Kidney Replacement Therapy

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<h1>Kidney Replacement Therapy</h1>
<h3>MBChB Teaching | 2024</h3>
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# Learning intentions

- what do the kidneys do?

- modalities of KRT

- three cases: complications of KRT

.RWH_footnote_right[.RWH_footer_style[slides at: https://www.kidneyfish.net/talks/]]

???

KRT currently preferred to RRT.

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# .white[What do the kidneys do?]

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# Kidneys

`Filtering the blood` - how much?: 
- water (volume) clearance 
- small solute clearance > electrolyte & acid-base homeostasis 
- clearance of larger solutes  
- clearance of xenobiotics (e.g. drugs)

<br>

`Other stuff`: 
- blood pressure regulation 
- vitamin D metabolism and bone health 
- erythropoetin  
- metabolism (e.g. gluconeogenesis)  
- other things we don't know about yet?

???

If GFR 100 ml/min = 1000L per week.

Renal blood flow is [~10,000L per week](https://homedialysis.org/news-and-research/blog/180-the-mathematics-of-dialysis-vs-two-normal-kidneys).

Makes sense if RPF ~50% of RBF and FF ~50%.

Maths easy because there are ~10,000 minutes in a week.

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# .white[KRT modalities]

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???

Present hypothetical cases with kidney failure - what is best KRT option?

Patient 1: (pre-emptive Tx) - e.g.  Laura, 45F, solicitor, IgAN, eGFR 19   
Patient 2: (HD) - e.g. Mohammed, 46M, DKD, anuric, lives in small tenament flat
Patient 3: (PD) - e.g. June, 72F retired teacher, chronic GN, eGFR 15, no co-morbidities, hates hospitals  
Patient 4: (cRRT) - e.g. John, 34M with meningococcal septicaemia and MOF  
Patient 5: (conservative care) e.g. Peter, 79M, COPD, housebound, eGFR 9 from renovascular disease.

Image credits:

- all pexels apart from ICU = https://www.theguardian.com/society/2020/nov/22/nhs-patients-at-risk-as-icus-routinely-understaffed-doctors-warn

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???

Image credits:

- https://www.ucl.ac.uk/immunity-transplantation/clinical-services/diseases-treatments/transplantation/kidney-transplantation  
- …and PEXELs

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???

Surface area of haemodialyser roughly the same as BSA and area of peritoneal membrane - see below (e.g. for FX80, A = 1.8 m^2, K_UF = 33 ml/hr/mmHg/m^2).

Image credits:

- patient = https://en.wikipedia.org/wiki/Kidney_dialysis  
- dialyser  = https://www.polymedicure.com/dialyzers/  
- Permcath = https://theii.org/hemodialysis-catheter  
- dialyser membrane = https://doi.org/10.1038/s41581-018-0002-x

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???

Notice hand gel.

Surface area of peritoneal membrane thought to be approximately equal to body surface area (i.e. 1.73 m^2).  Greatly increased by microvilli.

Image credits:

- patient = https://www.nhs.uk/conditions/dialysis/what-happens/  
- catheter = https://www.dpcedcenter.org/treatment/dialysis/peritoneal-dialysis/  
- peritoneum = Di Paolo & Sacchi (2000), PDI 20(3)

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# KRT modalities

- `iHD`: volume & small solute clearance only (10 - 15 ml/min and intermittent); need vascular access

- `PD`: volume & small solute clearance only (5 - 10 ml/min); need PD catheter

- `cKRT`: volume & small solute clearance only (20 - 30 ml/min)

- `transplant`: all kidney functions (up to 50 ml/min); need immunosuppression

???

Support for these numbers...

Total [blood flow to dialyser](https://homedialysis.org/news-and-research/blog/180-the-mathematics-of-dialysis-vs-two-normal-kidneys) = 250 - 300L!

[eGFR equivalence for HD](https://homedialysis.org/news-and-research/blog/188-hemodialysis-egfr-equivalence-why-more-and-more-often-matters) = c. 14 ml/min.

For PD, assuming weekly CrCl of 50L - 60L = 5 - 6 ml/min; [Kt/V 1.7 per week](https://doi.org/10.1093/ckj/sfy082) = 8 - 9 ml/min.   
For cRRT, assume flow rate of replacement fluid in CVVHF.

