Why the nephrologist sees it first — the cardio-renal-metabolic axis
Anyone trained in nephrology learns it early: the kidney is the system that warns first. The revolution of the last five years was the rest of medicine finally accepting it — and the trials of the last decade (DAPA-CKD, EMPA-KIDNEY, FIDELIO, FLOW) put the reading at the center of the table.
The biggest revolution in preventive medicine over the past five years was not a surgery, was not an isolated drug. It was a reorganization: understanding that heart, kidney, and metabolism are not three separate systems — they are a single system, with a single inflammatory root and a single therapeutic axis.
The technical name is the cardio-renal-metabolic axis, formalized by the American Heart Association in 2023 in a statement by Ndumele and colleagues. What it organizes, in practice, is the recognition that chronic kidney disease rarely begins in the kidney. It begins in long-standing metabolic inflammation, in poorly controlled hypertension, in silent hyperinsulinemia, in subclinical endothelial dysfunction.
And the kidney, by a simple physiologic feature — extremely high-precision filtration over a delicate vascular bed — usually signals first. Microalbuminuria, slow decline of estimated glomerular filtration rate, loss of functional reserve. Signs that appear ten or fifteen years before the severe picture. When I coordinated the nephrology residency at Santa Casa de Londrina, I observed it again and again — the kidney was almost always the first to confess.
That is why I think the nephrologist, when trained to look at the silent window, sees it first. The test most frequently ordered — kidney function — is, paradoxically, one of the best early markers of systemic disease.
The pharmacological landmarks of the last decade confirm the axis in clinical practice. SGLT2 inhibitors came first: DAPA-CKD (Heerspink, NEJM 2020) showed reduction in chronic kidney disease progression and cardiovascular death with dapagliflozin even in non-diabetic patients. EMPA-KIDNEY (NEJM 2023) confirmed the effect in a broader cohort. Finerenone, in FIDELIO-DKD (Bakris, NEJM 2020), demonstrated a reduction in renal and cardiovascular events in type-2 diabetes with nephropathy. More recently, FLOW (Perkovic, NEJM 2024) brought semaglutide into the game: a 24% reduction in the composite renal-cardiovascular endpoint in patients with T2D and CKD.
Three different drug classes, three different targets — all protecting the three systems in parallel. It is not coincidence. It is the clinical confirmation that the axis is real.
Preventive nephrology is not a new specialty. It is a way of reading nephrology that is finally being accepted.
Excerpt from Chapter 9 of the book BEFORE — The silent window between normal and optimal — a decade where health is decided.
- Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. "Dapagliflozin in Patients with Chronic Kidney Disease." N Engl J Med. 2020;383(15):1436-1446.
- EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. "Empagliflozin in Patients with Chronic Kidney Disease." N Engl J Med. 2023;388(2):117-127.
- Bakris GL, Agarwal R, Anker SD, et al. "Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes." N Engl J Med. 2020;383(23):2219-2229.
- Perkovic V, Tuttle KR, Rossing P, et al. "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes." N Engl J Med. 2024;391(2):109-121.
- Ndumele CE, Rangaswami J, Chow SL, et al. "Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association." Circulation. 2023;148(20):1606-1635.
Clinical review. Medical content authored by Dr. Getúlio Amaral Filho · CRM-PR 21,876 · RQE 16,038 (Nephrology).
This content is educational and does not constitute medical prescription. Each case is unique — for individual evaluation and care, consult a physician.
Pre-diabetes is not a phase. It is a five-year window.
An HbA1c between 5.7% and 6.4% is usually treated as a vague warning — "let's repeat it in a year." The literature is more uncomfortable: every year without action increases the probability of progression and narrows the window in which reversal is still the most likely outcome.
Lp(a): the test your father's cardiologist didn't order
One in five people has elevated lipoprotein(a). It is genetically determined, doubles or triples the risk of heart attack and aortic stenosis — and almost never appears on a checkup. Measuring it once in a lifetime changes decades of clinical decisions.
Ferritin between 30 and 100: the normality that drains women
The 'normal' stamp on a ferritin result is one of the most expensive errors in contemporary medicine. I have seen too many women pushed toward the psychiatrist with disabling fatigue — when the problem was the wrong ruler at the lab.