Potassium Conservation Research Articles

Loss and conservation of soil organic carbon and nutrients in arid and semiarid China during aeolian dust emissions

In this study, based on the application of the integrated wind erosion modeling system (IWEMS), we comprehensively simulated the loss and conservation of soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), and total potassium (TK) during aeolian dust emissions over 2001–2020 in the arid and semiarid areas of China (ASAC). It was found that the past two decades witnessed decreasing trends in nutrient losses over the central-eastern region of Inner Mongolia, most parts of Qinghai Province, the southern part of the Xinjiang Autonomous Region, and the northwestern part of the Tibet Autonomous Region. The results, being model-based estimates, showed that the ecosystems of the ASAC were crucial in preventing annual losses of SOC, TN, TP and TK: approximately 27318.25 Gg, 2311.18 Gg, 1077.28 Gg and 35780.10 Gg, respectively. Both the losses and conservation of SOC, TN, TP and TK were consistently greater in spring and winter than in summer and autumn. The losses of SOC and nutrients during aeolian dust emissions were more serious in the west of the ASAC than in the east, both in the actual situation and the potential degenerative status. The prevention rates of SOC, TN, TP and TK for different land cover types were all greater than 92%. Comparatively speaking, the prevention rates of SOC, TN, TP and TK were the lowest for barren or sparsely vegetated land (∼92.85%−93.12%), open shrublands (∼95.65%−96.10%) and grasslands (∼98.44%−98.50%). For other land cover types, the prevention rates of SOC, TN, TP and TK were all over 99.62%.

Aldosterone: Implications in Diabetic Nephropathy

Abstract: Objective: The focus of this review is to summarize the recent advancement to understand the molecular pathogenesis of diabetic nephropathy (DN). Also, to highlight the role of abnormal aldosterone secretion on the development and progression of diabetic nephropathy. Background: Diabetic Nephropathy (DN) is a progressive disease of nephron due to slow progressive failure of kidney tubule to perform its filtration process. It is often associated with proteinuria and glomerular stiffening which eventually leads to low glomerular filtration rate, finally succumbs the patient toward the end stage of kidney disease. The abnormal level of aldosterone in diabetes mellitus is a fatal combination to combat because of progressive development of diabetic nephropathy. Methods: We reviewed the literatures for implications of aldosterone in diabetic nephropathy. The literatures that were related to different aspects of diabetic nephropathy in relation to aldosterone were analyzed and summarized in this review article. Result & Conclusion: Aldosterone, a mineralocorticoid of corticosteroid hormones releases under the influence of adrenocorticotrophic hormone (ACTH) from zona glomerulosa of adrenal gland of kidney. In normal physiological condition it regulates the renin-angiotensin system of kidney, which regulates the resorption and conservation of sodium (Na+), potassium (K+) ions and water (H2O) from distal tubule. Aldosterone secretion, despite an important regulator to maintain the equilibrium of water and ions in the body, its non-regulated higher secretion gives rise to various pathological conditions. Additionally, we also discuss the risk factors associated with the use of mineralocorticoid receptor antagonist and renin-angiotensin-aldosterone therapy, and suggesting the need of robust and controlled methods to administer these drugs. Keywords: Aldosterone, Diabetic nephropathy (DN), Diabetes mellitus, Mmineralocorticoid receptor antagonists, Renin angiotensin system

Amiloride: A review.

Amiloride is a potassium retaining diuretic and natriuretic which acts by reversibly blocking luminal epithelial sodium channels (ENaCs) in the late distal tubule and collecting duct. Amiloride is indicated in oedematous states, and for potassium conservation adjunctive to thiazide or loop diuretics for hypertension, congestive heart failure and hepatic cirrhosis with ascites. Historical studies on its use in hypertension were poorly controlled and there is insufficient data on dose-response. It is clearly highly effective in combination with thiazide diuretics where it counteracts the adverse metabolic effects of the thiazides and its use in the Medical Research Council Trial of Older Hypertensive Patients, demonstrated convincing outcome benefits on stroke and coronary events. Recently it has been shown to be as effective as spironolactone in resistant hypertension but there is a real need to establish its potential role in the much larger number of patients with mild to moderate hypertension in whom there is a paucity of information with amiloride particularly across an extended dose range.

Dietary potassium and the kidney: lifesaving physiology.

