Renal: Anatomy, Physiology and Pharmacology

🫘 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?

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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

Segment	Main jobs	Drugs acting here	Disorders
Proximal tubule	Reabsorbs about 65% of sodium and water, all glucose (SGLT2), amino acids, most bicarbonate (carbonic anhydrase), phosphate, urate; secretes drugs (penicillins, methotrexate, furosemide reaches its target this way)	SGLT2 inhibitors, acetazolamide	Fanconi syndrome (glucose, amino acids, phosphate, bicarbonate lost -myeloma, tenofovir, ifosfamide); type 2 RTA
Loop of Henle -thick ascending limb	Reabsorbs about 25% of sodium via NKCC2; impermeable to water (dilutes urine and builds the concentration gradient in the medulla); reabsorbs calcium and magnesium between cells	Loop diuretics (furosemide, bumetanide)	Bartter syndrome (like taking a loop diuretic)
Distal tubule	Reabsorbs about 5–10% of sodium via NCC; reabsorbs calcium (controlled by PTH)	Thiazides	Gitelman syndrome (like taking a thiazide -low magnesium, low urine calcium)
Collecting duct -principal cells	Reabsorb sodium (ENaC, under aldosterone control) and secrete potassium; reabsorb water via aquaporin-2 (under ADH control)	Spironolactone, eplerenone, amiloride, triamterene; desmopressin; tolvaptan	Liddle syndrome (overactive ENaC); diabetes insipidus
Collecting duct -intercalated cells	Secrete acid (H+) or bicarbonate	-	Type 1 (distal) RTA

• 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

Hormone	Made by	Clinical relevance
Renin	Juxtaglomerular cells (low pressure, low salt, sympathetic stimulation)	Starts the RAAS → angiotensin II and aldosterone; high in renal artery stenosis, low in primary aldosteronism; target of ACE inhibitors, ARBs, aliskiren
Erythropoietin	Interstitial cells of the cortex, in response to low oxygen (HIF pathway)	Deficiency → normocytic anaemia of CKD (usually once eGFR is under about 30); excess → polycythaemia (kidney cancer, cysts, after transplant)
Calcitriol (active vitamin D)	Proximal tubule	Deficiency in CKD → low calcium, high PTH, bone disease; made outside the kidney by granulomas (sarcoid -hypercalcaemia)
Prostaglandins	Throughout the kidney	Keep the afferent arteriole open; blocked by NSAIDs
Kallikrein–bradykinin	Kidney and elsewhere	ACE also breaks down bradykinin -so ACE inhibitors raise bradykinin (cough, angioedema)

• 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

Feature	Nephrotic syndrome (podocyte leak)	Nephritic syndrome (inflammation)
Main features	Heavy proteinuria (over 3 g a day; PCR over about 300 mg/mmol), low albumin, oedema, high cholesterol	Haematuria (red cell casts), hypertension, reduced urine output, rising creatinine, some proteinuria
Complications	Blood clots (loss of antithrombin -renal vein thrombosis, PE), infections (loss of antibodies), high lipids, AKI	Rapid kidney failure (rapidly progressive GN -"crescents"), fluid overload
Causes	Minimal change disease (children; NSAIDs, lymphoma), membranous nephropathy (adults -PLA2R antibodies; cancer, drugs, hepatitis B), FSGS, diabetic kidney disease, amyloidosis	IgA nephropathy (haematuria 1–2 days after a sore throat), post-streptococcal GN (1–3 weeks after, low C3), ANCA vasculitis, anti-GBM disease (with lung bleeding), lupus nephritis
Key drugs	Steroids (minimal change), rituximab (membranous), ACE inhibitor or ARB, diuretics, statin, anticoagulation if albumin is very low	Steroids plus cyclophosphamide or rituximab (vasculitis), plasma exchange (anti-GBM), mycophenolate (lupus), BP control

• 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

Measure	Typical adult value (check your lab)
GFR	About 120 mL/min (eGFR over 90 mL/min/1.73m² is normal; falls with age)
Creatinine	About 60–110 micromol/L (men); 45–90 (women)
Urea	About 2.5–7.8 mmol/L
Sodium	135–145 mmol/L
Potassium	3.5–5.3 mmol/L
Bicarbonate	22–29 mmol/L
Adjusted calcium	2.2–2.6 mmol/L
Phosphate	0.8–1.5 mmol/L
Magnesium	0.7–1.0 mmol/L
Plasma osmolality	275–295 mOsm/kg
Urine osmolality	About 50–1,200 mOsm/kg (depends on hydration)
Urine ACR	Under 3 mg/mmol
Urine PCR	Under about 15 mg/mmol
Urine output	At least 0.5 mL/kg/hour
Renal threshold for glucose	About 10 mmol/L

