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7 most impactful clinical trials focussed on slowing progression of chronic kidney disease
A Thread 🧵
A highly subjective list, but these trials have been included as they have had a meaningful impact on guidelines, patients and clinicians at a global scale.
A Thread 🧵
A highly subjective list, but these trials have been included as they have had a meaningful impact on guidelines, patients and clinicians at a global scale.
1) IDNT: Irbesartan Diabetic Nephropathy Trial
Randomized, blinded, placebo-controlled trial designed to assess whether irbesartan or amlodipine slow the progression of nephropathy in patients with type 2 diabetes, independent of effects on systemic blood pressure (BP) lowering
Randomized, blinded, placebo-controlled trial designed to assess whether irbesartan or amlodipine slow the progression of nephropathy in patients with type 2 diabetes, independent of effects on systemic blood pressure (BP) lowering
The primary outcome, a composite of doubling of serum creatinine, onset of end-stage renal disease, serum creatinine ≥6.0 mg/dl, or death from any cause, was reduced by 23% compared to the amlodipine group (32.6% vs. 41.1%, p=0.006)
I'm putting together a lecture on AKI for emergency medicine doctors. Here is my outline. What am I missing? #AskRenal
I wanted to be practical and stick with the realities of AKI management today rather than forward looking technologies that may be impactful in the future.
Since the pretest probability that fluids will help AKI, physicians should not try to find volume depleted people, but should give fluids to everyone unless the fluids would be harmful.
The problem is nephrology created the GN schema with little pathophysiologic basis, it was mostly categorized by microscopic appearance. We are in the process of unwinding that with new scema for MPGN, new understanding of membranous and novel insights to MCD...etc.
Need a fresh rewrite of the textbooks with a pathophysiologic rather than a histologic approach.
If you eat yourself, will you get hyperkalemic?
Sorry, let me rephrase:
Can upper GI bleeding cause hyperkalemia in predisposed people?
I feel like I’ve gotten that vibe from a couple patients. I can’t find any reports from others.. but I can think of a mechanism...
1/
Sorry, let me rephrase:
Can upper GI bleeding cause hyperkalemia in predisposed people?
I feel like I’ve gotten that vibe from a couple patients. I can’t find any reports from others.. but I can think of a mechanism...
1/
Blood contains a lot of protein.
When a significant amount of it is introduced into the proximal GI lumen (and some of it absorbed), it can elevate your BUN, or trigger hepatic encephalopathy.
2/
When a significant amount of it is introduced into the proximal GI lumen (and some of it absorbed), it can elevate your BUN, or trigger hepatic encephalopathy.
2/
The concentration of potassium in RBCs is ~100 mMol, meaning 100 mEq/L. If you start at a hematocrit of 40 and bleed 20% of your blood volume into your stomach...
That’s ~1 liter blood = 400 cc of red cells = 40 mEq of potassium.
3/
That’s ~1 liter blood = 400 cc of red cells = 40 mEq of potassium.
3/
#AskRenal Patients can get hypotensive after relieving urinary obstruction. Does clamping the foley and slowing bladder decompression protect against the hypotension?
Not in this RCT: pubmed.ncbi.nlm.nih.gov/23859894/
Or in this Case Control trial: ncbi.nlm.nih.gov/pmc/articles/P…
Acute Kidney Failure
OR 🤔
Acute Kidney Success?
…bare with me while I explain 🧵
#NephTwitter #MedTwitter #Physiology #askrenal #tweetorial #aki #MedStudentTwitter #meded #FOAMed
OR 🤔
Acute Kidney Success?
…bare with me while I explain 🧵
#NephTwitter #MedTwitter #Physiology #askrenal #tweetorial #aki #MedStudentTwitter #meded #FOAMed
We make 1-2 L of urine per day to eliminate
❎excess solutes
❎H2O
❎toxins
AND
✅maintain homeostasis.
This process is accurate to the T.
❎excess solutes
❎H2O
❎toxins
AND
✅maintain homeostasis.
This process is accurate to the T.