Potassium often has a negative connotation in Nephrology as patients with chronic kidney disease (CKD) are prone to develop hyperkalaemia. Approaches to the management of chronic hyperkalaemia include a low potassium diet or potassium binders. Yet, emerging data indicate that dietary potassium may be beneficial for patients with CKD. Epidemiological studies have shown that a higher urinary potassium excretion (as proxy for higher dietary potassium intake) is associated with lower blood pressure (BP) and lower cardiovascular risk, as well as better kidney outcomes. Considering that the composition of our current diet is characterized by a high sodium and low potassium content, increasing dietary potassium may be equally important as reducing sodium. Recent studies have revealed that dietary potassium modulates the activity of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule (DCT). The DCT acts as a potassium sensor to control the delivery of sodium to the collecting duct, the potassium-secreting portion of the kidney. Physiologically, this allows immediate kaliuresis after a potassium load, and conservation of potassium during potassium deficiency. Clinically, it provides a novel explanation for the inverse relationship between dietary potassium and BP. Moreover, increasing dietary potassium intake can exert BP-independent effects on the kidney by relieving the deleterious effects of a low potassium diet (inflammation, oxidative stress and fibrosis). The aim of this comprehensive review is to link physiology with clinical medicine by proposing that the same mechanisms that allow us to excrete an acute potassium load also protect us from hypertension, cardiovascular disease and CKD.

Potassium conservation is impaired in mice with reduced renal expression of Kir4.1.

To better understand the role of the inward-rectifying K channel Kir4.1 (KCNJ10) in the distal nephron, we initially studied a global Kir4.1 knockout mouse (gKO), which demonstrated the hypokalemia and hypomagnesemia seen in SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC) expression. Lethality by ~3 wk, however, limits the usefulness of this model, so we developed a kidney-specific Kir4.1 "knockdown" mouse (ksKD) using a cadherin 16 promoter and Cre-loxP methodology. These mice appeared normal and survived to adulthood. Kir4.1 protein expression was decreased ~50% vs. wild-type (WT) mice by immunoblotting, and immunofluorescence showed moderately reduced Kir4.1 staining in distal convoluted tubule that was minimal or absent in connecting tubule and cortical collecting duct. Under control conditions, the ksKD mice showed metabolic alkalosis and relative hypercalcemia but were normokalemic and mildly hypermagnesemic despite decreased NCC expression. In addition, the mice had a severe urinary concentrating defect associated with hypernatremia, enlarged kidneys with tubulocystic dilations, and reduced aquaporin-3 expression. On a K/Mg-free diet for 1 wk, however, ksKD mice showed marked hypokalemia (serum K: 1.5 ± 0.1 vs. 3.0 ± 0.1 mEq/l for WT), which was associated with renal K wasting (transtubular K gradient: 11.4 ± 0.8 vs. 1.6 ± 0.4 in WT). Phosphorylated-NCC expression increased in WT but not ksKD mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in impaired K conservation, which appears to be mediated by reduced expression of activated NCC.

Potassium regulation in the neonate.

Potassium, the major cation in intracelluar fluids, is essential for vital biological functions. Neonates maintain a net positive potassium balance, which is fundamental to ensure somatic growth but places these infants, especially those born prematurely, at risk for life-threatening disturbances in potassium concentration [K+] in the extracellular fluid compartment. Potassium conservation is achieved by maximizing gastrointestinal absorption and minimizing renal losses. A markedly low glomerular filtration rate, plus adaptations in tubular transport along the nephron, result in low potassium excretion in the urine of neonates. Careful evaluation of clinical data using reference values that are normal for the neonate's postmenstrual age is critical to avoid over-treating infants with laboratory results that represent physiologic values for their developmental stage. The treatment should be aimed at correcting the primary cause when possible. Alterations in the levels or sensitivity to aldosterone are common in neonates. In symptomatic patients, the disturbances in [K+] should be corrected promptly, with close electrocardiographic monitoring. Plasma [K+] should be monitored during the first 72 h of life in all premature infants born before 30 weeks of postmenstrual age as these infants are prone to develop non-oliguric hyperkalemia with potential serious complications.

Molecular pathophysiology of Bartter's and Gitelman's syndromes.