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

Class	Site and target	Uses	Side effects
Loop -furosemide, bumetanide	Thick ascending limb -NKCC2	Fluid overload -heart failure, pulmonary oedema, nephrotic syndrome, CKD; hypercalcaemia (after fluids)	Low K, low Na, low Mg, low Ca, alkalosis, dehydration and AKI, gout, hyperglycaemia; ototoxicity with fast high-dose IV
Thiazide and thiazide-like -bendroflumethiazide, indapamide, chlortalidone, metolazone	Distal tubule -NCC	Hypertension (indapamide preferred -NICE NG136); calcium stones; nephrogenic DI; added to loops for diuretic resistance (metolazone)	Low Na (older women), low K, high Ca, high urate (gout), hyperglycaemia, raised lipids, erectile dysfunction, photosensitivity; less effective if eGFR under 30 (except metolazone)
Mineralocorticoid receptor antagonists -spironolactone, eplerenone	Collecting duct -aldosterone receptor	Heart failure, resistant hypertension, ascites, primary aldosteronism	High K, gynaecomastia (spironolactone), AKI, hyponatraemia
ENaC blockers -amiloride, triamterene	Collecting duct -sodium channel	Combined with thiazides or loops to save potassium; lithium-induced nephrogenic DI (amiloride)	High K
Carbonic anhydrase inhibitor -acetazolamide	Proximal tubule	Glaucoma, altitude sickness, idiopathic intracranial hypertension	Metabolic acidosis, low K, tingling, kidney stones; sulfonamide (allergy)
Osmotic -mannitol	Whole tubule (draws water)	Raised intracranial pressure	Fluid overload at first (heart failure), high sodium, AKI

• 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).

Drugs That Protect the Kidneys

• SGLT2 inhibitors (dapagliflozin, empagliflozin) -slow CKD progression and reduce heart failure and death, with or without diabetes (NICE TAs for CKD -broadly eGFR down to about 20–25 with diabetes or raised albuminuria):
  • Cause an early small dip in eGFR (expected -like ACE inhibitors) -don't stop for this.
  • Continue until dialysis even though glucose-lowering effect fades.
  • Risks -genital thrush, volume depletion, euglycaemic DKA in diabetes, sick day rules (see the Endocrine Anatomy, Physiology and Pharmacology chapter).
• Finerenone -a non-steroidal mineralocorticoid receptor antagonist; for CKD with type 2 diabetes and albuminuria (NICE TA) on top of an ACE inhibitor or ARB; reduces kidney and heart events; monitor potassium.
• Statins -atorvastatin 20 mg for all adults with CKD for cardiovascular protection (NICE); dose adjustments in advanced CKD for some statins.
• Antiplatelets -for established cardiovascular disease (higher bleeding risk in CKD).
• Tolvaptan -slows kidney enlargement in rapidly progressing ADPKD (specialist; liver monitoring, thirst and polyuria).
• Treating acidosis -oral sodium bicarbonate (see Bone, Phosphate and Acidosis Drugs).
• Vaccination -influenza, pneumococcal, COVID-19 and hepatitis B (before dialysis).

Treating Hyperkalaemia

• Severe hyperkalaemia -potassium 6.5 mmol/L or more, or any ECG changes -is an emergency (UK Kidney Association): cardiac monitoring, repeat level, treat at once.
• Protect the heart -IV calcium if there are ECG changes: calcium gluconate 10%, 30 mL IV over 5–10 minutes (or calcium chloride 10%, 10 mL via a large or central vein). Works in minutes, lasts 30–60 minutes, doesn't lower potassium; repeat if ECG changes persist. Caution with digoxin (give slowly).
• Move potassium into cells:
  • Insulin–glucose -10 units soluble insulin (e.g. Actrapid) with 25 g glucose IV over 15 minutes; lowers potassium by about 0.6–1.0 mmol/L within an hour, lasting 4–6 hours.
  • Hypoglycaemia is common (especially in CKD and low starting glucose) -check glucose regularly for at least 6 hours and give a glucose infusion if the starting glucose was low.
  • Nebulised salbutamol 10–20 mg -an add-on (not alone); avoid with tachyarrhythmias or ischaemic heart disease; causes tremor and tachycardia.
  • Sodium bicarbonate -only with significant metabolic acidosis (specialist advice).
• Remove potassium from the body:
  • Potassium binders -sodium zirconium cyclosilicate (Lokelma -fast; oedema from its sodium) or patiromer (Veltassa -slower; low magnesium, constipation) (NICE TAs); calcium resonium (older, slow, constipation -rarely used now).
  • Treat the cause; loop diuretics if not dehydrated; dialysis if refractory or in severe AKI.
• Prevent recurrence -stop potassium-raising drugs (ACE inhibitors, ARBs, spironolactone, trimethoprim, NSAIDs, potassium supplements, salt substitutes), low-potassium diet advice, treat acidosis; binders can allow heart and kidney protective drugs to continue.
• Recheck potassium -about 1, 2, 4, 6 and 24 hours after treatment.

