NephJC

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5 天前

Chapter 19

References Chapter 19, Part 12 Metabolic acidosis June 14, 2023 References Chapter 19, Part 2 Roger mentioned MELAS syndrome MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options Josh mentioned this blog on lactate- Understanding lactate in sepsis & Using it to our advantage We discussed the Warburg effect The Warburg Effect: How Does it Benefit Cancer Cells? - PMC and here’s a case from skeleton key- Skeleton Key Group Case #28: Mysterious Acidosis in Cancer - Renal Fellow Network Otto Warburg won the Nobel Prize in Physiology and Medicine in 1931 for describing how animal tumors produce large quantities of lactic acid (Wikipedia) Joel calls it the Lactate saline reflex, but the accepted term of art is Lacto-Bolo reflex The origins of the Lacto-Bolo reflex: the mythology of lactate in sepsis Buffer agents do not reverse intramyocardial acidosis during cardiac resuscitation. Josh mentioned this article the BICAR-ICU Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial - The Lancet Roger shared 3 quotes to make the point that there has been little movement in our knowledge the past 40 years: Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study from Cooper in the Annals Lactic Acidosis and Bicarbonate Therapy | Annals of Internal Medicine from Robert Hollander Lactic acidosis from Nick Madias Josh mentioned the use of sodium bicarbonate for CKD Eubicarbonatemic Hydrogen Ion Retention and CKD Progression - Kidney Medicine (Madias) Bicarbonate therapy for prevention of chronic kidney disease progression (from Wesson), Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real‐world Data Results from the AlcalUN Study Amy’s VoG on metabolic acidosis/KDIGO guidelines Very nice JASN review that describes the mechanisms of how metabolic acidosis leads to CKD progression First description by THE Dr. Bright 1930 Lancet description of benefit 2009 RCT that the 2012 KDIGO guidelines sort of based their 2b recommendations off of 2020 BiCARB Study 2021 META Analysis We discussed methanol toxicity : Case Study: Methanol Poisoning from Adulterated Liquor | Food Safety, Acute methyl alcohol poisoning: a review based on experiences in an outbreak of 323 cases and josh poking at the osmolar gap: PulmCrit- Toxicology dogmalysis: the osmolal gap and shared these guidelines: METHANOL | extrip-workgroup and Roger loves this: Urine fluorescence using a Wood's lamp to detect the antifreeze additive sodium fluorescein: a qualitative adjunctive test in suspected ethylene glycol ingestions From China to Panama, a Trail of Poisoned Medicine - The New York Times (diethylene glycol) . The Accidental Poison That Founded the Modern FDA - The Atlantic Outline: Chapter 19 Metabolic Acidosis Etiologies and Diagnosis Lactic Acidosis Pyruvate → lactate (LDH; NADH → NAD+) Normal production: 15–20 mmol/kg/day Metabolized in liver/kidney → pyruvate → glucose or TCA Normal lactate: 0.5–1.5 mmol/L; acidosis if > 4–5 mmol/L Causes: ↑ production: hypoxia, redox imbalance, seizures, exercise ↓ utilization: shock, hepatic hypoperfusion Malignancy, alcoholism, antiretrovirals D-lactic acidosis Short bowel/jejunal bypass Glucose → D-lactate (not metabolized by LDH) Symptoms: confusion, ataxia, slurred speech Special assay needed Tx: bicarb, oral antibiotics Treatment Underlying cause Bicarb controversial: may worsen intracellular acidosis, overshoot alkalosis, ↑ lactate Target pH > 7.1; prefer mixed venous pH/pCO2 Ketoacidosis (Chapter 25 elaborates) FFA → TG, CO2, H2O, ketones (acetoacetate, BHB) Requires: ↑ lipolysis (↓ insulin) Hepatic preference for ketogenesis Causes: DKA (glucose > 400) Fasting ketosis (mild) Alcoholic ketoacidosis Poor intake + EtOH → ↓ gluconeogenesis, ↑ lipolysis Mixed acid-base (vomiting, hepatic failure, NAGMA) Congenital organic acidemias, salicylates Diagnosis: AG, osmolar gap (acetone, glycerol) Ketones: nitroprusside only detects acetone/acetoacetate BHB can be 90% of total (false negative) Captopril → false positive Treatment: Insulin +/- glucose Renal Failure ↓ excretion of daily acid load GFR 40–50 mg/dL Early: respiratory alkalosis → Later: metabolic acidosis Treatment: bicarb, dialysis (>80 mg/dL or coma) Methanol Metabolized to formic acid → retinal toxicity Osmolar gap elevated Tx: bicarb, ethanol/fomepizole, dialysis Ethylene glycol → glycolic/oxalic acid → renal failure Same treatment + thiamine/pyridoxine Other Toluene, sulfur, chlorine gas, hyperalimentation (arginine, lysine) GI Bicarbonate Loss Diarrhea, bile/pancreatic drainage → loss of alkaline fluids Ureterosigmoidostomy → Cl-/HCO3- exchange in colon Cholestyramine → Cl- for HCO3-

5 天前

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1 小時 45 分鐘
8月8日

FF 82 DDAVP up the nose to prevent biopsy bleeding

The Filtrate Joel Topf Bluesky: @kidneyboy.bsky.social‬ AC @medpeedskidneys.bsky.social‬ Nayan Arora @captainchloride.bsky.social‬ Special Guest Vandana Niyyar Professor of Medicine at Emory School of Medicine Editing by Nayan Arora The Kidney Connection written and performed by by Tim Yau Show Notes American Society of Diagnostic and Interventional Nephrology (Website) ASDIN List of training sites Placement, performance and complications of the Ash Split Cath hemodialysis catheter (PubMed) Platelet Function Assay FAQ (PDF) Saint Clair’s Vascular Access Center where we do outpatient biopsies (Website) The studies: NephJC Summary Prasad Study KI Reports Chakrabarti in Kidney 360 Thromboelastogram (TEG) (Life in the Fastline) Elastigirl (Wikipedia) Association of Kidney Biopsy Needle Gauge with Post-Procedure Complications and Biopsy Adequacy (PubMed) Complications of Percutaneous Renal Biopsy (PubMed) Tubular Secretions Nayan Quarterback on Netflix (Wikipedia) AC The Rehearsal on HBO (Wikipedia) Joel The Detroit Tigers (MLB)

8月8日

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1 小時
7月12日

FF 81 Metformin Termination as explored by Target Trial Emulation

The Filtrate Joel Topf Bluesky: @kidneyboy.bsky.social‬ Jordy Cohen Bluesky: @jordybc.bsky.social‬ Swapnil Hiremath Bluesky: @hswapnil.medsky.social‬ Special Guest Edouard “call me Ed” Fu Assistant Professor and Medical Student, and second author of his second paper covered on NephJC. LinkedIn | Leiden University Medical Center Editing by Simon Topf and Sophia Ambruso The Kidney Connection written and performed by by Tim Yau Show Notes Ed’s first paper on NephJC: Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study (NephJC | BMJ) Phenformin Wikipedia | Boca Raton News The metformin black box (as part of the FDA Label) WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metforminassociated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL (see PRECAUTIONS). Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and PRECAUTIONS). If metformin-associated lactic acidosis is suspected, immediately discontinue metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS). Target Trial Emulation A Framework for Causal Inference From Observational Data. Miguel A. Hernán, MD, DrPH; Wei Wang, PhD; David E. Leaf, MD JAMA 2022 Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study (NephJC | PubMed) Toxicokinetics of Metformin During Hemodialysis (KI Reports)Metformin in People With Diabetes and Advanced CKD: Should We Dare? Editorial that ran in AJKD along side the Lambourg manuscript (AJKD) Immortal Time Bias in Cohort Studies of Kidney Transplant Recipients (Kim SJ Amer J Trans 2010) Ed’s Target trial review in JASN which Jordy mentioned and includes an explanation of the obesity paradox by depletion of the susceptibles. (Fu JASN 2023) Ed’s Grand Rounds at Ottawa on YouTube. Very good. Response by Cohen et al to Letter Regarding Article, “Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19” by Jordy and the crew Circ Res 2000 Review article on the issue: Evaluating sources of bias in observational studies of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use during COVID-19: beyond confounding Jordy and a different crew J Hyperten 2021 Figure S5: Weighted cumulative incidence curves for MACE, by treatment strategy The S4 image that Swap loved Tubular Secretions Jordy Andor Season 2 on Disney+ (Wikipedia) Swapnil Murderbot on Apple TV+ (Wikipedia) Eduoard: New house and grant Grant Grant (Wikipedia) Joel Topf Three Body Problem Audio book (Audible)

