HDCN Abstract:  ASN Annual Meeting 2020 -- Digital Meeting  

Najafian B, Mauer M, Fioretto P

Reversal of Diabetic Nephropathy After 10 Years of Pancreas Transplantation Occurs Despite Parallel Podocyte Loss

ASN Annual Meeting 2020 -- Digital Meeting
J Am Soc Nephrol (Oct) 31:35A 2020

BACKGROUND

Diabetic nephropathy (DN) is associated with podocyte (PC) injury and loss. PC injury is believed to play important role in DN progression. DN reversal following 10 years (10Y) of euglycemia after pancreas transplantation (PTx) is documented (N Engl J Med 1998; 339:69-75). We hypothesized that if PC loss is crucial for DN development, DN reversal would be associated with PC regeneration and improvement in PC structure

METHODS

Paired kidney biopsies prior to PTx (BL) and 10Y after PTx were compared for classical DN lesions, PC number and foot process width (FPW) using electron microscopy morphometry in 10 type 1 diabetic (T1D) patients with age 33 (30-54) years [median (range)], diabetes duration 23 (16-33) years and albumin excretion rate (AER) 134 (0- 951)µg/min at BL. The results were compared with biopsies from 10 age matched living donor biopsies [controls (C)].

RESULTS

Glomerular basement membrane (GBM) width, fractional volume of mesangium/glomerulus [Vv(Mes/glom)] and fractional volume of mesangial matrix/glomerulus [Vv(MM/glom)] and FPW were all increased at BL compared to C (data not shown). There were significant reductions in GBM width (30%; p=0.0002), Vv(Mes/glom) (21%; p=0.001), Vv(MM/glom) (30%; p=0.002), and glomerular volume (27%; p=0.02) at 10Y compared to BL. However, while PC number density did not change from BL to 10Y, there was a significant decrease in PC number/glomerulus (31%; p=0.049). FPW in T1D patients at BL (p=0.0008) or 10Y (p=0.002) was greater than C with no significant change from BL to 10Y. No relationship was found between change in GBM width, Vv(Mes/glom) or Vv(MM/glom) and PC number density, PC number per glomerulus or FPW. Creatinine clearance was reduced by 25% from BL to 5y post PTx in these calcineurin treated patients, and remained stable between 5 and 10Y. AER did not change significantly.

CONCLUSION

Substantial reversal of GBM and mesangial extracellular matrix (ECM) accumulation in T1D occurs following long term PTx despite decrease in PC number, persistence of foot process widening and no change in PC density. This study does not support PC loss to be an important mediator of glomerular extracellular dynamics in DN in T1D. Moreover, despite long-term normoglycemia, PC do not regenerate and PC injury does not regress in T1D patients.

c Copyright 2020 -2021 American Society of Nephrology. Reproduced with permission.
All ASN abstracts from the 2020 Annual Meeting are available at this link and also are archived in .pdf form at ASN-Online.org

Disclaimer: Abstracts often have errors, both typographical and otherwise. This posting is an electronic translation of submitted abstracts which has not been verified against the original submitted abstract nor with the authors for accuracy. As a result, there may be errors, especially with regard to drug doses, but not limited to these. Abstracts undergo only limited review, and data often are changed as a result of the peer review process, so their reliability is less than manuscripts published in peer-reviewed journals. In using these summaries, you are agreeing that you are aware of these limitations.

The materials are provided on an as-is basis without any warranty of any kind, either express or implied. In addition to errors, the information presented may be incomplete or outdated. The information contained is not intended nor recommended as a substitute for professional medical advice. You are advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each device to be used or drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other health care professional, relying on independent experience and knowledge of the patient, to determine drug, disease, and the best treatment for the patient.

To the fullest extent permitted by law, HDCN, ASN and their affiliates and suppliers disclaim all warranties, express or implied, including, but not limited to, any warranty of merchantability, non- infringement or fitness for a particular purpose.

In no event shall HDCN, ASN, or their affiliates or suppliers be liable for any damages whatsoever (including, but not limited to, direct, indirect, incidental, consequential, punitive or exemplary damages, or any damages for loss of profits, use, data, goodwill or other intangibles) arising from or in any way relating to these terms, the materials, or any information, goods or services obtained from or referred to in the materials, whether based on warranty, contract, tort (including, but not limited to, negligence), or any other legal theory, and whether or not any or all of the limited entities is advised of the possibility of such damages.