Answers for Day 2

1) A    –  ds-DNA in lupus is associated with disease activity (increased in active ongoing lupus nephritis)

2)  C  – HSP is associated with IgA deposition in mesangium. Note the fleeting type of symptoms, which is classic for HSP  a) Intermittent abdominal pain

b) Migratory polyarthritis

c) Waxing and Waning palpable purpuric rash

IgA nephropathy is a primary renal disease secondary to under galactosylated IgA and subsequent IgG orIgA1 antibody against the abnormal IgA with deposition of antigen + antibody complex in the mesangium. HSP is a systemic vasculitis !

3) B – MPO ANCA vasculitis with GPA presentation! Given the RPGN picture, cytoxan and glucocoticoids is the right answer. However, if this question is framed as a very mild case of MPO ANCA associated GPA, rituximab with glucocorticoids is the answer.(RITUXVAS)

4) C – APSGN.  Low C3 and normal C4 indicated alternate complement pathway activation(strep infection classically leads to alternate complement activation). You dont expect C1q, C4 in the biopsy !

5) A – Anti-GBM disease


6) D -C3 glomerulopathy. Uninhibited alternate complement pathway activation by the deficiency of complement regulatory factors! In this case factor H related proteins!



X linked diseases in kidney !

What about these X linked diseases in kidney !

From board stand point, Alport syndrome and  Fabry disease are important AND both these disorders are X linked.

Alport syndrome : Mutation in COL4A5 gene (Thin membrane disease is a structural anomaly secondary to mutation in COL4A3 and COL4A4)

Fabry disease : Mutation in alpha galactosidase A gene.

There are autosomal variants of these diseases and can rarely affect females but not tested in the boards usually!

Dent’s disease – familial nephrolithiasis is also X linked.

ADPKD  is autosomal dominant (as the name implies) – 40% associated with liver cysts, 5% associated with AVM . It is not cost effective to do screening for AVM in all patients with ADPKD. However, if there is a family history of Hemorrhagic stroke (where the risk of AVM goes up to 20%), Screening is recommended !

Medullary sponge kidney is usually a developmental anomaly but can have a hereditary predisposition!


Radiology for boards

1) Should be able to identify stone – hypoechoic shadow is a clue

2) Should be able to identify ADPKD, Aquired cystic disease of dialysis (history will be helpful), Benign cyst and RCC  – Understanding Bosniak classification of cyst is helpful for diagnosis

3) Irregular margin and contrast enhancing cyst is RCC

4) US screening for Renal artery stenosis –  RA/A >3.5/1

RA velocity>2mps

It is also useful to understand the downstream waveform in the lobar and lobular arteries- Tardus parvus waveform and loss of ESP(early systolic peak) notch suggests significant RAS

5) Should be able to identify hydronephrosis

6) RI in normal kidney is<75 and Transplant kidney is<80  . RI is systolic/systolic +diastolic flow. RI of1 indicates no diastolic flow.

7) Granulomatous pyelonephritis – easily identified. Needs nephrectomy!

8) Non contrast CT stone protocol has 98%PPV and 98%NPV

9) Calcification – Medullary calcification and cortical calcification is easily recognized by location. Irregular bilateral asymmetric medullary calcification is usually Medullary sponge kidney

10) In post transplant kidney – elevated RI and Elevated Peak systolic velocity in Renal artery >300 cm/sec doen not indicate stenosis and it should normalize within 72 hours of transplant.


These are some of the high yield points in imaging. Please tag other points you may consider worthwhile revising or for understanding.(tag to this post)


Answers to Day 1 questions (10 questions)

1) C – ANCA vasculitis treatment  – prednisone and Cyclophosphamide. There is plasmapheresis in the choice . If they specifically ask for initial therapy, then prednisone and plasmapheresis could be considered. This patient did not have pulmonary hemorrhage and was not sick !

