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TUTOR - Kidney Transplantation
  • Test Id: 1957468cea0bb6c52e
  • QId: 165261
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50-year-old female patient whos group B is being evaluated for kidney transplant surgery. She had ESRD secondary to analgesic nephropathy and is on hemodialysis for last 5 years. She has had multiple sensitization events in the form of 3 pregnancies and several blood transfusions. Her current calculated PRA against class I antigen is 97% and against class II antigen is 99%. She has been enrolled in the national highly sensitized recipient program.

Her husband who is blood group matched came forward as a potential kidney donor but she had positive Flow B and T Cell Cross match against him. Single antigen bead assay demonstrated that she has donor specific antibodies against class II across DQB*15 and DPB*14. This transplant did not materialize as patient declined desensitization protocol. Now her younger brother comes forward as a potential donor. He is blood group A and the flow B and T cell cross match is negative with no demonstrable donor specific antibodies against this donor.Patient wants to know more about ABO incompatible transplant.


Which of the following statements about the ABO incompatible transplant is correct?


A. Three-year graft survival is inferior to blood group compatible transplants.
B. The infectious and bleeding complications post ABOI kidney transplant are the same as blood matched kidney transplant.
C. All patients undergoing ABOI transplant need to undergo desensitization using IVIg, Plasma exchange, Rituximab irrespective of their donor/recipient pair Anti ABO titers for optimal outcomes.
D. C4d staining on protocol biopsies is common feature and does not necessarily mean an antibody mediated rejection process in the absence of allograft dysfunction.

Correct answer: Option D: C4d staining on protocol biopsies is common feature and does not necessarily mean an antibody mediated rejection process.


Explanation:


Choice A: Three-year graft survival is inferior to blood group compatible transplants is incorrect A comprehensive database analysis of 1420 ABOI living donor (LD) kidney transplants performed in 101 centers from 2005 to 2012 compared graft and patient survival to a matched cohort of ABO-compatible transplant recipients. Three-year graft and patient survival were ultimately identical. 1


Choice B: The infectious and bleeding complications post ABOI kidney transplant as same as blood matched kidney transplant is also incorrect. Using USRDS and Medicare data from 2000–2007, 119 ABOI (non-A2 donor) transplant recipients were identified. Compared with ABO-compatible recipients, the risks of infectious and hemorrhagic complications were significantly higher, with a 2.2-fold higher risk of pneumonia, a 3.5-fold higher risk of wound infections, a 56% higher risk of pyelonephritis, and a nearly 2- fold higher risk of hemorrhage 2


Choice C: All patients undergoing ABOI transplant need to undergo desensitization using IVIg, Plasma exchange, Rituximab irrespective of their donor/recipient pair Anti ABO titers for optimal outcomes is also an incorrect answer. Historically, ABOI transplantation has been successful when performed after desensitization with plasmapheresis, intravenous Ig (IVIG), rituximab, and/or splenectomy to achieve ABO IgG antibody titers 1:4. A recent publication demonstrated that these intensified treatments might not be necessary in donor/recipient pairs who have low-moderate titer ABO incompatibility 3


Choice D: C4d staining on protocol biopsies is common feature and does not necessarily mean an antibody mediated rejection process in the absence of allograft dysfunction is the correct answer C4d staining is not an uncommon feature seen in the protocol biopsies done in ABOI kidney transplant recipients. In the absence of allograft dysfunction, the C4d staining has no clinical relevance and is just a part of the graft accommodation.

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957468cea0bb6c52e
  • QId: 165264
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A 68-year-old gentleman, Caucasian descent, comes to clinic for follow up visit. He is known to have type 2 diabetes mellitus for the past 18 years. His father had diabetes from 40 years of age and developed kidney disease requiring dialysis after 15 years of diabetes. He reports no symptoms. He has been having hypertension and coronary artery disease with history of  PCI 2 years ago. He has non-proliferative diabetic retinopathy. His medications are sitagliptin, gliclazide and metformin in addition to losartan and hydrochlorothiazide. He has been monitoring blood sugar at home and reports no hypoglycemia. He exercises at least at least 30 minutes per day. His vitals recording shows BP of 168/66 mm Hg. His BMI is 29.2.  Systemic  examination is unremarkable.

His laboratory investigation is reported as follows.

Characteristic

value

Hemoglobin

12.2 gm/L

WBC count

6.8 X 103/cubic mm

Platelet count

241 X 103/cubic mm

Segmented Neutrophils

Lymphocytes

Monocytes

Band neutrophils

Eosinophils

Basophils

60%

36%

2%

0%

2%

0%

Sr. Sodium

139 mEq/L

Sr. Potassium

4.9 mEq/L

Sr. Creatinine

1.2 mg/dL

Sr. Bicarbonate

22 mEq/L

Sr. Chloride

101 mEq/L

Total Bilirubin

1.0 mg /dL

AST

16 U/L

ALT

18 U/L

Sr. Albumin

4.0 g/dL

HBA1C

7.8%

Sr. Calcium

10 mg/dL

Urine dipstick

pH- 5.4

Albumin-trace

 no blood

 no WBCs

24-hour urinary albumin

200 milligrams/day


What is the MOST LIKELY correct statement regarding clinical diagnosis of Diabetic Kidney Disease in this patient ?

A. Diabetic Kidney Disease previously called as diabetic nephropathy can be diagnosed clinically with renal biopsy only.  
B. Presence of microalbuminuria is adequate for clinical diagnosis of Diabetic Kidney Disease. 
C. Presence of hematuria without non-diabetic kidney disease is impossible in Diabetic Kidney Disease as diabetic kidney disease is a non-proliferative glomerular disease. 
D. Family history of Diabetic Kidney Disease is associated with renal involvement in Diabetes.

The Correct Answer is Option D: Family history of Diabetic Kidney Disease is associated with renal involvement in Diabetes.

 Explanation:

Familial studies have demonstrated clustering of diabetic nephropathy. Patients with DM with a first-degree relative with T1/T2DM and diabetic nephropathy have more risk for developing diabetic nephropathy than those without an affected relative. This familial clustering has also been well documented in the Pima Indian population. The candidate genes identified are glucose transporter 2(GLUT2), transforming growth factor beta (TGF- ?), and endothelial nitric oxide synthase (eNOS). 

Option A:  Diabetic nephropathy is a clinical syndrome characterized by the following:

·         Persistent albuminuria (>300 mg/d) that is confirmed on at least 2 occasions 3-6 months apart

·         Progressive decline in the glomerular filtration rate (GFR)

·         Elevated arterial blood pressure 

 Hence kidney biopsy is not a mandatory investigation to diagnose diabetic kidney disease.

 Option B:  If the amount of urine albumin exceeds 30 mg/d and is less than 300 mg/d it is called microalbuminuria, and if it is greater than 300 mg/d it is called macro albuminuria or overt albuminuria. Microalbuminuria is present in 5-7% of normal individuals and is associated with cardiovascular mortality and morbidity. It is marker of endothelial dysfunction in type 2 diabetes mellitus. Presence of microalbuminuria alone with diabetes cannot be clinically diagnostic of diabetic kidney disease.

Option C:  Micro hematuria has been demonstrated in biopsy studies with isolated diabetic nephropathy. Red blood cell casts have also been described in patients with diabetic nephropathy. However, it is important to rule out other glomerular and extra-glomerular causes of hematuria.

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957468cea0bb6c52e
  • QId: 167340
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A 40 year-old pleasant African man with ESRD secondary to FSGS started automated peritoneal dialysis. His prescription includes 2.5 L and 3 exchanges over 8 hours at night with a last fill of 2 L. He has a urine output of 1000 mL/day. A typical ultrafiltration on cycler is used at 1000 mL. Average drain volume of the day dwell was 1500 mL prior to going on the cycler at night. 

He came with complains of lower abdominal wall edema extending to the scrotum over the past 5 days. Without any change in the dialysis prescription, his drain volume before going on the cycler dropped to 900 mL, and the ultrafiltration volume on the cycler came down to 100 mL. He reports no pain with fill or drain. 

What is the next step?