⚠️ Safety Pearl: IV calcium protects the heart but doesn't lower potassium, and insulin–glucose lowers it for only a few hours -always find and treat the cause. Measure glucose regularly after insulin: hypoglycaemia is one of the commonest harms of hyperkalaemia treatment.

Bone, Phosphate and Acidosis Drugs

• Phosphate binders -taken with meals to bind dietary phosphate in the gut (CKD G4–G5 and dialysis, after dietary advice):
  • Calcium-based (calcium acetate, calcium carbonate) -cheap; risk of high calcium and vascular calcification.
  • Sevelamer -calcium-free; GI upset; also lowers cholesterol.
  • Lanthanum -chewable; GI upset.
  • Sucroferric oxyhydroxide -iron-based; black stools, diarrhoea.
  • Binders also bind other drugs (e.g. levothyroxine, quinolones) -separate doses.
• Active vitamin D -alfacalcidol or calcitriol (don't need kidney activation) -for low calcium and high PTH in CKD; can cause high calcium and high phosphate -monitor.
• Native vitamin D (colecalciferol) -replace deficiency in CKD too.
• Calcimimetics -cinacalcet (oral) or etelcalcetide (IV after dialysis) -make the parathyroid more sensitive to calcium → lower PTH; for secondary hyperparathyroidism on dialysis; low calcium, nausea. Parathyroidectomy if severe or tertiary.
• Osteoporosis drugs in CKD -oral bisphosphonates are avoided if eGFR is under about 30–35; denosumab causes severe hypocalcaemia in advanced CKD -specialist advice.
• Metabolic acidosis -oral sodium bicarbonate if eGFR is under 30 and bicarbonate is under 20 mmol/L (NICE NG203); side effects -sodium load (oedema, hypertension), bloating. IV bicarbonate is a specialist treatment.

Renal Anaemia Drugs

• Anaemia of CKD -mainly erythropoietin deficiency, plus iron deficiency (blood loss, poor absorption, high hepcidin) and inflammation; check for other causes first (B12, folate, bleeding, haemolysis, myeloma).
• Iron first -replace iron before or alongside ESAs:
  • IV iron is usually preferred in advanced CKD and dialysis (iron sucrose, ferric carboxymaltose, ferric derisomaltose).
  • Risks -rare serious allergic reactions (observe for at least 30 minutes, resuscitation equipment available); avoid in active infection; ferric carboxymaltose can cause low phosphate (repeated doses -osteomalacia).
  • Oral iron -GI upset, poor absorption; alternate-day dosing may help.
• Erythropoiesis-stimulating agents (ESAs) -epoetin alfa or beta, darbepoetin, methoxy polyethylene glycol-epoetin beta:
  • Target haemoglobin about 100–120 g/L -aiming higher increases stroke, thrombosis and death.
  • Side effects -hypertension, clotting of dialysis access, seizures (rapid rise), flu-like symptoms; rare pure red cell aplasia (antibodies against EPO); may worsen some cancers.
  • Poor response -iron deficiency, infection, inflammation, bleeding, hyperparathyroidism, B12 or folate deficiency, aluminium.
• HIF-prolyl hydroxylase inhibitors (e.g. roxadustat -oral) -stimulate the body's own EPO; specialist use in selected patients; thrombosis risk and interactions.
• Blood transfusion -avoid where possible in people who may have a kidney transplant (antibodies make matching harder).