In the last two decades, progress in cytogenetic and genome research has enabled investigators to unravel the underlying molecular mechanisms of inherited tubulopathies such as Bartter's and Gitelman's syndromes and helped physicians to better understand not only these two pathologic entities but also renal pathophysiology and salt sensitive hypertension. Articles collected from PubMed and open access journals included original articles, research articles, and comprehensive reviews. They were evaluated by the authors with an special emphasis on originality and up to date information about molecular pathophysiology. Bartter's and Gitelman's syndromes are two different inherited salt loosing tubulopathies. They are characterized by various inability of distal nephron to reabsorb sodium chloride with resultant extarcellular volume contraction and increased activity of the renin angiotensin aldosterone system. Hypokalemic metabolic alkalosis is a common feature of these two forms of tubulopathies. Hypercalciuria characterizes the majority of Bartter's syndrome, and hypomagnesemia with hypocalciuria characterizes Gitelman's syndrome. Low blood pressure is a common feature among patients who suffered from these tubulopathies. Bartter's syndromes encompass a heterogeneous group of ion channels defects localized at the thick ascending limp of Henle's loop with resultant loss of function of sodium-potassium-2 chloride cotransporter. These defects result in the impairment of the countercurrent multiplication system of the kidney as well as calcium, potassium and acid base disturbances which in the majority of cases are proved lethal especially in the antenatal and/or immediate postnatal life period. The underlying pathology in Gitelman's syndrome is defined to the distal convoluted tubule and is related to loss of function of the sodium-chloride cotransporter. The results of this defect encompass the inability of extracellular volume homeostasis, magnesium and potassium conservation, and acid base disturbances which are generally mild and in the majority of cases are not life-threatening. Recent advances in molecular pathophysiology of Bartter's and Gitelman's syndromes have helped physicians to better understand the underlying mechanisms of these pathologic entities which remain obscure. Data collected from experiments among genetically manipulated animals enable us to better understand the pathophysiology of mammalian kidney and the underlying mechanisms of salt sensitive hypertension and to lay a foundation for the future development of new drugs, especially diuretics and antihypertensive drugs.

Nuevas perspectivas de la diálisis peritoneal: ultrafiltración a un paciente con insuficiencia cardiaca refractaria a diuréticos

Una de las particularidades que desarrolla el síndrome cardiorenal (SCR) es un círculo en el que como consecuencia del bajo gasto cardíaco hay alteración en el equilibrio del óxido nítrico y en la liberación de la hormona antidiurética, entre otros; la inducción a la vasoconstricción renal y el aumento en la reabsorción en el túbulo proximal de agua y sodio reduce el aporte de agua y sodio al nivel del túbulo distal, lo que provoca la disminución en la diuresis del péptido natriurético y aumenta la sensibilidad a la acción de la aldosterona (secretada por las glándulas suprarrenales) que actúa en la conservación del sodio y secretando potasio e incrementando la presión sanguínea). Esto explica que en los pacientes con insufi ciencia cardíaca (IC), una de las características más evidentes es la hipervolemia y la retención de sodio. Datos recientes apoyan que, en el SCR, la retención de líquidos, de sodio y la posterior resistencia a los diuréticos, provocan una sobrecarga progresiva del volumen y empeoramiento de la IC, con reducción de gasto cardíaco y mayor disfunción renal. En consecuencia, se genera una situación con mal pronóstico y pocas opciones alternativas.

Nuevas perspectivas de la diálisis peritoneal: ultrafiltración a un paciente con insuficiencia cardíaca refractaria a diuréticos

One of the particularities that develops the cardiorenal syndrome (CRS) is a circle in which as a consequence of the low cardiac output there is an alteration in the balance of nitric oxide and in the release of antidiuretic hormone, among others; induction of renal vasoconstriction and increased reabsorption in the proximal tubule of water and sodium reduces the supply of water and sodium at the level of the distal tubule, which causes a decrease in the diuresis of the natriuretic peptide and increases sensitivity to the action of aldosterone (secreted by the adrenal glands) which acts in the conservation of sodium and secreting potassium and increasing blood pressure). This explains that in patients with cardiac insufficiency (CI), one of the most evident characteristics is hypervolemia and sodium retention. Recent data support that, in CRS, fluid and sodium retention and subsequent resistance to diuretics cause progressive volume overload and worsening of HF, with reduced cardiac output and increased renal dysfunction. Consequently, a situation with a poor prognosis and few alternative options is generated.

Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus-update and epidemiology.