A. Chest X ray PA and lateral view 
B. Drain the fluid middle of the day to reduce the dwell time
C. PD catheter manipulation
D. Abdominal CT scan with contrast in the dialysate
E. Switch to hemodialysis 
E. Pleurodesis 
The correct answer is D 

Abdominal CT scan with contrast in the dialysate

Explanation:

Typical ultrafiltration failure from peritoneal membrane failure presents gradually. More frequently, we see an apparent ultrafiltration failure from other reasons. 

Catheter malfunction can present with problem with inflow, outflow or both. A kink in the catheter poses problem with inflow and outflow. 

Omentum or blood clots clogging the catheter can cause only outflow problem. Fibrin clots, constipation with loaded rectum, and displaced PD catheter also cause outflow obstruction. X ray KUB is very helpful in diagnosing displaced catheter.   

FLUID LEAK leak into the abdominal wall causes swelling in the lower abdomen extending down to the scrotum or mons pubis and decrease in the drain volume. Usually this can be treated by temporarily doing low volume PD or transferring to HD for about 6 weeks. Such leaks starting few years after initiating PD usually do not respond to this approach and often requires placement of a new PD catheter.

A patent tunica vaginalis testes will cause UNILATERAL OR BILATERAL SCROTAL SWELLING without much swelling of the abdominal wall sometimes associated with decrease in the drain volume. A CT scan of the abdomen with ‘IV’ contrast into the peritoneal fluid can help in diagnosing the leak into the abdominal wall and scrotal leak. Patent tunica vaginalis testes requires surgery. Generally hemodialysis is not required after the surgery and low volume peritoneal dialysis can be resumed. This patient presents with signs of leak of fluid into the abdominal wall. A chest X ray is not required, so (Choice A) is wrong.

Draining during the middle of the day helps if the membrane is very permeable with very high D/P creatinine ratio on PET. This does not help in abdominal wall leak of dialysate. Therefore, (Choice B) is also wrong.

PD catheter manipulation (Choice C) is wrong because this patient does not have displaced PD catheter from the information given.

(Choice D) is the correct answer. If the clinical presentation is very convincing, most patients are treated with reducing the dialysate volume and if possible keeping the abdomen dry during the day. Sometimes these patients need to be switched to hemodialysis for 4-6 weeks before PD is resumed. Hence temporary switch to HD would be a correct answer, but unqualified switch to HD as is stated in answer E would be a wrong choice. Therefore, (Choice E) is the wrong or less appropriate answer.

ABDOMINAL ADHESIONS cause decrease in the drain volume as well and require surgical treatment with low volume PD or temporary HD after that.

DIAPHRAGMATIC LEAK into the pleural space presents with cough and shortness of breath without peripheral signs of fluid overload few weeks after starting peritoneal dialysis (not the presentation in this patient). Usually, such patients present with right sided pleural effusion clinically and on chest X ray PA and lateral view. These patients can be treated with temporary transfer to HD, pleuridesis and return back to PD 4-6 weeks later. Permanent switch to hemoidialysis without pleurodesis is another option.


TREATMENT OPTIONS OF VARIOUS ABDOMINAL/CHEST PROBLEMS AS MENTIONED ABOVE IN PATIENTS ON PERITONEAL DIALYSIS IS FREQUENTLY TESTED ON BOARDS. PLEASE KNOW THE TREATMENT OPTIONS.


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Last Modified: 08/06/2018

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TUTOR - Kidney Transplantation
  • Test Id: 1957468cea0bb6c52e
  • QId: 167345
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Cyclosporine nephrotoxicity in a renal transplant recipient is associated with all the below renal biopsy findings EXCEPT:

(THIS PICTURE BELOW IN LOW POWER SHOWS ONE OF THE CLASSICAL FINDINGS IN CSA TOXICITY)


A. Interstitial Fibrosis  
B. Tubular atrophy 
C. Endothelial cell swelling 
D. Glomerular thrombin deposits
E. Glomerular basement membrane thickening 
E. Double contours of the GB 
The correct answer is D

Glomerular thrombin deposits

Explanation:

In a patient with suspected cyclosporine nephrotoxicity, the renal biopsy reveals an obliterative arteriolopathy (which is classically seen in afferent renal arterioles) suggesting primary endothelial damage and subsequently endothelial cell swelling which may persist for months in a patient with elevated cyclosporine blood levels. This is also associated with thickened glomerular basement membrane and double contour pattern. In fact according to BANF thickened glomerular basement membrane and double contour pattern is most suggestive of chronic allograft nephropathy (CAN) also called as TRANSPLANT GLOMERULOPATHY. 

The other renal biopsy findings of cyclosporine nephrotoxicity include ischemic collapse or scarring of the glomeruli, vacuolization of the tubules, FSGS, and focal areas of tubular atrophy and interstitial fibrosis (producing a picture of “ZEBRA” or "STRIPED" fibrosis) These changes are seen with both low-dose and higher-dose cyclosporine therapy, although they seem to co-relate earlier with higher doses. 

(THE ABOVE PICTURE IN THE UPPER HALF SHOWS TUBULAR ATROPHY APPEARING DARK AND REDDISH ALTERNATING WITH LIGHT BLUE AREAS OF INTERSTITIAL FIBROSIS GIVING A "STRIPED" OR "ZEBRA" APPEARANCE)

THE PICTURE BELOW SHOWS TUBULAR ATROPHY, VACUOLIZATION OF THE TUBULES AND ISCHEMIC CHANGES:


Mild arteriolar hyalinosis at six months appears to be associated with high doses of cyclosporine and was reversible. However, after more than a year irreversible severe arteriolar hyalinosis and glomerulosclerosis were observed, despite decreased doses and trough levels of cyclosporine.

Glomerular thrombin deposits are typically seen in patients with Lupus, anti phospholipid syndromes and other vasculitides. It is typically not seen in cyclosporine nephrotoxicity.

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TUTOR - Physiology
  • Test Id: 1957468cea0bb6c52e
  • QId: 165262
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A 28-year-old gentleman, Caucasian descent, comes to clinic for follow up visit. He has been found to have type 1 diabetes mellitus since the age of 12 years of age. His cousin brother has the same disease. He reports no symptoms. He has been using insulin pump using insulin Aspart. He has been monitoring blood sugar using flash glucose monitor and uses carbohydrate count for boluses. He reports infrequent hypoglycemic episodes particularly 2 hours into post lunch, but, manages by himself. He exercises at least at least 60 minutes per day. His vitals recording shows BP of 118/66 mmHg. His BMI is 23.2.  System examination is unremarkable.


His laboratory investigation is reported as follows.


Characteristic

Value

Hemoglobin

14.2 gm/L 

WBC count

6.8 X 103/cubic mm

Platelet count

241 X 103/cubic mm

Segmented Neutrophils 

Lymphocytes

Monocytes

Band neutrophils 

Eosinophils

Basophils

60%

36%

2%

0%

2%

0%

Sr Sodium

139 mEq/L

Sr Potassium

4.4 mEq/L

Sr Creatinine

0.6 mg/dL

eGFR using CKD-EPI

136.8 ml/min/1.73m2

Sr Bicarbonate

24 mEq/L

Sr Chloride

101 mEq/L

Total Bilirubin

1.0 mg /dL

AST

16 U/L

ALT

18 U/L

Sr Albumin

4.0 g/dL

HBA1C

7.9%

Sr Calcium

10 mg/dL

Urine dipstick

pH- 5.4

Albumin-nil

 no blood

 no WBCs

24-hour urinary protein 

76 milligrams/day


What is the MOST LIKELY incorrect statement regarding hyperfiltration stage of Diabetic Kidney Disease in this patient?

A. Renal hyperfiltration is usually diagnosed when the GFR is more than 120 ml/min,which corresponds to a renal function that exceeds two standard deviation above mean GFR.
B. Renal hyper filtration usually precedes microalbuminuria in type 1 diabetes mellitus.
C. Renal hyper filtration is considered as a risk factor for future progression to chronic kidney disease (CKD) and end stage renal disease (ESRD) in type 1 DM.
D. eGFR equations like MDRD equation can be used predict hyper filtration.

