Recurrence of lupus nephritis after kidney transplantation.

The frequency and outcome of recurrent lupus nephritis (RLN) among recipients of a kidney allograft vary among single-center reports. From the United Network for Organ Sharing files, we estimated the period prevalence and predictors of RLN in recipients who received a transplant between 1987 and 2006 and assessed the effects of RLN on allograft failure and recipients' survival. Among 6850 recipients of a kidney allograft with systemic lupus erythematosus, 167 recipients had RLN, 1770 experienced rejection, and 4913 control subjects did not experience rejection. The period prevalence of RLN was 2.44%. Non-Hispanic black race, female gender, and age <33 years each independently increased the odds of RLN. Graft failure occurred in 156 (93%) of those with RLN, 1517 (86%) of those with rejection, and 923 (19%) of control subjects without rejection. Although recipients with RLN had a fourfold greater risk for graft failure compared with control subjects without rejection, only 7% of graft failure episodes were attributable to RLN compared and 43% to rejection. During follow-up, 867 (13%) recipients died: 27 (16%) in the RLN group, 313 (18%) in the rejection group, and 527 (11%) in the control group. In summary, severe RLN is uncommon in recipients of a kidney allograft, but black recipients, female recipient, and younger recipients are at increased risk. Although RLN significantly increases the risk for graft failure, it contributes far less than rejection to its overall incidence; therefore, these findings should not keep patients with lupus from seeking a kidney transplant.

Utility of static pressure ratio recording during angioplasty of arteriovenous graft stenosis.

Intra-access static pressure ratio (SPR) (intra-access pressure/mean arterial pressure) can be measured during angioplasty (PTA) to assess the functional importance of an arteriovenous graft (AVG) stenosis. We used SPR in 70 patients with AVGs who underwent 98 angioplasty procedures. SPR was measured during angioplasty by placing a catheter tip at mid-access. Inflow stenosis (IF) = stenosis proximal to the tip of the catheter. Outflow stenosis (OF) = stenosis distal to the tip of the catheter up to the superior vena cava-atrial junction. Post PTA, access flow (Qa) was assessed within 2 weeks. Complete data sets for both SPR and Qa were available in 83 procedures. Using a normal SPR ratio of 0.3-0.4 at mid-graft, three patterns of SPR were noted. In 63 of 83 (76%) cases SPR was elevated prior to PTA (0.71 +/- 0.13 SD). PTA reduced SPR toward normal range (0.44 +/- 0.12) in 53 cases (84%). In the remaining 10 (16%), SPR decreased to a low value (0.22 +/- 0.03) and normalized (0.40 +/- .0.11) only after PTA of a coexisting inflow stenosis. In 12 of 83 (14%) procedures, the initial SPR was low (0.18 +/- 0.04) and increased toward normal (0.3 +/- 0.08) following IF stenosis PTA in seven (58%) cases. For the remaining five (42%) cases SPR increased to a high value (0.70 +/- 0.21) and decreased toward normal range (0.33 +/- 0.07) only after OF stenosis angioplasty. In 8 of 83 (10%) procedures, initial SPR was normal (0.33 +/- 0.02). Angiography revealed coexisting IF and OF stenoses. SPR remained within the normal range after PTA of these lesions (0.33 +/- 0.02). Qa increased significantly in 74 of 83 (89%) procedures (before = 572 +/- 201, after = 1109 +/- 368 ml/min; p < 0.001). SPR measurements can assist in hemodynamic assessment of an AVG during angioplasty procedure.

David Ayman, MD: an early investigator of clinical hypertension.

Dr. David Ayman (1901-1986) was an astute clinician and observer who challenged medical dogma by performing placebo-controlled studies and by meticulous measurement of blood pressure under standardized conditions. He demonstrated that almost all drugs reported to have an antihypertensive effect in the early 20th century had achieved nothing more than placebo response. He noted the marked variability of blood pressure and devised methods to reduce that variability. These observations led to his publications concerning what is now known as "white coat" or office hypertension. He determined blood pressure personally in 1524 members of 277 families over three generations and made observations on the hereditary nature of hypertension that countered the single-gene thinking of the day. His work is proof that clinical inquisitiveness, hard work, and the courage to challenge conventional wisdom can result in significant contributions to medicine and science.

Sequential therapies for proliferative lupus nephritis.

BACKGROUND: Long-term therapy with cyclophosphamide enhances renal survival in patients with proliferative lupus nephritis; however, the beneficial effect of cyclophosphamide must be weighed against its considerable toxic effects. METHODS: Fifty-nine patients with lupus nephritis (12 in World Health Organization class III, 46 in class IV, and 1 in class Vb) received induction therapy consisting of a maximum of seven monthly boluses of intravenous cyclophosphamide (0.5 to 1.0 g per square meter of body-surface area) plus corticosteroids. Subsequently, the patients were randomly assigned to one of three maintenance therapies: quarterly intravenous injections of cyclophosphamide, oral azathioprine (1 to 3 mg per kilogram of body weight per day), or oral mycophenolate mofetil (500 to 3000 mg per day) for one to three years. The base-line characteristics of the three groups were similar, with the exception that the chronicity index was 1.9 points lower in the cyclophosphamide group than in the mycophenolate mofetil group (P=0.009). RESULTS: During maintenance therapy, five patients died (four in the cyclophosphamide group and one in the mycophenolate mofetil group), and chronic renal failure developed in five (three in the cyclophosphamide group and one each in the azathioprine and mycophenolate mofetil groups). The 72-month event-free survival rate for the composite end point of death or chronic renal failure was higher in the mycophenolate mofetil and azathioprine groups than in the cyclophosphamide group (P=0.05 and P=0.009, respectively). The rate of relapse-free survival was higher in the mycophenolate mofetil group than in the cyclophosphamide group (P=0.02). The incidence of hospitalization, amenorrhea, infections, nausea, and vomiting was significantly lower in the mycophenolate mofetil and azathioprine groups than in the cyclophosphamide group. CONCLUSIONS: For patients with proliferative lupus nephritis, short-term therapy with intravenous cyclophosphamide followed by maintenance therapy with mycophenolate mofetil or azathioprine appears to be more efficacious and safer than long-term therapy with intravenous cyclophosphamide.