7月12日

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1 小時 20 分鐘
4月22日

FF 79 REGENCY

The Filtered Fragments (OG Filtrate) Joel Topf Jennie Lin Swapnil Hiremath Special Guest Brad Rovin GN God and second author from The Ohio State Koyal Jain GN Specialist from UNC Alfred Kim Rheumatologist from Washington University Editing by Simon Topf and Nayan Arora The Kidney Connection written and performed by by Tim Yau Show Notes Joel’s monologue One of the most surprising facts of nephrology is that despite conventional wisdom that lupus nephritis is an antibody mediated disease, that over a decade ago, the LUNAR investigtors were unable to find a significant benefit when rituximab was added to conventional therapy. And this was after the equally negative phase 2 trial of rituximab, EXPLORER. In fact, despite this finding rituximab has been able to burough its way into treatment of many nephrologists and rheumatologists as well as the KDIGO guidelines where it is suggested for patients with persistent disease activity or inadequate response to initial standard-of-care therapy. This long conflict is now coming to an end. Obinutuzumab, a newer, better monoclonal antibody targeting the same CD20 that we grew to love with rituximab, but it has a number of advantages. One. It is humanized antibody rather than a chimeric mouse-human antibody Two. It’s cytotoxicity is not complement dependent an particular advantage if you want to deploy it ina disease where hypocomplementemia is a disease characteristic Three, and most importantly, it causes stronger and deeper b-cell depletion than rituximab. Better B-cell depletion in the blood and tissue. And this brings us to tonight’s topic, we had already seen the phase two results of obinutuzumab which, unlike EXPLORER, were positive, we will look at the phase three regency trial. This makes the third novel lupus nephritis drug in the last 4 years. We continue to remake glomerular nephritis. LUNAR: Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study Pubmed EXPLORER: Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial Pubmed REGENCY: Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis NEJM | NephJC NOBILITY: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Annals of Rheumatic Disease Comparison of intravenous and subcutaneous exposure supporting dose selection of subcutaneous belimumab systemic lupus erythematosus Phase 3 program PubMed Central Class 5 lupus nephritis is slow to respond Long-term Use of Voclosporin in Patients with Class V Lupus Nephritis: Results from the AURORA 2 Continuation Study ACR Meeting abstract Tubular Secretions Swap: Young Adult novel I Must Betray You by Ruta Sepetys (Amazon) Koyal: Taekwondo (Wikipedia) Jennie: these unprecedented times Trump NYT: Administration Freezes $1 Billion for Cornell and $790 Million for Northwestern, Officials Say Al: Acquired Podcast Brad: The Feather Thief by Kirk Wallace Johnson (Amazon) Joel: Paradise on Hulu (Wikipedia)

