantly less frequently performed than recommended. NICE recommends monitoring only from stage G4 [6]. Awareness of monitoring for CKD-MBD seems to be low, but so is the evidence for the benefits of monitoring on clinically relevant endpoints. Therefore, measuring markers for CKD-MBD should not be part of a quality indicator set unless there is better evidence.

The KDIGO guideline recommends annual monitoring of haemoglobin values from CKD G3a and every six months from stage G4 [2]. NICE recommends testing patients with symptoms indicative of anaemia and recommends annual monitoring only from stage G3b onwards [6]. Actual haemoglobin testing was slightly higher than recommended by KDIGO in stage G3b and well above the recommended number of tests in stage G5. Given the high frequency of haemoglobin measurements this is a dispensable quality indicator in the German health care setting.

KDIGO and NICE recommend referral to a nephrologist from stage G4, or earlier in the presence of e.g. albuminuria, persistent haematuria or progression [6, 2, 8]. The German Societies for Nephrology (DGfN) and Internal Medicine (DGIM) recommend referral from G3b, or from G3a, if additional criteria such as proteinuria or refractory hypertension are met [14]. This recommendation was not consented and is not agreed upon by German Society for General Practice and Family Medicine (DEGAM). The German guideline for Diabetes and CKD (NVL) recommends referral for persons ≤ 65 years from G3a and > 65 years from G3b [7]. International clinical practice guidelines do not distinguish between a one-time consultation to exclude specific kidney disease needing specific treatment and continuing co-treatment of patients [2, 8]. The observed nephrology consultation rate was 25% for stage G4, well below the recommendations. However, in our analysis, only 10 out of 1778 participants were in stages G4-5. A retrospective German study reports that 58% of patients with CKD in stage G1-4 had been seen by a nephrologist [32]. A similar rate was observed in an Italian study where co-treatment was reported in 56% of patients in stages G4 and above [20, 33]. From a nephrological point of view, many patients are referred too late [27]. From the primary care point of view, the progression to ESRD is a rare event and there is often no specific therapy for CKD that cannot be provided in general practice [31, 34]. The conflict in risk perception between general practitioners and nephrologists is evident when the KDIGO risk model is applied to the SHIP-START cohort (Fig. 2) [2]. This table categorises patients with warning colours in 4 risk categories and is displayed in many guidelines. Unlike one might assume this is not the risk of progressing to ESRD, but combined risk for five events (acute renal failure, CKD progression, ESRD, all-cause mortality, cardiovascular mortality) [2]. It is not quantified what is assumed to be a moderate or high risk. In fact, the risk is calculated for 1000 observed patients’ years, not adjusted for patient’s age. In this model, a patient with stage G3a and proteinuria A3 carries a risk of 5/1000 for ESRD and is classified as high risk, independent of age [2]. This is overstating the perceived and real risk of CKD and has been criticised [35].

The reasons for late or non-referral to nephrology of patients with CKD are complex as observed in our and many other studies. Causal factors that were identified were disease-specific, patient-related, as well as primary care physician related [31, 32]. Since monitoring of laboratory parameters can be carried out in general practice, patients with stable renal function and known underlying diseases may not have been referred. It is possible that some patients were seen by nephrologists before the observation period or as inpatients, which could not be recorded in our analysis. Another reason for the reluctance to refer is age-related decline of kidney function. A large proportion of people with CKD in our study were older than 75 years (Table 1). From a general practitioner's perspective, age, comorbidity, previous course and the need for a specific nephrological intervention should be incorporated for referral recommendations in addition to eGFR. Referral to nephrology co-supervision as a quality indicator for ambulatory care of patients with CKD is therefore only reasonable when a moderate performance target is set.