The Correct Answer is Option D : eGFR equations like MDRD equation can be used predict hyper filtration.


Explanation:


Supra physiologic elevation in GFR is observed early in the natural history of type 1 and type 2 diabetes mellitus which is due to glomerular hyper filtration  Pathogenesis of hyper filtration in diabetes is complex with a prominent role for hyperglycemia and distorted insulin levels especially in early diabetes and pre-diabetes. Dilatation of the afferent (pre-capillary) glomerular arteriole plays an important role in the hyper filtration response, by raising both the intra-glomerular pressure and renal blood flow.

 

Direct measurement of GFR is usually required to detect hyperfiltration because estimation equations, such as the Modification of Diet in Renal Disease (MDRD) usually underestimate the true GFR when it is normal or above normal. 

 

Option A : A definite cut off of GFR is lacking. However, renal hyper filtration is typically defined as a GFR of between 120 mL/min and 150 mL/min/1.73m2, or greater than 2 standard deviations above the mean GFR in normal, healthy individuals.

 

Option B: Hyper filtration in diabetes precedes the onset of albuminuria and/or decline in renal function, and predisposes to progressive nephron damage by increasing glomerular hydraulic pressure

 

Option C : Hyper filtration per se does not seem to fully explain adverse renal outcome, as the risk for ESRD in transplant donors is very low. However, in type 1 diabetes Rapid GFR decline is associated with renal hyper filtration and impaired GFR and may predict progressive DKD prior to loss of renal function.

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TUTOR - Glomerulonephritis
  • Test Id: 1957468cea0bb6c52e
  • QId: 165246
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A 32 year-old male is brought to renal clinic with history of hematuria, oedema feet, and puffiness of face. He gives a history of fever and sore throat a week ago. He also complains of breathlessness on exertion and oliguria. Physical examination shows: Pulse 100/min, BP 150/100 mm Hg, and Temp. 37.4 C. He is pale. He has puffiness of face and oedema feet. Systemic examination-unremarkable. Laboratory examination is as follows:

Hb   10.5 g/d

Hct   34%

Platelet 250,000 mm3

WBC  8,000 mm3

Differential count P 80% L 12% E 6% M 2%

ESR  9.8 mm/h


Urinalysis:

Protein   3000 mg/24 h

Glucose   None

RBC   50-60/hpf Dysmorphic

WBC   occasional

Leukocyte Esterase Negative

Nitrites   Negati

BUN   40 mg/dL

Creatinine  3.9 mg/dL

Sodium   140 mEq/L

Potassium  4.2 mEq/L

Bicarbonate  25.5 mEq/L

S. protein  5.5 g/dl

S. Albumin  2.5 g/dl

Calcium   9.2 mEq/L

Phosphorus  3.2 mg/dL

Glucose   100 mg/dL

Uric Acid   5.3 mg/dL

C 3    Low

C4     normal

HBsAg /HIV   Neg

ANA    Neg

Kidney Biopsy: Shows enlarged Glomeruli, lobular accentuation, mesangial hypercellularity, endo-capillary proliferation and double contour along the capillary wall. IF shows bright C3 in mesangium and capillary wall with absent immunoglobulin staining. 

Electron Microscopy: Suggestive of dense deposits.

What is the BEST treatment option for this patient?


A. Plasma exchange + Rituximab 
B. Rituximab 
C. Eculuzimab
D. Cyclophosphamide + Steroids 
The correct answer is C

Eculuzimab

Explanation:

This patient has nephritic-nephrotic picture with low C3. The Kidney biopsy along with clinical presentation is suggestive of MPGN. Negative Immunoglobulins along with positive C3 staining narrows it down to DDD (DENSE DEPOSIT DISEASE) or C3-GN (C3-GN GLOMERULONEPHRITIS)

DDD or Dense deposit disease is best treated with Eculuzimab. 
Rituximab has not been found to be useful in DDD or C3-GN. 

ECULUZIMAB : has been shown to be useful in:
1. DDD
2. Atypical HUS – used along with plasma exchange. If using Eculuzimab give meningococcal vaccine or give penicillin till the vaccine becomes effective.

However, (additional information not pertaining to this question)

RITUXIMAB : has been shown to be useful in:
1. ANCA vasculitis (can be used in induction or relapse – RAVE TRIAL)
2. Wegeners
3. HCV cryoglobulinemia
TTP

***** TREATMENT OPTIONS IN GLOMERULONEPHRITIS WITH RITUXIMAB AND ECULUZIMAB ARE FREQUENTLY TESTED CONCEPTS IN NEPHROLOGY BOARD EXAMS. PLEASE REVIEW THESE IN DETAIL.*****


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Last Modified: 08/06/2018

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TUTOR - Hypertension
  • Test Id: 1957468cea0bb6c52e
  • QId: 165243
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You are the nephrologist on call. The  ER calls you for an 18 year-old female who complaining of vomiting and diarrhea. Her serum sodium is 116 mEq/L and Serum potassium is 5.9 mEq/L. On physical examination the patient is drowsy, Pulse is 126/min, BP is 90/60 mm of Hg, and RR is  32/min. Her chest is clear. Her heart sounds are normal, and no murmur is visible. The patient is drowsy but arousable and there was no focal neurological deficit. Laboratory findings are as follows:

Hb    16 gm/dl 

WBC   12,800/cmm 

Polymorph  46% 

Lymphocytes  16% 

Eosinophils  4%

Monocytes  4%

Platelets   2,40,000/cmm.

CL    70 mEq/L

BUN  10 mg/dl

Creatinine  0.5 mg/dl

Na    116 mEq/L

K    5.8 mEq/L


Urinalysis:

pH    6.4

Protein  trace

Glucose  absent

microscopic occasional WBCs & RBCs

Urinary Na  90 mEq/L

Urinary K         20 mEq/L

ABG    

PH                   7.32

PCO2   36 

HCO3   20 mEq/L

PaO2   92

O2 saturation  98%

S. Cortisol  6.00 mg/dl

TSH   3.5 IU/m (Normal 0-5 IU/m ).

Both plasma Renin and Aldosterone are high. 

Which of the following conditions is most likely with these findings?


A. Type 4 RTA 
B. Pseudo-hypo-aldosteronism Type 1 
C. Gordon's syndrome
D.  Diarrhea
The correct answer is B
 
Pseudo hypo-aldosteronism type 1

Explanation:

This patient has hyponatremia with high urinary sodium. High serum potassium, low urinary potassium, and normal adrenal function. The serum aldosterone level is high, suggesting resistance to aldosterone action of target organ. These findings are characteristic of Pseudohypo aldosteronism type1 (PHA Type1)

PHA type1 is a rare hereditary disorder, characterized by generalized resistance to the action of aldosterone. It presents with 
1. Salt wasting 
2. Hypovolemia 
3. Normotension
4. Metabolic acidosis 
5. Hyperkalemia
6. High Renin and Aldosterone.  

NEPHROLOGY BOARD EXAM TAKERS REMEMBER THESE 6 POINTS FOR PHA TYPE 1

These are two different modes of inheritance:
1] Autosomal recessive.
2] Autosomal dominant.

Autosomal recessive affects the epithelial sodium channel and other target organs like kidney, colon, and sweat gland. There is a down regulation of the sodium channels and decreased sodium transport.

Autosomal dominant or sporadic form is due to heterozygous mutations in the NR3C2 gene coding for mineralocorticoid receptor. This is milder form than autosomal recessive disease in which only kidney is affected. The disease often improves with age.

Treatment consists of high salt diet. This prevents volume depletion and by enhancing sodium delivery to the distal tubules, potassium exertion increases, thereby bringing down the serum potassium. 

High dose Fludrocortisone (1 to 2 mg/day ), or Carbenoxolone is indicated if high salt intake is ineffective or not tolerated.

(Choice A) Type IV RTA will have low aldesterone and low renin level. Therefore, that is not the likely answer.

(Choice D) Diarrhea will have metabolic acidosis with hypokalemia and Net urine charge will be negative. This patient has positive Net urine charge with hyperkalemia which rules out diarrhea as a cause.

