Renal: Basics

• Anatomy: The Kidneys | Renal Blood Supply | The Nephron and Glomerulus | Ureters, Bladder, Prostate and Urethra | Kidney Development and Congenital Problems
• Physiology: Glomerular Filtration and Its Control | Measuring Kidney Function | What Each Part of the Tubule Does | Sodium, Water and Concentrating Urine | Potassium Balance | Acid–Base and the Kidney | Calcium, Phosphate and Magnesium | Kidney Hormones | How the Kidney Fails | Nephrotic and Nephritic Syndromes | Normal Values
• Pharmacology: Prescribing in Kidney Disease | Diuretics | ACE Inhibitors and ARBs | Drugs That Protect the Kidneys | Treating Hyperkalaemia | Bone, Phosphate and Acidosis Drugs | Renal Anaemia Drugs | Immunosuppression in Kidney Disease and Transplant | Stone, Prostate and Bladder Drugs | Antibiotics for Urinary Infection | Dialysis and Drugs | Drugs That Damage the Kidneys
• Revision: Drug Reference Table | Spot the Answer | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🫘 Renal anatomy, physiology and pharmacology — the kidneys filter about 180 litres of blood plasma a day and keep almost all of it, fine-tuning water, salt, potassium, acid and calcium, and getting rid of waste and drugs. Knowing what each part of the nephron does explains how diuretics work, why electrolytes go wrong, and why so many drugs need dose changes or cause kidney injury.
Your four questions for every drug: How does it work? What is it used for? What are the important side effects and safety issues? What does it interact with, and how is it monitored?

The Kidneys

• Position — behind the peritoneum (retroperitoneal) on the back wall of the abdomen, from about T12 to L3; the right kidney is slightly lower (pushed down by the liver). Each is about 11 cm long and weighs about 150 g.
• Coverings — renal capsule, perirenal fat, and the renal (Gerota's) fascia, which also encloses the adrenal gland.
• Relations — the 12th rib, diaphragm and pleura lie behind the upper pole (pneumothorax risk in kidney surgery and biopsy); the liver, duodenum and colon are in front on the right; the spleen, pancreas tail, stomach and colon on the left.
• The hilum — from front to back: renal vein, renal artery, renal pelvis ("VAP").
• Left renal vein — longer; crosses in front of the aorta under the SMA; receives the left gonadal and left adrenal veins — so a left renal tumour growing into the vein can cause a left varicocele. Compression between the aorta and SMA ("nutcracker") can cause haematuria.
• Internal structure — outer cortex (glomeruli), inner medulla (pyramids with loops of Henle and collecting ducts), papillae draining into the minor and major calyces and the renal pelvis.
• Nephrons — about 1 million per kidney; they can't be replaced, and numbers fall with age (about 1 mL/min/year of GFR after 40 in many people).
• Kidney pain — loin (flank) pain from stretching of the capsule (pyelonephritis, obstruction); renal colic — severe waxing and waning loin-to-groin pain from a ureteric stone.

Renal Blood Supply

• The kidneys receive about 20–25% of cardiac output (about 1 L of blood a minute) — far more than they need for oxygen, because their job is filtering.
• Arterial path — renal artery (from the aorta at about L1–L2) → segmental arteries (end arteries — blockage causes a wedge-shaped infarct) → interlobar → arcuate → interlobular → afferent arteriole → glomerulus → efferent arteriole → peritubular capillaries (cortex) and vasa recta (medulla).
• Two arterioles control filtration pressure:
  • Afferent (in) — kept open by prostaglandins; NSAIDs block these → afferent narrows → GFR falls (especially when the kidney is under stress — dehydration, heart failure, cirrhosis, CKD).
  • Efferent (out) — tightened by angiotensin II to keep pressure up; ACE inhibitors and ARBs relax it → GFR falls a little (and protein leak falls — the protective effect); a big fall suggests bilateral renal artery stenosis.
• The medulla has a poor oxygen supply (the slow vasa recta preserve the concentration gradient) — so it is easily damaged by low blood pressure, NSAIDs, sickle cell disease, diabetes and infection → papillary necrosis, and the thick ascending limb is very prone to acute tubular necrosis.
• Renal artery stenosis — atherosclerosis (older people, smokers, vascular disease) or fibromuscular dysplasia (young women — "string of beads"); causes hypertension, flash pulmonary oedema, unequal kidney sizes, and AKI with ACE inhibitors.
• Renal vein thrombosis — in nephrotic syndrome (especially membranous), dehydration in babies, tumours — flank pain, haematuria.