Immunosuppression in Kidney Disease and Transplant

• Corticosteroids -minimal change disease (prednisolone about 1 mg/kg, usually responds within weeks), vasculitis, lupus nephritis, transplant; see the side effects in the Endocrine Anatomy, Physiology and Pharmacology chapter.
• Cyclophosphamide -ANCA vasculitis, lupus nephritis: marrow suppression, haemorrhagic cystitis and bladder cancer (hydration; mesna with high doses), infertility (discuss sperm or egg storage), infections (co-trimoxazole for PCP prophylaxis).
• Rituximab (anti-CD20) -ANCA vasculitis, membranous nephropathy, relapsing minimal change: infusion reactions, infections, hepatitis B reactivation (screen), low antibody levels; rare PML.
• Mycophenolate mofetil -lupus nephritis and transplant: diarrhoea, marrow suppression, infections, skin cancer; teratogenic -highly effective contraception (MHRA), and men should use condoms.
• Calcineurin inhibitors -tacrolimus (main transplant drug) and ciclosporin:
  • Nephrotoxicity (constrict the afferent arteriole -acute and chronic), hypertension, high potassium, low magnesium, tremor, headache, PRES; diabetes (especially tacrolimus -new-onset diabetes after transplant); gum overgrowth and hirsutism (ciclosporin).
  • Narrow therapeutic range -trough levels are monitored; brand-specific prescribing.
  • CYP3A4 and P-glycoprotein interactions -levels rise (toxicity) with clarithromycin, erythromycin, azole antifungals, diltiazem, verapamil, grapefruit; levels fall (rejection) with rifampicin, carbamazepine, phenytoin, St John's wort. Always check before prescribing anything new.
• Azathioprine -check TPMT; marrow suppression; avoid with allopurinol (see the Gastroenterology Anatomy, Physiology and Pharmacology chapter).
• mTOR inhibitors (sirolimus, everolimus) -poor wound healing, mouth ulcers, high lipids, proteinuria, pneumonitis.
• Other targeted drugs (specialist) -basiliximab (induction), belatacept, plasma exchange (anti-GBM disease), avacopan (complement C5a receptor blocker in ANCA vasculitis -liver monitoring), eculizumab (atypical HUS -meningococcal vaccination), targeted-release budesonide (IgA nephropathy).
• Transplant patients long term -infections (CMV, BK virus, PCP, TB), skin cancer (sun protection, skin checks), lymphoma (post-transplant lymphoproliferative disorder), cardiovascular disease, bone disease; no live vaccines.

Stone, Prostate and Bladder Drugs

• Renal colic (NICE NG118):
  • NSAIDs first-line (e.g. diclofenac IM, oral or PR) if not contraindicated; IV paracetamol if NSAIDs can't be used; opioids only if both are unsuitable.
  • Alpha-blocker (tamsulosin) -helps pass distal ureteric stones under 10 mm (medical expulsive therapy).
  • Urgent decompression (nephrostomy or stent) if there is infection with obstruction, AKI or a single kidney.
• Stone prevention:
  • Drink enough to pass about 2–2.5 L of urine a day; reduce salt; normal calcium intake (low calcium diets increase oxalate stones).
  • Potassium citrate -calcium oxalate stones with low urine citrate; uric acid stones (alkalinises urine -uric acid stones can dissolve).
  • Thiazides -high urine calcium (calcium stones).
  • Allopurinol -high urate (uric acid and some calcium stones).
  • Stone types -calcium oxalate (most; visible on X-ray), uric acid (radiolucent), struvite (infection with urease-producing bacteria such as Proteus -"staghorn"), cystine (inherited).
• Benign prostatic enlargement (NICE CG97):
  • Alpha-blockers (tamsulosin, alfuzosin, doxazosin) -relax prostate and bladder-neck muscle; work in days; postural hypotension (first dose, falls), dizziness, retrograde ejaculation, floppy iris syndrome during cataract surgery (tell the eye surgeon).
  • 5-alpha-reductase inhibitors (finasteride, dutasteride) -shrink the prostate over 6 months or more; for large prostates; halve the PSA (double it when interpreting); reduced libido, erectile dysfunction; finasteride -depression and suicidal thoughts (MHRA); women who could be pregnant shouldn't handle crushed or broken tablets.
  • Combination for large prostates with significant symptoms; surgery if retention or failure.
• Overactive bladder (NICE NG123 and CG97):
  • Antimuscarinics (oxybutynin, solifenacin, tolterodine, trospium, fesoterodine) -dry mouth, constipation, blurred vision, urinary retention; confusion and possible dementia risk in older people (avoid immediate-release oxybutynin in frail older women; trospium crosses into the brain less).
  • Mirabegron (beta-3 agonist) -no anticholinergic burden; can raise blood pressure (avoid in severe uncontrolled hypertension; monitor).
  • Botulinum toxin bladder injections -may need self-catheterisation.
  • Desmopressin -nocturia from nocturnal polyuria (hyponatraemia risk -check sodium, especially over 65).
• Acute urinary retention -catheterise; start an alpha-blocker before a trial without catheter; review drugs (anticholinergics, opioids, decongestants, TCAs).

