Translating operational research to the medical community: using "guiding measurements" to improve the quality of healthcare delivery.

Despite the ubiquity problems with pay-for-performance and other quality improvement initiatives, there is little in the way of objective evidence that these efforts have improved the quality of care. In part, it may be because the measurements selected are used to "grade" instead of guide improvement efforts. We propose using operational research methods that include how to develop "guiding measurements" to improve care. We show that use of this type of guiding measurements can lead to improved patient understanding, throughput, and satisfaction in a pediatric nephrology ambulatory care clinic, and may have wider applications across the continuum of care.

Chronic kidney disease in the VACTERL association: clinical course and outcome.

Approximately 60% of VACTERL (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with atresia, renal defects/radial limb dysplasia) patients have renal anomalies that can be associated with chronic kidney disease (CKD). With improved medical care, a large proportion of these patients survive into adulthood. Longitudinal follow-up data regarding the management of kidney disease in these children is lacking. Twelve VACTERL patients with CKD stage 2-5 and 12 age-matched controls with similar urologic anomalies and CKD [mean follow-up period 15.0 +/- 1.4 (SE) and 11.9 +/- 2.1 years, respectively] were identified in a single center. Eight VACTERL patients progressed to end-stage renal disease (ESRD) compared to four controls (66.7 vs. 33.3%, respectively). Six VACTERL patients were dialyzed pre-transplant. Of the four patients on peritoneal dialysis (PD), three had to be switched to hemodialysis due to complications, whereas two of the three controls on PD did not experience significant problems. Seven VACTERL patients underwent renal transplantation compared to four controls. Mean creatinine clearance 2 years post-transplant was 65.8 +/- 6.3 in VACTERL patients vs. 87.8 +/- 7.1 ml/min per 1.73 m(2) in controls (p = 0.03). VACTERL patients had a significantly lower mean height standard deviation score than the controls (-2.34 +/- 0.41 vs. -1.27 +/- 0.24, respectively; p < 0.05). Based on these results, VACTERL patients with CKD develop ESRD more frequently, experience more complications with dialysis, may have a poorer transplant outcome, and have more severe growth failure than controls.

Development and differentiation of the ureteric bud into the ureter in the absence of a kidney collecting system.

Six1-/- mice were found to have apparently normal ureters in the absence of a kidney, suggesting that the growth and development of the unbranched ureter is largely independent of the more proximal portions of the UB which differentiates into the highly branched renal collecting system. Culture of isolated urinary tracts (from normal and mutant mice) on Transwell filters was employed to study the morphogenesis of this portion of the urogenital system. Examination of the ureters revealed the presence of a multi-cell layered tubule with a lumen lined by cells expressing uroplakin (a protein exclusively expressed in the epithelium of the lower urinary tract). Cultured ureters of both the wild-type and Six1 mutant become contractile and undergo peristalsis, an activity preceded by the expression of alpha-smooth muscle actin (alphaSMA). Treatment with a number of inhibitors of signaling molecules revealed that inhibition of PI3 kinase dissociates the developmental expression of alphaSMA from ureter growth and elongation. Epidermal growth factor also perturbed smooth muscle differentiation in culture. Moreover, the peristalsis of the ureter in the absence of the kidney in the Six1-/- mouse indicates that the development of this clinically important function of ureter (peristaltic movement of urine) is not dependent on fluid flow through the ureter. In keeping with this, isolated ureters cultured in the absence of surrounding tissues elongate, differentiate and undergo peristalsis when cultured on a filter and undergo branching morphogenesis when cultured in 3-dimensional extracellular matrix gels in the presence of a conditioned medium derived from a metanephric mesenchyme (MM) cell line. In addition, ureters of Six1-/- urinary tracts (i.e., lacking a kidney) displayed budding structures from their proximal ends when cultured in the presence of GDNF and FGFs reminiscent of UB budding from the wolffian duct. Taken together with the above data, this indicates that, although the distal ureter (at least early in its development) retains some of the characteristics of the more proximal UB, the growth and differentiation (i.e., development of smooth muscle actin, peristalsis and uroplakin expression) of the distal non-branching ureter are inherent properties of this portion of the UB, occurring independently of detectable influences of either the undifferentiated MM (unlike the upper portion of the ureteric bud) or more differentiated metanephric kidney. Thus, the developing distal ureter appears to be a unique anatomical structure which should no longer be considered as simply the non-branching portion of the ureteric bud. In future studies, the ability to independently analyze and study the portion of the UB that becomes the renal collecting system and that which becomes the ureter should facilitate distinguishing the developmental nephrome (renal ontogenome) from the ureterome.

Mycobacterial peritonitis in pediatric peritoneal dialysis patients.

Peritonitis is the most common complication and the leading cause of death in pediatric peritoneal dialysis (PD) patients. According to the most recent data available from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), approximately 25% of pediatric PD patients who die succumb to infection. There are no reported cases of Mycobacterium tuberculosis (MTB) or Mycobacterium avium-intracellulare peritonitis in the NAPRTCS registry. With an increasing incidence of MTB worldwide and the impairment of cellular immunity in chronic renal failure patients, it is not surprising that mycobacterium peritonitis can occur in PD patients. We report two pediatric PD patients with mycobacterial peritoneal infection diagnosed over an 11-year period at our institution. One patient presented with a malfunctioning Tenckhoff catheter and again 3 years later with hyponatremia and ascites. The other presented with recurrent culture-negative peritonitis. These cases illustrate the importance of more extensive evaluation of PD complications, to include evaluation for mycobacterium with special media or peritoneal biopsy, in the above clinical settings if the routine work-up is unrevealing.

Toward an etiological classification of developmental disorders of the kidney and upper urinary tract.

Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. There are a large number of developmental disorders and syndromes that affect the kidney and upper urinary tract. These have generally been classified according to morphological criteria established decades ago. Although these classifications have been useful, they are incomplete, including some developmental disorders while excluding others. Here, basic cellular and molecular biology studies of kidney and upper urinary tract development in both rodents and humans are utilized to suggest the basis of a new etiologic, if still tentative, classification scheme. This classification may help to identify candidate genes for human diseases by correlating morphology with pathogenetic mechanisms.