(Choice C)  = PHA TYPE 2 (Pseudohypoaldosteronism type 2) OR = Gordon’s syndrome is characterized by:
 1. Hypertension 
 2. Hyperkalaemia 
 3. Metabolic acidosis
 4. Low plasma Renin and Aldosterone. This is due to mutations in WNK kinases 1 and 4. These mutations result in increased  chloride reabsorption with sodium retention thereby resulting in hypertension.

NEPHROLOGY BOARD EXAM TAKERS REMEMBER THESE 4 POINTS FOR PHA TYPE 2 or GORDON's SYNDROME

IF YOU KNOW THESE 10 POINTS OF PSEUDOHYPOALDOSTERONISM TYPE 1 & 2 THAN YOU CAN ANSWER ALL QUESTIONS ON PHA 1, 2 AND GORDON'S SYNDROME WHICH ARE GOING TO BE ASKED FOR SURE ON THE BOARDS.

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TUTOR - Hypertension
  • Test Id: 1957468cea0bb6c52e
  • QId: 165212
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The ACCOMPLISH trial is the first major trial addressing the issue of combination therapy in 11,506 patients who were at high cardiovascular risk. The goal blood pressure was less than 130/80 mm Hg in the patients with diabetes or impaired renal function, and less than 140/90 mm Hg in the patients with prior cardiovascular disease.

Which of the following combinations of blood pressure medications was the best in reducing cardiovascular events and slowing the progression of nephropathy in patients with hypertension who were at high risk for such events?

A. ACEI + Diuretics
B. ACEI + CCB 
C. ACEI + Beta-blocker 
D. CCB + Beta-blocker 
The correct answer is B
ACEI + CCB

Explanation:

• The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension  - (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality.

• ACCOMPLISH ACCOMPLISH was a double-blind, randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals.

• The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

• The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events.

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TUTOR - Acute Kidney Injury / ICU Nephrology
  • Test Id: 1957468cea0bb6c52e
  • QId: 165256
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A 30 year-old man comes to your office for a painful rash on the neck. He has fever and malaise. He has history of HIV. He is currently taking Tenofovir, emtricitabine, and indinavir.  The rash is suggestive of Herpes Zoster rash :

Physical examination does not reveal any oral cavity lesions. His current CD4 count is 250/mm3. His chemistry is normal. He is started on an intravenous medication for his rash. Two days later his chemistry is as follows:

Na    135 mEq/L

K     4.5 mEq/L                  

CL    100 mEq/L

HCO3   24 mEq/L                  

BUN  21 mg/dL                       

Cr   2.0 mEq/L

Glucose  95 mg/dL

Calcium   9.4 mg/dl

Urinalysis shows needle-shaped crystals in the sediment.

Which of the following is most likely the cause of his renal problem?


A.  Indinavir
B.  Tumor lysis syndrome
C.  Antifreeze ingestion
D.  Acyclovir
E.  IV TMP/SMX
The correct answer is D

Acyclovir

Explanation:

This patient has a characteristic lesion of herpes zoster on his neck. The vesicles are 2-3 mm in size with erythematous base. They are in different stages of development. Herpes zoster is commonly seen in elderly and immunocompromised. This patient is 30 year old and immunocompromised (HIV positive with AIDS). The treatment of choice for herpes zoster in immunocompromised patient is IV acyclovir. High dose Acyclovir is one of the causes of crystal-induced nephropathy. The crystals are needle-shaped.

Indinavir (Choice A), a protease inhibitor, is a common cause of nephrolithiasis in HIV patients. Patients would often present with flank pain. Urinalysis would show hematuria and needle shaped crystals. This patient, however, had normal serum chemistry on presentation. Following two days of IV medication (acyclovir) his serum chemistry showed elevated creatinine suggesting acyclovir as the most likely cause.

Tumor lysis syndrome (Choice B) occurs in the setting of chemotherapy for lymphoma.  It leads to the formation of uric acid crystals which are also needle shaped. This patient has no such presentation.

Patients with Anti-freeze ingestion (Choice C) present with metabolic acidosis with an elevated anion gap. The initial test of urinalysis shows envelope-shaped oxalate crystals.

Trimethoprim-sulfamethoxazole (TMP/SMX) (Choice E) has sulfonamide in it. Sulfonamide also leads to crystal-induced nephropathy. The crystals are often dumb-bell shaped.

Educational Objective:

Drugs causing Crystal-induced nephropathy:

ACYCLOVIR --- Needle shaped crystals

INDINAVIR --- Needle shaped crystals

SULPHONAMIDE --- Dumbell shaped crystals

CALCIUM OXALLATE (Antifreeze) --- Envelope shaped crystal

CALCIUM PO4---- Coffin shaped crystals

URIC ACID --- Hexagonal crystals

CYSTIENE --- Hexagonal crystals


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Created On: 09/20/2017
Last Modified: 08/29/2018

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TUTOR - PHARMACOLOGY
  • Test Id: 1957468cea0bb6c52e
  • QId: 16521
  • 10 of 20
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As per the JNC VIII committee recommendation, for individuals that are part of the African American population, including those with diabetes, the initial treatment should include a thiazide type diuretic or calcium channel blocker (CCB).  

Which of the following thiazide type diuretic is preferred as the initial antihypertensive therapy?

 

A. Hydrochlorthiazide 
B. Chlorthalidone 
C. Indapamide 
D. Metalazone 
E. Polythiazide 
The correct answer is B 
Chlothalidone

Explanation:

• Chlorthalidone at the same dose is approximately 1.5 to 2 times as potent as hydrochlorothiazide.

• Chlothalidone has a longer duration action than hydrochlorothiazide.

• There are No randomized clinical trials that directly compare outcomes in hypertensive patients treated with hydrochlorothiazide versus chlorthalidone. A multiple treatment (network) meta-analysis of nine trials including 50,946 patients was conducted in which hydrochlorothiazide and chlorthalidone were indirectly compared by evaluating their efficacy against common comparative drugs (ACE inhibitors were compared with hydrochlorothiazide in ANBP2 trial and with chlorthalidone in ALLHAT trial). The major findings of this meta-analysis showed that chlorthalidone significantly reduced the risk of cardiovascular events compared to hydrochlorothiazide (relative risk 0.79, 95% CI 0.72 to 0.88) and heart failure (relative risk 0.77, 95% CI 0.61 to 0.98). The authors calculated that 27 patients would need to be treated with chlorthalidone instead of hydrochlorothiazide over five years to prevent one cardiovascular event. Chlorthalidone remained superior to hydrochlorothiazide even after the meta-analysis was controlled for achieved office systolic blood pressure (relative risk for cardiovascular events 0.82, 95% CI 0.70 to 0.97). This finding may reflect the longer duration of action and lower nocturnal blood pressure associated with chlorthalidone.

• Multiple Risk Factor Intervention Trial (MRFIT) - Men Hypertensive 2392 were treated with chlorthalidone and 4049 were treated with hydrochlorothiazide. During six years of follow-up, cardiovascular events (defined as myocardial infarction, stroke, coronary artery bypass surgery, heart failure, left ventricular hypertrophy, peripheral artery disease, or angina) were significantly less common with chlorthalidone compared with hydrochlorothiazide (hazard ratio 0.79, 95% CI 0.68 to 0.92). Through the course of the study, systolic blood pressure and LDL cholesterol levels were also lower with chlorthalidone compared with hydrochlorothiazide. 

• Indapamide - is a thiazide like diuretic and has a half-life of 14-16 hours. This drug has been used in HYVET trial alone or in combination with perindropril in treatment of hypertension in patients more than 80 years old. Study showed 30% reduction in stroke, 39% reduction in the rate of death .21%in death from any cause, 23%reduction in CV death and 64%reduction in the rate of heart failure. The trial has shown careful BP lowering in very elderly is beneficial. Indapamide is not preferred over chlorthalidone.

• Metalazone - There are many studies with metalazone available. An important additional property is its effectiveness as a diuretic at lower GFR value. The duration of action is about 24 hours.
It is not preferred over chlorthalidone.