To achieve this accuracy, plasma is continuously filtered and reprocessed by the kidneys. ♻️
How much plasma is filtered per day, you ask? 😳
Roughly 200 LITRES! 🌊
How much plasma is filtered per day, you ask? 😳
Roughly 200 LITRES! 🌊
1/ I often get asked about the presence of granular casts on the automated UA reported by the lab whether it is equivalent to seeing muddy brown casts.
❓Do you think granular casts can be used to diagnose ATN?
More to see in #NephMadness on #liquidbiopsy
@NSMCInternship
❓Do you think granular casts can be used to diagnose ATN?
More to see in #NephMadness on #liquidbiopsy
@NSMCInternship
2/ Spin the urine! This is one of the maneuvers that I enjoy doing with residents the most as there is a lot to uncover.
I totally underestimated the power of this test. How many times have you spun the urine yourself before nephrology training?
I totally underestimated the power of this test. How many times have you spun the urine yourself before nephrology training?
3/ The clinical properties of urine have long been described by the medical community.
‘Diabetic’ (polyuric) disorders were classified as ‘mellitus’ (honey-sweet) or ‘insipidus (flavorless) based on the urine’s taste!
#NephMadness #liquidbiopsy
‘Diabetic’ (polyuric) disorders were classified as ‘mellitus’ (honey-sweet) or ‘insipidus (flavorless) based on the urine’s taste!
#NephMadness #liquidbiopsy
What misconceptions do you commonly encounter among in-center dialysis staff and patients that deter people from home dialysis?
#askrenal
@NephJC @ASNCommunities @hdunews @DialysisAtHome
#askrenal
@NephJC @ASNCommunities @hdunews @DialysisAtHome
Bringing this to the thread.
@threadreaderapp unroll
I have a patient with anti-PLA2r + membranous nephropathy who was taking a lot of NSAIDs before the onset of disease. Does the anti-PLA2r antibodies exonerate the NSAIDs? #AskRenal
It is an incredibly interesting case. The patient, who was born in east Asia, presented to me years ago with a history of HIV (treated with tenofovir disoproxil fumarate) with a mild increase in cr. U/A showed heavy proteinuria.
Patient was not concerned with the increased proteinuria but the lower extremity edema. We treated with furosemide and did a biopsy. The biopsy was inadequate with only 2 gloms🤯
both sclerosed 🤯🤯🤯
both sclerosed 🤯🤯🤯
-BP is normal (110/60)
-Orthostatic BP not checked
-H/o chronic diarrhea , diagnosed with Irritable Bowel Syndrome 1 year ago
-15 lbs weight loss in 6 months
-Denies use of laxatives, PPIs or diuretics
-No h/o vomiting
-Orthostatic BP not checked
-H/o chronic diarrhea , diagnosed with Irritable Bowel Syndrome 1 year ago
-15 lbs weight loss in 6 months
-Denies use of laxatives, PPIs or diuretics
-No h/o vomiting
#ToughTxCase I am going to start an educational series for #transplant professionals/trainees on complex cases I have the privilege to see @UWHealth Patients have provided informed consent for us to discuss their condition in order to help other similar cases @uw_nephrology
#ToughTxCase #1 is the story of Tom, a 73 year old man, who received a living unrelated #kidney tx for #ESRD due to an unknown etiology. Low immunological risk, VXM (-), #CMV D+/R-, basiliximab induction, standard TAC/MPA/P maintenance Rx on Valgan prophylaxis x 6M @TxPharmD
At his 3M visit, Tom complains of #diarrhea, weight loss (4 lbs in 1 month) and poor energy. His kidney fxn is at baseline Scr 1.3 mg/dL. What is the most likely diagnosis? Please feel free to discuss! @uw_IMresidency @askrenal @Nephro_Sparks
#AskRenal in 2007 KI published this paper showing massive albumin filtration at the glomerulus in norml kidneys shattering decades of dogma regarding the negative charge in the glom. pubmed.ncbi.nlm.nih.gov/17228368/
This was followed by a Pro-Con debate in JASN in 2008
jasn.asnjournals.org/content/19/3/4…
jasn.asnjournals.org/content/19/3/4…
What is the current thought?
