Jorge Diego

Outcomes of Kidney Transplantation in HIV-Infected Recipients

BACKGROUND The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood. METHODS We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy. RESULTS Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications. CONCLUSIONS In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

BACKGROUND Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this 2×2 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline. RESULTS Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet × time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC × time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet × LC × time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. CONCLUSION The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3-4 and normal serum phosphate levels.

Renal mucormycosis in the HIV patient

Mucormycosis is an increasingly recognized opportunistic infection. It usually affects patients with debilitating conditions such as cancer, diabetes mellitus, renal failure, and extensive burns. Mucor infection has also been described in human immunodeficiency virus (HIV) patients. The most common clinical presentations are the cerebral, cutaneous, and renal forms. We describe a unique case of bilateral renal mucormycosis presenting with renal failure in an HIV-infected patient. In the immunosuppressed host, a history of intravenous (IV) drug abuse associated with symptoms of pyelonephritis should alert the clinician to the possibility of mucor infection. Blood and urine culture are often negative. The diagnosis is made histologically in most cases. The treatment of HIV patients with mucormycosis and renal failure includes hemodialysis, nephrectomy, and intravenous amphotericin in addition to antiretroviral therapy. Bilateral renal involvement with Mucor carries a poor prognosis.

Does catheter insertion by nephrologists improve peritoneal dialysis utilization? A multicenter analysis.

In contrast to hemodialysis (HD), peritoneal dialysis (PD) remains an underutilized form of renal replacement therapy in the United States. Although a variety of factors have been deemed responsible, timely insertion of a PD catheter may also be a contributory factor. We conducted a multicenter analysis to examine whether the establishment of a program for PD catheter insertion by nephrologists has a positive impact on the growth in the number of patients using PD. Data for catheter insertion performed by nephrologists were collected from three centers. Any change in the prevalent PD population at each respective center was compared to the number of PD patients during the period having the traditional surgical approach. Nephrologists at the three centers used the peritoneoscopic technique and performed catheter insertion under local anesthesia. In center 1, the PD population remained stable at between 38 and 45 patients (approximately 16% of the total end‐stage renal disease [ESRD] population) from 1993 to 2001. Nephrologists initiated a program for PD catheter insertion in 2001. The number of PD patients has increased to 101 (32% of the ESRD population). In center 2, the PD population remained stable at between 70 and 78 patients (approximately 17%) between 1988 and 1990. Catheter insertion by interventional nephrologists began in 1991. The number of PD patients has increased to 125 (22%). In center 3, the PD population remained at 20–30 patients (approximately 18%) between 1988 and 1991. Catheter placement by nephrologists was initiated in 1991. The number of PD patients increased to 97 (27%). Catheter insertion by interventional nephrologists was suspended in 2001. The number of PD patients has gradually declined to 25 (6%). This study suggests that catheter insertion by the nephrologist can have a positive impact on the utilization of PD.

American Society of Diagnostic and Interventional Nephrology Section Editor: Stephen Ash: Does Catheter Insertion by Nephrologists Improve Peritoneal Dialysis Utilization? A Multicenter Analysis

In contrast to hemodialysis (HD), peritoneal dialysis (PD) remains an underutilized form of renal replacement therapy in the United States. Although a variety of factors have been deemed responsible, timely insertion of a PD catheter may also be a contributory factor. We conducted a multicenter analysis to examine whether the establishment of a program for PD catheter insertion by nephrologists has a positive impact on the growth in the number of patients using PD. Data for catheter insertion performed by nephrologists were collected from three centers. Any change in the prevalent PD population at each respective center was compared to the number of PD patients during the period having the traditional surgical approach. Nephrologists at the three centers used the peritoneoscopic technique and performed catheter insertion under local anesthesia. In center 1, the PD population remained stable at between 38 and 45 patients (approximately 16% of the total end‐stage renal disease [ESRD] population) from 1993 to 2001. Nephrologists initiated a program for PD catheter insertion in 2001. The number of PD patients has increased to 101 (32% of the ESRD population). In center 2, the PD population remained stable at between 70 and 78 patients (approximately 17%) between 1988 and 1990. Catheter insertion by interventional nephrologists began in 1991. The number of PD patients has increased to 125 (22%). In center 3, the PD population remained at 20–30 patients (approximately 18%) between 1988 and 1991. Catheter placement by nephrologists was initiated in 1991. The number of PD patients increased to 97 (27%). Catheter insertion by interventional nephrologists was suspended in 2001. The number of PD patients has gradually declined to 25 (6%). This study suggests that catheter insertion by the nephrologist can have a positive impact on the utilization of PD.

Treatment of hepatitis C infection in patients with renal disease

Hepatitis C virus infects 20-40% of the end-stage renal disease population, and has been associated with essential mixed cryoglobulinemia and several forms of immune-complex glomerulonephritis. Overall, treatment with interferon alpha has been disappointing, although certain situations may benefit from dosing regimens that differ in the amount of drug and duration of treatment from the conventional interferon doses currently recommended for non-renal patients.

