Glomerular visceral epithelial cells, namely podocytes, are highly specialized cells and give rise to primary processes, secondary processes, and finally foot processes. The foot processes of neighboring podocytes interdigitate, leaving between them filtration slits. These are bridged by an extracellular substance, known as the slit diaphragm, which plays a major role in establishing size-selective barrier to protein loss. Furthermore, podocytes are known to synthesize matrix molecules to the glomerular basement membrane (GBM), including type IV collagen, laminin, entactin, and agrin. Because diabetic nephropathy is clinically characterized by proteinuria and pathologically by glomerular hypertrophy and GBM thickening with foot process effacement, podocytes have been the focus in the field of research on diabetic nephropathy. As a result, many investigations have demonstrated that the diabetic milieu per se, hemodynamic changes, and local growth factors such as transforming growth factor-beta and angiotensin II, which are considered mediators in the pathogenesis of diabetic nephropathy, induce directly and/or indirectly hypertrophy, apoptosis, and structural changes, and increase type IV collagen synthesis in podocytes. This review explores some of the structural and functional changes of podocytes under diabetic conditions and their role in the development and progression of diabetic nephropathy.

BackgroundProtein-energy wasting is common in patients with end-stage kidney disease. However, few studies have examined the relationship between early stages of chronic kidney disease (CKD) and sarcopenia.MethodsWe conducted a cross-sectional study based on data in the Korea National Health and Nutrition Examination Survey, 2008–2011. In total, 11,625 subjects aged 40 years or older who underwent dual-energy X-ray absorptiometry were analyzed. Sarcopenia was defined based on values of appendicular skeletal muscle mass as a percentage of body weight (ASM/Wt) two standard deviations below the gender-specific mean for young adults. Estimated glomerular filtration rates (eGFR) were calculated using the CKD-EPI equation.ResultsMean age, body mass index (BMI), and HOMA-IR were higher and caloric intake, physical activity, and vitamin D level were lower in the sarcopenia groups in both men and women. As the stage of CKD increased, the prevalence of sarcopenia increased, even in the early stages of CKD (normal and CKD1, 2, and 3-5: 2.6%, 5.6%, and 18.1% in men and 5.3%, 7.1%, and 12.6% in women, respectively; p < 0.001). In addition, a correlation analysis showed that GFR and ASM/Wt had significant correlations in both men and women. Logistic regression analyses, after adjusting for age, BMI, caloric intake, log(physical activity), vitamin D level, and log(HOMA-IR), showed that the odds ratio for sarcopenia with respect to CKD 3–5 was 1.93 (95% CI = 1.02–3.68) in men but was not statistically significant in women.ConclusionsThe prevalence of sarcopenia was higher in elderly Korean patients with even mildly reduced kidney function. Stage of CKD was associated with an increased prevalence of sarcopenia in men but not women. Thus, we should evaluate the risk of sarcopenia and work to prevent it, even in patients with early CKD.

Summary Background and objectives Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored. Design, setting, participants, & measurements A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration. Results Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up. Conclusions This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.

We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

Our study revealed that RRF and diabetes were risk factors for peritonitis. These results suggest that preservation of RRF should be viewed as a protective strategy to reduce peritonitis.

Background Long-term peritoneal dialysis (PD) is associated with the development of various structural and functional changes to the peritoneal membrane when bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this study, we looked at patients that were treated with conventional PDFs and then changed to novel biocompatible PDFs with a neutral pH and a low concentration of glucose degradation products (GDPs) to investigate whether this change could result in the arrest or reversal of peritoneal membrane deterioration. Methods In an open label, randomized prospective trial, the clinical effects of conventional PDFs and biocompatible PDFs with neutral pH and very low concentration of GDPs were compared in 104 patients equally divided between both study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests, and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The target variables were the ratio of dialysate-to-plasma (D/P) creatinine, peritoneal ultrafiltration, residual renal function, dialysis adequacy indices, and effluent cancer antigen 125 (CA125). Results D/P creatinine values were not different in the two groups. Peritoneal ultrafiltration was significantly higher in the low-GDP PDF group than in the conventional PDF group at all follow-up times (4 months: 9.1 ± 4.3 vs 6.0 ± 3.0; 8 months: 8.3 ± 3.4 vs 6.0 ± 3.0; 12 months: 8.9 ± 3.3 vs 6.1 ± 3.3 mL/g dextrose/day; p < 0.05). Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were significantly higher in the low-GDP PDF group than in the conventional PDF group. Residual renal function was not statistically significant. Effluent CA125 levels were significantly higher in the low-GDP PDF group at all follow-up visits (4 months: 37.8 ± 20.8 vs 22.0 ± 9.5; 8 months: 41.2 ± 20.3 vs 25.9 ± 11.3; 12 months: 40.4 ± 21.4 vs 28.6 ± 13.0 U/mL; p < 0.05). Among anuric patients, peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8 months, and CA125 levels at all follow-up visits were significantly higher in patients treated with low-GDP PDF than those treated with conventional PDF. However, among anuric patients, D/P creatinine showed no significant differences between the low-GDP PDF group and the conventional PDF group. Conclusion The use of biocompatible PDFs with neutral pH and low GDP concentration can contribute to improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an indicator of peritoneal membrane integrity in PD patients.

Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10(-8) M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RT-PCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immunohistochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P < 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P < 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.

Previous studies have shown that mineralocorticoid receptor (MCR) blocker reduces proteinuria in diabetic nephropathy (DN), but the role of aldosterone in podocyte injury has never been explored in DN. This study was undertaken to elucidate whether a local aldosterone system existed in podocytes and to examine its role in podocyte apoptosis under diabetic conditions. In vitro, immortalized podocytes were exposed to 5.6 mM glucose (NG), NG + 24.4 mM mannitol, and 30 mM glucose (HG) with or without 10(-7) M spironolactone (SPR). In vivo, 32 Sprague-Dawley rats were injected with diluent (C, n = 16) or streptozotocin intraperitoneally [diabetes mellitus (DM), n = 16], and 8 rats from each group were treated with SPR for 3 mo. Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay. Western blot for apoptosis-related molecules, Hoechst 33342 staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to determine apoptosis. CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels. Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli. Apoptosis determined by Hoechst 33342 staining and TUNEL assay were also significantly increased in podocytes under diabetic conditions. These changes in the expression of apoptosis-related proteins and the increase in apoptotic cells were inhibited by SPR treatment. These findings suggest that a local aldosterone system is activated and is involved in podocyte apoptosis under diabetic conditions.