Cause Of End-stage Renal Failure Research Articles

Serum Chemerin Level: Does It Have a Role in Progression of Diabetic Nephropathy

Background: Diabetic nephropathy has become the leading cause of end-stage renal failure in Europe, the United States and Japan (25-44%). Chemerin is a chemoattractant expressed in white adipose, liver and lung tissues. Chemerin is shown to be associated with inflammation which is involved in the pathogenesis of diabetic nephropathy. The aim of the present work is to estimate serum chemerin level and to correlate its level in the patients with the stage of the diabetic nephropathy disease. Patients and Methods: The present study included 60 subjects who were divided into 4 groups Group I: included 15 diabetic patients with norm albuminuria Group II: included 15 diabetic patients with microalbuminuria Group III: included 15 diabetic patients with macroalbuminuria Group IV: included 15 normal subjects as a control group. All patients and controls were subjected to estimation of body mass index. Blood urea, serum creatinine and estimated GFR, Urinary albumin to urinary creatinine ratio, complete lipid profile (LDL, HDL, TG) and Serum chemerin level by ELIZA. Results: Serum chemerin level was higher in diabetic than non-diabetic persons and was higher in patients with macroalbuminuria than those with normo and microalbuminuria and its level is correlated with markers of impaired renal function. Conclusion: chemerin could have a role in progression of diabetic nephropathy or its level could be elevated due to impaired renal excretion which should be further investigated.

Role of IgA receptors in the pathogenesis of IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) or Berger's disease is the most common form of primary glomerulonephritis in the world and one of the first causes of end-stage renal failure. IgAN is characterized by the accumulation of immune complexes containing polymeric IgA1 in mesangial areas. The pathogenesis of this disease involves the deposition of polymeric and hypogalactosylated IgA1 (Gd-IgA1) in the mesangium. Quantitative and structural changes of Gd-IgA1 play a key role in the development of the disease due to functional abnormalities of two IgA receptors: the FcαRI (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal Gd-IgA1 induces release of soluble CD89, which participates in the formation of circulating IgA1 complexes. These complexes are trapped by CD71 that is overexpressed on mesangial cells in IgAN patients together with the crosslinking enzyme transglutaminase 2 allowing pathogenic IgA complex formation in situ and mesangial cell activation. A humanized mouse model expressing IgA1 and CD89 develops IgAN in a similar manner as patients. In this model, a food antigen, the gliadin, was shown to be crucial for circulating IgA1 complex formation and deposition, which could be prevented by a gluten-free diet. Identification of these new partners opens new therapeutic prospects for IgAN treatment.

Causes of end stage renal failure among haemodialysis patients in Khartoum State/Sudan

BackgroundEnd stage renal failure (ESRF) has become a major health problem in Sub Saharan Africa (SSA). There were limited data about causes of ESRF in the Sudan.MethodsThis is a cross sectional hospital based descriptive study. The subjects of the study are ESRF adults’ patients on regular haemodialysis treatment in 15 haemdoialysis centres in Khartoum State—Sudan. Clinical and epidemiological data were obtained from 1583 patients. The medical files of each patient were reviewed to identify the cause of ESRF. Concerning the causes of ESRF, diabetes was diagnosed based on the past medical history and result of the glucose tolerance test, hypertension was diagnosed based on past history of hypertension based on blood pressure of more than 140/90 mmHg, glomerulonephritis was diagnosed based on results of previous kidney biopsies and on clinical grounds, polycystic kidney disease and obstructive uropathy were diagnosed based on abdominal ultrasound and other imaging modalities, sickle cell anaemia was diagnosed based on the result of haemoglobin electrophoresis, systemic lupus erythematosus was diagnosed based on the clinical criteria in addition to lab results of auto antibodies, and analgesic nephropathy was diagnosed based on past medical history of chronic analgesic drugs usage with no other identifiable risk factors. We included all ESRF patients on regular haemodialysis treatment. We excluded ESRF patients less than 18 years old.ResultsThe results showed that the mean age of ESRF Patients was 49 ± 15.8 (years) and 63.4 % were male and 76.3 % were unemployed. The mean duration of haemodialysis is 4.38 ± 4.24 (years). The most common cause of ESRF in our patients was hypertension (34.6 %) followed by chronic glomerulonephritis (17.6 %), diabetes mellitus (12.8 %), obstructive uropathy (9.6 %), autosomal dominant poly cystic kidney disease (ADPKD) (4.7 %), chronic pyelonephritis (4.6 %), analgesic nephropathy (3.5 %). However in (10.7 %) no cause was found. In patient aged less than 40 years old the leading cause of ESRF was glomerulonephritis (29.3 %) followed by hypertension (25 %). In patient aged between 40 to 60 years old the leading cause of ESRF was hypertension (38.5 %) followed by diabetes mellitus (14 %). In patient aged older than 60 years the leading cause of ESRF was hypertension (38.4 %) followed by diabetes mellitus (23.3 %).ConclusionsESRF in Sudan affects the economically productive age group; unemployment rate among ESRF patients is high. The study showed that hypertension is a leading cause of ESRF in Sudan followed by chronic glomerulonephritis. Hypertension and diabetes mellitus are the leading causes of ESRF among patients over 40 years old.

Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease.

Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10(5)) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p < 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 µl/min/g, p < 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 µl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p < 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.

Proteomic analysis of the kidney filtration barrier—Problems and perspectives

Diseases of the glomerular filter of the kidney are a leading cause of end-stage renal failure. The kidney filter is localized within the renal glomeruli, small microvascular units that are responsible for ultrafiltration of about 180 liters of primary urine every day. The renal filter consists of three layers, fenestrated endothelial cells, glomerular basement membrane, and the podocytes, terminally differentiated, arborized epithelial cells. This review demonstrates the use of proteomics to generate insights into the regulation of the renal filtration barrier at a molecular level. The advantages and disadvantages of different glomerular purification methods are examined, and the technical limitations that have been significantly improved by in silico or biochemical approaches are presented. We also comment on phosphoproteomic studies that have generated considerable molecular-level understanding of the physiological regulation of the kidney filter. Lastly, we conclude with an analysis of urinary exosomes as a potential filter-derived resource for the noninvasive discovery of glomerular disease mechanisms.

Renal Biopsy Diagnosis of IGA Nephropathy in Chin Refugees Living in the United States

IgA nephropathy (IgAN) is a common diagnosis in patients undergoing renal biopsy for hematuria and proteinuria, but histopathology may vary widely among affected patients. Worldwide, IgAN is the most common form of primary glomerulonephritis and is a leading cause of end-stage renal failure in patients presenting for renal replacement therapy. In the United States, prevalence rates of IgA nephropathy are only 2 to 10 percent while in Asia prevalence rates range from 20 to 40%. In Chin refugees relocated from Myanmar (formerly Burma) to a geographic area near our laboratory in the Midwestern United States (U.S.), IgAN was the most frequently encountered glomerulopathy detected in needle biopsy specimens. We report our biopsy experience with this small but unique cohort, many of whom have had little to no previous access to medical care.

Anks3 alters the sub-cellular localization of the Nek7 kinase

Nephronophthisis (NPH) is an autosomal recessive cystic kidney disease, and a frequent cause of end-stage renal failure in children. To date, 17 NPH-associated gene products (NPHPs) have been identified. Most NPHPs participate in large multi-protein complexes that localize to the cilium and/or basal body; however, the precise composition of these complexes and their biological function remain largely unknown. We recently observed that the ankyrin repeat protein Anks3 interacts with the NPH family member Anks6. Both Anks3 and Anks6 form complexes with multiple other NPHPs, suggesting that both proteins function in similar or overlapping signaling pathways. Here, we show that Anks3, but not Anks6 interacted with the NIMA-related kinase Nek7, and was heavily modified in the presence of Nek7, resulting in an approximately 20 kD increase in molecular weight. Although mass spectrometry revealed increased serine and threonine phosphorylation of Anks3 primarily within the N-terminal ankyrin repeats also required for Nek7 interaction, the molecular weight increase occurred even in the presence of a kinase-dead Nek7 mutant, indicating that this modification was not caused by Nek7-dependent Anks3 phosphorylation. Furthermore, the Anks3 modification was specific for Nek7, and did not occur in the presence of Nek8. Importantly, Anks3 retained Nek7 in the cytoplasm, suggesting that, Nek7 triggers the modification of Anks3, which in turn prevents the nuclear localization of Nek7.