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TUTOR - Kidney Transplantation
  • Test Id: 1957468cea0bb6c52e
  • QId: 165261
  • 11 of 20
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50-year-old female patient whos group B is being evaluated for kidney transplant surgery. She had ESRD secondary to analgesic nephropathy and is on hemodialysis for last 5 years. She has had multiple sensitization events in the form of 3 pregnancies and several blood transfusions. Her current calculated PRA against class I antigen is 97% and against class II antigen is 99%. She has been enrolled in the national highly sensitized recipient program.

Her husband who is blood group matched came forward as a potential kidney donor but she had positive Flow B and T Cell Cross match against him. Single antigen bead assay demonstrated that she has donor specific antibodies against class II across DQB*15 and DPB*14. This transplant did not materialize as patient declined desensitization protocol. Now her younger brother comes forward as a potential donor. He is blood group A and the flow B and T cell cross match is negative with no demonstrable donor specific antibodies against this donor.Patient wants to know more about ABO incompatible transplant.


Which of the following statements about the ABO incompatible transplant is correct?


A. Three-year graft survival is inferior to blood group compatible transplants.
B. The infectious and bleeding complications post ABOI kidney transplant are the same as blood matched kidney transplant.
C. All patients undergoing ABOI transplant need to undergo desensitization using IVIg, Plasma exchange, Rituximab irrespective of their donor/recipient pair Anti ABO titers for optimal outcomes.
D. C4d staining on protocol biopsies is common feature and does not necessarily mean an antibody mediated rejection process in the absence of allograft dysfunction.

Correct answer: Option D: C4d staining on protocol biopsies is common feature and does not necessarily mean an antibody mediated rejection process.


Explanation:


Choice A: Three-year graft survival is inferior to blood group compatible transplants is incorrect A comprehensive database analysis of 1420 ABOI living donor (LD) kidney transplants performed in 101 centers from 2005 to 2012 compared graft and patient survival to a matched cohort of ABO-compatible transplant recipients. Three-year graft and patient survival were ultimately identical. 1


Choice B: The infectious and bleeding complications post ABOI kidney transplant as same as blood matched kidney transplant is also incorrect. Using USRDS and Medicare data from 2000–2007, 119 ABOI (non-A2 donor) transplant recipients were identified. Compared with ABO-compatible recipients, the risks of infectious and hemorrhagic complications were significantly higher, with a 2.2-fold higher risk of pneumonia, a 3.5-fold higher risk of wound infections, a 56% higher risk of pyelonephritis, and a nearly 2- fold higher risk of hemorrhage 2


Choice C: All patients undergoing ABOI transplant need to undergo desensitization using IVIg, Plasma exchange, Rituximab irrespective of their donor/recipient pair Anti ABO titers for optimal outcomes is also an incorrect answer. Historically, ABOI transplantation has been successful when performed after desensitization with plasmapheresis, intravenous Ig (IVIG), rituximab, and/or splenectomy to achieve ABO IgG antibody titers 1:4. A recent publication demonstrated that these intensified treatments might not be necessary in donor/recipient pairs who have low-moderate titer ABO incompatibility 3


Choice D: C4d staining on protocol biopsies is common feature and does not necessarily mean an antibody mediated rejection process in the absence of allograft dysfunction is the correct answer C4d staining is not an uncommon feature seen in the protocol biopsies done in ABOI kidney transplant recipients. In the absence of allograft dysfunction, the C4d staining has no clinical relevance and is just a part of the graft accommodation.

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957468cea0bb6c52e
  • QId: 165264
  • 12 of 20
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A 68-year-old gentleman, Caucasian descent, comes to clinic for follow up visit. He is known to have type 2 diabetes mellitus for the past 18 years. His father had diabetes from 40 years of age and developed kidney disease requiring dialysis after 15 years of diabetes. He reports no symptoms. He has been having hypertension and coronary artery disease with history of  PCI 2 years ago. He has non-proliferative diabetic retinopathy. His medications are sitagliptin, gliclazide and metformin in addition to losartan and hydrochlorothiazide. He has been monitoring blood sugar at home and reports no hypoglycemia. He exercises at least at least 30 minutes per day. His vitals recording shows BP of 168/66 mm Hg. His BMI is 29.2.  Systemic  examination is unremarkable.

His laboratory investigation is reported as follows.

Characteristic

value

Hemoglobin

12.2 gm/L

WBC count

6.8 X 103/cubic mm

Platelet count

241 X 103/cubic mm

Segmented Neutrophils

Lymphocytes

Monocytes

Band neutrophils

Eosinophils

Basophils

60%

36%

2%

0%

2%

0%

Sr. Sodium

139 mEq/L

Sr. Potassium

4.9 mEq/L

Sr. Creatinine

1.2 mg/dL

Sr. Bicarbonate

22 mEq/L

Sr. Chloride

101 mEq/L

Total Bilirubin

1.0 mg /dL

AST

16 U/L

ALT

18 U/L

Sr. Albumin

4.0 g/dL

HBA1C

7.8%

Sr. Calcium

10 mg/dL

Urine dipstick

pH- 5.4

Albumin-trace

 no blood

 no WBCs

24-hour urinary albumin

200 milligrams/day


What is the MOST LIKELY correct statement regarding clinical diagnosis of Diabetic Kidney Disease in this patient ?

A. Diabetic Kidney Disease previously called as diabetic nephropathy can be diagnosed clinically with renal biopsy only.  
B. Presence of microalbuminuria is adequate for clinical diagnosis of Diabetic Kidney Disease. 
C. Presence of hematuria without non-diabetic kidney disease is impossible in Diabetic Kidney Disease as diabetic kidney disease is a non-proliferative glomerular disease. 
D. Family history of Diabetic Kidney Disease is associated with renal involvement in Diabetes.

The Correct Answer is Option D: Family history of Diabetic Kidney Disease is associated with renal involvement in Diabetes.

 Explanation:

Familial studies have demonstrated clustering of diabetic nephropathy. Patients with DM with a first-degree relative with T1/T2DM and diabetic nephropathy have more risk for developing diabetic nephropathy than those without an affected relative. This familial clustering has also been well documented in the Pima Indian population. The candidate genes identified are glucose transporter 2(GLUT2), transforming growth factor beta (TGF- ?), and endothelial nitric oxide synthase (eNOS). 

Option A:  Diabetic nephropathy is a clinical syndrome characterized by the following:

·         Persistent albuminuria (>300 mg/d) that is confirmed on at least 2 occasions 3-6 months apart

·         Progressive decline in the glomerular filtration rate (GFR)

·         Elevated arterial blood pressure 

 Hence kidney biopsy is not a mandatory investigation to diagnose diabetic kidney disease.

 Option B:  If the amount of urine albumin exceeds 30 mg/d and is less than 300 mg/d it is called microalbuminuria, and if it is greater than 300 mg/d it is called macro albuminuria or overt albuminuria. Microalbuminuria is present in 5-7% of normal individuals and is associated with cardiovascular mortality and morbidity. It is marker of endothelial dysfunction in type 2 diabetes mellitus. Presence of microalbuminuria alone with diabetes cannot be clinically diagnostic of diabetic kidney disease.

Option C:  Micro hematuria has been demonstrated in biopsy studies with isolated diabetic nephropathy. Red blood cell casts have also been described in patients with diabetic nephropathy. However, it is important to rule out other glomerular and extra-glomerular causes of hematuria.

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957468cea0bb6c52e
  • QId: 167340
  • 13 of 20
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A 40 year-old pleasant African man with ESRD secondary to FSGS started automated peritoneal dialysis. His prescription includes 2.5 L and 3 exchanges over 8 hours at night with a last fill of 2 L. He has a urine output of 1000 mL/day. A typical ultrafiltration on cycler is used at 1000 mL. Average drain volume of the day dwell was 1500 mL prior to going on the cycler at night. 

He came with complains of lower abdominal wall edema extending to the scrotum over the past 5 days. Without any change in the dialysis prescription, his drain volume before going on the cycler dropped to 900 mL, and the ultrafiltration volume on the cycler came down to 100 mL. He reports no pain with fill or drain. 

What is the next step?