See also dialysis handbook p220 - taken from [Metha, 2005](https://pubmed.ncbi.nlm.nih.gov/15673337/) - and [Tattersall, 2018](https://doi.org/10.1093/ckj/sfy082).

## Notes

### Modality choice

iHD will gain more rapid metabolic control (e.g. in hyperkalaemia) than CRRT.

For `poisonings`: dialysis (NOT filtration) is the mode of choice for almost all poisons (Li, sailcylates etc…)  In theory charcoal haemoperfusion could be used for carbemazepine / aminophylline – but not used in practice (evidence not great).  See EXTRIP!

<br>

### Principles of RRT

Solute transport may be via:

- `diffusion` = movement down a concentration gradient    
- `convection` =  bulk movement of solvent and solute = "solvent drag"

HD = almost all diffusion  
PD = both   
CVVHF = all convection  
HDF = both

Definitions:

- `dialysis` = modification of composition of two solutions by exposure to each other across a semi-permeable membrane

- `filtration` = passing a solution through a filter

- `ultrafiltration` = movement of solutes and fluid by convective transport through a semi-permeable membrane; may be driven by a `hydrostatic` (e.g. in HD) or `osmotic` (e.g. in PD) gradient

- `haemofiltration` = KRT method in which clearance is achieved through large-volume UF, with use of a replacement fluid

The term `ultrafiltration` was first used [in the early 1900s](https://www.oed.com/dictionary/ultrafiltration_n?tl=true&tab=meaning_and_use) to denote filtration through a filter that was sufficiently fine to retain colloids / virueses etc. In fluid mechanics, is distinct from microfiltration (larger pores) and nanofiltration (smaller pores).  It is often used synonymously with `convection`.

`Ultrafiltration` occurs physiologically in the glomeruli.  In HD circuits, it is achieved by applying a negative hydrostatic pressure to the dialysate (adjustable inflow valve; pump in efflux limb).  In PD, it is achieved by using glucose or icodextrin to generate an osmotic gradient.  For `isolated UF`, the dialysis machine is run without any dialysate flow.

The term `dialysis` was first coined by Thomas Graham (1860s) to describe the chemical process of serparating dissolved substances across a floating parchment membrane.  He termed retained substances "colloids".  (It has an alternative meaning in grammar - the splitting of one syllable into two - and obsolete meanings in rhetoric too.)  Etymology from "dia" meaning through or across and "lysis" meaning splitting.  The splitting of a solution across a membrane.

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# .white[Cases]

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# Case 1

`25M presenting with SOB`:

- ESKD due to "reflux nephropathy" - started dialysis at 18 years old

- frequently misses dialysis sessions

- in A&E today with shortness of breath

- SaO2 83% on air; 96% on high-flow O2

- ABP 210/120

- urea 21, creat 990, Na 131, K 5.9

???

What questions to ask a dialysis patient:

- target weight? - and talk through concept  
- do you pass urine?  
- FR?  
- typical UF?

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# Case 2

`25M presenting with rigor on dialysis`:

- T39

- under the weather for a few days

- new neck pain

- ABP 140/70; no obvious infective source o/e; tender C-spine

- Hb 91, WCC 11, CRP 140

???

SAB  
Risks of metastatic infection  
Where should we site the venflon for his antibiotics?

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![](images/biofilm.png)
???

Staphylococci enmashed in a biofilm in a central venous catheter.

Image credit = PMID 18720093.

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# Case 3

`60F presenting with SOB`:

- ESKF from IgAN

- 1st transplant 24 years ago; lasted 12 years

- 2nd transplant 8 years ago; early rejection episode

- periods of PD and HD in between

- new SOB and dry cough

- SaO2 91% on air; afebrile; chest sounds clear

- Hb 130, WCC 2.1, plt 210; SCr 142 mcM (baseline 120 mcM)

???

Exemplifies long patient KRT journey

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# Take-home points

- options for KRT are: transplant (from various sources), HD, PD, cKRT, conservative care

- best form of KRT will depend on the individual

- dialysis provides bare minimum replacement of normal kidney function

- complications of dialysis include: fluid overload, hyperkalaemia, infections, access failure, CVS disease

- complications of transplant include: surgical, rejection, opportunistic infections, malignancy, diabetes

.RWH_footnote_right[.RWH_footer_style[slides at: https://www.kidneyfish.net/talks/]]