Renal Tubule Disorders

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

– The symptoms reflect 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

Symptoms:

– Glycosuria + aminoaciduria + uricosuria + phosphateuria

– Loss of phosphate in the urine can cause bone demineralization giving osteomalacia

Management:

Replace phosphate

Bartter syndrome

This is an impairment of salt reabsorption in the thick ascending loop of Henle

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

– The severe loss of electrolytes can affect growth in children, the age-group it usually affects

Symptoms:

These mimic loop diuretic effects –> Hypokalemia, hypochloremia + Metabolic alkalosis

Management:

Salt replacement + NSAIDs (stop prostaglandins antagonizing action of ADH)

Gitelman syndrome

This is an impairment of the NaCl cotransporter in the DCT

– This is milder than Bartter syndrome –> presents in adulthood with incidental findings

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.

– RTA only used for patients with poor urinary acidification but otherwise well-functioning kidneys

– Can be caused by inability to excrete H+ ions, or inability to reabsorb HCO₃^– in the PCT.

i) Type 1:

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

Causes:

Genetic disease or secondary to autoimmune/toxins

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

ii) Type 2:

This is a failure of HCO₃ reabsorption in the PCT, giving urinary HCO₃ loss and metabolic acidosis

– Loss of HCO₃ means that Na+ is held back as major cation, increasing gradient for K+ loss

– However, the distal intercalated cells still work, so the acidosis is less severe than type 1

Causes:

Heavy metals, drugs –> usually accompanied with Fanconi syndrome

Symptoms:

Acidosis demineralizes bone + hypokalemia

Management:

HCO₃ and K+ replacement

iii) Type 3:

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

iv) 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 giving necrosis death of the tubule lining cells

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

Management:

– Hydration and cessation of nephrotoxic substance

– Recovery is seen within 1-3 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 or underlying connective tissue diseases

Symptoms:

– Signs of an allergy with rash and fever

– Joint paint

– Renal dysfunction –> Oliguria (low urine) + azotemia + Hypertension

– Key is eosinophilia which demonstrates that it is an allergic mediated inflammatory reaction

Diagnosis:

Sterile pyuria + white cell casts seen in the urine

Management:

Stop causative agent and can give steroids

It can be confusing to distinguish between ATN and ATIN:

– In ATN, there is blood AND protein found in the urine. In addition, there are similar levels of blood cells as WCC seen in the urine

– In ATIN, there can be both blood and protein found in the urine too. However, as it is a hypersensitivity reaction, there are more WCCs than blood cells in the urine

Chronic interstitial nephritis (CTIN)

This is a chronic condition of the interstitium and tubules

– Chronic inflammatory episodes eventually lead to fibrosis of the tubules impairing kidney function

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

Causes:

Most commonly due to drugs or infection

Treatment:

Stop causative agent and treat the progressive CKD