A. Chest X ray PA and lateral view 
B. Drain the fluid middle of the day to reduce the dwell time
C. PD catheter manipulation
D. Abdominal CT scan with contrast in the dialysate
E. Switch to hemodialysis 
E. Pleurodesis 
The correct answer is D 

Abdominal CT scan with contrast in the dialysate

Explanation:

Typical ultrafiltration failure from peritoneal membrane failure presents gradually. More frequently, we see an apparent ultrafiltration failure from other reasons. 

Catheter malfunction can present with problem with inflow, outflow or both. A kink in the catheter poses problem with inflow and outflow. 

Omentum or blood clots clogging the catheter can cause only outflow problem. Fibrin clots, constipation with loaded rectum, and displaced PD catheter also cause outflow obstruction. X ray KUB is very helpful in diagnosing displaced catheter.   

FLUID LEAK leak into the abdominal wall causes swelling in the lower abdomen extending down to the scrotum or mons pubis and decrease in the drain volume. Usually this can be treated by temporarily doing low volume PD or transferring to HD for about 6 weeks. Such leaks starting few years after initiating PD usually do not respond to this approach and often requires placement of a new PD catheter.

A patent tunica vaginalis testes will cause UNILATERAL OR BILATERAL SCROTAL SWELLING without much swelling of the abdominal wall sometimes associated with decrease in the drain volume. A CT scan of the abdomen with ‘IV’ contrast into the peritoneal fluid can help in diagnosing the leak into the abdominal wall and scrotal leak. Patent tunica vaginalis testes requires surgery. Generally hemodialysis is not required after the surgery and low volume peritoneal dialysis can be resumed. This patient presents with signs of leak of fluid into the abdominal wall. A chest X ray is not required, so (Choice A) is wrong.

Draining during the middle of the day helps if the membrane is very permeable with very high D/P creatinine ratio on PET. This does not help in abdominal wall leak of dialysate. Therefore, (Choice B) is also wrong.

PD catheter manipulation (Choice C) is wrong because this patient does not have displaced PD catheter from the information given.

(Choice D) is the correct answer. If the clinical presentation is very convincing, most patients are treated with reducing the dialysate volume and if possible keeping the abdomen dry during the day. Sometimes these patients need to be switched to hemodialysis for 4-6 weeks before PD is resumed. Hence temporary switch to HD would be a correct answer, but unqualified switch to HD as is stated in answer E would be a wrong choice. Therefore, (Choice E) is the wrong or less appropriate answer.

ABDOMINAL ADHESIONS cause decrease in the drain volume as well and require surgical treatment with low volume PD or temporary HD after that.

DIAPHRAGMATIC LEAK into the pleural space presents with cough and shortness of breath without peripheral signs of fluid overload few weeks after starting peritoneal dialysis (not the presentation in this patient). Usually, such patients present with right sided pleural effusion clinically and on chest X ray PA and lateral view. These patients can be treated with temporary transfer to HD, pleuridesis and return back to PD 4-6 weeks later. Permanent switch to hemoidialysis without pleurodesis is another option.


TREATMENT OPTIONS OF VARIOUS ABDOMINAL/CHEST PROBLEMS AS MENTIONED ABOVE IN PATIENTS ON PERITONEAL DIALYSIS IS FREQUENTLY TESTED ON BOARDS. PLEASE KNOW THE TREATMENT OPTIONS.


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TUTOR - Kidney Transplantation
  • Test Id: 1957468cea0bb6c52e
  • QId: 167345
  • 14 of 20
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Cyclosporine nephrotoxicity in a renal transplant recipient is associated with all the below renal biopsy findings EXCEPT:

(THIS PICTURE BELOW IN LOW POWER SHOWS ONE OF THE CLASSICAL FINDINGS IN CSA TOXICITY)


A. Interstitial Fibrosis  
B. Tubular atrophy 
C. Endothelial cell swelling 
D. Glomerular thrombin deposits
E. Glomerular basement membrane thickening 
E. Double contours of the GB 
The correct answer is D

Glomerular thrombin deposits

Explanation:

In a patient with suspected cyclosporine nephrotoxicity, the renal biopsy reveals an obliterative arteriolopathy (which is classically seen in afferent renal arterioles) suggesting primary endothelial damage and subsequently endothelial cell swelling which may persist for months in a patient with elevated cyclosporine blood levels. This is also associated with thickened glomerular basement membrane and double contour pattern. In fact according to BANF thickened glomerular basement membrane and double contour pattern is most suggestive of chronic allograft nephropathy (CAN) also called as TRANSPLANT GLOMERULOPATHY. 

The other renal biopsy findings of cyclosporine nephrotoxicity include ischemic collapse or scarring of the glomeruli, vacuolization of the tubules, FSGS, and focal areas of tubular atrophy and interstitial fibrosis (producing a picture of “ZEBRA” or "STRIPED" fibrosis) These changes are seen with both low-dose and higher-dose cyclosporine therapy, although they seem to co-relate earlier with higher doses. 

(THE ABOVE PICTURE IN THE UPPER HALF SHOWS TUBULAR ATROPHY APPEARING DARK AND REDDISH ALTERNATING WITH LIGHT BLUE AREAS OF INTERSTITIAL FIBROSIS GIVING A "STRIPED" OR "ZEBRA" APPEARANCE)

THE PICTURE BELOW SHOWS TUBULAR ATROPHY, VACUOLIZATION OF THE TUBULES AND ISCHEMIC CHANGES:


Mild arteriolar hyalinosis at six months appears to be associated with high doses of cyclosporine and was reversible. However, after more than a year irreversible severe arteriolar hyalinosis and glomerulosclerosis were observed, despite decreased doses and trough levels of cyclosporine.

Glomerular thrombin deposits are typically seen in patients with Lupus, anti phospholipid syndromes and other vasculitides. It is typically not seen in cyclosporine nephrotoxicity.

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TUTOR - Physiology
  • Test Id: 1957468cea0bb6c52e
  • QId: 165262
  • 15 of 20
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A 28-year-old gentleman, Caucasian descent, comes to clinic for follow up visit. He has been found to have type 1 diabetes mellitus since the age of 12 years of age. His cousin brother has the same disease. He reports no symptoms. He has been using insulin pump using insulin Aspart. He has been monitoring blood sugar using flash glucose monitor and uses carbohydrate count for boluses. He reports infrequent hypoglycemic episodes particularly 2 hours into post lunch, but, manages by himself. He exercises at least at least 60 minutes per day. His vitals recording shows BP of 118/66 mmHg. His BMI is 23.2.  System examination is unremarkable.


His laboratory investigation is reported as follows.


Characteristic

Value

Hemoglobin

14.2 gm/L 

WBC count

6.8 X 103/cubic mm

Platelet count

241 X 103/cubic mm

Segmented Neutrophils 

Lymphocytes

Monocytes

Band neutrophils 

Eosinophils

Basophils

60%

36%

2%

0%

2%

0%

Sr Sodium

139 mEq/L

Sr Potassium

4.4 mEq/L

Sr Creatinine

0.6 mg/dL

eGFR using CKD-EPI

136.8 ml/min/1.73m2

Sr Bicarbonate

24 mEq/L

Sr Chloride

101 mEq/L

Total Bilirubin

1.0 mg /dL

AST

16 U/L

ALT

18 U/L

Sr Albumin

4.0 g/dL

HBA1C

7.9%

Sr Calcium

10 mg/dL

Urine dipstick

pH- 5.4

Albumin-nil

 no blood

 no WBCs

24-hour urinary protein 

76 milligrams/day


What is the MOST LIKELY incorrect statement regarding hyperfiltration stage of Diabetic Kidney Disease in this patient?

A. Renal hyperfiltration is usually diagnosed when the GFR is more than 120 ml/min,which corresponds to a renal function that exceeds two standard deviation above mean GFR.
B. Renal hyper filtration usually precedes microalbuminuria in type 1 diabetes mellitus.
C. Renal hyper filtration is considered as a risk factor for future progression to chronic kidney disease (CKD) and end stage renal disease (ESRD) in type 1 DM.
D. eGFR equations like MDRD equation can be used predict hyper filtration.

