Training the next generation's nephrology workforce.

The subspecialty of nephrology faces several critical challenges, including declining interest among medical students and internal medicine residents and worrisome declines in the number of applicants for nephrology fellowships. There is an urgent need to more clearly define the subspecialty and its scope of practice, reinvigorate meaningful research training and activities among trainees, and ensure that fellows who complete training and enter the practice of nephrology are experts in the broad scope of nephrology. This need requires a critical look at fellowship training programs and training requirements. A new workforce analysis is also needed that is not focused on primarily meeting estimated future clinical needs but rather, ensuring that there is alignment of supply and demand for nephrology trainees, which will ensure that those entering nephrology fellowships are highly qualified and capable of becoming outstanding nephrologists and that there are desirable employment opportunities for them when they complete their training.

Critical and honest conversations: the evidence behind the "Choosing Wisely" campaign recommendations by the American Society of Nephrology.

Estimates suggest that one third of United States health care spending results from overuse or misuse of tests, procedures, and therapies. The American Board of Internal Medicine Foundation, in partnership with Consumer Reports, initiated the "Choosing Wisely" campaign to identify areas in patient care and resource use most open to improvement. Nine subspecialty organizations joined the campaign; each organization identified five tests, procedures, or therapies that are overused, are misused, or could potentially lead to harm or unnecessary health care spending. Each of the American Society of Nephrology's (ASN's) 10 advisory groups submitted recommendations for inclusion. The ASN Quality and Patient Safety Task Force selected five recommendations based on relevance and importance to individuals with kidney disease.Recommendations selected were: (1) Do not perform routine cancer screening for dialysis patients with limited life expectancies without signs or symptoms; (2) do not administer erythropoiesis-stimulating agents to CKD patients with hemoglobin levels ≥10 g/dl without symptoms of anemia; (3) avoid nonsteroidal anti-inflammatory drugs in individuals with hypertension, heart failure, or CKD of all causes, including diabetes; (4) do not place peripherally inserted central catheters in stage 3-5 CKD patients without consulting nephrology; (5) do not initiate chronic dialysis without ensuring a shared decision-making process between patients, their families, and their physicians.These five recommendations and supporting evidence give providers information to facilitate prudent care decisions and empower patients to actively participate in critical, honest conversations about their care, potentially reducing unnecessary health care spending and preventing harm.

A behavioral and systems view of professionalism.

Professionalism may not be sufficient to drive the profound and far-reaching changes needed in the US health care system, but without it, the health care enterprise is lost. Formal statements defining professionalism have been abstract and principle based, without a clear description of what professional behaviors look like in practice. This article proposes a behavioral and systems view of professionalism that provides a practical approach for physicians and the organizations in which they work. A more behaviorally oriented definition makes the pursuit of professionalism in daily practice more accessible and attainable. Professionalism needs to evolve from being conceptualized as an innate character trait or virtue to sophisticated competencies that can and must be taught and refined over a lifetime of practice. Furthermore, professional behaviors are profoundly influenced by the organizational and environmental context of contemporary medical practice, and these external forces need to be harnessed to support--not inhibit--professionalism in practice. This perspective on professionalism provides an opportunity to improve the delivery of health care through education and system-level reform.

Incident chronic kidney disease and the rate of kidney function decline in individuals with hypertension.

BACKGROUND: Little is known about the decline of kidney function in patients with normal kidney function at baseline. Our objectives were to (i) identify predictors of incident chronic kidney disease (CKD) and (ii) to estimate rate of decline in kidney function. METHODS: The study used a retrospective cohort of adult patients in a hypertension registry in an inner-city health care delivery system in Denver, Colorado. The primary outcome was development of incident CKD, and the secondary outcome was rate of change of estimated glomerular filtration rate (eGFR) over time. RESULTS: After a mean follow-up of 45 months, 429 (4.1%) of 10 420 patients with hypertension developed CKD. In multivariate models, factors that independently predicted incident CKD were baseline age [odds ratio (OR) 1.13 per 10 years, 95% confidence interval (CI), 1.03-1.24], baseline eGFR (OR 0.69 per 10 units, 95% CI 0.65-0.73), diabetes (OR 3.66, 95% CI 2.97-4.51) and vascular disease (OR 1.67, 95% CI 1.32-2.10). We found no independent association between age, gender or race/ethnicity and eGFR slope. In patients who did not have diabetes or vascular disease, eGFR declined at 1.5 mL/min/1.73 m(2) per year. Diabetes at baseline was associated with an additional decline of 1.38 mL/min/1.73 m(2). CONCLUSIONS: Diabetes was the strongest predictor of both incident CKD as well as eGFR slope. Rates of incident CKD or in decline of kidney function did not differ by race or ethnicity in this cohort.

Are two better than one? Angiotensin-converting enzyme inhibitors plus angiotensin receptor blockers for reducing blood pressure and proteinuria in kidney disease.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers each reduce proteinuria and blood pressure. Several studies have compared the antiproteinuric and antihypertensive effects of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with those of therapy with either drug class alone. This article reviews those trials as well as evidence suggesting a mechanism for the benefits observed with combination therapy.