Peritoneoscopic placement of peritoneal dialysis catheter and bowel perforation: experience of an interventional nephrology program.

BACKGROUND: Bowel perforation is an uncommon but serious complication of peritoneoscopic peritoneal dialysis (PD) catheter insertion. The approach to diagnosis of bowel perforation utilizing this technique has not been previously published. The authors report their experience with the diagnosis and management of bowel perforation in the context of peritoneoscopic placement of PD catheters. METHODS: The authors retrospectively reviewed the records of 750 PD catheters inserted over a 12-year period (January 1991 to May 2003) utilizing peritoneoscopic technique. RESULTS: Six (0.8%) patients experienced bowel perforation during the procedure. The diagnosis was made immediately during the procedure in 5 (83%) of the 6 patients. Of these 5, peritoneoscopy confirmed intrabowel position of the cannula by visualizing bowel mucosa (n = 3) and hard stool (n = 1). The fifth patient showed extrusion of fecal matter upon trocar withdrawal before peritoneoscopy. All 5 had emanation of foul-smelling gas through the cannula. Bowel rest and broad-spectrum intravenous antibiotics were initiated. Of the 5, 1 required surgery, whereas the others were discharged home after 3 days. The sixth patient had fever, severe peritoneal irritation, and polymicrobial peritonitis the morning after the procedure. In this patient, no evidence of bowel injury was noted during the procedure except for brief emanation of foul-smelling gas. He required surgical intervention. CONCLUSION: Bowel perforation can be diagnosed immediately in most patients undergoing peritoneoscopic PD catheter insertion. A majority of these patients can be treated medically. The surgical team should be consulted if the patient shows clinical deterioration or has signs of peritoneal irritation.

Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible mice.

Estrogen deficiency may contribute to the development and progression of glomerulosclerosis in postmenopausal women. The responsiveness to estrogens could be controlled by genetic traits related to those that determine the susceptibility to glomerular scarring. This study was undertaken to determine whether the intensity of the sclerotic response was modified by the estrogen status in sclerosis-prone ROP Os/+ mice. Ovariectomized ROP Os/+ mice developed more severe renal dysfunction and glomerulosclerosis than intact, ie, estrogen sufficient age-matched female mice. Ovariectomized ROP Os/+ exhibited increased accumulation of extracellular matrix, predominantly of laminin, and a marked distortion of the glomerular architecture. We found an increase in macrophage infiltration in the mesangium of ovariectomized ROP Os/+. Estrogen deficiency decreased glomerular estrogen receptor expression in ROP Os/+ mice, which we had previously found to be low in the parental ROP strain. Thus, although physiological estrogen levels in young ROP Os/+ mice could not prevent the development of glomerulosclerosis, estrogen deficiency accelerated the progression of glomerular scarring in this mouse strain. This suggests that estrogen replacement will slow but not prevent the progression of glomerulosclerosis. It underscores the importance of the genetic composition of individuals that determines the susceptibility to diseases as well as the response to treatment.

Resistance to glomerulosclerosis in B6 mice disappears after menopause.

The frequency of chronic renal failure increases with age, especially in women after menopause. Glomerulosclerosis is a common cause of chronic renal failure in aging. We reported that pre-menopausal female C57BL6 (B6) mice are resistant to glomerulosclerosis, irrespective of the type of injury. However, we now show that B6 mice develop progressive glomerulosclerosis after menopause. Glomerular lesions, first recognized in 18-month-old mice, consisted of hypertrophy, vascular pole sclerosis, and mesangial cell proliferation. Diffuse but moderate mesangial sclerosis and more marked hypertrophy were present at 22 months. At 28 to 30 months the glomerulosclerosis was diffuse and increased levels of type I and type IV collagen and transforming growth factor-beta 1 mRNA were present. Urine albumin excretion was significantly increased in 30-month-old mice. Mesangial cells isolated from 28-month-old mice retained their sclerotic phenotype in vitro. Comparison of the effects of uninephrectomy (Nx) in 20-month-old and 2.5-month-old mice revealed a 1.7-fold increase in urine albumin excretion, accelerated glomerulosclerosis, and renal function insufficiency in 20-month-old Nx mice, but not in 2.5-month-old Nx mice. Glycemic levels, glucose, insulin tolerance, and blood pressure were normal at all ages. Thus, B6 mice model the increased frequency of chronic renal failure in postmenopausal women and provide a model for studying the mechanism(s) of glomerulosclerosis in aging women.

Nitric oxide synthase and hypertension.

Nitric oxide, the metabolic product of L-arginine by the enzyme nitric oxide synthase, plays a pivotal role in the regulation of vascular homeostasis. Its complex interaction with the autocrine and paracrine systems, particularly angiotensin II, modulates vasoconstriction and vasodilatation as well as the architectural remodeling of the vascular bed. The major vascular hormones known to be involved are angiotensin II and endothelin-1. Upregulation of endothelin-1, a potent molecule, appears to be a consequence of the nitric oxide-angiotensin II imbalance that contributes to end-organ injury. Increased oxidative stress, common to different diseases including diabetes mellitus and hypertension, is also a determinant player in the interaction between angiotensin II and nitric oxide. The influence of a relative malfunction of the nitric oxide system on the vascular tone and vascular structure, and the effects of hypertension on this system, are discussed.