Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta...
-
Upload
truongxuyen -
Category
Documents
-
view
216 -
download
3
Transcript of Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta...
![Page 1: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/1.jpg)
Nephrology Grand Rounds
Vasishta Tatapudi, MD
January 24th, 2013
![Page 2: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/2.jpg)
Case Summary
Chief complaint: A twenty-six year old African American female veteran presented to ER with left flank pain for two days.
History of present illness: The patient complained of mild aching pain for several weeks. It worsened acutely two days prior to presentation. The patient had several episodes of similar pain in the past that resolved with bed rest.
She did not report frequency, dysuria, hematuria, fever, change in bowel habits or any recent injuries.
![Page 3: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/3.jpg)
Medical history: Hypertension, ‘kidney disease’, allergic rhinitis, recurrent urinary tract infections, PTSD.
Surgical history: none.
Medications: Lisinopril 10mg daily, loratidine 10mg daily, trimethoprim 100mg daily, citalopram 40mg daily.
Allergies: Iodinated radio contrast.
![Page 4: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/4.jpg)
Family history: Grandmother with ESRD, father with ‘kidney disease’.
Social history: occasional alcohol use, no smoking or drug use.
![Page 5: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/5.jpg)
Physical exam Vital signs: 99 F, HR 98, RR 20, BP 132/66
General: young female patient in acute distress.
HEENT: normal.
RS: normal vesicular breath sounds.
CVS: S1, S2 normal, no added sounds.
Abdomen: normal bowel sounds, no bruit, no palpable organomegaly, non tender, no guarding or rebound tenderness, no CVA tenderness.
CNS: no focal deficits.
Extremities: no edema, well perfused.
![Page 6: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/6.jpg)
Laboratory data
Hemoglobin 13.6 Sodium 141 Protein 7.9
Hematoctrit 39.1 Potassium 4.0 Albumin 4.6
MCV 83.1 Chloride 108 ALT 22
White count 5.3 Bicarbonate 24 AST 20
Platelets 374 Blood urea 24 ALP 58
Creatinine 0.6 Total Bilirubin 0.5
Glucose 107 Direct Bilirubin 0.2
Calcium 9.9 Amylase 51
AG 9.0 Lipase 24
![Page 7: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/7.jpg)
Urinalysis
Color Yellow
Specific Gravity 1.018
pH 6.5
Protein Negative
Glucose Negative
Bilirubin Negative
Ketones Negative
Blood Negative
Leuk. Est. Negative
Nitrite Negative
RBC 0-2
WBC 0-2
Bacteria Negative
• EKG: normal sinus rhythm.
• Chest x-ray: clear lung fields.
• CT abdomen/pelvis w/o contrast: Innumerable bilateral renal cysts. Several are hyperdense, compatible with hemorrhagic cysts. Liver demonstrates multiple hypodense lesions compatible with cysts.
![Page 8: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/8.jpg)
Polycystic kidney disease
![Page 9: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/9.jpg)
Introduction
• Polycystic kidney disease (PKD) includes inherited diseases that cause an irreversible decline in kidney function.
• PKD may be inherited as an autosomal dominant or recessive trait.
• The autosomal dominant form (ADPKD) is the most common genetic cause of chronic kidney disease.
• ADPKD is caused by mutations of either PKD1 or PKD2.
Patel V, et al, Curr Opin Nephrol Hypertens. 2009;18(2):99.
Torres VE, Harris PC, Kidney Int. 2009;76(2):149.
![Page 10: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/10.jpg)
Epidemiology
• Autosomal dominant PKD (ADPKD) occurs in all races.
• Reported prevalence is 1:400 to 1:1000.
• ADPKD is the underlying cause of kidney disease in approximately five percent of patients who initiate dialysis annually in the United States.
• It is the fourth leading cause of end-stage kidney disease in adults worldwide.
Torres VE, Harris PC, Kidney Int. 2009;76(2):149
![Page 11: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/11.jpg)
Epidemiology: PKD 1 vs PKD 2
• PKD1 mutations are more common (approximately 85 percent) than PKD2 mutations (approximately 15 percent).
• The relative frequency of PKD1 and PKD2 mutations depends on the age of the population being studied.
• Patients with PKD2 mutations present at an older age and progress more slowly than patients with PKD1 mutations.
• Median age of patients who presented with renal failure is 54 and 74 years for those with PKD1 and PKD2, respectively.
Rossetti S, et al, J Am Soc Nephrol. 2007;18(7):2143. Hateboer N, et al, Lancet. 1999;353(9147):103. •
![Page 12: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/12.jpg)
Clinical presentation
• Patients can present with hypertension, hematuria, proteinuria or renal insufficiency detected by routine laboratory examinations.
• Flank pain due to renal hemorrhage, calculi or urinary tract infection is the most common symptom reported by patients.
• Symptoms secondary to cysts in other organs - liver, pancreas, spleen, thyroid or epididymis.
Torres VE,Lancet. 2007;369(9569):1287.
![Page 13: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/13.jpg)
Progression of disease
• Patients develop renal enlargement prior to loss of renal function.
• Renal architecture is lost early.