Aetiology of Paediatric End-stage Renal Failure in Jordan: A Multicentre Study.

The purpose of this study was to find out the aetiology of end-stage renal failure (ESRF) in children in Jordan. This was a multicentre retrospective study at five participating hospitals. Data collection included medical record review for age, gender, aetiology of ESRF, modality of renal replacement therapy (RRT) and outcome. End-stage renal failure was defined as estimated glomerular filtration rate < 15 mL/min/1.73m2. There were 275 children with ESRF: 131males and 144 females. The most common causes of ESRF in children were congenital anomalies of the kidney and urinary tract (CAKUT), 45.8%, heredofamilial disorders, 23.2% and glomerulopathies, 26.2%. Neurogenic bladder, reflux nephropathy and posterior urethral valve accounted for 16.8%, 12.7% and 4.0%, respectively. Amongst the heredofamilial disorders, primary oxalosis and cystic disease accounted for 8.0% and 7.2% of the aetiologies of ESRF, respectively. Focal segmental glomerulosclerosis was the most common histological type amongst the glomerulopathies (10.2%), followed by mesangiocapillary glomerulonephritis (4.7%) and chronic glomerulonephritis (3.0%). The aetiology was unknown in 4% of the cases. The modality of dialysis included isolated peritoneal dialysis (PD) in 30.9%, isolated haemodialysis (HD) in 49.1%, alternating peritoneal and haemodialysis in 9.1%, transplanted in 8.7% and conservative treatment in 1.8%. Death occurred in 57.3% of PD patients versus 34.4% in HD patients. This is the first report on the aetiology of ESRF in children in Jordan. The most common aetiologies of ESRF were CAKUT 45.8%, heredofamilial disorders 23.2% and glomerulopathies 22.9%.

L-Carnosine attenuates the development of diabetic nephropathy in the BTBR ob/ob mouse model

Diabetic nephropathy (DN) is the most frequent cause for end-stage renal failure (ESRF) worldwide. It's pathophysiology is multi-factorial and current therapeutic options only retard the progression of DN. We hypothesize that L-Carnosine, a natural anti-oxidant and pH-stabilizing dipeptide, may be an alternative therapeutic compound for preventing or retarding the development of DN.

Factors affecting the progression of renal dysfunction and the importance of salt restriction in patients with type 2 diabetic kidney disease.

Type 2 diabetic kidney disease (DKD) is the most common cause of end-stage renal failure, and the prevention of its progression has been a topic of discussion. Sixty type 2 DKD patients were retrospectively evaluated for 1 year. Factors independently affecting the annual Ccr decline were examined by multivariable linear regression analysis. Patients were further divided into 2 groups based on their degree of renal function, and between-group differences at study initiation were evaluated. Ccr values were 21.0 ± 11.8 mL/min/1.73 m(2) at study initiation, and 15.7 ± 10.9 mL/min/1.73 m(2) after 1 year of observation. The multivariable linear regression analysis indicated salt intake (standardized coefficient: -0.34, P = 0.010) and urinary protein excretion (standardized coefficient: -0.33, P = 0.011) to be factors independently affecting the annual Ccr decline. Although decliners (-9.8 ± 4.7 mL/min/1.73 m(2)/year) had a significantly higher salt intake than non-decliners (-1.1 ± 3.8 mL/min/1.73 m(2)/year) at study initiation, this difference disappeared at the end of the study as a result of intensive dietary education. In 21 decliners with an additional year of follow-up, the annual Ccr decline significantly improved from -10.1 ± 5.3 to -5.3 ± 7.4 mL/min/1.73 m(2)/year (P = 0.02). Salt intake and urinary protein excretion were associated with annual Ccr decline in type 2 DKD patients. Furthermore, dietary education covering salt intake may have positively affected the change in Ccr.

