MADRID — A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.
During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians (SEMG), Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital in Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.
The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.
For his part, Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
Candidates for Screening
“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”
Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Alcázar. In his opinion, “the answer to whether we should be screening earlier…is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”
Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate <60 mL/min; and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio >30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
Two Related Parameters
Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”
On this point, Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of <60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (ie, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
Reducing Late Diagnosis
According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”
Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
Also fundamental is having a detailed understanding of how staging is performed. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.
Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”
He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
Reducing Cardiovascular Risk
Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels <130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure (SBP). If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”
For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be <100 mg/dL; for those at moderate risk, <70 mg/dL; and for those at severe risk, <55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Alcázar.
Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
When asked whether the course of chronic kidney disease can be changed, Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence, the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”
Regarding drug-based therapy, Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Alcázar.
What Professionals Expect
Benedito also explained the criteria for referral to a specialist: glomerular filtration rate <30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio >300 mg/g, acute worsening of renal function, progressively worsening of renal function of >5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of <10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.
Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”
Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”
This article was translated from the Medscape Spanish Edition.
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