It is clinically useful to distinguish between two types of hereditary nephrogenic diabetes insipidus (NDI): a ‘pure’ type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients with congenital NDI bearing mutations in the vasopressin 2 receptor gene, AVPR2, or in the aquaporin-2 gene, AQP2, have a pure NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride and calcium. Patients with hereditary hypokalemic salt-losing tubulopathies have a complex phenotype with loss of water and ions. They have polyhydramnios, hypercalciuria and hypo- or isosthenuria and were found to bear KCNJ1 (ROMK) and SLC12A1 (NKCC2) mutations. Patients with polyhydramnios, profound polyuria, hyponatremia, hypochloremia, metabolic alkalosis and sensorineural deafness were found to bear BSND mutations. These clinical phenotypes demonstrate the critical importance of the proteins ROMK, NKCC2 and Barttin to transfer NaCl in the medullary interstitium and thereby to generate, together with urea, a hypertonic milieu. This editorial describes two new developments: (i) the genomic information provided by the sequencing of the AQP2 gene is key to the routine care of these patients, and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families and (ii) the expression of AQP2 mutants in Xenopus oocytes and in polarized renal tubular cells recapitulates the clinical phenotypes and reveals a continuum from severe loss of function with urinary osmolalities <150 mOsm/kg H2O to milder defects with urine osmolalities >200 mOsm/kg H2O.

Inhibition of K+ secretion in the distal nephron in nephrotic syndrome: possible role of albuminuria

Nephrotic syndrome features massive proteinuria and retention of sodium which promotes ascite formation. In the puromycin aminonucleoside-induced rat model of nephrotic syndrome, sodium retention originates from the collecting duct where it generates a driving force for potassium secretion. However, there is no evidence for urinary potassium loss or hypokalaemia in the nephrotic syndrome. We therefore investigated the mechanism preventing urinary potassium loss in the nephrotic rats and, for comparison, in hypovolaemic rats, another model displaying increased sodium reabsorption in collecting ducts. We found that sodium retention is not associated with urinary loss of potassium in either nephrotic or hypovolaemic rats, but that different mechanisms account for potassium conservation in the two models. Collecting ducts from hypovolaemic rats displayed high expression of the potassium-secreting channel ROMK but no driving force for potassium secretion owing to low luminal sodium availability. In contrast, collecting ducts from nephrotic rats displayed a high driving force for potassium secretion but no ROMK. Down-regulation of ROMK in nephrotic rats probably stems from phosphorylation of ERK arising from the presence of proteins in the luminal fluid. In addition, nephrotic rats displayed a blunted capacity to excrete potassium when fed a potassium-rich diet, and developed hyperkalaemia. As nephrotic patients were found to display plasma potassium levels in the normal to high range, we would recommend not only a low sodium diet but also a controlled potassium diet for patients with nephrotic syndrome.

Diuretic Activity of Methanol Extracts of Rubus idaeus L.

The purpose of this article is to evaluate the diuretic potential of Rubus idaeus L. fruits. By measuring the urine volume of experimental animals, we find that methanol extract of Rubus idaeus L. fruits significantly increased the urine volume of experimental animals suggesting its diuretic effect. This is the first formal report on the diuretic activity of Rubus idaeus L. fruits. Moreover, four fractions isolated from the methanol extract were further studied and the results showed that ethyl acetate fraction (RIEA) has a direct relationship with the diuretic activity of Rubus idaeus L. fruits. The urinary electrolyte patterns of experimental animals were also analyzed, we find that Rubus idaeus L. fruits have an effect on the conservation of potassium, which is an interesting property in a phyto-diuretic.

Narrative review: evolving concepts in potassium homeostasis and hypokalemia.

Humans are intermittently exposed to large variations in potassium intake, which range from periods of fasting to ingestion of potassium-rich meals. These fluctuations would abruptly alter plasma potassium concentration if not for rapid mechanisms, primarily in skeletal muscle and the liver, that buffer the changes in plasma potassium concentration by means of transcellular potassium redistribution and feedback control of renal potassium excretion. However, buffers have capacity limits, and even robust feedback control mechanisms require that the perturbation occur before feedback can initiate corrective action. In contrast, feedforward control mechanisms sense the effect of disturbances on the system's homeostasis. This review highlights recent experimental insights into the participation of feedback and feedforward control mechanisms in potassium homeostasis. New data make clear that feedforward homeostatic responses activate when decreased potassium intake is sensed, even when plasma potassium concentration is still within the normal range and before frank hypokalemia ensues, in addition to the classic feedback activation of renal potassium conservation when plasma potassium concentration decreases. Given the clinical importance of dyskalemias in patients, these novel experimental paradigms invite renewed clinical inquiry into this important area.

