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In IDDM patients, an increased permeability of the glomerular capillaries has been associated with a general loss of negatively charged heparan sulfate proteoglycans (HSPGs) within basement membranes (BMs). In the [...]

Accumulation of matrix proteins is a prominent feature of diabetic nephropathy. Glomerular visceral epithelial cells (GVECs) are important contributors to extracellular matrix (ECM) production in the glomerulus. Factors involved with [...]

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of connective tissue that affects the skin, joints, kidneys, nervous system, and mucous membranes. SLE may be complicated by end-stage renal failure, or advanced kidney failure. In the past, patients with SLE complicated by disorders of several organ systems died before progression to uremia, a toxic condition resulting from the retention of nitrogen-containing wastes in the blood. High doses of corticosteroid agents have controlled various complications, but have been ineffective in preventing kidney-associated death and disease. Dialysis, the artificial filtration of the blood, is used to manage SLE patients with kidney disease, but kidney transplantation can permit the patient to resume a full and active life. Studies suggest that the survival of the transplanted kidney may be as good for patients with SLE as recipients without SLE. The outcome and disease activity of 28 patients with SLE and advanced kidney disease, who received kidney transplants, were assessed. The survival rates of the kidney graft were 68 percent at one year, and 54 percent at five years. The survival rate of the patients at one and five years was 87 percent. SLE disease activity did not influence the survival of the graft, and decreased after transplantation. Only one patient experienced recurrence of lupus nephritis, the inflammation of the kidney associated with SLE. These findings suggest that SLE patients with advance kidney disease are excellent candidates for kidney transplantation, which is associated with decreased SLE disease activity and rare recurrence of lupus nephritis. (Consumer Summary produced by Reliance Medical Information, Inc.)

PURPOSE: To compare disease activity in patients with systemic lupus erythematosus (SLE) (1) before and after the onset of end-stage renal failure and (2) during hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Records of 55 patients with SLE currently being treated with dialysis were reviewed. Disease activity was measured according to the SLE Disease Activity Index, event rates per 1,000 months' patient observation, and use of medication. RESULTS: In the majority of patients, deterioration of renal function was slowly progressive over more than 2 years. After the initiation of dialysis for end-stage renal failure, maximal extrarenal disease activity and use of medication decreased markedly, but event rates for specific nonrenal manifestations of lupus did not decrease. Overall survival with dialysis was 89% after 5 years. During dialysis no difference was found in disease activity and use of medication between treatment with either hemodialysis or CAPD. Thrombocytopenia and elevated levels of anti-double-stranded DNA, however, occurred more frequently during CAPD. CONCLUSION: Patients with SLE have excellent survival rates with dialysis; their disease activity is diminished during dialysis but not abolished. No difference in survival or disease activity was found between patients undergoing hemodialysis or CAPD., Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of connective tissue and may be complicated by renal or kidney disease in 50 to 80 percent of patients. Twenty percent of patients with lupus nephritis (LN), the inflammation of the kidney associated with SLE, develop end-stage (advanced) kidney failure within 10 years after the diagnosis of LN and require dialysis, the artificial filtration of the blood to remove wastes. In hemodialysis, the blood is filtered through tubes made of membranes that selectively filter and remove unwanted wastes. Continuous ambulatory peritoneal dialysis (CAPD) is a form of dialysis in which a catheter is implanted into the peritoneal (abdominal) cavity. Some studies have suggested that disease activity in SLE is worsened by CAPD. Hence the disease activity in 55 patients with SLE was assessed before and after advanced kidney failure, during hemodialysis and CAPD. Kidney function slowly deteriorated over more than two years in most patients. SLE disease activity and the use of medications decreased after the start of dialysis to treat kidney disease. However, dialysis did not improve the incidence of non-kidney-related complications of SLE. Eighty-nine percent of patients with SLE undergoing dialysis were surviving at five years. Disease activity and use of medications were similar among patients treated with hemodialysis or CAPD. However, patients treated with CAPD had a greater incidence of thrombocytopenia, which is a decreased number of platelets (cells involved in blood clotting), and of antibodies to deoxyribonucleic acid (DNA), the genetic material of the cell. These findings show that dialysis improves survival among patients with SLE, and inhibits but does not abolish disease activity. (Consumer Summary produced by Reliance Medical Information, Inc.)

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of connective tissue which affects the skin, joints, kidneys, and other tissues. In spite of the beneficial effects of steroids on patient survival, kidney (renal) disease as a result of SLE is still associated with high rates of illness and death. Recent evidence suggests that certain factors are predictive of kidney failure, including age at which the disease develops (under 23 years is associated with increased risk), increased blood levels of creatinine (indicator of kidney function), widespread lesions (as indexed by the World Health Organization), and a high index of chronic kidney structural alterations using a National Institutes of Health (NIH) scoring system. To determine the significance of these factors in determining chronic or irreversible disease, as opposed to active but reversible disease, 116 patients with SLE and kidney disease were evaluated. In particular, the value of information derived from medical examinations and biopsy examinations was compared. The results indicate that a histologic (microstructural biopsy) analysis showing chronic kidney disease using the NIH score was the best indicator of kidney death; the use of the same analysis and an age of less than 31 years at time of biopsy, was associated with poor survival. Medical parameters such as creatinine levels and protein in the urine correlated more often with the presence of active kidney disease than ongoing chronic kidney disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3–deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3–deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3–deficient animals. Supplementation with 1,25-vitamin D3or 1,25-vitamin D2prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3–deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3deficiency and 1,25-vitamin D3and 1,25-vitamin D2repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.