Great expectations for the World Health Organization: a Framework Convention on Global Health to achieve universal health coverage.

Establishing a reform agenda for the World Health Organization (WHO) requires understanding its role within the wider global health system and the purposes of that wider global health system. In this paper, the focus is on one particular purpose: achieving universal health coverage (UHC). The intention is to describe why achieving UHC requires something like a Framework Convention on Global Health (FCGH) that have been proposed elsewhere,(1) why WHO is in a unique position to usher in an FCGH, and what specific reforms would help enable WHO to assume this role.

Ethical dilemmas in patient selection for a new kidney transplant program in Guyana, South America.

INTRODUCTION: We describe ethical/moral issues in patient selection in a new living donor kidney transplant program in Guyana, South America. CASE REPORTS: Over 3 years, we screened 450 patients with chronic kidney disease among which 70 were suitable for kidney transplantation. There were five patients whose evaluations raised possible ethical dilemmas: one had nonadherence to dialysis; two of Guyanese origin living abroad wished to have the transplant performed in Guyana; a minor wished to donate to her mother; and another subject was considering commercialization of the transplant process. RESULTS: Since inception of the renal replacement program in 2008, we have completed 13 living kidney transplantations, 17 peritoneal dialysis placements, and 20 vascular access procedures. In the five patients wherein faced ethical dilemmas, three were rejected for consideration despite having living donors: one was nonadherent, the second excluded due to an attempt to commercialize the process, and the third, a minor who wished to donate to the mother. The other two patients were considered Guyanese ex-patriots acceptable for the program. DISCUSSION: The consequence of kidney failure in Guyana prior to introduction of renal replacement therapy was a virtual death sentence. These cases illustrate ethical dilemmas serving to throw into stark relief the implications of decisions made in a developing country versus those in a developing country.

The effects of tadalafil on cold-induced vasoconstriction in patients with Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a disorder characterized by episodic periods of vasoconstriction typically provoked by exposure to cold. Phosphodiesterase 5 (PDE5) inhibitors may improve digital blood flow and clinical symptoms in patients with RP, but the mechanisms are unknown. We examined the hypothesis that a PDE5 inhibitor, tadalafil, attenuates cold-induced vasoconstriction. Additionally, we examined whether tadalafil reduced vascular dysfunction following ischemia, thus altering the response to repeated cooling. We conducted a double-blind, placebo-controlled crossover study in 20 subjects with RP on two separate study days, when subjects received either placebo or tadalafil (10 mg). Digital blood flow (flux) was measured by laser Doppler flowmetry at rest and during two graduated local heat and cold exposure cycles. Temperature-response curves were evaluated by E(max) (maximal flux during heating), E(min) (minimal flux during cooling), and ET(50) and ET(90) (the local temperature at which flux decreased by 50% and 90% of E(max)-E(min), respectively). Tadalafil did not increase baseline flux (81.0+/-73.0 vs 91.3+/-114.0 arbitrary unit (AU), P=0.57), E(max) (280.0+/-107.6 vs 279.5+/-119.8 AU, P=0.94), ET(50) (25.4+/-4.4 vs 26.6+/-5.7 degrees C, P=0.62), or ET(90) (21.2+/-3.9 vs 21.8+/-5.0 degrees C, P=0.78), (cycle 1 values presented). There were no differences between cycles on either study day. In conclusion, in patients with RP, single-dose tadalafil does not increase digital blood flow at baseline or in response to heating, nor does it attenuate cold-induced vasoconstriction. Furthermore, it does not precondition the endothelium to resist a second cooling challenge. The clinical benefit in patients with RP treated with PDE5 inhibitors probably involves mechanisms other than acute inhibition of cold-induced vasoconstriction.

End-stage renal disease in diabetic persons: is the pandemic subsiding?

Analysis of data compiled by the United States Renal Data System and the National Health Interview Survey as reported in the Centers for Disease Control and Prevention's Weekly Morbidity and Mortality Report indicates that between 1990 and 2002, there has been a sharp decline in incidence rate of the number of persons with diabetes who develop end-stage renal disease. Although it is comforting to practitioners to attribute this improvement to a widely advocated regimen of renoprotection, consisting of careful regulation of hypertensive blood pressure, improved glycemic control, and lifestyle modification, evidence for this causal relationship is appearing only now. There is need to clarify the source of this epidemiologic change that will lessen the projected burden on medical and socioeconomic resources in the immediate future.

