Stages of chronic kidney disease according to glomerular filtration rate [8].
\r\n\t
",isbn:"978-1-83969-057-0",printIsbn:"978-1-83969-056-3",pdfIsbn:"978-1-83969-058-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"5f388543a066b617d2c52bd4c027c272",bookSignature:"Prof. Christophe Hano and Dr. Jen-Tsung Chen",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10539.jpg",keywords:"Plant Description, Botany, Phylogeny, Genome, Phytochemical Analysis, Extraction, Phytochemical Diversity, Phytochemical Analysis, Extraction, Phytochemical Diversity, Biotechnological Production, Traditional Medicinal Uses",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 8th 2020",dateEndSecondStepPublish:"November 23rd 2020",dateEndThirdStepPublish:"January 22nd 2021",dateEndFourthStepPublish:"April 12th 2021",dateEndFifthStepPublish:"June 11th 2021",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Assistant Professor at the University of Orleans at Research INRAE Lab LBLGC USC1328 and a member of the Cosm'ACTIFS Research Group (CNRS GDR3711). He authored and co-authored more than 100 scientific papers, reviews, and book chapters in internationally renowned journals.",coeditorOneBiosketch:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung in Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture in college. Dr. Chen's research interests are bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published over 60 research papers, reviewed over 260 manuscripts, and edited at least 150 papers in international peer-review journals.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"313856",title:"Prof.",name:"Christophe",middleName:null,surname:"Hano",slug:"christophe-hano",fullName:"Christophe Hano",profilePictureURL:"https://mts.intechopen.com/storage/users/313856/images/system/313856.jpg",biography:"Dr. Christophe Hano (male, 1978), who completed his PhD in 2005 in Plant Physiology, Biochemistry and Molecular Biology, is now Assistant Professor at the University of Orleans at Research INRAE Lab LBLGC USC1328 and a member of the Cosm'ACTIFS Research Group (CNRS GDR3711). His research career has focused on applied plant metabolism and plant biotechnology. He has written more than 100 scientific papers, reviews and book chapters in internationally renowned journals and edited one book as well as a variety of journal topical issues on plant secondary metabolism, including polyphenols. He is Academic, Assistant Editor and/or Editorial Board Member of several renowned Q1 Journals in Plant Biochemistry and Biotechnology (including Plos ONE, Biomolecules, Plant Cell Tissue and Organ Culture, Frontiers in Plant Science, Cosmetics). He was reviewers for more than 500 papers for ca 35 International Journals, and recognized scientific expert for several national and international Institutions. Currently, he is developing research projects aimed at studying plant secondary metabolism to lead to the development of natural products with interests in pharmacology or cosmetics. His research focuses on the green extraction and analytical methods applied to plant polyphenols, elucidation of biosynthetic mechanisms of plant natural products and their exploitation by metabolic engineering approaches. He was a leader (project manager) in 6 scientific projects and major investigator in several more. In this context he conducts research projects in cooperation with industrial companies and he coordinates in the European Le Studium® Consortium Action on the bioproduction of bioactive extracts for cosmetic applications through plant cell in vitro cultures. In this context, he explores the potential of the Loire Valley Flora Area for cosmetic applications. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"64145",title:"Pain Management in Patients with Impaired Kidney Function",doi:"10.5772/intechopen.81695",slug:"pain-management-in-patients-with-impaired-kidney-function",body:'\nAcross all subspecialties, pain is the most encountered problem. It is particularly difficult to deal with in patients with organ dysfunction such as acute or chronic kidney failure, due to the fact that most medications depend on kidneys for clearance. Moreover, pharmacokinetics becomes almost unpredictable due to fluctuations in kidney function depending on patient factors such as volume status, other medication actions, or enzyme build of certain individual.
\nThe prevalence of pain in patients with chronic kidney disease (CKD) has been shown in many epidemiologic studies, and all of them unanimously demonstrate that pain is more common in CKD patients than the general population.
\nMurtagh et al., in a cross-sectional survey of symptoms prevalence in stage 5 chronic kidney disease managed without dialysis, found that pain was present in 53% (42–63%) of total 66 patients with a mean age of 82 ± 6.6 years [1].
\nDavison et al. have analyzed publications from 1992 to 2009 and concluded that 58% of CKD patients are suffering from pain, 49% of those patients rated their pain as moderate to severe [2].
\nAs quality of life is greatly diminished by any kind of pain, it has been studied in CKD patients as part of symptom burden, for example [3], older patients found musculoskeletal symptoms, including pain in bones/joints (69% of 283 CKD Stage 1–5 patients), are more disturbing and bothersome, while younger patients found that reduced concentration is more intrusive. Perlman et al. also demonstrated that the presence of pain was associated with lower quality-of-life scores in a multicenter cross-sectional analysis of 634 patients with CKD [4].
\nAdditionally, in prospective cohort study of 205 Canadian hemodialysis (HD) patients, 50% of them reported pain which was related to those who was on longer HD therapy, 52.5 months with pain versus 37.7 months for those without pain.
\nThe etiology of pain was multiple in 18.4% of patients with pain, among which musculoskeletal was the most frequent (50.5%); same study found that almost one third of all patients with pain were not on any painkillers, and authors concluded that pain management was ineffective in 74.8 of patients [5].
\nPain in CKD patients is an important factor, which immensely affects quality of life. Weisbord et al. showed clear correlation between symptom excess and severity with diminished quality of life. If they had considered pain-related symptoms such as muscle cramps, headache, and chest pain in pain group, the prevalence would have increased to 50–85% [6].
\nMoreover, CKD patients with pain tend to decide to withdraw from HD more often; as shown by Davison and Jhangri, they also were more depressed and suffered sleep disturbances [7].
\nIt is very important to identify the degree of IKF and the nature of CKD and on what stage it is, because these factors will guide the management of pain and to some extent predict pain medication pharmacokinetics.
\nDefinition for CKD must have the following criteria:
Kidney damage for 3 months or more, represented by structural or functional abnormalities of the kidney, with or without decreased GFR and manifested by following:
Pathological abnormalities
Markers of kidney damage, such as abnormalities in the composition of the blood or urine, or abnormalities in imaging tests
GFR less than 60 mL/min/1.73 m2 for more than 3 months with or without kidney damage [8]
Evaluation of kidney function is more dependent on GFR or the presence of other markers of kidney damage rather than a single serum creatinine reading.
\nStages of CKD according to GFR are described in Table 1.
\nStages | \nGFR (mL/min/1.73 m2) | \nTerms/uremic symptoms | \n
---|---|---|
Stage 1 | \n90 or more | \nNormal function/asymptomatic | \n
Stage 2 | \n60–89 | \nMild/asymptomatic | \n
Stage 3 | \n30–59 | \nModerate/mild symptoms | \n
Stage 4 | \n15–29 | \nSevere/mild to moderate symptoms | \n
Stage 5 | \n15 or less | \nEnd-stage renal disease/moderate to severe symptoms, may require dialysis | \n
Stages of chronic kidney disease according to glomerular filtration rate [8].
