Renal Tubule Disorders

This is a group of disorders which can affect various parts of the nephron, leading to specific symptoms.

The symptoms reflect either an inability to reabsorb or excess reabsorption of solutes in the various segments. 

Fanconi syndrome

This is a disorder causing impairment of PCT function, preventing solute reabsorption.

It can be either inherited or acquired.

Symptoms

Glycosuria, aminoaciduria, uricosuria and phosphaturia

Phosphate loss can cause bone demineralisation resulting in osteomalacia

Management

Phosphate replacement is important

Bartter syndrome

This is an inherited condition which results in an impairment of salt reabsorption in the thick ascending loop of Henle, which usually affects children.

Sodium concentration increases further in the DCT, increasing the gradient for exchange with K+ and H+.

Symptoms

Hypokalaemia, hypochloraemia and metabolic alkalosis

The severe loss of electrolytes can affect growth in children

Management

Electrolyte replacement

NSAIDs and potassium sparing diuretics are used

Gitelman syndrome

This is an impairment of the NaCl cotransporter in the DCT.

It is milder than Bartter syndrome and usually presents in adults.

Symptoms

Mimic thiazide diuretic effects – hypokalemia, metabolic alkalosis, gout

Management

Electrolyte supplementation

Renal Tubular Acidosis (RTA)

This is a condition involving accumulation of acid in the body, due to a failure of the kidneys to acidify the urine.

The term RTA is only used for patients with poor urinary acidification but otherwise well-functioning kidneys.

It can be due to a primary tubule pathology (type 1 and 2) or secondary to low aldosterone or excessive use of potassium-sparing diuretics.

The problem is the metabolic acidosis which can demineralise bone.

Type 1

This is due to a failure of H+ excretion from the distal parts of the nephron, due to dysfunction of H+/K+ antiporter.

It can be primary (genetics) or secondary to autoimmune conditions and toxins.

It leads to hypokalaemia, hypocalcaemia and hyperchloraemia

High Ca2+ in urine increases the risk of urinary stones and nephrocalcinosis.

Symptoms

Gives hypokalemia, hypocalcaemia and hyperchloremia

High acid demineralizes bone (osteomalacia)

High Ca2+ in urine gives urinary stone + nephrocalcinosis (Kidney Ca2+ deposition)

Urine is not acidified

Management

HCO3- replacement to buffer acid and treat underlying disease

Type 2

This is due to an impairment of HCO3– reabsorption in the PCT, leading to urinary HCO3– loss, which contributes to a metabolic acidosis.

The loss of bicarbonate ions means that Na+ ions are held back as a cation, which increases the gradient for K+ loss.

The distal intercalated cells still work, so the acidosis is less severe than type 1.

It can be secondary to the ingestion of heavy metals and certain drugs.

Causes

Heavy metals

Drugs

Usually accompanied with Fanconi syndrome

Symptoms

Acidosis demineralizes bone and gives hypokalemia

Management

HCO3- and K+ replacement

Type 3

This is a combination of type 1 and 2 RTA which occurs in children

Type 4

This is a secondary RTA which is due to hypoaldosteronism

Causes

Aldosterone deficiency or resistance (due to drugs e.g. K+ sparing diuretic)

Symptoms

Gives hyperkalaemia, hypotension and metabolic acidosis

Acute Tubular Necrosis (ATN)

This is a condition resulting in necrosis of the tubule lining cells.

The necrotic cells fall off and can then obstruct the tubules decreasing the GFR

Causes

Poor renal blood flow (hypovolaemic/septic shock)

Drugs – NSAIDs, aminoglycoside antibiotics, iodine

Heavy metal poisoning – lead

Endogenous agents – urate (breakdown of tumour cells), so allopurinol used before chemotherapy to reduce urate-induced ATN

Symptoms

Oliguria phase often then followed by polyuria phase

AKI – poor urine output with raised urea and creatinine

Hyperkalaemia and metabolic acidosis

Key tests

Urine microscopy – presence of muddy brown, granular casts in urine

Blood tests – raised Cr and Urea

Kidney biopsy if diagnosis is unclear

Management

Hydration and cessation of nephrotoxic substance

Recovery is seen within a few weeks as the PCT cells are constantly replaced

Acute interstitial nephritis (ATIN)

This is a hypersensitivity reaction which causes inflammation of the nephron and the surrounding interstitial space

Causes

Drugs (NSAIDs, penicillin, diuretics, allopurinol)

Infection by Staphylococci

Underlying connective tissue diseases

Symptoms

Inflammatory signs – rash, low grade fever, joint pain

Renal dysfunction – oliguria (low urine), azotemia, hypertension

Key tests

Bloods may show an eosinophilia which demonstrates that it is an allergic mediated inflammatory reaction

Urine microscopy – shows white cell casts seen in the urine

Kidney biopsy – shows interstitial oedema and inflammatory cell infiltration

Management

Stop the causative agent.

Can also give steroids to dampen the immune system

Chronic interstitial nephritis (CTIN)

This is a chronic condition of the interstitium and tubules.

Chronic inflammatory episodes eventually lead to fibrosis of the tubules, leading to a deterioration in kidney function.

If left untreated, these patients will eventually suffer from chronic kidney disease.

Causes

Most commonly due to drugs or infection

Management

Stop causative agent and treat the progressive CKD