Payment for donor kidneys: pros and cons.

Continuous growth of the end stage renal disease population treated by dialysis, outpaces deceased donor kidneys available, lengthens the waiting time for a deceased donor transplant. As estimated by the United States Department of Health & Human Services: '17 people die each day waiting for transplants that can't take place because of the shortage of donated organs.' Strategies to expand the donor pool--public relations campaigns and Drivers' license designation--have been mainly unsuccessful. Although illegal in most nations, and viewed as unethical by professional medical organizations, the voluntary sale of purchased donor kidneys now accounts for thousands of black market transplants. The case for legalizing kidney purchase hinges on the key premise that individuals are entitled to control of their body parts even to the point of inducing risk of life. One approach to expanding the pool of kidney donors is to legalize payment of a fair market price of about 40,000 dollars to donors. Establishing a federal agency to manage marketing and purchase of donor kidneys in collaboration with the United Network for Organ Sharing might be financially self-sustaining as reduction in costs of dialysis balances the expense of payment to donors.

Improved survival in HIV-infected African-Americans with ESRD.

AIMS: To determine if there has been improvement in survival of HIV-infected patients with end-stage renal failure subsequent to widespread use of highly active antiretroviral therapy. METHODS: The United States Renal Data System is a national data system funded by the National Institute of Diabetes and Digestive and Kidney Disease with the Centers for Medicare and Medicaid. Using the United States Renal Data System Standard Analysis Files, we analyzed all African-American end-stage renal failure patients in the United States from 1990-2001. We compared survival rates for patients with HIV disease, sickle cell anemia, diabetes, and all other diagnoses for the time periods 1990-1994 and 1995-2001. The main outcome measure was one- and five-year survival in each cohort. RESULTS: One-year survival of African-American patients with end-stage renal disease and HIV increased from 46.6% during 1990-1994 to 65.1% during 1995-2001 (odds ratio 2.139). One-year survival decreased in the sickle cell group (odds ratio 0.595) and decreased slightly in the diabetic group (odds ratio 0.927) and all others (odds ratio 0.941). Five-year survival in the HIV group increased from 13.3% in 1990-1995 to 30.4% in 1995-2001 (odds ratio 2.847). There was no corresponding increase in survival for the sickle cell group (odds ratio 0.987), the diabetic group (odds ratio 1.06), or all others (odds ratio 1.137). CONCLUSIONS: We conclude that survival in African-American end-stage renal disease patients and HIV infection has substantially improved subsequent to introduction of highly active antiretroviral therapy. Our data support aggressive multi-drug treatment of end-stage renal failure patients with HIV infection.

Effects of erythropoietin and aminoguanidine on red blood cell deformability in diabetic azotemic and uremic patients.

Impaired red blood cell-deformability (RBC-df) is noted in patients with diabetes and may play a role in the pathogenesis of microvasculopathy and nephropathy. We report the effects of erythropoietin (EPO) alone and combined with aminoguanidine (AG) for 1 year on RBC-df in predialysis patients (P-DPs) with renal insufficiency and in end-stage renal disease (ESRD) patients on maintenance hemodialysis (DPs). Nine P-DPs who received EPO 50 U/kg by subcutaneous injection 3 times per week are compared with 5 P-DPs treated without EPO (mean serum creatinine 4.1 +/- 0.1 versus 4.2 +/- 0.6 mg/dL, respectively). Twelve DPs (Kt/V = 1.5 +/- 0.1) were studied. Six DPs received AG 200 mg/every other day by mouth and EPO 50 U/kg by intravenous (IV) injection, and 6 DPs received EPO (50 U/kg) and placebo and served as control. RBC-df improved significantly in 9 P-DPs treated with EPO at 6 months (from 2.7 +/- 0.1 to 1.6 +/- 0.2, P = 0.005). This positive effect was sustained at 12 months (P = 0.005); there was no change in RBC-df in P-DPs receiving usual care without EPO. RBC-df improved significantly and progressively at 6 and 12 months in DPs treated with EPO and AG (from 2.2 +/- 0.2 to 1.8 +/- 0.2; P = 0.01; 1.2 +/- 0.1; P = 0.001, respectively); there was limited improvement in RBC-df in DPs treated with EPO and placebo. We conclude that EPO treatment significantly improved RBC-df in diabetic P-DPs, but EPO alone has no significant effect on RBC-df after 12 months in diabetic DPs. The combination of EPO and AG restores RBC-df to near-normal levels in diabetic DPs. We speculate that the effect of EPO on RBC-df seen in P-DPs and DPs is related to increased synthesis and influx of new and younger RBCs. AG may confer protection of RBCs in DPs by blocking advanced glycosylated end-product (AGE) formation.

