Ajay K. Singh, MB., FRCP

Physician, Renal Division,

Brigham and Women’s Hospital,

Course Director, IRIM

Senior Associate Dean for Postgraduate Medical Education,

Harvard Medical School

Additional Pearls in Nephrology

Ajay K. Singh Bio

• Attending Nephrologist, Brigham and Women’s Hospital

• Senior Associate Dean for Postgraduate Medical Education, Harvard Medical School

• Research interests: Anemia of CKD and CKDu

• Clinical interests: managing patients with CKD

Disclosures

• ConsultingGSK

• Stock

Gilead

Clinical Scenarios In General Nephrology

• #1 CKD-Anemia

– 62-year-old woman with CKD and anemia

• #2 CKD-Hyperkalemia

– A 44-year old patient with CKD who has a K of 7.2

mEq/L

• #3 Kidney Stones

– 37-year-old man presents with 2 hours of excruciating

pain in left groin

#1 62-year-old woman with CKD and

anemia

62-yo woman with 10-year history of CKD from

diabetes; slowly worsening renal function. Past

medical history of a right CVA stroke. She sees

you in the office. Feels great. Working, exercising,

eating well. Lab data shows BUN 48 mg/dL, Cr 4.2

mg/dL, eGFR 18 ml/min/1.73m2, Hb 9.1 g/dL, Tsat

30%, ferritin 282.

Anemia in CKD patients

• Causes include

– Iron deficiency (reduced absorption, poor intake)

– Blood loss (frequent blood draws, GI bleeding)

– Relative erythropoeitindeficiency

SOURCE: Babbit and Lin, JASN 2013 https://jasn.asnjournals.org/content/23/10/1631

Anemia Treatment in Dialysis

and Non-Dialysis Patients

• Don’t need treatment if patient asymptomatic (usually start treatment Hb <10 g/dL)

• Make sure patient is iron replete

• TSAT >20%, Ferritin >100

• Target range - Hb 10-11 g/dL

• Use an ESA (2 ESA’s in US – Epo or Darbepoietin)

• Newer ESA’s – prolyl hydroxlase inhibitors (PHIs) not approved in US currently

• Be cautious with ESA treatment in patients with a history of stroke and/or cancer

ESAs Currently in Use in the U.S.

Source: Fishbane S et al, 2013http://www.nephrologynews.com/articles/109496-choice-of-erythropoiesis-stimulating-agent-in-esrd

* Methoxy polyethylene glycol epoetin beta. (Micera)

ESA’s globally

Published Feb 2021 SOURCE: https://www.datamintelligence.com/research-report/erythropoietin-stimulating-agents-market

#2 A 44-year old patient with CKD who has a K of 7.2 mEq/L

• A 44-year old woman with a history of stage 4 CKD is noted to have a serum K of 7.2 mEq/L. She denies N, V and diarrhea. No new medications

• On physical examination. Wt 72 Kg, BP 141/62 mmHg, heart and lung examination normal, no edema.

• EKG – see next slide….

ECG Changes of hyperkalemia

Peaked T wavesP wave wide and flatProlonged QRS interval with bizarre QRS morphology, High-grade AV block with slow junctional and ventricular escape rhythms, Conduction block (bundle branch blocks, fascicular blocks)(Development of a sine wave appearance (a pre-terminal rhythm))

http://www.aafp.org/afp/2006/0115/p283.html

Pre-terminal rhythm with very high K

SOURCE: https://www.slideshare.net/ravirajmenon/hyperkalemia-56833946

K= 9.9 mEq/L

Causes of Hyperkalemia• Increased intake

– K+ supplements, diet, transfusions, iatrogenic

• Decreased renal excretion– Renal disease, particularly with type IV RTA

– DRUGS (e.g., potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride; NSAIDs)

– Adrenal insufficiency

• Intra → extracellular shifts– Hyperosmolarity

– Insulinopenia

– Metabolic acidemia

– DRUGS (e.g., beta-blockade)

• Artifactual– in vitro hemolysis, leukocytosis, thrombocytosis

– “pseudohyperkalemia”

Management of Hyperkalemia as an Outpatient

K< 5.5 mEq/L K>6.0 mEq/LK 5.5-6.0 mEq/L

No structural CVD diseaseChronically on high side Hold K raising meds

Recheck

Structural CVD disease

Do EKGHold K raising medsDietTreat with resin

Do EKGHold K raising meds

Treat with resin

Emergency treatment

Do EKGIf EKG changes

Ca gluconateThen Insulin/Dex/resindialysis

No EKG ChangesRecheck KInsulin/dextrose/resinDiet

Treatment of Hyperkalemia

Mechanism Therapy Dose Onset Duration

Stabilize membrane

potential

Calcium 10% Ca-gluconate,

10 ml over 10 min.

1-3 min. 30-60

min

Cellular K+ uptake Insulin

β2-agonist

10 U R with 50 ml

of D50, if BS<250

nebulized albuterol,

10 mg

30 min.

