This Case Is Nuts PRESENTED BY: R LOGAN JONES, MD ACP – OREGON CHAPTER ANNUAL MEETING SALEM, OR; NOV 8TH 2018 New Patient to Clinic Chief Complaint : Right Flank Pain Generally healthy man in his 60s Non-substance user Proud Vegetarian CKD 3 without proteinuria Horseshoe kidney Recurrent oxalate renal stones Multiple procedures for nephrolithiasis No history of UTI Right CVA tenderness Recent CT with non-obstructive stones My Assessment RENAL COLIC SECONDARY TO RECURRENT NEPHROLITHIASIS “Pity the hurried practitioner” Reviewing outside records while staffing... Things get interesting! 24-Hour Urine Collection Urine Oxalate 460 mg/day EXTREME HYPEROXALURIA 460 mg/day “The Wise Counsel“The ofpractice the of “Extreme Hyperoxaluria” Specialistmedicine is requires Comforting”knowledge of basic science” Urology: • Impressed by magnitude of hyperoxaluira • Concerns for primary genetic disease – “Primary Hyperoxaluria” What now? Hyperoxaluria = Too Much Oxalate in the Urine Primary Hyperoxaluria • Too much endogenous oxalate production • Oxalate via collagen catabolism as a “dead-end” metabolic byproduct Secondary Hyperoxaluria Oxalate Primary Hyperoxaluria (PH) HEPATOCYTE PH 1 • Represents 80% of cases Peroxisome Cytosol • Usually presents in childhood • Nearly all are ESRD by 5th decade PH 2 • Represents ~10% of cases Mitochondria PH 3 • Presents during childhood/adolescence Cochat,P. N Engl J Med 2013; 369:649-658 Collagen Hydoxyproline Normal Physiology Glyoxylate Oxalate “PH” Related Glycolate Enzymes Glycine “HOMEOSTASIS” Cochat,P. N Engl J Med 2013; 369:649-658 Collagen Hydoxyproline DISEASE STATE Glyoxylate Oxalate “PH” Related Glycolate Enzymes Glycine PRIMARY HYPEROXALURIA Cochat,P. N Engl J Med 2013; 369:649-658 Hyperoxaluria = Too Much Oxalate in the Urine Primary Hyperoxaluria • Too much endogenous oxalate production • Oxalate via collagen catabolism as a “dead-end” metabolic byproduct Secondary Hyperoxaluria • Too much absorbed oxalate from exogenous sources • Mostly from plant-based foods Oxalate Secondary Hyperoxaluria Enteric Hyperoxaluria - Decreased Calcium & Increased Bile Acid Increased Total Oxalate Content - Oxalate Overload Bernadino,M, et al. CMAJ December 12, 2016 cmaj.151327 “Methodical examination leads to safe inductions” Recurrent Renal Stones: American Urologic Association Guidelines 1. Obtain a detailed medical and dietary history, serum chemistries and urinalysis 2. When a stone is available, clinicians should obtain a stone analysis at least once. 3. Clinicians should obtain or review available imaging studies to quantify stone burden. Pearle MS, et al. AUA. Medical Management of Kidney Stones. 2014. Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et al. World J Nephrol. May 6, 2015; 4(2): 235-244 Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90 mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et al. World J Nephrol. May 6, 2015; 4(2): 235-244 Progression of Primary Hyperoxaluria Stages of CKD by eGFR CKD 1-3 CKD 4-5 ESRD Cochat,P. N Engl J Med 2013; 369:649-658 Patient’s Imaging Example: Primary Hyperoxaluria Oxalosis • Oxalate crystal deposits in • Bone • Heart • Blood Vessels • Kidney 1. K. Sriram, Nitin S. Kekre, Ganesh Gopalakrishnan. Primary hyperoxaluria and systemic oxalosis. 2007 2. S. Strauss, et al. Pediatric RadiologyJanuary 2017, Volume 47, Issue 1, pp 96–103 1:800,000 live births 1:700,000 lifetime odds Risk of our patient developing adult onset Lifetime risk of being killed by an Primary Hyperoxaluria type 1 earth/space object collision (Alan Harris – Astronomer) Cochat,P. N Engl J Med 2013; 369:649-658 “Be satisfied with probabilities in diagnosis” Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90 mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et al. World J Nephrol. May 6, 2015; 4(2): 235-244 Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90 mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et al. World J Nephrol. May 6, 2015; 4(2): 235-244 “Listen to the patient, he is telling you the diagnosis” Detailed Patient History • I haven’t eaten meat in decades Family: Social: • Has one daughter,• I eat also a withbowl aof cashews• Recently and a bowlmoved of to Portland horseshoe kidney peanuts everyday• Does for proteinnot exercise • No history of end-stage kidney, liver, or heart disease • Lifelong vegetarian – eats mostly • I will also eat potatonuts chips, for protein and sometimes some veggies • He never smoked cigarettes, regularly consumed alcohol, or used illicit drugs. Our Patient’s Dietary Journal: Cumulative Daily Oxalate in milligrams 800 Our Patient’s Intake 700 600 500 400 300 Miligrams Miligrams Oxalateof 200 Average American Intake 100 0 0 1 2 3 4 5 6 7 8 9 Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90 mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et al. World J Nephrol. May 6, 2015; 4(2): 235-244 Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90 mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et al. World J Nephrol. May 6, 2015; 4(2): 235-244 Calcium Oxalate Monohydrate Calcium Oxalate Dihydrate (Whewhellite) (Weddelite) . Clouter,J et al. World J Urol. 2015; 33: 157–169 Daudon,M et al. Comptes Rendu Chemie. 19(11) · June 2016 Mixed stone: -80% calcium oxalate monohydrate - 20% calcium oxalate dihydrate. Clouter,J et al. World J Urol. 2015; 33: 157–169 Daudon,M et al. Comptes Rendu Chemie. 19(11) · June 2016 Approach to Hyperoxaluria Clinical feature Primary Hyperoxaluria Secondary Hyperoxaluria 24-hr Urinary Excretion > 90 mg per day < 90 mg per day -Usually before 5th decade -Recurrent renal stones -Recurrent stones Clinical Presentation -Occasional Nephrocalcinosis -Nephrocalcinosis -Occasional CKD and ESRD -ESRD or ESLD common Presence of Frequent part of the Less common Systemic Oxalosis presentation Family history is often History of GI tract disease or History suggestive with other affected dietary history may suggest relatives cause Composition of 95% calcium oxalate Mixed stones Renal Stones monohydrate (whewellite) (whewellite and weddellite) Adapted from: Bhasin,B, et