The Nephron and Glomerulus

• Parts of the nephron — glomerulus and Bowman's capsule → proximal convoluted tubule → loop of Henle → distal convoluted tubule → collecting duct.
• The filtration barrier — three layers that hold back blood cells and most protein (by size and negative charge):
  • Fenestrated endothelium — damaged in thrombotic microangiopathy (HUS, pre-eclampsia).
  • Glomerular basement membrane (type IV collagen) — targeted in anti-GBM disease (Goodpasture's); abnormal in Alport syndrome (with deafness and eye problems) and thin basement membrane disease.
  • Podocytes with slit diaphragms — injured in minimal change disease, FSGS and membranous nephropathy → nephrotic syndrome (heavy protein loss).
• Mesangial cells — support the capillary loops; IgA deposits here in IgA nephropathy.
• Juxtaglomerular apparatus — where the distal tubule touches its own glomerulus:
  • Macula densa cells sense salt in the distal tubule (tubuloglomerular feedback).
  • Juxtaglomerular (granular) cells in the afferent arteriole release renin.
• Cortical and juxtamedullary nephrons — the deep (juxtamedullary) nephrons have long loops of Henle and do most of the urine concentrating.
• Urine microscopy clues — red cell casts and dysmorphic red cells mean glomerular bleeding (glomerulonephritis); white cell casts — pyelonephritis or interstitial nephritis; muddy brown granular casts — acute tubular necrosis.

Ureters, Bladder, Prostate and Urethra

• Ureters — about 25–30 cm; carry urine by peristalsis; pass over the pelvic brim at the bifurcation of the common iliac artery, then under the uterine artery in women ("water under the bridge" — at risk in hysterectomy) and under the vas deferens in men.
• Three narrow points where stones get stuck — the pelviureteric junction, the pelvic brim, and the vesicoureteric junction (the narrowest).
• Bladder — the detrusor muscle; the trigone between the two ureteric openings and the urethra; usual capacity about 400–600 mL (first urge at about 150–250 mL).
  • Bladder filling and emptying — sympathetic (T10–L2) relaxes the detrusor and closes the bladder neck (filling); parasympathetic (S2–S4) contracts the detrusor (emptying); pudendal nerve controls the external sphincter (see the Neurology Anatomy, Physiology and Pharmacology chapter).
  • Drug targets — antimuscarinics and beta-3 agonists relax the detrusor; alpha-blockers relax the bladder neck and prostate.
• Urethra:
  • Female — about 4 cm long — the reason UTIs are much more common in women.
  • Male — about 20 cm (prostatic, membranous and penile parts) — catheterisation is harder; strictures after infection or instrumentation.
• Prostate — surrounds the urethra below the bladder:
  • Benign enlargement (inner transition zone) — compresses the urethra → poor stream, hesitancy, frequency, nocturia, retention.
  • Cancer (mostly in the outer peripheral zone) — felt as a hard, irregular gland on rectal examination; often no symptoms early.
  • Growth depends on DHT (testosterone converted by 5-alpha-reductase — blocked by finasteride).
• Obstruction anywhere in the tract causes post-renal AKI (if both kidneys, or a single kidney) and infection; an obstructed infected kidney is an emergency (urgent drainage — nephrostomy or stent).