Antineutrophil cytoplasmic antibodies (ANCA) and systemicvasculitis: update of assays, immunopathogenesis, controversies, and report of a novel de novo ANCA-associated vasculitis after kidney transplantation

Abstract Objectives: To characterize antineutrophil cytoplasmic antibodies (ANCA),their major autoantigens, disease associations, and pathophysiology in systemic vasculitides. To describe a patient with a novel de novo ANCA-associated vasculitis after kidney transplantation. Methods: We reviewed and compiled the literature on ANCA-related topicsand systemic vasculitis. Laboratory and clinical data from a cadaveric kidney transplant patient who developed necrotizing vasculitis involving glomerular capillaries, with crescent formation associated with P-ANCA and myeloperoxidase, were analyzed. Results: Large-scale multi-center testing of patient and normal sera by theEuropean ANCA Assay Standardization Project using immunofluorescence assays and enzyme immunoassays indicate the assays have good sensitivity and specificity, and diagnostic utility for ANCA-associated vasculitis. A few investigations covering basic and clinical research with ANCA remain controversial: whether endothelial cells do or do not express a 29-kd neutral serine protease termed proteinase-3 (PR-3), the target of ANCA in most individuals with Wegeners granulornatosis, and whether anti-myeloperoxidase (MPO) ANCAs recognize a restricted number of epitopes on MPO. This issue has relevance for using monoclonal antibodies to treat patients with vasculitis who have adverse effects from immunosuppressive drugs. The two allelic forms of FcγRlla (H131/R131) and the two of FcγRlllb (NA1/NA2) are discussed as possible inheritable genetic elements for vasculitic disorders and for signaling responses. Stimulatory and costimulatory molecules, and cytokine profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient described had a de novo ANCA associated small vessel vasculitis which developed after renal transplantation. Conclusions: There have been significant advances in the development ofsensitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA involves the constitutive FcγRs, ligands, and signaling responses to activate cytokine-primed neutrophils. This may lead to the generation of reactive oxygen intermediates, degranulation, and secretion of intracellular granule contents, and ultimately inflammation and vasculitis.

De novo ANCA-associated vasculitis occurring 14 years after kidney transplantation

A cadaveric kidney transplant recipient, with no history of a connective tissue disease, was admitted with malaise, arthralgias, diplopia, mild headache, and a painful left eye. The patient was on maintenance immunosuppression for 14 years with cyclosporine and methylprednisolone. Initial laboratory data indicated an elevated serum creatinine from baseline, 2+ proteinuria, and 50 to 100 red blood cells (RBCs)/high-power field (HPF) in the urine. Renal biopsy was consistent with necrotizing vasculitis involving glomerular capillaries, with crescent formation and an absence of immune complexes. Perinuclear antineutrophil cytoplasmic autoantibodies (P-ANCA) and anti-myeloperoxidase (MPO) were found to be elevated. To the best of our knowledge, this is the first reported case of an ANCA-associated small vessel vasculitis (SVV) developing in a renal transplant recipient without history of connective tissue disease.

Comparison of Mortality of ESRD Patients with Lupus by Initial Dialysis Modality

BACKGROUND AND OBJECTIVES Little is known regarding whether mortality among ESRD patients with SLE differs between those initiating with peritoneal dialysis (PD) versus hemodialysis (HD). This study compared the mortality risk of ESRD patients with SLE initiating with PD versus HD after matching their baseline sociodemographic and clinical factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Of 11,023 ESRD patients with SLE initiating dialysis with PD or HD between 1995 and 2006 with complete records in the US Renal Data System, 1352 pairs were matched on 13 predictors utilizing a predicted probability of group membership into the PD group using propensity score matching. The primary outcome was overall mortality. Secondary outcomes were cardiovascular-related and infection-related mortality. Outcomes were compared between groups with survival statistics. The period of observation ended on December 31, 2009. The median follow-up was 3 years. RESULTS Matched pairs were predominantly women (86%) with a median age of 39 years. Matched pairs had a balance (P ≥ 0.05) of all baseline factors. Matched pairs had a similar risk of overall mortality (hazard ratio, 0.96 [95% confidence interval, 0.82 to 1.13]; mortality, 21.4% [290 to 1352] versus 22.5% [304 to 1352] for PD versus HD) within the first 3 years of observation. Matched pairs also had similar cardiovascular-related mortality (10.5% versus 9.5% for PD versus HD) and infection-related mortality (3% versus 4.4% for PD versus HD). CONCLUSIONS In ESRD patients with SLE, the mortality was similar among those initiating with PD versus HD after predictors were matched between groups.

Factors that influence serum hyaluronan levels in hemodialysis patients.

Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.