4月22日

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1 小時 43 分鐘
6月2日

Chapter 19

References Chapter 19, Part 1 Metabolic acidosis June 14, 2023 American Society of Nephrology | Medical Students - Kidney TREKS this is the program that Josh mentioned at Mount Desert Island! Effects of pH on Potassium: New Explanations for Old Observations - PMC here’s the review melanie from Peter Aronson that clarifies the fact that there are no H+-K+ antiporters outside the kidney but rather coupled transport- We discussed whether we like “Winter’s formula” Quantitative Displacement of Acid-Base Equilibrium in Metabolic Acidosis | Annals of Internal Medicine Dr. R. W. Winters was charged with larceny https://www.nytimes.com/1982/05/16/nyregion/ex-columbia-u-doctor-charged-with-larceny.html JCI - The Maladaptive Renal Response to Secondary Hypocapnia during Chronic HCl Acidosis in the Dog this was a classic experiment exploring the respiratory response to an infusion of HCl but the animals were maintained in a high pCO2 milieu (not generalizable to humans!) Here’s the thoughtful Pulmcrit post (by Josh Farkas) that Josh mentioned regarding correction of anion gap for hypoalbuminemia: Mythbusting: Correcting the anion gap for albumin is not helpful JC mentioned that the anion gap does change in cirrhosis when the albumin is very low but using the correction factor may not change the clinical findings Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction Diagnostic Importance of an Increased Serum Anion Gap | NEJM Melanie mentioned the work of Patricia Gabow on the anion gap. In this review, she refers to work that she had done to try to identify all the organic anions in the anion gap but it falls short. Also, check out this critical look at the delta/delta: The Δ Anion Gap/Δ Bicarbonate Ratio in Lactic Acidosis: Time for a New Baseline? Roger mentioned near drowning in the Dead Sea and the unusual electrolytes in that instance. Near-Drowning in the Dead Sea: A Retrospective Observational Analysis of 69 Patients We discussed this classic NEJM article by Daniel Batlle The Use of the Urinary Anion Gap in the Diagnosis of Hyperchloremic Metabolic Acidosis Amy mentioned this review from Uribarri and Oh in JASN on the urine anion gap: The Urine Anion Gap: Common Misconceptions Joel has a great blog post on the urine osmolar gap. urine osmolar gap – Precious Bodily Fluids Anna’s VoG on the bicarb deficit: Kurtz, I Acid-Base Case Studies, 2nd Edition. Trafford Publishing 2004. And the Fernandez paper that derived a better equation Reference for Josh’s VoG: Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney disease Severe anion gap acidosis associated with intravenous sodium thiosulfate administration Unexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy Sodium Thiosulfate Induced Severe Anion Gap Metabolic Acidosis Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis Outline: Chapter 19 Metabolic Acidosis Overview Low arterial pH Reduced HCO3 Compensatory hyperventilation (↓ pCO2) Bicarb H2CO3 CO2 + H2O Acidosis results from H+ addition or HCO3 loss Response to Acid Load Extracellular buffering Example: Add 12 mmol H+/L → HCO3 falls from 24 → 12 → pH drops to 7.1 (40 to 80 nmol/L) Intracellular and bone buffering 55–60% buffered intracellularly and in bone 12 mEq/L acid load only reduces serum HCO3 by ~5 mEq/L H+ into cells → K+ out (hyperkalemia) Notably in diarrhea or renal failure Less effect with organic acidosis (e.g., DKA, lactic acidosis) Respiratory compensation Stimulates chemoreceptors → ↑ tidal volume (more than RR) Decreases pCO2, increases pH Begins within 1–2 hours; peaks at 12–24 hours Winters formula alternative: for every 1 mEq ↓ HCO3, pCO2 ↓ by 1.2 Chronic: respiratory compensation is blunted by renal adaptation Renal hydrogen excretion 50–100 mEq/day acid generated from diet 90% filtered HCO3 reabsorbed in PT Acid secreted: 10–40 mEq via titratable acid (TA) 30–60 mEq via NH3/NH4 (can ↑ to 250 mEq in acidosis) TA: phosphate (DKA → ketones act as TA) Max excretion up to 500 mEq/day in severe acidosis Generation of Metabolic Acidosis Mechanisms Inability to excrete H+ (slow) Addition of H+ or loss of HCO3 (rapid) Anion Gap (AG) Normal: 5–11 (falling due to rising Cl-) Mostly due to negatively charged proteins (albumin) Adjust for albumin: AG ↓ 2.5 per 1 g/dL albumin ↓ Revised: AG = unmeasured anions - unmeasured cations ↑ AG = addition of unmeasured anions (e.g., lactate, ketones) Hyperchloremic acidosis: ↓ HCO3 replaced by ↑ Cl (normal AG) Delta–Delta Analysis Adjust AG for albumin Normal ΔAG:ΔHCO3 = 1.6:1 (early 1:1) 4–5 mmol/L Causes: ↑ production: hypoxia, redox imbalance, seizures, exercise ↓ utilization: shock, hepatic hypoperfusion Malignancy, alcoholism, antiretrovirals D-lactic acidosis Short bowel/jejunal bypass Glucose → D-lactate (not metabolized by LDH) Symptoms: confusion, ataxia, slurred speech Special assay needed Tx: bicarb, oral antibiotics Treatment Underlying cause Bicarb controversial: may worsen intracellular acidosis, overshoot alkalosis, ↑ lactate Target pH > 7.1; prefer mixed venous pH/pCO2 Ketoacidosis (Chapter 25 elaborates) FFA → TG, CO2, H2O, ketones (acetoacetate, BHB) Requires: ↑ lipolysis (↓ insulin) Hepatic preference for ketogenesis Causes: DKA (glucose > 400) Fasting ketosis (mild) Alcoholic ketoacidosis Poor intake + EtOH → ↓ gluconeogenesis, ↑ lipolysis Mixed acid-base (vomiting, hepatic failure, NAGMA) Congenital organic acidemias, salicylates Diagnosis: AG, osmolar gap (acetone, glycerol) Ketones: nitroprusside only detects acetone/acetoacetate BHB can be 90% of total (false negative) Captopril → false positive Treatment: Insulin +/- glucose Renal Failure ↓ excretion of daily acid load GFR 40–50 mg/dL Early: respiratory alkalosis → Later: metabolic acidosis Treatment: bicarb, dialysis (>80 mg/dL or coma) Methanol Metabolized to formic acid → retinal toxicity Osmolar gap elevated Tx: bicarb, ethanol/fomepizole, dialysis Ethylene glycol → glycolic/oxalic acid → renal failure Same treatment + thiamine/pyridoxine Other Toluene, sulfur, chlorine gas, hyperalimentation (arginine, lysine) GI Bicarbonate Loss Diarrhea, bile/pancreatic drainage → loss of alkaline fluids Ureterosigmoidostomy → Cl-/HCO3- exchange in colon Cholestyramine → Cl- for HCO3- Renal Tubular Acidosis (RTA) Type 1 (Distal) ↓ H+ secretion in collecting duct → urine pH > 5.3 Etiologies: Sjögren, RA, amphotericin Features: nephrocalcinosis, stones, hypokalemia Diagnosis: NAGMA, persistent ↑ urine pH Treatment: alkali (1–2 mEq/kg/d adults; 4–14 kids), K+ if needed Type 2 (Proximal) ↓ HCO3 reabsorption Bicarb threshold reduced → self-limited Causes: multiple myeloma, Fanconi, ifosfamide Features: rickets/osteomalacia, no stones, pH variable Diagnosis: NAGMA, pH 5.3, high FE HCO3 when HCO3 loaded Treatment: alkali (10–15 mEq/kg/d), thiazides Type 4 Aldo deficiency/resistance → hyperkalemia + mild acidosis K+ inhibits NH4 generation Tx: correct K+, consider loop diuretics Symptoms Hyperventilation (dyspnea) pH 7.0–7.1 → arrhythmias, ↓ contractility Neurologic: lethargy → coma (CSF pH driven) Skeletal growth issues in children Treatment Principles No alkali needed for keto/lactic acidosis unless pH 7.2 Bicarbonate Deficit Deficit = HCO3 space * (desired - actual HCO3) HCO3 space: 50–70% of body weight Watch for: K+ shifts: beware hypokalemia when correcting acidosis Na+ load in CHF Dialysis if necessary

