Genetic and molecular markers of proteinuria and glomerulosclerosis

The clinical course of renal diseases depends on the type of renal disorder, genetic factors, environmental influences, and the severity of renal fibrosis. Proteinuria is the abnormal amount of proteins present in the urine. Proteinuria is an independent risk factor for development of renal insufficiency, in which glomerulosclerosis can be seen in biopsies. Experimental models described in this thesis show that different genetic factors are linked to proteinuria and glomerulosclerosis. Furthermore, bone marrow and kidney transplantations between proteinuria-prone and proteinuria-resistant rats, revealed that both renal and bone marrow-derived cells contribute to development of proteinuria or convey resistance to its development. The mechanism of development of segmental glomerulosclerosis is not completely known. We investigated glomerular morphology in hyperfiltration-mediated proteinuria before glomerulosclerosis was present. Segmental glomerulosclerosis started with segmental podocyte damage with loss of podoplanin protein. Focal and segmental glomerulosclerosis is a human renal disease with a wide range of glomerular morphology, a large range of clinical presentations, progression rates, and chances of developing recurrent FGSG after transplantation. A new histological classification was proposed in 2004 in hopes of separating new disease subentities. We found that in most cases FSGS recurred as the same variant, supporting the new classification. The results in this thesis may increase the insights in the development of proteinuria and glomerulosclerosis, hoping to result in earlier recognition of renal disease, better definition of patients and separation of distinct disease entities. This may lead to better and more disease-specific treatment options.UBL - phd migration 201

Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters: A retrospective cohort study

Background: The main limitations of central venous catheters for haemodialysis access are infections and catheter malfunction. Our objective was to assess whether precurved non-tunnelled central venous catheters are comparable to tunnelled central venous catheters in terms of infection and catheter malfunction and to assess whether precurved non-tunnelled catheters are superior to straight catheters. Materials and methods: In this retrospective, observational cohort study, adult patients in whom a central venous catheter for haemodialysis was inserted between 2012 and 2016 were included. The primary endpoint was a combined endpoint consisting of the first occurrence of either an infection or catheter malfunction. The secondary endpoint was a combined endpoint of the removal of the central venous catheter due to either an infection or a catheter malfunction. Using multivariable analysis, cause-specific hazard ratios for endpoints were calculated for tunnelled catheter versus precurved non-tunnelled catheter, tunnelled catheter versus non-tunnelled catheter, and precurved versus straight nontunnelled catheter. Results: A total of 1603 patients were included. No difference in reaching the primary endpoint was seen between tunnelled catheters, compared to precurved non-tunnelled catheters (hazard ratio, 0.91; 95% confidence interval, 0.70– 1.19, p=0.48). Tunnelled catheters were removed less often, compared to precurved non-tunnelled catheters (hazard ratio, 0.65; 9

Macrophages in diabetic nephropathy in patients with type 2 diabetes

Nephrolog

Nephrin Loss Can Be Used to Predict Remission and Long-term Renal Outcome in Patients With Minimal Change Disease

Minimal change disease is a common cause of nephrotic syndrome. In general, patients with minimal change disease respond to corticosteroids and have excellent long-term renal survival. However, some patients have less favorable outcome. These patients are often thought to have progressed to focal segmental glomerulosclerosis. We previously reported that a segmental loss of podocyte markers is present before the development of focal segmental glomerulosclerosis in a rat model. Here, we investigated whether loss of podocyte marker nephrin can serve as a biomarker for predicting poor outcome in patients with minimal change disease. Methods: We obtained 47 kidney biopsy samples from patients diagnosed with minimal change disease and stained sections with periodic acid−Schiff and for nephrin. Nephrin loss was scored by 2 independent researchers who were blinded to clinical outcome. Clinical data were collected retrospectively, and nephrin loss was correlated with clinical follow-up data. Results: Nephrin loss was present in 34% of the biopsy samples. During follow-up, patients with nephrin loss achieved remission less frequently (61%) compared to patients without (96%) (P = 0.002). Moreover, 5-year eGFR was lower in the patients with renal nephrin loss. The risk of eGFR decreasing to < 60 ml/min per 1.73m2 increased with each percentage of glomeruli with nephrin loss (hazard ratio = 1.044, 95% confidence interval = 1.02−1.07). Conclusion: These results indicate that nephrin loss in patients with minimal change disease can help predict both remission and long-term renal outcome

Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study

IntroductionWe aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 55 Dutch, 127 South-Asian Surinamese, 92 African Surinamese, 62 Ghanaian, 74 Turkish and 88 Moroccan origin participants with T2DM from the HEalthy LIfe in an Urban Setting study. Using linear regression analyses, we investigated differences in urinary monocyte chemoattractant protein-1 (MCP-1) and heparanase-1 (HPSE-1) levels across ethnic minorities compared with Dutch. Associations between the urinary markers and albuminuria (albumin:creatinine ratio (ACR)) was investigated per ethnicity.ResultsUrinary MCP-1 levels were higher in the Moroccan participants (0.15 log ng/mmol, 95% CI 0.05 to 0.26) compared with Dutch after multiple adjustments. Urinary HPSE-1 levels were lower in the African Surinamese and Ghanaian participants compared with the Dutch, with a difference of -0.16 log mU/mmol (95% CI -0.29 to -0.02) in African Surinamese and -0.16 log mU/mmol (95% CI -0.31 to -0.00) in Ghanaian after multiple adjustments. In all ethnic groups except the Dutch and Ghanaian participants, MCP-1 was associated with ACR. This association remained strongest after multiple adjustment in South-Asian and African Surinamese participants, with an increase in log ACR of 1.03% (95% CI 0.58 to 1.47) and 1.23% (95% CI 0.52 to 1.94) if log MCP-1 increased 1%. Only in the Dutch participants, an association between HPSE-1 and ACR was found, with increase in log ACR of 0.40% (95% CI 0.04 to 0.76) if log HPSE-1 increased 1%.ConclusionsWe found ethnic differences in urinary MCP-1 and HPSE-1 levels, in a multi-ethnic cohort of participants with T2DM. In addition, we found ethnic differences in the association of MCP-1 and HPSE-1 levels with albuminuria. These findings suggest differences in renal inflammation across ethnic groups

Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters:A retrospective cohort study

Clinical epidemiolog