The first appointment with a nephrologist: Brazilian patients’ demographic and kidney function characteristics. A retrospective study

ABSTRACT BACKGROUND: The number of nephrologists has risen slowly, compared with the prevalence of chronic kidney disease (CKD) in Brazil. Data on patients referred to nephrology outpatient clinics remains scarce. OBJECTIVE: To determine the demographic and kidney function characteristics of patients at their first appointment with a nephrologist. DESIGN AND SETTING: Retrospective study conducted at three nephrology outpatient clinics (public and private services), in São Paulo, Brazil. METHODS: From December 2019 to February 2020, we collected patient data regarding demographics, kidney function parameters and comorbidities. We then analyzed data on 394 patients who met a nephrologist for their first appointment. RESULTS: The main comorbidities were hypertension (63.7%), diabetes (33.5%) and nephrolithiasis (22.3%). Regarding CKD stages, 24.1%, 9.1%, 13.7%, 15.2%, 15.2% and 2.3% of the patients were in stages 1, 2, 3a, 3b, 4 and 5, respectively. Proteinuria was absent or mild, moderate and high in 17.3%, 15.2% and 11.7%, respectively; and 16.2% had not undergone previous investigation of serum creatinine or proteinuria (55.8%). For 17.5%, referral to a nephrologist occurred late. Patients in public services were older than those in private services (59 years versus 51 years, respectively; P = 0.001), more frequently hypertensive (69.7% versus 57.5%; P = 0.01) and reached a nephrologist later (22.4% versus 12.4%; P = 0.009). CONCLUSION: Referrals to a nephrologist were not being made using any guidelines for CKD risk and many cases could have been managed within primary care. Late referral to a nephrologist happened in one-fifth of the cases and more frequently in the public service.

that 52% of the patients assisted by a nephrologist did not need to be assessed or treated by this specialty at their first appointment. 13 Another study showed that 35.7% of the patients assessed by nephrologists had stages 1 and 2 of CKD and only a few of them (26%) presented higher levels of proteinuria or albuminuria, meaning that many patients could have continued to be cared for within primary care. 14

OBJECTIVE
Because of the need for accurate medical referral to nephrologists and the lack of these specialists, the aim of this study was to describe the characteristics (sociodemographic and CKD stages) of patients who were assessed by nephrologists at their first appointment, in both public and private services.

Study design and participants
This was a multicenter retrospective study based on medical records. We included three outpatient clinics in the metropolitan area of São Paulo: two clinics affiliated with private health insurance services and one public clinic within the Brazilian National Health System (Sistema Único de Saúde, SUS). We analyzed information on first appointments with a nephrologist that took place between December 2019 and February 2020, among patients who were ≥ 18 years old. We excluded those who had undergone kidney transplantation or who were on kidney replacement therapy. In the Brazilian public service, patients can only reach specialists through a medical referral from primary care or from other specialists. In private services, patients can reach specialists either through referrals or through their own initiative.
The protocol for this study was approved by the Ethics Committee of Universidade Federal de São Paulo on June 5, 2020 (CAAE 31053420.9.1001.5505).

