Abstract
Background and Aims
The bidirectional relationship between renal disease and malignancy is well known and requires specialized approaches. For this reason, onconephrology has emerged as a new evolving field in the last few years.
Method
In a dedicated nephrology clinic, we followed 54 metastatic cancer patients (pts) (23 F, 31 M; mean age 68.3 ± 9.8 yrs) during target therapy (TT). They were in treatment for different types of cancer (kidney n=32, colo-rectal n 6=, breast n=5, lung n=5, neuroendocrine n=2 and other n=4). 12 pts were taking anti-VEGF (group 1), 26 pts tyrosine kinase inhib (group 2), 7 pts mTOR inhb (group 3) and 9 pts immune-checkpoint (group 4). Kidney biopsies were not performed because of increased risk or for improvement of RI when changes in TT were performed.
Renal injury (RI) occurred on average after 8.9 months from the start of TT. We compared the effects of the different therapeutic interventions on changes of renal function between T0 (before TT) and T1 (during TT). We also documented changes in oncologic therapeutic prescription due to renal injury and their effects at T2 (follow up). Kidney biopsies were not performed because of increased risk or for improvement of RI when changes in TT were performed.
A two way repeated measures ANOVA (group x time) was used to compare the effects of the four groups on serum creatinine (sCr), creatinine clearance and proteinuria 24 h (PU) at T0 and T1.
Results
Mean basal sCr of pts taking antiVEGF was 0.95 mg/dl, eGFR (MDRD) 81.9 ml/min and PU 196 mg 24h. At T1 (8.37 months on average) sCr was 1.74 mg/dl, eGFR 62 ml/min and PU 1777 mg 24h.
Mean basal sCr of pts taking tyrosine kinase inhib was 1.24 mg/dl, eGFR 55 ml/min and PU 145 mg 24h. At T1 (13 months on average) sCr was 1.59 mg/dl, eGFR 46 ml/min, and PU 916 mg 24h.
Mean basal sCr of pts taking mTOR inhib was 1.28 mg/dl, eGFR 57 ml/min and PU 150 mg 24 h. At T1 (6.3 months on average) sCr was 2.1 mg/dl, eGFR 31.7 ml/min and Pu 345 mg 24 h.
Mean basal sCr of pts taking immune-checkpoint was 1.27 mg/dl, eGFR 59 ml/min and PU 150 mg 24h. At T1 (months on average) sCr was 3.74 mg/dl, eGFR 30 ml/min and PU 257 mg 24h.
A significant increase in sCr was observed when comparing T0 and T1 among the four groups but only a statistical trend (P = 0.088) was found for the group by time interaction thus not allowing us to speculate on potential differences between the different pharmacological interventions.
Lower Creatinine clearance and higher PU, were found at T1 in pts on anti-VEGF compared to those on immune-checkpoint inhibitors.
We generally observed an improvement of renal function after reduction of TT dose or its temporary discontinuation (27.8%), but definitive interruption was required in 31.8% of cases. In 2 diabetics pts on tyrosine kinase inhib we observed persistent nephrotic proteinuria and progressive worsening of renal function and beginning of chronic hemodialysis neverthless discontinuation.
At the end of follow-up 5 pts reached end-stage renal disease (1 pt was taking antiVEGF, 2 pts tyrosine kinase inhib, 2 immune-checkpoint) and 6 pts were dead (4 pts were taking antiVEGF and 2 pts tyrosin kinasi inhib).
Conclusion
Our findings suggest that careful monitoring of renal function is needed to optimize the use of TT, also considering that RI can be multifactorial. Onconephrologists work with the aim of trying to ensure the continuity of anti-tumoral therapy, knowing how far they can go to maintain a balance between kidney function (even sacrificing part of it) and patient survival. In conclusion, nephrologists should be increasingly familiar with the diagnosis, management and treatment of renal diseases and the complexity of this field may benefit from well-defined multidisciplinary management by a dedicated team
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