6月2日

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1 小時 45 分鐘
2021/11/09

Chapter 6: Effects of Hormones on Renal Function part 1

Chapter 6 part 1 In this review of vasopressin, you can find an excellent discussion of basic stimuli and vasopressin receptors: Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems | Physiological Reviews X-Linked Nephrogenic diabetes insipidus is very rare and there was theory that all patients originated from the same family and traveled to the US on the Hopewell ship JCI - X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis. This report describes another family from the Netherlands with nephrogenic DI including the finding that the urine osmolarity never exceeds 200 mOsm/kg. Hereditary Nephrogenic Diabetes Insipidus - GeneReviews® (and here’s a family with central diabetes insipidus https://academic.oup.com/jcem/article/81/1/192/2649423?login=true ) Although we have all learned that thiazides should be used with diabetes insipidus, to induce mild volume depletion, several case reports and animal data have found that acetazolamide might be the best diuretic for the job. Clinicians from Boston Medical Center tried it out in this report: Acetazolamide in Lithium-Induced Nephrogenic Diabetes Insipidus | NEJM based on exciting data in mice! https://jasn.asnjournals.org/content/27/7/2082.short ADH appears to have an effect on potassium excretion. This was investigated by Giebesch who found, with clearance and micropuncture studies in rats plus isolated perfused tubules, ADH increased potassium secretion Influence of ADH on renal potassium handling: A micropuncture and microperfusion study A corollary should be that inhibition of ADH would increase the risk of hyperkalemia but this was not observed in the SALT-1 and SALT-2 trials. 5% of patients developed hyperkalemia in both the tolvaptan group and the placebo group Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia | NEJM V1 vasopressin as a pressor Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock: Two Case Reports and Literature Review We wondered/debated on our observation that hyponatremia is not reliably seen in patients receiving vasopressin in the ICU. In the VASST trial, Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock, 1 patient in each study arm of nearly 400 patients developed hyponatremia. Note that patients with hyponatremia (130 mEq/L) were excluded from the study. Excellent review! Vasopressin and the Regulation of Aquaporin-2 This report looks at the PET scan in individuals who are thirsty. Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness Here’s a little discussion of Dr. Grant Liddle. In addition to his eponymous syndrome, he coined the term “ectopic” and developed the dexamethasone suppression test. Grant Liddle (1921–1989) : The Endocrinologist This is the sad case of licorice gluttony in NEJM which led to hypokalemia and a cardiac arrest. Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest In this review of the principal and intercalated cells, check out Figure 8 which has an excellent figure of the aldosterone paradox. https://cjasn.asnjournals.org/content/clinjasn/early/2015/01/30/CJN.08880914.full.pdf?with-ds=yes%3Fversioned%3Dtrue Remarkably, licorice has been used in dialysis patients to lower potassium in patients in this short term trial. Glycyr-rhetinic acid food supplementation lowers serum potassium concentration in chronic hemodialysis patients Animal studies on pregnant rats demonstrating the reset osmostat as predicted by Roger. Osmoregulation during Pregnancy in the Rat: EVIDENCE FOR RESETTING OF THE THRESHOLD FOR VASOPRESSIN SECRETION DURING GESTATION

