Urinary exosomal miRNA-663a shows variable expression in diabetic kidney disease patients with or without proteinuria.

Heterogeneity in the Diabetic Kidney Disease (DKD) diagnosis makes its rational therapeutics challenging. Although albuminuria characterizes DKD, reports also indicate its prevalence among non-proteinuric. Recent understanding of disease progression has thus inclined the focus on proximal tubular cell damage besides the glomeruli. A non-invasive approach exploiting exosomal miRNA derived from human kidney proximal tubular cell line was, hence, targeted. Upon miRNA profiling, three miRNAs, namely, hsa-miR-155-5p, hsa-miR-28-3p, and hsa-miR-425-5p were found to be significantly upregulated, while hsa-miR-663a was downregulated under diabetic conditions. Among these, hsa-miR-663a downregulation was more pronounced in non-proteinuric than proteinuric DKD subjects and was thus selected for the bioinformatics study. Ingenuity Pathway Analysis (IPA) narrowed on to IL-8 signaling and inflammatory response as the most enriched 'canonical pathway' and 'disease pathway' respectively, during DKD. Further, the putative gene network generated from these enriched pathways revealed experimentally induced diabetes, renal tubular injury, and decreased levels of albumin as part of mapping under 'disease and function'. Genes target predictions and annotations by IPA reiterated miR-663a's role in the pathogenesis of DKD following tubular injury. Overall, the observations might offer an indirect reflection of the underlying mechanism between patients who develop proteinuria and non-proteinuria.

Posterior Corneal Curvature Changes After Pre-Descemet's Endothelial Keratoplasty: A Prospective Analysis.

PURPOSE: To assess the changes in the posterior corneal curvature after pre-Descemet's endothelial keratoplasty (PDEK) and correlate with the visual outcomes. METHODS: Eyes with pseudophakic bullous keratopathy, aphakic bullous keratopathy, and Fuchs dystrophy undergoing PDEK were included. The main outcome measures were the topography (OrbscanIIz, Bausch and Lomb) indices-total corneal power (TCP) in diopters (D), radius of the posterior curvature (mm), and best-fit sphere of the posterior corneal surface (BFS in D) at preoperative and postoperative 1 month, 3 months, and 6 months. RESULTS: Overall, 43 eyes of 43 patients with a mean age of 68 ± 9.6 years were studied. The mean preoperative TCP 43.1 D ± 2.3 reduced to 42.4 D ± 2.6 at 3 months (P < 0.010). There was a statistically significant decrease in the mean posterior corneal curvature at 1 month and 3 months postoperatively (P = 0.002). There was no significant change in the TCP and posterior corneal curvature at 6 months (P > 0.05). The mean BFS showed an increase at 1 month (53.45 ± 5.2 D) and 3 months (52.95 ± 5.1 D) and decrease at 6 months (51.90 ± 5.3 D). The overall change in BFS (P > 0.05) was not significant. There was significant improvement in visual acuity (P < 0.05). The best-corrected visual acuity was ≥20/40 in 79.07% and ≥20/60 in 100% at 6 months. There was no statistically significant correlation between the change in the best-corrected visual acuity and TCP, posterior corneal curvature, or BFS. CONCLUSIONS: Although there was immediate postoperative change in the posterior curvature, no significant change was induced by PDEK.

Urinary exosomes: Potential biomarkers for diabetic nephropathy.

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney associated diseases with non-albuminuria further complicates a timely diagnosis and thus demands an early biomarker. Urinary exosomes, the nanovesicular entities are released by every epithelial cells of the nephron. Their protein or molecular cargo varies in the diseased state which may provide the pathophysiology of the kidney associated diseases. This drives them to be exploited as non-invasive biomarker. This review thus integrates the recent findings on the significance of the urinary exosomes as diagnostic biomarker in kidney-associated diseases, primarily in diabetic nephropathy.

Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.

BACKGROUND & OBJECTIVES: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to ß-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India. METHODS: A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2. RESULTS: The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups. INTERPRETATION & CONCLUSIONS: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.

SUMO4 163 G>A variation is associated with kidney disease in Indian subjects with type 2 diabetes.

Genetic susceptibility probably plays a role in the development and/or progression of diabetic kidney disease. Small ubiquitin-related modifier 4 (SUMO4) mRNA is expressed in human kidney. Substitution of methionine with valine at codon 55 (M55V) of SUMO4 gene induces higher nuclear factor-kB activity, which is known to mediate the development of kidney disease in individuals with diabetes. We investigated the association between the SUMO4 M55V (rs237025, c.163 G>A) and kidney disease in north Indian subjects with diabetes. A case-control analysis was performed using genomic DNA samples from 216 diabetic patients without nephropathy (DM) and 201 diabetic with nephropathy (DN). The SUMO4 c.163 G>A polymorphism was genotyped using polymerase chain reaction amplification followed by restriction digestion. The duration of diabetes was significantly greater in DN. The genotypic and allelic frequencies were different in DM and DN groups: GG genotype was significantly more frequent in DN as compared to DM (p = 0.018, OR 1.72, 95% CI 1.1-2.7). Similarly the G allele was more frequent in DN compared to DM (p = 0.017, OR 1.4, 95% CI 1.1-1.8). This study suggests that SUMO4 c.163 G>A polymorphism is associated with the susceptibility to diabetic nephropathy in north Indian subjects with type 2 diabetes.