The cause for acute pain is mainly acute injury such as surgery, procedures, and childbirth. It can be caused by acute inflammation or ischemia as well, for example, acute abdomen, colic, and ischemic heart diseases. Treatment should be directed to reduce the pain as soon as possible with multiple modalities; at the same time, the primary cause should be addressed.
\nBlocking the pain along different parts of pain pathway allows reducing the required doses and diminishing side effects. This approach has been defined as multimodal analgesia.
\nMultimodal analgesia can be achieved by combining systemic paracetamol, NSAID, opioids, and local anesthetics according to patient’s condition. All these medications may require dose adjustment, and locoregional anesthesia may raise a concern of hematoma formation due to reduced platelet activity and anticoagulant use in patients receiving hemodialysis [9].
\nChoice and dosage of medications depend on the condition of the kidneys; here the staging can roughly guide physicians to correct regimen.
\nFor example, in stages 1 and 2, kidney function is preserved well enough to excrete the medications and their metabolites. But still, kidney function tests should be frequently done so not to miss any deterioration due to trauma, dehydration, and surgical stress during perioperative period. In young patients who are not taking other nephrotoxic medications and in stage 1, acetaminophen plus short course of NSAIDs could be used. NSAIDs should not be used in stage 2 with GFR 60–89 mL/min/1.73 m2. Locoregional anesthesia must be used when applicable, especially for postoperative pain and trauma patients. In cases of moderate to severe pain, opioids should be added including tramadol, with or without gabapentinoids (Gabapentin or Pregabalin) to supplement for neuropathic pain, especially in trauma [9].
\nIn stages 3 and 4, kidney function significantly reduced (GFR between 15 and 59 mL/min/1.73 m2) which mandate all the pain medications to be dose adjusted and NSAIDs to be avoided. Acetaminophen should be used in regular doses for mild pain, reduced dose tramadol may be added, and for stronger pain, opioid such as fentanyl or hydromorphone may be useful. Morphine and codeine are not recommended. Regional anesthesia proves to be a valuable modality to avoid opioids and their undesired properties, especially in this stage, but should be avoided in individuals with impaired platelet function and/or coagulation. Reduced doses of gabapentinoids are considered in neuropathic pain, and caution should be taken when patients receive concomitant opioids. A decrease in around 50% of the dose for each 50% decline in GFR or CCr and an increase in the time interval between the doses are recommended [9, 10].
\nAcute pain management in end-stage renal disease (ESRD) patients follows the same abovementioned principles; in addition to it, more than half of them may already have been experiencing chronic pain as well. Moreover, these patients are usually malnourished and have many other multiple concomitant diseases. If they are already undergoing dialysis, sudden drop in serum concentration of pain medications and exacerbation of pain is expected. Acetaminophen may be used in regular doses of 4 g/day, but general condition of patient and other organ system diseases may require dose reduction. NSAIDs should be avoided in ESRD; even if nephrotoxicity is not of a concern, they cause gastrointestinal damage, electrolyte disturbances, and hypertension. Cyclo-oxygenase-2 inhibitors are also considered unsafe as they contribute to already existent multiple risk factors for myocardial ischemia in this group of patients [11].
\nMorphine, codeine, and meperidine produce active metabolites, in which clearance depends on kidney function. In ESRD patients, the accumulation of active metabolites of opioids produces excessive somnolence, as well as more dangerous complications such as respiratory depression, seizures, myoclonus, and exacerbation of acidosis. Safe alternative to these long-acting opioids are fentanyl, alfentanil, and adjusted dose of hydromorphone [12]. These can be best given as PCA in acute pain cases if strong opioids are required.
\nChronic pain is defined by Treede et al. as pain that persists past normal healing time [13] and hence lacks the acute warning function of physiological nociception [14]. It may be due to prolonged tissue injury with persistent activation of nociceptors or other undefined mechanisms [15].
\nRecommendations of the WHO for cancer pain and its three-step approach can be tailored to manage pharmacologic treatment of chronic pain in CKD patients [2, 15, 16]. In patients with mild pain, acetaminophen may suffice, and if NSAIDs are required, care should be taken to avoid other medications which worsen the hemodynamics (compounds that affect the renin-angiotensin-aldosterone system). NSAIDs should be avoided in patients with impaired cardiac output or with dehydration.
\nFor moderate pain, weak opioid tramadol may be added, but codeine and dihydrocodeine should not be prescribed. Tramadol dose is adjusted according to CKD stage, given in regular doses for stages 1 and 2, but is reduced by 50% in advanced stages of CKD.
\nSevere pain requires the use of strong opioids, preferably those without active metabolites such as methadone, fentanyl, and oxycodone. Although, oxycodone is mainly metabolized in the liver, around 20% is eliminated by kidneys. For that reason, it may be wise to reduce the dose according to CKD stage; in mild renal failure, up to 50% of normal dose should be given, and in advanced stages, 25% of normal dose and increase in dosing interval should be done. In patients with consistent pain, fentanyl patch can be a good option [15, 16].
\nIn all steps of WHO ladder, adjuvant medications should be added and tailored to a particular type of pain. If patient is experiencing neuropathic pain, antidepressants and anticonvulsants should be added to pain regimen. Musculoskeletal pain may have spastic component; thus muscle relaxants are beneficial. Bisphosphonates are considered adjuvant for bone pain due to malignancy. There is at least one meta-analysis to support the effect of omega-3 polyunsaturated fatty acids as an effective adjunct for joint pain (rheumatoid arthritis, inflammatory bowel disease) [17].
\nPharmacologic treatment of chronic neuropathic pain for adults should be done in a stepwise approach. The first line is tricyclic antidepressants (TCAs), followed by selective serotonin norepinephrine reuptake inhibitors (SSNRIs). Gabapentinoids are next to use.
\nTopical lidocaine should be considered alone or in combination with one the first-line therapies for localized peripheral neuropathic pain.
\nOpioid analgesics or tramadol could be used alone or in combination with one of the first-line therapies.
\nIn painful diabetic peripheral neuropathy, gabapentinoids are recommended.
\nAcetaminophen, chemical name N-acetyl-p-aminophenol, is used as a first-line medication for mild and moderate pain. It is very well absorbed from the gastrointestinal tract, mainly in the small intestine, via passive transport, and its serum concentration peaks around 2 hours. Any factors suppressing gastric emptying will slow paracetamol absorption, because negligible amount is absorbed in the stomach. It readily crosses the blood-brain barrier, and most antipyretic and analgesic actions are executed in the central nervous system.
