ASH 2024 | Factors affecting renal response in myeloma with acute renal failure due to cast nephropathy

I’m going to present the results of the cooperation between 16 academic centers in the US and Europe. Our aim was to analyze the parameters and factors which are associated with improvement of renal function in patients with cast nephropathy. Cast nephropathy is defined by disease, and it’s actually a medical emergency, a disease which is due to the binding of three light chains which is called Bence-Jones protein in the renal tubuli, and this is usually a small protein and small complexes can be reabsorbed by the tubular interstitial cells but if there is an overload of protein, an overload in the aim if there’s excess of light chain excreted via the glomeruli, the kidney is unable to, of course, to reabsorb it and then this leads to the disruption of the tubular endothelial cells. It comes to what we call cast formation. There’s obstruction of the tubuli and it can result in anuria and certainly renal impairment. But it is frequently an acute emergency. It can also develop more slowly. 

The question was, what are these factors which associate with improvement in renal function, in myeloma response and so on, in a large number of patients? And actually, for these analyses we are going to present at ASH, we included 343 patients. And in essence, what we found is, first of all, which was surprising to us, is that we found a high incidence of hypercalcemia, namely in about 30% of the patients. These hypercalcemia patients had a better outcome of renal function because you can easily correct hypercalcemia in myeloma, much easier than you can induce a myeloma response. So they responded better in terms of renal function, but hypercalcemia is also a hallmark of poor prognostic features, of poor prognosis, and so those patients had shorter survival. They had better renal impairment, improvement in renal function, but shorter survival. In a sense, of course, there is a correlation between myeloma response and renal response, but the correlation is not very strong because other factors may also impact on renal impairment. This may be due to infection, which complicates this cast formation. And so if you control for those, you can improve at least the renal function in a number of patients. 

So in a sense, patients which have a recovery of their renal function at least to stage 4, which is eGFR of greater than 15 ml per minute, they have better outcomes, better survival. And what we were anticipating was that there is a difference between survival and different renal recovery groups. There is a slight difference, but the difference is not, let’s say, very significant. The only difference is if the patients don’t recover their renal function to an eGFR of 15 or higher, those patients have severe problems, have shorter survival and a dismal outcome. We also had patients on dialysis at the start of inclusion at the moment when they were diagnosed. And about 50% of patients got rid of dialysis. And of course, those were the winners, had better outcome in all measures, renal function, survival. 

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