Antibiotics for Urinary Infection

• Lower UTI in non-pregnant women (NICE NG109) -3 days of:
  • Nitrofurantoin (modified-release 100 mg twice daily) if eGFR is 45 or more (BNF: avoid if under 45, though a short course may be used with caution at 30–44 when no alternative); or
  • Trimethoprim 200 mg twice daily if low risk of resistance.
  • Second-line -pivmecillinam or fosfomycin (single dose).
• Men -7 days (nitrofurantoin or trimethoprim); consider prostatitis.
• Pregnancy -always send a urine culture and treat (including asymptomatic bacteriuria): nitrofurantoin (avoid near term -neonatal haemolysis), amoxicillin (only if sensitive) or cefalexin; avoid trimethoprim in the first trimester (folate antagonist -neural tube defects).
• Pyelonephritis (NICE NG111) -cefalexin, co-amoxiclav (if sensitive), trimethoprim (if sensitive), or ciprofloxacin; IV options (e.g. gentamicin, cefuroxime, ceftriaxone) if severe.
• Key drug points:
  • Trimethoprim -raises potassium (blocks ENaC like amiloride -care with ACE inhibitors, ARBs and spironolactone) and raises creatinine (blocks its secretion); folate antagonist -dangerous with methotrexate (marrow suppression).
  • Nitrofurantoin -less effective and more toxic in CKD; lung reactions (acute pneumonitis, chronic fibrosis with long-term use), liver injury, peripheral neuropathy; turns urine brown.
  • Fluoroquinolones (ciprofloxacin) -MHRA: only when other antibiotics are inappropriate -tendon rupture (especially older people and with steroids), aortic aneurysm, long-lasting neuropsychiatric and nerve effects, low and high glucose, QT; lower the seizure threshold; raise theophylline and tizanidine levels.
  • Gentamicin -once-daily dosing by weight and kidney function; trough levels; nephrotoxicity and ototoxicity; avoid in myasthenia.
• Don't treat asymptomatic bacteriuria in older people or people with catheters (except in pregnancy or before urological procedures) -it doesn't help and drives resistance. Don't dipstick urine in people over 65 to diagnose UTI (NICE / UKHSA).
• Recurrent UTI prevention (NICE NG112) -behavioural advice, vaginal oestrogen in postmenopausal women, methenamine hippurate, then antibiotic prophylaxis.

Dialysis and Drugs

• Types -haemodialysis (usually 3 times a week, via an arteriovenous fistula, graft or line) and peritoneal dialysis (daily exchanges via an abdominal catheter); kidney transplant is the best treatment for suitable patients.
• Which drugs are removed by dialysis -those that are small, water-soluble, have low protein binding and a small volume of distribution:
  • Removed -gentamicin, many penicillins and cephalosporins, vancomycin (partly, with high-flux), lithium, metformin, salicylates, toxic alcohols (methanol, ethylene glycol), atenolol, gabapentin.
  • Not removed -digoxin, TCAs, amiodarone, warfarin, most highly protein-bound or fat-soluble drugs.
  • Give doses of removed drugs after dialysis.
• Dialysis in poisoning -lithium, salicylates, methanol and ethylene glycol (also fomepizole), metformin-associated lactic acidosis, theophylline, valproate (severe) (TOXBASE).
• Practical points:
  • Protect the fistula arm -no blood pressure cuffs, cannulas or blood tests on that arm; check for a thrill.
  • Heparin is used during haemodialysis -consider bleeding risk and timing of procedures.
  • Fluid and potassium -patients on dialysis often have fluid restrictions; check potassium before giving supplements or potassium-containing fluids; ask about their usual dry weight.
  • Peritonitis in peritoneal dialysis -cloudy fluid, abdominal pain; intraperitoneal antibiotics.
• Conservative kidney management -some older or frail patients choose not to have dialysis; focus on symptoms (itch, breathlessness, nausea, pain) with careful drug choice.