\nMechanism of action on receptors is not entirely made clear, but it has proposed actions on serotonergic pathways, potentiation of cannabinoid receptors, and inhibition of cyclooxygenase−3 and central prostaglandin production. Recent studies have questioned its biological activity regarding cyclooxygenase inhibition in peripheral tissues, and at least two recent studies experimentally proved that paracetamol possessed peripheral cyclooxygenase-2 inhibition [18, 19, 20].
\nAcetaminophen has been regarded as pain medication with very favorable side effect profile, when used within therapeutic range doses. But recently, some authors started to question its safety, especially possible association with kidney damage. In this study [21], CKD patients who were regularly taking acetaminophen were more likely to progress to ESRD, especially with increasing exposure. In another population-based, case-control study in Sweden, 926 patients were newly diagnosed with renal failure and acetaminophen was regularly consumed by 25% of them and only 12% of controls, and authors have concluded that the regular use of paracetamol increased the risk of CKD by 2.5 times from any cause [22]. Roberts et al. conducted systematic review of observational studies looking at acetaminophen’s side effects, and they found increased relative rate of mortality from 0.95 to 1.63 and for cardiovascular adverse events risk ratio of all events increased from 1.19 to 1.68 and also that gastrointestinal adverse events or bleeds were found to increase from 1.11 to 1.49; moreover, kidney damage odds ratio increased more than 30% [23]. Another notable paper published on acetaminophen’s cardiovascular side effect could only demonstrate small association with major cardiovascular events and short-term use of acetaminophen (odds ratio 1.21, 95% confidence interval 1.04–1.42) [24].
\nAcetaminophen’s well-known hepatotoxicity occurs when the liver’s glucuronide and sulfate stores are used up, forcing it to enter minor pathway, which is oxidation by CYP 450 enzymes and formation of N-acetyl-p-benzoquinone imine (NAPQI). This metabolite is harmless in the presence of glutathione but causes hepatotoxicity in patients with limited glutathione reserves.
\nThe exact mechanisms for acetaminophen’s renal toxicity have not been identified, whereas experimental research proposed that kidneys must be saturated and push acetaminophen via CYP 450 pathway for tubular damage to occur. Diminished glutathione reserve also exacerbated kidney toxicity [25]. Another possible mechanism is the formation of arylating intermediates by p-aminophenol, which is formed by deacetylation of acetaminophen [26]. Clinical manifestation of kidney injury appears as acute tubular necrosis, with corresponding urinary changes, such as granular casts, maybe with hematuria or pyuria, urine sodium increase, and azotemia as well [27]. Toxicity is exacerbated by factors such as fall in glutathione levels (any cachectic state, alcoholism) or induction of CYP 450 enzymes.
\nIn normal conditions, plasma half-life of acetaminophen is 1.5–2.5 hours, large portion of which is metabolized and excreted in urine as sulfate and glucuronide conjugates, and minor pathway comprising less than 5% produces mercapturic and cysteine conjugates. Approximately 4% is excreted as unchanged drug. All of these processes will vary with age and dose administered. Urine flow rate is the main factor determining the clearance of acetaminophen by kidneys, but glucuronide and sulfate conjugates are not dependent of urine flow, most of the time surpassing glomerular filtration rate [28]. In CKD patients, it has been proved that glucuronide and sulfate metabolites are significantly accumulated, for example, in moderate stage of CKD, they have half-life around 21.8–30.5 hours as opposed to 3 hours in a normal person [29]. In ESRD patients undergoing dialysis, acetaminophen is removed by hemodialysis, but not by peritoneal dialysis.
\nNonetheless, acetaminophen is still a preferred drug for mild to moderate pain, and no dose reductions are mandatory.
\nNSAIDs as a group are highly unfavorable for any patient with kidney damage; nevertheless, many epidemiologic researchers have identified them as popular analgesics among CKD patients.
\nNSAIDs can be classified according to their chemical structure. They are divided into propionic acid derivatives (ibuprofen, ketoprofen, fenoprofen, naproxen), fenamates (diclofenac, ketorolac, tolmetin), enolic acid derivatives (meloxicam, piroxicam, nabumetone), and acetic acid derivatives (indomethacin, etodolac, sulindac). All these group medications inhibit the formation of prostaglandins in the peripheral tissues and, centrally, from arachidonic acid [30], hence exhibiting to different degrees analgesic, antipyretic, and anti-inflammatory effects. The action is achieved by blocking the cyclooxygenase (COX), which has two isoforms. COX-1 produces the group of prostaglandins which are necessary to maintain various physiological processes such as kidney function, maintenance of the gastrointestinal mucosa, and platelet aggregation. Yet, COX-2 is an inducible enzyme, production of which is prompted by inflammatory mediators (lipopolysaccharides, cytokines, and growth factors) by upregulating the expression of the enzyme up to 20-fold following the insult. Despite the fact that COX-2 is regarded as an inducible enzyme of inflammation process, the recent findings show that it plays an important role in normal physiology as well. It was found as an integral part of developing kidneys and brain, being a necessary enzyme for maturation and function. COX-2 maintains water electrolyte balance, contributes to arterial pressure regulation, and is mainly expressed in the thick ascending loop of Henle, macula densa of the nephron. The same enzyme is thought to play an important role in various tumor developments; especially it is overexpressed in intestinal adenomas, supporting many epidemiologic studies on the role of NSAIDs for colorectal cancer risk reduction.
\nSome authors believe that classification of NSAIDs should be according to their COX-2-to-COX-1 ratio, to better reflect their side effect profile [31], but along with inconsistent laboratory data, epidemiologic studies also show discrepancies in side effect profile of many NSAIDs. Instead, tabulating them according to half-life is of much clinical importance, which lets us to schedule medicine around the clock and avoid long-acting representatives in certain patients, including CKD patients. If the use of NSAIDs is required in CKD patients, preference should be given to those with short to medium half-life, such as ibuprofen, diclofenac, ketoprofen, and indomethacin, which have half-life less than 6 hours. Long-acting NSAIDs as naproxen, phenylbutazone, piroxicam, sulindac, diflunisal, and meloxicam (with half-life more than 10 hours) should be avoided.
\nMost of the NSAIDs have good bioavailability from the gastrointestinal tract, and their hepatic clearance is low. They also have almost equivalent efficacy, and most studies have demonstrated even comparable efficacy between nonspecific NSAIDs (nsNSAIDs) and coxibs [32]. Detailed pharmacokinetics of each NSAID is beyond the scope of this chapter; instead we will review their comparable side effect profile and application in CKD patients.
\nAll NSAIDs possess to some extent of gastrointestinal, renal, and cardiovascular toxicities and fluid retention or aggravation of hypertension. Gastrointestinal toxicity is exacerbated by various additional risk factors such as preexisting Helicobacter pylori infection, advanced age, and the concomitant use of corticosteroids or aspirin. Coxibs are the least harmful to the gastrointestinal tract as compared to other nonselective NSAIDs, which increase the risk by 2–4 times [33]. The most hepatotoxic representatives are nimesulide, sulindac, and diclofenac [34].