2021/11/09

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1 小時 51 分鐘
2022/01/23

Chapter 6: Effects of Hormones on Renal Function part 2

Chapter 6 part 2. References Josh touts the PARADIGM-HF Trial Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure | NEJM which found this combination was superior to an ARB alone Joel mentions an early atrial natriuretic peptide trial by Julie Lewis et al. Atrial natriuretic factor in oliguric acute renal failure - American Journal of Kidney Diseases and here’s a metanalysis that put this option to bed: Atrial Natriuretic Peptide for Management of Acute Kidney Injury: A Systematic Review and Meta-analysis Snack attack? Check out “Snack induced ANP” Snack-Induced Release of Atrial Natriuretic Factor | NEJM Want more natriuretic peptides than we discussed? Check out this review! Cardiac natriuretic peptides | Nature Reviews Cardiology or this fantastic review: Here’s an excellent review of ANP effect on the kidney: ANP-induced signaling cascade and its implications in renal pathophysiology Cerebral salt wasting and elevated brain natriuretic peptide levels after traumatic brain injury: 2 case reports Joel mentions the study which probed CRIC cohort regarding NSAIDs. Association of Opioids and Nonsteroidal Anti-inflammatory Drugs With Outcomes in CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study - American Journal of Kidney Diseases and you may like the discussion on NephJC: No Pain for the Kidneys from NSAIDs — NephJC The KDIGO guidelines can be found here CKD-Mineral and Bone Disorder (CKD-MBD) – KDIGO Regulation and Effects of FGF23 in Chronic Kidney Disease Elegant work on the calcium sensing receptor by Martin Pollak https://doi.org/10.1016/0092-8674(93)90617-Ye Claudin 14, PTH, and calcium absorption in the loop of Henle: Parathyroid hormone controls paracellular Ca 2+transport in the thick ascending limb by regulating the tight-junction protein Claudin14 Carboxymaltose induced hypophosphatemia by increasing FGF-23. Randomized trial of intravenous iron-induced hypophosphatemia Current "corrected" calcium concept challenged. | The BMJ The Dialysis Encephalopathy Syndrome — Possible Aluminum Intoxication | NEJM NephMadness covered Aluminum binders in 2016. Roger mentioned the use of ferric citrate as a phosphate binder Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis | American Society of Nephrology Joel reminded us of the misadventures in efforts to normalize hemoglobin, first in hemodialysis patients The Effects of Normal as Compared with Low Hematocrit Values in Patients with Cardiac Disease Who Are Receiving Hemodialysis and Epoetin | NEJM Later, in patients with CKD, normalization was also not shown to be better: Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease | NEJM , Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia | NEJM A quick shout out for roxadustat and the Nephmadness Anemia region! Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis | NEJM, #NephMadness 2021: Anemia Region – AJKD Blog In this review of vasopressin, you can find an excellent discussion of basic stimuli and vasopressin receptors: Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems | Physiological Reviews X-Linked Nephrogenic diabetes insipidus is very rare and there was theory that all patients originated from the same family and traveled to the US on the Hopewell ship JCI - X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis. This report describes another family from the Netherlands with nephrogenic DI including the finding that the urine osmolarity never exceeds 200 mOsm/kg. Hereditary Nephrogenic Diabetes Insipidus - GeneReviews® (and here’s a family with central diabetes insipidus https://academic.oup.com/jcem/article/81/1/192/2649423?login=true ) Although we have all learned that thiazides should be used with diabetes insipidus, to induce mild volume depletion, several case reports and animal data have found that acetazolamide might be the best diuretic for the job. Clinicians from Boston Medical Center tried it out in this report: Acetazolamide in Lithium-Induced Nephrogenic Diabetes Insipidus | NEJM based on exciting data in mice! https://jasn.asnjournals.org/content/27/7/2082.short ADH appears to have an effect on potassium excretion. This was investigated by Giebesch who found, with clearance and micropuncture studies in rats plus isolated perfused tubules, ADH increased potassium secretion Influence of ADH on renal potassium handling: A micropuncture and microperfusion study A corollary should be that inhibition of ADH would increase the risk of hyperkalemia but this was not observed in the SALT-1 and SALT-2 trials. 5% of patients developed hyperkalemia in both the tolvaptan group and the placebo group Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia | NEJM V1 vasopressin as a pressor Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock: Two Case Reports and Literature Review We wondered/debated on our observation that hyponatremia is not reliably seen in patients receiving vasopressin in the ICU. In the VASST trial, Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock, 1 patient in each study arm of nearly 400 patients developed hyponatremia. Note that patients with hyponatremia (130 mEq/L) were excluded from the study. Excellent review! Vasopressin and the Regulation of Aquaporin-2 This report looks at the PET scan in individuals who are thirsty. Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness Here’s a little discussion of Dr. Grant Liddle. In addition to his eponymous syndrome, he coined the term “ectopic” and developed the dexamethasone suppression test. Grant Liddle (1921–1989) : The Endocrinologist This is the sad case of licorice gluttony in NEJM which led to hypokalemia and a cardiac arrest. Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest In this review of the principal and intercalated cells, check out Figure 8 which has an excellent figure of the aldosterone paradox. https://cjasn.asnjournals.org/content/clinjasn/early/2015/01/30/CJN.08880914.full.pdf?with-ds=yes%3Fversioned%3Dtrue Remarkably, licorice has been used in dialysis patients to lower potassium in patients in this short term trial. Glycyr-rhetinic acid food supplementation lowers serum potassium concentration in chronic hemodialysis patients Animal studies on pregnant rats demonstrating the reset osmostat as predicted by Roger. Osmoregulation during Pregnancy in the Rat: EVIDENCE FOR RESETTING OF THE THRESHOLD FOR VASOPRESSIN SECRETION DURING GESTATION