Indications for renal arteriography at the time of coronary arteriography: a science advisory from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease.

Atherosclerotic renal artery stenosis is commonly present in patients with clinically manifest atherosclerosis in other vascular beds and is independently associated with increased cardiovascular morbidity and mortality. Screening tests such as renal angiography should be selectively applied to patients at high risk for renal artery stenosis who are potential candidates for revascularization. This multispecialty consensus document describes the rationale for patient selection for screening renal angiography at the time of cardiac catheterization.

Evidence for involvement of 3'-untranslated region in determining angiotensin II receptor coupling specificity to G-protein.

The mRNA 3'-untranslated region (3'-UTR) of many genes has been identified as an important regulator of the mRNA transcript itself as well as the translated product. Previously, we demonstrated that Chinese-hamster ovary-K1 cells stably expressing angiotensin receptor subtypes (AT(1A)) with and without 3'-UTR differed in AT(1A) mRNA content and its coupling with intracellular signalling pathways. Moreover, RNA mobility-shift assay and UV cross-linking studies using the AT(1A) 3'-UTR probe identified a major mRNA-binding protein complex of 55 kDa in Chinese-hamster ovary-K1 cells. In the present study, we have determined the functional significance of the native AT(1A) receptor 3'-UTR in rat liver epithelial (WB) cell lines by co-expressing the AT(1A) 3'-UTR sequence 'decoy' to compete with the native receptor 3'-UTR for its mRNA-binding proteins. PCR analysis using specific primers for the AT(1A) receptor and [(125)I]angiotensin II (AngII)-binding studies demonstrated the expression of the native AT(1A) receptors in WB (B(max)=2.7 pmol/mg of protein, K(d)=0.56 nM). Northern-blot analysis showed a significant increase in native receptor mRNA expression in 3'-UTR decoy-expressing cells, confirming the role of 3'-UTR in mRNA destabilization. Compared with vehicle control, AngII induced DNA and protein synthesis in wild-type WB as measured by [(3)H]thymidine and [(3)H]leucine incorporation respectively. Activation of [(3)H]thymidine and [(3)H]leucine correlated with a significant increase in cell number (cellular hyperplasia). In these cells, AngII stimulated GTPase activity by AT(1) receptor coupling with G-protein alpha i. We also delineated that functional coupling of AT(1A) receptor with G-protein alpha i is an essential mechanism for AngII-mediated cellular hyperplasia in WB by specifically blocking G-protein alpha i activation. In contrast with wild-type cells, stable expression of the 3'-UTR 'decoy' produced AngII-stimulated protein synthesis and cellular hypertrophy as demonstrated by a significant increase in [(3)H]leucine incorporation and no increase in [(3)H]thymidine incorporation and cell number. Furthermore, [(125)I]AngII cross-linking and immunoprecipitation studies using specific G-protein alpha antibodies showed that in wild-type cells, the AT(1A) receptor coupled with G-protein alpha i, whereas in cells expressing the 3'-UTR 'decoy', the AT(1A) receptor coupled with G-protein alpha q. These findings indicate that the 3'-UTR-mediated changes in receptor function may be mediated in part by a switch from G-protein alpha i to G-protein alpha q coupling of the receptor. Our results suggest that the 3'-UTR-mediated post-transcriptional modification of the AT(1A) receptor is critical for regulating tissue-specific receptor functions.

Role of internalization in AT(1A) receptor function in proximal tubule epithelium.

Angiotensin II (ANG II), acting through angiotensin type I (AT(1)) receptors on apical and basolateral surfaces of proximal tubule epithelial cells, increases sodium reabsorption in proximal tubules. Apical and basolateral receptors internalize after exposure to ANG II, but the role of internalization in receptor signaling and transport is not well defined. To determine the role of receptor internalization in ANG II-mediated receptor signaling and sodium transport, we stably expressed full-length and truncated AT(1A) receptors in opossum kidney cells. After stimulation with ANG II, wild-type receptors on apical and basolateral surfaces rapidly internalized, inhibited adenylate cyclase, and increased transcellular sodium transport. Truncation of the cytoplasmic tail of the AT(1A) receptor (TL314) resulted in receptors that were expressed on apical and basolateral surfaces but did not internalize, inhibit adenylate cyclase, or increase sodium transport. Because the cytoplasmic tail contains putative G protein coupling sites, mutant receptors that leave G protein interaction sites intact were designed. Cells expressing the truncation (TK333) or deletion (Del 315-329) also failed to internalize. When ANG II was added to basolateral surfaces of TK333 or Del 315-329, adenylate cyclase activity was inhibited and sodium transport was increased. In contrast, apical addition of ANG II was not associated with decreases in adenylate cyclase or increases in sodium transport. In conclusion, internalization pathways are important for AT(1A) receptor function in polarized proximal tubule epithelial cells. Apical AT(1A) receptors internalize before they interact with G proteins and signal cAMP. In contrast, basolateral AT(1A) receptors interact with G proteins and signal cAMP without internalizing.