\nThe recent meta-analysis found that cardiovascular complications were significantly increased by both coxibs (rate ratio (RR) 1.37) and diclofenac (RR 1.41); the same analysis found ibuprofen increased coronary events significantly (RR 2.22), but naproxen was not found to contribute to major vascular events (RR 0.93). Heart failure risk was approximately increase by twofold by all representatives [33].
\nAll NSAIDs, including coxibs, adversely affect kidney physiology, which is expected considering the important role that prostaglandins play in regulation of renal perfusion and filtration. These effects manifest as hypertension, fluid retention, and in severe cases acute kidney failure [30]. Exacerbating factors are preexisting kidney dysfunction and dehydration. But it is not clear if the chronic use of NSAIDs leads to CKD or worsens its course. Several recent epidemiologic studies tried to elucidate this matter. In one meta-analysis [35], authors have concluded that regular-dose NSAIDs were not found to exacerbate the advancement of CKD (OD = 0.96), but CKD accelerated with increased-dose NSAID use (OD = 1.26). And authors have concluded that it was acceptable to use NSAIDs in moderate to severe CKD, but doses must be tailored to minimal and effective at the same time.
\nIn general, NSAIDs should be used in the short term and avoided in elderly, and precautions for gastric protection should be undertaken.
\nDespite well-known side effects and warnings, most of the CKD patients continue frequent consumption of NSAIDs, because these medications are easily available over the counter.
\nThe extent of opioid use among CKD patients is not well established. In recent review, it was reported to range around 18–36% [36].
\nAs mentioned above, the use of opioids is highly undesirable in CKD patients, but in practice physicians are obliged to, due to the severity and poor pain control with non-opioid medications.
\nMorphine as a prototype opioid should be avoided as much as possible; it produces active metabolites which depend on kidney functions for clearance. The liver converts morphine to morphine-3-glucoronide approximately 55%, morphine-6-glucoronide 10%, and normorphine 4%.
\nIn CKD patients accumulation of metabolites produces delayed suppression of respiratory drive; at the same time, other bothersome side effects such as pruritus can be challenging to manage. Morphine removed with hemodialysis up to 47%, but its metabolite, morphine-6-glucoronide, is fat-soluble and retained even after dialysis. It might be the cause of rebound phenomenon observed after dialysis.
\nStarting dose of morphine depends on glomerular filtration rate and should be around quarter to half of normal doses if it is 10–50 mL/min range and must be avoided at all if GFR is less than 10 mL/min.
\nCodeine is extensively metabolized to codeine-6-glucuronide (70%), to morphine by CYP2D6 enzymes (15%), and only 10–15% to norcodeine. About 5–15% of codeine is excreted by kidneys unchanged. Furthermore, morphine itself undergoes transformation to active metabolites as described above. All this makes codeine unsuitable for CKD patients; thus, no dosing regimen can be recommended at all.
\nTramadol is known for its other, non-opioid properties, namely, inhibition of serotonin reuptake, which increases serotonin concentration in the synaptic cleft and low abuse potential. Tramadol produces active metabolites by O-demethylation (M1), which is more potent than tramadol itself and less active N,O-didesmethyltramadol (M5). These metabolites then undergo glucuronidation and are excreted by kidneys, 60% of initial dose as metabolites, and 30% unchanged. In CKD patients tramadol and its metabolites accumulate significantly, increasing the risk for respiratory depression and seizures, as well as serotonin syndrome. Recommended dose for tramadol in CKD patients with CrCl less than 30 mL/min is maximum of 100 mg twice daily and only 50 mg twice daily for stage 5 patients who are usually on dialysis [15].
\nHydromorphone is considered relatively a better opioid option in CKD patients, despite the fact that it also produces active metabolite, hydromorphone-3-glucuronide, with seizure-inducing properties. This metabolite is removed via hemodialysis up to 40% [37]. Its analgesic properties are better than morphine, and some authors reported improvement of side effect profile, especially cognitive abilities after switching from morphine to hydromorphone [38]. Nevertheless, doses in CKD patients should be reduced, and dialysis patients should keep in mind that dialysis does not remove metabolites fully.
\nOxycodone has same analgesic potency as morphine but better bioavailability and higher abuse potential. It is converted to inactive noroxycodone (45% of total dose) and active oxymorphone (19%). The latter is more potent than morphine with less pronounced side effects. Around 72% is excreted via kidneys, of which 8% as oxycodone and the remaining as metabolites. In CKD patients, dose reduction is necessary, if GFR is less than 60 mL/min, the serum concentration of oxycodone reaches 50%; thus, starting dose should be 30% and titrated with lengthening the dosing interval. In stage 5 CKD patients, it is best to be avoided, although it is removed by dialysis.
\nMethadone was traditionally used in the treatment of opioid addiction but now increasingly prescribed for outpatient chronic pain patients. It has good bioavailability (mean value 75%), although pharmacokinetics greatly varies among individuals due to differences in CYP450 enzyme activity (which depends on genetics or patient’s other medications). Eventually it undergoes N-demethylation in the liver by CYP3A4 to inactive metabolite. It has long life, elimination half-life reaching approximately 22 hours. Limited number of studies showed that no significant accumulation in CKD patients occurs, making it a suitable medication for renally impaired population. Therefore no dose adjustments are mandatory, except in cases when the patient is taking other CYP450-altering medications.
\nBuprenorphine is also extensively metabolized by the liver producing weak analgesic, norbuprenorphine. Thirty percent of both parent drug and metabolite is cleared by kidneys. In CKD patients, it can be used in regular doses in stages 1–4 but in stage 5 used with caution and monitoring. It is dialyzed by both hemo- and peritoneal dialysis.
\nFentanyl is considered a safe opioid in CKD patients, and recommended route is transdermal patch (except in ESRD when it is avoided), but dose reduction should be up to 50% in severe to moderate CKD. It is mainly metabolized by oxidation in the liver, producing inactive metabolite, norfentanyl; 75% is excreted within 3 days. It is not dialyzed by either hemo- or peritoneal dialysis.
\nAlfentanil is similar to fentanyl, can be also used as a transdermal patch, and does not produce active metabolites. It is short and fast acting and also cannot be removed with dialysis. No dose reduction is required in CKD patients in any level.
\nWhen prescribing any opioid, all clinicians must follow safety precautions, explaining to patient treatment goals, using lowest dose to reach pain relief, following the patient regularly and frequent questioning of opioid need.
\nNon-pharmacological approach to pain management starts with working on psychological components of the pain. Devine et al. analyzed 191 studies and confirmed significance of psychological and educational care of surgical patients and its role in managing acute postoperative pain. It included providing patients with proper information about procedures and the expected level of pain, instructing them on proper coughing and breathing techniques, and providing emotional support [39].
\nTransition from acute to chronic pain conditions also involves several psychological factors such as depressive state, somatization, or significant distress [40].