Kidney Development and Congenital Problems

• The permanent kidney (metanephros) forms from two parts — the ureteric bud (becomes the collecting system — ureter, pelvis, calyces, collecting ducts) and the metanephric blastema (becomes the nephrons). The kidneys start in the pelvis and ascend.
• Horseshoe kidney — the lower poles fuse and get caught under the inferior mesenteric artery; linked to Turner syndrome; more stones, infections and obstruction.
• Duplex kidney — two ureters from one kidney; the upper moiety ureter may open ectopically (constant dribbling in girls) or end in a ureterocele.
• Pelviureteric junction obstruction — hydronephrosis; loin pain after drinking a lot (e.g. alcohol).
• Posterior urethral valves — boys; bladder outflow obstruction before birth — bilateral hydronephrosis, kidney damage.
• Vesicoureteric reflux — urine flows back up the ureter (short intramural tunnel) → recurrent pyelonephritis and scarring in children.
• Potter sequence — no fetal urine (kidney agenesis) → oligohydramnios → lung hypoplasia, squashed facial features and limb deformities.
• Autosomal dominant polycystic kidney disease (ADPKD — PKD1 about 85%, more severe; PKD2) — enlarging cysts, hypertension, haematuria, pain, CKD (often needing dialysis by middle age with PKD1), liver cysts, berry aneurysms (screen if family history of SAH), mitral valve prolapse; tolvaptan slows growth in selected patients.
• Autosomal recessive PKD — babies; large kidneys, liver fibrosis.

Glomerular Filtration and Its Control

• GFR — about 120 mL/min (about 180 L a day) in a healthy young adult; only about 1–2 L of urine is made — over 99% of the filtrate is reabsorbed.
• What drives filtration — pressure in the glomerular capillaries pushing fluid out, opposed by pressure in Bowman's space (rises with obstruction) and the pull of plasma proteins (oncotic pressure).
• Autoregulation — GFR stays fairly steady across a wide range of blood pressure (mean arterial pressure roughly 80–180 mmHg) by:
  • Myogenic response — the afferent arteriole tightens when stretched.
  • Tubuloglomerular feedback — the macula densa senses more salt and constricts the afferent arteriole.
  • Hormones — prostaglandins dilate the afferent arteriole; angiotensin II constricts the efferent arteriole.
• Autoregulation fails at low blood pressure (sepsis, bleeding, heart failure), with chronic hypertension (the "safe" range shifts upwards — older hypertensive people may get AKI at blood pressures that look normal), and when drugs block the protective hormones.
• The "triple whammy" — NSAID (afferent narrowing) + ACE inhibitor or ARB (efferent relaxation) + diuretic (less volume) → high risk of AKI, especially in older people with intercurrent illness.
• Hyperfiltration — high pressure in the remaining glomeruli in diabetes, obesity and CKD damages them over time; ACE inhibitors, ARBs and SGLT2 inhibitors lower this pressure — the reason they cause a small early dip in eGFR but protect the kidneys long term.

Measuring Kidney Function

• Creatinine — made by muscle at a steady rate and filtered by the kidney:
  • Depends on muscle mass — low in frail older people, amputees and the malnourished (who can have a "normal" creatinine with poor function); high in muscular people and after eating cooked meat.
  • The GFR can fall by about half before creatinine rises above the normal range.
  • Some drugs block creatinine secretion by the tubules (trimethoprim, cimetidine, some HIV drugs such as dolutegravir) → creatinine rises without a true fall in GFR.
  • In AKI, creatinine lags behind — it takes time to build up.
• eGFR — estimated from creatinine, age and sex (UK labs use the CKD-EPI equation, without an ethnicity adjustment — NICE NG203); only valid when kidney function is stable (not in AKI); less accurate at extremes of body size, in pregnancy, amputees and muscle disease.
• Cystatin C — less affected by muscle mass; used to confirm CKD when eGFR is borderline.
• Creatinine clearance (Cockcroft–Gault) — uses age, weight, sex and creatinine; the BNF recommends it for dosing drugs with a narrow therapeutic range (DOACs, aminoglycosides, vancomycin, digoxin, lithium) and in older people and those at extremes of weight.
• Urea — raised by dehydration, upper GI bleeding (digested blood protein), steroids, high protein intake and tissue breakdown; low in liver failure, malnutrition and pregnancy. A urea rising much faster than creatinine suggests dehydration or a GI bleed.
• Urine albumin-to-creatinine ratio (ACR) — the best test for kidney damage and risk:
  • Under 3 mg/mmol — normal (A1).
  • 3–30 mg/mmol — moderately increased (A2).
  • Over 30 mg/mmol — severely increased (A3); over 70 mg/mmol — consider referral.
• CKD — abnormal kidney structure or function for more than 3 months: eGFR stages G1 (90 or more, with other markers of damage), G2 (60–89), G3a (45–59), G3b (30–44), G4 (15–29), G5 (under 15); combined with the ACR category (A1–A3) to judge risk.
• AKI (KDIGO) — creatinine rise of 26.5 micromol/L or more within 48 hours, or 1.5 times baseline within 7 days, or urine output under 0.5 mL/kg/hour for 6 hours; staged 1–3.