Definitions and parameters of interest
Basic characteristics and clinical information relating to diagnoses of hypertension, diabetes mellitus (DM), urinary lithiasis, recurrent urinary tract infection, polycystic kidney disease and glomerulonephritis were obtained from the patients' charts.
We defined hypertension as the use of anti-hypertensive drugs or the presence of this diagnosis in the patient's chart. DM was defined from use of oral antidiabetic drugs or insulin therapies or the presence of this diagnosis in the patient's chart.
Laboratory assessments included serum creatinine and proteinuria. We used serum creatinine, age, and gender to determine the estimated glomerular filtration rate (eGFR), in accordance with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. 15 The racial factor was not included in the eGFR calculation because of the multiethnic composition of the Brazilian population and because of a previous study that demonstrated that this adjustment did not contribute to greater accuracy in this population. 16 CKD was defined as eGFR < 60 ml/min/1.73 m 2 or the presence of biomarkers for renal dysfunction, such as proteinuria, dysmorphic hematuria or abnormal kidney ultrasound. We classified CKD into five stages in accordance with the current guidelines: stage 1 (eGFR ≥ 90 ml/min/1.73 m² and any renal dysfunction biomarker); stage 2 (eGFR of 60-89 ml/min/1.73 m² and any renal dysfunction biomarker); stage 3a (eGFR of 45-59 ml/ min/1.73 m²), stage 3b (eGFR of 30-44 ml/min/1.73 m²); stage 4 (eGFR of 15-29 ml/min/1.73 m²); and stage 5 (eGFR < 15 ml/ min/1.73 m²). We considered stages 3b, 4 and 5 to be advanced CKD. 5 We used the following methods to determine the levels of proteinuria: urinalysis (dipstick); random urinary albumin-to-creatinine ratio (ACR); random urinary protein-to-creatine ratio (PCR); 24-hour albuminuria; and 24-hour proteinuria. We stratified the patients into three categories according to their level of proteinuria: absent or mild (urinalysis negative or 1+, ACR < 30 mg/g, PCR < 150 mg/g, 24-hour albuminuria < 30 mg or 24-hour proteinuria < 150 mg); moderate (1+ or 2+ on urinalysis, ACR of 30-300 mg/g, PCR of 150-500 mg/g, 24-hour albuminuria of 30-300 mg and 24-hour proteinuria of 150-1000 mg); and high (3+ on urinalysis, ACR > 300 mg/g, PCR > 500 mg/g, 24-hour albuminuria > 300 mg and 24-hour proteinuria > 1000 mg). 5 Among the reasons for referring patients to a nephrologist, we considered the following: hypertension, diabetes, nephrolithiasis, recurrent urinary tract infection, hematuria (red blood cells above the laboratory reference levels) and acute kidney injury (serum creatinine > 0.3 mg/dl, in comparison with the baseline serum creatinine, investigated within the preceding three months before data collection). 17 We collected data on the specialties from which patients were referred to a nephrologist (internal medicine, endocrinology, cardiology or urology). Also, we registered whether patients reached a nephrologist by themselves, with no medical referral. Late referral was defined as referral in stages 4 or 5. [7][8][9][10][11] Patients for whom serum creatinine and proteinuria information was available were classified into CKD risk groups: low risk, moderate risk, high risk and very high risk. 18
"Z (α/2) " is the critical value for a normal distribution when α/2 (confidence interval = 95%, α = 0.05 and critical value of 1.96), "p" represents the proportion of the referred patients in the sample, "error" is the estimated margin around "p", and "n" means the size of the population. We estimated that 40% of the patients were correctly referred to a nephrologist, in conformity with previous research. 12,13 We considered that the size of the population was 100,000 inhabitants. We set error and confidence intervals of 8% and 95%, respectively. In this manner, we determined that a minimum of 144 medical records from public and private services would need to be analyzed. We used the statistical package SPSS, version 18.0 (SPSS Inc., Chicago, Illinois, United States). We described the frequencies of the categorical variables. Age showed non-normal distribution and so we presented data on its median and interquartile range (IQR). We used χ² or Fisher exact tests to compare the frequencies, as appropriate. Also, we used the Mann-Whitney test to compare non-normal continuous variables. We set the significance level for P-values at < 0.05.

RESULTS
The demographic and clinical characteristics (renal data and comorbidities) of our sample are shown in According to the risk map for CKD, 19 19.9% of the patients were at low risk, 21% at moderate risk, 24% at high risk and 34.8% at very high risk ( Table 2). Compared with patients seen at private outpatient clinics, those seen within the public healthcare system presented lower probability of being at low risk of CKD (11.2% versus 32.4%, respectively; P < 0.001) and higher risk of CKD (69.4% versus 44.1%; respectively, P = 0.001) ( Table 3).

DISCUSSION
The Brazilian guidelines regarding CKD define that the risk stratification should be conducted within primary care through assessing serum creatinine and proteinuria levels. 6 The Brazilian guidelines for hypertension and DM also include serum creatinine and proteinuria tests performed annually, as a minimum. 20 This study showed that for one patient in six, no information on serum creatinine was available at the time of the first appointment with a nephrologist. Additionally, more than half of the patients were not investigated regarding urinary protein levels. Failure in screening for CKD has also been observed in other regions in which the rates of serum creatinine monitoring (32.5% to 73.5%) and proteinuria assessment (2.5% to 40%) were low. [21][22][23] Considering the impact of aging on the decline in renal function, 24 23 patients (5.9% of the sample) may not necessarily have needed to be referred to a nephrologist (patients aged > 75 years; eGFR < 60; and proteinuria assessment not performed or absent).
Nonetheless, most of them were referred without any assaying of proteinuria (20 patients).
The prevalences of hypertension and DM in our sample were 63.7% and 33.5%, respectively. According to a survey by the Brazilian Nephrology Society, 2 the most common causes of CKD stage 5 are hypertension and DM. Indeed, these diseases can be identified and prevented within primary care. [25][26][27][28] Proteinuria plays an important role in accelerating the progression rate of CKD, but its assessment was neglected among 52% of hypertensive and 44% of diabetic patients. Although testing of proteinuria levels is important, this was not usually performed.
Compared with the patients seen via the private healthcare service, the public service patients who reached a nephrologist showed higher rates of advanced CKD (stages 3b, 4, and 5), but serum creatinine and proteinuria were more frequently assessed before the referral. Because of the scarcity of nephrology appointments within the public service, those individuals may reach the

CONCLUSIONS
There are opportunities to improve the stratification of the risk of chronic kidney disease (CKD) in both public and private healthcare services. Proteinuria plays an important role in predicting CKD and seems to have been ignored in many patients who are at high risk of CKD, such as hypertensives and diabetics. Late referral to a nephrologist and unnecessary appointments with this specialist are common in public and private services, respectively.
Further research aimed at monitoring healthcare quality in the early stages of CKD may improve the way in which physicians refer their patients to a nephrologist.