Anti-phospholipase A2 receptor antibodies in recurrent membranous nephropathy.

About 70% of patients with primary membranous nephropathy (MN) have circulating anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease activity, but their predictive value in post-transplant (Tx) recurrent MN is uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without recurrence, with serial post-Tx serum samples and renal biopsies to determine if patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared to seronegative patients and to determine if post-Tx changes in anti-PLA2R correspond to the clinical course. In the recurrent group, 10/17 patients had anti-PLA2R at the time of Tx versus 2/7 patients in the nonrecurrent group. The positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the negative predictive value was 42%. Persistence or reappearance of post-Tx anti-PLA2R was associated with increasing proteinuria and resistant disease in 6/18 cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and biopsy evidence of recurrence in which the antibodies resolved with standard immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative at the time of recurrence. In conclusion, patients with positive pre-Tx anti-PLA2R should be monitored closely for recurrent MN. Persistence or reappearance of antibody post-Tx may indicate a more resistant disease.

Very early recurrence of anti-Phospholipase A2 receptor-positive membranous nephropathy after transplantation.

Membranous nephropathy is a common cause of adult nephrotic syndrome, with recent evidence suggesting that 70% of idiopathic disease is associated with anti-Phospholipase A(2) receptor autoantibodies. We describe a 63-year-old man with membranous nephropathy who underwent a kidney transplant and developed recurrent membranous nephropathy with fine granular co-localization of Phospholipase A(2) receptor and IgG evident on transplant biopsy on day 6 and elevated circulating levels of serum anti-Phospholipase A(2) receptor autoantibody that declined over time in conjunction with improvement in the serum creatinine and urinary protein. This is a very early case of Phospholipase A(2) receptor-associated recurrent membranous nephropathy with circulating anti-Phospholipase A(2) receptor autoantibody, which supports the emerging evidence that idiopathic membranous nephropathy is an autoimmune disease.

Screening and preventive health practices for the end-stage renal disease patient.

The population of end-stage renal disease (ESRD) patients continues to grow and to age. The nephrologist often is the sole or principal physician responsible for the total management of these patients. In this role, the nephrologist must address issues of routine health maintenance. Screening tests and preventive care should be continued to detect, prevent, or minimize comorbid conditions that could affect quality of life or survival. Effective primary and secondary prevention requires understanding the principles of screening tests and their appropriate use. Screening and counseling procedures recommended for healthy adults should be continued, although certain screening tests may appropriately be discontinued if the expected survival is 5 years or less. Secondary prevention for cardiovascular disease is particularly important in ESRD patients, in whom accelerated atherosclerosis is often the cause of morbidity and death. Aggressive counseling in smoking cessation and in management of hyperlipidemia should be undertaken, in the hopes of limiting this common comorbidity.

The aging kidney. Defending a delicate balance of fluid and electrolytes.

The aging kidney is characterized by reduced glomerular filtration rate, loss of tubular volume, and narrowed homeostatic control of water and electrolyte balance. It is unclear whether these physiologic changes represent normal aging or subclinical disease. With aging, there is an increased risk of hyper- or hypovolemia. Sluggish control of potassium concentration also makes hyperkalemia more common, particularly when the patient is using certain drugs. Water metabolism is particularly vulnerable in older patients, resulting in a frequent tendency toward dehydration and hyperosmolality. Understanding these limitations on fluid and electrolyte homeostasis can help the clinician recognize and prevent complications when caring for older patients.

Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact.