Peritoneal Dialysis in Asia

Background: There is a growing demand of dialysis in Asia for end-stage renal failure patients. Diabetes mellitus is the leading cause of end-stage renal failure in many countries in Asia. Summary: The growth of peritoneal dialysis (PD) in Asia is significant and seeing a good trend. With the enhanced practices of PD, the quality of care in PD in Asia is also improved. Overall, PD and hemodialysis (HD) are comparable in clinical outcome. There is a global trend in the reduction of peritonitis rates and Asian countries also witness such improvement. The socio-economic benefits of PD for end-stage renal failure patients in both urban and rural areas in the developed and developing regions of Asia are an important consideration. This can help to reduce the financial burden of renal failure in addressing the growing demand of patients on dialysis. Initiatives should be considered to further drive down the cost of PD in Asia. Key Messages: Growing demand for dialysis by an increasing number of end-stage renal failure patients requires the use of a cost-effective quality dialysis modality. PD is found to be comparable to HD in outcome and quality. In most countries in Asia, PD should be more cost-effective than HD. A ‘PD-first' or a ‘PD as first considered therapy' policy can be an overall strategy in many countries in Asia in managing renal failure patients, taking the examples of Hong Kong and Thailand. Facts from East and West: (1) PD is cheaper than HD and provides a better quality of life worldwide, but its prevalence is significantly lower than that of HD in all countries, with the exception of Hong Kong. Allowing reimbursement of PD but not HD has permitted to increase the use of PD over HD in many Asian countries like Hong Kong, Vietnam, Taiwan, Thailand, as well as in New Zealand and Australia over the last years. In the Western world, however, HD is still promoted, and the proportion of patients treated with PD decreases. Japan remains an exception in Asia where PD penetration is very low. Lack of adequate education of practitioners and information of patients might as well be reasons for the low penetration of PD in both the East and West. (2) Patient survival of PD varies between and within countries but is globally similar to HD. (3) Peritonitis remains the main cause of morbidity in PD patients. South Asian countries face specific issues such as high tuberculosis and mycobacterial infections, which are rare in developed Asian and Western countries. The infection rate is affected by climatic and socio-economic factors and is higher in hot, humid and rural areas. (4) Nevertheless, the promotion of a PD-first policy might be beneficial particularly for remote populations in emerging countries where the end-stage renal disease rate is increasing dramatically.

Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP) (group SP) and in age-matched Wistar-Kyoto (WKY) (group WKY) rats, following unilateral nephrectomy (UNX), and a vehicle was injected alone in UNX SHR-SP as control (group SC). Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR) are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

Plasmaphresis therapy for pulmonary hemorrhage in a pediatric patient with IgA nephropathy.

IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening manifestation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was comparable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosuppressive medication for treating IgA nephropathy with pulmonary hemorrhage.

Identification of people with autosomal dominant polycystic kidney disease using routine data: a cross sectional study.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) causes progressive renal damage and is a leading cause of end-stage renal failure. With emerging therapies it is important to devise a method for early detection. We aimed to identify factors from routine clinical data which can be used to distinguish people with a high likelihood of having ADPKD in a primary health care setting.MethodA cross-sectional study was undertaken using data from the Quality Intervention in Chronic Kidney Disease trial extracted from 127 primary care practices in England. The health records of 255 people with ADPKD were compared to the general population. Logistic regression was used to identify clinical features which distinguish ADPKD. These clinical features were used to stratify individual risk using a risk score tool.ResultsRenal impairment, proteinuria, haematuria, a diastolic blood pressure over 90 mmHg and multiple antihypertensive medications were more common in ADPKD than the general population and were used to build a regression model (area under the receiver operating characteristic curve; 0.79). Age, gender, haemoglobin and urinary tract infections were not associated with ADPKD. A risk score (range −3 to +10) of ≥0 gave a sensitivity of 70.2% and specificity 74.9% of for detection.ConclusionsStratification of ADPKD likelihood from routine data may be possible. This approach could be a valuable component of future screening programs although further longitudinal analyses are needed.

