Advantage of the Subcutaneous Immunoglobulin Replacement Therapy in Primary Immunodeficient Patients With or Without Secondary Protein Loss

In recent years subcutaneous immunoglobulin is widely used for primary immunodeficient patients. Subcutaneous administration provides a more stable and higher serum immunoglobulin levels due to continuous and steady transition from lymphatics to the systemic circulation. We aimed to evaluate the changes in serum immunoglobulin levels under subcutaneous immunoglobulin therapy in patients with primary immunodeficiency with or without secondary protein loss. Nine patients with primary immunodeficiency who switched to subcutaneous immunoglobulin were enrolled. Age, gender, diagnosis, reasons of transition to subcutaneous route, reasons of secondary protein loss were recorded. A questionnaire consisting of frequencies and types of infections, side effects observed with intravenous and subcutaneous routes; date and reason of transition to subcutaneous route were asked to all participants. Serum immunoglobulin levels at the 3rd and the 6th months before and after subcutaneous route were recorded. Of the 9 patients (M/F=4/5) the median age was 12 years (6.1-28.7) and 5 of them had protein loss. In total, 444 injections were applied, and all patients experienced local reactions. Infections were more frequent under intravenous than subcutaneous route (p=0.004). We observed an increase in immunoglobulin levels under subcutaneous route (p=0.069 at 3rd; p=0.13 at 6th month). This increase was evident at the 3rd month of transition to subcutaneous route in patients with protein loss (p=0.080). There was an increase in serum immunoglobulin levels under subcutaneous route. However, increase was not statistically significant since the study group was small. This increment was prominent in patients with protein loss. Subcutaneous administration may be a good alternative for primary immunodeficient patients with protein loss who have persistent low serum immunoglobulin levels despite increments in the intravenous immunoglobulin doses

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study

Background To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. Methods Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. Results IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). Conclusion RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels

Disruption of PTPRO Causes Childhood-Onset Nephrotic Syndrome

Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker—D12S1303—to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs∗3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome