Nephrology

1. What this chapter covers, and how NEET PG actually tests it

Stems give a rising creatinine with a urinalysis, an electrolyte abnormality, or an arterial blood gas requiring interpretation.

The organising principle is a fixed sequence of three questions.

Distinguishing acute from chronic comes first because it changes everything that follows. Acute injury is potentially reversible and demands a search for a cause; chronic disease is managed rather than reversed, and hunting for a reversible cause wastes time.

Small kidneys on ultrasound, anaemia and secondary hyperparathyroidism together establish chronicity, since none of them develops over days.

2. Acute kidney injury

2.1 Localising the problem

Pre-renal injury is hypoperfusion of a structurally normal kidney, intrinsic injury is damage to the parenchyma, and post-renal injury is obstruction.

Obstruction is excluded first with an ultrasound, because it is the one cause that is immediately and completely reversible.

The logic is that a hypoperfused but intact tubule reabsorbs sodium and water avidly, producing concentrated urine low in sodium, while a damaged tubule can do neither.

The fractional excretion of sodium is unreliable in a patient on diuretics, because the drug forces sodium out regardless of perfusion, and the fractional excretion of urea is used instead since urea handling is less affected.

2.2 The urinalysis as a compartment test

A bland sediment with acute kidney injury directs attention away from the parenchyma entirely, and that negative finding is as informative as any positive one.

2.3 Definition and dialysis

Injury is defined by a rise in creatinine of a small absolute amount within forty-eight hours, or a proportional rise within a week, or a sustained fall in urine output.

Urine output criteria matter because creatinine lags: a patient may have lost most of their filtration hours before the creatinine moves.

Urgent dialysis is indicated for refractory acidosis, refractory hyperkalaemia, certain intoxications, fluid overload unresponsive to diuretics, and uraemic complications such as pericarditis or encephalopathy.

Uraemia is dialysed for its complications rather than for a number, so a high urea alone in a well patient is not an indication.

3. Chronic kidney disease

Staging uses the estimated glomerular filtration rate together with the degree of albuminuria, since the two predict progression independently.

The mineral disorder is a chain rather than a list. Phosphate cannot be excreted, calcitriol production falls, calcium absorption falls, and parathyroid hormone rises to compensate, eventually becoming autonomous.

Phosphate binders and vitamin D analogues therefore address the beginning of the chain, whereas treating the calcium alone addresses only a downstream consequence.

Anaemia is treated with erythropoiesis-stimulating agents only after iron stores have been repleted, since the marrow cannot respond to the hormone without substrate.

Blood pressure control and renin-angiotensin blockade slow progression more than any other intervention, and the benefit is greatest in those with proteinuria.

The proteinuria itself is nephrotoxic rather than merely a marker, since protein filtered into the tubule provokes an inflammatory and fibrotic response in the interstitium.

That is why reducing proteinuria is a treatment target in its own right, and why a drug that lowers it slows decline even without lowering blood pressure further.

Sodium-glucose cotransporter 2 inhibitors now slow progression in both diabetic and non-diabetic chronic kidney disease, which has changed practice substantially in recent years.

A modest early fall in filtration rate after starting either drug class is expected and is not a reason to stop, since it reflects a reduction in intraglomerular pressure rather than injury.

4. Glomerular syndromes

Nephrotic syndrome carries a thrombotic risk because antithrombin is lost in the urine along with albumin, and infection risk because immunoglobulin is lost as well.

Renal vein thrombosis is the classic thrombotic complication and should be suspected with sudden flank pain and deterioration in a nephrotic patient.

4.1 Naming the lesion

The interval between the infection and the haematuria separates the two commonest nephritic presentations. Immunoglobulin A nephropathy produces haematuria almost simultaneously with the sore throat, because pre-existing antibody is deposited immediately, while post-streptococcal disease requires one to three weeks for immune complexes to form.

Complement is low in post-streptococcal disease and normal in immunoglobulin A nephropathy, which confirms the distinction when the history is unclear.

Rapidly progressive glomerulonephritis is defined by crescents on biopsy with a steep loss of function over days to weeks, and it is a nephrological emergency requiring immunosuppression before irreversible scarring occurs.

Diabetic nephropathy is the commonest cause of end-stage disease overall, and it progresses through hyperfiltration, then microalbuminuria, then overt proteinuria and declining filtration.

4.2 Drug and contrast injury

Contrast-associated injury peaks at two to three days and usually recovers, and prevention rests on volume expansion and on withholding other nephrotoxins.

Aminoglycosides cause non-oliguric tubular injury after several days of treatment, which is why the creatinine is checked during rather than only before a course.

