Nephrology

Question 1

What is pseudohypoaldosteronism?

Answer 1

Defect in ENAC receptor- not sensitive to Aldosterone
Results in hyponatremia and hyperkalemia (as ENAC not working)
Dehydration
High Aldosterone levels due to low circulating volume

BEWARE can occur in UTI

Question 2

How do you calculate the FeNA? (% of fraction excreted sodium)?

Answer 2

(urine Na x serum Cr)/ (urine Cr x serum Na) x100

Question 3

Idiopathic nephrotic syndrome

Answer 3

-Idiopathic NS (of which the most common form is minimal change disease – MCD) is steroid-responsive in most children.

• Approximately 30% of treated patients will not have a relapse and are therefore cured after the initial course of therapy.
• 10 to 20% will relapse several months after steroid treatment is discontinued, but will have less than four steroid-responsive episodes before permanent remission occurs.
• However, 30 to 40% of patients will have frequent relapses, defined as four or more relapses per year, and some patients will relapse while on steroid therapy (referred to as steroid dependent).
• In children with significant side effects of steroid therapy, other steroid-sparing agents (e.g. alkylating agents) that prolong remissions and reduce the dose of steroids should be considered. (1st line CYCLOPHOSPHAMIDE

Question 4

Treatment for MCD nephrotic syndrome

Answer 4

Treatment for minimal change nephrotic syndrome

1. high dose daily steroid for 6 weeks
   then alternate day for at least 4 weeks then tapered over the next 1-2 months

• if continues to have ++ proteinuria on daily steroid for 8 weeks = steroid resistant and should have renal biopsy
• if relapses while on alternate day steroid OR relapses within 28 days of successful steroid course = steroid dependent
• if responds well to steroids by relapse ≥4 times a year = frequent relapsers
• if steroid dependent, frequent relapser or steroid resistant - consider alternative therapies if high dose prednisone at 2mg/kg/day is not working (especially if there are steroid side effects)

Question 5

Treatments of MCD nephrotic syndrome when steroids are not working/ significant side effects

Answer 5

Cyclophosphamide – prolongs remission and decreases number of relapses (neutropaenia, disseminated varicella, haemorrhagic cystitis, alopecia, sterility, increased risk of future malignancy)

Cyclosporine/tacrolimus – induces and maintains remissions (HT, nephrotoxicity, HIRSUTISM, gingival hyperplasia)

Mycophenolate – helps maintain remission

Levamisole – reduces risk of relapse

ACEi/ARB – useful as adjunct to reduce proteinuria in steroid-resistant patients

Question 6

embryologically origins renal

Answer 6

Collecting system from URETERIC BUD (mesonephric duct):

• the collecting duct system
• major and minor calyces and the renal pelvis

Nephrons from METANEPHRIC BLASTEMA
Renal corpuscle – glomerulus, Bowman’s capsule
Renal tubule – proximal tubules, loops of Henle, distal convoluted tubules

Question 7

Nephronophthisis and medullary cystic kidney disease

Answer 7

• refer to two inherited diseases with similar renal morphology characterised by bilateral cysts and tubulointerstitial sclerosis leading to end-stage renal disease.
• MCKD is inherited in an autosomal dominant pattern and usually appears with adult-onset renal failure and no extrarenal involvement.
• Juvenile nephronophthisis is AR
• -> typically presents with polyuria, growth failure and unexplained anaemia
• -> causes chronic renal failure in late childhood or adolescence
• The histologic and biochemical characteristics of NPH indicate a defect of tubular basement membrane composition. This process, in turn, may lead to the destruction of the tubular basement membrane, which is a typical and early histologic finding in NPH-MCKD
• Get concentrating defect

Question 8

PSGN

Answer 8

ADD

Question 9

IgA nephropathy

Answer 9

ADD

Question 10

Membroproliferative GN

Answer 10

ADD

Question 11

Membranous GN

Answer 11

ADD

Question 12

Lupus nephritis

Answer 12

ADD

Question 13

Renal tubular acidosis type II

Answer 13

ADD

• proximal
• Failure of prox tubule to reabsorb HC03 from urine
• High HC03 in urine
• The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the alpha intercalated cells can produce H+ to acidify the urine to a pH of less than 5.3 THEREFORE urine still acidic rather than alkalotic
• Unless generalised defect can be mild
• Fanconi syndrome
• -> more generalised dysfunction of PT where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria.
• Cystinosis and Lowe syndrome
• P2197 nelsons

Question 14

Renal tubular acidosis type I

Answer 14

• Classical form of RTA
• characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated cells of the medullary collecting duct of the distal nephron.
• Medullary sponge kidney can get this type of RTA
• Normal anion gap metabolic acidosis/academia
• Hypokalemia (cos can’t excrete H+ so cannot reabsorb K+ as well as regular shift to maintain blood homeostasis)
• Hypocalcemia, Hyperchloremia

-Hypercalciuria –>Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate).