• May account for the lack of successful interventional trials designed to slow the progression.
• It is necessary to identify reliable markers of disease progression other than renal function.
Chapman AB, et al, Kidney Disease (CRISP) cohort. Kidney, Int 2003;64:1035-45.
![Page 14: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/14.jpg)
• Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. • Multicenter cohort study of 241 patients . • Ages between 15 and 45(32.4±8.9). • eCrCl >70ml/min(107±28). • MR measurement of total renal volume, cyst volume and their relation to GFR measured by iothalamate clearance.
![Page 15: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/15.jpg)
Standardization studies
Chapman AB, et al, Kidney Int. 2003;64(3):1035.
![Page 16: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/16.jpg)
Volume vs GFR
Chapman AB, et al, Kidney Int. 2003;64(3):1035.
![Page 17: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/17.jpg)
• 3 year multicenter cohort study of 241 patients . • Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease. • Ages between 15 and 45(32.4±8.9). • eCrCl >70ml/min(107±28). • MR measurement of total renal volume, cyst volume and their relation to GFR measured by iothalamate clearance. • Rate of growth in PKD1 vs PKD 2 patients.
![Page 18: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/18.jpg)
Volume vs age
Grantham, N Engl J Med. 2006;354(20):2122.
![Page 19: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/19.jpg)
Log transformed volume vs time
Grantham, N Engl J Med. 2006;354(20):2122.
![Page 20: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/20.jpg)
• The mean (±SD) total kidney volume was 1060±642 ml at baseline and increased by a mean of 204±246 ml over a three-year period.
• 5.27±3.92%per year.
• Total cyst volume increased by 218±263 ml (P<0.001) during the same period.
![Page 21: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/21.jpg)
Volume vs volume
Grantham, N Engl J Med. 2006;354(20):2122.
![Page 22: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/22.jpg)
Baseline volume vs slope of volume and GFR
Grantham, N Engl J Med. 2006;354(20):2122.
![Page 23: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/23.jpg)
PKD1 vs PKD 2
Grantham, N Engl J Med. 2006;354(20):2122.
![Page 24: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/24.jpg)
Discussion
• Patients with the largest kidneys at a given age should have the fastest rates of renal enlargement and decline in renal function.
• Total kidney volume is a marker of progression of disease.
• This supposition has practical value in judging the prognosis in individual patients.
• Study has implications for the design of clinical trials in ADPKD.
![Page 25: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/25.jpg)
Other risk factors for progressive disease
• Genetic factors (PKD1 versus PKD2).
• Hypertension.
• Early onset of symptoms including proteinuria and hematuria.
• Male gender.
• Dipstick detectable proteinuria.
• Low birth weight.
• Decreased renal blood flow.
• Copeptin.
![Page 26: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/26.jpg)
Genetic factors
• Careful attention to family history may allow the prediction of the mutation.
• Shown in a study of 484 patients from 90 families with well-characterized ADPKD mutations.
• The presence of at least one family member who developed ESRD before age 55 predicted a PKD1 mutation with a positive predictive value of 100 % and a sensitivity of 72 %.
• The presence of at least one family member who reached 70 years of age without ESRD predicted a PKD2 mutation with a positive predictive value of 100 % and a sensitivity of 74 %.
Barua, J Am Soc Nephrol. 2009;20(8):1833.
![Page 27: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/27.jpg)
Approach to treatment
• No specific treatment has been proven to prevent or delay progression of ADPKD.
• Promising therapies include:
• Vasopressin receptor antagonists, increased water intake, maximal inhibition of the renin-angiotensin-aldosterone system, use of mTOR inhibitors and rigorous blood pressure control.
• Non-specific measures: dietary protein restriction, a low salt diet, and statins.
• Supportive therapy: pain control, bed rest during gross hematuria, and treatment of infection.
![Page 28: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/28.jpg)
V2R antagonists
• In vitro evidence suggests that increased intracellular cyclic AMP (cAMP) plays a role in cystogenesis.
• cAMP plays a role in cyst epithelial cell proliferation and cyst fluid secretion in patients with PKD.
• Vasopressin leads to increased levels of cAMP in distal tubular epithelial cells.
• The vasopressin V2 receptor antagonists OPC-31260 and tolvaptan(OPC-41061) decrease cAMP levels, inhibit cystogenesis and prevent renal enlargement and dysfunction in three different murine models.
Calvet JP, Clin J Am Soc Nephrol. 2008;3(4):1205 Torres VE, Nat Med. 2004;10(4):363.
![Page 29: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/29.jpg)
Torres VE, Nat Med. 2004;10(4):363.
Torres VE, Nat Med. 2004;10(4):363.
![Page 30: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/30.jpg)
Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial
![Page 31: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/31.jpg)
Methods
• 3-year, multicenter, double-blind, placebo-controlled, trial involving 1445 patients.
• Inclusion criteria: Patients 18 to 50 years of age, who had ADPKD with kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more.
• Received tolvaptan at the highest of three twice-daily dose regimens or placebo.
![Page 32: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/32.jpg)
Methods
• Primary outcome: annual rate of change in the total kidney volume (MRI at baseline and at months 12, 24, and 36).
