Radiation nephropathy

Definition

Radiation nephropathy is the kidney parenchymal injury and loss of function caused by radiation exposure to the kidneys. Its typical form is caused by external beam ionizing radiation, by x-rays or gamma-rays. It may also be caused by radioisotope therapies that irradiate kidneys internally. It is not common in current clinical practice but remains a risk of accidental or belligerent radiation exposures. The term nephropathy is preferred instead of nephritis, because radiation nephropathy does not have major inflammatory features.

Historical recognition

Radiation nephropathy was first recognized in 1927. Earlier descriptions of kidney injury in irradiated subjects may have been caused by tumor lysis syndromes rather than true radiation injury to kidneys. The best cohort studies are those of Luxton and colleagues, in which radiation nephropathy is described in men who had undergone external beam x-irradiation for treatment of seminoma. ^, After delivery of 20 Gy or more x-irradiation in fractionated doses, over a period of 4 weeks, approximately 20% of thus-treated subjects developed radiation nephropathy of varying severity. Similar presentations were reported in case reports and smaller series over the next 25 years, in both adults and children. Structural and ultrastructural features were well-described.

Epidemiology

There are two modern congeners of radiation nephropathy. The first occurs in subjects that have undergone hematopoietic stem cell transplantation (HSCT) that is preceded by total body irradiation, as part of the conditioning regimen. ^, This has been called bone marrow transplant nephropathy ( BMT nephropathy ). The second may complicate the use of internal radioisotope therapies.

The 2017 Annual Data Report of the United States Renal Data System reports that of 700,000 prevalent patients on chronic dialysis in the USA, 159 have radiation nephropathy as their indicated cause of end-stage renal disease (ESRD). Eighty-nine patients on chronic dialysis are reported as a complication of HSCT. It is likely that these are underestimates, because the 2728 forms that indicate the diagnosis of ESRD are not reliable.

Clinical features

Radiation nephropathy presents typically at 3 or more months after sufficient irradiation, with azotemia and hypertension. There is nonnephrotic proteinuria. The more severe variants may develop thrombocytopenia and even microangiopathic hemolytic anemia, reminiscent of hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP).

Urinalysis shows proteinuria and microhematuria. The proteinuria is generally below the nephrotic range.

Radiation nephropathy may occur in children and in adults, in men and in women. No racial predisposition is known. But Judele et al. have reported complement regulatory defects in subjects who developed thrombotic microangiopathy after radiation-based HSCT, defects that are the same ones that are associated with HUS. It is not known whether these complement regulatory defects predispose to usual radiation nephropathy.

Previous or concurrent use of chemotherapy, such as cyclophosphamide or cis-platinum, may predispose to radiation nephropathy, much as some chemotherapies predispose to normal tissue radiation injury generally. It is likely, but not proven, that underlying kidney disease predisposes to radiation nephropathy.

Dose considerations

Histology

The light microscopic appearance of radiation nephropathy is characteristic, with decreased glomerular cellularity, increased mesangial matrix, and mesangiolysis ( Fig. 20.1 ).

There is no evidence for an immunopathogenesis of radiation nephropathy, which makes immunofluorescence studies unhelpful.

Electron microscopy often shows glomerular endothelial injury and dramatic expansion of the subendothelial space with a somewhat electron-lucent material ( Fig. 20.2 ).

There is tubulointerstitial scarring, as is expected for any chronic kidney disease.