Embryological data suggest that endothelial cells (ECs) direct the recruitment and differentiation of mural cell precursors. We have developed in vitro coculture systems to model some of these events and have shown that ECs direct the migration of undifferentiated mesenchymal cells (10T1/2 cells) and induce their differentiation toward a smooth muscle cell/pericyte lineage. The present study was undertaken to investigate cell proliferation in these cocultures. ECs and 10T1/2 cells were cocultured in an underagarose assay in the absence of contact. There was a 2-fold increase in bromodeoxyuridine labeling of 10T1/2 cells in response to ECs, which was completely inhibited by the inclusion of neutralizing antiserum against platelet-derived growth factor (PDGF)-B. Antisera against PDGF-A, basic fibroblast growth factor, or transforming growth factor (TGF)-beta had no effect on EC-stimulated 10T1/2 cell proliferation. EC proliferation was not influenced by coculture with 10T1/2 cells in the absence of contact. The cells were then cocultured so that contact was permitted. Double labeling and fluorescence-activated cell sorter analysis revealed that ECs and 10T1/2 cells were growth-inhibited by 43% and 47%, respectively. Conditioned media from contacting EC-10T1/2 cell cocultures inhibited the growth of both cell types by 61% and 48%, respectively. Although we have previously shown a role for TGF-beta in coculture-induced mural cell differentiation, growth inhibition resulting from contacting cocultures or conditioned media was not suppressed by the presence of neutralizing antiserum against TGF-beta. Furthermore, the decreased proliferation of 10T1/2 cells in the direct cocultures could not be attributed to downregulation of the PDGF-B in ECs or the PDGF receptor-beta in the 10T1/2 cells. Our data suggest that modulation of proliferation occurs during EC recruitment of mesenchymal cells and that heterotypic cell-cell contact and soluble factors play a role in growth control during vessel assembly.

Periodic health examination and screening tests in adults.

Whenever a patient presents for the annual health examination, clinicians must choose from a plethora of screening tests and conflicting sets of guidelines. A discussion of the underlying issues leads to practical tips on how select and when to abandon screening tests and when to treat or not treat patients with marginally positive test results.

Changes in renal function with aging.

Despite losing 20%-25% of their original kidney volume, older individuals maintain body fluid hemostasis under most circumstances; however, their ability to withstand environmental, disease-related, or iatrogenic stresses becomes progressively narrowed. Glomerular filtration rates fall with each decade, accompanied by limitations on sodium conservation, potassium ion secretion, and acid excretion. Medications used by older patients are a common cause of hyperkalemia through a number of pathophysiologic mechanisms. In addition, water homeostasis frequently fails due to defects in thirst, urinary concentrating ability, and free water excretion, resulting in hypernatremia or hyponatremia in many sick older patients.

Perioperative renal, fluid, and electrolyte management.

Normal physiologic changes of aging increase the likelihood of renal-electrolyte disorders in the elderly surgical patient. The most important of these changes are a decrease in the GFR, decreased urinary concentrating ability, and narrowed limits for the excretion of water, sodium, potassium, and acid. Because of the decrease in GFR, the elderly surgical patient is at increased risk for virtually every cause of acute renal failure, an outcome associated with a mortality of greater than 50%. Certain types of surgery, especially cardiac, aortic, and biliary tract operations, are associated with a higher risk of acute renal failure than are others. The most important principles of prevention in the elderly surgical patient are to maintain normal intravascular volume and avoid hypovolemia. Meticulous attention must be paid to salt and water balance and to drug dosing. Should perioperative renal insufficiency occur, evaluation and management in the elderly patient are similar to usual practices in a younger individual.

Integrating residency training in geriatrics into existing outpatient curricula.

In recent years, the need for increasing the geriatrics component of residency training has been repeatedly addressed; however, there are still many programs that have been unable to meet this need. While alternative sites, such as geriatric evaluation units and nursing homes, may be the ideal sites to teach some aspects of geriatrics, this article argues that the ambulatory care program, required in all residency programs, is the appropriate setting for teaching many of the core skills needed to care for most older adults. Teaching geriatrics in the ambulatory setting, which eliminates the strategic and financial obstacles of developing non-hospital-based sites, can be accomplished with relatively modest additional resources. This article describes the methods used to integrate geriatrics into the ambulatory care component of one internal medicine residency program and the necessary faculty resources as well as the documentation, via chart audit, of the interns' compliance with recommended practice patterns in five categories. With the exception of vaccination status, interns documented 18% or less of possible pieces of information for their patients. While this assessment showed statistically significant improvement in interns' care of older patients after the program intervention, the overall level of performance was still low, underscoring the need for the integration of geriatrics principles in the ambulatory curriculum.

Maintaining health with renal disease or dysfunction.

A decline in renal function, similar to mild chronic renal insufficiency, normally occurs in the elderly concomitantly with various anatomic and histologic changes in the kidney. These morphologic and physiologic changes result in diminished ability to respond to body fluid or solute stresses. Superimposition of chronic renal insufficiency upon these age-related physiologic changes can accelerate renal functional decline. However, with proper management, most elderly patients with renal disease can remain highly functional.