The Correct Answer is Option D : eGFR equations like MDRD equation can be used predict hyper filtration.


Explanation:


Supra physiologic elevation in GFR is observed early in the natural history of type 1 and type 2 diabetes mellitus which is due to glomerular hyper filtration  Pathogenesis of hyper filtration in diabetes is complex with a prominent role for hyperglycemia and distorted insulin levels especially in early diabetes and pre-diabetes. Dilatation of the afferent (pre-capillary) glomerular arteriole plays an important role in the hyper filtration response, by raising both the intra-glomerular pressure and renal blood flow.

 

Direct measurement of GFR is usually required to detect hyperfiltration because estimation equations, such as the Modification of Diet in Renal Disease (MDRD) usually underestimate the true GFR when it is normal or above normal. 

 

Option A : A definite cut off of GFR is lacking. However, renal hyper filtration is typically defined as a GFR of between 120 mL/min and 150 mL/min/1.73m2, or greater than 2 standard deviations above the mean GFR in normal, healthy individuals.

 

Option B: Hyper filtration in diabetes precedes the onset of albuminuria and/or decline in renal function, and predisposes to progressive nephron damage by increasing glomerular hydraulic pressure

 

Option C : Hyper filtration per se does not seem to fully explain adverse renal outcome, as the risk for ESRD in transplant donors is very low. However, in type 1 diabetes Rapid GFR decline is associated with renal hyper filtration and impaired GFR and may predict progressive DKD prior to loss of renal function.

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TUTOR - Glomerulonephritis
  • Test Id: 1957468cea0bb6c52e
  • QId: 165246
  • 16 of 20
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A 32 year-old male is brought to renal clinic with history of hematuria, oedema feet, and puffiness of face. He gives a history of fever and sore throat a week ago. He also complains of breathlessness on exertion and oliguria. Physical examination shows: Pulse 100/min, BP 150/100 mm Hg, and Temp. 37.4 C. He is pale. He has puffiness of face and oedema feet. Systemic examination-unremarkable. Laboratory examination is as follows:

Hb   10.5 g/d

Hct   34%

Platelet 250,000 mm3

WBC  8,000 mm3

Differential count P 80% L 12% E 6% M 2%

ESR  9.8 mm/h


Urinalysis:

Protein   3000 mg/24 h

Glucose   None

RBC   50-60/hpf Dysmorphic

WBC   occasional

Leukocyte Esterase Negative

Nitrites   Negati

BUN   40 mg/dL

Creatinine  3.9 mg/dL

Sodium   140 mEq/L

Potassium  4.2 mEq/L

Bicarbonate  25.5 mEq/L

S. protein  5.5 g/dl

S. Albumin  2.5 g/dl

Calcium   9.2 mEq/L

Phosphorus  3.2 mg/dL

Glucose   100 mg/dL

Uric Acid   5.3 mg/dL

C 3    Low

C4     normal

HBsAg /HIV   Neg

ANA    Neg

Kidney Biopsy: Shows enlarged Glomeruli, lobular accentuation, mesangial hypercellularity, endo-capillary proliferation and double contour along the capillary wall. IF shows bright C3 in mesangium and capillary wall with absent immunoglobulin staining. 

Electron Microscopy: Suggestive of dense deposits.

What is the BEST treatment option for this patient?


A. Plasma exchange + Rituximab 
B. Rituximab 
C. Eculuzimab
D. Cyclophosphamide + Steroids 
The correct answer is C

Eculuzimab

Explanation:

This patient has nephritic-nephrotic picture with low C3. The Kidney biopsy along with clinical presentation is suggestive of MPGN. Negative Immunoglobulins along with positive C3 staining narrows it down to DDD (DENSE DEPOSIT DISEASE) or C3-GN (C3-GN GLOMERULONEPHRITIS)

DDD or Dense deposit disease is best treated with Eculuzimab. 
Rituximab has not been found to be useful in DDD or C3-GN. 

ECULUZIMAB : has been shown to be useful in:
1. DDD
2. Atypical HUS – used along with plasma exchange. If using Eculuzimab give meningococcal vaccine or give penicillin till the vaccine becomes effective.

However, (additional information not pertaining to this question)

RITUXIMAB : has been shown to be useful in:
1. ANCA vasculitis (can be used in induction or relapse – RAVE TRIAL)
2. Wegeners
3. HCV cryoglobulinemia
TTP

***** TREATMENT OPTIONS IN GLOMERULONEPHRITIS WITH RITUXIMAB AND ECULUZIMAB ARE FREQUENTLY TESTED CONCEPTS IN NEPHROLOGY BOARD EXAMS. PLEASE REVIEW THESE IN DETAIL.*****


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TUTOR - Hypertension
  • Test Id: 1957468cea0bb6c52e
  • QId: 165243
  • 17 of 20
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You are the nephrologist on call. The  ER calls you for an 18 year-old female who complaining of vomiting and diarrhea. Her serum sodium is 116 mEq/L and Serum potassium is 5.9 mEq/L. On physical examination the patient is drowsy, Pulse is 126/min, BP is 90/60 mm of Hg, and RR is  32/min. Her chest is clear. Her heart sounds are normal, and no murmur is visible. The patient is drowsy but arousable and there was no focal neurological deficit. Laboratory findings are as follows:

Hb    16 gm/dl 

WBC   12,800/cmm 

Polymorph  46% 

Lymphocytes  16% 

Eosinophils  4%

Monocytes  4%

Platelets   2,40,000/cmm.

CL    70 mEq/L

BUN  10 mg/dl

Creatinine  0.5 mg/dl

Na    116 mEq/L

K    5.8 mEq/L


Urinalysis:

pH    6.4

Protein  trace

Glucose  absent

microscopic occasional WBCs & RBCs

Urinary Na  90 mEq/L

Urinary K         20 mEq/L

ABG    

PH                   7.32

PCO2   36 

HCO3   20 mEq/L

PaO2   92

O2 saturation  98%

S. Cortisol  6.00 mg/dl

TSH   3.5 IU/m (Normal 0-5 IU/m ).

Both plasma Renin and Aldosterone are high. 

Which of the following conditions is most likely with these findings?


A. Type 4 RTA 
B. Pseudo-hypo-aldosteronism Type 1 
C. Gordon's syndrome
D.  Diarrhea
The correct answer is B
 
Pseudo hypo-aldosteronism type 1

Explanation:

This patient has hyponatremia with high urinary sodium. High serum potassium, low urinary potassium, and normal adrenal function. The serum aldosterone level is high, suggesting resistance to aldosterone action of target organ. These findings are characteristic of Pseudohypo aldosteronism type1 (PHA Type1)

PHA type1 is a rare hereditary disorder, characterized by generalized resistance to the action of aldosterone. It presents with 
1. Salt wasting 
2. Hypovolemia 
3. Normotension
4. Metabolic acidosis 
5. Hyperkalemia
6. High Renin and Aldosterone.  

NEPHROLOGY BOARD EXAM TAKERS REMEMBER THESE 6 POINTS FOR PHA TYPE 1

These are two different modes of inheritance:
1] Autosomal recessive.
2] Autosomal dominant.

Autosomal recessive affects the epithelial sodium channel and other target organs like kidney, colon, and sweat gland. There is a down regulation of the sodium channels and decreased sodium transport.

Autosomal dominant or sporadic form is due to heterozygous mutations in the NR3C2 gene coding for mineralocorticoid receptor. This is milder form than autosomal recessive disease in which only kidney is affected. The disease often improves with age.

Treatment consists of high salt diet. This prevents volume depletion and by enhancing sodium delivery to the distal tubules, potassium exertion increases, thereby bringing down the serum potassium. 

High dose Fludrocortisone (1 to 2 mg/day ), or Carbenoxolone is indicated if high salt intake is ineffective or not tolerated.

(Choice A) Type IV RTA will have low aldesterone and low renin level. Therefore, that is not the likely answer.

(Choice D) Diarrhea will have metabolic acidosis with hypokalemia and Net urine charge will be negative. This patient has positive Net urine charge with hyperkalemia which rules out diarrhea as a cause.