What Each Part of the Tubule Does

• Glucose — completely reabsorbed until blood glucose exceeds about 10 mmol/L (the renal threshold), then it spills into urine (glycosuria → osmotic diuresis → thirst and polyuria). SGLT2 inhibitors lower the threshold so glucose is lost at normal levels; glycosuria with normal blood glucose also occurs in pregnancy and Fanconi syndrome.
• Why diuretic strength differs — loop diuretics block a segment handling 25% of sodium (strong); thiazides block 5–10% (moderate); potassium-sparing diuretics act on the last few percent (weak), but matter for potassium.
• Why diuretics lose potassium — more sodium and fluid reach the collecting duct, where sodium is swapped for potassium (and acid), worsened by the aldosterone rise that follows volume loss. Diuretics acting before the collecting duct (loop, thiazide) cause low potassium and alkalosis; those acting in it (spironolactone, amiloride) cause high potassium.
• Calcium — loop diuretics increase urine calcium (used in hypercalcaemia after fluids); thiazides reduce urine calcium (raise blood calcium; prevent calcium stones).

Sodium, Water and Concentrating Urine

• Two separate things are controlled:
  • Total body sodium determines extracellular fluid volume (oedema or dehydration) — controlled by the RAAS, sympathetic nerves and natriuretic peptides.
  • Water balance determines the sodium concentration (plasma osmolality) — controlled by ADH and thirst.
  • So hyponatraemia is usually a water problem (too much water relative to sodium), not a lack of salt.
• Concentrating urine — the loop of Henle builds a salty gradient in the medulla (countercurrent multiplier, helped by urea); when ADH opens water channels in the collecting duct, water flows out into this salty medulla → concentrated urine (up to about 1,200 mOsm/kg). Without ADH, urine can be as dilute as about 50 mOsm/kg.
• Loss of concentrating ability — loop diuretics (wash out the gradient), CKD, older age, sickle cell disease, lithium, high calcium, low potassium (nephrogenic DI), cranial DI.
• Thiazides and hyponatraemia — thiazides act in the cortex, so the kidney can still concentrate urine but can't dilute it well → water retention → hyponatraemia (especially older women, low salt intake, high fluid intake). Loop diuretics cause hyponatraemia less often.
• Interpreting urine sodium — under about 20 mmol/L suggests the kidney is trying to hold on to sodium (dehydration, heart failure, cirrhosis); over 30 mmol/L with low plasma osmolality suggests SIADH, diuretics, adrenal insufficiency or salt-wasting kidneys (misleading if on diuretics).
• Fluids — 0.9% sodium chloride stays mostly in the extracellular space; 5% glucose spreads throughout all body water (effectively free water — can cause hyponatraemia); large volumes of 0.9% saline cause hyperchloraemic acidosis — balanced crystalloids (Hartmann's, Plasma-Lyte) are often preferred (NICE CG174).

