Congenital Kidney Diseases

1. Renal agenesis (absence of kidney): 

  • when ureteric bud fails to develop
  • unilateral or bilateral

(Note ureteric bud induces the metanephric tissue to form metanephric blastema)

(a) Unilateral renal agenesis

  • ✓relatively common (therefore, a clinician should never presume that a patient always has two kidneys)
  • ✓more common in males
  • ✓asymptomatic and compatible with life because the other kidney hypertrophies to meet requirements of the body
  • ✓usually detected while carrying out investigation for some other diseases.

(b) Bilateral renal agenesis

  • ✓relatively uncommon
  • ✓incompatible with life and newborn infant usually dies shortly after birth, unless a suitable donor is available for a kidney transplant
  • ✓causes oligohydramnios  uterine wall compresses the fetus  Potter’s syndrome. 

Clinical features of Potter’s syndrome

  • ✓deformed limbs, wrinkling of skin, abnormal facial appearance.

2. Duplication or multiplication 

of the kidneys: More than one  kidney may be present either  on one or both sides. This  occurs due to early division of  the ureteric bud. 2.5 Renal Hypoplasia.

Fraser Syndrome

  • Rare disorder 
  • Characteristic features of this condition include:
  • cryptophthalmos, cutaneous syndactyly), genitourinary anomalies. 
  • usually fatal before or shortly after birth; less severe can live into childhood or adulthood.
  • most common urinary tract abnormality is renal agenesis. 
  • A variety of other signs and symptoms including cardiac malformations, abnormalities of larynx or other parts of respiratory tract, facial abnormalities, including ear or nose abnormalities or cleft lip and cleft palate.

Congenital polycystic kidney

  • numerous cysts filled with urine present in substance of kidney. usually bilateral Embryological basis is as under:
    (a) Earlier it was thought that it occurs when excretory/ secretory and collecting tubules fail to connect with each other.
    (b) But now it is thought that it occurs due to abnormal dilatation of different parts of uriniferous tubules, especially loops of Henle. relatively common hereditary disease
  • Clinically associated with cysts of the liver, pancreas, and lungs.
  • two types:
    • childhood type and
    • adult type
  • prevalence of childhood type is 1:5000 births and adult type is 1:600 births.

Autosomal dominant polycystic kidney disease (ADPKD)

  • A multisystem disorder multiple bilateral renal cysts associated with cysts in other organs such as the liver, pancreas and arachnoid membranes a genetic condition caused by mutation in one of two different genes (PKD1 and PKD2) and is expressed in an autosomal dominant pattern, with variable expression occurs worldwide and in all races, with a prevalence of genetically affected individuals at birth of 1:400 to 1:1000. does not usually manifest before 30 years of age and in some, it is never diagnosed.
  • Hypertension is the most common manifestation of ADPKD and a major contributor to renal disease progression and cardiovascular morbidity and mortality. After the age of 20 years, most patients are hypertensive.
  • Autosomal recessive polycystic kidney disease (ARPKD). ARPKD is the more rare form of PKD. Symptoms of this condition begin very early in life, even while still in the womb.
  • The main symptoms of polycystic kidney disease (PKD) include:
    • High blood pressure
    • Pain or tenderness in the abdomen
    • Hematuria Frequent
    • urination Pain in the flanks
    • Urinary tract infection
    • Kidney stones
  • Meckel–Gruber Syndrome
    • Rare disorder characterised by microcephaly with occipital encephalocele, cleft palate, polydactyly, and large cystic kidneys. 

Joubert syndrome

  • Characterised by :-
    • parrot-beak nose,
    • slightly low-set ears,
    • a distended abdomen,
    • polydactyly,
    • cerebellar vermis is absent,
    • kidneys loose their reniform shape, are large and polycystic.

Short-rib syndrome 

  • Characterised by :-
    • large cranium with large fontanelles,
    • cleft lip and palate,
    • bilateral anophthalmia,
    • short ribs leading to a very small thorax,
    • a protuberant abdomen,
    • short symmetrical extremities and cystic renal dysplasia. 

Bardet–Biedl syndrome

  • Characterised by :-
    • retinitis pigmentosa,
    • obesity,
    • renal dysplasia,
    • polydactyly,
    • learning disability,
    • hypogonadism. 

Horseshoe-shaped kidney (also called horseshoe kidney)

  • Inferior poles of both kidneys are fused.
  • During ascent, horseshoe kidney gets trapped underneath the inferior mesenteric artery. Hence, it usually lies at the level of lower lumbar vertebrae.
  • Ureters arise from the anterior surface of the kidney and pass in front of isthmus in a caudal direction.
  • Occurs because sometimes the kidneys are pushed so close together during their passage through the arterial fork (formed by the umbilical arteries) that their lower ends get fused.

Zellweger Syndrome

  • Characterized by :-
  • hypotonia,
  • long and narrow forehead,
  • small whitish or grayish-brown spots in the iris (Brushfield spots),
  • hypoplastic supraorbital ridges,
  • epicanthal folds,
  • abnormal brain gyri, and seizures,
  • renal cystic dysplasia,
  • persistent fetal lobulations,
  • horseshoe kidney and urethral duplication. 