A) The classic, glomeruli are impermeable to albumin
B) The rebel, glomeruli leak a lot of albumin that is normally reabsorbed in the proximal tubule
Please reply with the real answer the poll is for fun but won't help me answer my question
A) The classic, glomeruli are impermeable to albumin
B) The rebel, glomeruli leak a lot of albumin that is normally reabsorbed in the proximal tubule
Please reply with the real answer the poll is for fun but won't help me answer my question
Touch contamination: The overall rate of peritonitis was low after contamination (2012)
📌 Wet contamination was asso. w/ ⬆️ risk of peritonitis
📌 Prophylactic antibiotics after wet contamination were effective in preventing peritonitis #Nephpearls
👉🏼 ncbi.nlm.nih.gov/pmc/articles/P…
📌 Wet contamination was asso. w/ ⬆️ risk of peritonitis
📌 Prophylactic antibiotics after wet contamination were effective in preventing peritonitis #Nephpearls
👉🏼 ncbi.nlm.nih.gov/pmc/articles/P…
Touch contamination: Prophylactic antibiotics are usually recommended after wet contamination (if dialysis solution is infused after contamination, or if catheter administration set was open for an extended period) ca. 2016 from @ISPD1 #Nephpearls
👉🏼 pdiconnect.com/content/36/5/4…
👉🏼 pdiconnect.com/content/36/5/4…
Touch contamination: Algorithm ca. 2006 from @Kidney_Int #Nephpearls
👉🏼 kidney-international.org/article/S0085-…
👉🏼 kidney-international.org/article/S0085-…
Can anyone recommend a ml/kg/hour fluid replacement add on for each degree of fever above 37? Patients are not spiking, they are pyrexial for days. What’s the fluid replacement/insensible loss equation for this scenario?
Or perhaps more a SA rather than Kg issue 🤔 Anyway, all I can find is 250ml per degree per day from a surgical textbook. That seems reasonable for a temp spike whilst NBM awaiting theatre, but not the persistent temps.
Any ideas #askrenal?
Any ideas #askrenal?
It is very reassuring to find other people struggling to answer this problem. Please come back to me if you find a solution.
MINTAC: RCT of Tacrolimus and Prednisolone Monotherapy for Adults with De Novo Minimal Change Disease ca. 2020 from @CJASN
#NephJC #Nephpearls
#VisualAbstract by @PabloGarciaMD
👉🏼 cjasn.asnjournals.org/content/15/2/2…
#NephJC #Nephpearls
#VisualAbstract by @PabloGarciaMD
👉🏼 cjasn.asnjournals.org/content/15/2/2…
Minimal Change Disease ca. 2017 from @CJASN
#NephJC #Nephpearls
👉🏼 cjasn.asnjournals.org/content/clinja…
#NephJC #Nephpearls
👉🏼 cjasn.asnjournals.org/content/clinja…
Treatment of Minimal Change Disease (MCD)/ Focal Segmental Glomerulosclerosis (FSGS) ca. 2019 from @goKDIGO
#NephJC #Nephpearls
👉🏼 kdigo.org/wp-content/upl…
#NephJC #Nephpearls
👉🏼 kdigo.org/wp-content/upl…
Tweetorial: An amp of 8.4% NaBicarb in the ICU 💉. Panacea or poison?
#NephTwitter #askrenal #medtwitter @askrenal
Normally, at a pH of 7.4, what is the concentration of H+ in the arterial plasma?
#NephTwitter #askrenal #medtwitter @askrenal
Normally, at a pH of 7.4, what is the concentration of H+ in the arterial plasma?
Let’s begin with a mind excercise 🧮!
