Obstetric and long‐term kidney outcomes in renal transplant recipients: a 40‐yr single‐center study

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case?cohort study was performed identifying 83 pairs of pregnant and non‐pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre‐eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre‐pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non‐pregnant controls and a pregnancy was not associated with poorer 10‐yr transplant or 20‐yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long‐term transplant function.     

Readmissions related to antihypertensive medications used in chronic hemodialysis

Background: In hemodialysis, hypertension is treated by removing excess fluid and antihypertensive therapy. Commonly, the antihypertensives used to treat hypertension in earlier stages of kidney disease are continued as the patient progresses into end-stage renal disease and begins dialysis, without much evidence for benefit. Methods: This study is a single center, retrospective chart review that included hemodialysis patients admitted for congestive heart failure (CHF), fluid overload, or pulmonary edema as determined by ICD-9 code (428.x, 276.6, 518.4, 506.1). The primary objective was to determine if the number or class of antihypertensives used in the chronic hemodialysis population increased the number of readmissions related to CHF, fluid overload, or pulmonary edema. Patients were separated into two groups based on total number of antihypertensive medications, less than or equal to 2 medications for group 1 and greater than two medications for group 2. The primary endpoint was 30-day readmission for CHF, fluid overload, or pulmonary edema. Results: For the study period, 85 individual patient charts met inclusion criteria. Group 1 (n?=?44) experienced seven readmissions (16%) and group 2 (n?=?41) experienced eight readmissions (18%) (p?=?0.663). The most common antihypertensives at discharge were ACE inhibitors for group 1 (45%) and dihydropyridine calcium channel blockers for group 2 (66%). No difference in systolic blood pressures before, during and after hemodialysis was found between groups. Conclusions: Antihypertensive medications continue to play an important role in the hemodialysis population. This study suggests that drug class and quantity of antihypertensives do not alter readmission rate in the setting of fluid overload.     

Partial depletion of CD69low-expressing natural regulatory T cells with the anti-CD25 monoclonal antibody PC61

The role CD4(+) CD25(+) regulatory T cells (Treg) play in modulating the immune response has been investigated extensively over recent years. Much of the work to date has used the activation marker CD25 to define, enrich and deplete Treg. However, the identification of FoxP3 as a definitive marker of Treg has allowed us to study the effect of monoclonal antibodies against CD25 on regulatory T-cell populations. Recently, published data have indicated that Treg are inactivated, not depleted, through treatment with anti-CD25 monoclonal antibody. Using FoxP3-Green fluorescent protein reporter mice, we show that treatment with the CD25 MoAb PC61 depleted a subpopulation of Treg. The depleted Treg population expressed low levels of the CD69 marker, indicating an inactive phenotype. In addition, PC61 treatment altered the function of the remaining regulatory T-cell population, preventing their ability to modulate autoimmune diseases. Thus, our results have important implications with regard to interpreting experimental outcomes from in vivo anti-CD25 treatments.     

Analysis of the pentafecta learning curve for laparoscopic radical prostatectomy

Purpose

Laparoscopic radical prostatectomy (LRP) has a long learning curve; however, little is known about the pentafecta learning curve for LRP. We analysed the learning curve for a fellowship trained surgeon with regard to the pentafecta with up to 6-year follow-up.

Methods

A retrospective review was performed in 550 cases, by dividing these cases into 11 groups of 50 patients. Outcomes analysed were the following: (1) the pentafecta (complication rate, positive surgical margin (PSM) rate, continence, potency and biochemical recurrence); (2) operative time and blood loss; and (3) overall pentafecta attainment.

Results

The mean complication rate for the entire series was 9 %; this plateaued after 150 cases. The overall PSM rate for the series was 23.5 %, 16.3 % for pT2 and 40.5 % for pT3. PSM plateaued after 200 cases. Excluding the first 100 cases, the overall PSM rate for pT2 was 10.9 % and 37.8 % for pT3. The continence rate stabilised after approximately 250 cases. The rate of male sling/artificial urinary sphincter plateaued after 200 cases. The potency learning curve continues to improve after 250 cases of nerve-sparing (ns) endoscopic extraperitoneal radical prostatectomy (EERPE) as does the pentafecta learning curve which closely follows the pattern of the potency learning curve. The last group of nsEERPE achieved pentafecta in 63 %.

Conclusion

This study shows multiple learning curves: an initial for peri-operative outcomes, then stabilisation of oncologic outcomes and the final for stabilisation of functional outcomes. In this series over 250 cases were required to achieve the learning curve.     

Insulin-induced biphasic responses in rat mesenteric vascular bed: role of endothelin

The vasodilatory capacity of insulin has been widely reported, yet some investigators have not noted this effect. Because insulin has been shown to enhance endothelin release, we speculated that endothelin could be attenuating insulin-evoked vasodilation. We examined the effect of ex vivo insulin perfusion on vascular resistance by using the Sprague-Dawley rat mesenteric vascular bed. In methoxamine-preconstricted preparations, insulin (3.0 pmol/L to 10 nmol/L) evoked a concentration-dependent decrease in perfusion pressure (PP) with a maximal response of 42.0+/-9.2%, whereas continuous exposure to 10 nmol/L insulin induced a 51.8+/-3.5% relaxation. Further exposure to 10 nmol/L insulin resulted in the generation of endothelin and a subsequent loss of the vasodilatory response. Indomethacin had no effect on vascular responses. The vasodilatory response was significantly inhibited by nitric oxide synthase inhibition (20.5+/-4.2%; P<0.01) and calcium-activated potassium channel blockade (28.5+/-3.7%; P<0.05). Endothelial denudation attenuated the vasodilatory component (20.3+/-7.1%; P<0.01) and altered the biphasic pattern of the response. The decline in insulin-evoked vasodilation was significantly prevented by an endothelin-A antagonist (BQ123), an endothelin-B antagonist (BQ788), and nonselective endothelin blockade with both BQ123 and BQ788. These results demonstrate that the endothelium is intimately involved in regulating the vascular response to insulin. Insulin promotes the release of nitric oxide and endothelium-derived hyperpolarizing factor. During sustained exposure to higher concentrations, this vasodilatory effect is countered by the pathological generation of endothelin. Endothelin receptor blockade facilitates the maintenance of vasodilation despite high insulin concentrations.     

Molecular Genetic Analysis of the ABO Blood Group System: 2. cis-AB Alleles

We have determined the nucleotide sequence of the coding region in the last two coding exons of ABO genes from two cis -AB individuals (genotype cis -AB/O) with no consanguinity. In this region, cis -AB alleles from these 2 individuals were identical to one another while different from the A¹ allele by two nucleotide substitutions. Both of these nucleotide substitutions result in amino acid substitutions. The first substitution is identical to the one previously found in the A² allele. The other substitution is found at the fourth position of the four amino acid substitutions which discriminate A¹ and B transferases.