Non-steroidal anti-inflammatory drugs cause pre-renal injury by removing the prostaglandin-mediated afferent arteriolar dilatation that maintains filtration when perfusion falls.

That is why the combination of a non-steroidal drug, a renin-angiotensin inhibitor and a diuretic is particularly dangerous, since one blocks afferent dilatation, one blocks efferent constriction and the third reduces the volume being delivered.

Acute interstitial nephritis is a hypersensitivity reaction to a drug, classically with fever, rash and eosinophilia, though the full triad is present in a minority.

5. Electrolytes

5.1 Hyperkalaemia

Treatment follows a strict order, and each step does something the others do not.

Calcium does not lower the potassium at all, and giving it alone without proceeding to the shifting and removing steps leaves the patient in exactly the same danger once its brief effect wears off.

Electrocardiographic changes progress from peaked T waves through a widened QRS to a sine wave pattern, and their presence rather than the absolute level determines urgency.

5.2 Hyponatraemia

Volume status divides the causes and determines the treatment.

Correction of chronic hyponatraemia must not exceed the accepted daily limit, because the adapted brain cannot readapt quickly and osmotic demyelination follows.

Acute symptomatic hyponatraemia with seizures is the exception, where hypertonic saline is given promptly because cerebral oedema is the greater immediate danger.

5.3 Potassium loss and calcium

Hypokalaemia arises from gastrointestinal loss, renal loss or a shift into cells, and the urinary potassium separates the first two.

A low urinary potassium indicates gastrointestinal loss, since the kidney is appropriately conserving, while a high value indicates renal wasting from diuretics, hyperaldosteronism or a tubular disorder.

Magnesium must be corrected before potassium can be replaced successfully, because magnesium depletion promotes renal potassium wasting, and replacement simply passes into the urine until it is corrected.

Hypocalcaemia and hyperkalaemia together in a patient with acute kidney injury suggest rhabdomyolysis or tumour lysis, since both release potassium and phosphate that precipitates calcium.

Rhabdomyolysis is confirmed by a markedly raised creatine kinase and a urine dipstick positive for blood with no red cells on microscopy, because the dipstick detects myoglobin as well as haemoglobin.

6. Acid-base

6.1 The sequence

Interpretation follows four steps, and skipping any of them is what produces errors.

$\text{Anion gap}=\text{Na}-(\text{Cl}+\text{HCO3})$

First, look at the pH to identify acidaemia or alkalaemia. Second, decide whether the primary disorder is respiratory or metabolic. Third, check whether compensation is appropriate. Fourth, calculate the anion gap in every metabolic acidosis.

$\text{Expected pCO2}=1.5\times \text{HCO3}+8$

Winter formula gives the expected carbon dioxide tension in metabolic acidosis, and a value higher than predicted indicates an additional respiratory acidosis while a lower value indicates an additional respiratory alkalosis.

Compensation never fully corrects the pH, so a normal pH with abnormal values means two opposing primary disorders rather than perfect compensation.

6.2 The renal tubular acidoses

Type 4 is the one with a high potassium, and that single feature separates it immediately from the other two.

Type 1 causes stones and nephrocalcinosis because the persistently alkaline urine promotes calcium phosphate precipitation, while type 2 does not.

Proximal disease usually appears as part of a generalised tubular defect with glycosuria, aminoaciduria and phosphaturia, so isolated bicarbonate wasting is uncommon.

The causes of a high anion gap acidosis are the ones worth memorising as a group, being lactate, ketones, urate in renal failure, and the ingested acids and alcohols.

A normal anion gap acidosis has essentially two categories: bicarbonate lost from the gut in diarrhoea, or bicarbonate lost or acid retained by the kidney in a tubular acidosis.

The urinary anion gap distinguishes them, being negative in diarrhoea because the kidney is appropriately excreting ammonium, and positive in tubular acidosis because it cannot.

7. Urinary tract infection and stones

Asymptomatic bacteriuria is treated only in pregnancy and before urological procedures that breach the mucosa, and treating it otherwise selects resistance without benefit.

The exception in pregnancy exists because untreated bacteriuria progresses to pyelonephritis in a substantial proportion and is associated with preterm birth.

Struvite stones require the urine to be alkalinised by bacterial urease, which is why they are always associated with infection and why the stone must be removed for the infection to clear.

Uric acid stones are the only common type that can be dissolved medically, by alkalinising the urine, because their solubility depends directly on pH.

Adequate fluid intake reduces recurrence of every stone type and is the single most effective preventive measure, ahead of any dietary restriction.

Dietary calcium is not restricted in calcium oxalate stone formers, and restricting it increases recurrence, because dietary calcium binds oxalate in the gut and prevents its absorption.