How efficient is Bicarbonate as a buffer? 🧪
Remember:
[H+] = 24 x PCO2/[HCO3-]
pCO2 = 40
[HCO3-] = 24
Hence, normally:
[H+] = 24 x 40/24 = 40 nanoeq/L
If [H+] exceeds 160 nanoeq/L ➡️ pH = 6.8 ➡️ DEATH 💀
How efficient is Bicarbonate as a buffer? 🧪
Remember:
[H+] = 24 x PCO2/[HCO3-]
pCO2 = 40
[HCO3-] = 24
Hence, normally:
[H+] = 24 x 40/24 = 40 nanoeq/L
If [H+] exceeds 160 nanoeq/L ➡️ pH = 6.8 ➡️ DEATH 💀
Say a healthy individual presents after attempting suicide 🚫 by ingesting an acidic substance 💊, adding 12 MILLION nanoeQ/L (12 meQ/L) of H+ to circulating plasma (300,000 times normal [H+])- what pH do you expect at presentation, assuming NO respiratory compensation?
Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis ca. 2019
#VisualAbstract by @VickiSandys1
#NephJC #Nephpearls
👉🏼 jamanetwork.com/journals/jamai…
#VisualAbstract by @VickiSandys1
#NephJC #Nephpearls
👉🏼 jamanetwork.com/journals/jamai…
Chart showing cumulative Nephrogenic Systemic Fibrosis (NSF) cases reported to the NSF Registry by date of onset through 2012
📌 Important FDA announcements are marked on the timeline
#Nephpearls #NephJC
📌 Important FDA announcements are marked on the timeline
#Nephpearls #NephJC
Depiction of the current gadolinium-based contrast agents approved for clinical use in Canada 🇨🇦 #Nephpearls #NephJC
👉🏼 ncbi.nlm.nih.gov/pmc/articles/P…
👉🏼 ncbi.nlm.nih.gov/pmc/articles/P…
CRRT: What’s the highest ultrafiltration rate have you used (mL/hour)⁉️ #Nephpearls #AskRenal
Two third of practitioners (71 %) reported using CRRT w/ a net UF rate of median 80.0 mL/hr (IQR 49-111 mL/hr) for hemodynamically unstable & a maximal rate of 299.0 mL/hr (IQR 200-365 mL/hr) for hemodynamically stable patients #Nephpearls
👉🏼 journals.lww.com/ccmjournal/Abs…
👉🏼 journals.lww.com/ccmjournal/Abs…
Preparing for a 45-minute lecture on Review of Nephrology Literature 2019
📌 Please recommend noteworthy publications
🔲 Fluids & Electrolytes, Acid-Base
🔲 CKD
🔲 Hypertension
🔲 Glomerular Diseases
🔲 Cystic Disorders
🔲 Kidney Transplant
🔲 AKI
#Nephpearls #AskRenal
📌 Please recommend noteworthy publications
🔲 Fluids & Electrolytes, Acid-Base
🔲 CKD
🔲 Hypertension
🔲 Glomerular Diseases
🔲 Cystic Disorders
🔲 Kidney Transplant
🔲 AKI
#Nephpearls #AskRenal
CREDENCE: Canagliflozin reduces the risk of kidney failure or death due to CV or kidney disease by 30% compared to current standard of care ca. 2019 from @NEJM
#VisualAbstract by @brendonneuen
#Nephpearls
👉🏼 nejm.org/doi/pdf/10.105…
#VisualAbstract by @brendonneuen
#Nephpearls
👉🏼 nejm.org/doi/pdf/10.105…
Randomized Controlled Trial of Long-Term Safety and Efficacy of Veverimer for Treatment of Metabolic Acidosis
#Nephpearls
#Nephpearls
1/ Alright #medtwitter and #askrenal, in honor of our CJASN publication "Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR," I'm attempting my first #tweetorial. Here's what you need to know about opioids in CKD.
2/ First of all, pain is common for people with kidney disease because of vascular disease, diabetic neuropathy, and pain syndromes unique to kidney patients like osteodystrophy and calciphylaxis. In fact, an estimated 58% of people with advanced CKD experience pain.
3/ People with kidney disease have limited options for pain control. NSAIDs can lead to Na/K/H20 retention, AKI and CKD. Tylenol is okay, but never seems to work. As a result almost half of patients with advanced CKD are prescribed opioids.