Role of heparanase-driven inflammatory cascade in pathogenesis of diabetic nephropathy.

Renal involvement is a major medical concern in the diabetic population, and with the global epidemic of diabetes, diabetic nephropathy (DN) became the leading cause of end-stage renal failure in the Western world. Heparanase (the only known mammalian endoglycosidase that cleaves heparan sulfate) is essentially involved in DN pathogenesis. Nevertheless, the exact mode of heparanase action in sustaining the pathology of DN remains unclear. Here we describe a previously unrecognized combinatorial circuit of heparanase-driven molecular events promoting chronic inflammation and renal injury in individuals with DN. These events are fueled by heterotypic interactions among glomerular, tubular, and immune cell compartments, as well as diabetic milieu (DM) components. We found that under diabetic conditions latent heparanase, overexpressed by glomerular cells and posttranslationally activated by cathepsin L of tubular origin, sustains continuous activation of kidney-damaging macrophages by DM components, thus creating chronic inflammatory conditions and fostering macrophage-mediated renal injury. Elucidation of the mechanism underlying the enzyme action in diabetic kidney damage is critically important for the proper design and future implementation of heparanase-targeting therapeutic interventions (which are currently under intensive development and clinical testing) in individuals with DN and perhaps other complications of diabetes.

Mind the gap: connexins and cell-cell communication in the diabetic kidney.

Connexins, assembled as a hexameric connexon, form a transmembrane hemichannel that provides a conduit for paracrine signalling of small molecules and ions to regulate the activity and function of adjacent cells. When hemichannels align and associate with similar channels on opposing cells, they form a continuous aqueous pore or gap junction, allowing the direct transmission of metabolic and electrical signals between coupled cells. Regulation of gap junction synthesis and channel activity is critical for cell function, and a number of diseases can be attributed to changes in the expression/function of these important proteins. Diabetic nephropathy is associated with several complex metabolic and inflammatory responses characterised by defects at the molecular, cellular and tissue level. In both type 1 and type 2 diabetes, glycaemic injury of the kidney is the leading cause of end-stage renal failure, a consequence of multiple aetiologies, including increased deposition of extracellular matrix, glomerular hyperfiltration, albuminuria and tubulointerstitial fibrosis. In diabetic nephropathy, loss of connexin mediated cell-cell communication within the nephron may represent an early sign of disease; however, our current knowledge of the role of connexins in the diabetic kidney is sparse. This review highlights recent evidence demonstrating that maintenance of connexin-mediated cell-cell communication could benefit region-specific renal function in diabetic nephropathy and suggests that these proteins should be viewed as a tantalising novel target for therapeutic intervention.

P63 - The effect of natural polyphenols on the oxidative stress markers in patients with diabetic nephropathy

BackgroundNephropathy remains a significant cause of morbidity and mortality in the diabetic population and is the leading cause of end-stage renal failure, hence kidney transplantations. As a result of the diabetic milieu, increased generation of reactive oxygen species is thought to play a key role in the progression of diabetic nephropathy. Aim of this study was to evaluate the effect of Pycnogenol (Pyc), the extract from Pinus pinaster, on the level of glucose, advanced glycation end products (AGE) and oxidative stress markers in patients with Diabetic nephropathy (DN). Subject and MethodsTo double blind randomised placebo controlled exploratory study were enrolled 20 men with DN received daily Pyc (120mg) or a placebo. Patients were investigated before, one and three months after Pyc administration and after termination of drugs supplementation. ResultsThe level of glucose, AGEs, malondialdehyde (MDA), 8-isoprostanes (8-Iso), as well as protein carbonyls (PC) were increased in comparison to control group. We have found lower level of glucose, AGEs, MDA and 8-Iso after 3 months of Pyc administration in comparison to the beginning state and to placebo group, but these results did not reach significance. CP and TAS were not affected. ConclusionOur data allow us to conclude that Pycnogenoladministration reduces oxidative damage to lipids rather through the decreased glucose level than through the influence of antioxidant capacity of plasma.This study was supported by grant Ministry of Health 2012/8-ukba-8.