2022/01/23

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1 小時 52 分鐘
2022/12/31

Chapter Ten: Acid-Base Physiology

References for Chapter 10 We did not mention many references in our discussion today but our listeners may enjoy some of the references below. Effects of pH on Potassium: New Explanations for Old Observations - PMC although the focus of this article is on potassium, this elegant review by Aronson and Giebisch reviews intracellular shifts as it relates to pH and K+. Josh swooned for Figure 10-1 is this right? Which figure was it? which shows the relationship between [H+] and pH. You can find this figure in the original reference from Halperin ML and others, Figure 1 here. Factors That Control the Effect of pH on Glycolysis in Leukocytes Here’s Leticia Rolon’s favorite Henderson-Hasselbalch calculator website: Henderson-Hasselbalch Calculator | Buffer Solutions [hint! for this site, use the bicarbonate (or “total CO2”) for A- and PCO2 for the HA] There’s also a cooking tab for converting units! Fundamentals of Arterial Blood Gas Interpretation - PMC this review published posthumously from the late but beloved Jerry Yee and his group at Henry Ford Hospital, explores the details and underpinnings of our understandings of arterial blood gas interpretation (and this also addresses how our colleagues in clinical chemistry measure total CO2 - which JC referenced- but JC said “machine” and our colleagues prefer the word “instrument.”) Amy went deep on bicarbonate in respiratory acidosis. Here are her refs: Sodium bicarbonate therapy for acute respiratory acidosis Sodium Bicarbonate in Respiratory Acidosis Bicarbonate therapy in severe metabolic acidosis Effect of Intravenous Sodium Bicarbonate on Ventilation, Gas Exchange, and Acid-Base Balance in Patients with Chronic Pulmonary Insufficiency Bicarbonate Therapy in Severe Metabolic Acidosis | American Society of Nephrology this review article from Sabatini and Kurtzman addresses the issues regarding bicarbonate therapy including theoretical intracellular acidosis. Bicarbonate in DKA? Don’t do it: Bicarbonate in diabetic ketoacidosis - a systematic review Here’s a review from Bushinsky and Krieger on the effect acidosis on bone https://www.sciencedirect.com/science/article/abs/pii/S0085253822002174 Here is the primary resource that Anna used in here investigation of meat replacements Nutritional Composition of Novel Plant-Based Meat Alternatives and Traditional Animal-Based Meats We enjoyed this paper that Dr. Rose references from the Journal of Clinical Investigation 1955 in which investigators infused HCl into nephrectomized dogs and observed changes in extracellular ions. https://www.jci.org/articles/view/103073/pd We wondered about the amino acids/protein in some available meat alternatives they are explored in this article in the journal Amino Acids: Protein content and amino acid composition of commercially available plant-based protein isolates - PMC and you may enjoy this exploration of the nutritional value of these foods: Full article: Examination of the nutritional composition of alternative beef burgers available in the United States Outline Chapter 10: Acid-Base Physiology - H concentration regulated tightly - Normal H+ is 40 nm/L - This one millionth the concentration of Na and K - It needs to be this dilute because H+ f***s shit up - Especially proteins - Cool foot note H+ actually exists as H3O+ - Under normal conditions the H+ concentration varies little from normal due to three steps - Chemical buffering by extracellular and intracellular bufffers - Control of partial pressure of CO2 by alterations of alveolar ventilation - Control of plasma bicarbonate by changes in renal H+ excretion - Acid and bases - Use definition by Bronsted - Acid can donate protons - Base can accept protons - There are two classes of acids** - Carbonic acid H2CO3 - Each day 15000 mmol of CO2 are generated - CO2 not acid but combines with water to form carbonic acid H2CO3 - CO2 cleared by the lungs - Noncarbonic acid - Formed from metabolism of protein. Sulfur containing AA generate H2SO4. Only 50-100 mEq of acid produced from these sources. - Cleared by the kidneys - Law of Mass Action - Velocity of reaction proportional to the product of the concentrations of the reactants - Goes through mass action formula for water - Concludes that water has H of 155 nanoM/L, more than the 40 in plasma - Says you can do the same mass experiment for every acid in the body - Can do it also for bases but he is not going to. - Acids and Bases can be strong or weak - Strong acids completely dissociate - Weak acids not so much - H2PO4 is only 80% dissociated - Weak acids are the principle buffers in the body - Then he goes through how H is measured in the blood and it becomes clear why pH is a logical way to measure. - Then there is a lot of math - HH equation - Derives it - Then uses it to look at phos. Very interesting application - Buffers - Goes tot he phosphate well again. Amazing math describing how powerful buffers can be - Big picture the closer the pKa is to the starting pH the better buffer, i.e. it can absorb lots of OH or H without appreciably changing pH - HCO3 CO2 system - H2CO3 to H + HCO3 has a PKA of 2.72 but then lots of Math and the bicarb buffer system has a pKa of 6.1 - But the real power of the bicarb buffer is that it is not a sealed system. The ability to ventilate and keep CO2 constant increases the buffering efficiency by 11 fold and the ability to lower the CO2 below normal increases 18 fold. - Isohydric principle - There is only one hydrogen ion concentration and since that is a critical part of the buffer equation, all buffer eq are linked and you can understand all of them by understanding one of them. So we just can look at bicarb and understand the totality of acid base. - Bicarb is the most important buffer because - High concentration in plasma - Ability for CO2 to ventilate - Other buffers include - Bone - Bone is more than just inorganic reaction - Live bone releases more calcium in response to an acid load than dead bone - More effect with metabolic acidosis than respiratory acidosis - Hgb - Phosphate - Protein

2022/12/31

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1 小時 18 分鐘
2021/01/25

Chapter One: Introduction to Renal Function

The Channel Gang discusses the name of their new podcast and then discuss chapter one of The Book.

2021/01/25

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1 小時 5 分鐘
2021/03/29

Chapter 2 Part 2

The exciting conclusion to Chapter Two: Renal Circulation and Glomerular Filtration Rate

2021/03/29

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1 小時 38 分鐘

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