Long-Term Renal Effect of Cisplatin in Man

Abstract

Although the acute nephrotoxicity of cisplatin has been well documented, long-term follow-up studies are scanty. We have evaluated the renal function in 35 patients who have had completed therapy with cisplatin at least 3 months before the study. All patients had normal serum creatinine levels before chemotherapy. Evaluation of renal function included: serum creatinine, glomerular filtration rate (inulin clearance), effective renal plasma flow (p-aminohippurate clearance), urinary Β₂-microglobulin and N-acetyl-Β-D-glucosaminidase excretion, and renal tomography. The median cumulated dose of cisplatin was 603 ± 37 mg/m². The mean serum creatinine level was 78 ± 21 and 88 ± 3 µmol/l before and after chemotherapy, respectively (p < 0.05). Mean glomerular filtration rate (92 ± 4 ml/min) and effective renal plasma flow (362 ± 21 ml/min) were significantly lower than in controls (110 ± 3 and 436 ± 24 ml/min). The mean enzymuria and the renal size remained within the normal range. In 12 patients who were reevaluated 12 and 24 months later, glomerular filtration rate and effective renal plasma flow remained stable. These results suggest that at usual dosages cisplatin is associated with a nonprogressive loss of renal function which is of a moderate degree.

Long–Term Renal Outcomes after Cisplatin Treatment

“…Our study, which included a greater diversity of tumor types, supports this initial decline in eGFR. In previous studies in which GFR and renal plasma flow were measured using exogenous filtration markers and 24-hour creatinine clearance, the observed acute and chronic declines in GFR were of larger magnitude, ranging from 12% to 23% (12,13,15,(20)(21)(22). In our study, a lower median decline in eGFR of 10 ml/min per m 2 was observed.…”

“…Whether patient age at the time of onset of cisplatin treatment correlates with the incidence of AKI and long-term renal function is not well established. Some studies report a negative correlation between age and renal function (12,24,25), and others show no relationship (26). A possible explanation for this finding is that older patients had more subclinical renal injury that was not detected by SCr values compared with younger ones or that they may have other comorbidities that made them more susceptible to AKI from cisplatin.…”

“…Prior studies have found inconsistent relationships between CD of cisplatin and long-term declines in GFR (1,12,19,(22)(23)(24). Dose intensity and frequency have been previously shown to correlate with cisplatin nephrotoxicity (24).…”

“…Although its acute nephrotoxicity has been well recognized for decades, information on cisplatin's long-term effects on renal function in adults is limited by lack of long-term renal follow-up and small sample sizes in the available studies (12)(13)(14)(15). We took advantage of the large adult population that is treated with cisplatin across multiple tumor types at our institution and performed a study on adults to determine the incidence of AKI and the initial and long-term changes in eGFR after cisplatin.…”

Risk factors for chronic kidney disease after chemotherapy for testicular cancer

“…In contrast, limited data are available on long-term nephrotoxicity in testicular cancer survivors. The previous studies showed a 20-30% reduction in the GFR; however, most of these studies suffered from small sample sizes and relatively short-term follow-up periods; [7][8][9][10][11][12] this might be partly because GFR measurement is cumbersome. In addition, differences in the methods for GFR evaluation used in the studies make it difficult to interpret each result.…”