Drugs That Damage the Kidneys

Mechanism	Typical drugs
Reduced kidney blood flow (pre-renal)	NSAIDs, ACE inhibitors, ARBs, diuretics, SGLT2 inhibitors (volume), bowel preparation, calcineurin inhibitors, antihypertensives in low BP
Acute tubular necrosis	Aminoglycosides (gentamicin), vancomycin (especially with piperacillin–tazobactam), amphotericin, cisplatin, iodinated contrast, IV bisphosphonates (zoledronic acid), colistin, high-dose methotrexate, rhabdomyolysis (statins with fibrates or macrolides, cocaine, prolonged lie)
Acute interstitial nephritis	PPIs, NSAIDs, penicillins and cephalosporins, rifampicin, allopurinol, mesalazine, co-trimoxazole, diuretics, immune checkpoint inhibitors -may cause rash, fever and eosinophilia (often not); white cells in urine
Glomerular disease	NSAIDs (minimal change, membranous), penicillamine and gold (membranous), hydralazine and propylthiouracil (ANCA vasculitis), pamidronate (FSGS), VEGF inhibitors such as bevacizumab (proteinuria, hypertension)
Crystal nephropathy	Aciclovir (IV -hydrate), methotrexate, sulfonamides, some HIV drugs, orlistat (oxalate), ethylene glycol
Obstruction / retention	Anticholinergics, opioids, TCAs, decongestants (urinary retention); drugs causing stones (topiramate, acetazolamide, high-dose vitamin C, calcium with vitamin D)
Thrombotic microangiopathy	Calcineurin inhibitors, gemcitabine, mitomycin, VEGF inhibitors, quinine, clopidogrel (rare TTP)
Chronic kidney damage	Lithium (nephrogenic DI, chronic interstitial nephritis -monitor eGFR), calcineurin inhibitors, long-term NSAIDs (analgesic nephropathy, papillary necrosis), tenofovir disoproxil (Fanconi syndrome)
Electrolyte problems	High potassium (ACE inhibitors, ARBs, MRAs, trimethoprim, heparin, NSAIDs, tacrolimus); low magnesium (PPIs, diuretics, cisplatin); low sodium (thiazides, SSRIs, carbamazepine)
False rise in creatinine (no true GFR loss)	Trimethoprim, cimetidine, dolutegravir, some other HIV drugs

Drug Reference Table

Drug	Key points
Furosemide / bumetanide	Loop (NKCC2); fluid overload; low K, Mg and Na, AKI, gout, ototoxicity; bumetanide 1 mg ≈ furosemide 40 mg.
Indapamide / bendroflumethiazide	Thiazide (NCC); hypertension; low Na (older women), low K, high Ca and urate; weak if eGFR under 30.
Metolazone	Added to loops for resistance; severe low K and Na -daily U&E.
Spironolactone / eplerenone	MRA; heart failure, ascites, aldosteronism; high K; gynaecomastia (spironolactone).
Amiloride	ENaC blocker; potassium-sparing; lithium-induced DI.
Acetazolamide	Proximal tubule; metabolic acidosis, stones, tingling.
Ramipril / losartan	Reduce proteinuria; U&E at 1–2 weeks; accept under 30% creatinine rise; stop if K over 6.0; cough (ACEi), angioedema; not in pregnancy; never combine.
Dapagliflozin / empagliflozin	Slow CKD with or without diabetes; early eGFR dip expected; sick day rules.
Finerenone	Non-steroidal MRA for diabetic CKD with albuminuria; monitor K.
Atorvastatin	20 mg for all adults with CKD.
Calcium gluconate 10%	30 mL IV for hyperkalaemia with ECG changes; stabilises the heart; no K lowering.
Insulin–glucose	10 units with 25 g glucose; lowers K for 4–6 hours; watch for hypoglycaemia.
Salbutamol (nebulised)	Add-on for hyperkalaemia; 10–20 mg; tachycardia.
Sodium zirconium cyclosilicate / patiromer	Potassium binders; allow RAAS blockers to continue.
Sodium bicarbonate (oral)	CKD acidosis (eGFR under 30, bicarbonate under 20); sodium load.
Calcium acetate / sevelamer / lanthanum	Phosphate binders with meals; calcium load (calcium-based).
Alfacalcidol	Active vitamin D in CKD; high calcium and phosphate.
Cinacalcet	Calcimimetic for secondary hyperparathyroidism on dialysis; low calcium.
IV iron	Before or with ESAs; rare anaphylaxis -observe 30 min; ferric carboxymaltose lowers phosphate.
Epoetin / darbepoetin	Target Hb 100–120 g/L; hypertension, thrombosis, stroke if overcorrected.
Tacrolimus / ciclosporin	Transplant; trough levels; nephrotoxicity, high K, low Mg, diabetes; CYP3A4 interactions (clarithromycin, azoles up; rifampicin down).
Mycophenolate	Lupus nephritis and transplant; teratogenic; marrow suppression, diarrhoea.
Cyclophosphamide / rituximab	Vasculitis, lupus, membranous; haemorrhagic cystitis, infertility / infusion reactions, hepatitis B reactivation.
Tamsulosin	Prostate symptoms and distal ureteric stones; postural hypotension, floppy iris syndrome.
Finasteride	Shrinks prostate over 6+ months; halves PSA; sexual side effects, mood (MHRA).
Oxybutynin / solifenacin / mirabegron	Overactive bladder; anticholinergic confusion / raised BP (mirabegron).
Potassium citrate	Stone prevention; alkalinises urine.
Nitrofurantoin	Lower UTI if eGFR 45 or more; lung and liver reactions; avoid at term.
Trimethoprim	Raises potassium and creatinine; avoid with methotrexate and in first trimester.
Gentamicin	Levels; nephrotoxicity and ototoxicity; removed by dialysis.
Tolvaptan	ADPKD (and SIADH); liver toxicity; thirst.