(Choice C)  = PHA TYPE 2 (Pseudohypoaldosteronism type 2) OR = Gordon’s syndrome is characterized by:
 1. Hypertension 
 2. Hyperkalaemia 
 3. Metabolic acidosis
 4. Low plasma Renin and Aldosterone. This is due to mutations in WNK kinases 1 and 4. These mutations result in increased  chloride reabsorption with sodium retention thereby resulting in hypertension.

NEPHROLOGY BOARD EXAM TAKERS REMEMBER THESE 4 POINTS FOR PHA TYPE 2 or GORDON's SYNDROME

IF YOU KNOW THESE 10 POINTS OF PSEUDOHYPOALDOSTERONISM TYPE 1 & 2 THAN YOU CAN ANSWER ALL QUESTIONS ON PHA 1, 2 AND GORDON'S SYNDROME WHICH ARE GOING TO BE ASKED FOR SURE ON THE BOARDS.

Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 08/06/2018

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TUTOR - Hypertension
  • Test Id: 1957468cea0bb6c52e
  • QId: 165212
  • 18 of 20
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The ACCOMPLISH trial is the first major trial addressing the issue of combination therapy in 11,506 patients who were at high cardiovascular risk. The goal blood pressure was less than 130/80 mm Hg in the patients with diabetes or impaired renal function, and less than 140/90 mm Hg in the patients with prior cardiovascular disease.

Which of the following combinations of blood pressure medications was the best in reducing cardiovascular events and slowing the progression of nephropathy in patients with hypertension who were at high risk for such events?

A. ACEI + Diuretics
B. ACEI + CCB 
C. ACEI + Beta-blocker 
D. CCB + Beta-blocker 
The correct answer is B
ACEI + CCB

Explanation:

• The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension  - (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality.

• ACCOMPLISH ACCOMPLISH was a double-blind, randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals.

• The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

• The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events.

Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 01/25/2021

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TUTOR - Acute Kidney Injury / ICU Nephrology
  • Test Id: 1957468cea0bb6c52e
  • QId: 165256
  • 19 of 20
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A 30 year-old man comes to your office for a painful rash on the neck. He has fever and malaise. He has history of HIV. He is currently taking Tenofovir, emtricitabine, and indinavir.  The rash is suggestive of Herpes Zoster rash :

Physical examination does not reveal any oral cavity lesions. His current CD4 count is 250/mm3. His chemistry is normal. He is started on an intravenous medication for his rash. Two days later his chemistry is as follows:

Na    135 mEq/L

K     4.5 mEq/L                  

CL    100 mEq/L

HCO3   24 mEq/L                  

BUN  21 mg/dL                       

Cr   2.0 mEq/L

Glucose  95 mg/dL

Calcium   9.4 mg/dl

Urinalysis shows needle-shaped crystals in the sediment.

Which of the following is most likely the cause of his renal problem?


A.  Indinavir
B.  Tumor lysis syndrome
C.  Antifreeze ingestion
D.  Acyclovir
E.  IV TMP/SMX
The correct answer is D

Acyclovir

Explanation:

This patient has a characteristic lesion of herpes zoster on his neck. The vesicles are 2-3 mm in size with erythematous base. They are in different stages of development. Herpes zoster is commonly seen in elderly and immunocompromised. This patient is 30 year old and immunocompromised (HIV positive with AIDS). The treatment of choice for herpes zoster in immunocompromised patient is IV acyclovir. High dose Acyclovir is one of the causes of crystal-induced nephropathy. The crystals are needle-shaped.

Indinavir (Choice A), a protease inhibitor, is a common cause of nephrolithiasis in HIV patients. Patients would often present with flank pain. Urinalysis would show hematuria and needle shaped crystals. This patient, however, had normal serum chemistry on presentation. Following two days of IV medication (acyclovir) his serum chemistry showed elevated creatinine suggesting acyclovir as the most likely cause.

Tumor lysis syndrome (Choice B) occurs in the setting of chemotherapy for lymphoma.  It leads to the formation of uric acid crystals which are also needle shaped. This patient has no such presentation.

Patients with Anti-freeze ingestion (Choice C) present with metabolic acidosis with an elevated anion gap. The initial test of urinalysis shows envelope-shaped oxalate crystals.

Trimethoprim-sulfamethoxazole (TMP/SMX) (Choice E) has sulfonamide in it. Sulfonamide also leads to crystal-induced nephropathy. The crystals are often dumb-bell shaped.

Educational Objective:

Drugs causing Crystal-induced nephropathy:

ACYCLOVIR --- Needle shaped crystals

INDINAVIR --- Needle shaped crystals

SULPHONAMIDE --- Dumbell shaped crystals

CALCIUM OXALLATE (Antifreeze) --- Envelope shaped crystal

CALCIUM PO4---- Coffin shaped crystals

URIC ACID --- Hexagonal crystals

CYSTIENE --- Hexagonal crystals


Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 08/29/2018

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TUTOR - PHARMACOLOGY
  • Test Id: 1957468cea0bb6c52e
  • QId: 16521
  • 20 of 20
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As per the JNC VIII committee recommendation, for individuals that are part of the African American population, including those with diabetes, the initial treatment should include a thiazide type diuretic or calcium channel blocker (CCB).  

Which of the following thiazide type diuretic is preferred as the initial antihypertensive therapy?

 

A. Hydrochlorthiazide 
B. Chlorthalidone 
C. Indapamide 
D. Metalazone 
E. Polythiazide 
The correct answer is B 
Chlothalidone

Explanation:

• Chlorthalidone at the same dose is approximately 1.5 to 2 times as potent as hydrochlorothiazide.

• Chlothalidone has a longer duration action than hydrochlorothiazide.

• There are No randomized clinical trials that directly compare outcomes in hypertensive patients treated with hydrochlorothiazide versus chlorthalidone. A multiple treatment (network) meta-analysis of nine trials including 50,946 patients was conducted in which hydrochlorothiazide and chlorthalidone were indirectly compared by evaluating their efficacy against common comparative drugs (ACE inhibitors were compared with hydrochlorothiazide in ANBP2 trial and with chlorthalidone in ALLHAT trial). The major findings of this meta-analysis showed that chlorthalidone significantly reduced the risk of cardiovascular events compared to hydrochlorothiazide (relative risk 0.79, 95% CI 0.72 to 0.88) and heart failure (relative risk 0.77, 95% CI 0.61 to 0.98). The authors calculated that 27 patients would need to be treated with chlorthalidone instead of hydrochlorothiazide over five years to prevent one cardiovascular event. Chlorthalidone remained superior to hydrochlorothiazide even after the meta-analysis was controlled for achieved office systolic blood pressure (relative risk for cardiovascular events 0.82, 95% CI 0.70 to 0.97). This finding may reflect the longer duration of action and lower nocturnal blood pressure associated with chlorthalidone.

• Multiple Risk Factor Intervention Trial (MRFIT) - Men Hypertensive 2392 were treated with chlorthalidone and 4049 were treated with hydrochlorothiazide. During six years of follow-up, cardiovascular events (defined as myocardial infarction, stroke, coronary artery bypass surgery, heart failure, left ventricular hypertrophy, peripheral artery disease, or angina) were significantly less common with chlorthalidone compared with hydrochlorothiazide (hazard ratio 0.79, 95% CI 0.68 to 0.92). Through the course of the study, systolic blood pressure and LDL cholesterol levels were also lower with chlorthalidone compared with hydrochlorothiazide. 

• Indapamide - is a thiazide like diuretic and has a half-life of 14-16 hours. This drug has been used in HYVET trial alone or in combination with perindropril in treatment of hypertension in patients more than 80 years old. Study showed 30% reduction in stroke, 39% reduction in the rate of death .21%in death from any cause, 23%reduction in CV death and 64%reduction in the rate of heart failure. The trial has shown careful BP lowering in very elderly is beneficial. Indapamide is not preferred over chlorthalidone.

• Metalazone - There are many studies with metalazone available. An important additional property is its effectiveness as a diuretic at lower GFR value. The duration of action is about 24 hours.
It is not preferred over chlorthalidone.

Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 10/28/2024

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