Lobulated kidney

  • Persistence of normal lobulated fetal kidney
  • Metanephric kidney is lobulated throughout the fetal life, but this condition usually disappears during the first year after birth.
  • But if it fails to do so then it leads to lobulated kidney.

Pelvic kidney

kidney is located in the pelvis.

  • occurs when kidney fails to ascend
  • commonest cause of failure of ascent of kidney is presence of  sickle-shaped fold of peritoneum (containing umbilical artery) that projects from lateral pelvic wall.

Pancake kidney

  • Two kidneys fuse to form a single mass that lies in midline or on one side.

Supernumerary/aberrant renal arteries

  • Relatively common
  • Represent persistent fetal renal arteries.
  • Fetal renal arteries arise successively in sequence from the aorta as the kidney ascends from the pelvic to the lumbar region.
  • Occurrence of aberrant arteries is clinically important because they may cross the pelviureteric junction and obstruct the outflow of urine leading to hydronephrosis.

Congenital anomalies of ureter

  1. Double renal pelvis: upper end of ureter presents two renal pelvises: upper and lower. The upper renal pelvis drains the upper group of calyces whereas the lower renal pelvis drains the middle and lower groups of calyces
    due to premature division of the ureteric bud near its termination.
  2. Bifid ureter: upper end of the ureter is bifid. In lower third of course two ureters join and open by a common orifice into the urinary bladder due to premature division of the ureteric bud.
  3. Double ureters: Duplication of the abdominal part of ureter and renal pelvis is common. due to division of ureteric bud as it arises from mesonephric duct. one ureter crosses across its fellow and may produce a urinary obstruction. double pelvis and double ureters are more liable to get infected and to be the seat of calculus formation than normal ureter. In case of double ureters, the lower ureter opens in the bladder at normal site, whereas upper ureter migrates more caudally due to caudal shift of the terminal part of mesonephric duct and opens in the ectopic position because terminal part of mesonephric duct undergoes loop formation in the posterior wall of urinary bladder.
  1. Ectopic ureter: ureter does not open into the urinary bladder.
    (a) In males, into the neck of urinary bladder or into prostatic part of urethra.
    (b) In females, into bladder neck, urethra, or vagina.
    (c) incontinence of urine is a common complain and occurs because urine flowing from the orifice of ureter does not enter into the urinary bladder.
    (d) occurs when ureter is not incorporated into the trigone of urinary bladder.
  2. Retrocaval ureter: It occurs if right ureter ascends posterior to inferior vena cava.

Ureterocoele

  • Cystic enlargement of the intramural ureter probably due to atresia of the ureteric orifice.
  • In childhood, usually present with infection
  • When large, can obstruct the bladder neck or even contralateral ureteric orifice
  • In adults, typically present with stones in the lower ureter
  • Classic sign of on excretion urography is a ‘cobra head’
  • On cystoscopy, a bulging, translucent swelling involving the ureteric orifice is typical which fills with and empties of urine with ureteric peristalsis.

Congenital megaureter

  • Ureteric dilatation with or without obstruction
  • Most cases present in childhood with severe infections
  • Renal stones can easily form in the dilated systems. 

Posterior urethral valves

  • Obstructive membranes that develop in urethra, close to the bladder.
  • Affects only male infants 
  • Occurs in about 1 in 8,000 births. 
  • Obstruct / block the outflow of urine to a variable extent.
  • bladder, ureters and kidneys become progressively dilated.
  • Signs or symptoms that require treatment:
    • Urinary tract infection
    • Weak urine stream
    • Difficulty with urination
    • Urinary frequency
    • New onset of urinary incontinence.

Prune-Belly syndrome (Eagle-Barrett syndrome)

  • Rare disorder, exact cause is not known.
  • Characterized by :-
    • partial or complete absence of the stomach (abdominal) muscles,
    • failure of both testes to descend into the scrotum (bilateral cryptorchidism),
    • and/or urinary tract malformations – hydroureter, hydronephrosis, vesicoureteral reflux.
  • Complications may include pulmonary hypoplasia and/or chronic renal failure.

Trisomies

  • Renal anomalies are not a constant feature of trisomies.
  • However, numerous examples have been reported of children with trisomies 13, 18, and 21 who also have hydronephrosis, horseshoe kidney, duplex kidney/collecting system, cortical cysts and/or cystic dysplasia, glomerular microcysts, or renal hypoplasia.

Other Biochemistry Notes

Biochemistry of Proteins

Carbohydrate Metabolism

VITAMIN PYRIDOXINE AND BIOTIN

Vitamin A

VITAMIN D

Pyrimidine metabolism

Purine Metabolism

Cardiac Biomarkers

. Blood Metabolism (Heme synthesis and breakdown)

Haemoglobinopathies

DNA Repair

Regulation of gene expression

DNA Replication

Transcription

Protein synthesis and genetic code

Detoxification (Xenobiotics)

Liver Function Test

Transamination Deamination & Urea Cycle

METABOLISM OF INDIVIDUAL AMINO ACIDS

Hydroxy amino acids

ACIDIC AMINO ACIDS (Aspartate and Glutamate)

Inborn Error Of Phenyl alanine, Tyrosine Metabolism

Electron Transport Chain & Biological Oxidation

RENAL FUNCTION TEST

Biochemistry Of Sodium, Potassium & Chloride

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