\nMany kinds of questionnaires and tests were developed to be applied in chronic pain, discussion of which is beyond the scope of this chapter. Generally, psychological management of chronic pain patients should be carried out with the help of certified psychologist or psychiatrist.
\nConsidering the burden of musculoskeletal pain in CKD patients, therapies to reduce muscle tension and myofascial release should be applied, such as bed rest, bracing, traction, manipulation and mobilization, exercise, and heat/cold applications. Acupuncture was proven to be effective in lower back pain and knee pain; therefore, along with mindfulness, meditation and relaxation techniques prove to be safe and applicable to CKD patients too [41].
\nA considerable number of CKD patients experience acute pain at some point of their life, and even bigger portion of this population suffer from chronic pain. It is apparent from epidemiologic studies that pain can be experienced by more than 50% of CKD patients and greatly affects their quality of life. Moreover, poor pain control may lead to exacerbation of other psychological symptoms and contribute to further patient deterioration. If it is relatively clear how to manage acute pain in hospitalized patients, chronic pain remains mostly understudied and not fully understood. WHO stepwise approach to treating cancer pain may be tailored to CKD patients considering disturbances of pharmacodynamics of most medications in renal impairment. When there is a need to prescribe opioids, all precautions for side effects and addiction prevention must be taken. Pain practitioners should actively advocate non-pharmacological pain management techniques in appropriate patients.
\nNothing to declare.
0.12% of earth crust is made up of phosphorus mineral. P is a nonrenewable natural resource present in all types of rock and soils, in all living cells, and however can form complex compounds. Mineral deposits are the major supply of phosphorus. All phosphate mineral was derived from apatite by weathering. Mostly phosphate is found in different forms like quartz, calcite, dolomite, apatite, Fe-oxide minerals and clay minerals. Apatite mineral is used for manufacturing fertilizers. Extraction of phosphorus depends on the physical properties of the rocks and its geological setting.
Since ancient times man used natural resources such as manures, vegetables material, and bones as fertilizers. In 1840 Liebig, the German chemist, suggested the formation of superphosphate by dissolving bones in sulfuric acid that made the P more available to plants. This practice becomes so popular that bone supply is restricted in a very short time. To overcome this problem, some workers started extraction of phosphorus from rocks; in 1847 the first commercial production of P rocks from the mining of coprolites began in Suffolk in Great Britain and peaked in 1876 when about 25,000 metric tons were mined.
Presently all the Phosphate reserves that are found all over the world are not “mineable” deposits, as mining of them are not economically feasible. The United States is the highest phosphate-producing country in the world, while Morocco and China are the second and third countries with respect to phosphate production. Australia and Canada are recently known sites of phosphorus mining. There are rich deposits of phosphate found in Mongolia and Peru that will fulfill the need in the future. Florida phosphate industry becomes one of the major producer and exporter of phosphate fertilizer due to good transportation and industrial infrastructure facility in America and also because a substantial layer of phosphate is only 15 to 50 feet below a soft overburden. The phosphate mining in Central Florida overshadowed other sources because of low cost of mining, large deposits and the good quality of phosphate content of Florida rock. Florida is presently providing approximately 75% of the nation’s supply of phosphate fertilizer and about 25% of the world supply. In 2000, mining operations began in Ontario, Canada, of North America. Florida’s phosphate is part of a deposit that stretches across the state and up the coast to the Chesapeake Bay. The phosphate mining is expanded from Central Florida to Polk and Hillsborough counties, south, to Hardee, DeSoto, Manatee and Sarasota counties. In Northern Florida phosphate deposits are present in Hamilton, Columbia and Suwannee counties.
Some three decades ago in 1880, Dr. C. A. Simmonsin of England, who owned a rock quarry for building stone in Hawthorne, sends some of his rocks to Washington, DC, for analysis. The analysis determined the presence of phosphate in the rock samples, and in 1883 he made the first attempt for mining phosphate in Florida. But it was in 1889 by Albertus Vogt and others in Marion County who began the production of the first hard rock by the Marion Phosphate Company. This was later in 1890 followed by the Dunnellon Phosphate Company, in which Vogt had ownership interest, and in this way the area was flooded by thousands of prospectors, and the great Florida phosphate boom had begun. By 1894 more than 215 phosphate mining companies were operating statewide. The boom brought wealth. But in 1900 due to consolidation and capitalization, this number had dwindled to about 50. In 1881, Captain J. Francis LeBaron, chief engineer of the US Army Corps, during his survey of Peace River of Polk County, analyzed river pebbles and confirmed the presence of phosphate, but at that time this discovery did not catch much attention. In 1886 John C. Jones and Captain W. R. McKee, of Orlando, discovered high grade phosphate along the Peace River which led to the formation of an association known as the Peace River Phosphate. Mining activity along the Peace River proceeded both in the river itself and on the adjacent land. The so-called river pebble mining was the first to be exploited. In 1888, the first shipment of Peace River phosphate pebble was launched by Arcadia Phosphate Company about a year ahead of the Peace River Phosphate Company. This phosphate discovery was kept relatively quiet. Rumors of no phosphate in Central Florida spread as a result; Polk County’s phosphate deposit took a back seat the first 15 years to the hard rock region to the north. The Florida Phosphate Company and the Pharr Phosphate Company were the two phosphate mining plants found in pebble district till 1890. In 1891 Pharr started shipment of land pebble for the first time; due to this there occurred a boom in the rate of river pebble production in 1893. Phosphate mining came to North Florida in the 1960s when Occidental Petroleum Company was looking for a way to get into the fertilizer business to get profit. Occidental went north and opened a mine in White Springs where it mined phosphate until 1995, when the Potash Corporation of Saskatchewan (PCS) purchased the operation. Nowadays Mosaic and PCS Phosphate, White Springs, are the two phosphate mining companies in Florida, and the third one are US Agri-Chemicals which produce phosphate fertilizers in Central Florida.
A blanket of phosphate deposits covers much of the Peninsular Florida has a large phosphate deposits which consists of approximately equal parts phosphate rock, clay and sand, averages 12 to 15 feet in thickness. The matrix is buried beneath a soil that is 15–30 feet deep. By the end of 1999, approximately 300,000 acres of land, or more than 460 square miles, had been mined in Florida. Polk County is the heart of the Bone Valley mining region, and the mineable deposit in this area stretches to Hillsborough, Hardee, Manatee, and DeSoto counties. The large depositions were also found in mining in North Florida’s Hamilton County from a mineable area that extends into Columbia and Suwanee counties. Similar deposition is found in both the areas. Mining in Central Florida has been moving south. As sites mine out, the draglines move to where the contiguous deposit of phosphate pebble is found. Toward the south the quality of rock decreases which brings technological challenges for the mining industries. During the past years, mining is slowed down in Polk County’s southern fringe. In 2000 closing of IMC Clear Springs and Noralyn mines conveyed a close to active. Currently phosphate mining companies has opened new mining sites in Manatee, DeSoto and Hardee counties.