-Nephrocalcinosis (deposition of calcium in the substance of the kidney)
Bone demineralisation (causing rickets in children and osteomalacia in adults)

• Hypophosphaturia
• P2198 nelsons

Question 15

Anion gap

Answer 15

ADD see acute med

Question 16

Renal tubular acidosis type IV

Answer 16

• caused by hypoaldosteronism
• -> low production or hyporesponsiveness
• not associated with the syndromes like the other types of RTA
• associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in proximal tubular ammonium excretion (impaired ammoniagenesis), which is secondary to hypoaldosteronism, and results in a decrease in urine buffering capacity
• Its cardinal feature is hyperkalemia, and measured urinary acidification is normal

P 2198 nelsons

Question 17

Rickets assoc with RTA

Answer 17

ADD

P2200 nelsons

Question 18

Bartter syndrome

Answer 18

• rare
• AR
• hypokalemic metabolic alkalosis with HYPER calciuria (may have nephrocalcinosis), high urinary Na and K

2 types:

• neonatal (aka hyperprostaglandin E syndrome)
• -> presents in infancy
• > polyhyramnios, salt wasting, severe dehydration
• -> mutations NKCC2 channel (site of action of furosemide)
• classic barter
• -> presents in childhood
• > FTT, recurrent epsiodes of dehydration
• -> defect in NaK/Cl transport in ALOH. Loss of NaCl –> volume contraction –> stimulates RAAS –> worse hypokalemia + stimulates H+ ion loss distally –> worsens alkalosis
• -> defects in genes that produce basolateral chloride channel (ClC-Kb)

Dysmorphic features: triangular facies, protruding ears, large eyes with strabismus and drooping mouth

Question 19

Gitelman syndrome

Answer 19

Similar phenotype to Bartters (often called a variant)

• rare
• AR
• defect in NCCT (na/cl co-transporter) in DCT (Thiazide acts here)
• hypokalemic metabolic alkalosis
• HYPOcalciuria
• HYPOmagnesemia (and HYPERmagnesiuria)
• HYPOkalemia
• present later in childhood cf Bartter
• often have hx recurrent muscle cramps and spasms
• no hx of recurrent dehydration episodes
• renin and aldosterone normal
• FTT but not as prominent

RX: supplements with magnesium and K+. don’t need to give sodium supplements or Rx with prostaglandin inhibitors as don’t get volume depletion or elevated prostaglandin E secretion

Question 20

Dent disease

Answer 20

X-linked nephrolithiasis
recurrent stone formation
mutations in gene encoding voltage gated chloride channel (CLN5) present in the nephron

Question 21

Cystinuria

Answer 21

AR
Middle eastern
recurrent stone formation
defective high affinity transporter for L-cysteine and dibasic amino acids present in PT

Question 22

Multi-cystic dysplastic kidney disease

Answer 22

NOT the same as medullary cystic kidney disease

MCKD is the most common cause of abdominal mass in newborn. The kidney is replaced by cysts and does not function.
◾15% have contralateral VUR
◾5-10% have contralateral hydronephrosis
◾0.2-1.2% develop hypertension
◾0.3% risk of Wilms

There is complete cyst regression occurs by age 7 in nearly half of patients

Question 23

Type III RTA

Answer 23

• combined pRTA + dRTA
• very rare
• Carbonic anhydrase deficiency
• important as part of syndrome of renal tubular acidosis, cerebral calcification, and mental retardation

Question 24

Autosomal dominant polycystic kidney disease

Answer 24

A decrease in urine concentrating capability is an early manifestation of the disease.

Patients can develop renal failure usually in the forth to sixth decade of life.

It is a multisystemic and progressive disorder and not only do cysts form in the kidney but they can form in other organs too especially the liver, pancreas and spleen. Colonic diverticula occur in 80%.

Periportal fibrosis does NOT occur