2) B – Fabry disease. This is an X linked recessive disease which predominantly affects male ! Deficiency of Alpha galactosidase A causes accumulation of sphingolipids(glycolipids and in this disease specifically galactoacylcerebrosidase) in blood vessels , nerves kidney and heart. The manifestations are neurological(pain and tingling in extremities, progressive CKD-especially in 3 decade, Cardiac hypertrophy, abdominal pain(accumulation of sphingolipids in blood vessels supplying intestines) and skin rash(especially around the umbilicus)

3) D – Sickle cell/Tylenol/NSAID combination should raise suspicion about papillary necrosis

4)A – Arterial line is negative pressure and is causes dialysis catheter to flatten out!

5) B – most common cause of intradialytic hypotension is diastolic dysfunction. I was tempted to choose pericardial effusion given the stem of the case .

6) E – Hyperglycemia- very common cause of PD ultrafiltration failure since it decreases the solute gradient dramatically!

7) C – Isolated scrotal swelling should raise concerns about patent processes vaginalis in a new PD patient

8) E  -Gentamycin toxicity- hypomagnesemia

9) C – Cyclosporine toxicity causes hirsutism

10) B – Increased urine oxalate -pathogenesis for calcium oxalate stone in Chron’s disease


Hope the explanation helps!


Potassium and acid base

Hypokalemia is associated with alkalosis and Hyperkalemia is associated with acidosis! We have heard about this but did ‘t know if this had mechanistic/pathogenetic significance until we heard Dr.Weiner’s lecture today.

Hypokalemia increases ammonia production in proximal tubule which is absorbed into the interstitium in the ascending loop of Henle through NKCl cotransporter (since the concentration of ammonia is several hundred folds higher than potassium in hypokalemic state). The ammonia  decreases the activity of ENaC in the principal cell , which decreases potassium excretion(this is favourable in hypokaleic state since K is conserved by this) and ammonia combines with proton secreted in the alpha intercalating cell thereby increasing net acid excretion.

In short, hypokalemia signals the cortical collecting duct to decrease potassium excretion by increasing the production of ammonia.

Hyperkalemia decreases ammonia production in proximal tubule and the net acid excretion is decreased.

It was interesting to know the cause of hyperkalemia in acidosis!

This explanation based on ammonia generation hypothesis holds good only in chronic acidosis and not in acute acidosis such as DKA and lactic acidosis.


Water diuresis and osmotic diuresis

Both water diuresis and osmotic diuresis can lead to hypernatremia!  How do we differentiate?


Water diuresis and osmotic diuresis , both present with hypernatremia and polyuria!

In water diuresis, the osmolar excretion per day is less than 1000 mOsm/day (calculated from urine osmolar concentration and urine volume) and in osmotic diuresis, the osmolar excretion per day is>1000   mOsm/day.

Water diuresis occurs in Diabetes insipidus

Osmotic diuresis occurs in Parenteral nutrition with heavy protein intake(10 grams protein yield 50 mOsm of urea) and  Diabetes mellitus(glucose is the osmole in urine that drags water with it)

It is nice to understand this concept. However in clinical situation the numbers don’t matter so much and the free water loss  is usually  from a combination of several factors!

Like,  Critically ill intubated patient recovering from ATN on TPN for nutrition. Here you have no access to free water, water diuresis from recovering ATN(some degree of renal concentrating defect/nephrogenic DI) and osmotic diuresis from TPN!

Nevertheless, it helps us identify the major contributor !



Metabolic alkalosis – understanding the classification and pathogenesis


Metabolic alkalemia is difficult to sustain since Kidneys can excrete excess bicarb and correct alkalosis quickly. When there is chloride depletion or hypokalemia, kidneys have decreased ability to excrete the excess bicarb and metabolic alkalemia ensues.

This takes us to the next question!

1) Why does chloride deficient state decreases the ability to excrete excess bicarb?

2) How does hypokalemia contribute to maintaining metabolic alkalosis?