YKL-40, a Marker of Cardiovascular Disease and Endothelial Dysfunction, in Kidney Transplant Recipients

BackgroundYKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesion of atherosclerosis. Because cardiovascular mortality is the main cause of death, there are no data on kidney transplant recipients, so the aim of the study was to assess YKL-40 in that population, with particular attention being paid to the relationship with endothelial damage. MethodsWe studied 68 patients after kidney transplantation. Complete blood count, creatinine, lipids, and fasting glucose were studied with the use of standard laboratory methods. We assessed YKL-40; markers of inflammation high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor, thrombomodulin, interleukin-6, intracellular adhesion molecule, and vascular cell adhesion molecule; markers of hemostasis plasmin-antiplasmin complexes, thrombin-antithrombin complexes, prothrombin fragments 1+2; and marker of kidney function neutrophil gelatinase–associated lipocalin (NGAL) with the use of commercially available assays. ResultsMean levels of YKL-40 were significantly higher in kidney allograft recipients than in the control group (P < .001). YKL-40 was also significantly higher in patients with coronary artery disease, hypertension, and diabetes compared with their counterparts without these diseases. YKL-40, in univariate analysis, was related to NGAL, protein Z, plasmin-antiplasmin complex, mean corpuscular volume, cyclosporine level, and hs-CRP. YKL-40 was not related to serum lipids, markers of endothelial cell injury, or causes of end-stage renal failure. YKL-40 was predicted by cyclosporine level, NGAL, and hs-CRP, explaining 37% of the variation. ConclusionsElevated YKL-40 may contribute to enhanced risk of cardiovascular complication, mainly owing to endothelial cell injury and inflammation in patients after kidney transplantation treated with calcineurin inhibitors.

Dietary Management of Diabetic Chronic Kidney Disease

Diabetic chronic kidney disease (diabetic nephropathy) is the most common cause for end-stage renal failure and is associated with increased cardiovascular morbidity and mortality. Multiple interventions, including good control of blood pressure, blood glucose, and lipids, have been shown to slow its progression. Dietary management is being considered an adjunct to retard the progression of diabetic nephropathy. Several animal and human studies have evaluated the rationale and potential benefits of using various dietary interventions in patients with diabetic nephropathy. We provide an overview of the current evidence supporting the use of dietary measures in the management of diabetic chronic kidney disease.

Cell biology of diabetic nephropathy: Roles of endothelial cells, tubulointerstitial cells and podocytes.

Diabetic nephropathy is the major cause of end-stage renal failure throughout the world in both developed and developing countries. Diabetes affects all cell types of the kidney, including endothelial cells, tubulointerstitial cells, podocytes and mesangial cells. During the past decade, the importance of podocyte injury in the formation and progression of diabetic nephropathy has been established and emphasized. However, recent findings provide additional perspectives on pathogenesis of diabetic nephropathy. Glomerular endothelial damage is already present in the normoalbuminuric stage of the disease when podocyte injury starts. Genetic targeting of mice that cause endothelial injury leads to accelerated diabetic nephropathy. Tubulointerstitial damage, previously considered to be a secondary effect of glomerular protein leakage, was shown to have a primary significance in the progression of diabetic nephropathy. Emerging evidence suggests that the glomerular filtration barrier and tubulointerstitial compartment is a composite, dynamic entity where any injury of one cell type spreads to other cell types, and leads to the dysfunction of the whole apparatus. Accumulation of novel knowledge would provide a better understanding of the pathogenesis of diabetic nephropathy, and might lead to a development of a new therapeutic strategy for the disease.