The Role of the Endocrine System in the Regulation of Acid-Base Balance by the Kidney and the Progression of Chronic Kidney Disease.

Systemic acid-base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid-base balance in different ways.

Proteomic analysis of murine kidney proximal tubule sub-segment derived cell lines reveals preferences in mitochondrial pathway activity.

The proximal tubule (PT) is a nephron segment that is responsible for the majority of solute and water reabsorption in the kidney. Each of its sub-segments have specialized functions; however, little is known about the genes and proteins that determine the oxidative phosphorylation capacity of the PT sub-segments. This information is critical to understanding kidney function and will provide a comprehensive landscape of renal cell adaptations to injury, physiologic stressors, and development.

Regulation of Acid-Base Balance in Patients With Chronic Kidney Disease.

Normallly the kidneys handle the daily acid load arising from net endogenous acid production from the metabolism of ingested animal protein (acid) and vegetables (base). With chronic kidney disease, reduced acid excretion by the kidneys is primarily due to reduced ammonium excretion such that when acid excertion falls below acid porduction, acid accumulation occurs. With even mild reductions in glomerular filtration rate (60 to 90 ml/min), net acid excretion may fall below net acid production resulting in acid retention which may be initially sequestered in interstitial compartments in the kidneys, bones, and muscles resulting in no fall in measured systemic bicarbonate levels (eubicarbonatemic metabolic acidosis).

Effects of Prebiotic Fiber Xylooligosaccharide in Adenine-Induced Nephropathy in Mice.

Scope: This study evaluates the effect of the prebiotic fiber xylooligosaccharide (XOS) on kidney function and gut microbiome in mice with adenine-induced chronic kidney disease (CKD).

Method And Results: Mice are fed the control diet containing adenine for 3 weeks to induce CKD and are switched to XOS supplemented (2 or 7%) or control diets for another 3 weeks. Mice with CKD exhibit increased blood urea nitrogen (BUN), creatinine, and kidney histopathology.

Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison.

Regulation of Acid-Base Balance in Chronic Kidney Disease.

The kidneys play a major role in the regulation of acid-base balance by reabsorbing bicarbonate filtered by the glomeruli and excreting titratable acids and ammonia into the urine. In CKD, with declining kidney function, acid retention and metabolic acidosis occur, but the extent of acid retention depends not only on the degree of kidney impairment but also on the dietary acid load. Acid retention can occur even when the serum bicarbonate level is apparently normal.

Non-Anion Gap Metabolic Acidosis: A Clinical Approach to Evaluation.

Acid-base disturbances can result from kidney or nonkidney disorders. We present a case of high-volume ileostomy output causing large bicarbonate losses and resulting in a non-anion gap metabolic acidosis. Non-anion gap metabolic acidosis can present as a form of either acute or chronic metabolic acidosis.

Hyperchloremia - Why and how.

Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of chloride concentration through a variety of transporters that are present along the nephron. Nevertheless, hyperchloremia can occur when water losses exceed sodium and chloride losses, when the capacity to handle excessive chloride is overwhelmed, or when the serum bicarbonate is low with a concomitant rise in chloride as occurs with a normal anion gap metabolic acidosis or respiratory alkalosis.

Effects of acid challenges on type 2 angiotensin II receptor-sensitive ammonia production by the proximal tubule.

Angiotensin II (ANG II) acting through its type 1 (AT1) receptor stimulates total ammonia (tNH3) production by the proximal tubule. The present studies explored the role of ANG II type 2 (AT2) receptors in modulating the stimulatory effects of ANG II on tNH3 production. Mouse S2 proximal tubule segments derived from 18-h and 7-day acid-loaded mice, and non-acid-loaded controls were dissected and microperfused in vitro.

The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved?

The serum anion gap has been utilized to identify errors in the measurement of electrolytes, to detect paraproteins, and, most relevant to the nephrologist, to evaluate patients with suspected acid-base disorders. In regard to the latter purpose, traditionally an increased anion gap is identified when it exceeds the upper limit of normal for a particular clinical laboratory measurement. However, because there is a wide range of normal values (often 8-10 mEq/L), an increase in anion concentration can be present in the absence of an increased anion gap.

Reactive oxygen species and IRF1 stimulate IFNα production by proximal tubules during ischemic AKI.

We previously reported that expression of the transcription factor interferon regulatory factor 1 (IRF1) is an early, critical maladaptive signal expressed by renal tubules during murine ischemic acute kidney injury (AKI). We now show that IRF1 mediates signals from reactive oxygen species (ROS) generated during ischemic AKI and that these signals ultimately result in production of α-subtypes of type I interferons (IFNαs). We found that genetic knockout of the common type I IFN receptor (IFNARI-/-) improved kidney function and histology during AKI.

Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4.

Although leukocytes infiltrate the kidney during ischemic acute kidney injury (AKI) and release interleukin 6 (IL6), their mechanism of activation is unknown. Here, we tested whether Toll-like receptor 4 (TLR4) on leukocytes mediated this activation by interacting with high-mobility group protein B1 (HMGB1) released by renal cells as a consequence of ischemic kidney injury. We constructed radiation-induced bone marrow chimeras using C3H/HeJ and C57BL/10ScNJ strains of TLR4 (-/-) mice and their respective TLR4 (+/+) wild-type counterparts and studied them at 4 h after an ischemic insult.

Acid-base regulation of angiotensin receptors in the kidney.

Purpose Of Review: Angiotensin II (Ang II) is a major systemic regulator of blood pressure, blood volume, and acid-base homeostasis. However, the effects of local Ang II signaling in the kidney are less well known. Here we review the impact of Ang II on acid-base transport in specific nephron segments and discuss the recently described role of acid loading in sensitizing the proximal tubule to Ang II.

IRF-1 promotes inflammation early after ischemic acute kidney injury.

Acute renal ischemia elicits an inflammatory response that may exacerbate acute kidney injury, but the regulation of the initial signals that recruit leukocytes is not well understood. Here, we found that IFN regulatory factor 1 (IRF-1) was a critical, early proinflammatory signal released during ischemic injury in vitro and in vivo. Within 15 min of reperfusion, proximal tubular cells of the S3 segment produced IRF-1, which is a transcription factor that activates proinflammatory genes.

The top 10 things nephrologists wish every primary care physician knew.

Renal disease is commonly encountered by primary care physicians during their day-to-day visits with patients. Common renal disorders include hypertension, proteinuria, kidney stones, and chronic kidney disease. Despite their prevalence, many physicians may be unfamiliar with the diagnosis and initial treatment of these common renal disorders.

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II.

The proximal tubule defends the body against acid challenges by enhancing its production and secretion of ammonia. Our previous studies demonstrated an enhanced ammoniagenic response of the proximal tubule to ANG II added to the lumen in vitro after an in vivo acid challenge. The present study examined the effect of NH(4)Cl acid loading in vivo on renal cortical type 1 ANG II (AT(1)) receptor expression, the effect of low pH on AT(1) receptor expression in a proximal tubule cells in culture, and their response to ANG II.

Role of angiotensin II in the enhancement of ammonia production and secretion by the proximal tubule in metabolic acidosis.

Acidosis and angiotensin II stimulate ammonia production and transport by the proximal tubule. We examined the modulatory effect of the type 1 angiotensin II receptor blocker losartan on the ability of metabolic acidosis to stimulate ammonia production and secretion by mouse S2 proximal tubule segments. Mice given NH(4)Cl for 7 days developed metabolic acidosis (low serum bicarbonate concentration) and increased urinary excretion of ammonia.

Maladaptive role of IL-6 in ischemic acute renal failure.

The role of IL-6 was investigated in murine ischemic acute renal failure. The renal pedicles were clamped for 17 min, and the mice were studied at various times after reperfusion. We found that serum IL-6 increased after murine ischemic renal injury.

Sodium disorders in the elderly.

Disorders of sodium imbalance are commonly encountered in clinical practice and can have a substantial impact on the prognosis of the patient. These disorders are more common in the elderly. Sodium disorders can cause serious neurologic symptoms and even death, particularly among hospitalized patients.

Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG II.

ANG II has potent effects on ammonia production and secretion rates by the proximal tubule and is found in substantial concentrations in the lumen of the proximal tubule in vivo. Because our previous studies demonstrated that acid loading enhanced the stimulatory effects of ANG II on ammonia production and secretion by S2 proximal tubule segments, we examined the effect of ANG II on ammonia production and secretion by isolated, perfused S3 segments from nonacidotic control mice and acidotic mice given NH4Cl for 7 days. In the absence of ANG II, ammonia production and secretion rates were no different in S3 segments from acidotic and control mice.

Enhanced ammonia secretion by proximal tubules from mice receiving NH(4)Cl: role of angiotensin II.

Acidosis and angiotensin II (ANG II) stimulate ammonia production and transport by the proximal tubule. We examined the effect of short-term (18 h) in vivo acid loading with NH(4)Cl on ammonia production and secretion rates by mouse S2 proximal tubule segments microperfused in vitro with or without ANG II in the luminal microperfusion solution. S2 tubules from NH(4)Cl-treated mice displayed higher rates of luminal ammonia secretion compared with those from control mice.