Potassium Balance

• About 98% of potassium is inside cells — small shifts change the blood level a lot.
• Things that move potassium into cells (lower blood potassium) — insulin, beta-2 agonists (salbutamol), alkalosis, refeeding.
• Things that move potassium out (raise blood potassium) — acidosis, insulin deficiency (DKA — total body potassium is low despite a high level), cell breakdown (rhabdomyolysis, tumour lysis, haemolysis, burns), beta-blockers, digoxin toxicity, suxamethonium.
• Kidney excretion — mainly in the collecting duct, increased by aldosterone, more sodium and fluid reaching the collecting duct, and high potassium itself.
• Causes of high potassium:
  • Kidney failure (AKI, advanced CKD).
  • Drugs — ACE inhibitors, ARBs, spironolactone, eplerenone, finerenone, amiloride, trimethoprim (blocks ENaC like amiloride), heparin (suppresses aldosterone), NSAIDs, ciclosporin and tacrolimus, potassium supplements and salt substitutes.
  • Low aldosterone — Addison's disease, type 4 RTA (diabetes).
  • False high (pseudohyperkalaemia) — haemolysed sample, delayed processing, very high white cells or platelets, fist clenching — repeat if unexpected (but don't delay treatment if the ECG is abnormal).
• ECG changes of high potassium — tall tented T waves → flat or absent P waves, long PR → broad QRS → sine wave → VF or asystole. The ECG doesn't reliably reflect the level — treat a very high level even with a normal ECG.
• Causes of low potassium — diuretics (loop, thiazide), vomiting and diarrhoea, laxative misuse, insulin and salbutamol, Conn's and Cushing's, low magnesium (replace magnesium or potassium won't correct), refeeding. ECG — flat T waves, U waves, long QT; increases digoxin toxicity.

Acid–Base and the Kidney

• The kidneys keep the body's bicarbonate by:
  • Reabsorbing filtered bicarbonate (mostly in the proximal tubule, using carbonic anhydrase).
  • Making new bicarbonate for every acid ion excreted — as ammonium and phosphate ("titratable acid") in the collecting duct.
• CKD — less ammonium excretion → metabolic acidosis (first normal anion gap, then raised anion gap in advanced disease as phosphate and other acids build up) → bone loss, muscle wasting, faster CKD progression.
• Renal tubular acidosis (normal anion gap acidosis):
  • Type 1 (distal) — can't secrete acid; urine pH stays above 5.5; low potassium; kidney stones and nephrocalcinosis — Sjögren's, SLE, amphotericin, lithium, inherited.
  • Type 2 (proximal) — bicarbonate leaks out; low potassium; often part of Fanconi syndrome (myeloma, tenofovir, acetazolamide, ifosfamide).
  • Type 4 — low aldosterone or aldosterone resistance; high potassium; the commonest — diabetes, ACE inhibitors, ARBs, spironolactone, NSAIDs, heparin, trimethoprim.
• Metabolic alkalosis — kept going by the kidney when volume and chloride are low (vomiting, diuretics) — corrects with 0.9% saline and potassium; or from high aldosterone (Conn's — doesn't correct with saline).
• Compensation — in chronic respiratory acidosis (COPD), the kidneys keep bicarbonate over 2–5 days (see the Respiratory Anatomy, Physiology and Pharmacology chapter).

Calcium, Phosphate and Magnesium

• Calcium — mostly reabsorbed in the proximal tubule and loop (passively), fine-tuned in the distal tubule by PTH.
• Phosphate — reabsorbed in the proximal tubule; PTH and FGF-23 increase phosphate excretion.
• Vitamin D activation — the kidney makes active 1,25-dihydroxyvitamin D (calcitriol) using 1-alpha-hydroxylase (stimulated by PTH and low phosphate).
• CKD–mineral and bone disorder (from about CKD G3b–G4):
  • Less active vitamin D and phosphate retention → low calcium and high phosphate → high FGF-23 and secondary hyperparathyroidism (high PTH).
  • Consequences — renal bone disease (fractures, bone pain), vascular calcification (heart disease — the main cause of death in CKD), itch, calciphylaxis (painful skin necrosis).
  • Tertiary hyperparathyroidism — long-standing overactivity becomes autonomous → high calcium with very high PTH (often after a kidney transplant).
• Magnesium — mostly reabsorbed in the thick ascending limb; lost with loop and thiazide diuretics, PPIs (gut absorption), alcohol, diarrhoea, cisplatin, aminoglycosides, amphotericin, ciclosporin and tacrolimus. Low magnesium causes low potassium and low calcium (low PTH), arrhythmias (torsades) and seizures. High magnesium in CKD with magnesium-containing laxatives or antacids.
• Urate — filtered and partly reabsorbed in the proximal tubule; reduced excretion with CKD, thiazides, loop diuretics, low-dose aspirin, alcohol, ciclosporin → gout; losartan and SGLT2 inhibitors slightly increase excretion.

