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A chapter by chapter recap of Burton Rose’s classic, The Clinical Physiology of Acid Base and Electrolyte Disorders, a kidney physiology book for nephrologists, fellows, residents and medical students.

  1. Chapter One: Introduction to Renal Function

    EPISODIO 1

    Chapter One: Introduction to Renal Function

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

    1 h y 5 min

  2. EPISODIO 2

    Chapter 2 part 1

    Back by popular demand…all two of you…the second chapter of The Clinical Physiology of Acid Base and Electrolyte Disorders.

    1 h y 29 min

  3. EPISODIO 3

    Chapter 2 Part 2

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

    1 h y 38 min
  4. Chapter 3: The Proximal Tubule

    EPISODIO 4

    Chapter 3: The Proximal Tubule

    Chapter Three: How the proximal tubule is like Elizabeth Warren and other truths my friends from Boston taught me

    1 h y 22 min
  5. Chapter 4: The Loop of Henle and Counter Current Exchange

    EPISODIO 5

    Chapter 4: The Loop of Henle and Counter Current Exchange

    Show notes with a full set of references are available here: http://www.rosebook.club/episodes/2021/6/22/chapter-four Also, please fill out our listener survey: https://forms.gle/DVdcJikKZkzY56mXA

    1 h y 44 min
  6. Chapter 5: The Functions of the Distal Nephron

    EPISODIO 6

    Chapter 5: The Functions of the Distal Nephron

    References for Chapter 5--the Distal Nephron Roger pointed out the fact that the distal nephron can achieve very low urinary sodium as evidenced by observations in people from the Yanomamo tribe Blood pressure and electrolyte excretion in the Yanomamo Indians, an isolated population in this report, 84% of the participants had urinary sodium 1mmol/24 hours.  Information about the Yanomamo Tribe. It looks like they’re starting to make chocolate, now!  Yanomami The Yanomami are great observers of nature The Amazon's Yanomami utterly abandoned by Brazilian authorities: Report Yanomami Amazon reserve invaded by 20,000 miners; Bolsonaro fails to act I believe this is the original study looking at urine sodium and blood pressure in the Yanomamo Indians, but the INTERSALT trial linked above I believe had more robust urine data This study mentions the average lipid profile for men and women along with BMI.  I didn’t mention in the “Voice of God” overview, but there is some interest looking at the Yanomamo and rate of cancer as it relates to the correlation with intracellular potassium to sodium ratios Josh referred back to his notes and realized that the tightest junctions are in the TOAD not FROG bladders Physiology and Function of the Tight Junction An excellent review from McCormick and Ellison on the Distal convoluted tubule in Comprehensive Physiology. We flirt with the disorder of Gordon’s syndrome: Familial Hyperkalemic Hypertension | American Society of Nephrology and its alter ego, Gitelman syndrome: Gitelman Syndrome | Hypertension JC spoke about this beautiful report on how calcineurin inhibitors lead to hyperkalemia (and mimic Gordon’s syndrome). The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension This superb review of the DCT includes all the highlights of Rose’s chapter 5 with a modern lens including “braking” from DCT hypertrophy Distal Convoluted Tubule | American Society of Nephrology Echos of the lessons learned in the DCT can be seen in this review: Diuretic Treatment in Heart Failure | NEJM Anna reminds us of the ALL HAT trial which showed that chlorthalidone was superior to the lisinopril and amlodipine groups (and the alpha blocker dropped out earlier) ​​Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic Nice review of drug induced Hyperuricemia with a deep dive into the mechanisms of diuretic induced Hyperuricemia. Drug-induced hyperuricaemia and gout Plus, despite the concerns that thiazides are weaker than loop diuretics and may not work in CKD, this report suggests that it can still be of use. Chlorthalidone for poorly controlled hypertension in chronic kidney disease: an interventional pilot study If you love diuretics, you will love this classic paper from Craig Brater on diuretics Diuretic Therapy | NEJM which also includes the t1/2 of various diuretics and points out that chlorthalidone’s half life is 24-55 hours so eliminated after 4-10 days.  The hypercalcemia seen in some patients who take thiazides may be the unmasking of primary hyperparathyroidism Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades As we discussed the relative importance of DCT vs Proximal tubule for the hypercalcemia seen with thiazides, Amy reminded us of about the TRPV5 knockout mice: JCI - Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5  JC mentioned the defect in TRPM6 that can cause severe hypomagnesemia:  Novel TRPM6 Mutations in 21 Families with Primary Hypomagnesemia and Secondary Hypocalcemia We enjoyed talking about Liddle syndrome Hypertension caused by a truncated epithelial sodium channel γ subunit: genetic heterogeneity of Liddle syndrome We wondered about the role of pendrin which was discovered after this book was published. Here’s a nice review: The role of pendrin in renal physiology and also a potential therapeutic target for pendrin: Pendrin—A New Target for Diuretic Therapy? | American Society of Nephrology Bradykinen Bradykinin B2 receptor antagonist increases chloride and water absorption in rat medullary collecting duct More Bradykinen Chronic Overexpression of Bradykinin in Kidney Causes Polyuria and Cardiac Hypertrophy We ended on a high note when we considered the urothelium of the American black bear. These magnificent creatures have aquaporins 1 &3 that allow them to reabsorb their own urine during hibernation. The urothelium of a hibernator: the American black bear

    1 h y 35 min
  7. Chapter 6: Effects of Hormones on Renal Function part 1

    EPISODIO 7

    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

    1 h y 51 min

  8. EPISODIO 8

    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

    1 h y 52 min
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A chapter by chapter recap of Burton Rose’s classic, The Clinical Physiology of Acid Base and Electrolyte Disorders, a kidney physiology book for nephrologists, fellows, residents and medical students.

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