piperidines and Nephrotic-Syndrome

A 67-year-old woman with transverse myelitis and seizure disorder secondary to suspected central nervous system (CNS) systemic lupus erythematosus (SLE) and seropositive rheumatoid arthritis had two episodes of severe nephrotic syndrome 15 years apart. She underwent a renal biopsy in both episodes, showing tip lesion variant focal segmental glomerulosclerosis (FSGS). The patient responded both times to prednisone treatment, achieving a complete remission within 2 months in the first episode and remission 4 months in the second episode. A year after her second episode, the patient had a third episode of severe nephrotic syndrome. She achieved an equally rapid complete remission in 3 months without steroid treatment, as she was concomitantly treated with the Janus Kinase (JAK) inhibitor tofacitinib for a flare of rheumatoid arthritis. This case report suggests that JAK inhibitors may have therapeutic use in FSGS, which is supported by experimental data in the medical literature.

Topics: Aged; Arthritis, Rheumatoid; Female; Glomerulosclerosis, Focal Segmental; Humans; Janus Kinase Inhibitors; Janus Kinases; Male; Nephrotic Syndrome; Piperidines; Pyrimidines

Masitinib mesylate is a tyrosine-kinase inhibitor approved for the treatment of nonresectable or recurrent, Grade 2 or 3 mast cell tumors in dogs. This report describes nephrotic syndrome and acute kidney injury attributed to masitinib and illustrates the need for regular monitoring of serum creatinine concentration, urinalysis, and urine protein:creatinine ratio during its use.

Topics: Animals; Antineoplastic Agents; Azotemia; Benzamides; Dog Diseases; Dogs; Female; Mastocytoma; Nephrotic Syndrome; Piperidines; Protein-Tyrosine Kinases; Pyridines; Thiazoles

CC chemokines mediate leukocyte infiltration into inflamed tissue. We have recently shown that blockade of the CC chemokine receptor CCR1 reduces interstitial inflammation and fibrosis in murine obstructive nephropathy. However, it is not known whether CCR 1 blockade is protective in progressive renal injury associated with severe proteinuria. We therefore studied the effect of the small-molecule CCR1 antagonist BX471 in a murine model of adriamycin-induced focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome and progressive interstitial inflammation and fibrosis.. Adriamycin nephropathy with persistent proteinuria was induced in male BALB/c mice by two intravenous injections of adriamycin (13 mg/kg) at day 0 and 14. BX471 treatment was started at day 14 when proteinuria and interstitial inflammation had developed. At 6 weeks, renal histology was studied by morphometry and immunohistochemistry.. At week 6, adriamycin-treated mice showed FSGS, associated with tubulointerstitial injury consisting of tubular dilation and atrophy, interstitial leukocyte infiltration, and fibrosis. The mRNA expression of CCR1 and CC chemokines, including the CCR1 ligands CCL3 (MIP-1alpha) and CCL5 (RANTES), was up-regulated in diseased kidneys, with a prominent interstitial expression of CCL5. Compared to vehicle-treated controls BX471 significantly reduced the amount of macrophages and T lymphocytes in interstitial lesions by 51% and 22%, respectively. Markers of renal fibrosis such as interstitial fibroblasts (48%) and interstitial volume (23%) were significantly reduced by BX471 treatment. In contrast, the extent of proteinuria and glomerular sclerosis was not affected by BX471 treatment.. Blockade of CCR1 substantially reduced interstitial leukocyte accumulation and the subsequent renal fibrosis in a murine model of nephrotic syndrome and FSGS. These findings support a role for CCR1 in interstitial leukocyte recruitment and suggest that CCR1 blockade might be a new therapeutic strategy in progressive nephropathies such as FSGS.

Topics: Animals; Antibiotics, Antineoplastic; Chemokines; Doxorubicin; Fibrosis; Glomerulosclerosis, Focal Segmental; Kidney; Leukocytes; Male; Mice; Mice, Inbred BALB C; Nephritis, Interstitial; Nephrotic Syndrome; Phenylurea Compounds; Piperidines; Proteinuria; Receptors, CCR1; Receptors, Chemokine

Topics: Adult; Amides; Clopamide; Diuretics; Female; Heart Arrest; Humans; Male; Middle Aged; Nephrotic Syndrome; Piperidines