Kidney Hormones

• The kidney also clears hormones — insulin (so insulin and sulfonylurea needs fall in CKD — hypoglycaemia), PTH fragments, glucagon and others.
• Hypertension and the kidney — kidney disease causes hypertension (salt and water retention, renin), and hypertension damages the kidney — a vicious circle.

How the Kidney Fails

• Acute kidney injury — three types:
  • Pre-renal (most common) — not enough blood flow: dehydration, bleeding, sepsis, heart failure, cirrhosis, drugs (diuretics, ACE inhibitors, ARBs, NSAIDs). Kidney tissue is healthy; urine sodium is low; recovers quickly with treatment — but prolonged pre-renal AKI becomes acute tubular necrosis.
  • Intrinsic (renal) — acute tubular necrosis (prolonged low blood flow, sepsis, toxins — aminoglycosides, contrast, myoglobin in rhabdomyolysis), acute interstitial nephritis (drugs — PPIs, NSAIDs, penicillins; infection), glomerulonephritis, vascular (vasculitis, HUS, malignant hypertension, cholesterol emboli after angiography).
  • Post-renal — obstruction: prostate, stones, cancers, retroperitoneal fibrosis, blocked catheter.
• AKI basics — check urinalysis (blood and protein suggest glomerular disease — urgent), ultrasound within 24 hours if obstruction is possible (within 6 hours if an infected obstructed kidney is suspected), review drugs, assess fluid status, check potassium (NICE NG148).
• Indications for urgent dialysis (when not responding to treatment) — Acidosis, Electrolytes (high potassium), Intoxication (lithium, salicylate, toxic alcohols, metformin), Overload (pulmonary oedema), Uraemia (encephalopathy, pericarditis).
• CKD — common causes — diabetes, hypertension, glomerulonephritis, ADPKD, obstruction and reflux, renovascular disease, drugs (lithium, calcineurin inhibitors, NSAIDs).
• Consequences of CKD — hypertension, fluid overload, high potassium, acidosis, anaemia, bone disease, cardiovascular disease (the biggest risk — more patients die of heart disease than reach dialysis), drug accumulation, uraemic symptoms (itch, nausea, fatigue, poor appetite) in G5.
• Slowing CKD — control blood pressure, ACE inhibitor or ARB if albuminuria, SGLT2 inhibitor, statin, stop smoking, avoid nephrotoxins, treat acidosis, manage diabetes.

Nephrotic and Nephritic Syndromes

• Urinalysis with blood and protein plus a rising creatinine — think rapidly progressive glomerulonephritis — urgent nephrology referral (ANCA, anti-GBM, complement, ANA, immunoglobulins, kidney biopsy).