Gender modulates responsiveness to recombinant erythropoietin.

Several investigators reported that individuals with diabetes and women on hemodialysis treated with recombinant erythropoietin (EPO) attained lower hematocrits than individuals without diabetes and men. It is unclear whether these observed differences in achieved hematocrits are caused by inherent biological differences in responsiveness to EPO or undetected differences in modifiable factors that affect response to EPO. Also potentially modulating response to EPO is diurnal variation in the bioavailability of serum iron. To address these issues, we studied 309 patients undergoing hemodialysis in two large facilities in New York City. Retrospective data collected monthly for 3 months included patients' hematocrit, dose of EPO, urea reduction ratio (URR), total amount of intravenous iron administered, serum albumin concentration, transferrin saturation, and time of day patient underwent dialysis. The 309 study subjects (165 women, 144 men) included 207 blacks (67%), 74 Hispanics (24%), 23 whites (7%), and 5 Asians (2%) with a mean age of 55.4 +/- 15.6 (SD) years. Despite a greater mean URR (74% +/- 6.4% versus 71% +/- 6%; P = 0.001) and a 39% greater dose of EPO (97 +/- 65 versus 59 +/- 53 U/kg; P = 0.001), women (36% +/- 3.5%) had hematocrits equivalent with men (36.5% +/- 3.7%; P = not significant [NS]). There was no difference in the amount of intravenous iron administered to men (375 +/- 389 mg) and women (377 +/- 413 mg; P = NS). Diabetes mellitus (P = 0.48) did not significantly affect the odds of attaining a hematocrit greater than 33% after adjustment for URR, EPO dose, and amount of intravenous iron administered. The time of day a patient underwent dialysis (P = 0.93) had no effect on their response to EPO. We conclude that gender, but not diabetes status or time of dialysis, modulates response to EPO in hemodialysis patients.

A new method to control ultrafiltration in conventional continuous renal replacement therapy.

Conventional continuous arteriovenous hemofiltration/hemodialysis (CAVH/D) and slow continuous ultrafiltration (SCUF) are types of continuous renal replacement therapy (CRRT) in which the ultrafiltrate (UF) volume is controlled imprecisely with a UF clamp, which is labor intensive, demanding frequent adjustment to preclude excessive fluid removal. We devised a simple method for precise control of the UF volume. Seven CRRTs in the form of CAVH, CAVHD, and SCUF were performed in four patients with massive edema. A standard circuit was created in each case using blood tubing sets and an HF 400 hemofilter obtained from MinnTech. Standard intravenous infusion tubing connected to an infusion pump (IMED, Gemini PC-2 volumetric pump/controller) with its proximal end inserted into the dialysate port at the venous end of the hemofilter, and the distal end draining into a plastic bag, was used to control the UF rate. Dialysis was added to the circuit using another pump connected to the dialysate port at the arterial end of the hemofilter. Treatment time ranged from 27 to 78 hours. Target fluid removal was achieved in all treatments, and the net UF rate required only once daily adjustment for total fluid intake. Mean time to reporting a problem by the intensive care nurse was 30 hours (range, 25-30 hours), and mean time to filter clotting was 38 hours (range, 27-40 hours). This set-up is less labor intensive, more cost effective, and is applicable in areas lacking automated machines. Future development of tubing for UF designed as above may further reduce cost.

Funding ESRD care through charity: the paradigm of the National Kidney Foundation of Singapore.

