Maria V. DeVita

Increasing incidence of focal segmental glomerulosclerosis and an examination of demographic patterns.

BACKGROUND Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of the nephrotic syndrome in adults and an important cause of end-stage renal disease. Its incidence has dramatically increased in the last two decades and it is especially prevalent among black patients. The trend of FSGS incidence has not been reported beyond 1997. METHODS We retrospectively reviewed all renal biopsies performed at our institution between 1986 and 2002 and identified patients with diagnoses consistent with primary glomerulopathy (PG), which included: minimal-change disease (MCD), idiopathic focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN), IgA nephropathy (IgA), membrano-proliferative glomerulonephritis (MPGN) and mesangioproliferative glomerulonephritis. Patients with possible secondary causes for their renal disease were excluded. Clinical data at the time of biopsy and follow-up data were collected and analyzed. RESULTS During the period from January 1986-December 2002, 299 renal biopsies were performed and 132 patients were diagnosed with PG. FSGS was the most common form of PG representing 37.8% of all PG followed by IgA 27.3%, MGN 16.6% and MCD 9.1%. Among FSGS patients 59% were females, 64% had nephrotic range proteinuria and 54% had the nephrotic syndrome. Mean serum creatinine was 2.0 +/- 0.2 mg/dl and mean protein excretion was 6.1 +/- 1.0 g/day. The incidence of FSGS increased from 19.3% (1986-1991) and 16.6% (1992-1997) to 58.5% in the period from 2002. The increase occurred among black and Hispanic patients (33.3-79.2%) as well as white patients (12.5-51.5%). Black and Hispanic patients with PG presented for renal biopsy at a significantly younger age than white patients (p = 0.003), with mean age 37.5 +/- 2.0 years vs. 50.3 +/- 1.8 years. White FSGS patients were significantly older than white non-FSGS patients (mean age 56.4 +/- 3.2 years vs. 48.0 +/- 2.0 years, p = 0.03). Black and Hispanic FSGS patients were also older when compared to their non-FSGS counter-parts (mean age 40.6 +/- 2.8 years vs. 32.1 +/- 2.0 years, p = 0.04). When patients were stratified by age (< 45 years and > or = 45 years), FSGS was the most common diagnosis in both age groups among black and Hispanic patients (55.1% and 88.8%) but only among older white patients (36.2%). CONCLUSIONS The incidence of FSGS as a proportion of PG in our population has increased markedly in the most recent time period analyzed (1998-2002). The increase has occurred among both white and black and Hispanic patients. We also found that FSGS was most prevalent in patients > or = 45 years.

Safety and efficacy of local periadventitial delivery of sirolimus for improving hemodialysis graft patency: first human experience with a sirolimus-eluting collagen membrane (Coll-R)

BACKGROUND Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graft-venous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. METHODS A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of sirolimus release, success of Coll-R implantation and primary unassisted graft patency. RESULTS There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. CONCLUSIONS Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.

Troponin I levels in asymptomatic patients on haemodialysis using a high-sensitivity assay.