Spot the Answer

Clue	Answer
New left varicocele that doesn't empty lying down, with haematuria	Left renal tumour in the left renal vein
Stone stuck at the narrowest point of the ureter	Vesicoureteric junction
Ureter injured during hysterectomy	Passes under the uterine artery
Horseshoe kidney in a girl with short stature	Turner syndrome
Hypertension, kidney cysts and a family history of SAH	ADPKD (berry aneurysms)
Creatinine up 45% two weeks after starting ramipril	Suspect bilateral renal artery stenosis -stop and investigate
AKI in an older man on ramipril, furosemide and ibuprofen with diarrhoea	"Triple whammy" pre-renal AKI
Creatinine up 15% after starting trimethoprim with normal cystatin C	Blocked creatinine secretion (no true GFR fall)
Glycosuria with normal blood glucose	SGLT2 inhibitor, pregnancy or proximal tubule disorder (Fanconi)
Polyuria, thirst and rising sodium on long-term lithium	Nephrogenic diabetes insipidus
Normal anion gap acidosis, urine pH 6.5, low potassium and stones	Type 1 (distal) RTA
High potassium and mild acidosis in a diabetic on ramipril	Type 4 RTA (low aldosterone)
Low calcium, high phosphate and high PTH in CKD G4	Secondary hyperparathyroidism (CKD–MBD)
High calcium and very high PTH years after starting dialysis	Tertiary hyperparathyroidism
Tented T waves and broad QRS with K 7.2	Severe hyperkalaemia -IV calcium gluconate first
Potassium won't rise despite supplements; on omeprazole and furosemide	Low magnesium -replace it
Heavy proteinuria, albumin 18 and oedema in a 4-year-old	Minimal change disease -steroids
Haematuria 2 days after a sore throat	IgA nephropathy
Haematuria 2 weeks after a sore throat with low C3	Post-streptococcal glomerulonephritis
AKI with rash and white cells in urine 10 days after starting omeprazole	Acute interstitial nephritis
Rising tacrolimus level and AKI after a course of clarithromycin	CYP3A4 inhibition
Drowsy with myoclonus and small pupils on morphine with eGFR 18	Morphine metabolite accumulation
Dizzy and falling after starting a prostate drug	Alpha-blocker postural hypotension
PSA halved after 6 months on a prostate drug	5-alpha-reductase inhibitor (double the PSA to interpret)
Breathless with lung fibrosis after years of UTI prophylaxis	Nitrofurantoin

Exam-style Scenarios

1. An 81-year-old woman with heart failure on ramipril, furosemide and spironolactone has had diarrhoea for 3 days and has been taking ibuprofen for back pain. Creatinine 289 (baseline 102), K 7.1, ECG shows broad QRS complexes.
Answer: Pre-renal AKI ("triple whammy" plus spironolactone) with life-threatening hyperkalaemia.

• Calcium gluconate 10%, 30 mL IV over 5–10 minutes; cardiac monitoring; then insulin 10 units with 25 g glucose (glucose checks), nebulised salbutamol if suitable.
• Stop ramipril, spironolactone, furosemide and ibuprofen; careful IV fluids; urine output monitoring; potassium binder; renal team if not responding (dialysis).
• Afterwards -sick day rules education; avoid NSAIDs; restart heart failure drugs carefully as kidney function recovers.

2. A 70-year-old man with peripheral vascular disease starts ramipril for hypertension. Two weeks later his creatinine has risen from 105 to 170 micromol/L.
Answer: Rise over 30% -suspect bilateral renal artery stenosis.

• Stop ramipril; check for other causes (dehydration, NSAIDs, diuretics); repeat U&E.
• Imaging of the renal arteries (e.g. ultrasound Doppler, CT or MR angiography); look for unequal kidney sizes.
• Treat with a non-RAAS antihypertensive (e.g. a calcium channel blocker); statin and antiplatelet for vascular disease.

3. A 45-year-old woman with a kidney transplant on tacrolimus, mycophenolate and prednisolone is given clarithromycin by her GP for a chest infection. A week later she has a tremor, headache and her creatinine has doubled.
Answer: Tacrolimus toxicity due to CYP3A4 inhibition by clarithromycin.

• Check tacrolimus trough level, potassium, magnesium and glucose; stop clarithromycin (use a non-interacting antibiotic such as doxycycline or amoxicillin, with transplant team advice).
• Hold or reduce tacrolimus as advised; monitor levels and kidney function closely.
• Always check interactions before prescribing to transplant patients; rifampicin and St John's wort do the opposite (rejection).