30 min.

4-6 h

2-4 h

K+ removal Kayexalate

ZS9

Hemodialysis

30-60 g PO

5-10 g PO

hours

hours

Immediate

?

SOURCE: https://www.medscape.org/viewarticle/880329_2

*Kayexalate SPS= sodium polystyrene sulfonate

8.4 g PO qDay

VeltassaLokelma

10 g PO qDay30-60 g PO qDay

Kayexalate/SPS Complications

• Ischemic colitis and colonic necrosis- risk in enema form

- often fatal

- risk with sorbitol - but can occur without sorbitol and is associated with intestinal SPS crystals

- post-transplant and post-op patients at risk

• Volume overload

• Reduction in serum calcium

• Iatrogenic hypokalemia

Bicarb

Blumberg et al, Am J Med, 85, 1988

Changes in plasma K during IV infusion of

bicarbonate in HD patients

Values= means + SE

*P<0.5, + P<0..01 vs. baseline

Blumberg et al KI, 41: 369-374, 1992

#3 37-year-old man. After a few twinges

over past 2 months, presents with 2 hours of

excruciating pain in left groin

• A 37-year old man presents with 2 hrs of excruciating pain in the left groin. Started in left flank. Episode of gross hematuria. PMH of rt flank twinges.

• On physical examination. Looks in pain (writhing, sweaty), Wt 72 Kg, BP 155/80 mmHg, HR 105 bpm, afebrile, JVP 8 cm, normal skin turgor, moist mucous membranes, lungs clear, mild tenderness left flank, no guarding, no edema.

• Na 140, K 4.2, Cl 100, BUN 24, Cre 1.1, BG 98 mg/dL. UA SG 1015, pH 5.0, 4+ blood, 1+ leuks, rest neg. SedTNTC RBCs not dysmorphic, ocass WBC

Stones

• Calcium oxalate– 70-80%

• Uric Acid– 10-15%

• Magnesium ammonium phosphate (struvite infection related)– 10-15%

• Cystine– <1%

• Others – <1%

• Dehydration

– concentrates stone forming constituents

• Anatomic abnormalities

– promote stasis, infection and/or crystal adhesion

• Changes in urinary pH

– e.g. calcium oxalate less soluble in alkaline urine

• Diet

– high protein / salt intake promotes hypercalciuria

– diet high in oxalate promotes oxaluria

• Medications

– furosemide /ca wasting; acetozolamide /bicarb

Risk Factors for Stone Formation

Work-up

• Imaging

– Non-Contrast helical CT with Stone protocol is gold

std (detects stones not visible by KUB/IVP and has

significantly better sensitivity/specificity)

– Ultrasound: For patients needing avoidance of

radiation (pregnant, childbearing age)

– IVP: No longer favored due to lower sensitivity,

HIGHER radiation exposure

– KUB: Will miss radiolucent uric acid stones, small

stones, stones with overlying bony structures.

What stones don’t show up on imaging

• 85% of stones are radio-opaque

– Ca containing

– Cystine

• 15% radiolucent

– Uric acid

Treatment

• Urologic Intervention?

– X<5mm : most pass spontaneously. Possible observation and pain control

– X>5mm : less than 20% chance of passage and may need urologic intervention

• So when to consult urology?

– If > 5mm

– For ANY size with ….

• Urosepsis, AKI, anuria, unyielding N/V/Pain -> Inpatient consult

• Failed conservative management and stone did not pass spontaneously -> Inpatient or Outpatient consult depending on severity

Role of Tamsulosin (Flomax)

• Double-blind, placebo-controlled study • N= 3296 patients with distal ureteral stones, 30 centers• Evaluate the efficacy and safety of tamsulosin• Randomly assigned (1:1) into tamsulosin (0.4 mg) or placebo groups for 4 wk• Tamsulosin treated pts had higher stone expulsion (CT confirmed over 28-day period)

rate than placebo (86% vs 79%; p < 0.001) for distal ureteral stones. • Secondary end points: tamsulosin-treated patients shorter time to expulsion

(p < 0.001), required lower use of analgesics vs. placebo (p < 0.001), and significantly relieved renal colic (p < 0.001).

• Subgroup analysis: tamsulosin better for the treatment of large distal ureteral stones (>5 mm).

Summary

• #1 CKD-Anemia

– 62-year-old woman with CKD and anemia

• #2 CKD-Hyperkalemia

– A 44-year old patient with CKD who has a K of 7.2

mEq/L

• #3 Kidney Stones

– 37-year-old man presents with 2 hours of excruciating

pain in left groin

References

• N Engl J Med 2000; 342:1581-1589

• Blumberg et al KI, 41: 369-374, 1992

• N Engl J Med 2015; 372:222-231

• MED ARH 2011; 65(4): 213-215

• Am Fam Physician. 2011 Dec 1;84(11):1234-1242.

• Ann Intern Med. 2003;139:137-147

• Nat Rev Dis Primers. 2016 Feb 25, 25;2:16008