KIDNEY AMYLOIDOSIS

Alejandro Meraz-Munoz

@NephroGuy

ProteinsBiomolecules with a vast array of functions:o Enzymeso DNA replicationo Structureo Transporterso Defense

AmyloidosisProteinsMisfolded protein accumulation

Amyloidosis

Amyloidosis

AMYLOIDOSIS

DISEASE DISEASES

Al amyloidosiso Systemic diseaseo Most common and severeo 10 persons per million/yearo More common > 65 yo 70 % people > 1 organ affected

74% 60%

40% 18%

Al amyloidosis

Lightchain

Heavy chain

Disulphide bonds

Al amyloidosis

Related conditionso Multiple Myelomao Smoldering Myelomao Waldenström Macroglobulinemiao Lymphomaso MGRS

Symptoms

Al amyloidosiso Fatigueo Shortness of breatho Tingling/Numbnesso Weight losso Diarrheao Paino Frothy urineo Edema QOL

Kidney Amyloidosis

Nephrotic syndrome

Leak of proteins

Kidney Amyloidosis

20%

Nephrotic syndrome

Kidney AmyloidosisDiagnosis

M protein FLC Bony lesions

Kidney AmyloidosisDiagnosis

Kidney amyloidosis

Kidney Amyloidosis

Laser Micro-dissection

Mass spectrometry

Kidney Amyloidosis

Kidney AmyloidosisTreatment Objectives

However…

There is no cure for Amyloidosis

Even if we love kidneys…

Mean survival of untreated patients with advanced cardiac involvement is 3-6 months.

Response criteria

Response criteriao 50 % decrease in urine proteins

o 75 % is bettero 95 % is even better

o < 25% decline in renal functiono Doesn't really matter if the proteins

in the urine decreased 75%

Treatmento Melphalan + prednisolone (Dex).

o More 30 yearso Toxico New hematological cancerso 67% achieved CR

o Bendamustine

Back in the day

TreatmentNovel therapies

VSProteasome inhibitors

Treatment◦ Velcade + CFM + Dex (CyBorD)◦ Response rate 81%◦ Less toxic◦ Can be used in HF and CKD

◦ Ixazomib is the new kid on the block

Proteasome Inhibitors

Treatment◦ Side effect◦ Shingles◦ Nausea◦ Neuropathy◦ Infections◦ Bone disease◦ Fluid retention

Proteasome Inhibitors

Treatment◦ Lenalidomide◦ Response rate 50 %◦ Refractory cases

◦ Pomalidomide is the newest addition◦ 50% response in heavily treated patients.

Immuno-modulators

Treatment◦ Side effects◦ Cytopenia◦ Diarrhea◦ Fatigue◦ Fluid retention (Increase in NT-BNP)◦ Renal disfunction (44% reversible)◦ Birth defects

Immuno-modulators

TreatmentAutologous Stem Cell Transplant◦ Standard of care in low risk patients (20%)◦ CR: survival up to to 15 years.◦ High risk patients◦ > 65 years◦ > 2 affected organs◦ Severe CKD◦ Severe HF

TreatmentWhat is on the horizono I-Dox: Soft tissueo CPHPCo Daratumumab (response 76%)o Immunotherapyo Renal Transplant

THANK YOU