PubMed · 3952515
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P S Schein, F Cavalli. 1986. Prednimustine: the rationale for clinical development.. https://pubmed.ncbi.nlm.nih.gov/3952515/
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Although nondiabetic nephropathies are common among type 2 diabetic patients, very few cases of minimal change nephrotic syndrome have been reported in diabetic patients. We describe a type 2 diabetic patient that rapidly developed a nephrotic syndrome accompanied by a mild worsening of renal function. Proteinuria was negative one year before and no signs of diabetic retinopathy were found. Renal biopsy established the diagnosis of minimal change disease. Steroid treatment induced a complete remission of nephrotic syndrome and recovery of normal renal function. However, massive proteinuria relapsed two years later. A second cycle of steroids was followed by a disappearance of proteinuria, but a third bout of nephrotic syndrome was observed 6 months later. An 8-weeks cycle of steroids plus chlorambucil induced a complete and persistent remission. Throughout a five-year follow up, no relapse of the nephrotic syndrome was observed and microalbuminuria is negative.
To enable scFvs as multi-drug carriers, we designed and synthesized dendritic linker molecules bearing up to nine chlorambucil residues at the branch ends. A maleimide group was used at the focal point of the dendron for easy linkage to the scFv. Originally designed molecules showed poor water solubility. To address this problem, a lysine residue with an unprotected carboxylic acid group was inserted into the dendron branches. The new molecules showed excellent water solubility and are now suitable for conjugation. Such dendritic molecules will allow studies to understand the relationship between the drug/antibody ratio and the potency of the immunoconjugates. The dendritic approach could also be applied to drugs other than chlorambucil and carriers other than scFvs to greatly increase the drug/carrier ratio.