Evaluation of Late Nephrotoxicity in Long-Term Survivors of Hodgkin’s Disease

Abstract

Chemotherapy (Ctx) and/or radiotherapy (Rtx) are effective in the treatment of Hodgkin’s disease (HD) but potentially involve late toxicities, including nephrotoxic side effects. Therefore a follow-up study has been performed to screen patients for late signs of an impaired tubular or glomerular function and to correlate data of renal function with type of therapy and cumulative doses of cytotoxic agents applied. 81 patients in complete remission for at least 2 years and a median follow-up of 96 (39–304) months, and 53 controls were examined. Clinical routine parameters such as creatinine and electrolytes were determined. A differentiation of proteinuria into the albumin, high molecular weight (HMW) and low molecular weight (LMW) fractions made it possible to assess glomerular and tubular function based on the LMW/HMW ratio. The structural protein fibronectin served as an additional, sensitive marker of glomerular integrity. Routine parameters of kidney function did not show any signs of late nephrotoxicity. However, patients treated for HD had a higher ratio of LMW/HMW in comparison to the group of healthy volunteers (p < 0.01), indicating subclinical tubular renal damage. When the cutoff for tubular damage was defined as LMW/HMW > 1.5, 50% of the patients treated with combined modality, and 42 and 37% of the patients with Ctx or Rtx alone had subclinical tubular alterations, respectively. A tendency towards a higher prevalence of subclinical tubular changes was observed in patients with higher cumulative doses of methotrexate or ifosfamide and in patients with combined Ctx and Rtx with radiation fields involving the renal area. Changes in glomerular function were not observed. It is concluded that treatment of HD is not associated with clinically apparent long-term impairment of renal function but can lead to subclinical alterations. Further clinical implications of these subclinical tubular alterations cannot be assessed at present. A differentiation of proteinuria does not have to be performed routinely but might be useful in the follow-up of selected patients with an increased risk.

Yield of Urinalysis Screening in Pediatric Cancer Survivors

“…Moreover, a particularly strong criticism against urinalysis screening in asymptomatic children was the high rate of false positive test results or identification of only transient abnormalities . While pediatric cancer survivors screened according to the COG LTFU Guidelines have been exposed to renal and bladder toxic therapies,it remains unclear if repeated urinalysis screening is sensitive enough to separate late effects of cancer therapy from the underlying transient abnormalities seen in the nonexposed pediatric population. Prospective research comparing exposed and unexposed children is needed.…”

Renal tumours: long-term outcome

“…This alkylating agent is nephrotoxic, causing both tubular (Fanconi’s syndrome) and glomerular damage [26, 27]. The risk of developing nephrotoxicity is related to the total cumulative dose of Ifosfamide (>60–100 g/m 2 ) [25–27] and to patient-related factors such as the presence of a single kidney [28], renal irradiation [29] and young age [30–32]. Clearly, patients with WT are at particular risk.…”

Renal late effects in patients treated for cancer in childhood: A report from the Children's Oncology Group

“…Ifosfamide can have serious adverse effects on the kidney despite concurrent use of the uroprotectant mesna. The most common manifestation of ifosfamide‐induced nephrotoxicity is proximal tubular dysfunction, and less often, decreased GFR 8–18. During therapy, acute renal tubular dysfunction often resolves prior to the next course; however, permanent and potentially progressive kidney damage may also occur 16.…”