Characterization of the rabbit HKα2 gene promoter

The HKα2 gene directs synthesis of the HKα2 subunit of the H +, K +-ATPase. In the kidney and colon, the gene is highly expressed and is thought to play a role in potassium (K +) conservation. The rabbit has been an important experimental system for physiological studies of ion transport in the kidney, so the rabbit HKα2 gene has been cloned and characterized. The genomic clones and the previously reported HKα2a and HKα2c subunit cDNAs provided a means to address several issues regarding the structure and expression of the HKα2 gene. First, the genomic organization established that the rabbit HKα2 gene was unambiguously homologous to the mouse HKα2 gene and the human ATP1AL1 gene. Second, the mapping of the transcription start site for the alternate transcript, HKα2c, confirmed that it was an authentic rabbit transcript. Finally, isolation of DNA from the 5′ end of the HKα2 gene enabled us to initiate studies on its regulation in the rabbit cortical collecting duct. The promoter and two putative negative regulatory regions were identified and the effect of cell confluency on gene expression was studied.

Hereditary Polyuric Disorders: New Concepts and Differential Diagnosis

The identification, characterization, and mutational analysis of genes coding for key proteins to the mechanisms of urine concentration provide the basis for understanding the 2 types of hereditary nephrogenic diabetes insipidus (NDI): a pure type characterized by loss of water only, and a complex type characterized by loss of water and ions. Patients with hereditary NDI bearing mutations in AVPR2, the gene coding for the arginine vasopressin 2 receptor, or in AQP2, the gene coding for the vasopressin-sensitive water channel, have a pure NDI phenotype with loss of water, but normal conservation of sodium, potassium, chloride, and calcium. Patients bearing inactivating mutations in 1 of the 5 genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA, and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. The purpose of this article is to increase the general awareness of these congenital NDI patients to prevent severe episodes of dehydration and provide precise molecular diagnosis and treatment.

Molecular Biology of Hereditary Diabetes Insipidus

The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.

Electrolyte Disorders Following Oral Sodium Phosphate Administration for Bowel Cleansing in Elderly Patients

Background: Oral sodium phosphate is currently used for colon preparation before colonoscopy or barium enema. Sodium phosphate induces hyperphosphatemia, hypocalcemia, and hypokalemia. Elderly patients are at an increased risk for phosphate intoxication because of decreased glomerular filtration rate, medication use, and systemic and gastrointestinal diseases. We investigated these electrolyte disorders and their correlation with creatinine clearance, coexistent diseases, medications, and functional status. Methods: Thirty‐six hospitalized patients were included in the study. On day 1, patients were administered 2 doses of oral sodium phosphate. Venous blood samples for electrolyte determination were obtained at 7 am on days 1, 2 (the procedure day), and 3. Urine samples were obtained from 10 patients. Results: An increase in serum phosphorus level was correlated with a decreased creatinine clearance (R = ‐0.52; p = .001). Hypocalcemia and hypokalemia were present in 21 (58%) and 20 (56%) patients, respectively. Patients with a serum potassium concentration of 3.5 mEq/L or less on day 2 had a lower serum potassium concentration on day 1 vs those with a serum potassium concentration &gt;3.5 mEq/L on day 2 (p = .03). Five (dependent patients) had a serum potassium concentration of 3 mEq/L or less, and 2 had severe diarrhea, necessitating treatment. There were more demented patients with hypokalemia compared with normokalemic patients (p &lt; .05). Urinary fractional excretion of phosphorus tripled on day 2 (p = .01). Potassium and sodium fractional excretion remained unchanged. Conclusions: Sodium phosphate induces serious electrolyte abnormalities in the elderly. The frequency and severity of hypokalemia is due to intestinal potassium loss associated with inadequate renal potassium conservation and is apparently more prevalent in frail patients. Assessment of serum electrolytes, phosphorus, and calcium before sodium phosphate preparation is advised, and in selected patients, postprocedural assessment and correction may be required.

Electrolyte disorders following oral sodium phosphate administration for bowel cleansing in elderly patients.