The fertilizer that quickly became the item of commerce as most widely used by the growers today, and it had the highest concentration of phosphate and nitrogen at 18 N–46P2O5–0K2O.
This fertilizer is essentially the same as DAP, but it has a lower concentration of nitrogen at 11 N–52P2O5–0K2O. It is completely water soluble and has granular material; it mixes well and frequently serves as an ingredient in bulk-blended fertilizers.
It is very similar to the superphosphate fertilizer that provides 46% P2O5, some calcium and sulfur to plants. GTSP is formed by reaction of phosphate rock with phosphoric acid.
It’s an acid used to make a concentrated or fluid fertilizer. PCS is the acid produced only by Florida Company in North Florida.
Phosphoric acid is used in granulation plants where ammonia is added to phosphoric acid to produce the ammoniated phosphate fertilizer. Purified food-grade phosphoric acid is used in making soft drinks.
Defluorinated phosphate rock or phosphoric acid is used to make animal feed supplements by combining phosphate rock with phosphoric acid, sodium carbonate and then calcine or react it with lime to get dicalcium phosphate.
Sulfuric acid
This acid is used to produce phosphoric acid after reacting with phosphate rocks at phosphate plants.
Sedimentary marine phosphorites are the principle resources of phosphate rock. The world’s largest sedimentary reservoirs are found in North Africa, China, the Middle East, and the United States. Valuable igneous sedimentary reservoirs are also found in Brazil, Canada, Finland, Russia, and South Africa. Substantially large phosphate deposits have been spotted near the Atlantic Ocean and the Pacific Ocean shown in Table 1 and Figure 1. World resources of phosphate rock are more than 300 billion tons. There are no imminent shortages of phosphate rock.
Phosphate rock production worldwide in 2017, by country (in 1000 metric tons).
It was observed that applications of H3PO3 and phosphite (Phi) were less effective as compared to phosphoric acid (H3PO4) and its derivatives on the first crop. With increasing rates of phosphite (Phi), phytotoxic effects were detected on the crop yield. However, nutritive role of Phi in growth response was evident when compared to the zero-P control. Whereas researchers found Phi and H3PO3 treatments beneficial to the second crop, this was due to probable conversion of Phi to phosphate in the soil. In general, better yield was obtained when Phi materials were used on soils with limestone. Further scientific studies related with the significance of H3PO3 and its salts in agriculture did not occur for nearly 30 years, but rather their performance against plant diseases was mentioned [1]. During the disease control analysis, many incidents related to the plant’s physical and chemical mobility were observed when the plants were treated with H3PO3 or its salts in the absence of plant pathogens, some of which are described below. Ouimette and Coffey [2] reported that the Phi were more readily absorbed into plant tissues than phosphates—very important in crops with leaf surfaces that resist foliar spray uptake. In a comprehensive review given by Guest and Grant [3] related with the complex action of phosphonates, several unique features of this chemical group were recounted. For example, Phi is a rapidly absorbing nutrient, which translocates from xylem to phloem according to normal source-sink relationships for nutrient element materials. Guest and Grant [3] reported that the Phi is more persistent as it metabolized slowly in plant tissue as compared with phosphate and does not participate in all the same biochemical pathways as phosphate. Adam and Conrad and Casida [4, 5] confirmed their results through experiments where bacterium Pseudomonas fluorescens 195 showed the ability to oxidize Phi and also discharge it in the growth medium as phosphate. Malacinski and Konetzka [6] repeated the same work and reported that a short adaptive period was required before oxidation of Phi by organisms, and this whole process took 14–15 weeks. Bezuidenhout et al. [7] during their study reported first time that the Phi can also be converted microbially to phosphate within plant tissues and identified three genera of bacteria (Alcaligenes, Pseudomonas and Serratia). These findings complemented the previous observations given by Rothbaum [8] that elemental P in soil was oxidized non-enzymatically under particular temperature and water. Busman et al. [9] reported that the phosphate fertilizer applied to the soil will not be utilized by the crop in the first season. Rothbaum and Baillie [8, 10] observed that Phi was less adsorbed than phosphate by the same soil. This lower ‘phosphate fixation’ improved growth of Phi-treated soil, with a period gap, as compared to phosphate-treated soil. Rhone-Poulenc Ag Company of the United States expressed concern to the US Environmental Protection Agency (EPA) about classifying a fungicide based on H3PO3 salts as a biochemical pesticide and affirmed the non-enzymatic oxidation of Phi to phosphate occur naturally over time. Lovatt [11] discovered that foliar application of K3PO3 to P-deficient citrus seedlings restored plant growth. This demonstrated that through metabolic processes, Phi was readily taken up by plant leaves and replaced phosphate as a source of Frazier and Waerstad [12] tested the composition and solubility of Phi to analyze the potential of this class of materials for increasing the plant nutrient element content of liquid fertilizers. Albrigo [13] reported the positive response of Phi on winter pre-bloom foliar of Valencia oranges which were increased flower number, fruit set and yield, plus increased total soluble solids. Additional studies by Lovatt [14] on foliar fertilization of citrus showed that application of K3PO3 in May and July to navel orange significantly increased the number of large-size fruit, total soluble solids and the ratio of soluble solids to acid, compared to control fruit. Biagro Western Sales, Inc., Visalia, CA, took the lead in commercialization of Phi-supplying fertilizer products patented by the University of California Anon and Lovatt [15, 16]. Today farmers are well educated and formed community of producers; they analyze themselves the effect of new Phi products on both soil and crop. In a practical sense, acceptance by discriminating growers is strong evidence that the benefits of H3PO3-derived fertilizers are standing up to their ultimate test—the real world of agricultural crop production.
Rock phosphate is one of the basic raw materials needed in the manufacture of phosphatic fertilizers like single superphosphate, diammonium phosphate, nitrophosphates, etc. Commercial rock phosphate occurs in nature as deposits of apatites (bearing minerals) along with other accessory minerals such as quartz, silicates, carbonates, sulfates, sesquioxides, etc. Four types of rock phosphate minerals are carbonate apatite [3Ca3(PO4)2.CaCO3], fluorapatite [3Ca3 (PO4)2.CaF2], hydroxyapatite [3Ca3(PO4)2.Ca(OH)2], and sulpho apatite [3Ca3 (PO4)2.CaSO4]. Because of their well-developed crystalline formation property, the apatites of igneous and metamorphic origin are generally regarded as less reactive. However, the apatites of sedimentary rock deposits are soft minerals possessing microcrystalline structure and are of major commercial importance for direct application in the soil [17].
The classification of reserves of indigenous rock phosphate as done by the Indian Bureau of Mines, and the purpose for which each grade can be used is given in Table 2.
