The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.

Aquaporins in the Kidney: From Molecules to Medicine

The combination of acute renal failure and sepsis is associated with an ominous 70 percent mortality. This article discusses the substantial progress in understanding the mechanisms of sepsis-associated acute renal failure.

/pdf/acute-renal-failure-and-sepsis-1jdj5ma6gc.pdf

Acute renal failure and sepsis.

https://escholarship.org/content/qt5vj8413q/qt5vj8413q.pdf?t=ptt3h0

Fructose, weight gain, and the insulin resistance syndrome

Objective. —To assess the effects of supplementation with oral potassium on blood pressure in humans. Design. —Meta-analysis of randomized controlled trials. Data Sources. —English-language articles published before July 1995. Study Selection. —Thirty-three randomized controlled trials (2609 participants) in which potassium supplementation was the only difference between the intervention and control conditions. Data Extraction. —Using a standardized protocol, 2 of us independently abstracted information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results. Results. —By means of a random-effects model, findings from individual trials were pooled, after results for each trial were weighted by the inverse of its variance. An extreme effect of potassium in lowering blood pressure was noted in 1 trial. After exclusion of this trial, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of-3.11 mm Hg (-1.91 to-4.31 mm Hg) and-1.97 mm Hg (-0.52 to-3.42 mm Hg), respectively. Effects of treatment appeared to be enhanced in studies in which participants were concurrently exposed to a high intake of sodium. Conclusions. —Our results support the premise that low potassium intake may play an important role in the genesis of high blood pressure. Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium.

https://jamanetwork.com/journals/JAMA/articlepdf/416446/jama_277_20_033.pdf

Effects of Oral Potassium on Blood Pressure: Meta-analysis of Randomized Controlled Clinical Trials

This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community. Topics chosen for coverage by expert consensus documents are so designed because the evidence base, the experience with technology, and/or clinical practice are not considered sufficiently well developed to be evaluated by the formal ACCF/AHA practice guidelines process. Often the topic is the subject of considerable ongoing investigation. Thus, the reader should view the expert consensus document as the best attempt of the ACCF and document cosponsors to inform and guide clinical practice in areas where rigorous evidence may not yet be available or evidence to date is not widely applied to clinical practice. When feasible, expert consensus documents include indications or contraindications. Typically, formal recommendations are not provided in expert consensus documents as these documents do not formally grade the quality of evidence, and the provision of “Recommendations” is felt to be more appropriately within the purview of the ACCF/AHA practice guidelines. However, recommendations from ACCF/AHA practice guidelines and ACCF appropriate use criteria are presented where pertinent to the discussion. The writing committee is in agreement with these recommendations. Finally, some topics covered by expert consensus documents will be addressed subsequently by the ACCF/AHA …

ACCF/AHA Expert Consensus Document ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

Low-renin hypertension

Under normal physiologic conditions, acid–base balance is maintained by renal excretion of hydrogen ions generated during the metabolism of dietary protein and other metabolic processes. In normal subjects, these so-called fixed acids are produced at an average rate of approximately 1 mmol per kilogram of body weight, or 50 to 70 mmol per day, with a variety of organic acids accounting for half this amount and sulfuric and phosphoric acids for the remainder. When a disturbance in systemic pH occurs as the result of an excess or loss of acid or base, shifts in body buffers and ventilatory adjustment of . . .

Protection of Acid–Base Balance by pH Regulation of Acid Production

Relationship of renal ammonia production and potassium homeostasis.

Eleven of 13 patients with far advanced chronic renal disease of diverse etiologies were found to have urine that remained hypotonic to plasma in spite of the administration of a supramaximal dose of vasopressin. The vasopressin-resistant hyposthenuria seemed to be related more to the advanced nature of the disease than to the particular type of renal involvement. This defect has not previously been recognized as a common feature of end-stage renal disease, since before the present investigation, only a few patients with severe renal impairment had been studied. Possible pathophysiologic mechanisms resulting in this abnormality include anatomic derangement of the renal tubule or peritubular vasculature, an inhibitor of antidiuretic hormone, disordered calcium metabolism and osmotic diuresis per nephron. Although the urinary osmolality was always hypotonic it was not "fixed," every patient tested responding to a water load with further dilution.

https://www.nejm.org/doi/pdf/10.1056/NEJM196905222802101?listPDF=true

Richard L. Tannen

Papers

Low-renin hypertension

Protection of Acid–Base Balance by pH Regulation of Acid Production

Relationship of renal ammonia production and potassium homeostasis.

Vasopressin-resistant hyposthenuria in advanced chronic renal disease.

Indomethacin potentiates the vasoconstrictor actions of angiotensin II in normal man