Blood pressure and the renin-angiotensin system are where the mechanism of Chapter 2 meets the treatment of Part 2. Systemic hypertension is the pressure that the failing kidney transmits to its own glomeruli, and the renin-angiotensin system is the lever that both sustains glomerular hypertension and drives fibrosis. So the first two progression-slowing interventions are not separate ideas but two ways of relieving the same glomerular pressure — and the evidence for them, from SPRINT to the nephropathy trials, is among the strongest in the field.
Why blood pressure matters in CKD
Hypertension and CKD are locked in a two-way relationship: hypertension damages the kidney, and the damaged kidney raises blood pressure through sodium retention and neurohormonal activation. The renal harm is mechanistic. When systemic pressure rises and the afferent arteriole is dilated — as it is in the hyperfiltering kidney of Chapter 2 — that systemic pressure is transmitted into the glomerulus, raising intraglomerular pressure and feeding the final common pathway. Lowering systemic blood pressure therefore does double duty: it reduces the cardiovascular events that are the leading cause of death in CKD, and it lowers the glomerular pressure that drives progression. The two goals usually align.
The target, and why measurement is inseparable from it
The blood-pressure target in CKD has moved lower, and the reason is SPRINT, which compared a systolic target below 120 with one below 140 and found fewer cardiovascular events and lower mortality at the lower target, consistently in the CKD subgroup, at the cost of more — mostly reversible — AKI and electrolyte disturbance. On that basis KDIGO suggests a systolic target below 120 mmHg for most adults with CKD, individualised for frailty, falls risk, life expectancy, and tolerability. But the target cannot be separated from how it is measured. SPRINT used a standardised, frequently unattended, automated office measurement that reads several millimetres of mercury lower than the hurried cuff in a busy clinic. A target of 120 means a standardised 120, and applying it to a casually measured clinic pressure will over-treat — chasing a number that was never the number the trial used. The practical corollary is that the measurement method must match the target: standardised office readings, supported by home and ambulatory monitoring, not the corridor blood pressure.
RAAS blockade: relieving the glomerular pressure
If glomerular hypertension is the engine, the renin-angiotensin system is its throttle, because angiotensin II constricts the efferent arteriole to hold glomerular pressure up. Blocking the system — with an ACE inhibitor or an ARB — dilates the efferent arteriole, lowers intraglomerular pressure, and reduces proteinuria, the mediator of Chapter 2. And because angiotensin II is also directly profibrotic, blockade removes a fibrotic signal as well, which is why its benefit exceeds what its modest blood-pressure lowering alone would predict. The landmark trials established this across the spectrum: the captopril study in type 1 diabetic nephropathy, the losartan and irbesartan trials in type 2, the ramipril trials in non-diabetic proteinuric disease and in hypertensive nephrosclerosis. A consistent thread runs through them — the benefit is proportional to the baseline proteinuria, so the more protein the patient is leaking, the more RAAS blockade has to offer. This is the single most important drug class in proteinuric CKD.
The creatinine rise that means it is working
Starting RAAS blockade usually nudges the creatinine up, and this alarms the unwary into stopping the very drug that helps. The rise is the intended effect: dilating the efferent arteriole lowers glomerular pressure, and a lower glomerular pressure means a slightly lower GFR and a slightly higher creatinine. A rise of up to about 30% from baseline within the first weeks is expected and acceptable; it stabilises, and the drug should be continued, because that small functional drop is the price of the pressure relief that protects the kidney long-term. What is not acceptable is a steeper rise. A jump beyond roughly 30%, or a sharp one, should trigger a search for volume depletion, an NSAID, or — the classic catch — bilateral renal-artery stenosis, in which the efferent constriction was all that was maintaining filtration. Distinguishing the benign expected rise from the pathological one is a core skill of using these drugs well.
Hyperkalaemia: manage it, don't capitulate to it
The commonest reason RAAS blockade is stopped is hyperkalaemia, and stopping is usually the wrong response. Because the drug class is the cornerstone of progression-slowing therapy, the goal is to keep the patient on it by controlling the potassium rather than abandoning the protection. Dietary potassium restriction, a diuretic to enhance renal potassium excretion, correction of acidosis, and the modern potassium binders — patiromer and sodium zirconium cyclosilicate — all allow RAAS blockade to continue at effective doses. Reflexively withdrawing the ACE inhibitor at the first elevated potassium forfeits long-term kidney and cardiovascular benefit for a problem that is usually manageable. Stopping is reserved for hyperkalaemia that cannot be controlled by these means.
Two things not to do, and one to keep doing
Three evidence-based rules close the therapeutic story. First, do not combine an ACE inhibitor with an ARB: dual RAAS blockade was tested directly and caused more AKI and hyperkalaemia with no improvement in outcomes, and the combination with a direct renin inhibitor was worse still. One agent, titrated up, not two. Second — and more recent — do not routinely stop RAAS blockade as CKD advances. The long-standing worry that these drugs accelerate decline in advanced disease was tested in the STOP-ACEi trial, which found that stopping the inhibitor in advanced CKD did not preserve the GFR trajectory or improve outcomes compared with continuing. The implication reverses old habit: continue RAAS blockade even in advanced CKD rather than discontinuing it as the eGFR falls, unless there is a specific intolerance. Third, the positive instruction: titrate to the maximum tolerated dose, since the antiproteinuric and protective effect is dose-related, monitoring creatinine and potassium a week or two after each change, and substitute an ARB if an ACE inhibitor causes the bradykinin cough or angioedema.
Where the evidence is firm, and where it argues
The firm parts are substantial: that RAAS blockade slows proteinuric CKD beyond its blood-pressure effect, that dual blockade harms, and that lower blood pressure reduces cardiovascular events are all well established. The arguments are at the edges and they matter. The SPRINT-derived target of 120 is firm only for the measurement SPRINT used and the population it studied — it excluded diabetes and prior stroke, and ACCORD-BP found a neutral primary result in diabetics — so the target is a default to be individualised, not a universal mandate. How aggressively to push blood pressure in the frail and fall-prone, and how widely to apply the lower target outside the trial populations, remain genuine judgements. The honest position is to treat the strong evidence as strong and the extrapolations as extrapolations, and to let measurement method, proteinuria, age, and tolerability shape the target for the individual in front of you.