Normal Values

Prescribing in Kidney Disease

• Three questions for every drug in CKD or AKI:
  • Is it cleared by the kidney (does it build up)? — reduce the dose or extend the interval (check the BNF or the Renal Drug Database).
  • Is it nephrotoxic (will it make the kidneys worse)? — avoid or monitor.
  • Will it still work? — e.g. thiazides, nitrofurantoin and SGLT2 inhibitors (for glucose) work less well at low eGFR.
• Drugs that commonly build up and cause harm:
  • Morphine and codeine (active metabolites — drowsiness, myoclonus, respiratory depression) — prefer low-dose oxycodone, or fentanyl or alfentanil in advanced CKD and palliative care; tramadol with caution.
  • Gabapentin and pregabalin (confusion, falls, respiratory depression).
  • DOACs and low molecular weight heparin (bleeding — dose by creatinine clearance).
  • Metformin (lactic acidosis) and sulfonylureas (hypoglycaemia); insulin needs fall.
  • Digoxin, lithium, aminoglycosides, vancomycin (monitor levels).
  • Aciclovir (confusion, crystals), baclofen (encephalopathy), colchicine, allopurinol (start low), methotrexate, sotalol, spironolactone (potassium), nitrofurantoin, bisphosphonates.
• Sick day rules — temporarily stop drugs that cause dehydration-related AKI or harm during vomiting, diarrhoea or fever ("SADMANS"): Sulfonylureas, ACE inhibitors, Diuretics, Metformin, ARBs, NSAIDs, SGLT2 inhibitors; restart 24–48 hours after eating and drinking normally.
• In AKI — review every drug: stop nephrotoxins, hold antihypertensives if blood pressure is low, adjust doses of renally cleared drugs (and increase them again as function recovers — under-dosing antibiotics is also harmful).
• Iodinated contrast — risk of contrast-associated AKI is highest with eGFR under 30, AKI, and intra-arterial injection; give IV fluids (0.9% saline or sodium bicarbonate) to at-risk patients, hold metformin if eGFR is under 30 or AKI, and check creatinine afterwards. Don't withhold an important scan because of contrast worries alone.
• Gadolinium (MRI contrast) — rare nephrogenic systemic fibrosis in severe CKD with older agents.
• Pregnancy and CKD — ACE inhibitors, ARBs, SGLT2 inhibitors, statins and mycophenolate must be stopped (switch before conception).

Diuretics

• Dose equivalence — oral bumetanide 1 mg ≈ furosemide 40 mg; oral furosemide is about half as available as IV (variable — less absorbed with gut oedema in heart failure, so IV works better when very overloaded).
• Diuretic resistance — check salt intake and adherence; give IV; increase the dose (loop diuretics have a threshold — too low a dose does nothing); add a thiazide (e.g. metolazone) — sequential nephron blockade is powerful but causes severe low potassium, low sodium and AKI — daily U&E.
• Monitoring — U&E within 1–2 weeks of starting or changing (and during illness), weight, fluid balance, blood pressure (postural).
• Hydrochlorothiazide — linked to non-melanoma skin cancer with long-term use (MHRA) — sun protection.
• Diuretics don't treat oedema caused by calcium channel blockers (that's from capillary leak) — reduce or switch the CCB instead.

ACE Inhibitors and ARBs

• ACE inhibitors (ramipril, lisinopril, perindopril, enalapril) block angiotensin II production; ARBs (losartan, candesartan, irbesartan, valsartan) block its receptor.
• Kidney benefits — relax the efferent arteriole → lower glomerular pressure → less protein leak and slower CKD progression; also lower blood pressure.
• When to use in CKD (NICE NG203) — offer if:
  • Diabetes with ACR over 3 mg/mmol.
  • Hypertension with ACR over 30 mg/mmol.
  • ACR 70 mg/mmol or more, whatever the blood pressure or diabetes status.
• Blood pressure targets in CKD — under 140/90 if ACR is under 70; under 130/80 if ACR is 70 or more (NICE).
• Monitoring — U&E before starting, and 1–2 weeks after starting and each dose increase:
  • Accept a creatinine rise under 30% (eGFR fall under 25%) — this is expected.
  • Creatinine rise of 30% or more — stop or reduce, look for other causes (dehydration, NSAIDs) and consider renal artery stenosis.
  • Potassium over 6.0 mmol/L — stop (after reviewing other causes); consider potassium binders to allow continued use.
• Side effects — dry cough (ACE inhibitors, about 1 in 10 — bradykinin; switch to an ARB), angioedema (ACE inhibitors — more common in people of Black African or Caribbean family origin; can occur after years; can be life-threatening — stop and never restart), first-dose low blood pressure, high potassium, AKI, rash, taste changes.
• Never combine an ACE inhibitor with an ARB (or aliskiren) — more high potassium and AKI with no added benefit.
• Pregnancy — contraindicated (fetal kidney failure, oligohydramnios, skull defects in the 2nd and 3rd trimesters) — use effective contraception or switch before conception.
• Sacubitril–valsartan (heart failure) — don't give with an ACE inhibitor; leave 36 hours after the last ACE inhibitor dose (angioedema).