Avraham Z. Cooper, MD 🩺
Avraham Z. Cooper, MD 🩺

@AvrahamCooperMD

16 تغريدة 1 قراءة Jan 02, 2025
1/
Have you ever wondered why advanced renal disease often leads to often debilitating pruritis?
Why would kidney failure lead someone to itch uncontrollably?
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2/
The association b/w kidney and skin diseases, including pruritis, goes back centuries, at least to Richard Bright's early descriptions of uremia in the 1820s.
Bright wrote that "the sympathy between the skin and the kidney is a well-admitted fact".
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Pruritis is quite common in CKD, becoming more prevalent as patients near ESRD, and has major impacts on quality of life, mood, sleep, etc.
One study found a prevalence of 58% among CKD 5 patients on HD.
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4/
Uremic pruritis (UP) seems to be a Hickam's dictum-type situation, with more than one pathophysiologic cause.
The overall problem, not surprisingly, seems to relate to metabolic derangement from renal failure.
But why would that make someone itch so severely?
5/
The proposed pathophysiologic mechanisms for UP seem to break down along two broad categories: cutaneous/peripheral and systemic.
Let's start with cutaneous/peripheral.
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Perhaps the most straight forward explanation is that ESRD patients tend to have dry skin, which contributes to chronic pruritis.
This results from reduced eccrine sweat production, which leads to decreased stratum corneum hydration.
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Next let's pivot to systemic causes, starting w/ parathyroid hormone (PTH, which is increased in ESRD).
It turns out that PTH stimulates mast cell production, and skin pathology in UP shows extensive degranulated mast cells in the dermis.
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9/
The mechanistic association w/ PTH (or metabolic sequela of secondary/tertiary hyperparathyroidism) was supported by a 1968 case series showing resolution of UP in hypercalcemic ESRD patients after partial parathyroidectomy.
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10/
Related to hyperparathyroidism, elevated Ca may contribute to pruritis as well, possibly by subclinical precipitation within the skin.
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Increases in other serum divalent cations such as Mg might also play a role.
Going back to 1979, this patient's UP resolved within a week of decreasing dialysate Mg concentration.
This may reflect Mg's ability to impact nerve function.
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12/
Histamine almost certainly plays a role as well as it is known to mediate pruritis, and ESRD patients have elevated plasma histamine levels.
This results from both increased production and decreased clearance.
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13/
Yet another purported systemic mechanism involves possible over-expression of endogenous µ-opiate receptors in ESRD.
This association is supported by the observation that anti-opiate therapy can be effective in treating UP.
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14/
Some also have theorized that UP is an inflammatory condition, driven by T lymphocyte activation and cytokine production.
IL-2 offers an intriguing possible mechanistic explanation, as it can cause itchiness when injected into the skin.
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IL-2 might also explain a surprising association, where patients starting on HD experience new onset or worsening UP.
One theory to explain this is that reaction to the HD membranes elicits IL-2 release and worsening pruritis.
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16/SUMMARY
Hopefully it's clear that uremic pruritis is very much multifactorial. But when thinking about causes, local/cutaneous vs. systemic etiologies may be a helpful framework.
Itch scratched!

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