BACKGROUND Troponin I (TnI) is an effective marker for detecting myocardial injury, but the interpretation of levels in the setting of end-stage renal disease (ESRD) is still unclear. TnI levels have been noted to be increased in 5-18% of asymptomatic haemodialysis (HD) patients with standard assays, but newer-generation, high-sensitivity assays have not been examined. In addition, there is limited data on the variability of TnI levels in patients over time as well as the effect of HD on TnI levels. The aim of this study was to prospectively explore the incidence of TnI with a high-sensitivity assay, the variability of TnI levels over time and the effect of HD on levels. METHODS We enrolled 51 asymptomatic HD patients and checked TnI levels using a high-sensitivity assay. Levels were drawn pre-HD monthly for three consecutive months. As per manufacturer guidelines, levels were considered normal up to 0.034 ng/mL, indeterminate elevation (IE) if between 0.035 and 0.120 ng/mL and consistent with myocardial infarction (MI) if >0.120 ng/mL. In the third month, post-HD TnI was also drawn to determine change with dialysis. RESULTS At baseline, median TnI level was 0.025 ng/mL (range, 0-0.461 ng/mL). Baseline TnI levels were normal in 63% and elevated (≥0.035 ng/mL) in 37%. Of those with elevations, 79% were in the IE range and 21% in the acute myocardial infarction range. Higher TnI levels at baseline were associated with a history of coronary artery disease, left ventricular hypertrophy, lower cardiac ejection fraction and higher serum phosphate levels. Average incidence of elevated TnI was 41% over the 3 months. Thirty-six patients had stable levels without a change in classification over 3 months. Twelve varied over time. Forty-five (94%) had no change in classification pre- and post-HD. CONCLUSION Using a new-generation, high-sensitivity assay, over a third of asymptomatic ESRD patients have an elevated TnI. The significance of these low-level elevations is unclear at this time. TnI levels remain stable over a 3-month period in most patients. HD treatment does not appear to affect the TnI level.

Pregnancy in Peritoneal Dialysis: A Case Report and Review of Adequacy and Outcomes

A case of pregnancy in a 27-year-old woman on peritoneal dialysis is presented. The case report is a detailed description of her course including changes in her peritoneal dialysis regimen and the use of continuous cycling to maximize dialysis adequacy while addressing the patient’s recurrent abdominal pain and fullness. Also described is the management of complications including hypertension, gestational diabetes, and premature rupture of membranes. The discussion reviews the diagnosis of pregnancy, factors that may relate to outcome, and a detailed comparison of pregnancy outcomes in patients on dialysis to the general population.

ASSESSMENT OF RENAL OSTEODYSTROPHY IN HEMODIALYSIS PATIENTS

We performed a prospective study of 30 patients undergoing chronic hemodialysis to determine which of 6 generally available diagnostic procedures provided the most useful information for the assessment of bone disease in hemodialysis patients. The 6 procedures were: routine biochemical measurements, N-terminal parathyroid hormone (N-PTH), radiographic analysis of hands and clavicles, bone density determination by dual photon absorptiometry (DPA), deferoxamine stimulation test, and iliac crest bone biopsy. Serum N-PTH was elevated in 83% of patients but was not significantly associated with abnormalities of other biochemical parameters. No significant relationship was demonstrated between biochemical data and radiographic findings or between biochemical data and bone density by DPA. All patients with abnormal DPA had an elevation of N-PTH; therefore, DPA did not reveal any unsuspected disease. Bone biopsies were done in 20 patients and findings in each were consistent with uremic osteodystrophy, including osteitis fibrosa cystica in 11 patients and aluminum-associated bone disease in 2 patients. Six patients had mixed disease, and 1 patient had osteoporosis. Despite 11 positive deferoxamine tests, bone biopsy revealed aluminum deposition in only 7 of these patients, suggesting extraosseous aluminum accumulation in the remaining 4. Evaluation of the positive and negative predictive accuracies of DPA, x-ray analysis, N-PTH levels, and aluminum bone deposition revealed that normal DPA or x-ray findings do not exclude bone disease, that N-PTH level is a good marker for secondary hyperparathyroidism, and that a negative deferoxamine test excludes aluminum-associated bone disease. Discriminant analysis also reinforced these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Dual-energy X-ray absorptiometry: a review.

Dual-energy X-ray absorptiometry (DXA) has been recently used for body composition analysis in dialysis patients. It is based on the principle that X-rays passed through various body tissues have different attenuation and, therefore, can be differentiated. By using X-rays at two different energy levels, better tissue differentiation is possible compared with single energy systems. This article will review the evolution of DXA scanners and the role DXA has in assessing body composition in dialysis patients. Overall, this technique has excellent precision and holds promise for use in the serial evaluation of body composition and nutritional evaluation of dialysis patients.

A Review of the Nonpressor and Nonantidiuretic Actions of the Hormone Vasopressin

The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior, and cognitive function. Important cellular responses including cell proliferation, inflammation, and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic–pituitary–adrenal axis are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance.

