Keith C. Norris

Persons with chronic kidney disease (CKD) exhibit a disproportionate burden of elevated blood pressure (BP) with a high prevalence of premature end-stage renal disease and cardiovascular events. Results of recent randomized controlled clinical trials suggest that most patients with reduced estimated glomerular filtration rate (eGFR) and hypertension experience optimal clinical outcomes when SBP is less than 140 mmHg and DBP is less than 90 mmHg. The benefit of additional lowering of SBP to less than 130 mmHg and DBP to less than 80 mmHg remains controversial, and appears to be of most benefit to the subset of CKD patients with proteinuria (>300 mg/day). The combination of a diuretic and an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) has demonstrated particular promise in patients with reduced eGFR and proteinuria. A practical approach in clinical practice for the treatment of elevated BP in persons with CKD is to achieve a BP less than 140/90 mmHg with a combination of diuretic and an ARB or ACEI. Consideration for a lower BP goal and other therapeutic and nontherapeutic interventions can be made based on the cause of CKD, presence of proteinuria, or other coexisting medical conditions.

Background: Cell-cell communication occurs via a variety of mechanisms, including long distances (hormonal), short distances (paracrine and synaptic) or direct coupling via gap junctions, antigen presentation, or ligand-receptor interactions. We evaluated the possibility of neuro-hormonal independent, non-diffusible, physically disconnected pathways for cell-cell communication using dorsal root ganglion (DRG) neurons. Methods: We assessed intracellular calcium ([Ca²⁺]) in primary culture DRG neurons that express ATP-sensitive P2X3, capsaicinsensitive TRPV1 receptors modulated by estradiol. Physically disconnected (dish-in-dish system; inner chamber enclosed) mouse DRG were cultured for 12 hours near: a) media alone (control 1), b) mouse DRG (control 2), c) human neuroblastoma SHSY-5Y cells (cancer intervention), or d) mouse DRG treated with KCl (apoptosis intervention). Results: Chemosensitive receptors [Ca²⁺]_i signaling did not differ between control 1 and 2. ATP (10 μM) and capsaicin (100nM) increased [Ca²⁺]_i transients to 425.86 + 49.5 nM, and 399.21 ± 44.5 nM, respectively. 17β-estradiol (100 nM) exposure reduced ATP (171.17 ± 48.9 nM) and capsaicin (175.01±34.8 nM) [Ca²⁺]_i transients. The presence of cancer cells reduced ATP- and capsaicin-induced [Ca²⁺]_i by >50% (p2+]_i, flux four fold and abolished subsequent [Ca²⁺]_i, responses to ATP stimulation (p2+]_i responses were totally abolished. Conclusion: The local presence of apoptotic DRG or human neuroblastoma cells induced differing abnormal ATP and capsaicin-mediated [Ca²⁺]_i fluxes in normal DRG. These findings support physically disconnected, non-diffusible cell-to-cell signaling. Further studies are needed to delineate the mechanism(s) of and model(s) of communication.

African Americans have a disproportionate burden of chronic kidney disease (CKD), which tends to have an earlier onset and a more rapid progression in this population. Many of the factors responsible for the rapid progression of CKD in African Americans are detectable by screening and are modifiable with prompt therapy.

Chronic kidney disease (CKD) is an emerging public health problem and one of the most powerful predictors of premature cardiovascular disease. Emerging evidence suggests that the progression of CKD and many of the cardiovascular complications may be linked to hypovitaminosis D. Patients with CKD have an exceptionally high rate of severe vitamin D deficiency that is further exacerbated by the reduced ability to convert 25-(OH)vitamin D into the active form, 1,25 dihydroxy-vitamin D. As new evidence has improved our understanding of classical, as well as the non-classical, functions for vitamin D, it has become apparent that the autocrine role of vitamin D is an important modulator of several systems including the immune, renal and cardiovascular systems. In addition to the traditional supplementation of 1,25-vitamin D to CKD patients, by assessing and repleting 25-(OH)vitamin D deficiency, physicians will adequately fuel both the renal and extra-renal pathways of calcitriol synthesis maintaining the classical, as well as the non-classical, functions of vitamin D that ultimately influence clinical outcomes in this high-risk group of patients. Because of the high rates of hypovitaminosis D and progression of CKD to end-stage renal disease in minority populations, these findings are highly relevant to the national efforts to reduce health disparities. Healthcare providers are called to join the intensified efforts of public health officials to disseminate and implement updated guidelines and recommendations to halt the growing epidemic of vitamin D deficiency, particularly in high-risk populations.

The recognition of chronic kidney disease (CKD) as an important public health issue has fostered an increasing number of strategies to increase CKD awareness and to reduce both the prevalence and the complications of CKD. Despite these advances, end-stage renal disease (ESRD) and cardiovascular events remain the major complications of CKD. Although the ESRD epidemic is attributed in greater part to the increasing rate of diabetes, hypertension remains the second most common reported cause of ESRD and is present in approximately 90% of cases of diabetes-related ESRD. The disproportionately high prevalence of hypertension in ethnic minorities, as well as the difficulty of achieving adequate blood-pressure control in these populations, contributes substantially to the high rate of CKD progression and complications in these groups. Although the role of hypertension as a primary cause of CKD is debated, hypertension is commonly recognized as the most important CKD progression factor. Important differences have been reported in the degree and likelihood of blood-pressure response to antihypertensive medications between ethnic groups, but ethnicity seems to be less important as a determinant of clinical outcomes. In this Review we examine key ethnic variations in hypertensive CKD in terms of pathophysiology, response to antihypertensive therapy, clinical outcomes, and evidence-based recommendations for blood-pressure control, with an emphasis on African Americans.