8. Replacement therapy

Haemodialysis clears small solutes rapidly through diffusion across a membrane, while peritoneal dialysis uses the patient's own peritoneum as the exchange surface.

Peritoneal dialysis preserves residual renal function longer and avoids vascular access, but it is limited by peritonitis and by loss of membrane function over years.

Arteriovenous fistula is the preferred vascular access because it has the lowest infection and thrombosis rates, but it requires weeks to mature, so it must be created well before dialysis is needed.

That timing requirement is the practical reason for referring patients to nephrology early rather than at the point of decompensation.

Transplantation offers better survival and quality of life than dialysis for suitable candidates, and a living donor graft outperforms a deceased donor graft.

Recipients require lifelong immunosuppression, and the resulting risks are infection, particularly with cytomegalovirus and opportunistic organisms, and malignancy, especially of the skin and lymphoid tissue.

9. Worked examples

Example 1. A patient on furosemide has acute kidney injury with a fractional excretion of sodium of three per cent. What can be concluded?

Very little. Diuretics force sodium excretion regardless of perfusion, so the index is uninterpretable. The fractional excretion of urea should be used instead.

Example 2. A hyperkalaemic patient receives calcium gluconate and the electrocardiogram improves. What must follow?

Shifting and removal. Calcium protects the myocardium without altering the potassium at all, so insulin with dextrose and then definitive removal are still required.

Example 3. A patient has a metabolic acidosis with a normal anion gap and a urine pH of 6.5 with hypokalaemia. What is the diagnosis?

Distal renal tubular acidosis. The inability to acidify the urine below 5.5 in the presence of systemic acidosis is the defining feature, and hypokalaemia distinguishes it from type 4.

Summary

Ask in order whether the problem is acute or chronic, where it sits relative to the kidney, and which compartment is involved.

Small kidneys, anaemia and bone disease establish chronicity, since none develops over days.

Exclude obstruction first, because it is the one completely reversible cause.

Pre-renal injury concentrates urine and conserves sodium; tubular necrosis can do neither.

The fractional excretion of sodium is uninterpretable on diuretics, so use the urea equivalent.

Red cell casts mean glomerulus, muddy brown casts mean tubule, white cell casts mean interstitium.

Urine output criteria matter because creatinine lags behind the loss of filtration.

Dialyse for refractory acidosis, hyperkalaemia, intoxication, overload and uraemic complications.

Uraemia is dialysed for its complications, not for a number.

Chronic disease is staged by filtration rate together with albuminuria.

The mineral disorder is a chain beginning with phosphate retention, so binders act at the start of it.

Repletion of iron must precede erythropoiesis-stimulating agents.

Nephrotic syndrome loses antithrombin and immunoglobulin, giving thrombosis and infection risk.

Renal vein thrombosis presents with sudden flank pain in a nephrotic patient.

In hyperkalaemia, calcium stabilises without lowering, insulin shifts, and only the third step removes.

Electrocardiographic change rather than the absolute potassium determines urgency.

Volume status divides hyponatraemia and determines treatment.

Correct chronic hyponatraemia slowly, but treat hyponatraemic seizures promptly.

Interpret blood gases in four steps and calculate the anion gap in every metabolic acidosis.

Compensation never fully corrects the pH, so a normal pH with abnormal values means two disorders.

Type 4 renal tubular acidosis is the one with a high potassium.

Type 1 cannot acidify urine below 5.5 and causes stones and nephrocalcinosis.

Asymptomatic bacteriuria is treated only in pregnancy and before mucosa-breaching urological procedures.

Struvite stones require urease-producing organisms and cannot be cleared without removing the stone.

Immunoglobulin A nephropathy causes haematuria within days of infection; post-streptococcal disease takes one to three weeks and lowers complement.

Rapidly progressive glomerulonephritis shows crescents and needs immunosuppression before scarring occurs.

The combination of a non-steroidal drug, a renin-angiotensin inhibitor and a diuretic is particularly nephrotoxic.

Uric acid stones alone can be dissolved by alkalinising the urine.

Dietary calcium is not restricted in calcium oxalate stone formers, since it binds oxalate in the gut.

An arteriovenous fistula needs weeks to mature, which is why early nephrology referral matters.

Correct magnesium before replacing potassium, or the replacement is simply excreted.

Rhabdomyolysis gives a dipstick positive for blood with no red cells, because the strip detects myoglobin.

A high anion gap acidosis means lactate, ketones, urate or an ingested acid; a normal gap means gut or renal bicarbonate loss.

The urinary anion gap is negative in diarrhoea and positive in renal tubular acidosis.