Percentage body fat determination in hemodialysis and peritoneal dialysis patients: A comparison

OBJECTIVE To evaluate percentage body fat in hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN A prospective study of 20 HD patients and 20 PD patients. SETTING Sol Goldman Renal Therapy Center, Lenox Hill Hospital, New York, NY; Baumritter Kidney Center Albert Einstein College of Medicine, Bronx, NY; Body Composition Unit, St Lukes Roosevelt Hospital, Columbia University, New York, NY. PATIENTS Twenty HD (10 men, 10 women) patients, mean age 41.8 +/- 2.4 years and 20 PD (12 men, 8 women) patients, mean age 48.6 years +/- 3.0 years. INTERVENTION This is a noninterventional study. PATIENTS signed consent to undergo dual-energy x-ray absorptiometry, total body potassium counting bioelectrical impedance analysis, total body water determination, and anthropmetric evaluation. MAIN OUTCOME MEASURES Present and compare percentage body fat between HD and PD patients as determined by the methods used. RESULTS Percentage fat is not different between HD and PD patients. Differences in absolute values of percent fat between techniques exist. CONCLUSION HD patients and PD patients may be evaluated by the methods of body composition used. Percentage body fat will vary among techniques; therefore the same method should be used to follow a patient over time.

Renin-aldosterone system can respond to furosemide in patients with hyperkalemic hyporeninism

Thirty-four patients (65.3+/-3.3 years of age, mean+/-SEM) with hyperkalemia (serum potassium >5.0 mEq/L) had measurement of their renin-aldosterone system. Nineteen patients (56%) had plasma renin activity (PRA) >1.5 ng/mL/h, which was not low, while 15 (44%) had PRA <1.5. Twelve of the 15 hyporeninemic hyperkalemic patients were studied to determine whether their renin-aldosterone system responded to 2 weeks of furosemide, 20 mg daily. Four were nonresponders: PRA averaged 0.3+/-0.1 ng/mL/h, and it did not increase with furosemide or respond to captopril before or after furosemide. Eight patients were responders: PRA averaged 0.6+/-0.2 ng/mL/h and increased with furosemide to 5.5+/-3.4 ng/mL/h. Captopril failed to increase PRA before furosemide, but PRA increased to 15.3+/-8.4 ng/mL/h after furosemide. Plasma aldosterone was low in both nonresponders and responders (3.5+/-1.2 ng/dL vs 5.8+/-2.5 ng/dL) and did not increase significantly with furosemide (4.3+/-1.7 ng/dL vs 8.7+/-2.5 ng/dL). Serum potassium did not fall and therefore did not limit the rise in aldosterone. Renin responders had greater body weight, were predominantly female (6/8 vs 2/4) and were more likely to have diabetes mellitus (7/8 vs 0/4). Plasma atrial natriuretic peptide (ANP) fell with furosemide in 8 of 8 responders and in 1 of the 2 nonresponders in whom it was measured. Neither group had suppressed plasma prorenin levels, indicating no suppression of renin gene expression. These results indicate that many hyperkalemic patients do not have suppressed PRA. Further, a majority of patients with suppressed PRA have high levels of ANP and can respond to diuretic therapy with a rise in PRA and a fall in ANP, suggesting physiologic suppression of the renin system by volume expansion. A minority of hyperkalemic patients with suppressed PRA had PRA that did not increase under these study conditions.

A case of bovine ketoacidosis in a lactating woman

A 36 year-old 5 weeks postpartum lactating woman presented to the emergency room with severe nausea and vomiting for 48 hours. The patient was found to be in non-diabetic ketoacidosis with a serum pH 6.9 and a HCO3 of <5mEq/L. This condition rapidly improved with the administration of intravenous dextrose and bicarbonate and with the cessation of breast feeding. The course and pathophysiology of the rarely described phenomenon of bovine ketosis in a human is discussed here.