Given the prohibitive costs of end-stage renal disease (ESRD) care for certain countries and the increasing incidence of ESRD worldwide, alternative methods of funding dialysis care are increasingly necessary. We describe the paradigm of the National Kidney Foundation of Singapore (NKF-S), the provider of subsidized dialysis care and comprehensive rehabilitative services to approximately 60% of all ESRD patients in the country, whose activities are funded entirely by charitable public donations. Unique to the NKF-S model are the considerations of the donor as an "investor" in the health care of NKF-S dialysis patients, the personal responsibility of the dialysis patient as a recipient of this "investment" to play an active role in achieving good clinical and rehabilitative outcomes, and the fostering of community-based support systems to facilitate patient rehabilitation such as partnerships with employers willing to employ dialysis patients. The success of the system is shown by its clinical outcomes, which approximate those observed in the United States. We believe that several aspects of the NKF-S model for ESRD care may be implemented in other communities, particularly in countries that have yet to develop financially and clinically mature dialysis programs.

Common iliac artery stenosis presenting as renal allograft dysfunction in two diabetic recipients.

BACKGROUND: Suprarenal common iliac artery stenosis is an uncommon but reversible cause of allograft dysfunction in renal transplant recipients. METHOD: We describe two diabetic renal transplant recipients with worsening hypertension, edema, and azotemia. Magnetic resonance angiography (MRA) demonstrated tight stenoses in the common iliac artery proximal to the allograft anastomosis site with patent renal transplant artery in both cases. These findings were later confirmed with carbon dioxide angiography. RESULTS: No acute rejection was noted on renal biopsy in either case. Placement of percutaneous iliac artery Wallstents resulted in decrease of serum creatinine from 6.5 to 2.0 mg/dl and 1.7 to 1.0 mg/dl within 2 and 4 weeks, respectively. CONCLUSION: Common iliac artery stenosis should be suspected in renal transplant recipients presenting with worsening hypertension, edema and azotemia. MRA for screening followed by carbon dioxide angiography and placement of intravascular stents for focal vascular obstructive lesions reverses allograft dysfunction.

Preparing the azotemic diabetic patient for surgery.

Azotemic diabetic patients have more risk of complications during or after surgery than those without diabetes and azotemia. These complications include infection, excessive bleeding, cardiovascular events, and electrolyte imbalance. The appropriate preoperative evaluation, measures to be taken to avoid the complications, and how to adequately manage blood sugar during surgery is discussed.

Must we treat noncompliant ESRD patients?

Coping with the stress induced by ESRD patient noncompliance is a time consuming, nonproductive, demoralizing undertaking that is unavoidable. An orderly, non-confrontational approach encompassing measures to protect mentally incompetent and unaware patients as well as those too sick to comprehend and consent to therapy (dialysis) is provided. Individual practitioners should utilize all available resources including patient relatives and friends, collaborating psychiatrists, and institutional risk-management officers to assist in devising the best resolution to what may escalate into an onslaught against the renal care team. No single solution is applicable to the myriad variables that may impinge on a specific patient's seemingly apathetic or hateful behavior underlying noncompliance.

Adequacy of dialysis and differences in hematocrit among dialysis facilities.

Despite the clearly established relationship between adequacy of dialysis and response to erythropoietin, recent guidelines on anemia management in end-stage renal disease (ESRD) omit mention of dialysis adequacy while advocating the use of large amounts of intravenous iron. To determine the relative effects of adequacy of dialysis and intravenous iron on hematocrit, we studied 309 hemodialysis patients and analyzed data from 141 hemodialysis facilities in New York State (ESRD Network 2), as well as data from all 18 ESRD Networks in the United States, for the last quarter of 1997. Among the 309 subjects, mean hematocrit differed between quartiles of urea reduction ratio (URR; F statistic = 4; P: = 0.008). Patients with URRs greater than 70% were 2.6 times more likely to have hematocrits greater than 33% (odds ratio, 2.6; 95% confidence interval [CI], 1.3 to 5.3; P: = 0.009) after adjustment for other factors. Mean dialysis facility (n = 141) hematocrits correlated directly with mean URRs (r = 0.32; P: = 0.001). Facilities with a mean URR greater than 70% were three times more likely to have a mean hematocrit greater than 33% (odds ratio, 3; 95% CI, 1.2 to 7.5; P: = 0.02). The percentage of patients in each of the 18 ESRD Networks with hematocrits of 33% or greater correlated inversely with the percentage of patients administered intravenous iron (r = -0.53; P: = 0.03) after adjustment for dose of erythropoietin. We conclude that adequacy of dialysis predicts the response to erythropoietin at both patient and dialysis facility levels. Patients with low hematocrits primarily because of inadequate dialysis may inappropriately be administered excess intravenous iron intended as a corrective measure.