Bill & Melinda Gates Foundation.

No abstract

Bill & Melinda Gates Foundation.

Noncommunicable diseases (NCDs) are the most common causes of premature death and morbidity and have a major impact on health-care costs, productivity, and growth. Cardiovascular disease, cancer, diabetes, and chronic respiratory disease have been prioritized in the Global NCD Action Plan endorsed by the World Health Assembly, because they share behavioral risk factors amenable to public-health action and represent a major portion of the global NCD burden. Chronic kidney disease (CKD) is a key determinant of the poor health outcomes of major NCDs. CKD is associated with an eight- to tenfold increase in cardiovascular mortality and is a risk multiplier in patients with diabetes and hypertension. Milder CKD (often due to diabetes and hypertension) affects 5-7% of the world population and is more common in developing countries and disadvantaged and minority populations. Early detection and treatment of CKD using readily available, inexpensive therapies can slow or prevent progression to end-stage renal disease (ESRD). Interventions targeting CKD, particularly to reduce urine protein excretion, are efficacious, cost-effective methods of improving cardiovascular and renal outcomes, especially when applied to high-risk groups. Integration of these approaches within NCD programs could minimize the need for renal replacement therapy. Early detection and treatment of CKD can be implemented at minimal cost and will reduce the burden of ESRD, improve outcomes of diabetes and cardiovascular disease (including hypertension), and substantially reduce morbidity and mortality from NCDs. Prevention of CKD should be considered in planning and implementation of national NCD policy in the developed and developing world.

No abstract

Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%-5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.

Abstract. Ischemia-reperfusion injury

Chronic HCV infection is associated with cryoglobulinemia and membranoproliferative glomerulonephritis. The pathogenesis is unknown, but may relate to deposition within glomeruli of immune complexes containing HCV, anti-HCV IgG, and IgM rheumatoid factors.