Countries | Mine production | |
---|---|---|
2015 | 2016 | |
United States | 27,400 | 27,800 |
Algeria | 1400 | 1500 |
Australia | 2500 | 2500 |
Brazil | 6100 | 6500 |
China | 120,000 | 138,000 |
Egypt | 5500 | 5500 |
India | 1500 | 1500 |
Israel | 3540 | 3500 |
Jordan | 8340 | 8300 |
Kazakhstan | 1840 | 1800 |
Mexico | 1680 | 1700 |
Morocco and Western Sahara | 29,000 | 30,000 |
Peru | 3880 | 4000 |
Russia | 11,600 | 11,600 |
Saudi Arabia | 4000 | 4000 |
Senegal | 1240 | 1250 |
South Africa | 1980 | 1700 |
Syria | 750 | — |
Togo | 1100 | 900 |
Tunisia | 2800 | 3500 |
Vietnam | 2500 | 2800 |
Other countries | 2470 | 2410 |
World total (rounded) | 241,000 | 261,000 |
Showing world production of phosphate in 2015 and 2016.
Grade | P2O5 (%) | Reserve (mt) | Remarks |
---|---|---|---|
High | +30 | 15.27 | Considered for wet production of fertilizers |
Medium | 25–30 | 18.95 | Considered mainly for partially acid rock phosphate and for processed phosphates after less beneficiation |
Low | 11–25 | 55.22 | Approx. 20% P2O5 grade and relatively more reactive material may be considered for partially acidulated rock phosphate production and others for direct application |
Unclassified | 170.04 | ||
Total | 259.48 |
Classification of known reserves of indigenous rock phosphate in India.
Including all grades and types of rock phosphate, the known global resources are in the order of 163,000 million tons. Though globally adequate, rock phosphate is inequitably geographically distributed. Africa holds about 41%, the United States has 21%, former USSR 13%, the Middle East 10%, Asia 8%, and South America 3%, while Australia, New Zealand and Oceania together reported for only 2% and Europe >1%. Phosphate rock resources in India is, however, not very comfortable as it possesses a resource of only 260 million tons (0.19% of the world) of rock phosphate of all types and grades, catering the agricultural needs of 1/6 of the population of the world. Out of the total rock phosphate resource, the country has a predominance of low grade rock phosphate having only 15.27 million tons reserve of high grade rock phosphate (Table 1), and the remaining low grade rock phosphate is unacceptable to P fertilizer industry due to its very low P2O5 and high CaCO3 content [18]. The current annual domestic demand of high grade rock phosphate is of the order of 4 million tons. Out of which 95% is consumed in agriculture sector as a source of P fertilizer. The domestic production of about 1.4 million tons/year of rock phosphate could hardly meet 35% of the total demand, and the remaining (65%) demand is met through imports. P fertilizer industry largely depends on sulfur, phosphoric acid, and ammonia besides rock phosphate. India imports around 1.7 million tons of sulfur, 2–4 million tons of phosphoric acid, 1.5 million tons of NH3 and 4.9 million tons of rock phosphate for phosphate industry which constitutes a substantial part of our international trade in fertilizer raw material. Thus, the rapidly increasing price of soluble phosphatic fertilizer has raised interest in cheaper alternatives. Under such conditions, we must explore new methodologies for the utilization of indigenous low grade rock phosphate by converting it into a potential resource of P for direct application to the soil. The direct utilization of indigenous rock phosphate deposits could only alleviate the dependence of the country on foreign suppliers.
Soils has an eminent reserve of total P, but very little amount of P is actually available to the plants to support their growth to fulfill the requirement; continuous application of phosphate fertilizers is essential for increasing crop yield. Water solubility of phosphate fertilizers depends on both acidic and neutral to alkaline conditions. Several factors that influence the application of rock phosphate as P fertilizer are rate of dissolution, soil characteristics, plant species and fertilizer.
Factors which determine rock phosphate dissolution rate are its lattice composition, accessory mineral type and particle size. Solubility of apatites increased by substituting CO32− for PO43− in the lattice structure due to decrease a-dimension of the unit cell, and crystal instability [19]. Silverman et al. [20] reported Calcium carbonate as the soluble apatite as compared to other apatites. Rate of its dissolution increases with the concentration of Ca2+ and pH at the surface of apatite, and therefore it reduces the rate of rock phosphate dissolution in soil. The rate of dissolution reduced under field conditions due to leaching or plant uptake of calcium ions. The rate of dissolution increases as the particle size decreases; this might be because fine particle size has greater degree of contact between rock phosphate and soil.
The rate of dissolution of rock phosphate also depends on the chemical properties and type of soil to which it is applied. As compared to other parameters, pH buffering capacity was very important in soil. Earlier studies indicated that the amount of rock phosphate-P decreased with the increase in soil pH. The rate of dissolution of rock phosphate was highly sensitive to Ca2+ activity in the soil solution. A linear relationship between the log of Ca2+ activity and log of P in soil solution has been reported by Robinson and Syers [21]. Phosphate retention capacity and soil moisture also affect rock phosphate dissolution of the soil to retain P. Wet soil enhances the rate of phosphate dissolution by allowing the dissolution products. The product transported away from the surface of the rock phosphate particles and recognized the positive effect of organic matter on rock phosphate dissolution.
Ability of plants to extract P from rock phosphates was recognized by Merril, quoted in Flach et al. [22]. Plants affect the dissolution by the secreting acid or alkali, through Ca uptake, production of chelating organic acids such as citric, malic and 2-ketogluconic acids which complex Ca and deplete P in the soil. Roots of the plants induced change in rhizosphere pH which causes imbalance in the proportion of anionic (usually NO3−, H2PO4−, SO42− and Cl−) and cationic nutrient (K+, Ca2+, Mg2+ and Na+) uptake by the plants. The imbalance in the rhizosphere is maintained by the release of either H+ or OH−/HCO3−, thus balancing the pH of the rhizosphere. Acidic soil enhances the rate of rock phosphate dissolution. Effective rock phosphate utilization by plant species such as e.g., buckwheat and rapeseed has been responsible for their high Ca uptake. Flach et al. [22] assessed the ability of maize, pearl millet and finger millet to utilize P from rock phosphates by a pot experiment and concluded that plant species influence P dissolution; therefore, choice of crop is very important to maximize the solubility of rock phosphate.