Oral sodium phosphate is currently used for colon preparation prior to colonoscopy or barium enema. Sodium phosphate induces hyperphosphatemia, hypocalcemia, and hypokalemia. Elderly patients are at an increased risk for phosphate intoxication due to decreased glomerular filtration rate, medication use, and systemic and gastrointestinal diseases. We investigated these electrolyte disorders and their correlation with creatinine clearance, coexistent diseases, medications, and functional status. Thirty-six hospitalized patients were included in the study. On day 1, patients were administered 2 doses of oral sodium phosphate. Venous blood samples for electrolyte determination were obtained at 7 AM on days 1, 2 (the procedure day), and 3. Urine samples were obtained from 10 patients. An increase in serum phosphorus level was correlated with a decreased creatinine clearance (R = -0.52; P =.001). Hypocalcemia and hypokalemia were present in 21 (58%) and 20 (56%) patients, respectively. Patients with a serum potassium concentration of 3.5 mEq/L or less on day 2 had a lower serum potassium concentration on day 1 vs those with a serum potassium concentration greater than 3.5 mEq/L on day 2 (P =.03). Five (dependent patients) had a serum potassium concentration of 3 mEq/L or less and 2 had severe diarrhea, necessitating treatment. There were more demented patients with hypokalemia compared with normokalemic patients (P<.05). Urinary fractional excretion of phosphorus tripled on day 2 (P =.01). Potassium and sodium fractional excretion remained unchanged. Sodium phosphate induces serious electrolyte abnormalities in the elderly. The frequency and severity of hypokalemia is due to intestinal potassium loss associated with inadequate renal potassium conservation and is apparently more prevalent in frail patients. Assessment of serum electrolytes, phosphorus, and calcium prior to sodium phosphate preparation is advised, and in selected patients, postprocedural assessment and correction may be required.

Drug-induced Fanconi's syndrome

Fanconi's syndrome (FS) was first described by Lignac in 1924. Associated with numerous varieties of inherited and acquired conditions, FS is characterized by a generalized transport defect in the proximal tubules, leading to renal losses of glucose, phosphate, calcium, uric acid, amino acids, bicarbonates, and other organic compounds. Cardinal symptoms of the syndrome are hyperaminoaciduria, glucosuria in the face of a normal serum glucose level, and phosphate wasting. Other symptoms may be associated, such as defects in bicarbonate reabsorption; renal acidification; urate reabsorption; urinary concentration; potassium conservation; reabsorption of sodium, calcium, and low-molecular-weight proteins; and secretion of p-aminohippuric acid. Acquired renal tubular defects resulting in FS also have been described in association with many exogenous agents, whether administered or accidentally ingested. This review concentrates on drug-induced FS. Am J Kidney Dis 41:292-309.

New Therapy Update

Dyrenium® (triamterene, GlaxoSmithKline) is a potassium-sparing diuretic used in the treatment of edema associated with congestive heart failure, liver cirrhosis, nephrotic syndrome, and use of steroids or secondary hyperaldosteronism. The drug is also used in combination with other diuretics in the treatment of hypokalemia and hypertension. Triamterene inhibits the reabsorption of sodium in exchange for potassium and hydrogen in the distal tubule. The action of the drug is under the control of mineralocorticoid (aldosterone) activity. The more sodium reaching the distal tubule, the stronger the diuretic effect and potassium conservation. After oral administration, the drug is rapidly absorbed. The onset of action is in 2–4 hours, and peak effect occurs after several days of therapy. The duration of action is 7–9 hours. 80% of the drug is metabolized in the liver and 50% is excreted in the urine. The plasma half-life is 1.5–2.5 hours. The drug is contraindicated in patients with anuria or severe, progressive renal disease and diabetic nephropathy. It should not be given to patients with severe hepatic dysfunction. It should not be used in patients with elevated potassium levels or patients already taking another potassium-sparing diuretic. During triamterene administration, blood pressure, urine output, weight, and serum electrolytes should be monitored. Arrhythmias, orthostatic hypotension, and angina are the most common adverse cardiac reactions. Dehydration, fatigue, muscle cramps, nausea, and diarrhea are other reported adverse effects. The drug should not be used with other potassium-sparing diuretics, such as spironolactone and amiloride. Care must be taken when the drug is administered with other potassium-sparing agents, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking agents. Drug interactions have been reported with lithium, nonsteroidal anti-inflammatory agents, and cardiac glycosides. Triamterene can raise blood glucose levels in patients with adult-onset diabetes mellitus. Concomitant use of the drug with chlorpropamide can increase the risk of hyponatremia. The drug can be used in pregnancy if clearly indicated; it is not recommended during breast feeding. The usual starting dose is 100 mg/b.i.d. after meals. The daily dosage should not exceed 300 mg. Once symptoms of edema are controlled, the dosage can be reduced to administration every other day or to 50 mg/day. When triamterene is used in combination with other kaluretic diuretics, the initial dosage is 25 mg/day, with increases as needed to a maximum dose of 100 mg/day. Dyrenium® is a familiar potassium-sparing diuretic used in the treatment of symptomatic edema of various etiologies. The drug can also be used in combination with other diuretics in the treatment of hypertension. Monitoring of electrolytes is important to ensure its safe use.