Brief Introduction: Mr. R is a 49-year-old male with chronic kidney disease (CKD) stage 3b, hypertension, anemia, and secondary hyperparathyroidism who reports itching severely impairing his sleep, mood, and quality of life.

Chief Complaint: Itching

History of Present Illness: Mr. R is a 49-year-old male with CKD stage 3b.  You see him today and he says he’s extremely bothered by itching.  He can’t sleep and is constantly scratching himself.  

Past Medical History: CKD stage 3b secondary to diabetes; history of diabetes, complicated by nephropathy, neuropathy, and retinopathy; hypertension; anemia; secondary hyperparathyroidism

Medications: 
dapagliflozin 10 mg daily
amlodipine 10 mg daily
carvedilol 12.5 mg bid
losartan 100 mg daily
ergocalciferol 50,000 IU once monthly
diphenhydramine 25 mg PO TID PRN pruritus

Family History: +mother with diabetic kidney disease requiring HD for 3 years prior to death

Personal/Social/Development History: Disabled/retired; No tobacco, alcohol, or illicit drug use

Review of Systems: 
Gen: no weight loss or fever
HEENT: no recent vision change
CV: no recent chest pain; no syncope
Resp: lungs clear
GI: no recent abdominal, nausea, or vomiting
GU: decreased urinary output
Derm: as above
Neuro: +feet numbness
Psych: +poor sleep which he attributes primarily to itching at night; despite feeling somewhat depressed about his condition
Allergy: no history of asthma or hay fever

Patient Physical Examination Findings: 
Gen: middle aged male in no acute distress
HEENT: anicteric
CV: regular sinus rhythm
Resp: normal
Abd: soft, non-tender, non-distended
Ext: trace pitting symmetric bilateral lower extremity edema
Skin: +extensive scattered scratch marks with excoriations associated with xerosis (dry skin) throughout the back, abdomen, arms, and legs; no evidence of lice, scabies, or bedbugs
Neuro: alert; oriented; follows commands appropriately; loss of feet sensation on filament test
Psych: +somewhat anxious and distressed

Diagnostic Studies: 
eGFR 38
WBC 8.1, Hgb 10.1, Plt 302
Na 138, K 4.9, Cl 110, HCO3 24, BUN 30, SCr 2.1 Gluc 160, Ca 9.1, Mg 2, Phos 4.2
PTH 325, vitamin D 25(OH) 28 ng/mL
Alb 3.0 Alk Phos 82, AST 22, ALT 31
Ferritin 823, TSAT 33%
HIV, HCV, and HBV serologies are negative
TSH 3.2
Pruritus as measured by numerical rating scale (NRS): 8/10

Discussion: CKD-associated pruritus (CKD-aP) is a diagnosis of exclusion.  It is important that other systemic and dermatologic conditions are excluded (e.g., cholestatic liver disease, hypothyroidism, contact dermatitis, psoriasis, infestations).  There are no specific laboratory findings or diagnostic tests that definitively diagnose CKD-aP.  Skin findings are consistent with persistent scratching.  Patients characteristically present with diffuse, symmetric, and persistent itching and non-specific excoriations on the back, abdomen, arms and/or legs.  In severe cases, patients can develop areas of scarring and/or nodules (i.e., prurigo nodularis).  The pathophysiology of CKD-aP is poorly understood, but the leading theories include persistent inflammation, an imbalance in opiate receptors, and a neuropathic process. Though a commonly held belief, the best available evidence suggest that hyperparathyroidism and hyperphosphatemia do not play a major role in the pathogenesis of CKD-aP.  Likewise, though antihistamines are commonly used, CKD-aP does not appear to be mediated by histamine and antihistamine therapy is not recommended.
A stepwise approach to therapy for CKD-aP is advised.  First, patients should be educated on appropriate skin care (e.g., use of non-drying soaps, avoidance of scratching) and instructed to apply emollients 2-4 times daily, especially after bathing, especially if xerosis is noted.  Second, a trial of topical therapy is suggested (e.g., pramoxine, gamma linolenic acid, capsaicin if pruritus localized).  If the above steps fail, a trial of gabapentinoid, dosed appropriately for CKD could be initiated.  For refractory cases, UVB phototherapy can be tried.

Mr. R was diagnosed with CKD-aP as there was no evidence of any other systemic or dermatologic condition.  We initiated a stepwise approach to treatment of her condition.  We encouraged aggressive emollient use three times daily to treat his xerosis and recommended that he use a moisturizing soap.  Given his generalized symptoms, capsaicin was not practical, but we offered a trial of pramoxine.  With the topical therapy, his pruritus severity improved slightly (to an NRS of 6/10), but he still was reporting poor sleep at night due to itching.  We next initiated gabapentin.  Over the next few months, the dose was cautiously increased with close monitoring for signs of toxicity (e.g., somnolence, falls).  His pruritus ultimately improved to 3/10 on the NRS and he reported that his sleep quality and mood was much improved.

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* 1. Which of the following is TRUE about CKD-aP?

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* 2. What is your level of confidence that your choice is correct?

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* 3. Which of the following therapies has been FDA-approved (as of April 2022) for the treatment of CKD-aP in CKD patients not on dialysis?

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* 4. What is your level of confidence that your choice is correct?

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