Today growing extraction and consumption of phosphate is exhausting existing deposits, and therefore the rate of P reserves depleting. This means that at a certain point time comes when all the phosphorus reached to the alarming peak and that condition is called ‘peak phosphorus’ according to literatures. This condition will be calculated on the basis of phosphate rock reserves. Since no consensus was there on the size of these reserves, so nobody knows when will be the peak phosphorus stage will occur. Peak phosphorus has been calculated by the Global Phosphorus Research Initiative (GPRI). In 2009 the GPRI estimated that phosphorus production would peak around the year 2033 and that afterward production will continuously decrease until reserves are depleted within the next 50-100 years. The US Geological Survey (USGS) re-estimated reserves at 60,000 mmt up from previous estimates of 16,000 mmt; the IFDC stated that ‘there is no indication of “peak phosphorus” event within the next 20–25 years. The concept of peak phosphorus itself is contested; the main fault in the calculations of peak phosphorus is based on phosphate rock reserves not resources which provide the basis for estimation of static ranges. Phosphate rock reserve data explained by national geological surveys do not point out the absolute quantity of an element which is available for extraction, as the static paradigm would suggest. According to the ‘dynamic adaptive paradigm’, due to changes in economic feasibility, scarcity in the production of phosphate rock occurs. This paradigm led to scarcity which is a permanent feature of human existence: minerals become scarce as long as they are immensely valued in the society, and how much time and effort it takes to extract them, and they are related to all other goods and services in the society. Shortage of phosphate rock is an important issue when observed from a different angle that is other than relative availability. One of the reasons of fall in phosphate rock exports is the geopolitical turmoil in supplier regions. Scarcity may also result by lack of water available to the mining industry. Price inelasticity of supply, time and investments are the limiting factors which can lead to scarcity of phosphorous rock.
Nowadays the good news is that crisis can be averted. Almost 4/5 of the phosphorus mined for food production never actually reaches the food on our forks. We can therefore invest in renewable phosphate fertilizers or innovations in on-farm efficiency to safeguard our farmers, our agriculture and food consumers. In every sector recycling of phosphorous is efficiently taking place from agriculture and mining to sanitation sector to changing diet (Figure 2) [23]. To meet long-term phosphorous demand of society, we have to face the technical and institutional challenges for implementing practical solutions. An integrated, context-specific approach should be developed over partial measures. Technologies and practices with effective policy instruments (regulatory, economic, facilitation) are required to encourage and bear such measures.
Sustainable phosphorus measures: Efficiency, recycling and changing diets.
Food demand is rising globally with no slowing down in sight. Especially in China and other rapidly growing economies, more demand for meat and dairy means more demand for fertilizers, while human body only needs around 0.4 kg of P each year. 22.5 kg of phosphate rocks are mined to meet the requirement of phosphate for each person’s diet. For growing population water and energy are considered as critical for meeting future demands of food for increasing population. However, there is no approximated value of phosphorus scarcity in future as a limiting factor. Thus far we can say that without phosphorus, there would be no food and life on earth. There is no single international body responsible for managing global P resources currently in the long term, unlike oil, water and nitrogen.
Phosphorus can be recovered and used over and over again if present in sufficient concentrations dissimilar to oil, which is lost once it is used. Between the phosphate reserves and the food which we eat, up to 80% of P is lost in the process from production of fertilizers, application of phosphate on fields, in food processing and final consumption. With the increasing efficiency of phosphorous, we have to carry on recovery process of P from residues of crops, waste food items in dumpsters, manure, human excreta, struvite and other sources such as bone meal, ash and algae. A key opportunity to meeting the goal of global food security lies in the often overlooked link between addressing hunger and sanitation. In agriculture P plays a critical role as a nutrient, and but on the other hand, it is also considered as an environmental pollutant due to sewage emerging from human settlements. Human activities produce 3 million tons of P each year. If this P is recirculated back in agriculture fields from where they first came, we can maintain balance in sustaining food production in the decoupled communities which are dependent on globalized P fertilizer markets.
It may be concluded that evolution of phosphorous acid (H3PO3) and its salts as fertilizers owes much to both the early investigators searching for phosphate replacements and to the many scientists who later sorted out the relevant facts about plant response to Phi through phytopathological research. In recent years, scientific aroused their interest in the nutrient properties of H3PO3-derived products which stimulate their commercialization of H3PO3 as fertilizers. Trails of these fertilizers on crops have given fruitful results. The nutritive properties of Phi products proved to be a useful addition to producers’ resources. Phi fertilizers elicit positive responses to crop like it enhances flowering and fruit set in cirrus and are converted to phosphate through oxidation process. H3PO3 derivatives give similar responses as that of orthophosphate in fertilization of crops, despite sometimes delayed. Phosphorus acid-derived fertilizers provide a more readily available source of P than that which occurs in soil. Phi products provide more phosphorus to plants as compared to phosphate fertilizers due to their high efficacy of phosphorus uptake through plant foliage. Earlier concept of not using phi as P fertilizers is now changed due to positive results recorded by the scientist about the use of these products as fertilizers. Thus we can reduce a lot of financial burden from our economy by reducing the import of rock phosphate and other by-products required in the manufacture of commercial P fertilizer.
The authors are grateful to section of Ecology and Environmental Botany, Department of Botany, A.M.U, Aligarh.
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\\n\\nThe HTML version, as well as the PDF version of publications dated before 2012 that are accessible through a reader, are available to readers with no restriction.
\\n\\nThe full content of chapters can be read, copied and printed from the link location of the chapter and these actions are not limited or restricted in any way.
\\n\\nRegistration is requested only to download the PDF of the chapter. There are no subscription fees and there is no charge to user groups.
\\n\\nIntechOpen chapters are distributed under CC BY 3.0 licences allowing users to “copy, use, distribute, transmit and display the work publicly and to make and distribute derivative works, in any digital medium for any responsible purpose, subject to proper attribution of authorship...” and there is no non-commercial restriction.
\\n\\nAuthors may post published works to any repository or website with no delay, and Authors and Editors of IntechOpen books have direct access to the PDF of the full book.
\\n\\nAll published content can be crawled for indexing. Full text and metadata may be accessed with instructions publicly posted.
\\n\\nAll IntechOpen books are indexed in CLOCKSS and preservation of access to published content is clearly indicated.
\\n\\nPolicy last updated: 2021-02-26
\\n"}]'},components:[{type:"htmlEditorComponent",content:"All IntechOpen published chapters are available OPEN ACCESS can be read without the requirement for registration of any kind, immediately upon publication, without any barrier.
\n\nThe HTML version, as well as the PDF version of publications dated before 2012 that are accessible through a reader, are available to readers with no restriction.
\n\nThe full content of chapters can be read, copied and printed from the link location of the chapter and these actions are not limited or restricted in any way.
\n\nRegistration is requested only to download the PDF of the chapter. There are no subscription fees and there is no charge to user groups.
\n\nIntechOpen chapters are distributed under CC BY 3.0 licences allowing users to “copy, use, distribute, transmit and display the work publicly and to make and distribute derivative works, in any digital medium for any responsible purpose, subject to proper attribution of authorship...” and there is no non-commercial restriction.
\n\nAuthors may post published works to any repository or website with no delay, and Authors and Editors of IntechOpen books have direct access to the PDF of the full book.
\n\nAll published content can be crawled for indexing. Full text and metadata may be accessed with instructions publicly posted.
\n\nAll IntechOpen books are indexed in CLOCKSS and preservation of access to published content is clearly indicated.
\n\nPolicy last updated: 2021-02-26
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