Chloride deficient state increases bicarb reabsorption in proximal tubule and distal tubule(To maintain electro neutrality either chloride or bicarb( two predominant anions) has to be reabsorbed with sodium, so in chloride deficient state bicarb is reabsorbed). Also, in the cortical collecting duct(beta intercalated cell) chloride from the lumen is exchanged for bicarb from inside the cell. In the chloride deficient state, this is limited. I guess, these are good enough reasons for maintaing the alkalosis in chloride deficient states(what ever be the initial pathology that initiated the alkalosis)

Hypokalemia increases ammonia generation in proximal tubule and thereby facilitates acid excretion(even in alkalemic state). Hypokalemia also causes intracellular acidosis(protons exchanged for K  trying to mitigate hypokalemia)and extracellular alkalosis. This in proximal tubule will lead to increased acid excretion and bicarb reabsorption. Also, most cases of hypokalemia are associated with hyperaldosteronism (either primary or secondary ) which by itself increases acid excretion by activating H/K pump and also by K excretion in principal cell(in response to Na absorption through ENaC) which inturn is exchanged for proton .

Now we understand that to maintain metabolic alkalosis, there should be either chloride depletion or potassium depletion and it makes much more sense to classify metabolic alkalosis as

1) Metabolic alkalosis secondary to chloride depletion

2) Metabolic alkalosis secondary to potassium depletion



Chloride depletion occurs in vomiting, NG suction, diuretics (chloruretic diuretics in contrast to kaliuretic diuretics)

K depletion occurs  in the following conditions

  • Primary hyperaldosteronism
  • Cushing’s syndrome
  • Secondary hyperaldosteronism
  • Kaliuretic diuretics
  • Excessive licorice intake
  • Bartter’s syndrome 
    Severe potassium depletion

The rest of the causes of metabolic alkalosis are usually not sustainable without chloride deficient state or a potassium deficient state(milk alkali syndrome, persistent bone resorption-where kidneys will step up alkali excretion)

Vomiting, NG suction, Diuretic use, Hyperaldosteronism(primary and secondary) and Severe potassium depletion accounts for 90% of the cases of metabolic alkalosis!

Hope this helps to quickly know the differentials of metabolic alkalosis and to quickly think about the pathogenesis .





Follow up/ 03/17/2014 from commentary section

Dr.Weiner’s lecture today gives us the reason why Hypokalemia in RTA is not associated with increase in ammonia production!. The defect in Type 2 RTA is NBE2 in the basolateral membrane(most likely pathogenesis) . This increases bicarb concentration intracellularly in the proximal tubular cells and thereby the systemic acidosis is masked and the proximal tubular cells spill bicarb in the urine much more than what can be reabsorbed by distal mechanism.
In Type 1 RTA although NH3 production is increased proximally, this has to be reabsorbed in the ascending loop of Henle(NKCl cotransporter is used for ammonia reabsorption) and subsequently this reabsorbed ammonia should be secreted in the distal tubule to help H+ excretion. The defect in H+ ATP prevents NH4 + production. So the net Ammonium production is decreased in type 2 RTA and this contributes to acidosis.


Aquired Gitelman syndrome in Sjogren’s

66 y/o f with long history of Sjogren’s syndrome and RA presented with hypokalemia, hyponatremia and metabolic alkalosis. She had a TTKG> 10 when her K was 2.9 indicating K wasting. She had normal calcium level and magnesium level. Aldosterone level was elevated and Plasma renin activity was not suppressed.

24 hour urine K was increased and calcium was pending.


We suspected Gitelman syndrome!

I was very hesitant to agree with this diagnosis given the age of onset of symptomatology and the long history of Sjogren syndrome. A diagnosis which will go with her history of autoimmune disorder would have made more sense.

On reviewing  Sjogren syndrome related hypokalemia, I understood that,

1) SS can lead to Type 1 RTA (hypokalemia and acidosis) – However, the pt had alkalosis and not acidosis

2) SS can lead to Na wasting  and this subsequently leads to K wasting in principle cell(in exchange for sodium). This mechanism is entirely different from RTA

3) Autoantibodies targeted against NCC and subsequently leading to Aquired Gitelman syndrome.


Well, the third possibility sounds reasonable in this clinical setting!

Follow the link to study more about aquired Gitelman in Sjogren syndrome



Update from commentary section

There are other references for the aquired Gittelman Syndrome which I am presenting below.