Low-density lipoprotein apheresis for recurrent focal segmental glomerulosclerosis post renal transplant in pediatric patients.

Low-density lipoprotein (LDL) apheresis has been shown to improve remission in patients with steroid-resistant nephrotic syndrome (SRNS). Here, we report a case study of two patients who failed apheresis treatment for SRNS and required transplant with subsequent recurrence of nephrotic syndrome and response to apheresis treatment. Two patients were treated with 12 sessions of LDL apheresis for SRNS without improvement and subsequently required renal transplantation. The first patient received an ABO-incompatible kidney transplant requiring plasma exchange (PE) with subsequent recurrence of focal segmental glomerulosclerosis. The second patient also received a renal transplant after treatment failure and subsequently developed recurrence of nephrotic syndrome in the transplanted kidney. Both patients underwent repeat therapy with lipoprotein apheresis. The first patient underwent lipoprotein apheresis after completing PE with significant improvement in serum creatinine and urine protein creatinine ratio. Three years later, he continued to do well and remains in remission. The second patient also responded well to repeat therapy with lipoprotein apheresis and had significant improvement with a urine protein creatinine ratio of 0.8 and a serum creatinine of 0.9 mg/dL 6 months after transplant. Lipoprotein apheresis was able to result in remission of nephrotic syndrome in these patients with posttransplant recurrence of disease. This is the first report of patients not responding to treatment pretransplant but responding posttransplant. Lipoprotein apheresis should be considered in patients with recurrence of nephrotic syndrome after renal transplantation even with a history of treatment failure prior to transplantation.

Liposorber® LA-15 system for LDL apheresis in resistant nephrotic syndrome patients.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a major cause of stage 5 chronic kidney disease (CKD 5) in children. LDL apheresis (LDL-A) is now FDA approved for the treatment of pediatric focal segmental glomerulosclerosis (FSGS). Effective management of hyperlipidemia with LDL-A in SRNS patients may prevent progression of kidney disease and lead to remission. We report a case series of patients who received LDL-A for treatment of SRNS METHODS: We describe five children with SRNS who were treated with 12 sessions of LDL-A. Partial remission (PR) is defined as urine protein to creatinine ratio (UPC) of 0.2-2 (g/g) or decrease in UPC ≥ 50%, and complete remission (CR) is defined as UPC < 0.2 (g/g). RESULTS: One patient achieved CR and three achieved PR. One patient did not respond to therapy. The earliest that a patient achieved PR was at treatment #10 and some did not respond until after LDL-A was completed. Those who responded stayed in either CR or PR for extended periods of time. LDL-A was successful at significantly reducing LDL (p < 0.001), total cholesterol (p < 0.001), and triglyceride (p < 0.001). CONCLUSIONS: LDL-A was able to significantly decrease the lipid levels in these patients and induce CR and PR in the majority. The current study confirms previous studies showing those with a higher glomerular sclerosis burden were less likely to respond. LDL-A should be considered in patients with treatment-resistant SRNS and should be considered before there is a high burden of glomerular sclerosis to provide the best chance of success.

Immunoglobulin A Nephropathy and Immunoglobulin A Vasculitis.

Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are common glomerulopathies in the pediatric population that deserve special attention. In some cases the primary care provider can follow the patient but others need more intensive management. Delaying this treatment can lead to worse morbidity. This article provides information on the pathogenesis, outcomes, and follow-up strategies that will aid in the diagnosis and referral of patients at risk for kidney disease.

Safety and utility of surveillance biopsies in pediatric kidney transplant patients.

There is currently no way to diagnose a rejection before a change in serum creatinine. This had led some to start doing SB, but little data exist on the utility and safety of SB in pediatric patients. There is also little known on practice patterns of pediatric nephrologists. A retrospective review of pediatric kidney transplant SB between January 2013 and January 2017 at a single center was performed. A survey went to the PedNeph email list. There were 47 SB; 15 at 6 months, 12 at 1 year, 13 at 2 years, and 7 at 3 years. There were 3 minor (1 gross hematuria and 2 hematomas) and no major complications. On 6-month SB, 1 had SC 1A ACR (6.7%) with no BR ACR. On the 12-month SB, there were 5 with SCBR ACR (41.7%) and 1 with SC AMR (8.3%). On the 2-year SB, there were 4 that had SCBR ACR (30.8%), and 1 with SC AMR (7.7%). On the 3-year SB, 1 had chronic transplant glomerulitis (14.3%). The survey showed that 34.3% of pediatric nephrologists perform SB. SB can be performed safely. By early identification of histological lesions, SB gives us an opportunity for individualized immunosuppressive regimens that may prevent chronic allograft dysfunction and improve long-term graft outcome.

Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21, -200c, and -423.

Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD patients without clinical diagnosis of AKI compared with healthy volunteers. In a longitudinal cohort of patients with malignant mesothelioma receiving intraoperative cisplatin (Cp) therapy (n = 108) the 4 biomarkers increased significantly (P < .0014) over time after Cp administration, but could not be used to distinguish patients with or without AKI. Evidence for human proximal tubular epithelial cells (HPTECs) being the source of miRNAs in urine was obtained first, by in situ hybridization based confirmation of increase in miR-21 expression in the kidney sections of AKI patients and second, by increased levels of miR-21, -200c, and -423 in the medium of cultured HPTECs treated with Cp and 4-aminophenol (APAP degradation product). Target prediction analysis revealed 1102 mRNA targets of miR-21, -200c, and -423 that are associated with pathways perturbed in diverse pathological kidney conditions. In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423.

Discovery, biological evaluation, and structure-activity relationship of amidine based sphingosine kinase inhibitors.

Sphingosine 1-phosphate (S1P), a potent phospholipid growth and trophic factor, is synthesized in vivo by two sphingosine kinases. Thus these kinases have been proposed as important drug targets for treatment of hyperproliferative diseases and inflammation. We report here a new class of amidine-based sphingosine analogues that are competitive inhibitors of sphingosine kinases exhibiting varying degrees of enzyme selectivity. These inhibitors display K(I) values in the submicromolar range for both sphingosine kinases and, in cultured vascular smooth muscle cells, decrease S1P levels and initiate growth arrest.