Tubular Diseases of the Kidney

• The tubular diseases of the kidney have various pre­sentations.

POLYCYSTIC KIDNEY DISEASE

Autosomal dominant polycystic kidney disease

• This is a relatively common cause of end-stage renal disease (ESRD).
• The kidneys are enlarged with multiple cysts.
• The cysts contain straw-colored or hemorrhagic fluid. The cysts are spherical and may be even a few ems in size.
• There is also i’nterst’itial fibrosis and nephrosclerosis.

Clinical Features of POLYCYSTIC KIDNEY DISEASE

• · May present ~t any age.
• · Symptoms begin in 3^rd or 4^th decade.
• · There is chronic pain in the flanks.
• · Acute pain may be due to UTI, and urinary tract
• obstruction by clot, stone or haemorrhage.
• · Nocturia may be present.
• · Nephrolithiasis (renal stones) is common.
• · There is hypertension especially in adults.
• · ESRD sets in rapidly after 3^rd decade.
• · There is renal failure due to hypertension, infec­tions, ureteral obstruction.
• · There may be cysts in the spleen, pancreas and ovaries.
• · There may be intracranial aneurysms and sub­arachnoid haemorrhage.
• · There may be MVP (mitral valve prolapseL AR, TR.
• · Urine pH is low.

Diagnosis

• Ultrasound – is the best technique for polycystic dis­ease.
• CT scan

POLYCYSTIC KIDNEY DISEASE  Treatment

• Control of hypertension Treatment of infections Dialysis, Renal transplant

Autosomal recessive polycystic kidney disease

• Here the disease usually leads to death in neonatal or childhood period. There is hepatic fibrosis, portal hypertension and liver failure.
• It is diagnosed by ultrasound.

Treatment

• Treat hypertension and UTI Dialysis and transplant
• For hepatic fibrosis and haemorrhage – sclero-­therapy and portosystemic shunts.

VON HIPPEL–LINDAU DISEASE

• This autosomal dominant disease is characterized by hemangioblastomas of retina and central nervous system.
• There are bilateral renal cysts.

MEDULLARY SPONGE KIDNEY

• It is a congenital autosomal dominant disease with bilateral renal involvement.
• There are cystic dilatations of collecting ducts. Patients have renal stones, infection, hematuria.
• Diagnosis–
  • IVP (Intravenous Pyelogram), and ultra­sound.
• Treatment-
  • Treat stones, infections, metaboli[.: ab­normalities.

MEDULLARY CYSTIC NEPHRONOPHTHISIS

• Presents during childhood with polyuria, growth re­tardation, anaemia, renal failure.

LIDDLE’S SYNDROME

• It is au(osomal dominant with hyperaldosteronism­consisting of hypertension, hypokalemia, metabolic alkalosis.
• Treatment
  •  is low-sodium diet and potassium-spar­ing diuretics.

BARTTER’S SYNDROME

• There is hypokalemia, metabolic alkalosis, low blood pressure, growth retardation, nephrocalcinosis.
• Treatment –
  • Potassium supplement, increased in­take of sodium, spironolactone, NSAIDs, ACE inhibi­tors.

GITELMAN’S SYNDROME

• There is hypokalemia, metabolic alkalosis, normal blood pressure, hypomagnesemia, hypocalciuria.

RENAL TUBULAR ACIDOSIS

• It is a disorder of renal acidification.
• There is hyperchloremic metabolic acidosis with nor­mal serum anion gap {Na+ – (Cl- + HC0₃‘)}.
• There is defective bicarbonate reabsorption from proximal tubule.
• There is decreased production of ammonia, decreased secretion of proton from the distal tubule.

There are four types of RTA

• Type 1 and’ 2 may be inherited or acquired.
• Type 3 is very rare.
• Type 4 is usually acquired and associated with hypoaldosterorlism.
• 
  

  Type 1 RTA -This is also called distal RTA.

  • The distal nephron does not lower the urine pH be­cause the collecting ducts permit diffusion of hydro­gen ions back into the blood from the lumen of the duct.
  • Chronic acidosis lowers the tubular reabsorption of calcium leading to hypercalciuria and secondary hy­perparathyroidism.
  • The hypercalciuria, alkaline urine and low levelS-of urine citrate lead to calcium phosphate stones and nephrocalcinosis.
  • There is growth retardation. There is bone disease.
  • There is polyuria and hypokalemia.
  • There may be intercurrent illnesses.
  • Acidosis and hypokalemia can lead to death. There is normal anion gap metabolic acidosis. Urine pH is >5.5
  • On administration of ammonium chloride urine pH does not fall below 5.5 and systemic acidosis wors­ens.
• Treatment -,
  • Alkali supplements – Sodium bicarbonate and Shohl’s solution are used.
  • Relatives of type 1 RTA should be screened for the disease.
• 
  

  Type 2 or Proximal RTA

   

  • Type 2 RTA occurs as a part of generalized disorder of proximal tubule.
  • There is hyperchloremic acidosis like Fanconi syn­drome.
  • Bicarbonate absorption is defective therefore there is bicarbonaturia.
  • There is hypophosphatemia and low calcitriol levels leading to rickets and osteomalacia.
  • There is hypercalciuria.
  • In Type 2 – RTA the urine is not so much alkaline as in type 1 RTA. The urine anion gap is positive.
• Treatment
  • Alkali is given in large amounts 5-15 meqjkg body weight j day.
  • Thiazide diuretic and low salt diet is given.
  • Potassium supplements may also be given with alkali.
• 
  

  Type 4 RTA It is also called hyperkalemic distal RTA.

  • There is abnormal distal tubule secretion of potas­sium and hydrogen ions leading to hyperchloremic acidosis and hyperkalemia.
  • It is an acquired disorder. There is renal insufficiency.
  • The urine is acidic with pH <5.5.
  • Etiology of Type 4 RTA may be hyporeninemic hypoaldosteronism, diabetic nephropathy, obstructive uropathy, sickle cell disease, NSAIDs, ACE inhibitors, heparin, potassium sparing diuretics.
• Treatment
  • Low potassium diet Potassium lowering therapy Loop diuretics
  • Exchange resins
  • Stop aldosterone antagonists.
  • It is a generalized defect in proximal tubule trans­port. There is proximal or Type 2 RTA.
  • There is glucosuria with normal serum glucose, hy­pophosphatemia, hypouricaemia, hypokalemia.
  • Rickets and osteomalacia are common due to hypo­phosphatemia.
  • Metabolic acidosis, polyuria, hypokalemia may be severe.
• Treatment . ,
  • Phosphate supplement and calcitriol
  • Alkali
  • Increase salt and water intake Potassium alkali salts.