Sepsis is the leading cause of death in critically ill patients in the United States. Yet the individual host response to septicemia is variable, depending on the patient's immune response, age, nutritional status, and coexisting conditions, as well as on the virulence of the organism and the size of the inoculum. This review examines evolving concepts of sepsis and discusses new and potential therapies. Recent clinical advances include therapy with activated protein C, stringent control of blood glucose, and early goal-directed therapy to treat cellular oxygen deficit. Future therapies may be focused on modulating the immune response in the light of the characteristics of the specific pathogen, the genetic profile of the patient, and the duration of the disease.

https://www.nejm.org/doi/pdf/10.1056/NEJMra021333

The pathophysiology and treatment of sepsis.

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

/pdf/the-classification-of-glomerulonephritis-in-systemic-lupus-4qgi5j1hw3.pdf

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in wegener's granulomatosis

Ischemic kidney injury often occurs in the context of multiple organ failure and sepsis. Here, we review the major components of this dynamic process, which involves hemodynamic alterations, inflammation, and endothelial and epithelial cell injury, followed by repair that can be adaptive and restore epithelial integrity or maladaptive, leading to chronic kidney disease. Better understanding of the cellular pathophysiological processes underlying kidney injury and repair will hopefully result in the design of more targeted therapies to prevent the injury, hasten repair, and minimize chronic progressive kidney disease.

/pdf/cellular-pathophysiology-of-ischemic-acute-kidney-injury-2hp9tr2zgu.pdf

Cellular pathophysiology of ischemic acute kidney injury

The classification of glomerulonephritis in systemic lupus erythematosus revisited

The morphology of "acute tubular necrosis" in man: analysis of 57 renal biopsies and a comparison with the glycerol model.

Although it is generally considered that vasculitis of the polyarteritis nodosa (PAN) group and Wegener's granulomatosis (WG) is immune complex (IC) mediated, there are no simultaneous data on circulating IC, complement levels and deposits of Ig and complement in the kidney. Therefore we have performed a retrospective study of 43 patients suffering from PAN and WG. Ig glomerular deposits were uncommon and scanty, except in two patients with WG; C3 deposits were detected in 12 patients, whereas fibrinogen was constantly found when lesions were recent and active. Similar data were obtained for the renal vessel walls. Contrasting with these results, rheumatoid factors and cryoglobulins, suggestive of the presence of circulating IC, were detected respectively in nine of 39 and seven of 37 patients, and IC‘activity’ assessed by the Raji cell assay and the C1q binding assay was found respectively in six of 17 and nine of 10 patients before treatment, and in none of 10 and five of seven patients in remission. Haemolytic complement activity and complement components were never decreased, but the C3d breakdown product of C3 was elevated in all the eight patients studied before treatment. Signs of persistent hepatitis B virus (HBV). infection were detected in five of 25 patients of the PAN group, whereas three of eight patients with WG had only anti-HBV antibodies. Furthermore, cytomegalovirus (CMV) could be isolated from the blood in a case of WG before the treatment was started. Persistent interferonaemia was detected in one of five patients. These results suggest either that renal deposition of CIC is transient, the paucity of Ig deposits being due to rapid clearance of IC by phagocytic cells; or alternatively that vascular and glomerular lesions are not caused by CIC, as in some cases of experimental vasculitis induced by infectious agents.

Immunopathological studies of polyarteritis nodosa and Wegener's granulomatosis: a report of 43 patients with 51 renal biopsies.

Renal function, proteinuria and renal histology, including five biopsies and 13 autopsies, were studied in 16 patients with Waldenstrom's macroglobulinemia. Glomerular abnormalities included amyloidosis in three cases and in six cases the presence of striking deposits, located on the endothelial aspect of the basement membrane, sometimes so voluminous as to occlude the capillary lumen, resembling thrombi. Immunofluorescent analysis of these deposits or thrombi suggested that they contained exclusively lgM. The morphologic aspect, as well as the composition, of these deposits may indicate a passive deposition of circulating lgM that is perhaps due to hyperviscosity. Interstitial infiltration, found in 10 cases, was of the same type as that observed in the bone marrow. In contrast to patients with myeloma, tubular casts with macrophagic reaction were never detected.

https://www.nejm.org/doi/pdf/10.1056/NEJM197007162830304?listPDF=true

Pathology of the kidney in Waldenström's macroglobulinemia. Study of sixteen cases.

Prognostic importance of vascular lesions in acute renal failure with microangiopathic hemolytic anemia (hemolytic-uremic syndrome): Clinicopathologic study in 20 adults

Liliane Morel-Maroger

Papers

The morphology of "acute tubular necrosis" in man: analysis of 57 renal biopsies and a comparison with the glycerol model.

Immunopathological studies of polyarteritis nodosa and Wegener's granulomatosis: a report of 43 patients with 51 renal biopsies.

Pathology of the kidney in Waldenström's macroglobulinemia. Study of sixteen cases.

Prognostic importance of vascular lesions in acute renal failure with microangiopathic hemolytic anemia (hemolytic-uremic syndrome): Clinicopathologic study in 20 adults

The course of lupus nephritis: contribution of serial renal biopsies.