Secondary end points:
• composite of clinical progression.
• rate of kidney-function (inverse of Cr) decline.
Composite outcome:
• Worsening kidney function(eGFR by CKD EPI).
• Kidney pain.
• Hypertension.
• Albuminuria.
Stratification: Age, gender, hypertension, GFR, total kidney volume.
![Page 33: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/33.jpg)
Enrollment and outcomes
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 34: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/34.jpg)
Enrollment and outcomes
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 35: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/35.jpg)
Baseline characteristics
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 36: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/36.jpg)
Baseline characteristics
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 37: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/37.jpg)
Baseline characteristics
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 38: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/38.jpg)
Effect on total kidney volume
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 39: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/39.jpg)
Effect on total kidney volume
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 40: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/40.jpg)
Effect on kidney function
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 41: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/41.jpg)
Effect on kidney function
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 42: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/42.jpg)
Secondary end points
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 43: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/43.jpg)
Secondary endpoints
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 44: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/44.jpg)
Adverse effects
Torres VE, et al, N Engl J Med. 2012;367(25):2407.
![Page 45: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/45.jpg)
Summary of results
• Over the 3-year period, total kidney volume increased by 2.8% per year (95% CI, 2.5 to 3.1) with tolvaptan versus 5.5% per year (95% CI, 5.1 to 6.0) with placebo.
• Slope of kidney function with a slope of −2.61 (mg per milliliter)−1 per year, as compared with −3.81 (mg per milliliter)−1 per year with placebo.
• Fewer ADPKD-related events with tolvaptan than with placebo (44 vs. 50 events; hazard ratio, 0.87; 95% CI, 0.78 to 0.97; P = 0.01).
![Page 46: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/46.jpg)
Discussion
• Adverse effects and discontinuation.
• Long term outcome data.
• Tolvaptan effect on development of hypertension was not studied.
• Effect of water intake.
![Page 47: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/47.jpg)
![Page 48: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/48.jpg)
Methods
• 13 ADPKD patients and 10 healthy controls .
• The diagnosis of ADPKD was based on a positive family history and ultrasonographic diagnostic criteria.
• Inclusion criteria: older than 18 years, eGFR > 60 ml/min
• per 1.73 m2 using the MDRD equation.
• Exclusion criteria: no history of syndrome of antidiuresis, vasopressin agonist or antagonist therapy, serum sodium concentrations of > 135 mEq/L, PTH levels.
• (MRI) to assess kidney volumes .
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 49: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/49.jpg)
Methods
• The effects of acute and sustained water loading on levels of urine osmolality (Uosm) and cAMP in 13 subjects with ADPKD and 10 healthy controls were studied.
• Uosm and cAMP concentrations were measured before and after water loading.
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 50: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/50.jpg)
Acute water loading
• No food or drink for 12 hours before study visit to achieve maximal AVP secretion and urine concentration.
• No caffeine.
• A urine sample was obtained at the end of the thirsting period.
• 200 ml of bottled water every 15 minutes for 2.5 hours, for a total of 2L.
• A “post-water loading” urine sample was collected.
• All samples were aliquoted and frozen at 80°C within an hour of collection.
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 51: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/51.jpg)
Chronic water loading
• Participants collected a baseline 24-hour urine on their usual fluid intake.
• Subjects were then instructed to drink at least 3 L of water daily for 7 days.
• On days 6 and 7 of sustained water loading, participants collected two consecutive 24-hour urines, which were stored at 4°C. Aliquots of the 24-hour collections were frozen at 80°C until further analysis.
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 52: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/52.jpg)
Statistical analysis
• Changes in urine cAMP concentration were indexed to urine osmolality in the acute water loading part of the study to account for effects of dilution.
• In the chronic water loading phase, 24-hour total urine cAMP amount was indexed to 24-hour total urine creatinine.
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 53: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/53.jpg)
Baseline characteristics
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 54: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/54.jpg)
Effect of acute water load on cAMP
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 55: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/55.jpg)
Correlation between osmolality and cAMP
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 56: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/56.jpg)
Effect of chronic water load on cAMP
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 57: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/57.jpg)
Discussion
Possibilities that could account for the inability to detect predictable changes in urine cAMP during chronic water loading:
• Other agonists can generate cAMP in the kidney, including PTH, catecholamines, caffeine, and a forskolin-like molecule
• Insufficient water intake to suppress AVP levels.
• Urine cAMP may not closely reflect kidney cAMP levels in some patients.
• Urine cAMP measurements to predict responders to water therapy.
• A larger longitudinal study will be needed to determine the potential of water as therapy for ADPKD using hard endpoints.
Barash I, Ponda MP, Goldfarb DS, Skolnik EY, Clin J Am Soc Nephrol. 2010;5(4):693.
![Page 58: Nephrology Grand Rounds - NYU Langone Health · PDF fileNephrology Grand Rounds Vasishta Tatapudi, MD January 24 th, 2013 . Case Summary Chief complaint: A twenty-six year old African](https://reader035.fdocuments.in/reader035/viewer/2022062907/5ab80bd27f8b9a684c8c528e/html5/thumbnails/58.jpg)
Thank you.