4. A 76-year-old man with CKD G4 (eGFR 18) is started on morphine sulfate 10 mg four times a day for pain from a hip fracture. Two days later he is drowsy, confused, with pinpoint pupils, twitching and a respiratory rate of 8.
Answer: Opioid toxicity due to accumulation of morphine metabolites in CKD.

• Stop morphine; naloxone in small titrated doses (repeat or infusion -metabolites last longer than naloxone); oxygen, monitor breathing.
• Switch to a safer opioid at a low dose (e.g. oxycodone with caution, or fentanyl or alfentanil with specialist advice); regular paracetamol; consider a nerve block for the hip.
• Review other renally cleared drugs (gabapentinoids, antibiotics); laxatives.

5. A 62-year-old woman with rheumatoid arthritis on weekly methotrexate has symptoms of cystitis. Her eGFR is 38.
Answer: Choose an antibiotic that avoids both the kidney and drug interaction problems.

• Avoid trimethoprim -with methotrexate it causes dangerous marrow suppression (both are folate antagonists).
• Avoid nitrofurantoin -eGFR under 45 (less effective and more toxic).
• Use pivmecillinam or fosfomycin (per local guidance and urine culture); check FBC if there are signs of methotrexate toxicity.

Key Points

• Kidneys get 20–25% of cardiac output; segmental arteries are end arteries; the medulla is easily starved of oxygen.
• Hilum from front to back: vein, artery, pelvis; left renal vein receives the left gonadal vein (varicocele).
• Stones stick at the PUJ, pelvic brim and VUJ; the ureter runs under the uterine artery.
• NSAIDs narrow the afferent arteriole; ACE inhibitors and ARBs relax the efferent -together with diuretics, the "triple whammy".
• Creatinine depends on muscle mass and lags in AKI; trimethoprim raises it without true GFR loss.
• Use creatinine clearance (Cockcroft–Gault) for DOACs, aminoglycosides, digoxin and lithium.
• CKD is staged by eGFR (G1–G5) and ACR (A1–A3); ACR is the best marker of risk.
• Proximal tubule -glucose (SGLT2), bicarbonate; loop -NKCC2 (25% of sodium); distal -NCC; collecting duct -aldosterone and ADH.
• Loops and thiazides lower potassium; MRAs and amiloride raise it; thiazides raise calcium and cause hyponatraemia.
• Hyponatraemia is usually a water problem; sodium content sets fluid volume.
• 98% of potassium is inside cells; insulin and salbutamol move it in; acidosis moves it out.
• RTA type 1 -low K, stones, urine pH over 5.5; type 4 -high K (diabetes, ACE inhibitors).
• CKD causes low calcium, high phosphate, high PTH, anaemia and acidosis.
• Sick day rules: SADMANS.
• ACE inhibitors and ARBs: U&E at 1–2 weeks; accept a creatinine rise under 30%; stop if K over 6.0; never combine; not in pregnancy.
• SGLT2 inhibitors protect kidneys even without diabetes; an early eGFR dip is expected.
• Hyperkalaemia: calcium gluconate for ECG changes, then insulin–glucose (check glucose), then remove potassium.
• Iron before ESAs; Hb target 100–120 g/L.
• Tacrolimus: trough levels; clarithromycin and azoles raise levels; rifampicin lowers them.
• Morphine and gabapentinoids accumulate in CKD; prefer fentanyl or alfentanil in advanced CKD.
• Nitrofurantoin if eGFR 45 or more; trimethoprim raises potassium and interacts with methotrexate.
• Don't treat asymptomatic bacteriuria in older or catheterised people (except in pregnancy).

Guidelines and Further Reading

• NICE NG203: Chronic kidney disease -assessment and management
• NICE NG148: Acute kidney injury -prevention, detection and management
• KDIGO clinical practice guidelines (AKI, CKD, glomerular disease)
• UK Kidney Association: Clinical practice guideline -treatment of acute hyperkalaemia in adults
• NICE NG8: Chronic kidney disease -managing anaemia
• NICE TAs: dapagliflozin and empagliflozin for CKD; finerenone; potassium binders
• NICE NG109, NG111, NG112: Urinary tract infection -lower, pyelonephritis, recurrent
• NICE NG118: Renal and ureteric stones
• NICE CG97: Lower urinary tract symptoms in men; NICE NG123: Urinary incontinence in women
• NICE CG174: Intravenous fluid therapy in adults in hospital
• Royal College of Radiologists / Think Kidneys: contrast and kidney function guidance
• BNF: Prescribing in renal impairment; Renal Drug Database
• BNF -for current doses